title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
[Results of the operative treatment of the ruptured aneurysm: prospective clinical study]. | Aneurysmal subarachnoid hemorrhage (SAH) is a dramatic, frequently fatal event. With the incidence of 10 to 15 in 100 000 and a total mortality which even today is 40-50%, it represents a significant problem. Early surgical care for the hemorrhaging aneurysms has, without doubt, an importance in prevention of the rupture, however different series show different results as regards surgical timing and they are very different as regards giving advantage to the early or delayed time of the operation. Our aim was to perceive the results of the treatment in our group of 197 consequently operated patients for ruptured aneurysms with a special attention to the time of operation. This was a prospective clinical study and it was carried out at the Institute for Neurosurgery in Belgrade. Mortality of the operative treatment was a total of 15.74% in the entire group. According to operative intervals from the early to the delayed mortality the range is 35.71%, 22.22%, 11.63% and 8.88% respectively. The results of the treatment are in direct connection with the seriousness of the clinical picture. Being in the group graded from 1-3 decreases the probability of a fatal outcome, and graded from 1-2 decreases probability of morbidity. Early operated patients who in our group included also the most serious cases, life endangered ones, although with higher mortality do not have higher morbidity. | 18,792,579 |
Identifying variables that predict falling asleep at the wheel among long-haul truck drivers. | Analysis of data from 843 long-haul truck drivers was conducted to determine the variables that predicted falling asleep at the wheel. Demographics, sleep-specific questions, and the Epworth Sleepiness Scale were used for analysis. More than 25% of the participants (n = 247) scored 10 or higher on the Epworth Sleepiness Scale, indicating chronic sleepiness. Eight initial predictor variables were included in the logistic regression analysis. Four of the eight original variables were retained in the final model to predict falling asleep at the wheel within the past 12 months. Four variables were retained in the final model to predict falling asleep at the wheel within the past 30 days. Screening for excessive sleepiness using the Epworth Sleepiness Scale and an extensive history of medication use should be conducted for all long-haul truck drivers. | 18,792,612 |
[True aneurysm of common digital artery--case report]. | Aneurysms of digital arteries are considered to be rarity. They could be true or false. False aneurysms are usually the result of penetrating trauma, while the causes of development of true aneurysms are various, such as blunt trauma, and rarely atherosclerosis, vasculitis and infection. Also, they can be idiopathic. Reviewing the literature we found 13 cases of previously described true aneurysms of digital arteries. None of them referred to the common digital artery aneurysm. We report a case of an idiopathic true aneurysm of the common digital artery, with its clinical presentation and a corresponding multislice CT arteriogram. Surgical treatment by ligation and excision of the aneurysm was performed. As mentioned above, true aneurysms of digital arteries are very rare, so they are of little clinical importance. The most common symptom of digital artery aneurysms is pain, with a tender pulsatile mass on examination. Since natural healing cannot be expected, surgical treatment of true digital artery aneurysms is recomended for pain relief and avoidance of complications which may occur and are related to the aneurysm presence. Aneurysm resection and ligation of a blood vessel can be performed. Also, artery reconstruction can be performed by primary end-to-end anastomosis or the placement of a reversed interposition vein graft. | 18,792,628 |
[Impact of valproates on haemostasis and blood cell count in children]. | Epilepsy is a highly prevalent disease affecting 0.5-1.5% of the world's population. One of the most frequently used antiepileptics are valproates. These medicines show a negative impact on haemostasis and peripheral blood count. The objective of the study was to examine the negative impact of valproates on haemostasis and peripheral blood count in children and to analyse whether these disturbances were dependent on the dosage of valproates and drug level in blood. A two-year research was conducted. The research included: 35 children using valproates, 12 children using the therapy of both valproates and carbamazepine and 30 healthy children. Complete peripheral blood count, screening tests of haemostasis (bleeding time, prothrombin time, prothrombin ratio, activated partial thromboplastin time, fibrinogen) and capacity of thrombocyte aggregation research were done in all the children. We found significantly more common frequency of leukopenia and neutropenia in children using valproates in comparison with the healthy children group. We also found the more common frequency of eosinophilia in comparison with healthy children. The children with the valproate therapy have lower approximate values of the number of platelets, fibrinogen and platelet aggregation in comparison with healthy children, but they have a higher approximate value of bleeding time and prothrombin time. These disturbances are in correlation with the dosage and the level of the medicine in blood. Valproates have a negative effect on certain blood count parameters and haemostasis in children. Drug dosage and blood drug level are correlated with their negative impact on haemostasis parameters. | 18,792,624 |
[Detection of bone marrow-derived cells in neointimal thickening in the rat carotid artery by nested polymerase chain reaction]. | The bone marrow origin of cells involved in neointimal formation after injury of the luminal surface of the vessel was confirmed by highly sensitive nested polymerase chain reaction on isolated vascular wall cells. The model of intimal hyperplasia after balloon angioplasty of the carotid artery in radiation bone marrow chimeras between male and female Wistar rats was used. The Y chromosomes of rat male donors of the bone marrow for irradiated females were used as a marker of bone marrow-derived cells. This approach demonstrated a bone marrow origin of a large fraction of alpha-actin-positive (smooth muscle) neointimal cells. | 18,792,640 |
Integrative Self-Knowledge Scale: correlations and incremental validity of a cross-cultural measure developed in Iran and the United States. | The authors used Iranian (N = 723) and American (N = 900) samples to develop an Integrative Self-Knowledge Scale for measuring a temporally integrated understanding of processes within the self. They administered this new instrument, the Mindfulness Scale (K. W. Brown & R. M. Ryan, 2003), the Reflective and Experiential Self-Knowledge Scales (N. Ghorbani, M. N. Bing, P. J. Watson, H. R. Davison, & D. L. Lebreton, 2003), and additional sample-specific measures to 3 separate groups of university students in each society. The Integrative Self-Knowledge Scale displayed internal reliability and measurement equivalence, along with convergent, criterion, discriminant, and incremental validity. This new instrument may be useful in promoting cross-cultural research in positive psychology. | 18,792,651 |
Reproductive interference between animal species. | Although sexual interactions between species (reproductive interference) have been reported from a wide range of animal taxa, their potential for determining species coexistence is often disregarded. Here, we review evidence from laboratory and field studies illustrating that heterospecific sexual interactions are frequently associated with fitness loss and can have severe ecological and evolutionary consequences. We define reproductive interference as any kind of interspecific interaction during the process of mate acquisition that adversely affects the fitness of at least one of the species involved and that is caused by incomplete species recognition. We distinguish seven types of reproductive interference: signal jamming, heterospecific rivalry, misdirected courtship, heterospecific mating attempts, erroneous female choice, heterospecific mating, and hybridization. We then discuss the sex-specific costs of these types and highlight two typical features of reproductive interference: density-dependence and asymmetry. Similar to competition, reproductive interference can lead to displacement of one species (sexual exclusion), spatial, temporal, or habitat segregation, changes in life history parameters, and reproductive character displacement. In many cases, patterns of coexistence might be shaped by reproductive interference rather than by resource competition, as the presence of a few heterospecifics might substantially decrease reproductive success. Therefore, interspecific sexual interactions should receive more attention in ecological research. Reproductive interference has mainly been discussed in the context of invasive species or hybrid zones, whereas its influence on naturally-occurring sympatric species pairs has rarely been addressed. To improve our knowledge of the ecological significance of reproductive interference, findings from laboratory experiments should be validated in the field. Future studies should also focus on ecological mechanisms, such as temporal spatial, or habitat partitioning, that might enable sexually interacting species to coexist. Reproductive interference also has implications for the management of endangered species, which can be threatened by sexual interactions with invasive or common species. Studies of reproductive interference might even provide new insights for biological pest control. | 18,792,662 |
Building type study 883: Introduction: Health care. Flex and flow. | Hospital owners know that spalike environments mean shorter, more healing hospital stays, and flexible and expandable facilities are essential for growing communities. Enter the architects. | 18,792,663 |
[Impact of the anxiety characteristics and depression on clinical aspects and quality of life in patients with irritable bowel syndrome]. | Anxiety and depression have been related with seeking medical care by IBS patients, however their impact over the clinical characteristics and health related quality of life (HRQOL) of the patients, is unknown. To evaluate the impact of these traits over the symptoms, number of consultations and HRQOL in IBS. Consecutive moderate to severe IBS-Rome I patients that consulted a reference center in Mexico City, answered the HAD, a Bowel Symptom Questionnaire and the SF-36. Patients were compared according to the presence or absence of anxiety or depression. Anxiety was found in 70%, depression in 46% and both traits among 40%. The majority of those with depression were single compared to a married majority in those without this trait (p = 0.03). Those with anxiety (p = 0.03) and depression (p = 0.006) reported more number of days with abdominal pain/ discomfort and both traits (p = 0.000) were associated with a higher frequency of fullness, distention, abdominal pain, incomplete evacuation, abnormal bowel movements and lower HRQOL. Patients with anxiety reported a more severe IBS and those with depression a higher frequency of diarrhea predominance (p = 0.047). Traits anxiety and depression negatively impacted over the number of days, symptom frequency and HRQOL of patients with moderate to severe IBS. More studies are needed to determine if these psychological symptoms are causing these outcomes or if the gastrointestinal symptoms and poor HRQOL are triggering anxiety and depression in IBS. | 18,792,667 |
The two-component network and the general stress sigma factor RpoS (sigma S) in Escherichia coli. | The general stress sigma factor RpoS (sigma s) is induced during entry into stationary phase and in response to multiple stress conditions. RpoS is regulated at the levels of transcription, translation, proteolysis and protein activity. A key factor in RpoS control is the two-component response regulator RssB, which acts as a direct recognition and targeting factor for ClpXP-mediated RpoS proteolysis. A major, but not the only phosphodonor for RssB is the complex histidine sensor kinase ArcB. ArcB coordinates RpoS proteolysis with rpoS transcription by also phosphorylating the response regulator ArcA, which besides controlling a large regulon, also acts as a transcriptional repressor for rpoS. ArcB activity depends on the redox state of the respiratory chain, which links RpoS control to the balance between energy supply and available respiratory electron acceptor. In addition, the BarA/UvrY and Rcs phosphorelay systems can activate rpoS transcription and translation, respectively. These systems are involved in the control of motility, biofilm formation and/or virulence, suggesting that further studying a potential role of RpoS in these physiological functions may be rewarding. | 18,792,681 |
Small RNAs controlled by two-component systems. | Two-component systems (TCSs) allow bacteria to monitor diverse environmental cues and to adjust gene expression accordingly at the transcriptional level. It has been recently recognized that prokaryotes also regulate many genes and operons at a posttranscriptional level with the participation of small, noncoding RNAs which serve to control translation initiation and stability of target mRNAs, either directly by establishing antisense interactions or indirectly by antagonizing RNA-binding proteins. Interestingly, the expression of a subset of these small RNAs is regulated by TCSs and in this way, the small RNAs expand the scope of genetic control exerted by TCSs. Here we review the regulatory mechanisms and biological relevance ofa number of small RNAs under TCS control in Gram-negative and -positive bacteria. These regulatory systems govern, for instance, porin-dependent permeability of the outer membrane, quorum-sensing control of pathogenicity, or biocontrol activity. Most likely, this emerging and rapidly expanding field of molecular microbiology will provide more and more examples in the near future. | 18,792,682 |
Adhesive luting of all-ceramic restorations--the impact of cementation variables and short-term water storage on the strength of a feldspathic dental ceramic. | To investigate the impact of resin cement luting variables and short-term water storage on the strength of an adhesively luted all-ceramic restorative material. An understanding of the strengthening mechanisms will result in optimisation of operative techniques and materials selection criteria. The "fit" surfaces of 480 disk-shaped feldspathic porcelain specimens were alumina air abraded to introduce a clinically relevant surface texture and consistent surface defect population. Thirty specimens randomly allocated to each of 16 groups were coated with silane, unfilled resin or filled resin cement, or a combination. Eight groups were stored either dry or wet for 24 h prior to bi-axial flexure testing (ball-on-ring). Statistical analysis of the flexure strength data involved a three-factor general linear model (p < 0.05) prior to a Weibull analysis. Resin coating the porcelain surface resulted in a significant increase in the characteristic stress (sigma(o)), and strengthening was dependent on coating type (p < 0.001). Silane priming resulted in additional strengthening when preceding filled resin cement coating. Water immersion for 24 h resulted in a strength degradation of both the uncoated control and coated specimens, whereby the magnitude of strength degradation was dependent on coating type (p < 0.001). Resin luting of dental ceramics results in significant strengthening likely to impact on clinical performance. The strengthening is dependent on the creation of a resin-ceramic hybrid layer sensitive to cementation variables and clinical placement technique. Short-term water immersion results in a significant degradation of strengthening sensitive to the characteristics of the resin-ceramic hybrid layer. | 18,792,699 |
Influence of free-hand vs uniform irradiation on tensile bond strength in Er:YAG-lased dentin. | To compare effects of free-hand and mechanically applied uniform irradiation on tensile bond strength of 4-META/MMA-TBB resin to Er:YAG laser-irradiated dentin using an X-Y moving stage. Three different laser conditions were evaluated: 1.0 W, 100 mJ/pulse, 10 pps; 1.0 W, 50 mJ/pulse, 20 pps; 1.0 W, 33 mJ/pulse, 30 pps. Samples of bovine dentin were set on a moving stage and mechanically irradiated with an Er:YAG laser at a scanning speed of 1.0 mm/s or subjected to free-hand irradiation. The lased dentin surfaces were acid conditioned with 10% citric acid/3% ferric chloride for 15 s, rinsed, and dried. The surfaces were bonded to PMMA rods with 4-META/MMA-TBB resin, and mini-dumbbell-shaped bonded specimens were prepared. Tensile bond strength was measured and compared with the results for free-hand irradiated samples obtained under the same conditions in an earlier study. SEM observations of fractured surfaces after tensile bond testing were also performed. A significant difference was found in tensile bond strength among the 3 laser settings in both free-hand and mechanically uniform irradiations. A comparison of free-hand laser irradiation and mechanically performed uniform laser irradiation revealed no significant difference under either laser condition (p > 0.05). SEM observation of the fractured surfaces showed no difference between the two irradiation methods under all laser conditions. No significant difference was found in tensile bond strength between free-hand and mechanically irradiated dentin. Significant differences were found, however, with changes in laser setting in both groups. | 18,792,700 |
