text
stringlengths 1.03k
99.1k
|
|---|
['We aimed to evaluate the effect of the mutant Wld(S) (slow Wallerian degeneration; also known as Wld) gene in experimental diabetes on early experimental peripheral diabetic neuropathy and diabetic retinopathy.', 'The experiments were performed in four groups of mice: wild-type (WT), streptozotocin (STZ)-induced diabetic WT, C57BL/Wld(S) and STZ-induced diabetic C57BL/Wld(S). In each group, intraperitoneal glucose and insulin tolerance tests were performed; blood glucose, glycated haemoglobin and serum insulin were monitored. These mice were also subjected to the following behavioural tests: grasping test, hot-plate test and von Frey aesthesiometer test. For some animals, sciatic-tibial motor nerve conduction velocity, tail sensory nerve conduction velocity and eye pattern electroretinogram were measured. At the end of the experiments, islets were isolated to detect glucose-stimulated insulin secretion, ATP content and extent of apoptosis. The NAD/NADH ratio in islets and retinas was evaluated. Surviving retinal ganglion cells were estimated by immunohistochemistry.', 'We found that the Wld(S) gene is expressed in islets and protects beta cells against multiple low doses of STZ by increasing the NAD/NADH ratio, maintaining the ATP concentration, and reducing apoptosis. Consistently, significantly higher insulin concentrations, lower blood glucose concentrations, and better glucose tolerance were observed in Wld(S) mice compared with WT mice after STZ treatment. Furthermore, Wld(S) alleviated abnormal sensory responses, nerve conduction, retina dysfunction and reduction of surviving retinal ganglion cells in STZ-induced diabetic models.'] |
['S-nitrosylation of mitochondrial enzymes involved in energy transfer under nitrosative stress may result in ATP deficiency. We investigated whether α-lipoic acid, a powerful antioxidant, could alleviate nitrosative stress by regulating S-nitrosylation, which could result in retaining the mitochondrial enzyme activity.', 'In this study, we have identified the S-nitrosylated forms of subunit 1 of dihydrolipoyllysine succinyltransferase (complex III), and subunit 2 of the α-ketoglutarate dehydrogenase complex by implementing a fluorescence-based differential quantitative proteomics method.', 'We found that the activities of these two mitochondrial enzymes were partially but reversibly inhibited by S-nitrosylation in cultured endothelial cells, and that their activities were partially restored by supplementation of α-lipoic acid. We show that protein S-nitrosylation affects the activity of mitochondrial enzymes that are central to energy supply, and that α-lipoic acid protects mitochondrial enzymes by altering S-nitrosylation levels.'] |
['Pseudotumors are sterile inflammatory lesions found in the soft tissues surrounding metal-on-metal (MOM) and metal-on-polyethylene hip arthroplasties. In patients with MOM hip arthroplasties, pseudotumors are thought to represent an adverse reaction to metal wear debris. However, the pathogenesis of these lesions remains unclear. Currently, there is inconsistent evidence regarding the influence of adverse cup position and increased wear in the formation of pseudotumors.', 'We therefore determined whether pseudotumor formation was associated with (1) adverse cup position, (2) raised metal ion levels, and (3) increased wear rates of the retrieved components.', 'We retrospectively reviewed all 352 patients for whom we had retrieved specimens from revisions of a current-generation MOM hip prosthesis between February 2008 and September 2010; of these, 105 met our inclusion criteria. We used multivariate logistic regression analysis to compare acetabular orientation, metal ion levels before revision, and component wear rates between patients with (n = 72) and without (n = 33) pseudotumors, according to findings on metal artifact reduction sequence MRI.', 'The proportion of patients demonstrating evidence of a pseudotumor in well-positioned hips was similar to those with adverse cup positions (67% and 66%, respectively). Patients revised with pseudotumors had similar whole-blood metal ion levels and component wear rates to those who were not revised.'] |
['To evaluate the utility of using predictive genetic screening of the population for susceptibility to smoking.', 'The results of meta-analyses of genetic association studies of smoking behaviour were used to create simulated data sets using Monte Carlo methods. The ability of the genetic tests to screen for smoking was assessed using receiver operator characteristic curve analysis. The result was compared to prediction using simple family history information. To identify the circumstances in which predictive genetic testing would potentially justify screening we simulated tests using larger numbers of alleles (10, 15 and 20) that varied in prevalence from 10 to 50% and in strength of association [relative risks (RRs) of 1.2-2.1].', 'A test based on the RRs and prevalence of five susceptibility alleles derived from meta-analyses of genetic association studies of smoking performed similarly to chance and no better than the prediction based on simple family history. Increasing the number of alleles from five to 20 improved the predictive ability of genetic screening only modestly when using genes with the effect sizes reported to date.'] |
['Ethnic differences in genotype frequency provide a natural condition for assessing the contribution of gene variations to the causes and treatments of disease. Accordingly, the purpose of this study was to determine whether ethnic variations in allele frequencies of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene were related to the response to the treatment of depression.', 'African-Americans (n=101) and Caucasians (n=100) with major depressive disorder were treated with the antidepressant citalopram (20-60mg/day) for 8weeks. Genotyping for the long (L) and short (s) alleles (LL, Ls, and ss) of the SLC6A4 gene was performed and the association between genotype and treatment response was assessed.', 'Subjects in both ethnic groups showed a significant reduction in depression scores over time (p<.0001). However, in spite of a significantly greater frequency of the L allele in African-Americans as compared to Caucasians, a comparable clinical response between the two groups was found with 5-HTTLPR polymorphism not significantly associated with clinical response in either ethnic group.'] |
['The objective of this study was to assess the accuracy and safety of two pre-defined checklists to identify prehospital post-ictal or hypoglycemic patients who could be discharged at the scene.', 'A retrospective cohort study of lower acuity, adult patients attended by paramedics in 2013, and who were either post-ictal or hypoglycemic, was conducted. Two self-care pathway assessment checklists (one each for post-ictal and hypoglycemia) designed as clinical decision tools for paramedics to identify patients suitable for discharge at the scene were used. The intention of the checklists was to provide paramedics with justification to not transport a patient if all checklist criteria were met. Actual patient destination (emergency department [ED] or discharge at the scene) and subsequent events (eg, ambulance requests) were compared between patients who did and did not fulfill the checklists. The performance of the checklists against the destination determined by paramedics was also assessed.', 'Totals of 629 post-ictal and 609 hypoglycemic patients were identified. Of these, 91 (14.5%) and 37 (6.1%) patients fulfilled the respective checklist. Among those who fulfilled the checklist, 25 (27.5%) post-ictal and 18 (48.6%) hypoglycemic patients were discharged at the scene, and 21 (23.1%) and seven (18.9%) were admitted to hospital after ED assessment. Amongst post-ictal patients, those fulfilling the checklist had more subsequent ambulance requests (P=.01) and ED attendances with seizure-related conditions (P=.04) within three days than those who did not. Amongst hypoglycemic patients, there were no significant differences in subsequent events between those who did and did not meet the criteria. Paramedics discharged five times more hypoglycemic patients at the scene than the checklist predicted with no significant differences in the rate of subsequent events. Four deaths (0.66%) occurred within seven days in the hypoglycemic cohort, and none of them were attributed directly to hypoglycemia.'] |
['Gastrointestinal stromal tumors (GISTs) and malignant lymphomas (MLs) in the abdomen are often observed as tumors of unknown origin on F-18 FDG PET/CT. The purpose of this study was to evaluate the intratumoral metabolic heterogeneity of F-18 FDG uptake on PET to determine if it might be helpful to discriminate between these tumors.', "The F-18 FDG PET/CT findings of 21 large abdominal tumors were retrospectively evaluated (9 GISTs and 12 MLs). Intratumoral heterogeneity was evaluated by visual scoring (visual score: 0, homogeneous; 1, slightly heterogeneous; 2, moderately heterogeneous; 3, highly heterogeneous) and by the cumulative standardized uptake value (SUV) histograms on transaxial PET images at the maximal cross-sectional tumor diameter. Percent tumor areas above a threshold from 0 to 100% of the maximum SUV were plotted and the area under curve of the cumulative SUV histograms (AUC-CSH) was used as a heterogeneity index, where lower values corresponded with increased heterogeneity. Correlation between the visual score and the AUC-CSH was investigated by the Spearman's rank test.", 'GISTs exhibited heterogeneous uptake of F-18 FDG, whereas MLs showed rather homogeneous uptake on visual analysis (visual score: 2.67\xa0±\xa00.50 and 0.58\xa0±\xa00.79, respectively; p\xa0<\xa00.001). The AUC-CSH was significantly lower for the GISTs than for the MLs (0.41\xa0±\xa00.14 and 0.64\xa0±\xa00.08, respectively; p\xa0<\xa00.001). Significant correlations were observed between the visual score and the AUC-CSH (ρ\xa0=\xa0-0.866, p\xa0<\xa00.001).'] |
['The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk.', "Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5'-splicing site of exon 5 of ESR1.", 'The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models.', 'Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (beta=0.008; p=0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score< -2.5 at the spine: OR 2.46, 95% CI 1.30-4.65; at the hip: OR 3.79(1.64-8.74)) and low trauma fractures (OR 2.31(1.29-4.14)) than those with >or= 18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with >or= 18 repeats (-1.96% vs. -1.61%, p = 0.029).'] |
['To investigate whether rheumatoid factor isotypes and anti-cyclic citrullinated peptide (anti-CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor alpha (TNFalpha) inhibitors.', 'The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease-modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow-up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti-CCP antibodies were assessed by ELISA both before anti-TNFalpha treatment and 1 year later.', 'The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non-responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non-responder group (130.4 U/ml (interquartile range 13.8-276.7) v 24.8 U/ml (10.2-90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti-CCP antibody levels were not significantly affected.'] |
['To determine whether a literature-based guideline, powered by educational meetings and individual feedback, improves manual hyperinflation (MH) performance by intensive care unit (ICU) nurses.', 'MH is frequently applied in intubated and mechanically ventilated ICU patients. MH is a complex intervention, and large variation in its performance has been found.', 'First, a literature-based guideline on MH was developed. The intervention consisted of education of this guideline and individual feedback. Before and 3 months after the intervention, ICU nurses performed MH maneuvers in a skills laboratory. Data collected included applied volumes, peak inspiratory flows (PIF) and peak expiratory flows (PEF), and the use of inspiratory holds.', 'Eighty nurses participated. Decrease of PIF was not statistically significant. PEF increased from 52 ± 7 to 83 ± 23 L/min (P < 0·01). PIF to PEF ratio decreased from 1·4 [1·1-1·7] to 0·8 [0·6-1·1] (P < 0·01). Peak inspiratory pressures decreased from 40 ± 14 to 19 ± 6 cm H2 O (P < 0·01). The proportion of nurses applying inspiratory holds increased from 14% to 58%; use of rapid release of the resuscitation bag, considered mandatory, increased from 4% to 61%.'] |
['Insufficient blood supply to the heart results in ischemic injury manifested clinically as myocardial infarction (MI). Following ischemia, inflammation is provoked and related to the clinical outcomes. A recent basic science study indicates that complement factor MASP-2 plays an important role in animal models of ischemia/reperfusion injury. We investigated the role of MASP-2 in human acute myocardial ischemia in two clinical settings: (1) Acute MI, and (2) Open heart surgery.', 'A total of 187 human subjects were enrolled in this study, including 50 healthy individuals, 27 patients who were diagnosed of coronary artery disease (CAD) but without acute MI, 29 patients with acute MI referred for coronary angiography, and 81 cardiac surgery patients with surgically-induced global heart ischemia. Circulating MASP-2 levels were measured by ELISA.', 'MASP-2 levels in the peripheral circulation were significantly reduced in MI patients compared with those of healthy individuals or of CAD patients without acute MI. The hypothesis that MASP-2 was activated during acute myocardial ischemia was evaluated in cardiac patients undergoing surgically-induced global heart ischemia. MASP-2 was found to be significantly reduced in the coronary circulation of such patients, and the reduction of MASP-2 levels correlated independently with the increase of the myocardial necrosis marker, cardiac troponin I.'] |
['The aim of the present study was to assess the prevalence and severity of dental caries among 18-year-old Brazilian males and to test the associations between dental caries and socioeconomic conditions.', 'It was carried out a cross-sectional study among 18-year-old male conscripts of the Brazilian Army in Blumenau, Southern Brazil. The main outcomes measured were the occurrence of dental caries (decayed, missing and filled teeth [DMFT] > or = 1) and high dental caries (DMFT > or = 8). Socioeconomic variables were collected by interviews. Simple and multiple regression analysis were performed.', "The mean DMFT was 5.7 (95% confidence interval [CI] 5.3-6.1), the proportion of caries-free subjects was 11.4% (95% CI 8.5-14.3) and the proportion of subjects with all 28 natural teeth was 67.2% (95% CI 63.0-71.4). In the multiple regression analysis, mothers' educational level remained associated with dental caries after being controlled by conscripts' schooling. It was observed that the lower the mothers' and the conscripts' schooling, the stronger the risk of the conscripts to show a high dental caries status."] |
