title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
|---|---|---|
Oriented films of layered rare-earth hydroxide crystallites self-assembled at the hexane/water interface. | Layered rare-earth hydroxide crystallites self-assembled at the hexane/water interface were transferred to various substrates to form a monolayer film, which exhibited photoluminescence properties and ion-exchange ability. | 18,931,731 |
Encapsulation of charge-diffuse peralkylated onium cations in the cavity of cucurbit[7]uril. | Cucurbit[7]uril binds, with considerable size selectivity, NR(4)(+), PR(4)(+), and SR(3)(+) cations (R=Me, Et, (n)Pr, (n)Bu), with the smaller guests inside its cavity, rather than at the carbonyl-lined portals. | 18,931,744 |
Solubility switch of gold nanoparticles through hydrogen bond association. | Gold nanoparticles (AuNPs) coated with hexafluoroisopropanol moieties were prepared, and their surface was changed through simple hydrogen bond association with various amines, which allow orientation of the solubility of these AuNPs in determined organic solvents. | 18,931,750 |
Repetitive lagging strand DNA synthesis by the bacteriophage T4 replisome. | Our studies on the T4 replisome build on the seminal work from the Alberts laboratory. They discovered essentially all the proteins that constitute the T4 replisome, isolated them, and measured their enzymatic activities. Ultimately, in brilliant experiments they reconstituted in vitro a functioning replisome and in the absence of structural information created a mosaic as to how such a machine might be assembled. Their consideration of the problem of continuous leading strand synthesis opposing discontinuous lagging strand synthesis led to their imaginative proposal of the trombone model, an illustration that graces all textbooks of biochemistry. Our subsequent work deepens their findings through experiments that focus on defining the kinetics, structural elements, and protein-protein contacts essential for replisome assembly and function. In this highlight we address when Okazaki primer synthesis is initiated and how the primer is captured by a recycling lagging strand polymerase--problems that the Alberts laboratory likewise found mysterious and significant for all replisomes. | 18,931,782 |
Supramolecular helical porphyrin arrays using DNA as a scaffold. | A diphenyl porphyrin substituted nucleotide was incorporated site specifically into DNA, leading to helical stacked porphyrin arrays in the major groove of the duplexes. The porphyrins show an electronic interaction which is significantly enhanced compared to the analogous tetraphenyl porphyrin (TPP) as shown in the large exciton coupling of the porphyrin B-band absorbance. Analogous to the TPP-DNA, an induced helical secondary structure is observed in the single strand porphyrin-DNA. The modified DNA can be hybridised to an immobilised complementary strand leading to fluorescent beads. | 18,931,790 |
Optimisation of chemical protein cleavage for erythropoietin semi-synthesis using native chemical ligation. | Selective protein cleavage at methionine residues is a useful method for the production of bacterially derived protein fragments containing an N-terminal cysteine residue required for native chemical ligation. Here we describe an optimised procedure for cyanogen bromide-mediated protein cleavage, and ligation of the resulting fragments to afford biologically active proteins. | 18,931,805 |
Transannular rearrangement of activated 2,5-diketopiperazines: a key route to original scaffolds. | An efficient and original stereocontrolled transannular rearrangement starting from activated 2,5-diketopiperazines has been developed, an opportunity for the medicinal chemistry field, which requests access to novel biological scaffolds. This powerful ring contraction, which can be related to a stereoselective aza-version of the Chan rearrangement, allows for example the one-step synthesis of various tetramic acids, access to 2-disubstituted statins, or the synthesis of relevant lactam-constrained dipeptide mimetics using a TRAL-RCM sequence. | 18,931,807 |
An efficient synthesis of chiral phosphinyl oxide pyrrolidines and their application to asymmetric direct aldol reactions. | Chiral pyrrolidine-based phosphinyl oxides were synthesized and their performance as organocatalysts for asymmetric direct aldol reactions was evaluated. High enantioselectivities and diastereoselectivies were achieved for a range of cyclic ketones and aromatic aldehydes. | 18,931,808 |
Electrophilicity of aromatic triflones in sigma-complexation processes. | The kinetics of sigma-complexation of 2,6-bis(trifluoromethanesulfonyl)-4-nitroanisole (4) have been investigated over a large pH range of 2-15.68 in methanol. Two competitive processes have been identified with the initial addition of MeO(-) at the unsubstituted 3-position of 4 to give a 1,3-dimethoxy adduct (4b-Me) and a subsequent and slow conversion of this species into the 1,1-dimethoxy isomer (4a-Me). Both 4a-Me and 4b-Me are more stable than the related adducts of 2,6-dinitro-4-trifluromethanesulfonylanisole, i.e.5a-Me and 5b-Me, and 2,4,6-trinitroanisole, i.e.6a-Me and 6b-Me, the latter compound being a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high thermodynamic stability of 4a-Me (pK(a) = 10.48) and 4b-Me (pK(a) = 12.23) relative to 5a-Me (pK(a) = 10.68) and 6a-Me (pK(a) = 12.56) or 5b-Me (pK(a) = 15.38) and 6b-Me (pK(a) = 16.46), is shown to derive from an especially high capacity of a para or an ortho SO(2)CF(3) group to stabilize a negative charge through Fpi-type polarization effects. From the kinetic data, it appears that the contribution of a methanol pathway to the formation of 4a-Me is much weaker than that found to operate in the formation of the 1,1-complex 5a-Me of 2,6-dinitro-4-trifluromethanesulfonylanisole, the experimental evidence suggesting that the reactivity of 4 and 5 is located just beyond the region defining the boundary between super- and normal-electrophilicity in methanol. Comparison of our results with available literature data show that this boundary corresponds to a pK(MeOH)(a) value of approximately 10, in agreement with our previous finding of a very effective solvent contribution to the sigma-complexation of 1,3,5-tris(trifluoromethanesulfonyl)benzene (13; pK(MeOH)(a) = 9.12) in methanol. Taking advantage of our observation that pK(MeOH)(a) and pK(H(2)O)(a) values for sigma-complexation at unsubstituted ring positions are related by a nice linear correlation, an approximate ranking of the electrophilicity of our aromatic triflones on the E scale developed by Mayr (Acc. Chem. Res. 2003, 36, 66) can be made. | 18,931,813 |
An unexpected epoxidation of benzil derivatives in their reaction with a germene. | The germene Mes(2)Ge=CR(2) (Mes = 2,4,6-trimethylphenyl, CR(2) = fluorenylidene) reacts with various benzil derivatives to lead to germanium-containing bicyclic epoxides by an unexpected new type of epoxidation reaction. | 18,931,816 |
The microstructure of cornea verticillata in Fabry disease and amiodarone-induced keratopathy: a confocal laser-scanning microscopy study. | The purpose of this study is to describe cornea verticillata in Fabry disease and in amiodarone-induced keratopathy and to compare the corneal microstructure of both types. Ten eyes from ten normal subjects, 28 eyes from 22 patients with Fabry disease confirmed by molecular genetic studies, and 16 eyes from 11 patients receiving amiodarone were examined by slit-lamp microscopy and in-vivo confocal laser-scanning microscopy (CLSM) with following three-dimensional reconstruction of the individual corneal layers. Five patients with Fabry disease were monitored during the course of enzyme replacement therapy (ERT). Evidence of cornea verticillata was found by slit-lamp microscopy both in patients with Fabry disease and in those with amiodarone-induced keratopathy; CLSM revealed the same pattern of hyper-reflective deposits in the basal cell layer of corneal epithelium in both sets of patients. Microdot changes in the anterior stroma were more prevalent in patients receiving amiodarone but do not presuppose the simultaneous presence of cornea verticillata. The bulbar conjunctiva was found to be normal in all patients. The tarsal conjunctival epithelium contained round hyper-reflective structures, which are also encountered physiologically, but these were more common in patients with Fabry disease. In one out of the five patients examined, monitoring of corneal changes over time during ERT disclosed a regressive tendency of the deposits in the epithelial basal cell layer documented by CLSM. The microstructural corneal changes typically seen in cornea verticillata in both Fabry disease and in amiodarone-induced keratopathy can be successfully visualized by confocal in-vivo microscopy at the level of the basal cell layer. By analogy, with the grading system for cornea verticillata based on slit-lamp microscopy, staging of these deposits in the basal cell layer can also be performed following in-vivo CLSM. The microdots in the anterior stroma as well as the changes observed in the tarsal conjunctiva should be regarded as having less diagnostic value because such changes may also occur in normal subjects. The utility of CLSM as a tool for monitoring ERT in Fabry disease over time needs to be confirmed in studies with larger sample sizes conducted over a longer period. | 18,931,853 |
Treatment of severe Henoch-Schönlein and immunoglobulin A nephritis. A single center experience. | Our aim was to report the effect of two treatment regimens in 43 cases of severe Henoch-Schönlein nephritis (HSN) and immunoglobulin A nephritis (IgAN) (24 HSN, 19 IgAN). Group A, 11 HSN and 7 IgAN, 88% with an International Study of Kidney Disease in Children (ISKDC) biopsy grade > or = III and severe clinical features, were treated with corticosteroids, cyclophosphamide (CYC-P) and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB). Group B, 12 HSN and 13 IgAN, 72% with biopsy findings as above and 52% with severe clinical features, were treated with ACEi/ARB +/- corticosteroids. The outcome classification was: (a) healthy; (b) mild proteinuria, normal glomerular filtration rate (GFR); (c) active renal disease; (d) chronic renal failure. Twenty-six patients had a good outcome (a + b). The 17 children with poor outcome (c + d) had lower GFR at onset and at follow-up, higher albumin excretion at follow-up, and higher percentage of segmental glomerulosclerosis in the renal biopsy, than those with good outcome. Treatment with corticosteroids, CYC-P and ACEi/ARB was effective in increasing GFR, reducing proteinuria and decreasing the disease activity index. The proteinuria had decreased at follow-up in both groups. In group A, GFR increased and histopathological activity index declined after treatment. The outcome did not differ between groups A and B. The effects of treatment did not differ between HSN and IgAN. | 18,931,859 |
Undertreatment of nausea and other symptoms in hospitalized cancer patients. | This survey aimed to provide a symptom profile, in particular for nausea and its treatment, of advanced cancer patients prior to implementation of a clinical practice guideline for nausea. An audit of 82 advanced cancer patients admitted to a major Australian teaching hospital was undertaken. While nausea was present in 26 (32%) of respondents, antiemetics were prescribed in 52 (68%), a higher proportion than in the past, and being taken by 32 (39%). Patients reporting moderate-to-severe nausea often missed out on treatment. These findings underscore the need for more attention to education of hospital staff in the assessment and treatment of this frequently bothersome symptom, and raise issues for study design of symptom control research. | 18,931,863 |
A case of acute ischemic duodenal ulcer associated with superior mesenteric artery dissection after transarterial chemoembolization for hepatocellular carcinoma. | We report a case of transarterial chemoembolization (TACE)-related acute ischemic duodenal ulcer that developed in association with dissection of the superior mesenteric artery. We conclude that the acute duodenal ulcer was developed by ischemia related to superior mesenteric artery dissection during TACE. TACE should be conducted carefully with continuous observation of abdominal arteries. | 18,931,873 |
Patient dose reference levels for interventional radiology: a national approach. | A set of patient dose reference levels (RLs) for fluoroscopically guided interventional procedures was obtained in a survey launched by the National Society of Interventional Radiology (IR), involving 10 public hospitals, as recommended by the European Medical Exposures Directive. A sample of 1391 dose values (kerma area product [KAP]) was collected randomly during clinical procedures for seven of the most frequent procedures. Third quartiles of the KAP distributions were used to set the RLs. A regular quality control of the X-ray systems and a calibration of the dose meters were performed during the survey. The fluoroscopy time and total number of digital subtraction angiography images per procedure were also analyzed. The RL values proposed were 12 Gy cm(2) for fistulography (hemodialysis access; sample of 180 cases), 73 Gy cm(2) for lower limb arteriography (685 cases), 89 Gy cm(2) for renal arteriography (55 cases), 80 Gy cm(2) for biliary drainage (205 cases), 289 Gy cm(2) for hepatic chemoembolization (151 cases), 94 Gy cm(2) for iliac stent (70 cases), and 236 Gy cm(2) for uterine embolization (45 cases). The provisional national RL values are lower than those obtained in a similar survey carried out in the United States from 2002 to 2004. These new values could be used to improve the practice of centers consistently working with doses higher than the RLs. This national survey also had a positive impact, as it helped increase the awareness of the members of the National Society of IR on a topic as crucial as patient dose values and programs on radiation protection. | 18,931,875 |
In search of a good death. | Spirituality and storytelling can be resources in aging successfully and in dying well given the constraints of modern day Western culture. This paper explores the relationship of aging to time and the dynamic process of the life course and discusses issues related to confronting mortality, including suffering, finitude, spirituality, and spiritual closure in regard to death. And, finally, the role of narrative in this process is taken up. | 18,931,891 |
Ethnic, gender, and acculturation influences on sexual behaviors. | Much research has been conducted on ethnic differences in sexuality, but few studies have systematically assessed the importance of acculturation in sexual behavior. The present study assessed general differences in normative sexual practices in healthy Euro-American, Asian, and Hispanic populations, using measures of acculturation to analyze the relative effects of heritage and mainstream cultures within each group. A total of 1,419 undergraduates (67% Euro-American, 17% Hispanic, 16% Asian; 33% men, 67% women) completed questionnaires which assessed sexual experience and causal sexual behaviors. In concordance with previous studies, Asians reported more conservative levels of sexual experience and frequency of sexual behaviors, fewer lifetime partners, and later ages of sexual debut than Euro-American or Hispanic counterparts. Hispanic reported sexual experiences similar to that of Euro-Americans. There was a significant interaction between mainstream and heritage acculturation in predicting number of lifetime sexual partners in Asian women such that the relationship between heritage acculturation and casual sexual behavior was stronger at lower levels of mainstream acculturation. On the other hand, in Hispanic men, higher levels of mainstream acculturation predicted more casual sexual behavior (one-time sexual encounters and number of lifetime sexual partners) when heritage acculturation was low but less casual sexual behavior when heritage acculturation was high. These results suggest that, for sexual behavior, Hispanic men follow an "ethnogenesis" model of acculturation while Asian women follow an "assimilation" model of acculturation. | 18,931,901 |