Reshaping students' attitudes toward individuals with mental illness through a clinical nursing clerkship. | The purpose of this study was to evaluate the degree to which a psychiatric clinical clerkship alters nursing students' attitudes toward individuals with mental illness. The goal of the 4-week clerkship is to provide students with the knowledge, skills, and professional attitudes that will enable them to care for individuals with mental illness in different health care settings. A pencil-and-paper questionnaire was administered to 126 third-year students before and after the clerkship. Students were presented with four hypothetical patients with schizophrenia and were asked to what extent the patient was responsible for his condition, the emotions students felt, and whether students were willing to care for the patient or to segregate him in the hospital. After the clinical clerkship, students became more compassionate and less frightened by psychiatric patients, were more willing to care for individuals with mental illness, and expressed less need to segregate them from the community. In addition, in accord with professional attitudes, students became aware of their own attitudes (the responsibility attributed to patients) and their emotional responses, but these were no longer associated with reluctance to provide care. | 18,792,706 |
Back to the future with hands-on science: students' perceptions of learning anatomy and physiology. | This article examines student perceptions of learning related to anatomy and physiology in a bachelor of nursing program. One strategy to teach the sciences is simulated learning, a technology that offers exciting potential. Virtual environments for laboratory learning may offer numerous benefits: teachers can convey information to a larger group of students, reducing the need for small laboratory classes; less equipment is required, thus containing ongoing costs; and students can learn in their own time and place. However, simulated learning may also diminish access to the teacher-student relationship and the opportunity for guided practice and guided linking of theory with practice. Without this hands-on experience, there is a risk that students will not engage as effectively, and thus conceptual learning and the development of critical thinking skills are diminished. However, student perceptions of these learning experiences are largely unknown. Thus, this study examined students' perceptions of anatomy and physiology laboratory experiences and the importance they placed on hands-on experience in laboratory settings. | 18,792,709 |
Self-assembly drives quantum dot photoluminescence. | Engineering the spectral properties of quantum dots can be achieved by a control of the quantum dots organization on a substrate. Indeed, many applications of quantum dots as LEDs are based on the realization of a 3D architecture of quantum dots. In this contribution, we present a systematic study of the quantum dot organization obtained on different chemically modified substrates. By varying the chemical affinity between the quantum dots and the substrate, the quantum dot organization is strongly modified from the 2D monolayer to the 3D aggregates. Then the photoluminescence of the different obtained samples has been systematically studied and correlated with the quantum dot film organization. We clearly show that the interaction between the substrate and the quantum dot must be stronger than the quantum dot-quantum dot interaction to avoid 3D aggregation and that these organization strongly modified the photoluminescence of the film rather than intrinsic changes of the quantum dot induced by pure surface chemistry. | 18,792,763 |
Characterization and membrane gene-based phylogenetic analysis of avian infectious bronchitis virus Chinese strain HH06. | A Chinese isolate of avian infectious bronchitis virus (IBV) designated HH06 was isolated from the kidney tissues of a chicken flock experiencing an outbreak of nephritis. In vivo pathogenicity of the IBV isolate HH06 was determined by inoculating specific pathogen-free (SPF) chickens. The clinical signs and related gross lesions of HH06 infected chickens were similar with those of the field-infected chickens. SPF embryonated eggs were inoculated with virus suspension for serial passage and their genomic RNA was extracted. RT-PCR technique was utilized to amplify the M gene sequence encoding membrane protein of IBV. Recombinant plasmid named T-vector-M was constructed via inserting the M gene into the TA cloning vector, pMD 18-T. The sequenced M gene and its deduced amino acid (aa) sequences were compared with the published sequences of reference strains. The M gene is of 687 bp in length encoding the M protein of 228 amino acids with a predicted molecular weight of 25.4 kDa. The sequences of the M gene and M protein share 83.9-97.9% and 83.6-96.5% homologous identities, respectively, compared with 29 IBV reference strains derived from different regions or countries, which revealed that there are still significant variations between strains. Furthermore, a phylogenetic tree based on these M DNA sequences was generated, and the tree topology suggests that some Chinese IBV strains may have a common ancestor; however, HH06 is a new local IBV isolate that is responsible for the field outbreak of nephritis. | 18,792,774 |
Coordinate expression of the human pregnancy-specific glycoprotein gene family during induced and replicative senescence. | Pregnancy-specific glycoproteins (PSGs) comprise a family of highly similar polypeptides encoded by 11 transcriptionally active genes that compactly cluster on band 19q13.2. All members of the PSG family were found to be markedly up-regulated by addition of 5-bromodeoxyuridine in HeLa cells. Similarly, all of the members were markedly up-regulated during replicative senescence in normal human fibroblasts. Promoter analysis of the PSG1, 4, and 11 genes in HeLa cells did not reveal a cis-regulatory element responsive to 5-bromodeoxyuridine in their 5'-flanking sequences. These results suggest that the PSG genes are regulated at a level of higher order chromatin structure besides by a signal of pregnancy. | 18,792,801 |
Association between the G1001C polymorphism in the GRIN1 gene promoter and schizophrenia in the Iranian population. | Schizophrenia is a complex genetic disorder to which genetic variation in the glutamatergic signaling pathways is believed to play a substantial role in the etiology of the disease. Association studies have implicated the N-methyl-D-aspartate receptor subunit gene, GRIN1, as a candidate gene for schizophrenia. In this report, we used a case control study to establish the possible association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia in an Iranian cohort of 200 unrelated patients and 200 controls. The allelic and genotypic frequencies of the polymorphism were determined using polymerase chain reaction restriction fragment length polymorphism. Data analysis using logistic regression and the Mantel-Haenszel chi-square test revealed a strong association between the G1001C polymorphism and schizophrenia (CG genotype: odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.34-3.48, P = 0.001 and CC genotype: OR = 29.10, 95% CI 3.40-565.78, P < 0.001). Furthermore, the C allele is significantly associated with an increasing risk of schizophrenia. | 18,792,810 |
Evolution of antimicrobial susceptibility patterns of aerobic and facultative gram-negative bacilli causing intra-abdominal infections: results from the SMART studies 2003-2007. | Study for Monitoring Antimicrobial Resistance Trends (SMART) is an ongoing global antimicrobial surveillance program focused on clinical isolates from intra-abdominal infections (IAI). The objective of this subanalysis was to assess the evolution of the antimicrobial susceptibility patterns among aerobic and facultative gram-negative bacilli (GNB) recovered over a 5-year period at our institution. We tested the in vitro activity of the antimicrobials, commonly used to treat IAI, against consecutive unique isolates from IAI using microdilution techniques according to the CLSI guidelines for MIC testing. All isolates were screened phenotypically for extended-spectrum beta-lactamase (ESBL) production. Isolates recovered within 48 h of hospitalization were considered community-acquired (CA). Over the study period a total of 572 aerobic and facultative gram-negative bacilli were recovered from 510 patients, of which 258 (45%) were CA. Enterobacteriaceae composed 91% of the total isolates. Escherichia coli was the most common isolated species (52%). Susceptibility rates of Enterobacteriaceae ranged from 96.5 %-100 % to ertapenem, 96.5 %-100 % to imipenem, 87.7%-94.3% to piperacillin-tazobactam, 85.1%-94.3% to cefotaxime, 89.5%-100% to cefepime, 76.3%-84.8% to ciprofloxacin, and 93.8%-100% to amikacin. ESBL were detected in 6.3% of E. coli, 5.7% of Klebsiella spp. and 2.7% of Enterobacter spp. ESBL producers generally had a more antibiotic- resistant profile than non-ESBL producers and 16% of them were CA. Susceptibility rates to ertapenem, imipenem, piperacillin-tazobactam, ceftazidime, cefepime, ciprofloxacin and amikacin were, respectively, for P. aeruginosa: 28.2 %, 58.9%, 82%, 84.6 %, 76.9 %, 71.8% and 82%; for Acinetobacter baumannii: 33.3 %, 100 %, 66.6 %, 66.6 %, 66.6%, 66.6% y 66.6%, and for Stenotrophomonas maltophilia: 0%, 0%, 0%, 28.6%, 0%, 42.9% and 14.3%. Over the 5 year-study period we have not observed significant increases in resistance of aerobic and facultative GNB causing IAI to commonly used beta-lactam antimicrobial drugs. A minority of ESBL-producing Enterobacteriaceae were CA. Carbapenems, including group I agents like ertapenem, were the most reliably active drugs in vitro against isolates producing IAI. | 18,792,817 |
Knowing where but not what: impaired thematic roles and spatial language. | We describe case J.P. who, following a left inferior frontal lesion, made frequent role confusions in comprehension and production (e.g., saying "The boy kicks the girl" for a picture showing a girl kicking a boy). J.P.'s preserved ability to judge the grammaticality of sentences rules out a syntactic deficit as the primary cause of the role confusions. Thematic role assignment is also required with spatial prepositions such as in or above, and J.P.'s thematic role assignment was also severely impaired with spatial prepositions. We capitalized on prior linguistic analyses and behavioural studies to design accurate tests of the semantics of spatial terms, spatial relations, and critical features of objects. Fine-grain semantic tests revealed that the semantics of spatial terms and objects was intact. We hypothesize that J.P.'s role confusions reflected a failure to integrate objects within semantic representations that define the thematic roles. Our data suggest that properties of objects and thematic roles are specified by distinct semantic processes, which have different brain localizations. J.P.'s lesion further suggests that left inferior frontal regions are critical in thematic role assignment, thus contributing to the understanding of the linguistic functions of these regions. | 18,792,829 |
Computational study of growth and remodelling in the aortic arch. | Opening angles (OAs) are associated with growth and remodelling in arteries. One curiosity has been the relatively large OAs found in the aortic arch of some animals. Here, we use computational models to explore the reasons behind this phenomenon. The artery is assumed to contain a smooth muscle/collagen phase and an elastin phase. In the models, growth and remodelling of smooth muscle/collagen depends on wall stress and fluid shear stress. Remodelling of elastin, which normally turns over very slowly, is neglected. The results indicate that OAs generally increase with longitudinal curvature (torus model), earlier elastin production during development, and decreased wall stiffness. Correlating these results with available experimental data suggests that all of these effects may contribute to the large OAs in the aortic arch. The models also suggest that the slow turnover rate of elastin limits longitudinal growth. These results should promote increased understanding of the causes of residual stress in arteries. | 18,792,831 |
A community study of psychosocial functioning and weight in young children and adolescents. | Children with either underweight or overweight may be at risk for mental health problems and require mental health service use. The present study investigated the relationship between weight status and psychosocial dysfunctioning in children of two different age groups (5-6 and 13-14 years). Using height and weight measurements collected during routine medical examinations of all children in a circumscribed geographical region, measures of underweight and overweight were calculated in young children (aged 5-6 years; n=797) and in adolescents (13-14 years; n=614). In addition, parent-reported questionnaires (young children) and adolescent-reported questionnaires (adolescents), including the Strengths and Difficulties Questionnaire (SDQ), provided information on psychopathology subscales including emotional symptoms, conduct problems, hyperactivity-inattention, peer problems and prosocial behaviour. Few associations were apparent after controlling for confounding variables. Young children who were underweight (but not severely underweight) less frequently displayed conduct problems, while adolescents who were overweight or obese reported more peer problems and less prosocial behaviour than did children of normal weight. Children who were underweight and children who were overweight did not score higher on any of the other psychopathology scales than did children of normal weight in either age group. Our findings suggest that the domains of weight problems and psychopathology do not display strong associations. However, there are indications that some areas of psychopathology may be differentially associated with weight problems. Further longitudinal research is warranted. | 18,792,853 |
Cognitive profiles of healthy siblings of schizophrenia patients: application of the cognitive domains of the MATRICS consensus battery. | Even though a large body of data suggests the presence of various types of cognitive deficits in the unaffected relatives of schizophrenia patients, more study is needed to clarify the comparative sensitivities of specific cognitive measures for relative-control differences. In this study, the authors compared the cognitive profiles of unaffected siblings of schizophrenia patients and those of patients and normal controls, and attempted to identify cognitive markers that might be associated with genetic liability to schizophrenia. Eighty-eight clinically stable schizophrenia patients, 44 healthy patient siblings, and 100 normal controls were evaluated using comprehensive neuropsychological tests. The domain structure of the MATRICS consensus cognitive battery was adopted, and both domain scores and individual test scores were used in the analysis. Performances of the sibling group were intermediate between those of patients and controls on most measures. A significant difference between the sibling and control groups was observed only in the Category Fluency Test. This cognitive deficit might be caused by familial predisposition to schizophrenia and could be a candidate of endophenotype for schizophrenia. | 18,792,857 |
[Postoperative cognitive dysfunction in geriatric patients]. | Postoperative cognitive dysfunction occurs in geriatric patients after major operations and influences morbidity and mortality of these patients. Clinical observations and neuropsychological tests can be used to diagnose cognitive disorders after an operation. Until today no specific medical treatment is known for the therapy of cognitive dysfunctions after an operation and, therefore, in high risk patients perioperative preventive measures is the only way to decrease the incidence and extend of this disease. | 18,792,864 |
[Incident reporting systems in anesthesiology--methods and benefits using the example of PaSOS]. | Preventing patient harm is one of the main tasks for the field of anesthesiology from early on. With the introduction of the national German incident reporting system PaSOS, which is hosted by the German anesthesia society, anesthesiology is again leading the field of patient safety. Important elements, success factors and background information for the introduction of successful incident reporting systems in an organization are given. Examples by and from PaSOS are given. | 18,792,866 |
Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function? | The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when compared to pre-OGL values, most significantly at 3 h post-OGL, on the following days: on the first study day termed "Baseline day" (p=0.04); on both days after 3 months of nateglinide treatment [with nateglinide administered on study-day "acute+chronic" (p=0.01); and without nateglinide on study-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0.02). Insulin concentrations increased while glucose concentrations decreased on study-days with nateglinide when compared to study-days without (p=<0.001 for both insulin and glucose). Comparisons for insulin and glucose concentrations between days with nateglinide, and likewise between days without, showed no significant difference. Postglucose load endothelial dysfunction can be prevented by administration of nateglinide, however, after 3 months of nateglinide treatment, this effect is abolished. Chronically increased insulin secretion could counteract the initial beneficial effect of reduced glucose excursions. We found no relationship between postprandial hyperglycemia and post-OGL FMD. | 18,792,871 |
The role of inflammation in vascular insulin resistance with focus on IL-6. | The present review focuses on the possible role of interleukin-(IL)-6 in vascular insulin resistance. The endothelium plays an important role in regulating the tone of the vasculature by releasing nitric oxide (NO) to the smooth muscles of the vessels, thereby regulating the distribution of blood flow to the various tissues in relation to their energy demand. A dysfunctioning endothelium has been associated with both initiation and progression of atherosclerotic cardiovascular (CV) disease and has been shown to predate the onset of hyperglycemia in the natural history of type 2 diabetes. It is likely that chronic low-level inflammation plays an important role in developing endothelial dysfunction mainly through proinflammatory actions of tumor necrosis factor alpha (TNF-alpha). TNF-alpha induces production of IL-6 and it has been suggested that a causal relationship exists between endothelial dysfunction and these cytokines. With regard to vascular insulin resistance, the available data point to a direct pathogenic role of TNF-alpha in mediating endothelial dysfunction, whereas with regard to IL-6 evidence is sparse and does not allow any firm conclusions. | 18,792,875 |
Leptin decreases postprandially in people with type 2 diabetes, an effect reduced by the cooking method. | Leptin modulates satiety and increases in obesity and type 2 diabetes mellitus in parallel with leptin resistance. Postprandial leptin regulation has been previously postulated to depend on meal composition, but data are controversial. The hypothesis of our study was that in people with type 2 diabetes mellitus, a postprandial leptin regulation exists that can be regulated not only by meal composition but also by the cooking method. In 20 inpatients with type 2 diabetes (mean age: 55.9 years), the acute effects of 2 meals, a high-heat-processed meal HHPM or a low-heat-processed meal LHPM, on leptin levels were studied on 2 different days in a randomized, crossover design. Both test meals had similar ingredients and differed only in the cooking method used. Parameters were measured after an overnight fast and at 2, 4, and 6 h postprandially. The HHPM induced a marked decrease in leptin levels, from 8 717+/-2 079 pg/ml at baseline to 6 788+/-1 598 pg/ml at 2 h postprandially (-1 929 pg/ml, -22%*), an effect significantly reduced by the LHPM, where values were 8 563+/-1 900 pg/ml at baseline and 7 425+/-1 591 pg/ml at 2 h postprandially (-1 138 pg/ml, -13%* (double dagger)) (*p<0.05 vs. baseline, (double dagger)p<0.05 vs. HHPM). Parameters of oxidative stress and blood AGEs increased only following the HHPM, while postprandial glucose, triglycerides, and insulin excursions were similar between meals. Postprandial leptin decreases following a HHPM meal in people with T2DM, an effect reduced by the cooking method. | 18,792,885 |
Effects of postpartum exercise program on fatigue and depression during "doing-the-month" period. | This study explored the effectiveness of an exercise program on reducing levels of fatigue and depression among postpartum women who were "doing-the-month" in a maternity center in Taiwan. Previous studies related to postpartum have focused on depression rather than women's feelings of fatigue, and no study related to exercise has previously been conducted in a Taiwan maternity center. A low-intensity exercise program was specifically designed and administered to 31 subjects in the study's intervention group. Another 30 subjects (the control group) followed a traditional, non-physically active postpartum care regimen. Those in the intervention group were required to participate in at least 6 exercise program sessions during their one month postpartum stay. All subjects were asked to fill out a fatigue and depression questionnaire before and after the program. A Fatigue Symptom Checklist (FSC) was used to measure fatigue, and the Center for Epidemiological Studies Depression (CESD) was used to confirm the development of depression. Results showed statistically significant differences between the two groups in terms of fatigue levels, with statistical improvements (p < .05) registered by the intervention group in terms of levels of physical and psychological fatigue and fatigue symptoms. However, no significant changes in depression between the two groups were found. Study results demonstrate that a low-intensity exercise program can offer a good platform for clinicians and researchers to help reduce fatigue in postpartum women. | 18,792,887 |
Role of the feline immunodeficiency virus L-domain in the presence or absence of Gag processing: involvement of ubiquitin and Nedd4-2s ligase in viral egress. | RNA-enveloped viruses bud from infected cells by exploiting the multivesicular body (MVB) pathway. In this context, ubiquitination of structural viral proteins and their direct interaction with cellular factors involved in the MVB biogenesis through short proline rich regions, named late domains (L-domains), are crucial mechanisms. Here we report that, in contrast with the human immunodeficiency virus (HIV), the feline immunodeficiency virus (FIV), a non-primate lentivirus, is strictly dependent for its budding on a "PSAP"-type L-domain, mapping in the carboxy-terminal region of Gag, irrespective of a functional viral protease. Moreover, we provide evidence that FIV egress is related to Gag ubiquitination, that is, linked to the presence of an active L-domain. Finally, although FIV Gag does not contain a PPxY motif, we show that the Nedd4-2s ubiquitin ligase enhances FIV Gag ubiquitination and it is capable to rescue viral mutants lacking a functional L-domain. In conclusion, our data bring to light peculiar aspects of FIV egress, but we also demonstrate that a non-primate lentivirus shares with HIV-1 a novel mechanism of connection to the cellular budding machinery. | 18,792,916 |
Oxidation products of polyunsaturated fatty acids in infant formulas compared to human milk--a preliminary study. | Information about lipid oxidation in fresh and stored human milk compared with infant formulas is scarce. We aimed to assess n-6 and n-3 PUFA oxidation in these milks by measuring the 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE) content. Human milk samples (n = 4), obtained from volunteer mothers, were analyzed fresh and after 1 wk at 4 degrees C or 24 h at 18 degrees C. Vitamin E and malondialdehyde (MDA) were measured by HPLC and fatty acid profile by GC. The 4-HHE and 4-HNE contents were measured by GC-MS. Infant formulas (n = 10) were tested; their fat droplet size was measured by laser light scattering and observed by confocal laser scanning microscopy. Human milk samples contained 31.0 +/- 6.3 g/L of lipids and 1.14 +/- 0.26 mg/L of vitamin E. Fat droplets were smaller in infant formulas than reported in human milk. The (4-HHE/n-3 PUFA) ratio was 0.19 +/- 0.01 microg/g in fresh human milk (unchanged after storage) versus 3.6 +/- 3.1 microg/g in dissolved powder formulas and 4.3 +/- 3.8 microg/g in liquid formula. (4-HNE/n-6 PUFA) was 0.004 +/- 0.000 microg/g in fresh milk (0.03 +/- 0.01 microg/g after storage) versus 1.1 +/- 1.0 microg/g in dissolved powder formulas and 0.2 +/- 0.3 microg/g in liquid formula. Infant formulas also contained more MDA than human milk. n-3 PUFA were more prone to oxidation than n-6 PUFA. Whether threshold levels of 4-HHE and 4-HNE would be of health concern should be elucidated. | 18,792,926 |
The Gene Ontology (GO) project: structured vocabularies for molecular biology and their application to genome and expression analysis. | Scientists wishing to utilize genomic data have quickly come to realize the benefit of standardizing descriptions of experimental procedures and results for computer-driven information retrieval systems. The focus of the Gene Ontology project is three-fold. First, the project goal is to compile the Gene Ontologies; structured vocabularies describing domains of molecular biology. Second, the project supports the use of these structured vocabularies in the annotation of gene products. Third, the gene product-to-GO annotation sets are provided by participating groups to the public through open access to the GO database and Web resource. This unit describes the current ontologies and what is beyond the scope of the Gene Ontology project. It addresses the issue of how GO vocabularies are constructed and related to genes and gene products. It concludes with a discussion of how researchers can access, browse, and utilize the GO project in the course of their own research. | 18,792,943 |
Creating databases for biological information: an introduction. | The essence of bioinformatics is dealing with large quantities of information. Whether it be sequencing data, microarray data files, mass spectrometric data (e.g., fingerprints), the catalog of strains arising from an insertional mutagenesis project, or even large numbers of PDF files, there inevitably comes a time when the information can simply no longer be managed with files and directories. This is where databases come into play. This unit briefly reviews the characteristics of several database management systems, including flat file, indexed file, and relational databases, as well as ACeDB. It compares their strengths and weaknesses and offers some general guidelines for selecting an appropriate database management system. | 18,792,944 |
Biodegradable honeycomb collagen scaffold for dermal tissue engineering. | Tissue engineering requires a mechanically stable, biocompatible, and biodegradable scaffold that permits cell adherence and proliferation, allows preservation of cell-specific properties, and suitable for surgical implantations. In this study, honeycomb collagen sheet was used for three-dimensional (3D) cultures of human skin fibroblasts and characterized as an effective and suitable scaffold for dermal tissue engineering. About 1-mm-thick honeycomb collagen sheets, prepared from bovine dermal atelocollagen, cross-linked by UV-irradiation, and sterilized by heat, were placed on the proliferating fibroblasts on day 3 of the culture. The cells attached quickly to the collagen scaffold, proliferated inside the honeycomb pores, and formed a structure similar to dermis within 60 days. On day 60, total cellular DNA content of the 3D cultures was 12-fold higher when compared with the 2D control cultures without the scaffold. Measurement of procollagen type I in the media demonstrated a 20-fold increase. Scanning electron microscopy of the 3D cultures showed a well-formed structure similar to dermis and biodegradation of the honeycomb collagen scaffold. Our study proved that honeycomb collagen sheet is a mechanically stable, biocompatible and biodegradable scaffold for dermal tissue engineering, and also potentially useful for other cell-based therapies and tissue engineering applications. | 18,792,951 |
Laurin-Sandrow syndrome: review and redefinition. | We report on a newborn infant with characteristics of Laurin-Sandrow syndrome (LSS). She had hypertelorism, flat nose with grooved collumella, "V" shaped mouth with thin lips, 7 well-recognized and fused digits and 1 additional postaxial bilateral appendix on each hand. The right and left feet had 12 and 11 toes, respectively, the 4 external ones were recognizable, and the rest were fused in a uniform mass but with independent nails. There was also a 2.3 cm-long digitiform appendix in the internal part of both feet. Radiographs showed seven metacarpals and seven metatarsals with similar morphology; both hands lacking thumbs. The four lateral-most toes had regular shaped phalanges and the rest were irregular. The left digitiform appendix had three bones and the right only two. Tibiae were shorter than fibulae. Central Nervous System examination showed an abnormally shaped olivary nucleus, cerebellar cortical heterotopias, gray matter ectopias in both spinal cord and hemispheric white matter, marked ventricular dilatation, and moderate diffuse white matter gliosis. Karyotype was 46XX. A complete necropsy study is presented and all reported cases are reviewed focusing on their phenotypic differences and their nosologic classification. We propose the entity LSS only in cases with symmetric tetrameric polysyndactyly, especially cup-shaped hands and mirror feet, in association with nasal anomalies. | 18,792,985 |
Time-of-day differences in dopamine clearance in the rat medial prefrontal cortex and nucleus accumbens. | Circadian rhythms influence cocaine-seeking behavior in rats, and this behavior may be mediated by variability in the rate of extracellular dopamine clearance across the day:night cycle. We used rotating disk electrode voltammetry to examine dopamine clearance and inhibition of clearance by cocaine in the rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Rats were housed under light:dark conditions (LD, 12 h:12 h) or in constant darkness (DD), the latter given just prior to the day of sacrifice. Tissue was collected at 4-h intervals under LD and DD conditions. Under LD, dopamine clearance in both brain regions was greatest at 4h after lights on. Under DD, there was a blunted but still rhythmic pattern of dopamine clearance across the 24-h cycle. Cocaine-induced inhibition of dopamine clearance in the mPFC was not different across the day:night cycle in rats under LD. Paradoxically, under DD, dopamine clearance in the mPFC was enhanced by cocaine at ZT16, 4 h into the subjective night, and only minimally inhibited at other times. In the NAc, cocaine inhibition of dopamine clearance was lowest at ZT4 under LD, and did not vary under DD. We conclude that dopamine clearance varies both in a diurnal and possibly in a circadian manner in the mPFC, and in a diurnal manner in the NAc. These results indicate that light itself may be used to manipulate molecules implicated in drug addiction. | 18,792,987 |
Peace psychology for a peaceful world. | Although the literature in peace psychology has been growing rapidly, many American psychologists are unaware of how conflict is resolved and peace is conceptualized and achieved. This article reviews the long history and broadening scope of peace psychology and introduces a model of peace that is useful for organizing the literature. The model suggests that peace can be facilitated at four different points of intervention. The authors discuss relationships between positive and negative peace, structural and direct violence, and peacekeeping, peacemaking, and peacebuilding. They advance some challenges for peace psychologists and conclude that peace psychology is a crucial field for grappling with humanity's most pressing problems in the coming decades. | 18,793,041 |
Locomotor experience affects self and emotion. | Two studies investigated the role of locomotor experience on visual proprioception in 8-month-old infants. Visual proprioception refers to the sense of self-motion induced in a static person by patterns of optic flow. A moving room apparatus permitted displacement of an entire enclosure (except for the floor) or the side walls and ceiling. In Study 1, creeping infants and prelocomotor/walker infants showed significantly greater postural compensation and emotional responses to side wall movement than did same-age prelocomotor infants. Study 2 used true random assignment of prelocomotor infants to locomotor-training (via a powered-mobility device) and no-training conditions. Experimental infants showed powerful effects of locomotor training. These results imply that locomotor experience is playing a causal role in the ontogeny of visual proprioception. | 18,793,056 |
The prevalence of perceived discrimination among African American and Caribbean Black youth. | The present study examined ethnic, gender, and age differences in perceived discrimination and the association between perceived discrimination and psychological well-being in a nationally representative sample of Black adolescents. Data are from the National Survey of African Life (NSAL), which includes 810 African American and 360 Caribbean Black youth. Results indicate that the majority of Black youth perceived at least 1 discriminatory incident in the previous year. Adolescents at later stages of development perceived more discrimination than those at earlier stages, and African American and Caribbean Black males perceived more discrimination than their female counterparts. Perceptions of discrimination were positively linked to depressive symptoms and were negatively linked to self-esteem and life satisfaction, regardless of ethnicity. However, Caribbean Black youth appear to be more vulnerable when they perceive high levels of discrimination. | 18,793,063 |