['A major problem in pain medicine is the lack of knowledge about which treatment suits a specific patient. We tested the ability of quantitative sensory testing to predict the analgesic effect of pregabalin and placebo in patients with chronic pancreatitis.', 'Sixty-four patients with painful chronic pancreatitis received pregabalin (150-300 mg BID) or matching placebo for three consecutive weeks. Analgesic effect was documented in a pain diary based on a visual analogue scale. Responders were defined as patients with a reduction in clinical pain score of 30% or more after three weeks of study treatment compared to baseline recordings. Prior to study medication, pain thresholds to electric skin and pressure stimulation were measured in dermatomes T10 (pancreatic area) and C5 (control area). To eliminate inter-subject differences in absolute pain thresholds an index of sensitivity between stimulation areas was determined (ratio of pain detection thresholds in pancreatic versus control area, ePDT ratio). Pain modulation was recorded by a conditioned pain modulation paradigm. A support vector machine was used to screen sensory parameters for their predictive power of pregabalin efficacy.', 'The pregabalin responders group was hypersensitive to electric tetanic stimulation of the pancreatic area (ePDT ratio 1.2 (0.9-1.3)) compared to non-responders group (ePDT ratio: 1.6 (1.5-2.0)) (P\u200a=\u200a0.001). The electrical pain detection ratio was predictive for pregabalin effect with a classification accuracy of 83.9% (P\u200a=\u200a0.007). The corresponding sensitivity was 87.5% and specificity was 80.0%. No other parameters were predictive of pregabalin or placebo efficacy.'] |
['The level of inhibition of the human Ether-à-go-go-related gene (hERG) channel is one of the earliest preclinical markers used to predict the risk of a compound causing Torsade-de-Pointes (TdP) arrhythmias. While avoiding the use of drugs with maximum therapeutic concentrations within 30-fold of their hERG inhibitory concentration 50% (IC(50)) values has been suggested, there are drugs that are exceptions to this rule: hERG inhibitors that do not cause TdP, and drugs that can cause TdP but are not strong hERG inhibitors. In this study, we investigate whether a simulated evaluation of multi-channel effects could be used to improve this early prediction of TdP risk.', 'We collected multiple ion channel data (hERG, Na, L-type Ca) on 31 drugs associated with varied risks of TdP. To integrate the information on multi-channel block, we have performed simulations with a variety of mathematical models of cardiac cells (for rabbit, dog, and human ventricular myocyte models). Drug action is modelled using IC(50) values, and therapeutic drug concentrations to calculate the proportion of blocked channels and the channel conductances are modified accordingly. Various pacing protocols are simulated, and classification analysis is performed to evaluate the predictive power of the models for TdP risk. We find that simulation of action potential duration prolongation, at therapeutic concentrations, provides improved prediction of the TdP risk associated with a compound, above that provided by existing markers.'] |
['Severity in psoriasis and atopic dermatitis (AD) is commonly assessed with the Psoriasis Area and Severity Index (PASI) and the SCORing Atopic Dermatitis (SCORAD), respectively. Until today no serum marker is available to reflect the clinical scoring in both diseases. As mast cells play an important role in the pathogenesis of early psoriasis and AD, tryptase, a major compound of mast cell granules that is released upon activation, could in principle serve as such a marker.', 'To assess the correlation between serum tryptase and severity of psoriasis and AD as well as the correlation between total IgE levels and severity of AD.', 'Serum samples from patients hospitalized for psoriasis and AD were collected at time of admission and time of discharge from hospital. PASI and SCORAD assessments were performed at the same time points. Outpatients presenting with naevi and other benign noninflammatory skin lesions served as control group. Serum tryptase values and total IgE levels of patients with AD were measured using a fluoroenzyme immunoassay technique.', 'No correlation of serum tryptase level with either the severity of psoriasis or the severity of AD was seen. Total IgE levels in patients with AD at time of admission and discharge from hospital remained the same.'] |
['Sensory symptoms within the median nerve distribution are a primary clinical diagnostic criterion for the diagnosis of carpal tunnel syndrome (CTS). However, the distribution of the sensory symptoms in CTS varies from patient to patient. This study identifies the clinical and electrophysiological findings that correlate with the distribution of sensory symptoms in an Asian population with CTS.', 'In a prospective study of 105 patients with electrophysiologically confirmed CTS, clinical and educational data were correlated with sensory symptom distribution.', 'Median nerve distribution was strongly associated with more severe nerve conduction abnormality, male gender, and relief by movement. Patients with a complete median sensory distribution had more electrophysiological abnormality than those with an incomplete median distribution. Extra-median distribution was associated with the least nerve conduction abnormality. Educational qualification, age, symptom duration and body mass index were not associated with the pattern of sensory symptoms.'] |
['Acute pancreatitis following endoscopic retrograde cholangiopancreatography presents a unique opportunity for prophylaxis and early modification of the disease process because the initial triggering event is temporally well defined and takes place in the hospital. We report a prospective, single-center, randomized, double-blind controlled trial to determine if rectal diclofenac reduces the incidence of pancreatitis following cholangiopancreatography.', 'Entry to the trial was restricted to patients who underwent endoscopic retrograde pancreatography or had manometrically verified sphincter of Oddi hypertension. Immediately after endoscopy, patients were given a suppository containing either 100 mg diclofenac or placebo. Estimation of serum amylase levels and clinical evaluation were performed in all patients.', 'A total of 220 patients entered the trial, and 110 received rectal diclofenac. Twenty-four patients developed pancreatitis (11%), of whom 7 received rectal diclofenac and 17 received placebo (P < 0.05).'] |
['Highly concentrated lidocaine has been reported to induce irreversible loss of membrane potential in crayfish nerve, which implies membrane disruption as one of the direct mechanisms of lidocaine-induced neurotoxicity. To confirm lidocaine-induced membrane disruption in mammalian nerve, a lactate dehydrogenase (LDH) leakage from rat sciatic nerve was measured in vitro. Before applying lidocaine, the desheathed nerve was incubated for 60 min in Krebs-Ringer solution at 37 degrees C to examine basal LDH activity. It was then incubated in 80 mM lidocaine solution at pH 7.3 for 15, 30, 60, or 120 min. Other nerves were immersed in 800 mM choline solution for 120 min. Total LDH activity per wet weight of nerve tissue was assayed using spectrophotometry. It was also determined using nerves cut into 10 segments and incubated in distilled water for 60 min. The LDH activity in the lidocaine group showed a time-dependent increase. After the 60- and 120-min incubation with lidocaine, the amount of LDH activity was significantly increased compared with the choline group and was similar to that of the group incubated in distilled water. We conclude that 80 mM lidocaine may be sufficient to cause membrane damage and facilitate the leakage of enzymes from cytoplasm.'] |
['Persistent infection with high-risk (HR) human papillomavirus (HPV) genotypes is required for the development of cervical carcinoma, and integration of HPV testing into cervical screening programs is under investigation. For the clinical value of HPV testing to be fully established, genotyping studies are needed to identify HR HPV persistence in samples of known cytology and histology, and to determine the relationship with clinical outcome. To date, methods for genotyping have been research-based, and subject to variation. The availability of the Roche prototype line blot assay (LBA) offers a PCR-based, reproducible genotyping method, with a 37-type target spectrum and many potential applications.', 'We applied the LBA to determine persistence of HR HPV in 54 women with low-grade histology. Median interval between genotyping was 12.5 months (range 5-48).', 'All 15 lesions that progressed to CIN3 (PD) were associated with HR HPV persistence. Regression of lesions (REM) was observed in 31 HPV+ women, of whom nine had clearance of existing HPV infections, with one patient then acquiring additional types. Eight HPV+ patients had no change in lesions observed (NC). Persistence of HPV type 16 was more common in the PD group (60%), compared with the REM group (27%) and the NC group (38%).'] |
['Methamphetamine (Meth) abuse continues to be a major illicit drug of abuse. Neuroimaging findings suggest that Meth is neurotoxic and may alter various brain structures, but the effect of Meth on the aging brain has not been studied.', 'The aim was to determine regional volumes of cortical gray matter in the brains of adult Meth users versus healthy control subjects, and their interaction with age and Meth-usage variables.', 'Cross-sectional study', 'Magnetic resonance imaging (MRI) Research Center located in a university-affiliated hospital.', 'Thirty-four Meth-dependent subjects (21 men and 13 women; ages 33.1 ± 8.9 years), diagnosed according to DSM-IV criteria, and 31 healthy non-Meth user comparison subjects (23 men and 8 women ages 35.7 ± 8.4 years).', 'Regional gray matter volumes were segmented automatically in all subjects and evaluated in relation to age, using high-resolution MRIs at 3.0 Tesla.', 'After adjustment for the effects of cranium size, the Meth users showed enhanced cortical gray matter volume loss with age in the frontal (analysis of covariance interaction P = 0.02), occipital (interaction P = 0.01), temporal (interaction P < 0.001) and the insular lobes (interaction P = 0.01) compared to controls, independently of Meth-usage patterns. Additionally, Meth users showed smaller gray matter volumes than control subjects in several subregions (dorsolateral prefrontal: P = 0.02; orbitofrontal: P = 0.03; prefrontal: P = 0.047; superior temporal: P = 0.04).'] |
['In this study, we estimated the effect of blastocoele expansion, ICM and TE quality after warming and culture on the rates of clinical pregnancy, live birth and miscarriage in vitrified-warmed single-blastocyst transfer cycle in a Chinese population.', 'A retrospective analysis of 263 cycles of vitrified-warmed single-blastocyst transfers was performed.', "The blastocysts with higher TE grade significantly increased the rates of clinical pregnancy (OR\u2009=\u20090.59, 95 % CI, 0.35-0.99, P\u2009=\u20090.045, grade (A\u2009+\u2009B) vs grade C) and live birth (OR\u2009=\u20090.55, 95 % CI, 0.32-0.94, P\u2009=\u20090.029, grade (A\u2009+\u2009B) vs grade C). And the association between TE grade and the rate of live birth didn't change after the number of repeated cycles was adjusted (OR\u2009=\u20090.55, 95 % CI, 0.32-0.95, P\u2009=\u20090.033, grade (A\u2009+\u2009B) vs grade C). The number of repeated cycles was a confounding factor significantly different between the live birth and no live birth groups. By contrast, neither blastocoele expansion nor inner cell mass was statistically related to the rates of clinical pregnancy, live birth and miscarriage."] |
['Epicardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiovascular disease and arrhythmogenesis, but little is known about the relationship between epicardial fat and PR-Interval prolongation. The purpose of this study was to investigate the association between epicardial adipose tissue (EAT) volume and PR-interval prolongation as assessed by computed tomography (CT) and Twelve-lead ECGs.', 'Patients (n=287) were referred for 64-slice CT for exclusion of coronary artery disease and EAT volumes were determined. Twelve-lead ECGs were obtained from each subject and were evaluated by two independent readers.', 'Patients with significant PR interval prolongation had higher median EAT volume than patients with normal PR interval. Statistically significant correlations were observed between the EAT volume and the PR interval (p = 0.183, p = 0.003), and QRS duration (p = 0.144, p = 0.018). Multivariate and trend analyses confirmed that EAT volume was independently associated with the presence of PR interval prolongation. The receiver operator characteristics curve of EAT volume showed that an EAT volume >144.4 cm³ was associated with PR interval prolongation.'] |
['Little is known about cytokine and angiogenic factors (CAFs) in gastric cancer (GC) in terms of tumor classification and prognostic value. Here, we aimed to correlate CAF signature with overall survival (OS) in GC.', 'We measured pretreatment serum levels of 52 kinds of CAFs in 68 GC patients who were treated with fluoropyrimidine and platinum combination chemotherapy using multiplex bead immunoassays and enzyme-linked immunosorbent assay. We evaluated correlations between CAF levels and pathological features and OS.', "Three distinct patient groups were identified: one with high levels of proangiogenic factors, another with high levels of proinflammatory factors, and the other with high levels of both factors. Eleven CAFs [interleukin (IL)-2 receptor-alpha, growth-regulated alpha protein, hepatocyte growth factor, macrophage colony-stimulating factor, stromal cell-derived factor, IL-6, IL-8, IL-10, interferon-gamma, vascular endothelial growth factor, and osteopontin] were independently correlated with poor OS. Clustering analysis of these 11 CAFs revealed distinct high and low 11-CAF signature groups. High 11-CAF signature was associated with shorter OS (10.1 vs. 17.9\xa0months, p\xa0=\xa00.026) along with poor performance status, and the presence of signet ring cell components in multivariate analysis of OS (HR 1.76, p\xa0=\xa00.029). The patients' traditional clinicopathological characteristics were not significantly different between the high and low 11-CAF signature groups."] |
["Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 microg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 microg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 microg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = -6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = -3%, 16%; P = 0.11)."] |
['To determine the frequency of occurrence of hypoadrenalism in patients with human immunodeficiency virus (HIV) infection and document the clinical correlates of hypoadrenalism for this group of patients.', "A descriptive study was carried out on 66 hospitalized HIV patients in a semi-urban setting of South Africa. Hypoadrenalism was diagnosed based on a basal cortisol level of less than 400 nmol/l with or without overt signs and symptoms. Clinical and biochemical parameters of hypoadrenalism were compared between subjects with suboptimal and normal cortisol levels. Statistical analysis included Student's t test, χ(2) and Pearson's correlation coefficient tests.", 'The prevalence of hypoadrenalism was 27% with a high occurrence of contributory factors (cytomegalovirus infection in 100% and tuberculosis in 68.2% of the study subjects). Typical features of hypoadrenalism included: hyponatremia, 19.6%; hyperkalemia, 6.1%; mucosal hyperpigmentation, 12%, and loss of axillary hair, 15%. Comparison of clinical and biochemical parameters of hypoadrenalism did not show a correlation between CD4 count and cortisol levels (r = 0.1 and p = 0.3).'] |
['Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation.', 'Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined.', 'Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P < or = .002 in each case).'] |
['Secreted Frizzled related proteins (SFRPs) are extracellular regulators of Wnt signaling. These proteins contain an N-terminal cysteine rich domain (CRD) highly similar to the CRDs of the Frizzled family of seven-transmembrane proteins that act as Wnt receptors. SFRPs can bind to Wnts and prevent their interaction with the Frizzled receptor. Recently it has been reported that a splice variant of human Frizzled-4 (FZD4S) lacking the transmembrane and the cytoplasmic domains of Frizzled-4 can activate rather than inhibit Wnt-8 activity in Xenopus embryos. This indicates that secreted CRD containing proteins such as Frizzled ecto-domains and SFRPs may not always act as Wnt inhibitors. It is not known how FZD4S can activate Wnt/beta-catenin signaling and what biological role this molecule plays in vivo.', 'Here we report that the Xenopus frizzled-4 is alternatively spliced to give rise to a putative secreted protein that lacks the seven-transmembrane and the cytoplasmic domains. We performed functional experiments in Xenopus embryos to investigate how this novel splicing variant, Xfz4S, can modulate the Wnt/beta-catenin pathway. We show that Xfz4S as well as the extracellular domain of Xfz8 (ECD8) can act as both activators and inhibitors of Wnt/beta-catenin signaling dependent on the Wnt ligand presented. The positive regulation of Wnt/beta-catenin signaling by the extracellular domains of Frizzled receptors is mediated by the members of low density lipoprotein receptor-related protein (LRP-5/6) that act as Wnt coreceptors.'] |
['Transient lower esophageal sphincter relaxation (TLESR) appears to be the most frequent motor event responsible for gastroesophageal reflux. Because TLESRs are considered to be triggered by activation of gastric mechanoreceptors, and because the gamma-aminobutyric acid type B (GABA(B))-receptor agonist baclofen is known to inhibit transmitter release from mechanosensitive afferents, the effects of baclofen on TLESRs in the dog were assessed.', 'A total of 183 recordings of the pharyngeal, esophageal, lower esophageal sphincter, and gastric pressures as well as measurement of esophageal pH were performed in 15 awake dogs. Racemic baclofen, its enantiomers, and the GABA(B)-receptor antagonist CGP36742 were administered before stimulation of TLESRs by a liquid meal and air insufflation. The pharmacodynamics of baclofen were compared with its pharmacokinetics.', 'Baclofen dose-dependently inhibited TLESRs, with a 50% effective dose (ED(50)) of 1.0 micromol/kg after intravenous administration. The maximal inhibition amounted to approximately 80%. Intragastric baclofen was almost equally effective (ED(50), 1.8 micromol/kg), compatible with the complete oral availability of the drug (100%). The inhibitory effect of baclofen resided in the pharmacologically active R enantiomer, and CGP36742 reduced some of the effects of baclofen.'] |
['Leifsonia xyli is a xylem-inhabiting bacterial species comprised of two subspecies: L. xyli subsp. xyli (Lxx) and L. xyli subsp. cynodontis (Lxc). Lxx is the causal agent of ratoon stunting disease in sugarcane commercial fields and Lxc colonizes the xylem of several grasses causing either mild or no symptoms of disease. The completely sequenced genome of Lxx provided insights into its biology and pathogenicity. Since IS elements are largely reported as an important source of bacterial genome diversification and nothing is known about their role in chromosome architecture of L. xyli, a comparative analysis of Lxc and Lxx elements was performed.', 'Sample sequencing of Lxc genome and comparative analysis with Lxx complete DNA sequence revealed a variable number of IS transposable elements acting upon genomic diversity. A detailed characterization of Lxc IS elements and a comparative review with IS elements of Lxx are presented. Each genome showed a unique set of elements although related to same IS families when considering features such as similarity among transposases, inverted and direct repeats, and element size. Most of the Lxc and Lxx IS families assigned were reported to maintain transposition at low levels using translation regulatory mechanisms, consistent with our in silico analysis. Some of the IS elements were found associated with rearrangements and specific regions of each genome. Differences were also found in the effect of IS elements upon insertion, although none of the elements were preferentially associated with gene disruption. A survey of transposases among genomes of Actinobacteria showed no correlation between phylogenetic relatedness and distribution of IS families. By using Southern hybridization, we suggested that diversification of Lxc isolates is also mediated by insertion sequences in probably recent events.'] |
['Dominant mutations in cellular junction proteins are the major cause of arrhythmogenic cardiomyopathy, whereas recessive mutations in those proteins cause cardiocutaneous syndromes such as Naxos and Carvajal syndrome. The Hutterites are distinct genetic isolates who settled in North America in 1874. Descended from <100 founders, they trace their origins to 16th-century Europe.', 'We clinically and genetically evaluated 2 large families of the Alberta Hutterite population with a history of sudden death and found several individuals with severe forms of biventricular cardiomyopathy characterized by mainly left-sided localized aneurysms, regions of wall thinning with segmental akinesis, in addition to typical electric and histological features known for arrhythmogenic right ventricular cardiomyopathy. We identified a homozygous truncation mutation, c.1660C>T (p.Q554X) in desmocollin-2 (DSC2), in affected individuals and determined a carrier frequency of this mutation of 9.4% (1 in 10.6) among 1535 Schmiedeleut Hutterites, suggesting a common founder in that subgroup. Immunohistochemistry of endomyocardial biopsy samples revealed altered expression of the truncated DSC2 protein at the intercalated discs but only minor changes in immunoreactivity of other desmosomal proteins. Recombinant expressed mutant DSC2 protein in cells confirmed a stable, partially processed truncated protein with cytoplasmic and membrane localization.'] |
['Dopamine agonists nonselective for dopamine receptor subtypes, such as apomorphine, reduce prepulse inhibition of the startle reflex. It has been suggested that either D2 or D3 dopamine receptors mediate this action of apomorphine.', 'The present study investigated whether a selective D2 agonist with relatively low affinity for D3 receptors can reduce prepulse inhibition.', 'Rats (n=48) were treated with vehicle or one of three doses ( 15, 30 or 60 microg/kg, s.c.) of the specific dopamine D2 receptor agonist (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) for 11 days. On days 1, 6 and 11 of treatment, the rats (n=12 in each group) were tested for their acoustic startle reflexes (105-dB, 40-ms white noise) and for prepulse inhibition (5-kHz tone, 5 dB above a 65 dB background white noise). Prepulses were presented with a range of stimulus onset asynchronies (SOAs: 5-160 ms) or lead times between the onset of the prepulse and the onset of the startle stimulus. In a second experiment, two groups of rats (n=10 in each group) were tested in a similar manner after vehicle or apomorphine (0.8 mg/kg, s.c.) to verify the sensitivity of the present procedure to agonist-induced reductions in prepulse inhibition.', 'At doses that increased motor activity, PHNO increased prepulse inhibition at SOAs less than 80 ms and had no effect on prepulse inhibition at SOAs of 80 ms or above. However, all doses decreased startle amplitudes on trials in which only the startle-eliciting stimulus was presented. Apomorphine reduced prepulse inhibition under the same conditions.'] |
['The serine protease thrombin can dramatically alter endothelial gene expression in a manner that confers a proinflammatory phenotype. Recent studies have identified the Kruppel-like factor 2 (KLF2) as a critical regulator of endothelial gene expression. Herein, we provide evidence that KLF2 inhibits thrombin-mediated endothelial activation via alterations in expression of its principal receptor protease-activated receptor-1 (PAR-1).', 'Forced expression of KLF2 in human umbilical vein endothelial cells potently inhibited the ability of thrombin to induce multiple prothrombotic factors (tissue factor, CD40L, plasminogen activator inhibitor-1), cytokines/chemokines (eg, monocyte chemotactic protein-1, interleukin-6 [IL-6], IL-8), and matrix degrading enzymes (eg, matrix metalloproteinases 1, 2, and 9). Mechanistically, KLF2 inhibits PAR-1 expression and, as a consequence, thrombin-mediated nuclear factor kappaB (NF-kappaB) nuclear accumulation and DNA binding. Conversely, small interfering RNA-mediated knockdown of KLF2 increases PAR-1 expression and thrombin-mediated induction of NF-kappaB activation.'] |
['To study whether embryo associated immunosuppressor factor (EASF) is synthesized at the maternal-fetal interface.', 'Anti-EASF monoclonal antibody H5D12 was used to identify EASF. Paraffin-embedded sections were prepared from placental and fetal tissues and immunohistochemistry was done by the avidin-biotin-peroxidase technique. EASF was affinity purified using H5D12-Sepharose 4B from culture media of placental villi and analyzed for immunosuppressive activity (by Concanavalin A-induced lymphocyte proliferation assay) and molecular weight identity (by metabolic labeling studies with 35S-methionine followed by immunoprecipitation and SDS-PAGE).', 'Immunohistochemical studies demonstrates intense immunostaining of villous syncytiotrophoblast and cytotrophoblast cells of first trimester placental tissues. Hoffbauer cells and decidual cells stained positive. The same cells in second and third trimester placental tissues stained weakly. However, the endothelium and smooth muscle cells of fetal blood vessels, fetal ovarian stroma and primordial follicles, kidney epithelium, cerebral neurons, and glial cells all stained negative. The affinity-purified EASF from the conditioned media of placental villi (less than 12 wk gestational age) was identified as a 37-kDa molecule with immunosuppressive activity. Metabolic labeling studies revealed that placental villi from early gestational age secretes a major factor of 37-kDa and minor factors of 41-kDa and 47-kDa molecular weight.'] |
['Current guidelines for ST-elevation myocardial infarction (STEMI) recommend early revascularization with optimal ischemic time (IT)\u2009<\u2009120 min and door-to-balloon (D2B) time\u2009<\u200990 min. The focus of most studies has been D2B time, while IT is not frequently reported. We tested the hypothesis that total IT is a better predictor than D2B time for mortality and infarct size.', 'Between December 2008 and April 2013, 786 patients with STEMI were treated in our STEMI center, and 262 of these had cardiac magnetic resonance imaging 3-5 days after the index event. Total IT was defined as time from symptom onset to device activation, while D2B time was defined as hospital arrival to device activation. Patients were divided into three groups according to IT (<120, 120-239, ≥240 min) and into four groups according to D2B time (<30, 30-59, 60-89, ≥90 min). Baseline demographics including age, cardiac risk factors, and LAD infarct location were similar between groups. The 30-day mortality rate significantly increased across IT groups but did not correlate with D2B time groups. Similarly, infarct size significantly increased across IT groups but did not correlate with D2B time groups.'] |
['Previously, it was shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury.', 'The role of ClC-2 was investigated in TJ barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2 knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was measured electrophysiologically and by transepithelial mannitol fluxes. Selected TJ and associated proteins were Western blotted, cytokines were measured using quantitative PCR, and human colonic biopsies were examined with immunohistochemistry.', 'ClC-2 mice had a higher disease activity index, higher histological scores, and increased paracellular permeability compared with wild-type mice when treated with DSS. DSS-treated ClC-2 mice had increased claudin-2 expression, greater loss of occludin in the membrane, increased association of occludin with caveolin-1, and significantly increased tumor necrosis factor-α and interleukin-1β messenger RNA. ClC-2 knockdown in human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance in the event of epithelial injury. The restoration of colonic barrier function after DSS colitis was delayed in ClC-2 mice. In human colonic biopsies, the protein and messenger RNA expression of ClC-2 was found to be reduced in patients with ulcerative colitis.'] |
['Osborne-Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/Pl (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats.', 'Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high-fat (55% kcal) or low-fat (10% kcal) diet. Experiment 2 investigated the effects of a 2\u2009h high-fat meal after a 24\u2009h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of exendin-4 (GLP-1 receptor agonist) administration on the intake of a high-fat or a low-fat diet in OM and S5B rats.', 'Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high-fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose dependently decreased food intake to a greater extent in S5B rats compared to OM rats. The intake of low-fat diet, compared to the intake of high-fat diet, was more sensitive to the effects of exendin-4 in these strains.'] |
['Femoroacetabular impingement (FAI) is increasingly diagnosed clinically. Controversy exists about the significance of radiographic findings. Our goal is to determine the prevalence of radiographic FAI types and parameters in a hospital population clinically not suspected of having FAI. In addition we assessed whether pain, age and gender are associated with higher prevalences.', "Three hundred ten patients were included in this retrospective study. After applying the exclusion criteria, 262 patients (522 hips) remained. Two observers scored for radiographic parameters. A generalised estimation equation, Pearson's χ(2) test and logistic regression model were used.", 'Radiographic signs of FAI were absent in only 58 hips (11.1 %). In the 40 hips (7.7 %) with cam impingement, males were more affected (P\u2009<\u20090.001). In the 330 hips (63.2 %) with pincer impingement, females were more often affected (P\u2009<\u20090.001). In the 82 hips (15.7 %) with signs of mixed type impingement, male hips were significantly (P\u2009<\u20090.001) more often affected. Age had some effect on the prevalence of coxa vara, acetabular index and acetabular retroversion. No correlation with pain was found.'] |