The NIfETy method for environmental assessment of neighborhood-level indicators of violence, alcohol, and other drug exposure. | There are limited validated quantitative assessment methods to measure features of the built and social environment that might form the basis for environmental preventive interventions. This study describes a model approach for epidemiologic assessment of suspected environmental determinants of violence, alcohol and other drug (VAOD) exposure and fills this gap in current research. The investigation sought to test the feasibility of a systematic and longitudinal assessment of residential block characteristics related to physical and social disorder and indicators of VAOD exposure. Planometric data were used to establish a stratified random sample of street segments within defined neighborhoods of an urban metropolitan area. Field rater assessments of these neighborhood street segments were conducted using the Neighborhood Inventory for Environmental Typology (NIfETy). This report provides a detailed description of the NIfETy Method, including metric properties of the NIfETy Instrument and outcomes of training procedures and quality control measures. Also presented are block-level characteristics and estimates of observable signs of VAOD activity. This work is a first step toward developing future community-level environmental preventive interventions geared to reduce community VAOD exposure among youthful urban populations and may prove to be useful to other public health research groups as well. | 18,931,911 |
Quantification of urbanization in relation to chronic diseases in developing countries: a systematic review. | During and beyond the twentieth century, urbanization has represented a major demographic shift particularly in the developed world. The rapid urbanization experienced in the developing world brings increased mortality from lifestyle diseases such as cancer and cardiovascular disease. We set out to understand how urbanization has been measured in studies which examined chronic disease as an outcome. Following a pilot search of PUBMED, a full search strategy was developed to identify papers reporting the effect of urbanization in relation to chronic disease in the developing world. Full searches were conducted in MEDLINE, EMBASE, CINAHL, and GLOBAL HEALTH. Of the 868 titles identified in the initial search, nine studies met the final inclusion criteria. Five of these studies used demographic measures (such as population density) at an area level to measure urbanization. Four studies used more complicated summary measures of individual and area level data (such as distance from a city, occupation, home and land ownership) to define urbanization. The papers reviewed were limited by using simple area level summary measures (e.g., urban rural dichotomy) or having to rely on preexisting data at the individual level. Further work is needed to develop a measure of urbanization that treats urbanization as a process and which is sensitive enough to track changes in "urbanicity" and subsequent emergence of chronic disease risk factors and mortality. | 18,931,915 |
An in silico strategy identified the target gene candidates regulated by dehydration responsive element binding proteins (DREBs) in Arabidopsis genome. | Identification of downstream target genes of stress-relating transcription factors (TFs) is desirable in understanding cellular responses to various environmental stimuli. However, this has long been a difficult work for both experimental and computational practices. In this research, we presented a novel computational strategy which combined the analysis of the transcription factor binding site (TFBS) contexts and machine learning approach. Using this strategy, we conducted a genome-wide investigation into novel direct target genes of dehydration responsive element binding proteins (DREBs), the members of AP2-EREBPs transcription factor super family which is reported to be responsive to various abiotic stresses in Arabidopsis. The genome-wide searching yielded in total 474 target gene candidates. With reference to the microarray data for abiotic stresses-inducible gene expression profile, 268 target gene candidates out of the total 474 genes predicted, were induced during the 24-h exposure to abiotic stresses. This takes about 57% of total predicted targets. Furthermore, GO annotations revealed that these target genes are likely involved in protein amino acid phosphorylation, protein binding and Endomembrane sorting system. The results suggested that the predicted target gene candidates were adequate to meet the essential biological principle of stress-resistance in plants. | 18,931,920 |
Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region. | Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease. | 18,931,923 |
Defining useful surrogates for user participation in online medical learning. | "School for Surgeons" is a web-based distance learning program which provides online clinical-based tutorials to surgical trainees. Our aim was to determine surrogates of active participation and to assess the efficacy of methods to improve usage. Server logs of the 82 participants in the "School for Surgeons" were assessed for the two terms of the first year of the program. Data collected included total time online, mean session time, page requests, numbers of sessions online and the total number of assignments. An intervention regarding comparative peer usage patterns was delivered to the cohort between terms one and two. Of the 82 trainees enrolled, 83% (85% second term) logged into the program. Of all participants 88% (97% second term) submitted at least one assignment. Median submissions were four (eight second term) per trainee. Assignment submission closely correlated with number of sessions, total time online, downloads and page requests. Peer-based comparative feedback resulted in a significant increase in the number of assignments submitted (p < 0.01). Despite its recent introduction, "School for Surgeons" has a good participation rate. Assignment submission is a valid surrogate for usage. Students can be encouraged to move from passive observation to active participation in a virtual learning environment by providing structured comparative feedback ranking their performance. | 18,931,929 |
Optimization of fermentation conditions for the biosynthesis of L-threonine by Escherichia coli. | In this study, the fed-batch fermentation technique was applied to improve the yield of L-threonine produced by Escherichia coli TRFC. Various fermentation substrates and conditions were investigated to identify the optimal carbon source, its concentration and C/N ratio in the production of L-threonine. Sucrose was found to be the optimal initial carbon source and its optimal concentration was determined to be 70 g/L based on the results of fermentations conducted in a 5-L jar fermentor using a series of fed-batch cultures of E. coli TRFC. The effects of glucose concentration and three different feeding methods on the production of L-threonine were also investigated in this work. Our results showed that the production of L-threonine by E. coli was enhanced when glucose concentration varied between 5 and 20 g/L with DO-control pulse fed-batch method. Furthermore, the C/N ratio was a more predominant factor than nitrogen concentration for L-threonine overproduction and the optimal ratio of ammonium sulfate to sucrose (g/g) was 30. Under the optimal conditions, a final L-threonine concentration of 118 g/L was achieved after 38 h with the productivity of 3.1 g/L/h (46% conversion ratio from glucose to threonine). | 18,931,947 |
Engineering of cysteine residues leads to improved production of a human dipeptidase enzyme in E. coli. | Low yields, poor folding efficiencies and improper disulfide bridge formation limit large-scale production of cysteine-rich proteins in Escherichia coli. Human renal dipeptidase (MDP), the only human beta-lactamase known to date, is a homodimeric enzyme, which contains six cysteine residues per monomer. It hydrolyses penem and carbapenem beta-lactam antibiotics and can cleave dipeptides containing amino acids in both D: - and L: -configurations. In this study, MDP accumulated in inactive form in high molecular weight, disulfide-linked aggregates when produced in the E. coli periplasm. Mutagenesis of Cys361 that mediates dimer formation and Cys93 that is unpaired in the native MDP led to production of soluble recombinant enzyme, with no change in activity compared with the wild-type enzyme. The removal of unpaired or structurally inessential cysteine residues in this manner may allow functional production of many multiply disulfide-linked recombinant proteins in E. coli. | 18,931,951 |
Bioindication of trace metals in Brachythecium rutabulum around a copper smelter in Legnica (Southwest Poland): Use of a new form of data presentation in the form of a self-organizing feature map. | Concentrations of the elements Al, Be, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn were measured in the terrestrial moss Brachythecium rutabulum and the soil on which it grew. Soil and moss plants were sampled at sites situated 1.5, 3, 6, 9 and 15 km to the north, south, east and west of the Legnica copper smelter (SW Poland). The self-organizing feature map (SOFM) or Kohonen network was used to classify the soil and moss samples according to the concentrations of the elements. The self-organizing map yielded distinct groups of B. rutabulum and soil samples, depending on the distance from and direction to the source of pollution. When the map-identified groups of sites with similar soil metal concentrations were combined with the map-identified groups of sites with similar metal concentrations in B. rutabulum, these maps were found to correspond closely. The SOFMs accurately represented the least polluted, moderately polluted and severely polluted sites, reflecting the distribution of metals that is typical of the smelter area, caused by the prevailing westerly and northerly winds. | 18,931,962 |
[New perspectives in the laboratory diagnosis of dementia]. | Over the past 10 years, the status of laboratory analysis in dementia has increasingly changed from its use for exclusion diagnoses for secondary causes of dementias to determining positive diagnoses of neurodegenerative dementias. This especially applies to the cerebrospinal fluid diagnosis of Alzheimer's disease (AD). Just a few years ago, a lumbar puncture was advised only with sufficiently founded clinical suspicion and with higher priority for the exclusion of inflammatory causes of cognitive dementias. In contrast, pathologically changed biomarkers in the cerebrospinal fluid have already been indexed as supportive attributes of the diagnosis in the 2007 amended research criteria of AD. The lumbar puncture is therefore increasingly becoming part of the clinical routine diagnosis of demential processes and has, to some extent, far-reaching consequences. In this article, we discuss some of the important aspects. | 18,931,988 |
[Testosterone substitution with special regard to prostate cancer]. | Testosterone substitution is used to treat the symptoms of low testosterone in men who do not produce enough natural testosterone. Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality and also affect quality of life. The regular investigation of PSA, prostate, and ultrasound is necessary. | 18,931,991 |
Combining microchip and cell technology for creation of novel biodevices. | Microchip technology has matured over the years into an important field in which novel technologies are being constantly invented, and down-sizing and incorporation of already existing methodologies into the microscale is increasing assay performance and bearing the promise of future total integration for simple, widespread use. One rapidly growing sub-discipline of the microchip research field is focused around the integration of microchip technology and cell biology. In this review, we recapitulate progress here at the Kitamori laboratory in direct relation to cell and microchip technologies, and show some examples of successful integration of the two, going from controlled patterning of cells, on-chip cell culture stimulation, and cardiovascular systems on a chip, to bio-microdevices integrating cardiovascular cells and microtechnology to create novel biodevices such as biocompatible, miniature pumps. | 18,931,993 |
Chiral separation of raltitrexed by cyclodextrin-modified micellar electrokinetic chromatography. | A rapid and effective method was developed for the chiral separation of raltitrexed (RD) enantiomers by carboxymethyl-beta-cyclodextrin (CM-beta-CD)-modified micellar electrokinetic chromatography (MEKC). Optimization of conditions including the type and concentration of the chiral selector, concentration of sodium dodecyl sulfate (SDS), pH and concentration of the background electrolyte (BGE), capillary temperature, and applied voltage was investigated. The enantiomers of raltitrexed could be separated with satisfactory resolution and linear response by using 75 mM Tris-phosphate at pH 8.0 containing 30 mM SDS and 8 mM CM-beta-CD as buffer system. Furthermore, the usefulness of this method was demonstrated in a purity test of a real synthetic drug sample. | 18,931,995 |
Association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density: a meta-analysis. | The association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density (BMD) has been studied, but results have been mixed. Accordingly, the authors performed a meta-analysis on studies on the association between the A1330V LRP5 polymorphism and BMD. Appropriate studies were identified using MEDLINE and by manual searching. A total of 7 separate comparisons were considered in this meta-analysis. Individuals with the AA genotype showed significantly higher lumbar BMD than those with the AV/VV or VV genotype. Weighted mean differences (WMDs) were 0.147 g/cm(2) (95% confidence interval [CI] 0.069-0.224, P < 0.001) and 0.182 g/cm(2) (95% CI 0.024-0.340, P = 0.024) without between-study heterogeneity for AA versus AV/VV and AA versus VV, respectively. Six studies analyzed femur neck (FN) BMD. Individuals with the AA genotype had a significantly higher FN BMD than those with the AV/VV genotype (WMD = 0.165 g/cm(2), 95% CI = 0.087-0.215, P < 0.001), without between-study heterogeneity. Trochanter BMD was measured in three studies. Results showed that subjects with the AA genotype tended to have higher BMD than patients with the AV or VV genotype (WMD = 0.136 g/cm(2), 95% CI = -0.002 to 0.274, P = 0.053). In conclusion, this meta-analysis shows that the LRP5 A1330V polymorphism is associated with BMD, and that individuals with the AA genotype have a higher BMD than those with the AV/VV or VV genotype. | 18,932,002 |
[Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD]. | There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD. | 18,932,031 |
Effect of dietary alpha-ketoglutarate on blood lipid profile during hypercholesterolaemia in rats. | The aim of the study was to determine the effect of alpha-ketoglutarate on the blood lipid profile using a rat animal model with experimentally induced hypercholesterolaemia. The female and male (30/30) Wistar rats had ad libitum access to a diet containing cholesterol (1 %) and lard (10 %) throughout the entire experimental period (120 days). On day 60 of the study, both the females and the males were divided into three groups, the first receiving a mixture of drinking water adjusted to pH 4.6 using HCl (control), the other two (experimental groups) receiving a solution containing 0.01 M and 0.1 M alpha-ketoglutarate (AKG) (pH adjusted to 4.6). Blood samples were taken on days 0, 30, 60 and 120. The concentrations of total cholesterol, triglycerides, HDL and LDL, respectively, in the blood serum were estimated spectrophotometrically. During the entire experimental period the total cholesterol, triglycerides and LDL levels of the control rats increased, whereas that of HDL decreased. The serum concentrations of total cholesterol, LDL and triglycerides in both the experimental groups receiving AKG decreased (days 60 to 120) (p<0.05), while the HDL concentration tended to increase. The body gain in all groups receiving AKG was significantly lower than in the control group. These observations clearly prove that oral treatment with AKG can decrease the risk of hypercholesterolaemia developing and can lower the body weight. The relative concentrations of the plasma LDL and HDL changed to a more favourable ratio promoting good health. | 18,932,049 |