Follow-up of HIV-infected women diagnosed by antenatal screening in Barbados from 1996-2004. | A follow-up study was undertaken to analyze the impact of the early diagnosis of HIV in women by antenatal voluntary counseling and testing (VCT) by way of making a difference to their health status and the social behavior of these women. This is a descriptive study. The study population included all HIV-infected women in this country who were diagnosed to be HIV infected by way of VCT during 1996-2004. Sixty-one (37.4%) never attended the HIV clinic for their care or treatment. The median delay between the time of diagnosis of HIV infection and the time of their presentation to the follow-up clinic was 36 months. Of the 79 women who reported to have been sexually active only 33 had a steady partner; 54 had had one or more casual sex partners at some point in time since their HIV diagnosis. One third never used condoms with their steady partner and one sixth never used condoms with casual partners. Overall, 89 women had one or more repeated pregnancy, mostly from different partners. In conclusion, many of the women diagnosed from antenatal VCT fail to utilize the available health care facilities and continue to engage in risk-taking behaviors. | 18,793,086 |
Assuring the quality of clinical microbiology test results. | The role of microbiology laboratories in the care of patients with suspected or known infections has been described in previous articles in this series of medical microbiology updates. This review addresses the broader role of clinical microbiology laboratories in the quality of care and patient safety. The importance of microbiology laboratories in the care of patients with infectious diseases is obvious, but microbiology laboratories also play an indirect role in patient care that, from a broader perspective, is equally important. | 18,793,099 |
Monogamy and the battle of the sexes. | Sexual conflict has been suggested to be important in the evolution of reproductive traits, with much recent theoretical and empirical evidence emphasizing its role in generating sexually antagonistic coevolution in the context of promiscuous mating. Here we shift attention to the role of sexual conflict in a monogamous mating context. Conflicts can arise, for example, when males are successful in imposing monandry at a cost to female fitness, or when females impose monogyny on males. Conflict over remating can also generate monogamy. For example, when males invest heavily in attempting to impose female monandry, the cost of their investment may prevent them from securing additional mates. We emphasize that sexual conflicts need not always generate sexually antagonistic coevolution, and that it is important to consider whether mating decisions are controlled primarily by males or females. Finally, we briefly discuss approaches to distinguish between conflict and classical modes of sexual selection, as this highlights difficulties associated with deciding whether monogamy is enforced by one sex or the other. We suggest that documenting the current fitness consequences of mate choice and mating patterns provides insight into the relative importance of classic and conflict modes of selection. | 18,793,102 |
Cellular and molecular aspects of rhabdovirus interactions with insect and plant hosts. | The rhabdoviruses form a large family (Rhabdoviridae) whose host ranges include humans, other vertebrates, invertebrates, and plants. There are at least 90 plant-infecting rhabdoviruses, several of which are economically important pathogens of various crops. All definitive plant-infecting and many vertebrate-infecting rhabdoviruses are persistently transmitted by insect vectors, and a few putative plant rhabdoviruses are transmitted by mites. Plant rhabdoviruses replicate in their plant and arthropod hosts, and transmission by vectors is highly specific, with each virus species transmitted by one or a few related insect species, mainly aphids, leafhoppers, or planthoppers. Here, we provide an overview of plant rhabdovirus interactions with their insect hosts and of how these interactions compare with those of vertebrate-infecting viruses and with the Sigma rhabdovirus that infects Drosophila flies. We focus on cellular and molecular aspects of vector/host specificity, transmission barriers, and virus receptors in the vectors. In addition, we briefly discuss recent advances in understanding rhabdovirus-plant interactions. | 18,793,103 |
Off-label use of stents: bare-metal versus drug-eluting stents. | Drug-eluting stents (DES) became the default strategy for percutaneous revascularization due to their improved intermediate-term outcomes when compared with bare-metal stents (BMS) in the pivotal randomized, controlled trials. The excellent results of DES in on-label or US FDA-approved indications led to extrapolation of the results to more complex situations that were excluded from initial pivotal trials; such as off-label indications. Safety concerns began to grow after reports of increased late thrombosis and possibly associated increased death and myocardial infarction with DES, especially in the off-label situations. Recently, however, several important published registries have calmed some of those uncertainties and reassured the cardiology community of the safety and efficacy of DES compared with BMS. There is an overall poorer outcome with off-label use of any stent (BMS or DES) compared with standard or on-label use. This difference in outcome is most likely related to patient or specific coronary lesion characteristics or comorbidities that predispose an individual to adverse outcomes regardless of the stent type used. It is accepted now that DES use does result in a small increased risk of late thrombosis, but that risk is offset by a significant reduction in restenosis. Overall, the current data suggest that the use of DES in most lesion subsets is at least as safe as and clearly more efficacious than use of BMS in similar situations. | 18,793,112 |
Cardiovascular disease prevention tailored for women. | Cardiovascular disease prevention is most effective when it is tailored for individual risk, since the benefit of any preventive intervention should outweigh its potential side effects and costs. Recognition of important gender differences in cardiovascular disease prevention has led to the formulation of specific guidelines for women. Based on a rigorous review of evidence, the 2007 American Heart Association guidelines for cardiovascular disease prevention in women differ little from the guidelines for men. The main difference pertains to the role of aspirin in primary cardiovascular prevention and to the appreciation of diabetes as a more detrimental risk factor in women than men. These guidelines provide a valuable framework to select the optimal preventive strategy for women of all ages, based on individual risk stratification, potentially supplemented with appropriate use of novel imaging modalities. Observational data continue to identify discrepancies between women and men, which target areas of need for future research. | 18,793,115 |
Modelling the dynamics of signalling pathways. | In the present chapter we discuss methodologies for the modelling, calibration and validation of cellular signalling pathway dynamics. The discussion begins with the typical range of techniques for modelling that might be employed to go from the chemical kinetics to a mathematical model of biochemical pathways. In particular, we consider the decision-making processes involved in selecting the right mechanism and level of detail of representation of the biochemical interactions. These include the choice between (i) deterministic and stochastic chemical kinetics representations, (ii) discrete and continuous time models and (iii) representing continuous and discrete state processes. We then discuss the task of calibrating the models using information available in web-based databases. For situations in which the data are not available from existing sources we discuss model calibration based upon measured data and system identification methods. Such methods, together with mathematical modelling databases and computational tools, are often available in standard packages. We therefore make explicit mention of a range of popular and useful sites. As an example of the whole modelling and calibration process, we discuss a study of the cross-talk between the IL-1 (interleukin-1)-stimulated NF-kappaB (nuclear factor kappaB) pathway and the TGF-beta (transforming growth factor beta)-stimulated Smad2 pathway. | 18,793,120 |
Parameter estimation and optimal experimental design. | Mathematical models are central in systems biology and provide new ways to understand the function of biological systems, helping in the generation of novel and testable hypotheses, and supporting a rational framework for possible ways of intervention, like in e.g. genetic engineering, drug development or treatment of diseases. Since the amount and quality of experimental 'omics' data continue to increase rapidly, there is great need for methods for proper model building which can handle this complexity. In the present chapter we review two key steps of the model building process, namely parameter estimation (model calibration) and optimal experimental design. Parameter estimation aims to find the unknown parameters of the model which give the best fit to a set of experimental data. Optimal experimental design aims to devise the dynamic experiments which provide the maximum information content for subsequent non-linear model identification, estimation and/or discrimination. We place emphasis on the need for robust global optimization methods for proper solution of these problems, and we present a motivating example considering a cell signalling model. | 18,793,133 |
Much to know about proteolysis: intricate proteolytic machineries compromise essential cellular functions. | Proteolysis has traditionally been considered as a radical way to terminate the function of a protein. However, protein destruction also is the starting point for many processes as they can only occur when the way has been cleared for the action of other proteins. Protein destruction can occur virtually in all compartments and organelles of the cell, associated with cell membranes or large protein complexes, it determines subcellular partitioning, association with positive or negative regulators which conditions the action of many critical cellular factors. The third intracellular proteolysis meeting held by the University La Laguna, Canary Islands, Spain, included speakers working with some of the most important proteolytic systems present in higher eukaryotes, such as the UPS (ubiquitin-proteasome system) and autophagy. Owing to the fact that these pathways directly or indirectly regulate many cell functions, this meeting brought together an audience with a wide range of research interests, including genetic, cell biological, biochemical and structural aspects of protein degradation. Some of these topics inspired interesting discussions and a significant number of these are developed in the issues reviewed herein. | 18,793,136 |
Chaperone-driven proteasome assembly. | Assembly of the 34-subunit, 2.5 MDa 26S proteasome is a carefully choreographed intricate process. It starts with formation of a seven-membered alpha-ring that serves as a template for assembly of the complementary beta-ring-forming 'half-proteasomes'. Dimerization results in a latent 20S core particle that can serve further as a platform for 19S regulatory particle attachment and formation of the biologically active 26S proteasome for ubiquitin-dependent proteolysis. Both general and dedicated proteasome assembly chaperones regulate the efficiency and outcome of critical steps in proteasome biogenesis, and in complex association. | 18,793,141 |
Is there an alternative to the proteasome in cytosolic protein degradation? | While it is clear that the proteasome is the major player in degradative proteolysis in the nucleus and cytosol, there is a lack of complete agreement on whether there are alternative proteolytic pathways or activities responsible for a significant degradation of cytosolic/nuclear substrates. Particularly relevant is the case of the aminopeptidase TPPII (tripeptidyl peptidase II), which has been suggested to be able to perform some of the proteasome functions. However, the current evidence seems to support only a limited role for these cytosolic alternatives. On the other hand, there is evidence of an alternative, autophagy, a pathway involving the delivery of cytosolic substrates to the lysosome for degradation. | 18,793,147 |
Lipases in the pancreatic beta-cell: implications for insulin secretion. | Lipids have been implicated in beta-cell stimulus-secretion coupling. In such a role, lipases in beta-cells would be required to generate lipid coupling factors. We have shown previously that glucose stimulates lipolysis in rodent islets. In addition, lipolysis and diacylglycerol lipase activity in islets are abolished by orlistat, an irreversible lipase inhibitor with a broad specificity for substrates. Moreover, orlistat dose-dependently inhibits glucose- and forskolin-stimulated insulin secretion, while leaving glucose oxidation and the rise in the ATP/ADP ratio intact. In an effort to identify beta-cell lipase(s), we found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent beta-cells. To resolve the role of this lipase, we have created global and beta-cell-specific knockout mice. Although our line of global HSL-knockout mice is moderately glucose-intolerant owing to reduced peripheral insulin sensitivity and exhibits normal islet metabolism and insulin secretion, other HSL-knockout lines have displayed impaired insulin secretion under certain conditions. In contrast, beta-cell-specific HSL-knockout mice, which are less prone to genetic redundancy, are hyperglycaemic, presumably caused by a perturbation of first-phase insulin secretion. Thus studies by us and others demonstrate that lipases, such as HSL, play a regulatory role in beta-cell stimulus-secretion coupling. | 18,793,156 |
Significance of protein crowding, order and mobility for photosynthetic membrane functions. | Natural photosynthesis requires diffusion-based processes either for the functional communication of protein complexes or for the adaptation, maintenance and biogenesis of the photosynthetic apparatus. A conceptual problem with lateral diffusion in photosynthetic membranes arises from the fact that these membranes are densely packed with membrane integral protein complexes (molecular crowding). Theoretical analysis of PQ (plastoquinone) and protein diffusion in higher plant grana thylakoids reveal very inefficient lateral diffusion. In contrast, measurement of protein mobility in grana membranes shows that a fraction of protein complexes can move surprisingly fast. It is postulated that organization of protein complexes in supercomplexes and large-scale ordering of Photosystem II and light-harvesting complex II could be strategies for the optimization of diffusion in crowded thylakoid membranes. | 18,793,171 |
The role of multihaem cytochromes in the respiration of nitrite in Escherichia coli and Fe(III) in Shewanella oneidensis. | The periplasmic nitrite reductase system from Escherichia coli and the extracellular Fe(III) reductase system from Shewanella oneidensis contain multihaem c-type cytochromes as electron carriers and terminal reductases. The position and orientation of the haem cofactors in multihaem cytochromes from different bacteria often show significant conservation despite different arrangements of the polypeptide chain. We propose that the decahaem cytochromes of the iron reductase system MtrA, MtrC and OmcA comprise pentahaem 'modules' similar to the electron donor protein, NrfB, from E. coli. To demonstrate this, we have isolated and characterized the N-terminal pentahaem module of MtrA by preparing a truncated form containing five covalently attached haems. UV-visible spectroscopy indicated that all five haems were low-spin, consistent with the presence of bis-His ligand co-ordination as found in full-length MtrA. | 18,793,179 |
Wine yeasts for the future. | International competition within the wine market, consumer demands for newer styles of wines and increasing concerns about the environmental sustainability of wine production are providing new challenges for innovation in wine fermentation. Within the total production chain, the alcoholic fermentation of grape juice by yeasts is a key process where winemakers can creatively engineer wine character and value through better yeast management and, thereby, strategically tailor wines to a changing market. This review considers the importance of yeast ecology and yeast metabolic reactions in determining wine quality, and then discusses new directions for exploiting yeasts in wine fermentation. It covers criteria for selecting and developing new commercial strains, the possibilities of using yeasts other than those in the genus of Saccharomyces, the prospects for mixed culture fermentations and explores the possibilities for high cell density, continuous fermentations. | 18,793,201 |