["Extracorporeal membrane oxygenation (ECMO) can replace the lungs' gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. As a first step towards this aim, we hypothesized that coating the oxygenator's gas exchange membrane with proteins might positively influence the attachment and proliferation of arterial endothelial cells.", 'Sheets of polypropylene (PP), polyoxymethylpentene (TPX) and polydimethylsiloxane (PDMS), typical material used for oxygenator gas exchange membranes, were coated with collagen, fibrinogen, gelatin or fibronectin. Tissue culture treated well plates served as controls. Endothelial cell attachment and proliferation were analyzed for a period of 4 days by microscopic examination and computer assisted cell counting.', 'Endothelial cell seeding efficiency is within range of tissue culture treated controls for fibronectin treated surfaces only. Uncoated membranes as well as all other coatings lead to lower cell attachment. A confluent endothelial cell layer develops on fibronectin coated PDMS and the control surface only.'] |
['To investigate the relationship between cysteine-rich protein 61 (Cyr61) and phosphatidylinositol 3-kinase (PI3K) signal pathway on cell proliferation and apoptotic in human ovarian carcinoma cells.', 'Recombinant human Cyr61 (rhCyr61) was pretreated with ovarian carcinoma cells. The expression of Cyr61 protein was detected by confocal spectral microscopy. Then treated the ovarian carcinoma cells with PI3K transduction inhibitors (LY294002) for 24 hours. Cell apoptosis was detected by flow cytometry (FCM). Cell viability was determined by methyl thiazolyl tetrazolium (MTT) method. The mRNA expressions of Cyr61, the protein levels of protein kinase B (PKB), phospho-PKB and Cyr61 were assayed by real time-PCR and western blot analysis, respectively.', 'The Cyr61 and phospho-PKB protein expression in two ovarian carcinoma cells (OV2008 and OVCAR-3) were increased in rhCyr61 pretreated group. The decreasing of cell apoptosis [(1.4 ± 0.9)%, (2.1 ± 1.0)%] and increasing of cell proliferation [(124.0 ± 1.8)%, (133.0 ± 2.2)%] was detected in the same time, compared with negative control group, there were significant difference (P < 0.05). After exposed to LY294002 for 24 hours, the apoptosis rate of OV2008 and OVCAR-3 in pretreated with rhCyr61 group exposed to LY294002 were (21.1 ± 1.6)% and (26.4 ± 1.5)%, respectively. Cells viability [(59.0 ± 2.3)%, (51.0 ± 2.0)%] was also significantly decreased in OV2008 and OVCAR-3 pretreated with rhCyr61 cells. Meanwhile, the mRNA expressions of Cyr61 (3.2 ± 0.8, 6.2 ± 1.1) and the protein levels of phospho-PKB and Cyr61 were greatly decreased. Compared with negative control group, there were significant difference in OV2008 and OVCAR-3 cells (all P < 0.01).'] |
['Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers. The 1G/2G single nucleotide polymorphism (SNP) in the MMP-1 promoter at position -1607 bp has been reported to affect the transcriptional activity. In the light of these findings, we investigated whether this SNP in the MMP-1 promoter is associated with the development, differentiation, and progression of gastric cancer.', 'The 215 gastric cancer patients and 166 controls were used in this study. The SNP of the MMP-1 promoter was analyzed by PCR-RFLP and sequencing. The genotype frequency was compared between cases and controls, and the association with clinicopathological parameters among cases was studied.', 'The frequency of 1G/2G genotypes in gastric cancer patients was similar to those in controls (p=0.57). The degree of tumor invasion, the presence of lymph node metastasis, and clinical stage showed no significant association with the SNP. On the other hand, we found a significant association with histological differentiation and gender among gastric cancer patients (p<0.05, respectively).'] |
['Neuroendocrine abnormalities, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, are associated with obesity; however, few large-scale population-based studies have examined HPA axis and markers of obesity. We examined the cross-sectional association of the cortisol awakening response (CAR) and diurnal salivary cortisol curve with obesity.', 'The Multiethnic Study of Atherosclerosis Stress Study includes 1,002 White, Hispanic, and Black men and women (mean age 65 ± 9.8 years) who collected up to 18 salivary cortisol samples over 3 days. Cortisol profiles were modeled using regression spline models that incorporated random parameters for subject-specific effects. Cortisol curve measures included awakening cortisol, CAR (awakening to 30-min postawakening), early decline (30 min to 2-h postawakening), late decline (2-h postawakening to bedtime), and the corresponding areas under the curve (AUC). Body mass index (BMI) and waist circumference (WC) were used to estimate adiposity.', 'For the entire cohort, both BMI and WC were negatively correlated with awakening cortisol (P < 0.05), AUC during awakening rise, and early decline and positively correlated to the early decline slope (P < 0.05) after adjustments for age, race/ethnicity, gender, diabetes status, socioeconomic status, β-blockers, steroids, hormone replacement therapy, and smoking status. No heterogeneities of effects were observed by gender, age, and race/ethnicity.'] |
['The prognosis for gastric cancer remains dismal; novel agents that target specific molecular pathways are needed as adjuvant therapy. Camptothecin (CPT), on inhibitor of topoisomerase I, is effective in the treatment of certain solid tumors; its effects on gastric cancer are largely undefined. The purpose of this study was to (1) characterize the effects of CPT on the growth of a human gastric cancer and (2) assess potential cellular mechanisms responsible for CPT-mediated growth inhibition.', 'The human gastric cancer SIIA was transplanted subcutaneously into athymic nude mice. After tumors reached approximately 100 mm2, mice were randomized into 3 groups to receive either CPT (5 or 10 mg/kg) or vehicle (control) intraperitoneally 3 days per week for 3 weeks; tumor size was measured biweekly. To assess potential mechanisms of CPT-mediated inhibition, SIIA cells were treated with CPT (20 mumol/L) and cells were counted over a time course; apoptosis was assessed by Hoechst stain and DNA laddering. Expression of p53 (a tumor suppressor), p21Waf1 and p27Kip1 (cell cycle inhibitors), and Bcl-2 and Bcl-XL (antiapoptotic proteins) was determined.', 'CPT (5 and 10 mg/kg) significantly inhibited tumor growth of SIIA gastric cancers compared with controls. CPT-mediated inhibition of SIIA cell proliferation was associated with an increase in apoptosis. Moreover, CPT treatment resulted in induction of p53, p21Waf1, and p27Kip1 and a decrease in Bcl-2 and Bcl-XL RNA and protein levels.'] |
['It has been shown that the main apolipoprotein of HDL, Apo A-1, is subjected to nitration by myeloperoxidase (MPO) and this oxidative modification renders HDL proatherogenic. The aim of this study is to evaluate the relationship between plasma MPO levels, and the severity of coronary artery disease.', 'Forty-eight patients with coronary artery narrowing and 30 control subjects were enrolled in this study. The severity of the disease was assessed by Gensini scoring after angiography. MPO concentrations were determined by using an enzyme immunoassay. A subgroup of 30 patients underwent computerized tomography to determine the calcium load of coronary arteries. Plasma MPO levels were found significantly higher in patients with coronary artery disease than controls (4.27 [1.60 to 42.43] ng/mL vs. 2.93 [1.00 to 9.25] ng/mL, P = 0.002). MPO was positively correlated with both Gensini (r = 0.228, P = 0.044) and coronary calcium scores (r = 0.433, P = 0.017). The atherosclerotic burden was more strongly correlated with MPO levels than the traditional markers such as total cholesterol and HDL.'] |
['Previous studies indicate that human papillomavirus 16 (HPV16) infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC). We aim to detect the influence of HPV16 infection on ESCC patient prognosis.', "Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR), and phosphatidylinositol 3-kinase (PI3K) was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People's Republic of China.", 'HPV16 E6 expression was significantly higher in the ESCC group (P<0.05). HPV16 E6 expression was significantly higher in men than in women (P<0.05). p75NTR expression was higher in those aged >56 years (P<0.05). PI3K expression was higher in those with a more advanced histopathological grade (P<0.05). There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001) and between p75NTR and PI3K expression (r=0.364, P<0.001). In 100 evaluable patients, the 5-year overall survival (OS) rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05), 5-year OS (P<0.05), and progression-free survival (P<0.05).'] |
['Trapa natans L. has a folkloric reputation as nutrient, appetizer and astringent. Its utility as antidiabetic, anticancer, diuretic, aphrodisiac, antidiarrhoeal and in many other maladies is well reported in the literature. Therefore, the present study has been carried out to study the antihyperglycemic effect of root extract of Trapa natans L. and its various fractions. Furthermore, hepatotoxic effects and lipid peroxidation risks have also been evaluated.', 'The ethanol extract and its successive fractions obtained from roots of Trapa natans have been administered in sucrose loaded and STZ- induced diabetic Wistar rats at doses of 50, 100 and 200mg/kg b.w. Glibenclamide was used as positive control. The evaluation of protective effects of extract as well as fractions against hepatotoxicity and lipid peroxidation at 600mg/kg b.w. has also been carried out.', 'The methanol fraction emerged as the most potent antihyperglycemic fraction. It has also been found that the ethanolic extract as well as its fractions did not cause any lipid peroxidation and hepatotoxicity risks.'] |
['We tested the hypothesis that titration of sevoflurane using bispectral index (BIS) of the electroencephalogram decreases postoperative nausea and vomiting and improves recovery after outpatient gynecologic laparoscopy. After propofol induction, anesthesia was maintained in all patients with sevoflurane in 65% nitrous oxide and oxygen. In the BIS-Titrated group (n = 32), sevoflurane was titrated to maintain the BIS between 50 and 60 during surgery. In the Control group (n = 30), sevoflurane was adjusted to keep hemodynamic variables within 25% of control values. The severity of pain, postoperative nausea and vomiting, and recovery variables were recorded. In the Control group, 30% of the patients had BIS <40 during surgery (versus 0 in the BIS-Titrated group). Orientation and ability to drink were achieved earlier in the BIS group (P < 0.05). At 30 min after cessation of nitrous oxide, patients in the BIS group performed better in the psychomotor recovery test (P < 0.01). In Phase II recovery room, these patients had significantly less vomiting than the patients in the Control group (16% versus 40% of the patients, respectively, P < 0.05). No differences were found in times to achieve home readiness.'] |
['Blunt cerebrovascular artery injury (BCI) remains difficult to diagnose but is recognized with increasing frequency after motor vehicle collisions (MVCs). Failure to detect this injury in a timely fashion can be devastating. Criteria that can be used to heighten the suspicion of this injury have been suggested; however, more encompassing screening has been recommended. To address this need, we sought to describe occupant, vehicle, and collision characteristics among MVC occupants who sustained a BCI.', 'All cases of BCI identified in the National Automotive Sampling System Crashworthiness Data System, a national probability sample of passenger vehicles involved in police-reported tow-away MVCs, between 1993 and 2001 were selected. Information on occupant (e.g., demographics, seating position, and restraint use), collision (e.g., collision type and severity), and vehicle characteristics were obtained and summarized using descriptive statistics.', 'Nine-hundred forty individuals with BCI were identified in the Crashworthiness Data System data files. Over half were belted (57.4%) and 82.3% had airbag deployment; 16.2% were partially or completely ejected from the vehicle. Head and thoracic injuries were common (44.4% and 40.8%, respectively); 27.8% sustained a cervical spine fracture and 21.0% sustained a soft-tissue injury to the neck. The mean Injury Severity Score was 33.6. The case fatality rate was 44.5%. The majority of BCI occupants were drivers (76.0%). Among belted occupants, the lap/shoulder was the most commonly attributed as the injury source (61.4%). Among unbelted occupants, frequent injury sources included air bags (15.0%), windshield (13.7%), and other interior objects. With respect to collision characteristics, the average change in velocity (Delta V) was 43.3 km/h. The majority of collisions were frontal (76.2%).'] |
['To investigate the phenomenon of recurrent adnexal torsion during the same pregnancy, describe its risk factors, and suggest possible management of this entity.', 'Retrospective case-control study (Canadian Task Force classification II-3).', 'Gynecologic endoscopy unit in a university hospital.', 'Pregnant women with surgically proved adnexal torsion were retrospectively identified from 1993 to 2007. Details of clinical presentation, method of conception, preoperative ultrasound findings, and operative findings were analyzed.', 'Comparison of characteristics of patients with recurrent episodes of adnexal torsion during the same pregnancy vs a single episode of torsion.', 'Thirty-three pregnant women with 38 episodes of adnexal torsion were included in the study. Seventeen pregnancies (51.5%) were spontaneously conceived. Twenty-eight women had a single episode of torsion, and 5 women (15.1%) had recurrent episodes of torsion during the same pregnancy. No significant differences were found between the 2 groups in age, method of conception, and gestational age at time of torsion. However, ultrasound studies demonstrated that multicystic ovaries were significantly more common in women with recurrent torsion compared with women with a single episode of torsion (80% vs 25%; p =.02). The interval between the first and second episodes of torsion ranged from 1 to 4 weeks.'] |
['Pressure distention of veins during preparation for bypass surgery is believed to impair vascular integrity and reduce graft patency. We previously suggested a combination of pharmacologic vasodilatators as an alternative to distention. Vascular homeostasis is largely regulated by nitric oxide. We investigated the role of distention in comparison with pharmacologic vasorelaxation in the regulation of nitric oxide synthases, nitric oxide bioavailability, and vascular reactivity in vein grafts.', 'In a porcine model the internal jugular vein from either side received pressure distention or the combination of vasodilators (alpha-adrenergic antagonist, phenoxybenzamine, 10 micromol/L; Rho-kinase inhibitor, HA-1077 [fasudil], 50 mumol/L; calcium blocker, nicardipine, 1 micromol/L) and then was grafted into the carotid artery. Regulation of nitric oxide synthase, as well as nitrate and nitrite levels, were examined in vein grafts after 2 weeks of implantation.', 'Distention of jugular veins resulted in reduction of vasoconstriction in response to depolarization and agonist stimulation. Arterial grafting doubled inducible nitric oxide synthase expression in both grafts but caused a pronounced upregulation of endothelial nitric oxide synthase protein (by 57.3% +/- 5%) only in drug-treated grafts, whereas in distended grafts the endothelial nitric oxide synthase level was decreased by 27.5% +/- 2.7%. The downregulated endothelial nitric oxide synthase level in the distended grafts was accompanied by a 45.2% +/- 3.1% reduction of phospho-endothelial nitric oxide synthase Ser1177 levels and by a significant reduction in nitric oxide synthase activity (12.1% +/- 1.2%) and nitrate production (48.9% +/- 5.6%) in comparison with that seen in drug-treated grafts.'] |