Seasonal variations in the chemical composition of vine-grape leaf surface. | Surface leaf metabolites of two seedlings of a Bulgarian winemaking cultivar Storgozia I(1) were analyzed in two seasons - summer (July) and autumn (October). The resistance towards some fungal pathogens of one of the plants was estimated as superior to the resistance of the other one. Significant seasonal variations in the chemical constituents of the two seedlings were observed. The main metabolites of the summer samples were sterols, terpenes, fatty acids and heterocyclic compounds. In autumn, sterol and fatty acid contents decreased, mono- and diterpenes and heterocyclic compounds disappeared and instead of them hydrocarbons and alcohols were detected. Some individual components - stearic acid, alpha-amyrin, lupeol and squalene - correlated with the estimated resistance and were therefore proposed as biomarkers for the fungal resistance in grape-vine leaves. | 18,932,086 |
Endoscopic approach to tensor fold in patients with attic cholesteatoma. | The endoscopic approach to attic cholesteatoma allows clear observation of the tensor fold area and consequently, excision of the tensor fold, modifying the epitympanic diaphragm. This permits good removal of cholesteatoma and direct ventilation of the upper unit, preventing the development of a retraction pocket or attic cholesteatoma recurrence, with good functional results. An isthmus block associated with a complete tensor fold is a necessary condition for creation and development of an attic cholesteatoma. During surgical treatment of attic cholesteatoma, tensor fold removal is required to restore ventilation of the attic region. Use of a microscope does not allow exposure of the tensor fold area and so removal of the tensor fold can be very difficult. In contrast, the endoscope permits better visualization of the tensor fold area, and this aids understanding of the anatomy of the tensor fold and its removal, restoring attic ventilation. In all, 21 patients with limited attic cholesteatoma underwent an endoscopic approach with complete removal of the disease. Patients with a wide external ear canal were operated through an exclusively endoscopic transcanal approach; patients with a narrow external ear canal or who were affected by external canal exostosis were operated through a traditional retroauricular incision and meatoplasty followed by the endoscopic transcanal approach. In 18/21 patients, the endoscope permitted the discovery of different anatomical morphologies of the tensor fold. Sixteen patients presented a complete tensor fold (one with an anomalous transversal orientation), one patient presented an incomplete tensor fold and one patient presented a bony ridge in the cochleariform region. In all 16 cases of complete tensor tympani fold, the fold was removed and anterior epitympanic ventilation was restored. The ridge bone over the cochleariform process was also removed with a microdrill. | 18,932,099 |
[Social inequality in medical rehabilitation]. | The association of social inequality and health is well known and well documented. Numerous studies have shown that a lower socio-economic status is associated with higher morbidity and mortality. This association is caused by various circumstances such as unfavourable work and living conditions, unhealthy life styles and risk factors and, last but not least, the access to medical care depending on socio-economic status. These aspects are correlated in various ways, at any rate they cause a higher prevalence of diseases and lower quality of life in persons with lower socio-economic status. The present article discusses the association between social inequality and medical rehabilitation, a problem which is rarely investigated in present research on social inequality and health. In our study, 911 rehabilitation patients were included. Analyses of socio-economic differences with respect to rehabilitation care address the following questions: are there differences in access to medical rehabilitation, in rehabilitation care, with respect to success of rehabilitation and satisfaction with rehabilitation? To assign patients to a social class - lower, middle and upper class - we constructed an indicator of social status based on education, occupation and income level. Our findings in a sample of rehabilitation patients are in line with the results of existing research on social inequality and health. Patients from the lower social class enter the rehabilitation care system with a poorer health state and leave it with less favourable results than patients with higher social status. However, with regard to the effect of rehabilitation care, middle class patients benefit least. It can be speculated that systematic information of patients about the aims of the rehabilitation programme and specific after care focusing on relevant aspects of daily living may reduce the disadvantages of lower class patients. | 18,932,119 |
On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. | Based on genotype-phenotype correlation analysis of 80 Wolf-Hirschhorn syndrome (WHS) patients, as well as on review of relevant literature, we add further insights to the following aspects of WHS: (1) clinical delineation and phenotypic categories; (2) characterization of the basic genomic defect, mechanisms of origin and familiarity; (3) identification of prognostic factors for mental retardation; (4) chromosome mapping of the distinctive clinical signs, in an effort to identify pathogenic genes. Clinically, we consider that minimal diagnostic criteria for WHS, defining a "core" phenotype, are typical facial appearance, mental retardation, growth delay and seizures (or EEG anomalies). Three different categories of the WHS phenotype were defined, generally correlating with the extent of the 4p deletion. The first one comprises a small deletion not exceeding 3.5 Mb, that is usually associated with a mild phenotype, lacking major malformations. This category is likely under-diagnosed. The second and by far the more frequent category is identified by large deletions, averaging between 5 and 18 Mb, and causes the widely recognizable WHS phenotype. The third clinical category results from a very large deletion exceeding 22-25 Mb causing a severe phenotype, that can hardly be defined as typical WHS. Genetically, de novo chromosome abnormalities in WHS include pure deletions but also complex rearrangements, mainly unbalanced translocations. With the exception of t(4p;8p), WHS-associated chromosome abnormalities are neither mediated by segmental duplications, nor associated with a parental inversion polymorphism on 4p16.3. Factors involved in prediction of prognosis include the extent of the deletion, the occurrence of complex chromosome anomalies, and the severity of seizures. We found that the core phenotype maps within the terminal 1.9 Mb region of chromosome 4p. Therefore, WHSCR-2 should be considered the critical region for this condition. We also confirmed that the pathogenesis of WHS is multigenic. Specific and independent chromosome regions were characterized for growth delay and seizures, as well as for the additional clinical signs that characterize this condition. With the exception of parental balanced translocations, familial recurrence is uncommon. | 18,932,124 |
General solutions to multiple testing problems. Translation of "Sonnemann, E. (1982). Allgemeine Lösungen multipler Test probleme. EDV in Medizin und Biologie 13(4), 120-128". | The introduction of sequentially rejective multiple test procedures (Einot and Gabriel, 1975; Naik, 1975; Holm, 1977; Holm, 1979) has caused considerable progress in the theory of multiple comparisons. Emphasizing the closure of multiple tests we give a survey of the general theory and its recent results in applications. Some new applications are given including a discussion of the connection with the theory of confidence regions. | 18,932,150 |
Aesthetics and power considerations in multiple testing--a contradiction? | In this paper we discuss aesthetical concepts and requirements for reasonable multiple test procedures. Aesthetical considerations lead to logical decision patterns which are conceivable and, if possible, simple to use and to communicate. Such considerations are sometimes contradictory to the ubiquitous requirement of maximizing power for a multiple test procedure. We illustrate the necessary trade-offs with several examples. We start by considering important logical properties and then discuss three different concepts of monotonicity. Afterwards we have a closer look at the recently proposed "fallback procedure" and show that it has some less appealing properties. Finally, we investigate the distribution of the numbers of significant results with respect to both expectation and variance. | 18,932,151 |
Ion-responsive behavior of ionic-liquid surfactant aggregates with applications in controlled release and emulsification. | We propose a simple but efficient, rapid, and quantitative ion-responsive micelle system based on counter-anion exchange of a surfactant with an imidazolium unit. The ion-exchange reaction results in the amphiphilic-to-hydrophobic transition of the imidazolium salt, leading to the destruction of the micelles, which has been successfully applied to controlled release and emulsification. The proposed design offers a novel alternative stimulus to control these smart physical aggregates besides pH, temperature and light-with extra advantages. Our finding greatly benefits both fundamental research and industry. | 18,932,155 |
The proximal promoter governs germ cell-specific expression of the mouse glutathione transferase mGstm5 gene. | To explain the tissue-selective expression patterns of a distinct subclass of glutathione S-transferase (GST), transgenic mice expressing EGFP under control of a 2 kb promoter sequence in the 5'-flanking region of the mGstm5 gene were produced. The intent of the study was to establish whether the promoter itself or whether posttranscriptional mechanisms, particularly at the levels of mRNA translation and stability or protein targeting, based on unique properties of mGSTM5, determine the restricted expression pattern. Indeed, the transgene expression was limited to testis as the reporter was not detected in somatic tissues such as brain, kidney or liver, indicating that the mGstm5 proximal promoter is sufficient to target testis-specific expression of the gene. EGFP expression was also more restricted vis-a-vis the natural mGstm5 gene and exclusively found in germ but not in somatic cells. Real-time quantitative PCR (qPCR) data were consistent with alternate transcription start sites in which the promoter region of the natural mGstm5 gene in somatic cells is part of exon 1 of the germ cell transcript. Thus, the primary transcription start site for mGstm5 is upstream of a TATA box in testis and downstream of this motif in somatic cells. The 5' flanking sequence of the mGstm5 gene imparts germ cell-specific transcription. | 18,932,202 |
Staircase but not posttetanic potentiation in rat muscle after spinal cord hemisection. | Spinal cord hemisection (SCH) results in atrophy of skeletal muscle and altered contractile properties. In this study our purpose was to assess staircase and posttetanic potentiation in the rat gastrocnemius muscle in situ, 1 week after SCH. Tetanic force was reduced by SCH, but twitch amplitude was not. The time course and magnitude of staircase during stimulation at 5 HZ (for 21 s) was similar in the control, sham-operated, and SCH groups. However, posttetanic potentiation observed after 100-, 500-, and 1000-ms tetanic (200 HZ) contractions was absent or drastically reduced after SCH. Twitch force increased 44+/-8.7%, 47+/-7.4%, and 15+/-2.8% for the control, sham, and SCH groups, respectively, after the 1000-ms tetanic contraction. After the 1000-ms tetanic contraction, twitch active force decreased in all groups and was significantly reduced at 5 min relative to pretetanic twitch. In the control and sham groups, but not SCH, the active force recovered to the pretetanic level by 15 min. Resting regulatory light chain (RLC) phosphorylation was 15.4+/-2.5% and 10.97+/-3.3% for the control and SCH groups, respectively. After the 1-s tetanic contraction, values were 41.6+/-2.8% and 9.3+/-2.9%, respectively. The potentiation observed in the SCH animals with 1000-ms contraction apparently occurred without increases in RLC phosphorylation. One week after SCH there were clear changes in the contractile properties typically associated with prior activation. It is concluded that activity-dependent potentiation can occur by a mechanism that is independent of RLC phosphorylation, and accelerated fatigue can mask the potentiating effects of prior activity. | 18,932,208 |
Knockout of striatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. | STriatal Enriched protein tyrosine Phosphatase (STEP) is a brain-specific protein that is thought to play a role in synaptic plasticity. This hypothesis is based on previous findings demonstrating a role for STEP in the regulation of the extracellular signal-regulated kinase1/2 (ERK1/2). We have now generated a STEP knockout mouse and investigated the effect of knocking out STEP in the regulation of ERK1/2 activity. Here, we show that the STEP knockout mice are viable and fertile and have no detectable cytoarchitectural abnormalities in the brain. The homozygous knockout mice lack the expression of all STEP isoforms, whereas the heterozygous mice have reduced STEP protein levels when compared with the wild-type mice. The STEP knockout mice show enhanced phosphorylation of ERK1/2 in the striatum, CA2 region of the hippocampus, as well as central and lateral nuclei of the amygdala. In addition, the cultured neurons from KO mice showed significantly higher levels of pERK1/2 following synaptic stimulation when compared with wild-type controls. These data demonstrate more conclusively the role of STEP in the regulation of ERK1/2 activity. | 18,932,218 |
Altered netrin-1 receptor expression in dopamine terminal regions following neonatal ventral hippocampal lesions in the rat. | Neonatal ventral hippocampal (nVH) lesions in rats, which model certain features of schizophrenia, alter dopamine (DA)-mediated behaviors in adulthood. The precise mechanisms underlying these effects remain elusive; however, neuronal reorganization within the medial prefrontal cortex (mPFC) has been suggested. Netrins are developmental cues that organize brain wiring, including the mesocorticolimbic DA circuitry. We showed recently that the netrin-1 receptors DCC and UNC5H are highly expressed by DA neurons and that variation in DCC levels during development lead to profound changes in mesocorticolimbic DA function and behavior in adulthood. We hypothesized that changes in netrin-1 receptor function could be one of the mechanisms producing enduring changes in DA function in nVH-lesioned animals. To begin to explore this idea, we examined the effects of nVH lesions on DCC and UNC5H expression in brain regions receiving robust DA innervation; the mPFC, striatum, and nucleus accumbens (NAcc) at three developmental time points; 3 days after lesion, before puberty and during early adulthood. Expression was also examined in the cerebellar simple lobule; a brain region deprived of DA innervation. Neonatal VH lesions produced dynamic changes in DCC expression in the mPFC and NAcc. The direction and magnitude of these changes depended on the developmental age and brain region examined and were specific to regions receiving DA innervation. Although further studies are required to understand the functional significance of these changes, these results raise the interesting possibility that nVH lesions, and perinatal insults in general, may exert their neuronal reorganizational effects by modulating netrin-1 function. | 18,932,228 |
Clinical significance of low expression of Prostasin mRNA in human gastric cancer. | Prostasin is considered to have suppressive activities against tumor progression. The aim of this study was to clarify its clinical significance in gastric cancer. Tumor and the corresponding normal samples were prepared from a total of 108 gastric cancer patients. Prostasin expression was assayed by real time reverse transcription (RT)-polymerase chain reaction (PCR) and by immunohistochemistry. Epigenetic silencing of the expression was examined by demethylation treatment. Survival was examined in Kaplan-Meier plots, and the relationship between its expression and clinicopathologic factors was statistically analyzed. Prostasin mRNA expression was significantly down-regulated in tumor tissues. Immunohistochemistry confirmed loss of Prostasin expression in gastric cancer. Gastric cancer cell lines that did not express Prostasin mRNA retrieved its expression following demethylation treatment. In those patients whose tumor expressed Prostasin mRNA at reduced levels, we observed shorter survival (P = 0.0110), due to a higher incidence of lymph node metastasis (P = 0.0087), lymphatic permeation (P = 0.0542) and venous permeation (P = 0.0492). Prostasin mRNA expression was frequently down-regulated in gastric cancer. Loss of expression might be regulated by epigenetic factors, contributing to the shorter survival. Reduced Prostasin mRNA expression might be a novel indicator for biological aggressiveness in gastric cancer. | 18,932,242 |
Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer : implications for management. | Among screened populations, it is unknown whether men with prostate cancer (PC) diagnosed at the initial screening (prevalent cases) have a different outcome than men who are diagnosed at subsequent screenings (incident cases) after adjusting for known prognostic factors. The current study cohort was comprised of 1923 men from a prospective PC screening study who underwent radical prostatectomy (RP) between September 19, 1989 and May 22, 2002. Cox regression multivariate analysis was used to determine whether having prevalent PC versus incident PC was associated with the time to prostate-specific antigen (PSA) failure after RP after adjusting for PSA level, Gleason score, clinical tumor (T) classification, and year of RP. Men with prevalent PC had higher PSA levels (P < .001) and more advanced clinical T classification (P < .001) than men with incident PC. After a median follow-up of 6.1 years, factors that were associated with a significantly shorter time to PSA failure after RP were prevalent PC (adjusted hazard ratio [AHR], 1.8; 95% confidence interval [95% CI], 1.3-2.6; P = .0005), baseline PSA (AHR, 1.07; 95%CI, 1.04-1.09; P < .001), Gleason 7 disease (AHR, 2.5; 95% CI, 1.9-3.3; P < .001), Gleason 8 to 10 disease (AHR, 2.3; 95%CI, 1.5-3.5; P < .001), and the year of RP (AHR, 0.92; 95%CI, 0.86-0.97; P = .003). Men with prevalent PC also had worse outcomes after adjusting for their more advanced pathologic features. After adjusting for known prognostic factors, men with prevalent PC had a poorer outcome after RP than men with incident PC. The authors believe that this finding should be taken into consideration when weighing the risk of recurrence and treatment options for men who are diagnosed with PC on their initial screening. | 18,932,254 |
Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-gamma. | To examine the role of Fibrinogen-like protein 2 (fgl2)/fibroleukin in tumor development. Fgl2 has been reported to play a vital role in the pathogenesis in MHV-3 (mouse hepatitis virus) induced fulminant and severe hepatitis, spontaneous abortion, allo- and xeno- graft rejection by mediating "immune coagulation". Tumor tissues from 133 patients with six types of distinct cancers and the animal tumor tissues from human hepatocellular carcinoma (HCC) model on nude mice (established from high metastasis HCC cell line MHCC97LM6) were obtained. Hfgl2 was detected in tumor tissues from 127 out of 133 patients as well as tumor tissues collected from human HCC nude mice. Hfgl2 was highly expressed both in cancer cells and interstitial inflammatory cells including macrophages, NK cells, and CD8(+) T lymphocytes and vascular endothelial cells. Hfgl2 mRNA was localized in cells that expressed hfgl2 protein. Fibrin (nogen) co-localization with hfgl2 expression was determined by dual immunohistochemical staining. In vitro, IL-2 and IFN-gamma increased hfgl2 mRNA by 10-100 folds and protein expression in both THP-1 and HUVEC cell lines. One-stage clotting assays demonstrated that THP-1 and HUVEC cells expressing hfgl2 had increased procoagulant activity following cytokines stimulation. The hfg12 contributes to the hypercoagulability in cancer and may induce tumor angiogenesis and metastasis via cytokine induction. | 18,932,275 |
Is ineffective esophageal motility associated with gastropharyngeal reflux disease? | To evaluate the association between ineffective esophageal motility (IEM) and gastropharyngeal reflux disease (GPRD) in patients who underwent ambulatory 24-h dual-probe pH monitoring for the evaluation of supraesophageal symptoms. A total of 632 patients who underwent endoscopy, esophageal manometry and ambulatory 24-h dual-pH monitoring due to supraesophageal symptoms (e.g. globus, hoarseness, or cough) were enrolled. Of them, we selected the patients who had normal esophageal motility and IEM. The endoscopy and ambulatory pH monitoring findings were compared between the two groups. A total of 264 patients with normal esophageal motility and 195 patients with the diagnosis of IEM were included in this study. There was no difference in the frequency of reflux esophagitis and hiatal hernia between the two groups. All the variables showing gastroesophageal reflux and gastropharyngeal reflux were not different between the two groups. The frequency of GERD and GPRD, as defined by ambulatory pH monitoring, was not different between the two groups. There was no association between IEM and GPRD as well as between IEM and GERD. IEM alone cannot be considered as a definitive marker for reflux disease. | 18,932,282 |
Endoscopic ultrasound-guided choledochoduodenostomy in patients with failed endoscopic retrograde cholangiopancreatography. | Endoscopic ultrasonography (EUS)-guided biliary drainage was performed for treatment of patients who have obstructive jaundice in cases of failed endoscopic retrograde cholangiopancreatography (ERCP). In the present study, we introduced the feasibility and outcome of EUS-guided choledochoduodenostomy in four patients who failed in ERCP. We performed the procedure in 2 papilla of Vater, including one resectable case, and 2 cases of cancer of the head of pancreas. Using a curved linear array echoendoscope, a 19 G needle or a needle knife was punctured transduodenally into the bile duct under EUS visualization. Using a biliary catheter for dilation, or papillary balloon dilator, a 7-Fr plastic stent was inserted through the choledochoduodenostomy site into the extrahepatic bile duct. In 3 (75%) of 4 cases, an indwelling plastic stent was placed, and in one case in which the stent could not be advanced into the bile duct, a naso-biliary drainage tube was placed instead. In all cases, the obstructive jaundice rapidly improved after the procedure. Focal peritonitis and bleeding not requiring blood transfusion was seen in one case. In this case, pancreatoduodenectomy was performed and the surgical findings revealed severe adhesion around the choledochoduodenostomy site. Although further studies and development of devices are mandatory, EUS-guided choledochoduodenostomy appears to be an effective alternative to ERCP in selected cases. | 18,932,289 |
Orthotopic heart transplantation: ten years' clinical experience. | Heart transplantation is the "gold standard" in the treatment of patients with end-stage heart failure who satisfy strict selection criteria. We reviewed ten years' clinical experience (1996-2006) from 53 orthotopic transplants in our centre. Low perioperative (3.7%) and long-term (7.5%) mortality rates yielded a 95% survival rate in the first year, 92% at five years, and 70% at ten years--significantly better than the corresponding rates worldwide. In addition, excellent functional recovery was achieved in all transplant recipients. The strict application of international criteria in the selection of both candidates and donors, together with uninterrupted, multidisciplinary follow up, have made it feasible to perform heart transplantation with excellent results, despite the curiously low number of potential recipients and the shortage of acceptable donor hearts. | 18,935,709 |
Health-related quality of life measurement in patients admitted with coronary heart disease and heart failure to a cardiology department of a secondary urban hospital in Greece. | The aim of this study was to measure the quality of life in patients with coronary heart disease and heart failure, who make up the majority of admissions to an acute hospital cardiology unit. The study was undertaken in the General Hospital of Agios Nikolaos, Crete, and recruited 153 patients. The SF-36 and EQ-5D questionnaires were administered to evaluate health-related quality of life at hospital admission, discharge and one month after the discharge date. The analysis indicates that the quality of life of coronary disease patients is quite low and improved very marginally between admission and one month post discharge. The same applies for heart failure patients, who are associated with even lower quality of life scores. As illness affects all aspects of life, such as physical functioning, emotional balance, social role and general wellbeing, measurement of quality of life is considered to be an important factor in the assessment of the objective and subjective status of the individual's health. It appears in this context that patients with cardiac conditions suffer a significant deterioration in their quality of life status. | 18,935,711 |
Abdominal aortic aneurysm in a renal transplant patient. | Repair of an abdominal aortic aneurysm in a renal transplant recipient poses many different problems due to warm ischaemia to the grafted kidney. This is a case of 50-year-old gentleman who had a pervious renal transplant with abdominal aortic aneurysm. To reduce the effects of warm ischaemia on the transplanted kidney, an axillo unifemoral bypass was done prior to aneurysm repair. This ensured continued perfusion to the transplanted kidney. The post operative period was complicated by Methicillin Resistant Staphyloccus Aureus infection of the graft. | 18,935,743 |
[Assessment of health related quality of life--Part 1--Direct measures]. | Assessment of the impact of medical interventions on patient's quality of life is becoming a major aspect in evaluating the effectiveness of these interventions. Based on the concept of combining life expectancy and quality of life in a single value, many tools for measuring this effect have been developed in the last few decades. Quality-adjusted life years (QALYs) are calculated by multiplying life expectancy by a factor representing the quality of life during that period. Health related quality of life may be measured directly by several methods. The most commonly used are Visual Analogue Scale (VAS), Standard gamble (SG) and Time Trade-Off (TTO). This article reviews these three methods, their applications and their advantages and disadvantages. It also addresses some of the problems characteristic of each measure, their theoretical and practical differences and the implications of those differences on the values obtained from each one. Finally, the article discusses the attempts to map the relationships between the three measures, in order to be able to convert values from one to another. | 18,935,765 |
Prevention of mother-to-child transmission of HIV: the Georgian experience. | The objective of this paper is to review experience in prevention of mother-to-child transmission (PMTCT) of HIV in Georgia. PMTCT is one of the strategic priorities in Georgia. The first case of HIV infection in pregnant women was reported in 1999. Starting 2005 the National Programme on PMTCT became operational. One hundred sixteen HIV voluntary counselling and testing (VCT) centers operate throughout the country at antenatal clinics. According to the National PMTCT protocol, all first time attending pregnant women are offered Voluntary Counselling and Testing (VCT). Testing on HIV/AIDS is based on identification of HIV antibodies by screening method and all positive results are referred to the Infectious Diseases, AIDS and Clinical Immunology Research Center (IDACIRC) for the further investigation (confirmation by Western Blot assay) and further management. Data collection was made retrospectively, using information from IDACIRC National HIV/AIDS Data Base, VRF for the period 1999-2007. Prevalence of HIV among pregnant women availing VCT services in 2006 was 0.03%. As of December, 2007 total 69 pregnancies of 64 women were registered at the IDACIRC. Fifty eight women (90.6%) acquired infection through heterosexual contact. None of the HIV positive women reported intravenous injection of illicit drugs. The majority of the HIV infected pregnant women had one sexual partner (90.6%). Of children delivered by 51 positive partners 41(80%) were infected through injecting drugs intravenously and 10 (20%) persons through heterosexual contacts. Throughout the period 1999-2007 14 pregnant women received PMTCT services only partially. In 2 cases children were HIV-infected. In 12 pregnancies women received AZT in about the 28th week of pregnancy. No case of HIV transmission to child was recorded in this group. In 32 cases pregnant women received full prophylaxis therapy and all children were negative for HIV infection. Among 6 pregnant women admitted at IDACIRC later than the 28th week of pregnancy only 1 child was infected. As of December 2007, 5 women are still pregnant. Three of them receive antiretroviral drugs (ARV) prophylaxis with AZT+3TC+SQV/r. Two women are under 28 weeks of gestational age. Over the last several years the national response to AIDS in Georgia achieved significant progress. The provision of comprehensive packages of PMTCT services in Georgia has been shown to minimize the risk of vertical transmission. As described above none of the women completing full course of ARV prophylaxis, combined with appropriate infant feeding, transmitted HIV to their children. PMTCT programmes are indisputably the main entry point not only for HIV related care and treatment for women, but also for other comprehensive care and prevention. | 18,935,779 |
Postoperative residual curarization: clinical observation in the post-anesthesia care unit. | Neuromuscular blocking agents (NMBAs) are widely used during the induction and maintenance of anesthesia. Postoperative residual curarization (PORC) following the use of NMBAs still occurs even though intermediate-acting NMBAs were used. Train-of-four (TOF) stimulation is used to quantify the degree of neuromuscular blockade. The TOF ratio of 0.7 in the adductor pollicis muscle was associated with normal respiratory function. Pharyngeal function returned to normal while the TOF ratio reached 0.9. The aim of this study was to survey the PORC in the post-anesthesia care unit (PACU). In this observational study, 308 patients who received general anesthesia with NMBAs were enrolled. Residual curarization was evaluated using the TOF-Watch acceleromyograph upon arrival in the PACU. Three consecutive TOF stimulations were applied and recorded at 15-second intervals. Two thresholds of TOF ratios (0.9 and 0.7) were used to assess the presence of residual curarization. TOF ratios less than 0.7 and 0.9 were observed in 15 (5%), and 97 (31%) patients, respectively. The differences of the TOF ratios between the male and female patients were significant (p = 0.014). In terms of weight, the differences between the patients with ratios > 0.9 and < or = 0.9 were significant (p = 0.013). There were 67, 49, 15, and three patients who received reversal medication in the > 0.9 group, < or = 0.9 and > 0.7 group, and < or = 0.7 group, respectively. The differences of the TOF ratios between the patients who received and those who did not receive reversal medication were not significant (p = 0.91). PORC is still a clinical problem in the modern PACU. Objective neuromuscular monitoring needs to be performed to ensure patient safety. | 18,935,794 |
Implantable hearing aids. | The aim of this article is to give readers a general overview of the concepts involved in the latest generation of implantable hearing aids. A section on ear biomechanics has also been included to familiarize readers with the basic concepts involved. These devices have been developed over the last 20 years, driven by problems with conventional hearing aids and by advances in the understanding of middle-ear mechanics. The use of technology borrowed from cochlear implants has enabled the first generation of fully implantable aids to be trialled. The author examines the theoretical advantages and disadvantages of implantable hearing aids over conventional aids and then reviews the technology and clinical results of a range of devices that have been trialled. | 18,935,801 |