Mexiletine for refractory chronic daily headache: a report of nine cases. | To describe the use of mexiletine in the treatment of chronic daily headache in a refractory headache population. Intravenous lidocaine is a novel treatment for chronic daily headache with medication overuse and SUNCT syndrome. Mexiletine is a similar but orally active anti-arrhythmic that has been demonstrated to be an effective analgesic in various types of neuropathic pain. We looked at mexiletine as a preventative treatment for headache in refractory patients. We reviewed the medical records of all patients with an order for mexiletine. For each patient, we determined diagnosis, presence of medication overuse on initial evaluation, pain scores, and if the patient received intravenous lidocaine before starting the medication. We then contacted patients by phone to confirm their dose, to review side effects and current pain scores, and to obtain a global impression of effectiveness. We identified 9 patients with a chronic daily headache, including chronic migraine or new daily persistent headache, with significant clinical improvement while using mexiletine as a headache preventative. Each patient had failed to respond to multiple preventative and acute treatments. Seven of the 9 rated mexiletine "much more effective" and 2 "more effective" than previous preventative headache medications. The daily dose ranged from 600 mg/day to 1500 mg/day. Side effects were common and occurred in 7 patients. The majority of patients with an order for mexiletine did not respond to treatment or had intolerable side effects. The preliminary study suggests mexiletine is a useful preventative treatment for some patients with chronic daily headache, including refractory patients with medication overuse or those who have failed multiple preventatives in the past. | 18,793,209 |
Regulation of macrophage nitric oxide production by the protein tyrosine phosphatase Src homology 2 domain phosphotyrosine phosphatase 1 (SHP-1). | Nitric oxide (NO) is a potent molecule involved in the cytotoxic effects mediated by macrophages (MØ) against microorganisms. We previously reported that Src homology 2 domain phosphotyrosine phosphatase 1 (SHP-1)-deficient cells generate a greater amount of NO than wild-type cells in response to interferon-gamma (IFN-gamma). We also reported that the Leishmania-induced MØ SHP-1 activity is needed for the survival of the parasite within phagocytes through the attenuation of NO-dependent and NO-independent mechanisms. In the present study, we investigated the role of SHP-1 in regulating key signalling molecules important in MØ NO generation. Janus tyrosine kinase 2 (JAK2), mitogen-activated extracellular signal-regulated protein kinase kinase (MEK), extracellular signal-regulated kinases 1 and 2 (Erk1/Erk2) mitogen-activated protein kinases, p38 and stress-activated mitogen-activated protein kinases/c-Jun NH(2)-terminal kinase (SAPK/JNK) were examined in immortalized bone marrow-derived MØ (BMDM) from both SHP-1-deficient motheaten mice (me-3) and their respective littermates (LM-1). The results indicated that Erk1/Erk2 and SAPK/JNK are the main kinases regulated by SHP-1 because the absence of SHP-1 caused an increase in their phosphorylation. Moreover, only Apigenin, the specific inhibitor of Erk1/Erk2, was able to block IFN-gamma-induced inducible nitric oxide synthase (iNOS) transcription and translation in me-3 cells. Transcription factor analyses revealed that in the absence of SHP-1, activator protein-1 (AP-1) was activated. The activation of AP-1, and not nuclear factor-kappaB (NF-kappaB) or signal transducer and activator of transcription-1 alpha (STAT-1 alpha), may explain the enhanced NO generation in SHP-1-deficient cells. These observations emphasize the involvement of the MAPKs Erk1/Erk2 and SAPK/JNK in NO generation via AP-1 activation. Collectively, our findings suggest that SHP-1 plays a pivotal role in the negative regulation of signalling events leading to iNOS expression and NO generation. Furthermore, our observations underline the importance of SHP-1-mediated negative regulation in maintaining NO homeostasis and thus preventing the abnormal generation of NO that can be detrimental to the host. | 18,793,215 |
A ceramide-1-phosphate analogue, PCERA-1, simultaneously suppresses tumour necrosis factor-alpha and induces interleukin-10 production in activated macrophages. | Tight regulation of the production of the key pro-inflammatory cytokine tumour necrosis factor-alpha (TNF-alpha) is essential for the prevention of chronic inflammatory diseases. In vivo administration of a synthetic phospholipid, named hereafter phospho-ceramide analogue-1 (PCERA-1), was previously found to suppress lipopolysaccharide (LPS)-induced TNF-alpha blood levels. We therefore investigated the in vitro anti-inflammatory effects of PCERA-1. Here, we show that extracellular PCERA-1 potently suppresses production of the pro-inflammatory cytokine TNF-alpha in RAW264.7 macrophages, and in addition, independently and reciprocally regulates the production of the anti-inflammatory cytokine interleukin-10 (IL-10). Specificity is demonstrated by the inability of the phospholipids ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) to perform these activities. Similar TNF-alpha suppression and IL-10 induction by PCERA-1 were observed in macrophages when activated by Toll-like receptor 4 (TLR4), TLR2 and TLR7 agonists. Regulation of cytokine production is demonstrated at the mRNA and protein levels. Finally, we show that, while PCERA-1 does not block activation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases by LPS, it elevates the intracellular cAMP level. In conclusion, the anti-inflammatory activity of PCERA-1 seems to be mediated by a cell membrane receptor, upstream of cAMP production, and eventually TNF-alpha suppression and IL-10 induction. Thus, identification of the PCERA-1 receptor may provide new pharmacological means to block inflammation. | 18,793,216 |
Thoracoscopic pulmonary vein isolation after previous percutaneous atrial septal defect closure. | Atrial fibrillation (AF) is the main cause of morbidity among patients over 40 years of age with atrial septal defect (ASD). The closure of ASD in older patients does not decrease the occurrence of AF.(1-3) However, percutaneous ASD closure devices eliminate the possibility of a transseptal approach for future catheter-based procedures such as AF ablation. Epicardial pulmonary vein isolation with a bipolar radiofrequency clamp has been shown to be a safe and effective practice in surgical treatment of AF.(4,5) More recently, this technology has been utilized in a minimally invasive approach through bilateral thoracotomies. We present the case of a thoracoscopic-assisted pulmonary vein isolation on a patient with an atrial septal occlusion device. | 18,793,225 |
Occurrence of enteric viruses in shellfish and relation to climatic-environmental factors. | To investigate the presence of enteric viruses [hepatitis A (HAV) and norovirus (NoV)] in shellfish harvested from the deltaic area of the Po river in relation to environmental factors. Fortnightly sampling of shellfish was carried out in two lagoon areas (category B production areas) and one sea area (category A). Environmental parameters in the lagoon and hydrometric level of the tributary river were monitored throughout the sampling period. Samples (n = 120) were analysed for bacterial (E. coli and Salmonella) and viral (HAV and NoV) contamination; samples from category B areas were analysed before and after purification treatment. All the samples were negative for HAV whereas 10 samples (8.3%), all harvested in the lagoon areas, were positive for NoV. Sequencing identified the strains as genotypes II.4 and II.b. None of the samples was found to be contaminated after depuration. The monitoring showed a low frequency of NoV presence; viral contamination, detected exclusively in shellfish collected from the deltaic area (category B), could be influenced by the flow of the tributary river. The data collected are useful for the design of targeted prevention strategies and for the modulation of control plans after meteorological events. | 18,793,257 |
Plant pharming of a full-sized, tumour-targeting antibody using different expression strategies. | The aims of this work were to obtain a human antibody against the tumour-associated antigen tenascin-C (TNC) and to compare the yield and quality of plant-produced antibody in either stable transgenics or using a transient expression system. To this end, the characterization of a full-sized human immunoglobulin G (IgG) [monoclonal antibody H10 (mAb H10)], derived from a selected single-chain variable fragment (scFv) and produced in plants, is presented. The human mAb gene was engineered for plant expression, and Nicotiana tabacum transgenic lines expressing both heavy (HC) and light (LC) chain were obtained and evaluated for antibody expression levels, in vivo assembly and functionality. Affinity-purified H10 from transgenics (yield, 0.6-1.1 mg/kg fresh weight) revealed that more than 90% of HC was specifically degraded, leading to the formation of functional antigen-binding fragments (Fab). Consequently, H10 was transiently expressed in Nicotiana benthamiana plants through an Agrobacterium-mediated gene-transfer system. Moreover, the use of the p19 silencing suppressor gene from artichoke mottled crinkle virus raised antibody expression levels by an order of magnitude (yields of purified H10, 50-100 mg/kg fresh weight). Approximately 75% of purified protein consisted of full-sized antibody functionally binding to TNC (K(D) = 14 nm), and immunohistochemical analysis on tumour tissues revealed specific accumulation around tumour blood vessels. The data indicate that the purification yields of mAb H10, using a transient expression system boosted by the p19 silencing suppressor, are exceptionally high when compared with the results reported previously, providing a technique for the over-expression of anticancer mAbs by a rapid, cost-effective, molecular farming approach. | 18,793,269 |
Development and growth in very preterm infants in relation to NIDCAP in a Dutch NICU: two years of follow-up. | To study development and growth in relation to newborn individualized developmental and assessment program (NIDCAP) for infants born with a gestational age of less than 30 weeks. Developmental outcome of surviving infants, 25 in the NIDCAP group and 24 in the conventional care group, in a prospective phase-lag cohort study performed in a Dutch level III neonatal intensive care unit (NICU) was compared. Main outcome measure was the Bayley scales of infant development-II (BSID-II) at 24 months corrected age. Secondary outcomes were neurobehavioral and developmental outcome and growth at term, 6, 12 and 24 months. Accounting for group differences and known outcome predictors no significant differences were seen between both care groups in BSID-II at 24 months. At term age NIDCAP infants scored statistically significant lower on neurobehavioral competence; motor system (median [IQR] 4.8 [2.9-5.0] vs. 5.2 [4.3-5.7], p = 0.021) and autonomic stability (median [IQR] 5.7 [4.8-6.7] vs. 7.0 [6.0-7.7], p = 0.001). No differences were seen in other developmental outcomes. After adjustment for background differences, growth parameters were comparable between groups during the first 24 months of life. At present, the strength of conclusions to be drawn about the effect of NIDCAP on developmental outcome or growth at 24 months of age is restricted. Further studies employing standardized assessment approaches including choice of measurement instruments and time points are needed. | 18,793,293 |
Complex seasonal patterns of primary producers at the land-sea interface. | Seasonal fluctuations of plant biomass and photosynthesis are key features of the Earth system because they drive variability of atmospheric CO(2), water and nutrient cycling, and food supply to consumers. There is no inventory of phytoplankton seasonal cycles in nearshore coastal ecosystems where forcings from ocean, land and atmosphere intersect. We compiled time series of phytoplankton biomass (chlorophyll a) from 114 estuaries, lagoons, inland seas, bays and shallow coastal waters around the world, and searched for seasonal patterns as common timing and amplitude of monthly variability. The data revealed a broad continuum of seasonal patterns, with large variability across and within ecosystems. This contrasts with annual cycles of terrestrial and oceanic primary producers for which seasonal fluctuations are recurrent and synchronous over large geographic regions. This finding bears on two fundamental ecological questions: (1) how do estuarine and coastal consumers adapt to an irregular and unpredictable food supply, and (2) how can we extract signals of climate change from phytoplankton observations in coastal ecosystems where local-scale processes can mask responses to changing climate? | 18,793,308 |
Diversity of deep-water cetaceans in relation to temperature: implications for ocean warming. | Understanding the effects of natural environmental variation on biodiversity can help predict response to future anthropogenic change. Here we analyse a large, long-term data set of sightings of deep-water cetaceans from the Atlantic, Pacific and Indian Oceans. Seasonal and geographic changes in the diversity of these genera are well predicted by a convex function of sea-surface temperature peaking at c. 21 degrees C. Thus, diversity is highest at intermediate latitudes - an emerging general pattern for the pelagic ocean. When applied to a range of Intergovernmental Panel on Climate Change global change scenarios, the predicted response is a decline of cetacean diversity across the tropics and increases at higher latitudes. This suggests that deep-water oceanic communities that dominate > 60% of the planet's surface may reorganize in response to ocean warming, with low-latitude losses of diversity and resilience. | 18,793,309 |
Yeast Yak1 kinase, a bridge between PKA and stress-responsive transcription factors, Hsf1 and Msn2/Msn4. | Hsf1 and Msn2/Msn4 transcription factors in Saccharomyces cerevisiae play important roles in cellular homeostasis by activating gene expression in response to multiple stresses including heat shock, oxidative stress and nutrient starvation. Although it has been known that nuclear import of Msn2 is inhibited by PKA-dependent phosphorylation, the mechanism for PKA-dependent regulation of Hsf1 is not well understood. Here we demonstrate that Yak1 kinase, which is under the negative control of PKA, activates both Hsf1 and Msn2 by phosphorylation when PKA activity is lowered by glucose depletion or by overexpressing Pde2 that hydrolyses cAMP. We show that Yak1 directly phosphorylates Hsf1 in vitro, leading to the increase in DNA binding activity of Hsf1. We also demonstrate that Yak1 phosphorylates Msn2 in vitro, but does not affect DNA binding activity of Msn2 or nuclear localization of Msn2 upon glucose depletion. These results suggest a central role for Yak1 in mediating PKA-dependent inhibition of Hsf1 and Msn2/Msn4. | 18,793,336 |
PDCD4 gene silencing in gliomas is associated with 5'CpG island methylation and unfavourable prognosis. | Programmed cell death 4 (PDCD4) is a newly described tumour suppressor that inhibits oncogenesis by suppressing gene transcription and translation. Loss of PDCD4 expression has been found in several types of human cancers including the most common cancer of the brain, the gliomas. However, the molecular mechanisms responsible for PDCD4 gene silencing in tumour cells remain unclear. Here we report the identification of 5'CpG island methylation as the predominant cause of PDCD4 mRNA silencing in gliomas. The methylation of the PDCD4 5'CpG island was found in 47% (14/30) of glioma tissues, which was significantly associated with the loss of PDCD4 mRNA expression (gamma=-1.000, P < 0.0001). Blocking methylation in glioma cells using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the PDCD4 gene expression, inhibited their proliferation and reduced their colony formation capacity. Longitudinal studies of a cohort of 84 patients with gliomas revealed that poor prognosis of patients with high-grade tumours were significantly associated with loss of PDCD4 expression. Thus, our current study suggests, for the first time, that PDCD4 5'CpG island methylation blocks PDCD4 expression at mRNA levels in gliomas. These results also indicate that PDCD4 reactivation might be an effective new strategy for the treatment of gliomas. | 18,793,349 |
Immunohistochemical localization of Toll-like receptors 1-10 in periodontitis. | In periodontitis, bacteria and pathogen-associated molecular patterns are sensed by Toll-like receptors (TLRs), which initiate intracellular signaling cascades that may lead to host inflammation. In this study, the expression and distribution of TLRs (TLR-1 to TLR-10) were immunohistochemically detected in gingival epithelium and connective tissue. Immunohistochemistry was used for the localization of TLRs in gingival tissue samples from 10 patients with chronic periodontitis and 10 healthy controls; these samples were obtained during routine periodontal flap operations and during extraction operations performed for retained wisdom teeth, respectively. For the evaluation, epithelial layers were stratified to basal, spinous, and superficial layers, and the percentages of TLR-positive cells were determined. Both healthy and periodontitis gingival tissues expressed all TLRs except TLR-10. In patients with periodontitis, epithelial cells showed increased TLR expression towards the basal layer. Healthy controls showed more variable cellular TLR expression and distribution between the layers of epithelium. In the connective tissue, consistently higher TLR expression was found within the periodontitis group compared to the healthy group. For the first time, the cellular expression and distribution of TLR-1 to TLR-10 have been studied in periodontitis, indicating that TLR-1 to TLR-9 are differentially expressed both in connective tissue and epithelial layers. Except for TLR-7 and TLR-8, all the other TLRs showed statistically significant differences between patients with periodontitis and healthy controls, suggesting their involvement in the pathogenesis of periodontitis. | 18,793,367 |