['Cytoplasmic retention of β-catenin will lead to its nuclear translocation and subsequent interaction with the transcription factor TCF/LEF that regulates target gene expression. We have previously demonstrated aberrant expression of β-catenin in a model of asthma induced by toluene diisocyanate (TDI). The aim of this study was to examine whether the receptor for advanced glycation end products (RAGE) can regulate β-catenin expression in TDI-induced asthma.', 'Male BALB/c mice were sensitized and challenged with TDI to generate a chemically-induced asthma model. Inhibitors of RAGE, FPS-ZM1 and the RAGE antagonist peptide (RAP), were injected i.p. after each challenge. Airway resistance was measured in vivo and bronchoalveolar lavage fluid was analysed. Lungs were examined by histology and immunohistochemistry. Western blotting and quantitative PCR were also used.', 'Expression of RAGE and of its ligands HMGB1, S100A12, S100B, HSP70 was increased in TDI-exposed lungs. These increases were inhibited by FPS-ZM1 or RAP. Either antagonist blunted airway reactivity, airway inflammation and goblet cell metaplasia, and decreased release of Th2 cytokines. TDI exposure decreased level of membrane β-catenin, phosphorylated Akt (Ser(473) ), inactivated GSK3β (Ser(9) ), dephosphorylated β-catenin at Ser(33) /(37) /Thr(41) , which controls its cytoplasmic degradation, increased phosphorylated β-catenin at Ser(552) , raised cytoplasmic and nuclear levels of β-catenin and up-regulated its targeted gene expression (MMP2, MMP7, MMP9, VEGF, cyclin D1, fibronectin), all of which were reversed by RAGE inhibition.'] |
['Many studies have demonstrated that repeated injections of nicotine can produce progressive increases in locomotor activity and enhanced expression of c-fos and tyrosine hydroxylase (TH) in brain dopaminergic areas. Paecilomyces japonica (PJ) is a herbal medicine that is commonly used to treat opiate and other addictions in Eastern Asia. However, its influence on nicotine addiction has not been examined. This study was carried out to investigate the effects of PJ on repeated nicotine-induced behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry.', 'Rats were pretreated with PJ (10, 25, 50, 100, and 200 mg/kg, intraperitoneally) 30 min before repeated injections of nicotine (0.4 mg/kg, subcutaneously, twice daily for 7 days). Locomotor activity was measured in rats during 7-day nicotine treatments. On the seventh day, c-Fos and TH expression were assessed.', 'Pretreatment with PJ decreased the development of nicotine-induced sensitization, c-Fos expression in the nucleus accumbens and striatum, and TH expression in the ventral tegmental area. PJ decreased nicotine-induced locomotor activity by modulating brain dopaminergic systems.'] |
['The SELH/Bc mouse inbred strain, with a high frequency of nonsyndromic, genetically-multifactorial exencephaly, is a model for human cranial neural tube defects (NTDs). Maternal diet affects risk of human NTDs.', 'Exencephaly frequencies in SELH/Bc embryos were compared in 8 studies in which dams were fed alternative commercial Purina diets (5015 and 5001) or semisynthetic diets, and in several studies in which maternal diet was supplemented with a specific nutrient, either in drinking water or food before and during pregnancy, or by intraperitoneal injection on E7 and/or E8.', "The exencephaly frequency in SELH/Bc embryos was 2- to 8-fold higher when the dams were fed Purina 5015 (averaging 23% exencephaly) or a semisynthetic diet modeled on Purina 5015 (averaging 28%) or NIH-31 standard diet (23%), compared with Purina 5001 (averaging 7%). The exencephaly frequency remained high (41%) on a semisynthetic diet modeled on Purina 5001. The exencephaly frequency was not reduced significantly by maternal supplementation with folic acid, nor with each of zinc, methionine, niacin, brewers' yeast, riboflavin, vitamin B12, or inositol. Nor was it reduced by maternal diets with supplemental methyl donors and cofactors or with reduced fat."] |
['Cross-sectional study.', 'The purpose of this study was to determine if a sustained fatiguing contraction of the dorsiflexor muscles alters the dynamic position sense (proprioception) and the associated central nervous system processing time of information from the ankle.', 'Ankle injury has been hypothesized to be related to altered proprioception as a consequence of fatiguing exercise. Previous reports assessing proprioception include tests of motor performance (balance and limb repositioning) or tests of a joint under static conditions. This study used a novel experimental approach to test the effects of exercise on the somatosensory system of the ankle.', 'Nineteen healthy subjects were tested on their ability to extend the metacarpophalangeal joint of their left index finger when their left ankle was passively plantar flexed (0 degrees-40 degrees, 10 velocities) through a predetermined target angle (20 degrees). Testing occurred before and after a fatiguing contraction of the dorsiflexor muscles.', 'Subjects accurately indicated the ankle target angle up to ankle velocities of 70 degrees/s (300 ms) both before and after the sustained fatiguing contraction. At velocities above 70 degrees/s all subjects could no longer scale to accurately indicate the target angle with the index finger and consequently overshot the target. The central nervous system processing time was estimated to be approximately 85 milliseconds before and after the sustained contraction.'] |
['With regard to a deficiency in atrial natriuretic peptide (ANP) secretion, the relationship between plasma ANP and left atrial diameter measured by echocardiography was examined and the efficacy of postoperative supplementation was evaluated.', '(1) Ninety-six patients with mitral valve disease from 1997 to 2002 (M:F = 65:31, mean-age 65.3 +/- 8.9 years) were studied for relationship analyses. (2) Twenty-six patients with mitral stenosis and left atrial diameter > or = 60 mm undergoing mitral valve replacement (M:F = 17:9, mean-age 67.4 +/- 7.5 years) were randomly allocated to one of two groups; ANP-treated group (n = 13, 0.05 microg/kg/min of synthetic human alpha-ANP was postoperatively administered) and Control group (n = 13).', '(1) There were significant positive correlations between left atrial diameter and plasma renin-activity (r = 0.690, P < 0.01) and between left atrial diameter and plasma aldosterone (r = 0.757, P < 0.01). The maximum value of plasma ANP was 249.5 pg/mL accompanied with 56.2 mm of left atrial diameter in 29 patients suffering from mitral stenosis. There was a significant negative correlation between left atrial diameter and ANP in patients with left atrial diameter > 56.2 mm (r = - 0.725, P < 0.0001), whereas there was a significant positive correlation in patients with left atrial diameter < or = 56.2 mm (r = 0.529, P = 0.0066). (2) At 24 hours after operation, the ANP-treated group showed significantly lower plasma renin-activity (9.2 +/- 3.3 versus 36.2 +/- 7.4 ng/mL/h) and aldosterone (113.6 +/- 36.9 versus 473.8 +/- 95.8 pg/mL) than the Control group.'] |
['Lung cancer is one of the leading causes of cancer death worldwide. Even with complete resection, the prognosis of early-stage non-small cell lung cancer is poor due to local and distant recurrence, and it remains unclear which biomarkers are clinically useful for predicting recurrence or for determining the efficacy of chemotherapy. Recently, several lines of evidence have indicated that the enzymatic activity of cyclin-dependent kinases could be a clinically relevant prognostic marker for some cancers. We investigated whether the specific activity of cyclin-dependent kinases 1 and 2 could predict recurrence or death in early non-small cell lung cancer patients.', 'Patients with newly diagnosed, pathologically confirmed non-small cell lung cancer were entered into this blinded cohort study. The activity of cyclin-dependent kinases was determined in 171 samples by the C2P® assay, and the results were subjected to statistical analysis with recurrence or death as a clinical outcome.', 'The Cox proportional hazards model revealed that the activity of cyclin-dependent kinase 1, but not 2, was a predictor of recurrence, independent of sex, age, and stage. By contrast, cyclin-dependent kinase 2 activity was a predictor of death, independent of sex and stage.'] |
['Preeclampsia is a leading cause of maternal and perinatal mortality worldwide. The exact etiology of preeclampsia is unknown, but the inflammatory process is postulated as one of the etiologies. Red blood cell distribution width (RDW) is a measure of anisocytosis (variation of red cell size) and is associated with hypertension and diabetic ketoacidosis. There are few data on the association between RDW and preeclampsia. This study aimed to investigate the association between RDW and preeclampsia.', 'A case-control study was conducted at Khartoum Hospital, Sudan, during June to August 2012. Cases were women with preeclampsia and healthy women were controls. Sociodemographic characteristics, obstetrics, and clinical data were recorded. The complete blood count, including RDW, was measured using an automated hematology analyzer.', 'The cases and controls (65 women in each arm) were matched in their basic characteristics. There was no difference in the mean (SD) RDW between women with preeclampsia and controls (14.5\u2009±\u20091.8% vs. 14.4\u2009±\u20091.4%, P\u2009=\u20090.710). There was also no difference in the mean RDW between women with mild and severe preeclampsia (14.7\u2009±\u20091.9% vs. 13.9\u2009±\u20091.4%, P\u2009=\u20090.144. In logistic regression, there was no association between RDW and preeclampsia (OR\u2009=\u20090.9, CI\u2009=\u20090.7-1.1, P\u2009=\u20090.952).'] |
['To determine the phylogenetic group and the production of different virulence factors (VFs) of a collection of Escherichia coli strains overproducing their chromosomal AmpC cephalosporinase.', 'Fifty-five E. coli strains, isolated over a 12 year period, and previously identified as AmpC overproducers by increased MICs of third-generation cephalosporins without extended-spectrum beta-lactamase production (negative double-disc synergy test), were phylogrouped by multiplex PCR. As a comparison, 100 E. coli clinical isolates, susceptible to all beta-lactams, were also tested by the same method. The ampC promoter sequence was determined for all these isolates. ERIC-2 PCR (where ERIC stands for enterobacterial repetitive intergenic consensus) was used to compare the isolates. Search for virulence-associated genes (papG alleles, sfa/foc, hly and iucC) was performed by multiplex PCR for the 55 AmpC overproducers.', 'Most of the AmpC overproducers (47/55) belonged to phylogenetic group A, correlated with a low prevalence of the main VFs in these strains. The - 32, -42 and - 11 mutations, responsible for AmpC overproduction, were usually associated with DNA polymorphisms at positions - 88, - 82, -18, +1 and + 58 in the ampC promoter. In the control susceptible isolates, these polymorphisms were detected in 13 ampC promoters (9 group B1 and 4 group A). These polymorphisms were never associated with the main phylogenetic group B2, representing 66% of the susceptible isolates.'] |
['Eosinophilic pleural effusion (EPE) is characterized by greater than 10% eosinophilia and is frequently associated with air and/or blood in the pleural cavity. Primary spontaneous pneumothorax (PSP), defined as the spontaneous presence of air in the pleural space, is one of the most common causes of EPE. Recent studies have shown that type 2 immune responses play important roles in eosinophilic airway inflammation resulting in pleural pathology.', 'To determine the predominant immune responses associated with PSP in humans, and to examine whether IL-33, thymic stromal lymphopoietin (TSLP), or type 2 innate lymphoid cell (ILC2)-mediated immune responses are associated factors.', 'Eosinophil-associated cytokines were measured in the pleural fluid of patients with PSP and control subjects. Th2 cell and ILC2 responses in the pleural cavity and peripheral blood were also evaluated by in vitro restimulation and intracellular cytokine staining of T cells and ILC2s in patients with PSP (n = 62) and control subjects (n = 33). IL-33-mediated IL-5 production by ILC2s was also evaluated.', 'Significantly higher concentrations of IL-5 and eotaxin-3 were detected in the pleural fluid of patients with PSP, in addition to significantly higher concentrations of IL-33 and TSLP. Although IL-5 production was induced by IL-33 treatment of ILC2s, other Th2 cell-mediated immune responses were not detected.'] |
['Physician counseling on the risks of tobacco smoking and the benefits of cessation has been shown to be an effective method of increasing the rate of smoking cessation. Using the "Help Your Patients Quit Smoking: A Coaching Guide" also referred to as the "7A\'s of Smoking Cessation" guideline from the New York City Department of Health and Mental Hygiene is thought to be effective to convey the importance of smoking cessation.', 'To study the efficacy of the "7A\'s of Smoking Cessation" guideline counseling conducted by osteopathic medical students.', 'Osteopathic medical students were trained to counsel smokers for 3-10 min based on New York City Department of Health\'s "7A\'s of Smoking Cessation" guidelines by a licensed physician. Students then counseled health fair participants who were cigarette smokers for 3-10 min. Postcounseling, participants were administered an 4 question survey to evaluate the effect counseling had on their desire to quit smoking. Survey data were collected and analyzed. Institutional Review Board approval was obtained for this study.', 'A total of 13 anonymous health fair participants who were also smokers were administered both counseling sessions and surveys. 11/13 (84.6%) participants stated that the session motivated them to quit smoking. 9/13 (69.2%) participants responded that they were now motivated to discuss smoking cessation with their doctor after being counseled. Of these participants 12/13 (92.3%) had previously attempted to quit smoking without success.'] |