Compliant layer bearings in artificial joints. Part 1: the effects of different manufacturing techniques on the interface strength between an elastomeric layer and a rigid substrate. | The premise that elastomeric materials could be used as one or more of the articulating components in both hip and knee prostheses was postulated first by Unsworth and co-workers. It was thought that such materials might have the capacity to mimic natural joint behaviour more closely than the more rigid bearing surfaces commonly in use. A more natural joint function in artificial joints should promote better tribology, with full fluid-film lubrication being the goal. Early tests showed that this objective could potentially be achieved with a judicious choice of materials and carefully controlled manufacturing techniques. This paper (Part 1 of a two-part series) describes and explains the techniques used to verify the material selection as well as to determine the most appropriate manufacturing procedure to obtain a strong and robust interface between the support and bearing material of the prosthesis. Two polycarbonate urethane (PU) materials with different hardness values (Corethane 80A and Corethane 75D) gave sufficient interfacial strength when moulded under optimum conditions. Corethane 80A was used as the soft bearing material while Corethane 75D provided the rigid backing component. Peel tests revealed strong interface bonds, varying with processing conditions between 350 and 862 N. Fourier transform infrared spectroscopy and micro-thermal analysis showed that a fusion bond over 30 microm thick formed at the interface. The results of the range of tests and analyses, which have been used in this study, have provided sufficient evidence to validate the process used to manufacture these components. | 18,935,802 |
Objective functional assessment of total hip arthroplasty following two common surgical approaches: the posterior and direct lateral approaches. | Despite the high number of total hip arthroplasty (THA) procedures performed each year, there is no common consensus on the best surgical approach. Gait is known to improve following THA although it does not return to what is typically quantified as normal, and surgical approach is believed to be a contributing factor. The current study evaluates postoperative hip function and provides an objective assessment following two common surgical approaches: the McFarland-Osborne direct lateral and the southern posterior. Faced with the common problem of providing an objective comparison from the wealth of data collected using motion analysis techniques, the current study investigates the application of an objective classification tool to provide information on the effectiveness of each surgery and to differentiate between the characteristics of hip function following the two approaches. Seven inputs for the classifier were determined through statistical analysis of the biomechanical data. The posterior approach group exhibited greater characteristics of non-pathological gait and displayed a greater range of functional ability as compared with the lateral approach cohort. The classification tool has proved to be successful in characterizing non-pathological and THA function but was insufficient in distinguishing between the two surgical cohorts. | 18,935,806 |
A biomechanical assessment of the coupling of torsion and tension in the human scapholunate ligament. | The mechanical behaviour of human scapholunate ligaments is not well described in the literature with regard to torsion. In this study, intact scapholunate specimens were mechanically tested in torsion to determine whether a simultaneous tensile load was generated. Human intact scapholunate specimens (n = 19) were harvested. The scaphoid and lunate bones were potted in square chambers using epoxy cement, while the interposing ligament remained exposed. Each specimen was mounted rigidly in a specially designed test jig and remained at a fixed axial length during all tests. Specimens were subjected to a torsional load regime that included cyclic preconditioning, ramp-up, stress relaxation, ramp-down, rest, and torsion to failure. Torque and axial tension were monitored simultaneously. The relationship between torsion and tension was determined. Graphs of torque versus tension were generated, from which outcome measures were extracted. Tests demonstrated a clear relationship between applied torsion and the resulting generation of tension for the ligament during ramp-up (torsion-to-tension ratio, 38.86 +/- 29.00 mm; linearity coefficient R2 = 0.89 +/- 0.15; n = 19), stress relaxation (torsion-to-tension ratio, 23.43 +/- 15.84 mm; R2 = 0.90 +/- 0.09; n = 16), and failure tests (torsion-to-tension ratio, 38.81 +/- 26.39mm; R2 = 0.77 +/- 0.20; n = 16). No statistically significant differences were detected between the torsion-to-tension ratios (p = 0.13) or between the linearity (R2) of the best-fit lines (p > 0.085). A strongly coupled linear relationship between torsion and tension for the scapholunate ligament was exhibited in all test phases. This may suggest interplay between these two parameters in the stabilization of the ligament during normal motion and for injury cascades. | 18,935,807 |
Effect of curing characteristics on residual stress generation in polymethyl methacrylate bone cements. | Residual stresses resulting from the shrinkage of polymethyl methacrylate (PMMA) bone cement have been implicated in the formation of cracks in cement mantles following total hip arthroplasty. This study investigates whether two such cements, with differentiated solidification characteristics (i.e. working and setting times), display significant differences in their residual stress characteristics in an experiment designed to replicate the physical conditions of total hip arthroplasty. Experiments were performed using a representative femoral construct to measure and compare the temperatures and residual strains developed for standard PMMA cement mantles (CMW 1 Gentamicin) and slow curing cement mantles (SmartSet HV Gentamicin) during and following polymerization. These experimental results revealed no statistically significant difference (t-test, p > 0.05) for peak exotherm temperature and residual strain levels between the cements (measured after 3 h). The tailored polymerization characteristics of the slow-curing cement do not significantly affect residual stress generation, compared with the standard cement. It is often considered that residual stresses significantly relax following polymerization and before biomechanical loads are first applied during rehabilitation (up to 3 days later). This was examined for durations of 18 h to 3 days. Axial strains in the model femur and stem reduced by averages of 5.5 and 7.9 per cent respectively, while hoop strains in the stem exhibited larger reductions. An axisymmetric transient thermoelastic finite element model of the experiment was developed, allowing residual stresses to be predicted based on differential scanning calorimetry (DSC) measurements of the heat released throughout the exothermic curing reaction. The model predictions closely replicated the experimental measurements of both temperature and residual strain at 3 h, suggesting that residual strains can be fully accounted for by the thermal contraction mechanism associated with cooling after solidification. | 18,935,810 |
Natural frequency analysis of tooth stability under various simulated types and degrees of alveolar vertical bone loss. | The aim of this study was to test natural teeth stability under various simulated types and degrees of alveolar vertical bone loss, as well as to assess the role that the surrounding bone played for maintaining tooth stability. A three-dimensional finite element model of the human maxillary central incisor with surrounding tissue, including periodontal ligament, enamel, dentin, pulp, and alveolar bone, was established. One side and multiple vertical bone loss were simulated by means of decreasing the surrounding bone level apically from the cemento-enamel junction in 1 mm steps incrementally downward for 10 mm. Natural frequency values of the incisor model with various types and degrees of bone loss were then calculated. The results showed that, with one-sided bone resorption, the model with labial bone loss had the lowest natural frequency decreasing rates (8.2 per cent). On the other hand, in cases of multiple bone loss, vertical bone resorption at the mesial and distal sides had more negative effects on tooth stability compared to vertical bone losses on facial and lingual sides. These findings suggest that the natural frequency method may be a useful, auxiliary clinical tool for diagnosis of vertical periodontal diseases. | 18,935,815 |
Laser-induced breakdown spectroscopy for analysis of chemically etched polytetrafluoroethylene. | Laser-induced breakdown spectroscopy (LIBS) is used to analyze chemically etched polytetrafluoroethylene (PTFE). The elements O, F, H, and Na are determined qualitatively in the depth dimension. It is shown that O, H, and Na signals are greatest at the surface and decrease as the laser burrows through the etched layer into the bulk. In contrast, the fluorine signal is a minimum at the surface and increases with depth. The average ablation rate for PTFE under the experimental conditions is found to be 1.9 microm per pulse. Using this value, the depth of the etched layer is determined to be 8 microm. A calibration curve produced by analysis of different polymers gives mole fractions of O, F, and H at the surface of the etched PTFE of 0.2, 0.3, and 0.1, respectively. | 18,935,827 |
The lived experience and meaning of stress in acute mental health nurses. | While studies into stress in mental health nursing are small, studies specifically looking at acute mental health nurses are even fewer. Acute mental health nurses work in environments that are challenging and unpredictable, and care for some of the most seriously ill patients. This area, therefore, needs staff that are physically and psychologically fit for purpose. However, little is known about this cohort of nurses. In an attempt to address this imbalance, this study aims to ascertain the stressors--the lived experience and meaning--for acute qualified mental health staff. Using a hermeneutical phenomenological tradition, eight qualified staff from a London mental health Trust were interviewed. Heavy workloads and violent and aggressive behaviours were among the stressors giving rise to staff experiencing difficulties with switching off from work, poor support from management and fear of blame. These experiences culminated in feeling professionally compromised, less valued and struggling for recognition of the therapeutics of nursing interventions. There is an urgent need to implement stress reduction strategies in this nursing specialty. | 18,935,838 |
IV therapy: recognizing the differences between infiltration and extravasation. | Infiltration and extravasation are complications that can occur during intravenous therapy administered via either peripheral or central venous access devices. Both can result in problems with the siting of future venous access devices, nerve damage, infection and tissue necrosis. The nurse is the key to reducing the risk of infiltration and extravasation, through her knowledge and skill in cannulation and the intravenous administration of drugs (by bolus injection or infusion). The nurse must also be able to recognize the early signs and symptoms of infiltration and extravasation and act promptly and effectively to limit tissue damage. The first sign of possible leakage of drugs into the tissues is pain and discomfort, so patients must be informed of what symptoms to look out for and be asked to report any change in sensation as soon as they are aware of it. Finally, accurate documentation of the event is vital to facilitate patient care and in case of litigation. | 18,935,841 |
Is it "every man's right to have babies if he wants them"? Male pregnancy and the limits of reproductive liberty. | Since the 1980s, a number of medical researchers have suggested that in the future it might be possible for men to become pregnant. Given the role played by the right to reproductive liberty in other debates about reproductive technologies, it will be extremely difficult to deny that this right extends to include male pregnancy. However, this constitutes a reductio ad absurdum of the idea of reproductive liberty. One therefore would be well advised to look again at the extent of this purported right in other contexts in which it is deployed. | 18,935,924 |
Integrative holism in psychiatric-mental health nursing. | In this era of high-tech care, many Americans seek more holistic approaches and alternative and complementary treatments for health problems, including mental illness. Psychiatric-mental health (PMH) nurses need to be aware of these approaches as they assess clients, maintain a holistic approach, and in some cases, provide skilled, specific modalities. This article reviews holistic philosophy and integrative approaches relevant to PMH nurses. The emphasis is that whichever modality PMH nurses practice, a holistic framework is essential for providing optimal PMH care. | 18,935,934 |
Primary triage, evacuation priorities, and rapid primary distribution between adjacent hospitals--lessons learned from a suicide bomber attack in downtown Tel-Aviv. | Terrorist attacks have occurred in Tel-Aviv that have caused mass-casualties. The objective of this study was to draw lessons from the medical response to an event that occurred on 19 January 2006, near the central bus station, Tel-Aviv, Israel. The lessons pertain to the management of primary triage, evacuation priorities, and rapid primary distribution between adjacent hospitals and the operational mode of the participating hospitals during the event. Data were collected in formal debriefings both during and after the event. Data were analyzed to learn about medical response components, interactions, and main outcomes. The event is described according to Disastrous Incidents Systematic AnalysiS Through-Components, Interactions and Results (DISAST-CIR) methodology. A total of 38 wounded were evacuated from the scene, including one severely injured, two moderately injured, and 35 mildly injured. The severe casualty was the first to be evacuated 14 minutes after the explosion. All of the casualties were evacuated from the scene within 29 minutes. Patients were distributed between three adjacent hospitals including one non-Level-1 Trauma Center that received mild casualties. Twenty were evacuated to the nearby, Level-1 Sourasky Medical Center, including the only severely injured patient. Nine mildly injured patients were evacuated to the Sheba Medical Center and nine to Wolfson Hospital, a non-Level-1 Trauma Center hospital. All the receiving hospitals were operated according to the mass-casualty incident doctrine. When a mass-casualty incident occurs in the vicinity of more than one hospital, primary triage, evacuation priority decision-making, and rapid distribution of casualties between all of the adjacent hospitals enables efficient and effective containment of the event. | 18,935,948 |
Preparedness of primary healthcare centers for critical emergency situations in southwest Turkey. | Primary healthcare centers (PHCCs) frequently are contacted for emergency reasons and are expected to provide basic and advanced life support during emergency situations. The aim of this study was to assess the availability of emergency equipment and the knowledge of the staff working in PHCCs. The survey was conducted in 21 PHCCs located in the rural city of Isparta, Turkey, in 2001. The availability of emergency equipment, emergency drugs, intravenous parenteral solutions, and diagnostic-therapeutic equipment was evaluated. Knowledge of basic life support of the staff (n = 195) was evaluated using a 10-item test. Two (9.5%) PHCs had a complete emergency kit with an airways bag, mask, intravenous parenteral solutions, emergency drugs, and other diagnostic equipment. Emergency equipment was easily accessible in 19 PHCCs (90.5%), while in the remaining centers, the equipment and drugs were stored in locked cabinets. The staff that was evaluated consisted of 43 doctors (22%), 132 nurses and midwifes (67%), and 20 health officers (11%). Doctors scored the highest knowledge score (65.5%), followed by nurses and midwives (58.6% and 56.7%, respectively), and health officers (52.5%). Primary healthcare centers were not prepared to provide advanced life support. Knowledge scores were low and the staff was in need of basic life support training. Further arrangements must be stressed to make PHCC's "emergency-friendly centers" in Isparta, Turkey. | 18,935,949 |