Ecology and ethnoecology of dusky grouper [garoupa, Epinephelus marginatus (Lowe, 1834)] along the coast of Brazil. | Dusky grouper (garoupa, Epinephelus marginatus) is an important catch for several artisanal small-scale fisheries along the Brazilian coast. It is a sedentary, monandric, and late maturing protogynous species, which makes it vulnerable to overharvesting even though it is mainly caught through hook and line or spear fishing through free diving. Lack of information on the ecology and biology of this species in Brazil is astonishing. Much of the information found in the literature concerns Mediterranean dusky groupers. Studies compiling local knowledge (ethnoecology) about fish species complement biological data, and have been fundamental for effective fisheries management. In this study, our objectives are to obtain data about dusky grouper through fish catches and analysis of stomach contents and gonad maturation (macroscopic analyses), along with interviews from fishermen from six small-scales communities from the southern (Pântano do Sul, Florianópolis, Santa Catarina State) to the northern Brazilian coast (Porto Sauípe, Bahia State). We conclude that precautionary approaches and 'data-less' management approaches are needed in the coast of Brazil. Research on this species and on the potential of aquaculture for its cultivation, are urgent, due to the apparent vulnerability and decrease of dusky grouper along the coast of Brazil. | 18,793,394 |
Design and methods for a randomized clinical trial treating comorbid obesity and major depressive disorder. | Obesity is often comorbid with depression and individuals with this comorbidity fare worse in behavioral weight loss treatment. Treating depression directly prior to behavioral weight loss treatment might bolster weight loss outcomes in this population, but this has not yet been tested in a randomized clinical trial. This randomized clinical trial will examine whether behavior therapy for depression administered prior to standard weight loss treatment produces greater weight loss than standard weight loss treatment alone. Obese women with major depressive disorder (N = 174) will be recruited from primary care clinics and the community and randomly assigned to one of the two treatment conditions. Treatment will last 2 years, and will include a 6-month intensive treatment phase followed by an 18-month maintenance phase. Follow-up assessment will occur at 6-months and 1- and 2 years following randomization. The primary outcome is weight loss. The study was designed to provide 90% power for detecting a weight change difference between conditions of 3.1 kg (standard deviation of 5.5 kg) at 1-year assuming a 25% rate of loss to follow-up. Secondary outcomes include depression, physical activity, dietary intake, psychosocial variables and cardiovascular risk factors. Potential mediators (e.g., adherence, depression, physical activity and caloric intake) of the intervention effect on weight change will also be examined. Treating depression before administering intensive health behavior interventions could potentially boost the impact on both mental and physical health outcomes. NCT00572520. | 18,793,398 |
Ultrasonographically detected gallbladder polyps: a reason for concern? A seven-year follow-up study. | The management of coincidental detected gallbladder polyps (GP) is still nebulous. There are few published data regarding their long-term growth. Objective of the present study was to investigate the prevalence and growth of gallbladder polyps in a survey of unselected subjects from the general population of a complete rural community. A total of 2,415 subjects (1,261 women; 1,154 men) underwent ultrasound examination of the gallbladder, in November 1996 as part of a prospective study. Subjects in whom GP were detected at the initial survey underwent follow-up ultrasound examinations after 30 and 84 months. At the initial survey gallbladder polyps were detected in 34 subjects (1.4%; females: 1.1%, range 14 to 74 years; males: 1.7%, range 19 to 63 years). Median diameter was 5 +/- 2.1 mm (range 2 to 10 mm) at the initial survey, 5 mm +/- 2.8 mm (range 2 to 12 mm) at 30 months and 4 +/- 2.3 mm (range 2 to 9 mm) at 84 months. At the time of first follow-up no change in diameter was found in 81.0% (n = 17), reduction in diameter in 4.8% (n = 1) and increase in diameter in 14.3% (n = 3). At the time of second follow-up no increase in polyp diameter was found in 76.9% (n = 10) and reduction in diameter in 7.7% (n = 1). No evidence of malignant disease of the gallbladder was found. Over a period of seven years little change was measured in the diameter of gallbladder polyps. There was no evidence of malignant disease of the gallbladder in any subject. | 18,793,401 |
Should countries implementing an artemisinin-based combination malaria treatment policy also introduce rapid diagnostic tests? | Within the context of increasing antimalarial costs and or decreasing malaria transmission, the importance of limiting antimalarial treatment to only those confirmed as having malaria parasites becomes paramount. This motivates for this assessment of the cost-effectiveness of routine use of rapid diagnostic tests (RDTs) as an integral part of deploying artemisinin-based combination therapies (ACTs). The costs and cost-effectiveness of using RDTs to limit the use of ACTs to those who actually have Plasmodium falciparum parasitaemia in two districts in southern Mozambique were assessed. To evaluate the potential impact of introducing definitive diagnosis using RDTs (costing $0.95), five scenarios were considered, assuming that the use of definitive diagnosis would find that between 25% and 75% of the clinically diagnosed malaria patients are confirmed to be parasitaemic. The base analysis compared two ACTs, artesunate plus sulfadoxine/pyrimethamine (AS+SP) costing $1.77 per adult treatment and artemether-lumefantrine (AL) costing $2.40 per adult treatment, as well as the option of restricting RDT use to only those older than six years. Sensitivity analyses considered lower cost ACTs and RDTs and different population age distributions. Compared to treating patients on the basis of clinical diagnosis, the use of RDTs in all clinically diagnosed malaria cases results in cost savings only when 29% and 52% or less of all suspected malaria cases test positive for malaria and are treated with AS+SP and AL, respectively. These cut-off points increase to 41.5% (for AS+SP) and to 74% (for AL) when the use of RDTs is restricted to only those older than six years of age. When 25% of clinically diagnosed patients are RDT positive and treated using AL, there are cost savings per malaria positive patient treated of up to $2.12. When more than 29% of clinically diagnosed cases are malaria test positive, the incremental cost per malaria positive patient treated is less than US$1. When relatively less expensive ACTs are introduced (e.g. current WHO preferential price for AL of $1.44 per adult treatment), the RDT price to the healthcare provider should be $0.65 or lower for RDTs to be cost saving in populations with between 30 and 52% of clinically diagnosed malaria cases being malaria test positive. While the use of RDTs in all suspected cases has been shown to be cost-saving when parasite prevalence among clinically diagnosed malaria cases is low to moderate, findings show that targeting RDTs at the group older than six years and treating children less than six years on the basis of clinical diagnosis is even more cost-saving. In semi-immune populations, young children carry the highest risk of severe malaria and many healthcare providers would find it harder to deny antimalarials to those who test negative in this age group. | 18,793,410 |
Serum anticholinergic activity and cerebral cholinergic dysfunction: an EEG study in frail elderly with and without delirium. | Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence. 61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained. 15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 +/- 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Delirium-associated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels. In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis. | 18,793,418 |
Allele distribution and genetic diversity of VNTR loci in Salmonella enterica serotype Enteritidis isolates from different sources. | Salmonella enterica serotype Enteritidis (S. Enteritidis) is a zoonotic pathogen, which can be found in many sources including animals and the environment. However, little is known about the molecular relatedness among S. Enteritidis isolates from different sources. We have applied multiple-locus variable number tandem repeat analysis (MLVA) to study the genetic diversity of S. Enteritidis isolates from human and non-human sources. We identified 38 unique MLVA types using nine VNTR loci markers for discrimination between 145 S. Enteritidis isolates from different sources including humans (n = 41), chickens (n = 45), and eggs (n = 40). There were 20 distinct MLVA types identified from human isolates, 17 distinct MLVA types from chicken isolates, and 5 from egg isolates. We compared allele distribution and frequency for each VNTR marker and measured allelic polymorphism within each VNTR locus of S. Enteritidis isolates from the sources using Nei's diversity index (D). Differences in allele distribution and frequency were detected in most loci of study isolates. Different genetic diversity for certain loci was identified in isolates from different sources. The average of genetic diversity (D) was lower in egg isolates (0.16) compared to human (0.41) and chicken (0.30). However, for loci SE3, SE7, and SE9, human isolates showed significantly higher diversity than both chicken and egg isolates. Whereas for loci SE5 and SE10, chicken isolates had significantly higher diversity than both human and egg isolates. Minimum-spanning tree (MST) comprised one major cluster, a minor cluster, and four clonal expansions. MLVA application enabled a cluster analysis by the MST of the S. Enteritidis isolates by sources, which allows a great insight into the genetic relatedness and the possible flow of these organisms between different reservoirs and humans. Differences in allele distribution and genetic diversity of VNTR loci in S. Enteritidis isolates from different sources were found. Polymorphism in most of the VNTR loci was more frequent among human S. Enteritidis isolates than isolates from chickens or eggs. Therefore, VNTR profiles of S. Enteritidis isolates from a specific source should be further evaluated as potential markers in epidemiologic investigations to trace S. Enteritidis to their probable source. | 18,793,420 |
Targeted physiotherapy for patellofemoral joint osteoarthritis: a protocol for a randomised, single-blind controlled trial. | The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA. 90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction. This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce the personal and societal burden of this increasing public health problem. Australia New Zealand Clinical Trials Registry ACTRN12608000288325. | 18,793,446 |
Social capital, economics, and health: new evidence. | In introducing this Special Issue on Social Capital and Health, this article tracks the popularization of the term and sheds light on the controversy surrounding the term and its definitions. It sets out four mechanisms that link social capital with health: making information available to community members, impacting social norms, enhancing the health care services and their accessibility in a community, and offering psychosocial support networks. Approaches to the measurement of social capital include the Social Capital Community Benchmark Survey (SCCBS) developed by Robert Putnam, and the Petris Social Capital Index (PSCI), which looks at community voluntary organizations using public data available for the entire United States. The article defines community social capital (CSC) as the extent and density of trust, cooperation, and associational links and activity within a given population. Four articles on CSC are introduced in two categories: those that address behaviors -- particularly utilization of health services and use of tobacco, alcohol, and drugs; and those that look at links between social capital and physical or mental health. Policy implications include: funding and/or tax subsidies that would support the creation of social capital; laws and regulations; and generation of enthusiasm among communities and leaders to develop social capital. The next steps in the research programme are to continue testing the mechanisms; to look for natural experiments; and to find better public policies to foster social capital. | 18,793,475 |
Social capital and the social formation of health-related preferences and behaviours. | Social capital appears to be an important determinant of health production and health utilization and demand. However, there is limited evidence on the mechanisms underlying this relationship. In this article we draw on the evidence and insights reported in this special issue along with findings from the economic and other social science literature to develop a discussion on the explanations of the likely (behavioural) mechanisms that underpin the connection between social capital and health. An important and under-explored influence mediating the relationship between social capital and health (behaviour) lies in the individuals face in determining their life-styles and in using health care. In particular, we point to the interdependence in how individuals in the first place perceive and also respond to common health risks and the role of cultural transmission and social identity as conveyors of this process. We argue that an emerging body of evidence suggesting that interdependent preferences influence health calls for further re-formulation of traditional demand for and production of health models. Additionally, methodological problems are highlighted and possible ways forward suggested. | 18,793,480 |
Effect of dental finishing instruments on the surface roughness of composite resins as elucidated by atomic force microscopy. | Roughness increases significantly after finishing procedures. The aim of this study was to assess by the atomic force microscope (AFM) the effect of finishing instruments on the surface roughness of composite resins. A nanofiller composite resin (Filtek Supreme, 3M-F) and a microhybrid composite resin (Point 4, Kerr-P) were selected. The finishing procedures were done with a 30-blade carbide bur (C) and a 30-microm finishing diamond bur (D). Standardized specimens were produced and divided into six experimental groups (n=4) according to (1) composite resin, (2) absence of finishing (Mylar matrix-M), and (3) finishing instrument (FM, PM, FC, FD, PC, PD). The mean surface roughness was evaluated by AFM in the contact mode. FM and PM groups were assessed statistically by the Student's T test, and FC, FD, PC, PD groups were submitted to variance analysis (ANOVA), both at 5% significance. The mean surface roughness values, in nanometers, were FM, 23.63 (b); FC, 283.88 (c); FD, 510.55 (d); PM, 12.52 (a); PC, 343.98 (c); PD, 531.64 (d). Microhybrid composite displayed less roughness than nanofiller composite in the absence of finishing procedures. The 30-blade carbide bur produced less roughness compared to the extra fine diamond bur. | 18,793,482 |
A new evaluation tool to obtain practice-based evidence of worksite health promotion programs. | The Centers for Disease Control and Prevention developed the Swift Worksite Assessment and Translation (SWAT) evaluation method to identify promising practices in worksite health promotion programs. The new method complements research studies and evaluation studies of evidence-based practices that promote healthy weight in working adults. We used nationally recognized program evaluation standards of utility, feasibility, accuracy, and propriety as the foundation for our 5-step method: 1) site identification and selection, 2) site visit, 3) post-visit evaluation of promising practices, 4) evaluation capacity building, and 5) translation and dissemination. An independent, outside evaluation team conducted process and summative evaluations of SWAT to determine its efficacy in providing accurate, useful information and its compliance with evaluation standards. The SWAT evaluation approach is feasible in small and medium-sized workplace settings. The independent evaluation team judged SWAT favorably as an evaluation method, noting among its strengths its systematic and detailed procedures and service orientation. Experts in worksite health promotion evaluation concluded that the data obtained by using this evaluation method were sufficient to allow them to make judgments about promising practices. SWAT is a useful, business-friendly approach to systematic, yet rapid, evaluation that comports with program evaluation standards. The method provides a new tool to obtain practice-based evidence of worksite health promotion programs that help prevent obesity and, more broadly, may advance public health goals for chronic disease prevention and health promotion. | 18,793,506 |