['To examine the hypothesis that induction of heat shock proteins in human endothelial cells (ECs) by either heat shock or sodium arsenite could prevent subsequent EC necrosis induced by activated human polymorphonuclear neutrophil leukocytes (PMNs).', 'Cultures of ECs were exposed to heat shock (42 degrees C, 30 to 60 minutes) or sodium arsenite (40 to 320 mumol/L) for 6 hours to induce the expression of a heat shock protein of 72-kd molecular weight (HSP-72). Activated PMNs were subsequently added to these ECs for 24 hours to evaluate the ability of HSP-72 to prevent activated PMN-mediated EC necrosis.', 'Neither EC necrosis nor apoptosis was induced by heat shock. Sodium arsenite (40 to 80 mumol/L) did not induce EC necrosis, although 320-mumol/L sodium arsenite caused a significant increase in EC necrosis. Sodium arsenite (80 to 320 mumol/L) also induced dose-dependent EC apoptosis. Endothelial cells exposed to heat shock and sodium arsenite (40 and 80 mumol/L) significantly attenuated subsequent EC necrosis induced by activated PMNs. However, sodium arsenite at 320 mumol/L aggravated activated PMN-mediated EC necrosis. Expression of HSP-72 was detected after ECs were treated both with heat shock and sodium arsenite (40 to 320 mumol/L) for 6 hours.'] |
['We attempted to determine the molecular mechanism of fluid shear stress-induced lipocalin-type prostaglandin D synthase (l-PGDS) expression in vascular endothelial cells.', "We examined the promoter region of the l-PGDS gene by loading laminar shear stress (20 dyne/cm2), using a parallel-plate flow chamber, on endothelial cells transfected with luciferase reporter vectors containing the 5'-flanking regions of the human l-PGDS gene. A deletion mutant analysis revealed that a shear stress-responsive element resided in the region between -2607 and -2523 bp. A mutation introduced into the putative binding site for activator protein-1 (AP-1) within this region eliminated the response to shear stress. In an electrophoretic mobility shift assay, shear stress stimulated nuclear protein binding to the AP-1 binding site, which was supershifted by antibodies to c-Fos and c-Jun. Shear stress elevated the c-Jun phosphorylation level in a time-dependent manner, similar to that of l-PGDS gene expression. SP600125, a c-Jun N-terminal kinase inhibitor, decreased the c-Jun phosphorylation, DNA binding of AP-1, and l-PGDS expression induced by shear stress. Additionally, an mRNA chase experiment using actinomycin D demonstrated that shear stress did not stabilize l-PGDS mRNA."] |
['While a relationship between alcohol and cardiovascular risk factors is well established, data suggest that the type of alcoholic beverage could modulate this relationship.', 'To determine whether drinking patterns modulate the relationship between alcohol and cardiovascular risk factors.', "We tested the relationship between preference of alcoholic beverages and atherosclerotic risk factors in a cross-sectional study of 2,126 men. A hierarchical clustering method determined six drinking patterns, 'low drinkers', 'high quality wines', 'beer and cider', 'digestives', 'local wines', and 'table wines', according to the preferential intake of alcoholic beverages. Logistic models estimated the relative risk of abnormal markers in the drinking patterns compared with low drinkers. Unadjusted estimates investigated the relationship with the cluster as a group, while adjustment on alcohol, nutritional and socio-demographic factors investigated the relationship with the preference of alcoholic beverage in itself.", 'Abstainers had high total plasma homocysteine (tHcy), even after full adjustment (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.8). Drinkers of high quality wine had low lipoprotein( a), high tHcy and high body mass index; beer and cider drinkers had high tHcy and waist circumference. Drinkers of digestives had high triacylglycerol; after adjustment they were at risk of low apolipoprotein A-I (OR = 3.1, 95% CI: 1.2, 7.3), and high tHcy (OR = 4.9, 95% CI: 1.2, 33.3). Local wines drinkers were similar to low drinkers. Table wine drinkers had high apolipoprotein B, high triacylglycerol, and high waist-to-hip ratio.'] |
['Galectin-3 (gal-3) participates in a variety of biological events, including cell adhesion, proliferation, differentiation and apoptosis. The aim of this study was to determine the relationship of gal-3 expression with clinicopathological findings and prognosis in patients with gastric cancer.', 'Gal-3 and Ki-67 expressions were assessed by immunohistochemistry in 115 patients with gastric cancer. PCR-single strand conformation polymorphism (SSCP)-sequence analysis and the levels of gal-3 mRNA were also examined.', 'The present study demonstrated that gal-3 expression was correlated with nodal status, lymphatic inivasion, pathological stage and histological parameters. On the other hand, gal-3 expression did not correlate with the expression of Ki-67. Reduced expression of gal-3 was significantly associated with a poor prognosis and multivariate analysis showed that gal-3 expression was an independent prognostic factor. On PCR-SSCP-sequence analysis, 2 single nucleotide polymorphisms (SNPs) were detected in the gal-3 gene, but none showed mutations.'] |
['Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or to artesunate were compared with patients treated with parenteral treatment with quinine or artesunate but who did not receive ET. ET was executed using a standardized manual isovolumetric exchange protocol.', 'All patients in the Rotterdam Malaria Cohort treated for severe P. falciparum malaria at the Institute for Tropical Diseases of the Harbour Hospital between 1999 and 2011 were included in this retrospective follow-up study. Both a two-stage approach and a log-linear mixed model approach were used to estimate parasite clearance times (PCTs) in patients with imported malaria. Severe malaria was defined according to WHO criteria.', 'A total of 87 patients with severe malaria was included; 61 received intravenous quinine, whereas 26 patients received intravenous artesunate. Thirty-nine patients received ET as an adjunct treatment to either quinine (n = 23) or artesunate (n = 16). Data from 84 of 87 patients were suitable for estimation of parasite clearance rates. PCTs were significantly shorter after administration of artesunate as compared with quinine. In both models, ET did not contribute significantly to overall parasite clearance.'] |
['Hepatocellular carcinoma (HCC) frequently arises in the context of chronic injury that promotes DNA damage and chromosomal aberrations. The cyclin-dependent kinase inhibitor p21 is an important transcriptional target of several tumor suppressors, which promotes cell cycle arrest in response to many stimuli. The aim of this study was to further delineate the role of p21 in the liver during moderate and severe injury and to specify its role in the initiation and progression of HCC. Deletion of p21 led to continuous hepatocyte proliferation in mice with severe injury allowing animal survival but also facilitated rapid tumor development, suggesting that control of compensatory proliferation by high levels of p21 is critical to the prevention of tumor development. Unexpectedly, however, liver regeneration and hepatocarcinogenesis was impaired in p21-deficient mice with moderate injury. Mechanistically, loss of p21 was compensated by activation of Sestrin2, which impaired mitogenic mammalian target of rapamycin (mTOR) signaling and activated cytoprotective Nrf2 signaling.'] |
['To determine whether field photodynamic therapy (PDT) of actinic keratoses using a novel preparation of 5-aminolevulonic acid (novel ALA) results in fewer subsequent invasive skin cancers developing on the face of individuals with previous facial cutaneous malignancy in a prospective randomized controlled trial.', 'Intervention patients received two treatments of novel ALA 2 weeks apart. Controls were observed. Patients were followed up with biopsy of any suspicious lesions for 3 years.', 'The trial was suspended early because of problems with trial governance and the reporting of severe adverse events. Sixty-four patients who were recruited at that time at one center were monitored. Their average age was 71, and 57% were male. Patients were randomized to intervention (n = 34) or observation (n = 29). Over the subsequent 3 years, 13 intervention patients (38%) developed 30 new cutaneous malignancies in the field treated, and 11 control patients (38%) developed 22 new malignancies. Some intervention patients experienced prolonged adverse events, including permanent scarring.'] |
['Children and adolescents are encouraged to maintain a habitually active lifestyle because of the known health benefits associated with regular physical activity, but there are some reports that a high level of activity may be associated with increased fracture risk. This prospective controlled exercise intervention study in prepubertal children evaluated if a school-based exercise intervention could enhance growth-related gains in muscle strength and muscular function without affecting fracture risk.', 'Fractures were registered in 417 girls and 500 boys age 7-9 yr in the intervention and in 836 age-matched girls and 872 boys. The intervention included 40 min·d of school physical education for 2 yr, whereas the controls achieved 60 min·wk. In a subsample consisting of 49 girls and 80 boys in the intervention and 50 girls and 53 boys in the control group, body composition was measured by dual-energy x-ray absorptiometry, muscle strength by isokinetic peak torque (PT) of the knee extensors, and flexors at 60 and 180°·s by a computerized dynamometer and neuromuscular performance by vertical jump height.', 'The rate ratio (95% confidence interval) for children in the intervention group to sustain a fracture was 1.07 (0.66-1.68). The annual gain in knee extensor PT at 180°·s was significantly higher for both girls (P < 0.001) and boys (P < 0.01) in the intervention compared with the control group. Boys in the intervention group also had a greater annual gain in knee flexion PT at 180°·s (P < 0.001), and girls had a greater gain in vertical jump height (P < 0.05).'] |
['To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.', "Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA).", 'Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages.'] |
["Crohn's disease frequency has increased in recent years in Iran. Genetic and environmental factors predispose people to this disease. Mutation in Caspase Recruitment Domain 15 (CARD15) gene is the most well known genetic predisposing factor to this disease. Frequency of three common CARD15 mutations has been studied in different ethnic groups. We aimed to study the frequency of these mutations in Iranian patients affected with Crohn's Disease.", 'One hundred fifteen proved cases of Crohn Disease and 115 age and sex matched normal controls were recruited in this study. Lf1007fs, R702W and G908R mutations were studied by Polymerase Chain Reaction-Restriction Fragment Length Polymorphims (PCR-RFLP) followed by sequencing the positive cases.', 'Lf1007fs and G908R mutations were not found in either patients or age-sex matched controls. Just in two patients, R702W mutation was proved by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing. None of these patients had illeal or fibrostenotic type of disease while 14.7% of total patients had stricturing type of disease. No complication was seen in these two patients while 50.4% of patients had acquired complications during the course of disease.'] |
['The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure.', 'Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei.', 'Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2 days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1beta exposure.'] |
['The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial.', 'To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury.', 'Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity.', 'A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days.'] |
['The purpose of this study was to investigate why low-risk nulliparae were not willing to participate in a randomised controlled trial (RCT) of place of birth.', 'Prospective study.', 'The Netherlands.', 'All low-risk nulliparous women starting their pregnancy under midwife.', 'A questionnaire for 107 nulliparae who were willing to participate in a cohort study on place of birth, but at an earlier stage in their pregnancy declined to participate in a RCT of place of birth. This questionnaire included 12 items on a 4-point Likert scale but was not subjected to formal validation.', 'Reasons why nulliparae did not accept randomisation of place of birth.', 'The most important reason why women refused participation in the trial was that they had already chosen their place of birth before they were asked to participate at 12 weeks of pregnancy. From their answers, it became clear that pregnant women strongly value their autonomy of choice. The decision not to participate in the trial was not influenced by the information given by the midwife and the additional written information.'] |
['The RHO C110Y mutation has been recently reported to cause a phenotypically unspecified form of autosomal dominant retinitis pigmentosa (adRP). The study of a family affected with this mutation allowed us to hereby describe the genotype/phenotype correlation associated with the RHO C110Y mutation.', 'A six-generation pedigree cosegregating adRP and RHO C110Y in ten accessible individuals was ophthalmologically investigated. All family members affected with RP went through complete eye examination and ERG testing.', 'The disease first manifested with nyctalopia during adulthood and slowly progressed over the next decades towards tubular visual field defects and relatively preserved central vision. Ophthalmoscopically, the fundus remained almost unaltered until the end of the third decade of life, and then slowly progressed towards typical RP changes with minimal macular involvement by the eighth decade. Color vision remained unaltered. Earliest ERG alteration was limited to the rod system followed by a rod-cone pattern. Scotopic and photopic ERG were recordable until the fourth and sixth decades, respectively.'] |
['To study the cellular mechanisms involved in the regression of diabetic nephropathy, bone marrow-derived cells must be identified. The aim of this study was to obtain a diabetic chimeric model with bone marrow cells expressing enhanced green fluorecence protein (EGFP), without modifying the course of diabetic nephropathy.', 'Bone marrow transplantation (BMT) was performed in an obese type 2 diabetic murine model (db/db) owing to a mutation in the leptin receptor gene. Whole bone marrow from female donor C57BL/6 EGFP+ mice was transplanted into 8-week-old C57BL/6 mice and into 8- and 24-week-old female C57BLKS (db/db) EGFP- mice. Recipient mice received total body irradiation (TBI) followed by bone marrow (BM) cell infusion. We tested various irradiation doses (Gy) and numbers of BM cells.', 'When a low TBI dose and a small number of BM cells were administered, only syngeneic C57BL/6 mice became chimeric, whereas allogeneic db/db mice showed rejection. When Gy dose and BM cells were increased, db/db mice became chimeric. However, 8-week-old db/db mice lost the obese phenotype and became normoglycemic, probably due to peripheral BM cell infiltration. Conversely, 24-week-old db/db mice remained obese showing similar blood glucose values, body weights, albuminuria, and glomerular lesions at nontransplanted db/db mice.'] |