Accuracy of computer simulation to predict patient flow during mass-casualty incidents. | Although most hospitals have an emergency department disaster plan, most never have been implemented in a true disaster or been tested objectively. Computer simulation may be a useful tool to predict emergency department patient flow during a disaster. The aim of this study was to compare the accuracy of a computer simulation in predicting emergency department patient flow during a mass-casualty incident with that of a real-time, virtual, live exercise. History, physical examination findings, and laboratory results for 136 simulated patients were extracted from the disastermed.ca patient database as used as input into a computer simulation designed to represent the emergency department at the University of Alberta Hospital. The computer simulation was developed using a commercially available simulation software platform (2005, SimProcess, CACI Products, San Diego CA). Patient flow parameters were compared to a previous virtual, live exercise using the same data set. Although results between the computer simulation and the live exercise appear similar, they differ statistically with respect to many patient benchmarks. There was a marked difference between the triage codes assigned during the live exercise and those from the patient database; however, this alone did not account for the differences between the patient groups. It is likely that novel approaches to patient care developed by the live exercise group, which are difficult to model by computer software, contributed to differences between the groups. Computer simulation was useful, however, in predicting how small changes to emergency department structure, such as adding staff or patient care areas, can influence patient flow. Computer simulation is helpful in defining the effects of changes to a hospital disaster plan. However, it cannot fully replace participant exercises. Rather, computer simulation and live exercises are complementary, and both may be useful for disaster plan evaluation. | 18,935,951 |
The public health dimension of disasters--health outcome assessment of disasters. | A broad range of health problems are related to disasters. Insight into these health problems is needed for targeted disaster management. Disaster health outcome assessment can provide insight into the health effects of disasters. During the 15th World Congress on Disaster and Emergency Medicine in Amsterdam (2007), experts in the field of disaster epidemiology discussed important aspects of disaster health outcome assessment, such as: (1) what is meant by disaster health outcome assessment?; (2) why should one conduct a disaster health outcome assessment, and what are the objectives?, and (3) who benefits from the information obtained by a disaster health outcome assessment? A disaster health outcome assessment can be defined as a systematic assessment of the current and potential health problems in a population affected by a disaster. Different methods can be used to examine these health problems such as: (1) rapid assessment of health needs; (2) (longitudinal) epidemiological studies using questionnaires; (3) continuous surveillance of health problems using existing registration systems; (4) assessment of the use and distribution of health services; and (5) research into the etiology of the health effects of disasters. The public health impact of a disaster may not be immediately evident. Disaster health outcome assessment provides insight into the health related consequences of disasters. The information that is obtained by performing a disaster health outcome assessment can be used to initiate and adapt the provision of health care. Besides information for policymakers, disaster health outcome assessments can contribute to the knowledge and evidence base of disaster health outcomes (scientific objective). Finally, disaster health outcome assessment might serve as a signal of recognition of the problems of the survivors. Several stakeholders may benefit from the information obtained from a disaster health outcome assessment. Disaster decision-makers and the public health community benefit from performing a disaster health outcome assessment, since it provides information that is useful for the different aspects of disaster management. Also, by providing information about the nature, prevalence, and course of health problems, (mental) health care workers can anticipate the health needs and requirements in the affected population. It is important to realize that the disaster is not over when the acute care has been provided. Instead, disasters will cause many other health problems and concerns such as infectious diseases and mental health problems. Disaster health outcome assessments provide insight into the public health impact of disasters. | 18,935,960 |
Saporin induces multiple death pathways in lymphoma cells with different intensity and timing as compared to ricin. | Ribosome-inactivating protein (RIP)-containing immunotoxins are currently used in clinical trials as anti-tumour drugs, in particular against haematological malignancies. In cell killing-based therapies it is important to identify the death pathways induced by the cytotoxic agent. The purpose of this work was to compare the pathways of cell death induced by the RIP saporin with those carried out by ricin in the L540 human Hodgkin's lymphoma-derived cell line. Protein synthesis inhibition, activation of caspases, DNA fragmentation and loss of viability have been evaluated. The two toxins triggered a similar DNA fragmentation and cell death, at concentrations giving the same level of cell protein synthesis inhibition, although the inhibitory effect of ricin on protein synthesis was more rapid than that of saporin. Moreover, the intrinsic apoptotic pathway was equally activated by both toxins, whilst ricin activated the extrinsic caspase pathway and the effector caspase-3/7 more efficiently than saporin. The complete inhibition of caspases by Z-VAD was only partially effective in cell rescue which appeared to be time limited. Necrostatin-1, a new inhibitor of non-apoptotic death, rescued cells from death by RIPs, although the effect was also partial and temporary. Despite the high RIP doses used no necrosis was detectable by Annexin V/Propidium Iodide (PI) test. These results suggest that more than one death mechanism was elicited by both ricin and saporin, however, with different timing and strength. The perspective of modulating cell death of neoplastic lymphocytes through different pathways could add new opportunities to reduce side effects and develop combined synergic immuno-chemotherapy. | 18,935,973 |
Syndromes, disorders and maternal risk factors associated with neural tube defects (V). | Fetuses with neural tube defects (NTDs) may suffer from associated syndromes and disorders. This article provides a comprehensive review of the syndromes and disorders associated with NTDs, including Pallister-Hall syndrome, Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy, MURCS association, Roberts syndrome, cerebro-costo-mandibular syndrome, laterality sequences, hydrolethalus syndrome, Knobloch syndrome, oculoauriculovertebral spectrum (hemifacial microsomia), cervico-oculo-acoustic syndrome, Fanconi anemia, Miller-Dieker lissencephaly syndrome, Fraser syndrome, frontonasal dysplasia, Adams-Oliver syndrome, CHILD syndrome, dyssegmental dysplasia, and monozygotic twinning. NTDs associated with these syndromes and disorders are a rare but important cause of NTDs. The risk of NTDs in subsequent fetuses and the preventive effect of maternal folic acid intake in NTDs associated with syndromes and disorders may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes and disorders associated with NTDs, and prompt thorough etiologic investigation and genetic counseling. | 18,935,987 |
Trial of labor after one cesarean: role of the order and number of prior vaginal births on the risk of emergency cesarean delivery and neonatal admission. | To evaluate the influences of mode of immediate preceding delivery and number of prior vaginal births on the risk of repeat cesarean and neonatal admission at attempted vaginal birth after cesarean. We performed a retrospective study of the risk factors for emergency repeat cesarean delivery and neonatal admission in a trial of labor after prior cesarean section. The study comprised 342 women at term with at least one prior vaginal delivery in addition to one previous lower transverse cesarean. Clinical variables with crude p < 0.2 on Fisher's exact test for the defined primary outcomes of repeat cesarean and neonatal admission were included in the model for multivariable logistic regression analysis. Cesarean as the immediate preceding mode of delivery (adjusted odds ratio, 5.3; 95% confidence interval, 2.5-10.8) was an independent predictor of emergency repeat cesarean delivery but not of neonatal admission. Higher parity of two or more previous vaginal deliveries compared with only one prior vaginal delivery was not associated with repeat cesarean or neonatal admission. In women who have had prior vaginal birth attempting a trial of labor after cesarean, a vaginal delivery before cesarean delivery is an independent risk factor for repeat cesarean. Women with two or more prior vaginal births have a similar risk for repeat cesarean and neonatal admission to women with only one prior vaginal birth. | 18,935,994 |
Successful treatment of twin-twin transfusion syndrome by occlusion of placental vessel anastomoses using enbucrilate. | Twin-twin transfusion syndrome is a serious obstetric complication unique to monochorionic twin gestations. Occlusion of vessel anastomoses is recommended to improve the perinatal outcome. A 36-year-old, gravida 1, woman had a monochorionic twin pregnancy which was found to be affected by twin-twin transfusion syndrome at 26 weeks' gestation. The condition was successfully treated by occlusion of placental vessel anastomoses using enbucrilate under color Doppler ultrasonographic guidance. At 35 weeks of gestation, two male infants were delivered by cesarean section. The birth weights of the babies were 2,470 and 1,750 g, and both were thriving. Targeted therapeutic ablation of vessel anastomoses involved in twin-twin transfusion syndrome using color Doppler ultrasonographic guidance is minimally invasive and may effectively obliterate interfetal transfusion, contributing to the survival of both twins. | 18,935,999 |
CT protocol for acute stroke: tips and tricks for general radiologists. | Acute stroke services have been installed in most hospitals in the industrialized world, and dealing with hyperacute stroke has become one of the most frequently performed tasks of the on-call radiologist. Imaging plays a key role in current guidelines for thrombolysis, and knowledge of classic early ischemic signs or depiction of hemorrhage at nonenhanced computed tomography (CT) is necessary (although not sufficient) for a satisfactory imaging study. A modern CT examination must also include perfusion CT and CT angiography. Perfusion CT delineates the ischemic tissue (penumbra) by showing increased mean transit time with decreased cerebral blood flow (CBF) and normal or increased cerebral blood volume (CBV), whereas infarcted tissue manifests with markedly decreased CBF and decreased CBV. CT angiography can depict the occlusion site, help grade collateral blood flow, and help characterize carotid atherosclerotic disease. A complete CT study (nonenhanced CT, perfusion CT, and CT angiography) may be performed and analyzed rapidly and easily by general radiologists using a simple standardized protocol and may even facilitate diagnosis by less experienced radiologists in affected patients. | 18,936,029 |
Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins. | Post-translational hydroxylation has been considered an unusual modification on intracellular proteins. However, following the recognition that oxygen-sensitive prolyl and asparaginyl hydroxylation are central to the regulation of the transcription factor hypoxia-inducible factor (HIF), interest has centered on the possibility that these enzymes may have other substrates in the proteome. In support of this certain ankyrin repeat domain (ARD)-containing proteins, including members of the IkappaB and Notch families, have been identified as alternative substrates of the HIF asparaginyl hydroxylase factor inhibiting HIF (FIH). Although these findings imply a potentially broad range of substrates for FIH, the precise extent of this range has been difficult to determine because of the difficulty of capturing transient enzyme-substrate interactions. Here we describe the use of pharmacological "substrate trapping" together with stable isotope labeling by amino acids in cell culture (SILAC) technology to stabilize and identify potential FIH-substrate interactions by mass spectrometry. To pursue these potential FIH substrates we used conventional data-directed tandem MS together with alternating low/high collision energy tandem MS to assign and quantitate hydroxylation at target asparaginyl residues. Overall the work has defined 13 new FIH-dependent hydroxylation sites with a degenerate consensus corresponding to that of the ankyrin repeat and a range of ARD-containing proteins as actual and potential substrates for FIH. Several ARD-containing proteins were multiply hydroxylated, and detailed studies of one, Tankyrase-2, revealed eight sites that were differentially sensitive to FIH-catalyzed hydroxylation. These findings indicate that asparaginyl hydroxylation is likely to be widespread among the approximately 300 ARD-containing species in the human proteome. | 18,936,059 |
Evidence for an inhibitory role of bone morphogenetic protein(s) in the follicular-luteal transition in cattle. | Bone morphogenetic proteins (BMPs) and their receptors are expressed in ovarian theca cells (TC) and granulosa cells (GC) and BMPs have been implicated in the regulation of several aspects of follicle development including thecal androgen production and granulosal oestrogen production. Their potential involvement in luteal function has received less attention. In this study, we first compared relative abundance of mRNA transcripts for BMPs, activin-betaA and BMP/activin receptors in bovine corpus luteum (CL) and follicular theca and granulosa layers before undertaking functional in vitro experiments to test the effect of selected ligands (BMP6 and activin A) on luteinizing bovine TC and GC. Relative to beta-actin transcript abundance, CL tissue contained more BMP4 and -6 mRNA than granulosa, more BMP2 mRNA than theca but much less activin-betaA mRNA than both granulosa and theca. Transcripts for all seven BMP/activin receptors were readily detected in each tissue and two transcripts (BMPRII, ActRIIA) were more abundant in CL than either theca or granulosa, consistent with tissue responsiveness. In vitro luteinization of TC and GC from antral follicles (4-6 mm) was achieved by culturing with 5% serum for 6 days. Treatment with BMP6 (0, 2, 10, and 50 ng/ml) and activin A (0, 2, 10 and 50 ng/ml) under these conditions dose-dependently suppressed forskolin-induced progesterone (P4) secretion from both cell types without affecting cell number. BMP6 reduced forskolin-stimulated upregulation of STAR mRNA and raised 'basal' CYP17A1 mRNA level in theca-lutein cells without affecting expression of CYP11A1 or hydroxy-Delta-5-steroid dehydrogenase, 3 beta- and steroid Delta-isomerase 1 (HSD3B1). In granulosa-lutein cells, STAR transcript abundance was not affected by BMP6, whereas forskolin-induced expression of CYP11A1, HSD3B1, CYP19A1 and oxytocin transcripts was reduced. In both cell types, follistatin attenuated the suppressive effect of activin A and BMP6 on forskolin-induced P4 secretion but had no effect alone. Granulosa-lutein cells secreted low levels of endogenous activin A ( approximately 1 ng/ml); BMP6 reduced this, while raising follistatin secretion thus decreasing activin A:follistatin ratio. Collectively, these findings support inhibitory roles for BMP/activin signalling in luteinization and steroidogenesis in both TC and GC. | 18,936,084 |