Enforcement of state indoor tanning laws in the United States. | Twenty-eight US states have passed legislation for indoor tanning facilities. To our knowledge, whether these state laws are actually enforced has not been evaluated previously in all 28 states. Therefore, we interviewed key informants in these states to assess enforcement practices. Two trained interviewers used a structured survey instrument to interview 28 key informants who were knowledgeable about enforcement practices for laws regarding indoor tanning. Respondents provided information specific to the most populous city in their states. Licensure for indoor tanning businesses was required in 22 of the 28 cities. Slightly less than half of the cities gave citations to tanning facilities that violated state law. Approximately 32% of the cities did not inspect indoor tanning facilities for compliance with state law, and another 32% conducted inspections less than annually. Of those cities that inspected at all, most conducted unannounced inspections. The relatively low rates of annual inspections and citations are of concern. We recommend that future studies assess whether legislation, enforcement practices, or a combination of the 2 affects the practices of indoor tanning facilities or of consumers. | 18,793,513 |
Conversion from sirolimus to everolimus in maintenance renal transplant recipients within a calcineurin inhibitor-free regimen: results of a 6-month pilot study. | To provide data on conversion of kidney transplant patients from sirolimus to everolimus. In this 6-month prospective, open-label pilot study, maintenance renal transplant patients receiving sirolimus, mycophenolic acid and corticosteroids without concomitant calcineurin inhibitor (CNI) therapy were converted to everolimus 8 mg/day (8 - 15 ng/ml), and followed for 6 months. Mycophenolic acid and corticosteroid therapy were continued unchanged. Patients with acute rejection within the previous 3 months were excluded. 11 patients were recruited and completed the study (mean 5.1 +/- 1.8 years post transplant). Mean everolimus trough level remained within target throughout the study. Mean GFR remained stable (Day 0, 48.4 +/- 8.4 ml/min/1.73 m2, Month 6, 49.5 +/- 17.3 ml/ min/1.73 m2 (p = 0.966), as did mean renal phosphate threshold (TmPO4/GFR) (Day 0, 0.41 +/- 0.15 mmol/l, Month 6, 0.40 +/- 0.17 mmol/l (p = 0.966)). Serum phosphates increased significantly from 0.71 to 0.77 mmol/l (p = 0.01), but tubular reabsorption of phosphates and 24-h phosphaturia remained unchanged and mean PTH concentration tended to decrease. No patient died, lost their graft or experienced biopsy-proven acute rejection after conversion. There were no cases of CMV infection. Tolerability remained similar post conversion. Hematological and lipid parameters remained stable. Liver enzymes and sex hormones remained within normal ranges. This pilot study suggests that converting kidney transplant patients receiving CNI-free maintenance immunosuppression from sirolimus to everolimus, at relatively high exposure levels, is safe and easily manageable. There was no consistent evidence for a change in GFR or proximal tubular function. | 18,793,527 |
Is Cystatin C more sensitive than creatinine in detecting early chronic allograft nephropathy? | Cystatin C (CyC) has been suggested as a more accurate indicator of renal function than creatinine (Crea). CyC performance against graft histopathology has not been investigated. To compare CyC and Crea-based methods as predictors of chronic allograft damage index (CADI). 105 protocol biopsies obtained at 6 months post-transplantation were classified with Banff'97 and CADI. CyC and Crea were measured concomitantly. Histology was correlated to CyC, Crea, their reciprocals, CyC-estimated GFR (Larsson), Cockroft and Gault (C&G) and abbreviated MDRD using Kendall's Tau. The area under ROC curve (ROC-auc),sensitivity/specificity, positive and negative predictive values were calculated at CADI cut-off of 2. Mild histological changes were best revealed by Crea, although with modest sensitivity/ specificity. A Crea threshold of 111 micromol/l distinguished 74% of the patients with CADI > 2 and excluded this condition in 66%. For Crea, ROC-auc was 0.72 (p < 0.001). Crea and 1/Crea correlated best to CADI, chronic allograft nephropathy, chronic inflammation, tubular atrophy, vascular changes and glomerulopathy. Neither C&G nor MDRD improved Crea performance alone. CyC and Larsson formula performed the same (ROC-auc 0.67). A CyC threshold of 1.12 mg/l distinguished 69% of the patients with CADI > 2 and excluded it in 60%. Significant Tau correlation was found between CyC, 1/CyC and Larsson with CADI, chronic inflammation, tubular atrophy and chronic vascular changes. CyC, 1/CyC and Larsson-estimated GFR did not offer significant advantages over Crea in predicting mild histological allograft changes. Protocol biopsy provides information that cannot be sensitively predicted by biochemical measurements used in clinical practice. | 18,793,544 |
Sexual function in women undergoing hemodialytic treatment assessed using the female sexual function index (FSFI) and the somatic inkblot series (SIS) test. | Female sexuality in end-stage renal disease has so far only been explored using non-validated tools. The aim of this study was to compare sexual function among hemodialyzed (HD) patients and healthy controls using validated questionnaires. Two internationally validated tests have been administrated: the female sexual function index (FSFI) questionnaire and a set of tables from the somatic inkblot series (SIS) test which focus specifically on the area of sexuality. 25 consecutive HD patients were assessed for sexual function using the FSFI. Nine SIS inkblots concerning sexuality were also administered to obtain more detailed information about the psychological component of sexuality. An equal number of control healthy volunteers perfectly matched for age, marital status and educational level underwent the same evaluations, and the results of the two groups were compared. HD patients had significantly lower scores than the controls for all FSFI domains except sexual desire even when stratified by age and marital status. All sexually related thematic areas of the SIS except body perception were significantly affected in the HD group compared to the control group. Chronic renal failure requiring HD treatment adversely affects female sexual function. The psychological impact on patients is significant when compared to an age-matched control group. Both the FSFI questionnaire and the SIS test may be considered useful tools for an integrated medical and psychological screening of FSD. | 18,793,548 |
Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method. | The aim of this study was to construct the population pharmacokinetic model in Chinese adult patients and to characterize the factors that affect the parameters of remifentanil pharmacokinetics. 15 patients were divided randomly into two groups: Index (modeling) group and validation group. 10 patients including 99 blood samples were in the Index group and 5 patients including 56 blood samples were in the Validation group. A LC-MS/MS method was developed to determine the whole blood concentration of remifentanil. Meanwhile, population modeling was performed using the NONMEM (nonlinear mixed-effect modeling) program with a 2-compartment pharmacokinetic model. The forward inclusion-backward elimination method was used to investigate the different covariates, including age, height, total bilirubin, etc. Liquid-liquid extraction was used to extract remifentanil from the blood. The calibration curve was linear from 0.5 to 50 ng/ml and the lowest limit of quantification (LOQ) was 0.5 ng/ml. The analytical method was rapid, selective and highly sensitive. The population pharmacokinetic results indicated that total bilirubin, age, alkaline phosphatase activity and gender significantly affected the parameters of remifentanil. The estimation of CL1, V1, CL2 and V2 were 1.85 l/min, 8.47 l, 1.28 l/min and 29.7 l, respectively. The population model was validated by another group of patients indicating that the model was effective and robust. The LC-MS/MS method for the quantification of remifentanil in human whole blood was rapid, selective and highly sensitive. The population model was acceptable and would be helpful for clinicians to assess the remifentanil pharmacokinetic parameters based on patient's specific demographic characteristics. | 18,793,578 |
Utility of the Roussel Uclaf Causality Assessment Method (RUCAM) to analyze the hepatic findings in a clinical trial program: evaluation of the direct thrombin inhibitor ximelagatran. | Causality assessment in drug-induced liver injury is often based on circumstantial evidence rather than a formal, systematic review. The Roussel Uclaf Causality Assessment Method (RUCAM) provides a more objective means of assessing causality of a suspected hepatotoxin but, to our knowledge, has never been used in the assessment of a single drug with unknown hepatotoxic potential in a clinical trial setting. We studied the utility of RUCAM in assessing the hepatic events during the long-term clinical trials of the oral direct thrombin inhibitor ximelagatran, which has been associated with an increased incidence of alanine aminotransferase (ALT) elevations. A total of 233 subjects with elevated ALT values signalling possibly severe hepatic injury were eligible for RUCAM analysis (198 ximelagatran and 35 comparator anticoagulants). RUCAM scores, calculated independently by the assessors, using the existing numerical criteria provided in its methodology, suggested a possible or probable causal relationship between ALT and ximelagatran in 37 and 27% of cases, respectively. Causality was excluded or unlikely in the remaining 36% of cases. However, in the course of utilizing RUCAM, several limitations to the methodology came to light, including awarding additional points for age > 55 years, an unspecified use of alcohol, and a latency period of < 90 days, which may have had the unintentional effect of raising the overall score. Moreover, rechallenge is highly rewarded by RUCAM but is seldom done in clinical practice or in clinical trials. We also found ambiguities in the extent to which other causes of liver injury were excluded, what constitutes a significant hepatotoxic concomitant medication, and whether a clinical trial drug should be considered as having an unknown hepatotoxic potential for purposes of RUCAM scoring. Increasing familiarity with the RUCAM over the course of the study allowed for only a slight improvement in concordance between and among the assessors regarding the scoring. While the results indicate that RUCAM can provide for an objective assessment of causality of the hepatotoxicity of a drug under development in the clinical trial setting, this study highlights a number of problems with the current scoring system that should be addressed by future enhancements of the methodology. | 18,793,587 |
Periodontal conditions in Williams Beuren syndrome: a series of 8 cases. | Williams Beuren syndrome (WBS) is an unusual hereditary connective tissue disease caused by a microdeletion at position 7q11-23 and a haploinsufficiency at the elastin gene. The most frequent specific features are elf-like face, alteration of cognitive functions and cardiovascular diseases including isolated supravalvular aortic stenosis. A number of clinical findings have been reported, but none of the studies evaluating this syndrome consider the oral cavity. It is equally surprising that the gingival tissue, which carries a perfectly structured elastic fibre network, has not yet been investigated. It is important to verify whether subjects affected by WBS are more susceptible to periodontal disease than healthy subjects who are not that much affected, for periodontal disease may have deleterious effects on the cardiovascular system. In an attempt to address this issue, the oral manifestations of 8 patients (ages from 5 to 12 years) with WBS have been investigated: dental examination, periodontal examination (gingival phenotype, plaque control record, gingival index, bone quality). All patients had oral parafunction, tooth number abnormalities and malocclusions. Average gingival height and width were greater than normal. Plaque index was always very high except for one patient, but the gingival inflammation was not linked to the quantity of clinical plaque index. There was no obvious loss of attachment. As with collagen, elastin is a structural macromolecule of the gingiva. These components play an important role in gingival function and in the resistance of the periodontium to daily aggressions. Unlike genetic diseases characterized by impairment of collagen macrofibrils, it is suggested that the hemizygous gene encoding elastin does not result in periodontal disease. In addition there is an existence of a possible concordance between the elastin gene haploinsufficiency and the periodontal phenotype. There might be some adaptive process to this deficiency. | 18,793,597 |
Case report: scurvy in an epileptic child on a ketogenic diet with oral complications. | Epilepsy is a symptom of cerebral dysfunction, where there is a sudden and disorganised discharge of electrical activity from a group of neurones, producing symptoms that range from sensory absences to convulsive movements and unconsciousness. Fasting is recognised as reducing the frequency of epileptic seizures in difficult to control patients. The ketogenic diet is a high fat, low carbohydrate and adequate protein diet that mimics the biochemical effects of fasting. It is deficient in some essential elements that require supplementation. A 9-year old girl with learning difficulties, developmental delay and refractory epilepsy was placed on the ketogenic diet in 2003. Prior to starting the diet she had had as many as 12 tonic seizures/day, with prolonged periods of non-convulsive status epilepticus. Subsequent to being placed on the diet, the frequency of her seizures reduced markedly; there were long periods during which she had none. In late 2006, the patient inhaled a primary molar. This was retrieved by emergency bronchoscopy and at the same time the remaining primary teeth were extracted. Three weeks later she was admitted to hospital with low-grade fever, persistently bleeding sockets, oedema of her hands and feet, a petechial rash and bruising. A differential diagnosis included: liver disease, bleeding dyscrasia, oncological pathology or scurvy. The most striking finding amongst a number of investigations was a vitamin C level of 0.7 micromol/l (Deficiency: < 11 micromol/l). Accordingly a diagnosis of scurvy was made. The patient was prescribed ascorbic acid 500 mg twice/day. Three weeks later the patient's vitamin C level was 141.5 micromol/l; the dose was therefore reduced to 250 mg once/day. At two-month review, the signs and symptoms of scurvy had resolved. Inhaling a tooth and scurvy are both rare occurrences. Paediatric dentists should be aware of the possible implications of a ketogenic diet. | 18,793,598 |
A high-throughput assay based on fluorescence polarization for inhibitors of the polo-box domain of polo-like kinase 1. | The serine/threonine kinase polo-like kinase 1 (Plk1) is critically involved in multiple mitotic processes and has been established as an adverse prognostic marker for tumor patients. Plk1 localizes to its substrates and its intracellular anchoring sites via its polo-box domain (PBD), which is unique to the family of polo-like kinases. Therefore, inhibition of the Plk1 PBD has been suggested as an approach to the inhibition of Plk1 that circumvents specificity problems associated with the inhibition of the conserved adenosine triphosphate (ATP) binding pocket. Here we report on the development of a high-throughput assay based on fluorescence polarization that allows the discovery of small-molecule inhibitors of the Plk1 PBD. The assay is based on binding of the Plk1 PBD to a phosphothreonine-containing peptide comprising its optimal binding motif with a K(d) of 26+/-2 nM. It is stable with regard to dimethyl sulfoxide (DMSO) and time, and it has a Z' value of 0.73+/-0.06 in a 384-well format. | 18,793,607 |
Serum nitric oxide metabolites in subjects with metabolic syndrome. | Evidence are available showing that higher nitric oxide production is associated with metabolic disorders. The aim of this study was to determine serum nitric oxide metabolites (NOx) concentration in subjects with metabolic syndrome (MetS). In a cross-sectional study, NOx was measured in 3505 subjects, aged 20-94 years, using the Griess reaction. After excluding subjects taking medications for hypertension and dyslipidemia, data for 3148 subjects were analyzed. There was a direct association between the numbers of metabolic risk factors and serum NOx values in both genders (p for trend<0.05). After multivariable adjustment, serum NOx concentration was significantly higher in subjects with MetS [(31.9 (29.4-34.6) vs. 29.8 (27.6-32.1), p<0.01) or type 2 diabetes (34.6 (31.3-38.2) vs. 30.2 (27.9-32.6), p<0.001) as compared to their corresponding controls. Higher NOx concentrations in subjects with MetS and type 2 diabetes support the existing hypothesis that NO overproduction affects insulin's metabolic actions. | 18,793,628 |