['We update our previous reports on the use of hypofractionated proton beam radiation therapy for early-stage lung cancer patients.', 'Eligible subjects had biopsy-proven non-small cell carcinoma of the lung and were medically inoperable or refused surgery. Clinical workup required staging of T1 or T2, N0, M0. Subjects received hypofractionated proton beam therapy to the primary tumor only. The dose delivered was sequentially escalated from 51 to 60 Gy, then to 70 Gy in 10 fractions over 2 weeks. Endpoints included toxicity, pulmonary function, overall survival (OS), disease-specific survival (DSS), and local control (LC).', 'One hundred eleven subjects were analyzed for treatment outcomes. The patient population had the following average characteristics; age 73.2 years, tumor size 3.6 cm, and 1.33 L forced expiratory volume in 1 second. The entire group showed improved OS with increasing dose level (51, 60, and 70 Gy) with a 4-year OS of 18%, 32%, and 51%, respectively (P=.006). Peripheral T1 tumors exhibited LC of 96%, DSS of 88%, and OS of 60% at 4 years. Patients with T2 tumors showed a trend toward improved LC and survival with the 70-Gy dose level. On multivariate analysis, larger tumor size was strongly associated with increased local recurrence and decreased survival. Central versus peripheral location did not correlate with any outcome measures. Clinical radiation pneumonitis was not found to be a significant complication, and no patient required steroid therapy after treatment for radiation pneumonitis. Pulmonary function was well maintained 1 year after treatment.'] |
['To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma.', 'The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases.', 'Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3.'] |
['Evaluate the addition of long-distance heart procurement on a heart transplant program and the status of heart transplant recipients waiting list.', 'Between September 2006 and October 2012, 72 patients were listed as heart transplant recipients. Heart transplant was performed in 41 (57%), death on the waiting list occurred in 26 (36%) and heart recovery occurred in 5 (7%). Initially, all transplants were performed with local donors. Long-distance, interstate heart procurement initiated in February 2011. Thirty (73%) transplants were performed with local donors and 11 (27%) with long-distance donors (mean distance=792 km±397).', 'Patients submitted to interstate heart procurement had greater ischemic times (212 min ± 32 versus 90 min±18; P<0.0001). Primary graft dysfunction (distance 9.1% versus local 26.7%; P=0.23) and 1 month and 12 months actuarial survival (distance 90.1% and 90.1% versus local 90% and 86.2%; P=0.65 log rank) were similar among groups. There were marked incremental transplant center volume (64.4% versus 40.7%, P=0.05) with a tendency on less waiting list times (median 1.5 month versus 2.4 months, P=0.18). There was a tendency on reduced waiting list mortality (28.9% versus 48.2%, P=0.09).'] |
['Systemic treatment of endometrial carcinoma with distant metastases is currently performed, inter alia, with anthracyclines, platinum, paclitaxel, if osfamid or progestins. This is the first report presenting experience in treatment of metastatic endometrial carcinoma with docetaxel.', 'A 69-year-old women with adenocarcinoma of the endometrium was treated with primary combined radiotherapy. Two years later disseminated bilateral pulmonary metastases were detected and the patient was submitted to chemotherapy with epirubicin. After three cycles of chemotherapy with epirubicin examinations revealed metastatic progression. Thus, chemotherapy was changed to docetaxel.', 'After three cycles of chemotherapy with docetaxel examinations revealed remission of the described pulmonary metastases more than 50%. A further three cycles of chemotherapy with docetaxel lead to continuing shrinkage of the detectable metastases to less than 25% of the original size. Because of various side effects, like increasing fatigue and asthenia, uncomfortable acral paresthesia and allergic skin reactions, the patient refused to continue chemotherapy.'] |
['This study was aimed at deciphering the secretome of adipose-derived mesenchymal stromal cells (ADSCs) cultured in standard and hypoxic conditions to reveal proteins, which may be responsible for regenerative action of these cells.', 'Human ADSCs were isolated from 10 healthy donors and cultured for 3-4 passages. Cells were serum deprived and cell purity was assessed using multiple cell surface markers. Conditioned media was collected and analyzed using LC-MS with a focus on characterizing secreted proteins.', 'Purity of the ADSC assessed as CD90+/CD73+/CD105+/CD45-/CD31- cells was greater than 99 % and viability was greater than 97 %. More than 600 secreted proteins were detected in conditioned media of ADSCs. Of these 100 proteins were common to all cultures and included key molecules involved in tissue regeneration such as collagens and collagen maturation enzymes, matrix metalloproteases, matricellular proteins, macrophage-colony stimulating factor and pigment epithelium derived factor. Common set of proteins also included molecules, which contribute to regenerative processes but were not previously associated with ADSCs. These included olfactomedin-like 3, follistatin-like 1 and prosaposin. In addition, ADSCs from the different subjects secreted proteins, which were variable between different cultures. These included proteins with neurotrophic activities, which were not previously associated with ADSCs, such as mesencephalic astrocyte-derived neurotrophic factor, meteorin and neuron derived neurotrophic factor. Hypoxia resulted in secretion of 6 proteins, the most prominent included EGF-like repeats and discoidin I-like domains 3, adrenomedullin and ribonuclease 4 of RNase A family. It also caused the disappearance of 8 proteins, including regulator of osteogenic differentiation cartilage-associated protein.'] |
['Ischemic preconditioning (PC) is a powerful mechanism in reducing infarct size of the heart. Protection can be performed either by an ischemic stimulus of the heart itself or by ischemia of an organ distant to the heart (remote PC). We have previously shown that remote PC by infrarenal occlusion of the aorta [IOA] in the rat is as powerful as classical ischemic PC. This protection may be transmitted by humoral factors, and protein kinase C is a mediator in the signal transduction mechanism. Focus of the present study was to address the question whether remote preconditioning is dependent on the activation of the delta1-opioid receptor and/or free radicals, the infarct size was determined after either inhibition of the delta1-opioid receptor or scavenging free radicals.', 'IOA was performed in rats by occlusion of the infrarenal aorta for 15 min followed by a 10-min reperfusion period. Infarction of the heart was induced by 30 min regional ischemia followed by 30 min of reperfusion. The area of infarct was determined by propidium iodide and the risk zone was demarcated by zinc cadmium sulfide fluorescent particles. Control hearts (30 min regional ischemia of the heart followed by 30 min of reperfusion; no IOA) had an infarct size of 54 +/- 3%, whereas classical preconditioning by three ischemia/reperfusion [I/R] cycles, 5 min each, reduced it to 12 +/- 1% of the risk zone (p<0.05). Fifteen minutes IOA with 10 min of reperfusion was highly protective and reduced the infarct size to 20 +/- 5% (p<0.05 vs. control). Inhibition of the delta1-opioid receptors by 7-benzylidenenaltrexone [BNTX] blocked the protection obtained by PC and IOA (41 +/- 4% and 44 +/- 2%, respectively; p<0.05 vs. the group without BNTX). BNTX in control hearts had no influence on infarct size (52 +/- 2%). Inhibition of endogenously released radicals by N-2-mercaptopropionyl glycine [MPG] blocked the infarct size reduction of IOA (46 +/- 3%; p<0.05 vs. IOA), but had no influence on the protection in classically preconditioned hearts protected by three cycles I/R (13 +/- 4%). Only if the number of the preconditioning stimuli was reduced to one was MPG able to overcome the protection (43 +/- 4%, p<0.05 vs. PC with one I/R cycle (21 +/- 4%)).'] |
['Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear.', 'We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60+/-9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly (with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R2 0.06 to 0.28 [SAT] and 0.07 to 0.29 [VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 (SAT versus VAT comparison: isoprostanes, R2 0.07 versus 0.10, P=0.002; monocyte chemoattractant protein-1, R2 0.07 versus 0.08, P=0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein (P=0.0003 for women; P=0.006 for men), interleukin-6 (P=0.01), isoprostanes (P=0.0002), and monocyte chemoattractant protein-1 (P=0.008); SAT only remained associated with fibrinogen (P=0.01).'] |
['To determine which of the standard cardiovascular risk factors have the strongest associations with prevalent coronary artery calcification (CAC).', 'A cross-sectional study of 6086 consecutive subjects who underwent electron beam computed tomography for CAC at a private, university-affiliated disease prevention center in San Diego, CA.', 'The correlation between age and coronary calcium score in men (r=0.463) was twice that of the next highest correlation (0.218) for percent body fat. A similar relationship was found for women (0.413 vs. 0.238). Calcium scores increased incrementally by age category in both men and women. This pattern of increase was not present for LDL cholesterol. Men and women over the age of 74 had highly elevated risks for the presence of any calcified coronary atherosclerosis compared to those under the age of 45 (OR [95% CI]: 11.08 [6.186-19.859] and 11.81 [6.718-20.746], respectively). Addition of the other traditional cardiovascular risk factors did not significantly increase the discriminatory power beyond that provided by age on ROC analysis.'] |
["Adenocarcinoma arises in Barrett's esophagus by progression from metaplasia to cancer through grades of dysplasia. Our aim in this exploratory study was to characterize the broad changes in gene expression that underlie this histologic progression to cancer and assess the potential for using these gene expression changes as a marker predictive of malignant progression in Barrett's epithelium.", "Microarray analysis was used to obtain individual gene expression profiles from endoscopic biopsies of nine esophageal adenocarcinomas and the Barrett's epithelia from which three of the cancers had arisen. Pooled samples from the Barrett's epithelia of six patients without cancer or dysplasia served as a reference.", "Barrett's epithelia from which cancer had arisen differed from the reference Barrett's epithelia primarily by underexpression of genes, many of which function in governing cell differentiation. These changes in gene expression were found even in those specimens of Barrett's epithelia from which cancer had arisen that lacked dysplasia. Each cancer differed from the Barrett's epithelium from which it had arisen primarily by an overexpression of genes, many of which were associated with tissue remodeling and invasiveness. Cancers without identifiable Barrett's epithelium differed from cancers that had arisen from a Barrett's epithelium by having an even greater number of these overexpressed genes."] |
['Local ablation therapy has been shown to be effective for small hepatocellular carcinoma (HCC); however, HCC recurrence is very frequent even after apparently curative treatment. In particular, recurrent HCC may be more prone to subsequent recurrence, although quantitative data are lacking. The aim of this study was to evaluate the difference in the risk for subsequent recurrence, if any, between primary and recurrent cases.', 'A retrospective analysis was conducted of 376 patients with HCC (uninodular and <or=5 cm, or 2-3 nodules each <or=3 cm) who underwent local ablation therapy. There were 207 primary cases (group I), 100 with first recurrence (group II), and 69 with second or later recurrence (group III). After confirming complete ablation, each patient was followed up for recurrence. Risk factors for recurrence-free survival were analyzed using proportional hazard regression.', 'The median time to recurrence, as estimated by Kaplan-Meier method, was 30 months in group I, 23 months in group II, and 11 months in group III (P < 0.001). Multivariate proportional hazard regression analysis reveled that group (i.e. previous recurrence) was the strongest predictor of subsequent recurrence; compared to group I, group II showed a hazard ratio of 1.456 (P = 0.015) and group III, 3.011 (P < 0.0001). alpha-Fetoprotein level >100 ng/mL, treatment other than radiofrequency ablation, HCV antibody positivity, and tumor multinodularity also remained as significant predictors.'] |
['A parental occupation such as anesthesia care provider can involve exposure of the parent to various chemicals in the work environment and has been correlated to skewed offspring sex ratios.', 'The objective was to conduct a nation-wide survey to observe (a) whether firstborn offspring sex ratio (OSR) in anesthesia providers is skewed towards increased female offspring, and (b) to identify potential factors influencing firstborn OSR, particularly those relating to the peri-conceptional practice of inhalational anesthesia induction among anesthesia providers.', 'After institutional review board approval, a questionnaire was uploaded on SurveyMonkey and sent to anesthesia providers through their program coordinators in United States (US) to complete the survey.', "The current US national total-population sex ratio is 0.97 male (s)/female with an at-birth sex ratio of 1.05 male (s)/female; comparatively, the results from anesthesia providers' survey respondents (n = 314) were a total OSR of 0.93 male (s)/female (P = 0.61) with firstborn OSR 0.82 male (s)/female (a 6% increase in female offspring; P = 0.03), respectively. The only significant peri-conceptional factor related to anesthesia providers' firstborn OSR's skew was inhalational induction practice by anesthesia care provider favoring female offspring (P < 0.01)."] |
['The high frequency of thrombocytopenia in post-cardiac surgery patients makes it challenging to diagnose heparin-induced thrombocytopenia (HIT). Two platelet count profiles are reported as indicating possible HIT in these patients: profile 1 describes a platelet count fall that begins between postoperative days 5 and 10, whereas profile 2 denotes early-onset thrombocytopenia that persists beyond day 5.', 'To examine how these platelet count profiles correlate with antibody status and HIT post-cardiac surgery.', 'We prospectively screened 581 cardiac surgery patients for heparin-dependent antibodies by platelet factor 4 (PF4)-heparin immunoassay and platelet-activation test, and performed daily platelet counts (until day 10) with 30-day follow-up.', 'All three patients with platelet count profile 1 tested positive for platelet-activating anti-PF4-heparin IgG antibodies [odds ratio (OR) 521.7, 95% confidence interval (CI) 3.9-34,000, P = 0.002], and were judged to have HIT. In contrast, none of 25 patients with early-onset and persisting thrombocytopenia (profile 2) was judged to have HIT, including five patients testing positive for platelet-activating anti-PF4-heparin IgG antibodies. In these patients, the frequency of heparin-dependent antibodies did not differ from that in non-thrombocytopenic controls, either for anti-PF4-heparin IgG (OR 1.7, 95% CI 0.7-4.1, P = 0.31) or for platelet-activating antibodies (OR 1.9, 95% CI 0.6-5.7, P = 0.20). Multivariate analysis revealed that type of cardiac surgery, but not HIT antibody status, predicted early-onset and persisting thrombocytopenia. Together, these findings show that HIT was uncommon in this study population [overall frequency, 3/581 (0.5%), 95% CI 0.1-1.5%].'] |