Assembly of high order G alpha q-effector complexes with RGS proteins. | Transmembrane signaling through G alpha(q)-coupled receptors is linked to physiological processes such as cardiovascular development and smooth muscle function. Recent crystallographic studies have shown how G alpha(q) interacts with two activation-dependent targets, p63RhoGEF and G protein-coupled receptor kinase 2 (GRK2). These proteins bind to the effector-binding site of G alpha(q) in a manner that does not appear to physically overlap with the site on G alpha(q) bound by regulator of G-protein signaling (RGS) proteins, which function as GTPase-activating proteins (GAPs). Herein we confirm the formation of RGS-G alpha(q)-GRK2/p63RhoGEF ternary complexes using flow cytometry protein interaction and GAP assays. RGS2 and, to a lesser extent, RGS4 are negative allosteric modulators of Galpha(q) binding to either p63RhoGEF or GRK2. Conversely, GRK2 enhances the GAP activity of RGS4 but has little effect on that of RGS2. Similar but smaller magnitude responses are induced by p63RhoGEF. The fact that GRK2 and p63RhoGEF respond similarly to these RGS proteins supports the hypothesis that GRK2 is a bona fide G alpha(q) effector. The results also suggest that signal transduction pathways initiated by GRK2, such as the phosphorylation of G protein-coupled receptors, and by p63RhoGEF, such as the activation of gene transcription, can be regulated by RGS proteins via both allosteric and GAP mechanisms. | 18,936,096 |
Positive association of genetic variants in the upstream region of NKX2-3 with Crohn's disease in Japanese patients. | A number of genome-wide association studies have been performed as a robust means of identifying susceptibility loci for Crohn's disease (CD). The loci detected after the completion of the HapMap project are quite concordant among these studies, suggesting that the results are reliable. Recently, the Wellcome Trust Case Control Consortium (WTCCC) reported the primary scanning of 17,000 individuals for seven diseases, including CD, and a subsequent study has validated these susceptible genetic variants in independent UK sample sets. The purpose of this study was to study the possible association of the variants reported by the WTCCC with CD in a Japanese population. A total of 484 patients with CD and 470 healthy controls were examined. Seventeen genetic variants at eight newly identified loci, including IRGM, NKX2-3 and PTPN2, were genotyped using the TaqMan assay or the invader assay. A positive association signal presumably common to different ethnic groups for rs10883365 was detected in the upstream region of NKX2-3 (p = 0.019 under the genotypic model, p = 0.0065 under the allelic model, p = 0.019 under the recessive model, p = 0.036 under the dominant model). In addition to rs10883365, marginal associations for two single nucleotide polymorphisms (SNPs) were detected in the Japanese population; rs6887695 near IL12B and rs10761659 on 10q21. Further genotype-phenotype analysis found a significant association between rs6887695 and patients with pure ileal CD. The results indicate that the three loci are possible candidates for conferring susceptibility to CD in people of different ethnicities. | 18,936,107 |
Simultaneous estimation of null alleles and inbreeding coefficients. | Although microsatellites are a very efficient tool for many population genetics applications, they may occasionally produce "null" alleles, which, when present in high proportion, may affect estimates of key parameters such as inbreeding and relatedness coefficients or measures of genetic differentiation. In order to account for the presence of null alleles, it is first necessary to estimate their frequency within studied populations. However, the commonly used null allele frequency estimators are not of general applicability because they can produce upwardly biased estimates when a population under study experiences some inbreeding. In such a case, 2 formerly described approaches, population inbreeding model and individual inbreeding model, can be applied for simultaneous estimation of null allele frequencies and of the inbreeding coefficient. In this study, we demonstrate the properties and utility of these 2 methods and show that they outperform the commonly used approaches in the estimation of null allele frequencies based on genotypic data. The methods are applied to empirical data from a natural population of European beech (Fagus sylvatica L.), and results are briefly discussed. The methods presented in this paper are implemented in the Windows-based user-friendly INEST computer program (available free of charge at http://genetyka.ukw.edu.pl/INEst10_setup.exe). | 18,936,113 |
Endoscopic anatomical nerve observation and minimally invasive management of cubital tunnel syndrome. | Experience with the use of the Universal Subcutaneous Endoscope (USE) system in surgical treatment of cubital tunnel syndrome in 35 patients is reported. Patients included in the study had pre- and postoperative clinical and electrophysiological data, and had undergone a minimum follow-up period of 13 months. Mean patient age was 59.5 years and the mean follow-up period was 25.9 months. The operation was performed under local anaesthesia without pneumatic tourniquet and on an out-patient basis. A 1.5 cm portal is made at the cubital tunnel and the USE system is inserted next to the ulnar nerve, first distally and then proximally. The nerve is endoscopically assessed and only the tissue that compresses the nerve is released, in keeping with the principles of minimally invasive treatment. Preoperative tingling sensations disappeared postoperatively in 63% of cases. Pain and sensory disturbance recovered to normal in 92% and 89% of cases, respectively. Abnormal motor nerve conduction velocities improved in 77%. Abductor digiti minimi weakness MMT 0, 1, 2 in 16 hands recovered to MMT 4 or 5 in eight. First-dorsal interosseous weakness in 18 hands recovered to MMT 4 or 5 in seven. There were no complications in this series. The endoscopic approach facilitates inspection of the ulnar nerve so that selective release of the tissue that compresses the nerve can readily be performed. The technique has proven effective in the treatment of cubital tunnel syndrome. | 18,936,128 |
The clinical significance of malunion of fractures of the neck and shaft of the little finger metacarpal. | The outcomes of 218 little finger metacarpal shaft and neck fractures that had been treated non-operatively, with no attempt at fracture reduction, were compared with those of 44 that had been treated operatively with fracture reduction and fixation (plates or K-wires). Outcome measures included the grip strength of the little finger and the DASH score. Fracture malunion was assessed by clinical measurement of little finger ray shortening and measurement of palmar angulation on the initial radiographs. The severity of palmar angular deformity did not affect the outcome of the 105 metacarpal neck or 113 metacarpal shaft fractures that had been treated non-operatively. There were no differences between the outcomes of the 18 metacarpal neck fractures treated operatively and the 105 treated non-operatively. The DASH score (P = 0.001) and aesthetic outcome (P = 0.013) were significantly better for the 113 metacarpal shaft fractures treated non-operatively than for the 26 treated operatively. | 18,936,129 |
Scaphotrapezial arthritis after a carpometacarpal fusion in a patient with Marfan's Syndrome: case report. | We report a case of scaphotrapezial arthritis that developed in a patient with Marfan's syndrome many years after a carpometacarpal fusion, which placed the thumb metacarpal in adduction. This problem was effectively treated with an abduction/opposition osteotomy, which both increased the patient's first web space and improved her arthritic symptoms. | 18,936,131 |
Human ocular-derived virus-specific CD4+ T cells control varicella zoster virus replication in human retinal pigment epithelial cells. | Varicella zoster virus (VZV)-induced retinitis is characterized by the presence of virus-infected cells in the retinal layer and the ocular infiltration of VZV-specific T cells. Herein, the susceptibility of human retinal pigment epithelial (RPE) cells to VZV infection and the ability of virus-specific CD4(+) T cells to control VZV infection in RPE cells in vitro is addressed. Human primary RPE cell cultures (n=2) were infected with a VZV strain expressing green fluorescent protein. The infection and viability of infected RPE cells was monitored by flow cytometry or by a fluorescent imager on RPE monolayers. RPE cells, pretreated with or without interferon-gamma (IFN-gamma), were infected with VZV and subsequently cultured with VZV-specific CD4(+) T-cell clones (TCCs; n=3) recognizing disparate VZV proteins presented by different HLA class II alleles. IFN-gamma production and cytotoxicity of the TCCs in response to VZV-infected RPE cells was determined by flow cytometry. Human RPE cells are permissive to a productive VZV infection. VZV-infected RPE cells presented the cognate antigen to the CD4(+) TCCs only if the RPE cells were pretreated with IFN-gamma and expressed the appropriate HLA class II allele. VZV-specific TCCs inhibited productive VZV infection in RPE cells, which was in part attributed to TCC-mediated killing of the VZV-infected RPE cells. The results presented suggest that RPE cells may play a role as retina-resident antigen-presenting cells in the intraocular, VZV-specific, T cell-mediated inflammatory response of VZV-induced uveitis. | 18,936,136 |
Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2. | Mouse embryonic fibroblasts (MEFs) deficient for pocket proteins (i.e., pRB/p107-, pRB/p130-, or pRB/p107/p130-deficient MEFs) have lost proper G(1) control and are refractory to Ras(V12)-induced senescence. However, pocket protein-deficient MEFs expressing Ras(V12) were unable to exhibit anchorage-independent growth or to form tumors in nude mice. We show that depending on the level of pocket proteins, loss of adhesion induces G(1) and G(2) arrest, which could be alleviated by overexpression of the TBX2 oncogene. TBX2-induced transformation occurred only in the absence of pocket proteins and could be attributed to downregulation of the p53/p21(CIP1) pathway. Our results show that a balance between the pocket protein and p53 pathways determines the level of transformation of MEFs by regulating cyclin-dependent kinase activities. Since transformation of human fibroblasts also requires ablation of both pathways, our results imply that the mechanisms underlying transformation of human and mouse cells are not as different as previously claimed. | 18,936,168 |
The cytoplasmic domain of anthrax toxin receptor 1 affects binding of the protective antigen. | The protective antigen (PA) component of anthrax toxin binds the I domain of the receptor ANTXR1. Integrin I domains convert between open and closed conformations that bind ligand with high and low affinities, respectively; this process is regulated by signaling from the cytoplasmic domains. To assess whether intracellular signals might influence the interaction between ANTXR1 and PA, we compared two splice variants of ANTXR1 that differ only in their cytoplasmic domains. We found that cells expressing ANTXR1 splice variant 1 (ANTXR1-sv1) bound markedly less PA than did cells expressing a similar level of the shorter splice variant ANTXR1-sv2. ANTXR1-sv1 but not ANTXR1-sv2 associated with the actin cytoskeleton, although disruption of the cytoskeleton did not affect binding of ANTXR-sv1 to PA. Introduction of a cytoplasmic domain missense mutation found in the related receptor ANTXR2 in a patient with juvenile hyaline fibromatosis impaired actin association and increased binding of PA to ANTXR1-sv1. These results suggest that ANTXR1 has two affinity states that may be modulated by cytoplasmic signals. | 18,936,178 |
Methionine-adequate cysteine-free diet does not limit erythrocyte glutathione synthesis in young healthy adult men. | Most methods of determining amino acid (AA) requirements are based on endpoints that determine adequacy for protein synthesis. However, the sulfur AA (SAA) cysteine is believed to be the rate-limiting substrate for synthesis of the most abundant intracellular antioxidant, glutathione (GSH). Our objectives were to determine whether supplementation of cysteine in a diet containing adequate SAA for protein synthesis, as methionine, increased GSH synthesis by measuring the fractional and absolute synthesis rates, and if concentration of GSH changed in response to feeding 5 graded intakes of cysteine (0, 10, 20, 30, and 40 mg x kg(-1) x d(-1)) in a random order with a fixed methionine intake of 14 mg x kg(-1) x d(-1) and a protein intake of 1 g x kg(-1) x d(-1). Each subject received a multivitamin and choline supplement during the study. Four healthy adult men each underwent 5 isotope infusion studies of 7-h duration after a 2-d adaptation to the level of cysteine intake being studied on the isotope infusion day. The isotope used was [U-(13)C(2)-(15)N]glycine. Analyses included erythrocyte GSH synthesis rates and concentration and urinary sulfate excretion. The GSH synthesis rates and concentration, measured at a methionine intake of 14 mg x kg(-1) x d(-1), did not change with increasing intakes of cysteine. Urinary sulfate excretion showed a significant positive relationship with cysteine intake (r = 0.92; P < 0.01). In conclusion, this study provides preliminary evidence that consumption of SAA adequate to meet the requirement for protein synthesis does not limit GSH synthesis in healthy adult men receiving an otherwise adequate diet. | 18,936,215 |
Increased elongase and desaturase gene expression with stearidonic acid enriched diet does not enhance long-chain (n-3) content of seawater Atlantic salmon (Salmo salar L.). | Atlantic salmon (Salmo salar L.) can produce (n-3) long-chain (LC)-PUFA when fed biosynthetic precursors. This has potential for developing sustainable aquafeeds. Echium oil (EO) is rich in stearidonic acid [SDA; 18:4(n-3)] and bypasses the initial Delta6 desaturase (FAD6) step in the (n-3) LC-PUFA biosynthetic pathway. EO was fed to seawater Atlantic salmon for 12 wk and compared with fish fed a diet containing canola oil (CO), a source of alpha-linolenic acid [ALA; 18:3(n-3)] or fish oil (FO) that provides (n-3) LC-PUFA. Fatty acid (FA) composition of liver, white muscle, and whole fish was measured to show whether dietary precursors were endogenously biosynthesized to LC-PUFA. Gene expression of liver FA elongase and FAD5 was upregulated in EO fish compared with FO fish. Furthermore, dietary precursors affected the FA concentrations of direct biosynthetic products in all tissues. The increased gene expression in the EO fish was reflected by an increased FA concentration of eicosapentaenoic acid [20:5(n-3)] in the liver compared with the CO fish. However, the high concentrations of (n-3) LC-PUFA found in seawater Atlantic salmon fed diets rich in FO were not attained via biosynthesis from precursors (ALA or SDA) in diets. | 18,936,216 |
Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation. | Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34(+) cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity. | 18,936,236 |
Protein localization by actin treadmilling and molecular motors regulates stereocilia shape and treadmilling rate. | We present a physical model that describes the active localization of actin-regulating proteins inside stereocilia during steady-state conditions. The mechanism of localization is through the interplay of free diffusion and directed motion, which is driven by coupling to the treadmilling actin filaments and to myosin motors that move along the actin filaments. The resulting localization of both the molecular motors and their cargo is calculated, and is found to have an exponential (or steeper) profile. This localization can be at the base (driven by actin retrograde flow and minus-end myosin motors), or at the stereocilia tip (driven by plus-end myosin motors). The localization of proteins that influence the actin depolymerization and polymerization rates allow us to describe the narrow shape of the stereocilia base, and the observed increase of the actin polymerization rate with the stereocilia height. | 18,936,243 |
Identification of specific histidines as pH sensors in flavivirus membrane fusion. | The flavivirus membrane fusion machinery, like that of many other enveloped viruses, is triggered by the acidic pH in endosomes after virus uptake by receptor-mediated endocytosis. It has been hypothesized that conserved histidines in the class II fusion protein E of these viruses function as molecular switches and, by their protonation, control the fusion process. Using the mutational analysis of recombinant subviral particles of tick-borne encephalitis virus, we provide direct experimental evidence that the initiation of fusion is crucially dependent on the protonation of one of the conserved histidines (His323) at the interface between domains I and III of E, leading to the dissolution of domain interactions and to the exposure of the fusion peptide. Conserved histidines located outside this critical interface were found to be completely dispensable for triggering fusion. | 18,936,253 |