LAU-0901, a novel platelet-activating factor antagonist, is highly neuroprotective in cerebral ischemia. | Platelet-activating factor (PAF) is a bioactive phospholipid that accumulates during ischemia-reperfusion and is involved in the activation of platelets, neutrophils, and pro-inflammatory signaling. PAF has been suggested to enhance brain ischemia-reperfusion damage. LAU-0901, a novel PAF receptor antagonist, was examined in models of focal cerebral ischemia in rats and mice. Sprague-Dawley rats were anesthetized and received 2-hour middle cerebral artery occlusion (MCAo) by intraluminal suture. LAU-0901 (30, 60, 90 mg/kg; n=9-11) or vehicle (n=11) was administered i.p. at 2 h after onset of MCAo. The neurological status was evaluated at 60 min, and on days 1, 2, 3 and 7 after MCAo. In the dose-response study in mice, C57BL/6 mice were anesthetized and received 1 h MCAo by intraluminal suture. LAU-0901 (15, 30, 60 mg/kg; n=7-9) or vehicle (n=8) was given i.p. at 1 h after onset of MCAo. Local cerebral blood flow (LCBF) was measured at 1, 2, 4, and 6 h after MCAo in mice. LAU-0901 treated rats showed improved neurological score throughout the 7-day survival period. LAU-0901 treatment (30, 60 and 90 mg/kg) reduced total corrected infarct volume compared to vehicle rats by 76, 88 and 90%, respectively. Mice treated with LAU-0901 (30 and 60 mg/kg) reduced total infarction by 29% and 66%, respectively. LCBF was improved by treatment with LAU-0901 (30 mg/kg) by 77% of baseline at 6 h. In conclusion, we demonstrate for the first time that LAU-0901 improves behavioral scores, LCBF and reduces infarct volume after focal cerebral ischemia in rats and mice. Thus, this PAF receptor antagonist exhibits potent and sustained neuroprotection that may be of value for the design of stroke therapies. | 18,793,637 |
Cysteine peptidases in the tomato trypanosomatid Phytomonas serpens: influence of growth conditions, similarities with cruzipain and secretion to the extracellular environment. | We have characterized the cysteine peptidase production by Phytomonas serpens, a tomato trypanosomatid. The parasites were cultivated in four distinct media, since growth conditions could modulate the synthesis of bioactive molecules. The proteolytic profile has not changed qualitatively regardless the media, showing two peptidases of 38 and 40kDa; however, few quantitative changes were observed including a drastic reduction (around 70%) on the 40 and 38kDa peptidase activities when parasites were grown in yeast extract and liver infusion trypticase medium, respectively, in comparison with parasites cultured in Warren medium. The time-span of growth did not significantly alter the protein and peptidase expression. The proteolytic activities were blocked by classical cysteine peptidase inhibitors (E-64, leupeptin, and cystatin), being more active at pH 5.0 and showing complete dependence to reducing agents (dithiothreitol and l-cysteine) for full activity. The cysteine peptidases were able to hydrolyze several proteinaceous substrates, including salivary gland proteins from Oncopeltus fasciatus, suggesting broad substrate utilization. By means of agglutination, fluorescence microscopy, flow cytometry and Western blotting analyses we showed that both cysteine peptidases produced by P. serpens share common epitopes with cruzipain, the major cysteine peptidase of Trypanosoma cruzi. Moreover, our data suggest that the 40kDa cysteine peptidase was located at the P. serpens cell surface, attached to membrane domains via a glycosylphosphatidylinositol anchor. The 40kDa peptidase was also detected in the cell-free culture supernatant, in an active form, which suggests secretion of this peptidase to the extracellular environment. | 18,793,639 |
Thermodynamics, kinetics, and salt dependence of folding of YopM, a large leucine-rich repeat protein. | Small globular proteins have many contacts between residues that are distant in primary sequence. These contacts create a complex network between sequence-distant segments of secondary structure, which may be expected to promote the cooperative folding of globular proteins. Although repeat proteins, which are composed of tandem modular units, lack sequence-distant contacts, several of considerable length have been shown to undergo cooperative two-state folding. To explore the limits of cooperativity in repeat proteins, we have studied the unfolding of YopM, a leucine-rich repeat (LRR) protein of over 400 residues. Despite its large size and modular architecture (15 repeats), YopM equilibrium unfolding is highly cooperative, and shows a very strong dependence on the concentration of urea. In contrast, kinetic studies of YopM folding indicate a mechanism that includes one or more transient intermediates. The urea dependence of the folding and unfolding rates suggests a relatively small transition state ensemble. As with the urea dependence, we have found an extreme dependence of the free energy of unfolding on the concentration of salt. This salt dependence likely results from general screening of a large number of unfavorable columbic interactions in the folded state, rather than from specific cation binding. | 18,793,647 |
Aspects of the progesterone response in Hortaea werneckii: Steroid detoxification, protein induction and remodelling of the cell wall. | Progesterone in sublethal concentrations temporarily inhibits growth of Hortaea werneckii. This study investigates some of the compensatory mechanisms which are activated in the presence of progesterone and are most probably contributing to escape from growth inhibition. These mechanisms lead on the one hand to progesterone biotransformation/detoxification but, on the other, are suggested to increase the resistance of H. werneckii to the steroid. Biotransformation can detoxify progesterone efficiently in the early logarithmic phase, with mostly inducible steroid transforming enzymes, while progesterone biotransformation/detoxification in the late logarithmic and stationary phases of growth is not very efficient. The relative contribution of constitutive steroid transforming enzymes to progesterone biotransformation is increased in these latter phases of growth. In the presence of progesterone, activation of the cell wall integrity pathway is suggested by the overexpression of Pck2 which was detected in the stationary as well as the logarithmic phase of growth of the yeast. Progesterone treated H. werneckii cells were found to be more resistant to cell lysis than mock treated cells, indicating for the first time changes in the yeast cell wall as a result of treatment with progesterone. | 18,793,662 |
Proprioceptive sensibility in the elderly: degeneration, functional consequences and plastic-adaptive processes. | As the percentage of individuals over the age of 60 years continues to rise, determining the extent and functional significance of age-related declines in sensorimotor performance is of increasing importance. This review examines the specific contribution of proprioceptive feedback to sensorimotor performance in older adults. First, a global perspective of proprioceptive acuity is provided assimilating information from studies where only one of several aspects of proprioceptive function (e.g. sense of position, motion or dynamic position) was quantified, and/or a single joint or limb segment tested. Second, the consequences of proprioceptive deficits are established with particular emphasis placed on postural control. Lastly, the potential for plastic changes in the aging proprioceptive system is highlighted, including studies which relate physical activity to enhanced proprioceptive abilities in older adults. Overall, this review provides a foundation for future studies regarding the proprioceptive feedback abilities of elderly individuals. Such studies may lead to greater advances in the treatment and prevention of the sensorimotor deficits typically associated with the aging process. | 18,793,668 |
Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel. | In this work, a series of biodegradable triblock poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers were successfully synthesized by ring-opening copolymerization, and were characterized by (1)H NMR, FT-IR, GPC, and DSC. Aqueous solutions of PECE copolymers underwent thermosensitive sol-gel-sol transition as temperature increases when the concentration was above corresponding critical gel concentration (CGC). Sol-gel-sol phase transition diagrams were recorded using test tube inverting method, which depended on hydrophilic/hydrophobic balance in macromolecular structure, as well as some other factors, including topology of triblock copolymers and solution composition of the hydrogel. As a result, the sol-gel-sol transition temperature range could be varied, which might be very useful for its application as injectable drug delivery systems. The in vivo gel formation and degradation behavior was conducted by injecting aqueous PECE solution into KunMing mice subcutaneously. In vitro degradation behavior, in vitro drug release behavior, and cytotoxicity were also investigated in this paper. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PECE hydrogel is believed to be promising for in situ gel-forming controlled drug delivery system. | 18,793,709 |
Immunological and pathological changes in the placenta during infection with Listeria monocytogenes in pregnant guinea pigs. | Exposure to Listeria monocytogenes during pregnancy can result in spontaneous abortion and stillbirths; however, the mechanisms are unknown. Our objective was to determine the effects of infection on specific inflammatory and anti-inflammatory cytokine mRNA expression and apoptosis in the placenta after infection with L. monocytogenes. Pregnant guinea pigs were treated on gestation day (gd) 35 with 10(8) colony forming units L. monocytogenes and sacrificed on gd 37, 41, 44, or 55. At gd 41, IFN-gamma and IL-2 mRNA expression was significantly decreased in placentas from treated dams (0.0012-fold and 0.131-fold, respectively). At gd 55, TNF-alpha mRNA expression was significantly decreased (0.19-fold), while IFN-gamma mRNA expression was significantly increased (32-fold), and apoptosis was detected in 100% of placentas from treated dams. In conclusion, inflammatory cytokine mRNA expression is altered and apoptosis is increased in the placenta after treatment with L. monocytogenes, and these changes may contribute to fetal death. | 18,793,713 |
Recombinant expression, purification, and characterization of XorKII: a restriction endonuclease from Xanthomonas oryzae pv. oryzae. | An endonuclease from Xanthomonas oryzae pathovar oryzae (Xoo) KACC10331, XorKII, was recombinantly produced in Escherichia coli by applying the stationary state induction method, which was necessary to prevent the unwanted lysis of E. coli cells. XorKII was purified by immobilized metal affinity chromatography on an FPLC system. The yield was 3.5mg of XorKII per liter of LB medium. The purified recombinant XorKII showed that it recognized and cleaved to the same site as PstI. It behaved as a dimer as evidenced by the size exclusion chromatography. The specific activity of the purified XorKII was determined to be 31,300 U/mg. The enzyme activity was monitored by cleaving lambda DNA or YEp24 plasmid as substrates. The enzyme was the most active at 10mM Tris-HCl pH 7.0, 10 mM MgCl(2), 1mM dithiothreitol at 37 degrees C. XorKII was easily inactivated by heating at 65 degrees C for 5 min, but retained most of the original activity after incubation at 37 degrees C for 24h. | 18,793,728 |
Evidence for abnormalities of cortical development in adolescent-onset schizophrenia. | Voxel-Based Morphometry (VBM) identifies differences in grey matter brain structure in patients with schizophrenia relative to healthy controls, with particularly prominent differences found in patients with the more severe, adolescent-onset form of the disease. However, as VBM is sensitive to a combination of changes in grey matter thickness, intensity and folding, specific neuropathological interpretations are not possible. Here, we attempt to more precisely define cortical changes in 25 adolescent-onset schizophrenic patients and 25 age- and sex-matched healthy volunteers using Surface-Based Morphometry (SBM) to disambiguate the relative contributions of cortical thickness and surface area differences to changes in regional grey matter (GM) density measured with VBM. Cortical changes in schizophrenia were widespread, including particularly the prefrontal cortex and superior temporal gyrus. Nine regions of apparent reduction in GM density in patients relative to healthy matched controls were found using VBM that were not found with SBM-derived cortical thickness measures. In Regions of Interest (ROIs) derived from the VBM group results, we confirmed that local surface area differences accounted for these VBM changes. Our results emphasize widespread, but focally distinct cortical pathology in adolescent-onset schizophrenia. Evidence for changes in local surface area (as opposed to simply cortical thinning) is consistent with a neurodevelopmental contribution to the underlying neuropathology of the disease. | 18,793,730 |
Large-scale brain networks account for sustained and transient activity during target detection. | Target detection paradigms have been widely applied in the study of human cognitive functions, particularly those associated with arousal, attention, stimulus processing and memory. In EEG recordings, the detection of task-relevant stimuli elicits the P300 component, a transient response with latency around 300 ms. The P300 response has been shown to be affected by the amount of mental effort and learning, as well as habituation. Furthermore, trial-by-trial variability of the P300 component has been associated with inter-stimulus interval, target-to-target interval or target probability; however, understanding the mechanisms underlying this variability is still an open question. In order to investigate whether it could be related to the distinct cortical networks in which coherent intrinsic activity is organized, and to understand the contribution of those networks to target detection processes, we carried out a simultaneous EEG-fMRI study, collecting data from 13 healthy subjects during a visual oddball task. We identified five large-scale networks, that largely overlap with the dorsal attention, the ventral attention, the core, the visual and the sensory-motor networks. Since the P300 component has been consistently associated with target detection, we concentrated on the first two brain networks, the time-course of which showed a modulation with the P300 response as detected in simultaneous EEG recordings. A trial-by-trial EEG-fMRI correlation approach revealed that they are involved in target detection with different functional roles: the ventral attention network, dedicated to revealing salient stimuli, was transiently activated by the occurrence of targets; the dorsal attention network, usually engaged during voluntary orienting, reflected sustained activity, possibly related to search for targets. | 18,793,734 |
Natural-cycle in vitro fertilization in poor responder patients: a survey of 500 consecutive cycles. | To determine the role of the natural cycle for in vitro fertilization (IVF) in poor responder patients. Retrospective survey. Private center for assisted reproduction. 294 women who were poor responders in a previous IVF cycle. Analysis of 500 consecutive natural cycles IVF. Number of cycles with oocytes, pregnancy rate per cycle, per transfer, and implantation rate. Oocytes were found in 391 cases (78.1%), and cleaving embryos suitable for transfer were obtained in 285 cycles (57.0%). Pregnancy was observed in 49 cases, with a pregnancy rate of 9.8% per cycle, 17.1% per transfer, and 16.7% per patient. The patients were subdivided arbitrarily by the women's age into three groups. Patients 35 years old or younger showed a pregnancy rate of 18.1% per cycle, 29.2% per transfer, and 31.7% per patient. Women aged between 36 and 39 years showed a pregnancy rate of 11.7% per cycle, 20.6% per transfer, and 20.3% per patient. Women 40 years old or older showed a pregnancy rate of 5.8% per cycle, 10.5% per transfer, and 9.7% per patient. No differences were found for any of the evaluated parameters, independent of which cycle was the first, the second, third, fourth, or fifth, or further consecutive cycle. In poor responder patients, natural-cycle IVF is an effective treatment, especially in younger women. | 18,793,777 |
Induction of the cytokine TWEAK and its receptor Fn14 in ischemic stroke. | Stroke outcome is determined by delayed neuronal cell death and edema formation. TWEAK, a cytokine of the TNF superfamily, and its membrane receptor Fn14 promote ischemia-induced neuronal apoptosis and leakage of the blood-brain barrier. Both TWEAK and Fn14 are upregulated in experimental stroke models. In this study, we investigated whether TWEAK and Fn14 are upregulated in stroke patients. We measured serum concentrations of TWEAK in stroke patients and matched control subjects by ELISA. Expression of Fn14 in the brain was evaluated by real-time RT-PCR and immunohistochemistry. TWEAK serum concentrations were elevated in stroke patients. In autopsy samples, we found elevated mRNA levels of the receptor Fn14 and a trend towards higher TWEAK mRNA levels. In the infarcted and peri-infarct tissue immunostaining for Fn14 was enhanced. These data show that the cytokine TWEAK and its membrane receptor Fn14 are upregulated in stroke and suggest that they contribute to stroke outcome. | 18,793,781 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.