["The use of chromium-containing dietary supplements is widespread among patients with type 2 diabetes. Chromium's effects in patients at high risk for developing diabetes, especially those with metabolic syndrome, is unknown. The objective of this study was to determine the effects of chromium picolinate (CrPic) on glucose metabolism in patients with metabolic syndrome.", 'A double-blind, placebo-controlled, randomized trial was conducted at a U.S. academic medical center. Sixty three patients with National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)-defined metabolic syndrome were included. The primary end point was a change in the insulin sensitivity index derived from a frequently sampled intravenous glucose tolerance test. Prespecified secondary end points included changes in other measurements of glucose metabolism, oxidative stress, fasting serum lipids, and high sensitivity C-reactive protein.', 'After 16 weeks of CrPic treatment, there was no significant change in insulin sensitivity index between groups (P = 0.14). However, CrPic increased acute insulin response to glucose (P 0.02). CrPic had no significant effect on other measures of glucose metabolism, body weight, serum lipids, or measures of inflammation and oxidative stress.'] |
['Guidelines recommend collecting urine with suprapubic aspiration or urethral catheterisation in infants with a suspected urinary tract infection (UTI), but the invasiveness of these methods continues to drive research on new urine collection devices. We studied children with a suspected UTI, who had not been toilet trained, to compare a new midstream urine collector and catheterisation.', 'During this prospective controlled diagnosis study of 94 children, urine collection was performed using the midstream collector and then controlled via catheterisation when the urine dipstick was positive.', 'When end stream samples collected by the midstream collector were compared to catheter samples, the results were inconsistent in 23.4% of cases, similar to the inconsistent results between first stream samples discarded by the device and the catheter samples (21.3%). Interestingly, the overall rate of sample contamination in the bag of the midstream collector was lower than that reported in previously published studies and there were no false positive bag results.'] |
['While psychosocial factors have been associated with poorer outcomes after knee and hip arthroplasty, we hypothesized that augmented pain perception, as occurs in conditions such as fibromyalgia, may account for decreased responsiveness to primary knee and hip arthroplasty.', 'A prospective, observational cohort study was conducted. Preoperative phenotyping was conducted using validated questionnaires to assess pain, function, depression, anxiety, and catastrophizing. Participants also completed the 2011 fibromyalgia survey questionnaire, which addresses the widespread body pain and comorbid symptoms associated with characteristics of fibromyalgia.', 'Of the 665 participants, 464 were retained 6 months after surgery. Since individuals who met criteria for being classified as having fibromyalgia were expected to respond less favorably, all primary analyses excluded these individuals (6% of the cohort). In the multivariate linear regression model predicting change in knee/hip pain (primary outcome), a higher fibromyalgia survey score was independently predictive of less improvement in pain (estimate -0.25, SE 0.044; P\u2009<\u20090.00001). Lower baseline joint pain scores and knee (versus hip) arthroplasty were also predictive of less improvement (R(2)\u2009=\u20090.58). The same covariates were predictive in the multivariate logistic regression model for change in knee/hip pain, with a 17.8% increase in the odds of failure to meet the threshold of 50% improvement for every 1-point increase in fibromyalgia survey score (P\u2009=\u20090.00032). The fibromyalgia survey score was also independently predictive of change in overall pain and patient global impression of change.'] |
['We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers.', 'Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers.'] |
['Atopic dermatitis is an inflammatory skin disease that is characterized by a reduced skin barrier function, reduced filaggrin (FLG) expression as well as increased colonization by Staphylococcus aureus.', 'This study focused on the possible involvement of FLG in epidermal colonization by S. aureus and/or whether it affects the epidermal defence mechanisms, including the expression of antimicrobial peptides (AMPs) and enzymes involved in stratum corneum barrier lipid synthesis. Furthermore, IL-31 has been shown to reduce FLG expression, but its effects on bacterial colonization and on the expression of AMPs and enzymes involved in the barrier lipid synthesis are not known.', 'We established N/TERT-based epidermal models (NEMs), after FLG knockdown (FLG-KD) and/or cultured with IL-31, that were colonized with S. aureus for 24 h.', 'Both FLG-KD and IL-31 supplementation resulted in significantly increased epidermal S. aureus colonization, as well as in an up-regulation of S. aureus-induced IL-8 expression. IL-31, but not FLG-KD, prevented S. aureus-induced up-regulation of mRNA expression for the AMPs human β-defensin 2 and -3 and RNAse7, whereas psoriasin expression remained unchanged. Furthermore, the S. aureus colonization induced changes in mRNA expression of ELOVL4 was not affected by FLG-KD, but was blocked by IL-31. Expression of SCD-1 and Gcase mRNA was reduced by IL-31, but not by FLG-KD.'] |
['To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC).', 'HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR.', 'EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P = 0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95% CI = 1.34-8.14, respectively].'] |
['Genome-wide dense markers have been used to detect genes and estimate relative genetic values. Among many methods, Bayesian techniques have been widely used and shown to be powerful in genome-wide breeding value estimation and association studies. However, computation is known to be intensive under the Bayesian framework, and specifying a prior distribution for each parameter is always required for Bayesian computation. We propose the use of hierarchical likelihood to solve such problems.', 'Using double hierarchical generalized linear models, we analyzed the simulated dataset provided by the QTLMAS 2010 workshop. Marker-specific variances estimated by double hierarchical generalized linear models identified the QTL with large effects for both the quantitative and binary traits. The QTL positions were detected with very high accuracy. For young individuals without phenotypic records, the true and estimated breeding values had Pearson correlation of 0.60 for the quantitative trait and 0.72 for the binary trait, where the quantitative trait had a more complicated genetic architecture involving imprinting and epistatic QTL.'] |
['Colorectal cancer (CRC) incidence and mortality are highest among African Americans. African Americans lag behind whites in CRC screening rates. Research has examined the role of CRC screening knowledge and beliefs and their relationship to CRC screening adherence. However, studies have not examined the effect cultural identity, social support, CRC beliefs, an informed decision, and having a chronic disease has on CRC screening among African Americans.', 'This study examined CRC screening adherence among African Americans within the context of sociocultural variables, an informed decision, and health factors.', 'A secondary data analysis was performed on survey data collected from 129 African American men and women.', 'Social support and family influence were related to having a colonoscopy. Having diabetes was negatively related to having a colonoscopy. There was no relationship between having a primary care provider and making an informed decision about CRC screening. Religiosity and having a primary care provider predicted colonoscopy.'] |
['To evaluate the possible existence of a genetically determined innate factor that could exert a profound influence on the development of analgesic overuse in chronic tension-type headache (CTTH).', 'Many patients with CTTHs report the regular use of analgesics. Continuous use of analgesics results in the ultimate worsening of headaches. The factors related to development of analgesic overuse, however, remain poorly understood. The genetic factors for serotonin metabolism and the harm avoidance (HA) personality dimension are known to be associated with various substance abuse patterns.', 'We performed serotonin transporter protein (5-HTT) gene-linked polymorphic region (5-HTTLPR) genotype polymorphism analyses, and investigated serotonin-related personality traits by assessing the HA dimension using tridimensional personality questionnaire, given to 48 patients with CTTHs and reported analgesic overuse (CTTH-AO), in 50 patients with CTTHs without analgesic overuse (CTTH-NO), and in 100 healthy controls. We compared their headache characteristics using standardized questionnaires.', 'We discovered an excess frequency of 5-HTTLPR short allele and a different genotypic distribution in patients with CTTH-AO. The S/S genotype frequency was significantly higher in patients with CTTH-AO (83%) than in CTTH-NO (72%) and control (59%; P= .010) groups. Patients with CTTH-AO exhibited the highest HA scores (23.3 +/- 5.4), as compared to CTTH-NO (19.9 +/- 6.7) and control (16.3 +/- 6.1) groups. Individuals with the S/S genotype showed a greater tendency toward analgesic overuse (13.3 +/- 11.3 days per month) than did those with the non-S/S genotype (7.0 +/- 8.6 days per month: P= .02).'] |
['Genetic variation in the serotonin-2C receptor encoded by the HTR2C gene is one of the genetic determinants of antipsychotic-induced weight gain. Peroxisome proliferator-activated receptors are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. In this cross-sectional study, we investigated whether HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T genotypes were associated with metabolic syndrome (MetS) in patients with schizophrenia taking clozapine.', 'One hundred forty-six Korean patients using clozapine for more than one year were genotyped for the HTR2C-759C/T, HTR2C-697G/C, PPARα V227A, and PPARγ 161C/T polymorphisms, and their weight, waist circumference, blood pressure, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, and glucose were measured. We used the criteria for MetS proposed by the National Cholesterol Education Program-adapted Adult Treatment Panel III.', 'The prevalence of MetS was 47.3% and was similar among men (49%) and women (42.9%). We found no significant differences between patients with and without MetS in terms of genotypes or allele frequencies. Logistic regression analyses also revealed no association between MetS and each genotype.'] |
['Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients.', 'To determine how frequently transfusion after trauma is associated with microchimerism.', 'We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range.', 'Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR.'] |
['We hypothesized that without the analgesic effects of volatile anesthetics, caudal 0.20% ropivacaine would be less effective during surgical stimulation than 0.20% bupivacaine or 0.20% levobupivacaine. This trial was designed to examine whether the combination of a caudal block with 0.20% ropivacaine and i.v. anesthesia resulted in reduced analgesic efficacy during surgery compared with caudal 0.20% levobupivacaine or 0.20% bupivacaine in children.', 'Ninety ASA I-II children between 1 and 7 years old, scheduled for inguinal hernia repair or orchidopexy under propofol anesthesia were randomized to receive a caudal block with 1 ml x kg(-1) of 0.2% bupivacaine, 0.2% ropivacaine or 0.2% levobupivacaine. The primary outcome measure of the study was the clinical efficacy of the caudal block during surgery. Secondary outcome measures were postoperative pain relief and residual motor blockade.', 'Four children were excluded and 86 were analyzed. The proportion of children with effective caudal block during surgery was significantly higher in children receiving levobupivacaine (26/28) or bupivacaine (27/29) compared with patients receiving ropivacaine (21/29) (P = 0.03). There were no significant differences among groups in the analgesic onset time (P = 0.1), incidence of residual motor blockade (P = 0.4), number of patients requiring analgesia after operation or in the time from caudal injection to the first administration of analgesic medication (P = 0.3).'] |
["Analgesic effects of oxytocin and it's the other physiological effects were well-known. The aim of present study was determination of nitric oxide role on analgesic effects of oxytocin in mice.", '216 male Albino mice were divided randomly into two experimental groups, tail flick and formalin test. Each experimental group consists of three main groups including: saline, L-arginine (50 mg/kg) and L-NAME (10 mg/kg) intraperitoneal (IP) injection. 15 min after injection in each of the following groups, the animals in each groups divided to the three subgroups including: saline (n=12), oxytocin (1 mg/kg) (n=12) and oxytocin (1 mg/kg) + atosiban (1 mg/kg) (n=12) was injected IP and then after 30 min of use the formalin test and tail flick were to evaluate the response to pain.', 'Area under the curve (AUC) in the late phase of the formalin test, in sub-groups oxytocin + saline and L-NAME were significantly decreased compared with saline + saline group (P<0.05 to P< 0.001), and AUC in L-arginine + saline and atosiban + saline + oxytocin were significantly increased compared with oxytocin + saline group (P<0.05). Tail flick tests as well as a significant reduction in the AUC in oxytocin + L-arginine and atosiban + saline + oxytocin groups were compared with Oxytocin + Saline group (P<0.001).'] |
['To analyze the correlation between dose-volume parameters of the corpora cavernosa and erectile dysfunction (ED) after external beam radiotherapy (EBRT) for prostate cancer.', 'Between June 1997 and February 2003, a randomized dose-escalation trial comparing 68 Gy and 78 Gy was conducted. Patients at our institute were asked to participate in an additional part of the trial evaluating sexual function. After exclusion of patients with less than 2 years of follow-up, ED at baseline, or treatment with hormonal therapy, 96 patients were eligible. The proximal corpora cavernosa (crura), the superiormost 1-cm segment of the crura, and the penile bulb were contoured on the planning computed tomography scan and dose-volume parameters were calculated.', 'Two years after EBRT, 35 of the 96 patients had developed ED. No statistically significant correlations between ED 2 years after EBRT and dose-volume parameters of the crura, the superiormost 1-cm segment of the crura, or the penile bulb were found. The few patients using potency aids typically indicated to have ED.'] |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.