What Australians know and believe about bird flu: results of a population telephone survey. | The avian influenza A (A/H5N1) virus has attracted the attention of governments and health organizations throughout the world because of its pandemic potential. Despite the emerging nature of A/H5N1, there is limited research on public knowledge and perceptions of this disease. This study is based on a computer-assisted telephone interviewing survey conducted in May 2006 to determine the Australian public's knowledge of A/H5N1, their willingness to engage in preventive behaviors, and their acceptance of potential messages for communication campaigns. Awareness and concern about bird flu is low (lower than a recent survey of U.S. residents). There appears to be widespread support for bird flu control measures initiated by the federal government, although less agreement regarding personal protective behaviors. Our study and those examining the severe acute respiratory syndrome epidemic suggest that governments, including the Australian government, will encounter a number of significant communication challenges in the event of a bird flu outbreak. | 18,936,262 |
The characteristics of the outdoor school environment associated with physical activity. | The school is an important setting for physical activity. The purpose of the present study was to examine the association between physical environmental characteristics and participation in daily physical activity during school breaks. Data from 130 schools and 16 471 students (Grades 4-10) in Norway were obtained in 2004 through self-administered questionnaires to principals and students. Multilevel logistic regression models revealed that boys at secondary level with a larger number of outdoor facilities at school had 2.69 times [95% confidence interval (CI) = 1.21-5.98] and girls 2.90 times (95% CI = 1.32-6.37) higher odds of being physically active compared with students in schools with fewer facilities. Boys at secondary level with areas for hopscotch/skipping rope had 2.53 times (95% CI = 1.55-4.13), with a soccer field 1.68 times (95% CI = 1.15-2.45), with playground equipment 1.66 times (95% CI = 1.16-2.37) and with a sledding hill 1.70 times (95% CI = 1.23-2.35) higher odds to be physically active compared with students in schools without these facilities. A sledding hill was also associated with girls' physical activity participation in secondary school (odds ratio = 1.58, 95% CI = 1.11-2.24). Outdoor facilities in secondary schools are associated with students' daily physical activity participation during school breaks. Therefore, improving the outdoor environment should be considered in physical activity promotion school programs in secondary schools. | 18,936,270 |
Reciprocal thalamocortical connectivity of the medial pulvinar: a depth stimulation and evoked potential study in human brain. | The thalamic medial pulvinar nucleus (PuM) is fully developed only in primates and reaches its greatest extent in humans. To assess the reciprocal functional connectivity between PuM and cortex, we studied intracerebral-evoked responses obtained after PuM and cortical electrical stimulation in 7 epileptic patients undergoing depth electroencephalographic recordings. Cortical-evoked potentials (CEPs) to PuM stimulation were recorded from all explored cortical regions, except striate cortex, anterior cingulated, and postcentral gyrus. Percentages of cortical contacts pairs responding to PuM stimulation (CEPs response rate) ranged from 80% in temporal neocortex, temporoparietal (TP) junction, insula, and frontoparietal opercular cortex to 34% in mesial temporal regions. Reciprocally, PuM-evoked potentials (PEPs) response rates were 14% after cortical stimulation in insula and frontoparietal opercular cortex, 67% in the TP junction, 76% in temporal neocortex, and 80% in mesial temporal regions. Overall, our study of functional PuM connectivity in the human brain converges with most of the data from anatomical studies in monkeys, except for a strong amygdalohippocampal functional projection to PuM and an unexpected imbalance between some of the reciprocal pathways explored. This functional quantitative approach helps to clarify the functional role of PuM as well as its implication in temporal lobe epileptic seizures. | 18,936,272 |
Bicycle-related injuries among children and adolescents in the United States. | The objective of this study is to describe the epidemiology of bicycle-related injuries among children and adolescents 18 years and younger on a national level. This is a retrospective analysis of data from the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission for patients 18 years and younger who were seen in emergency departments (EDs) between January 1, 1990, and December 31, 2005, for injuries received while operating a bicycle. During the 16-year study period, there were an estimated 6 228 700 individuals 18 years and younger treated in US EDs for bicycle-related injuries. Children with head injuries were more than 3 (relative risk, 3.63) times as likely to require hospitalization and were almost 6 (relative risk, 5.77) times more likely to have their injuries result in death. The large number of annual bicycle related-injuries is evidence that prevention of these injuries should remain an important area of bicycle safety research and practice. | 18,936,286 |
Meningitis due to hematogenous dissemination of community-associated methicillin-resistant Staphylococcus aureus (MRSA) in a patient with AIDS. | Meningitis due to methicillin-resistant Staphylococcus aureus is a rare clinical presentation but has been well documented in postneurosurgical patients. To our knowledge, no case of methicillin-resistant Staphylococcus aureus meningitis has been previously reported in a nonneurosurgical patient with AIDS. In this case report we describe a person with AIDS who had no history of a neurosurgical procedure, shunt devices, head trauma, or recent hospitalization that presented with methicillin-resistant Staphylococcus aureus meningitis. The infection was successfully treated. Methicillin-resistant Staphylococcus aureusshould be considered in the differential of meningitis in people with AIDS. | 18,936,290 |
Frequency and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure. | To determine the frequency and histopathologic basis of hepatic surface nodularity at imaging in patients with fulminant hepatic failure. The committee on human research approved this HIPAA-compliant study and waived written informed consent. Thirty-five consecutive patients [24 female [mean age, 38 years +/- 19 (standard deviation); range, 1-67 years] and 11 male [mean age, 29 years +/- 22; range, 2-61 years]] with a mean age of 35 years +/- 20 (range, 1-67 years) who underwent liver transplantation for fulminant hepatic failure at our institution during a 5-year period were retrospectively identified. Pretransplant ultrasonographic (n = 38; three patients each had two studies) and computed tomographic (n = 2) studies were retrospectively and independently reviewed for hepatic surface nodularity. Liver explant histopathologic findings (n = 33; slides unavailable in two patients) were reviewed for cirrhosis and for the combination of alternating foci of confluent regenerative nodules and necrosis. Differences among patients with nodular versus smooth liver surfaces in the proportion with the two histopathologic findings were compared with Fisher exact test. Differences in illness duration and maximum liver biochemical indices were compared with Mann-Whitney Rank Sum test. Fifteen of 35 patients (43%) demonstrated hepatic surface nodularity at pretransplant imaging, none of whom had cirrhosis at histopathologic examination. One patient with a smooth liver surface had cirrhosis. Compared with those who had a smooth liver surface, patients with hepatic surface nodularity had a significantly greater proportion with the histopathologic finding of a combination of alternating foci of confluent regenerative nodules and necrosis (12 of 14 vs one of 19, P < .001), longer illness duration (31 days +/- 32 vs 13 days +/- 13, P = .029), and lower maximum liver biochemical indices. Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status. | 18,936,312 |
Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition. | Inducible nitric oxide synthase (iNOS) is an obligatory mediator of the late phase of ischemic preconditioning, but the mechanisms of its cardioprotective actions are unknown. In addition, it remains unclear whether sustained elevation of iNOS in myocytes provides chronic protection against ischemia/reperfusion injury. Constitutive overexpression of iNOS in transgenic mice (alpha-myosin heavy chain promoter) did not induce contractile dysfunction and did not affect mitochondrial respiration or biogenesis, but it profoundly decreased infarct size in mice subjected to 30 minutes of coronary occlusion and 24 hours of reperfusion. In comparison with wild-type hearts, isolated iNOS-transgenic hearts subjected to ischemia for 30 minutes followed by 40 minutes of reperfusion displayed better contractile recovery, smaller infarct size, and less mitochondrial entrapment of 2-deoxy-[(3)H]-glucose. Reperfusion-induced loss of NAD(+) and mitochondrial release of cytochrome c were attenuated in iNOS-transgenic hearts, indicating reduced mitochondrial permeability transition. The NO donor NOC-22 prevented permeability transition in isolated mitochondria, and mitochondrial permeability transition-induced NAD(+) loss was decreased in wild-type but not iNOS-null mice treated with the NO donor diethylene triamine/NO 24 hours before ischemia and reperfusion ex vivo. iNOS-mediated cardioprotection was not abolished by atractyloside. Reperfusion-induced production of oxygen-derived free radicals (measured by electron paramagnetic resonance spectroscopy) was attenuated in iNOS-transgenic hearts and was increased in wild-type hearts treated with the mitochondrial permeability transition inhibitor cyclosporin A. Cardiomyocyte-restricted expression of iNOS provides sustained cardioprotection. This cardioprotection is associated with a decrease in reperfusion-induced oxygen radicals and inhibition of mitochondrial swelling and permeability transition. | 18,936,326 |
Deep dissecting hematoma: an emerging severe complication of dermatoporosis. | To outline the characteristics of deep dissecting hematoma (DDH). Retrospective medical record review. Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland. Thirty-four patients with DDH. Deep incision or surgical debridement was performed in all the patients. Direct closure of the incision was possible in 6 patients, and split-thickness skin grafting was applied to 17 patients. Sex of the patient, the affected area, presence of dermatoporosis, presence of systemic treatment, initial and late symptoms, anatomic location of DDH, and the mean length of hospital stay. Most frequently, elderly women were affected (mean age, 81.7 years); women outnumbered men by a ratio of 5:1. In all the patients, the leg was the affected part of the body. All the patients, except for the 2 youngest ones, had advanced dermatoporosis, and the most severe form was seen in the older patients who were receiving long-term treatment with systemic corticosteroids. Half of the patients were receiving anticoagulation drugs. The initial symptoms in all the patients were pain and swelling of the leg. Erythema and edema without fever were observed. Skin necrosis developed as a late manifestation. Erysipelas was the initial diagnosis in up to 14 patients who had been treated with antibiotics before admission. The mean delay before hospital referral was 16.4 days. Magnetic resonance imaging and histopathological analysis confirmed deep anatomical location of DDH. Hospital treatment consisted mainly of deep incision and debridement followed by direct closure, skin grafting, or wound healing per secundam. The mean length of hospital stay was 3.5 weeks. Deep dissecting hematoma is an emerging clinical entity and a major complication of dermatoporosis. Prompt diagnosis and treatment is a major factor for the prognosis. Health care professionals, especially general practitioners, should be aware of the symptoms and signs of this condition as well as the risk factors involved. Given the high cost of treatment, in addition to the inconvenience it causes for the patient, preventive measures should be implemented early. | 18,936,393 |
Use of evidence-based therapies after discharge among elderly patients with acute myocardial infarction. | Postdischarge use of evidence-based drug therapies has been proposed as a measure of quality of care for myocardial infarction patients. We examined trends in the use of evidence-based drug therapies after discharge among elderly patients with myocardial infarction. We performed a cross-sectional study in a retrospective population-based cohort that was created using linked administrative databases. We included patients aged 65 years and older who were discharged from hospital with a diagnosis of myocardial infarction between Apr. 1, 1992, and Mar. 31, 2005. We determined the annual percentage of patients who filled a prescription for statins, beta-blockers and angiotensin-modifying drugs within 90 days after discharge. The percentage of patients who filled a prescription for a beta-blocker increased from 42.6% in 1992 to 78.1% in 2005. The percentage of patients who filled a prescription for an angiotensin-modifying drug increased from 42.0% in 1992 to 78.4% in 2005. The percentage of patients who filled a prescription for a statin increased from 4.2% in 1992 to 79.2% in 2005. In 2005, about half of the hospitals had rates of use for each of these therapies that were less than 80%. The temporal rate of increase in statin use after discharge was slower among noncardiologists than among cardiologists (3.5%-2.8% slower). The rate of increase was 4.8% slower for among physicians with low volumes of myocardial infarction patients than among those with high volumes of such patients and was 5.7% greater at teaching hospitals compared with nonteaching hospitals. Use of statins, beta-blockers and angiotensin-modifying drugs increased from 1992 to 2005. The rate of increase in the use of these medications after discharge varied across physician and hospital characteristics. | 18,936,454 |
Factors associated with the use of evidence-based therapies after discharge among elderly patients with myocardial infarction. | In an accompanying article, we report moderate between-hospital variation in the postdischarge use of beta-blockers, angiotensin-modifying drugs and statins by elderly patients who had been admitted to hospital with acute myocardial infarction. Our objective was to identify the characteristics of patients, physicians, hospitals and communities associated with differences in the use of these medications after discharge. For this retrospective, population-based cohort study, we used linked administrative databases. We examined data for all patients aged 65 years or older who were discharged from hospital in 2005/06 with a diagnosis of myocardial infarction. We determined the effect of patient, physician, hospital and community characteristics on the rate of postdischarge medication use. Increasing patient age was associated with lower postdischarge use of medications. The odds ratios (ORs) for a 1-year increase in age were 0.98 (95% confidence interval [CI] 0.97-0.99) for beta-blockers, 0.97 (95% CI 0.97-0.98) for angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers and 0.94 (95% CI 0.93-0.95) for statins. Having a general or family practitioner, a general internist or a physician of another specialty as the attending physician, relative to having a cardiologist, was associated with lower postdischarge use of beta-blockers, angiotensin-modifying agents and statins (ORs ranging from 0.46 to 0.82). Having an attending physician with 29 or more years experience, relative to having a physician who had graduated within the past 15 years, was associated with lower use of beta-blockers (OR 0.71, 95% CI 0.60-0.84) and statins (OR 0.81, 95% CI 0.67-0.97). Patients who received care from noncardiologists and physicians with at least 29 years of experience had substantially lower use of evidence-based drug therapies after discharge. Dissemination strategies should be devised to improve the prescribing of evidence-based medications by these physicians. | 18,936,455 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.