Immunopathogenesis of hepatitis C virus infection

The interplay of viral characteristics and the host’s immunologic defense is responsible for the viral persistence and pathogenesis seen in chronic hepatitis C infection. The polyclonal and multispecific CD4 T-helper response seen in patients with chronic hepatitis C lacks the vigor and epitope specificity, compared with acutely infected patients. Although a dominant explanation for the weak antiviral response still eludes us, some potential explanations have been immunologic tolerance, not so favorable type 2 cytokine profile, and rapid replication rate. The emergence of cytotoxic T-lymphocyte escape variants, the consequence or the explanation for the high viral mutation rates, in addition to virally induced immune suppression, may be yet another explanation. However, the role of immune response in controlling viral replication disease pathogenesis, including autoimmune phenomenon, has been clearly demonstrated. Further research is required to increase our understanding of the various host and viral factors in viral persistence in order to develop successful vaccines.     

Incremental Accuracy of Blood Biomarkers for Predicting Clinical Outcomes After Intracerebral Hemorrhage

BackgroundIntracerebral hemorrhage (ICH) is associated with high mortality, morbidity, and recurrence. Studies have reported the accuracy of several blood biomarkers in predicting clinical outcomes; however, their independent contribution in prediction remains to be established.AimTo investigate the incremental accuracy in predicting clinical outcomes in patients with ICH in a north Indian population using blood-based biomarkers.MethodsIn this study, a total of 250 ICH cases were recruited within 72 hours of onset. Baseline clinical and CT scan measurement were recorded. Homocysteine (HCY), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP9), E-selectin (SELE), and P-selectin (SELP) levels were measured through ELISA. Telephonic follow-up was done by using mRS scale at three months.ResultsThe mean age of cohort was 54.9 (SD±12.8) years with 64.8% patients being male. A total of 109 (43.6%) deaths were observed over three months follow-up. Area under the receiver operating characteristics curve-(AUROC) for 90-day mortality were 0.55 (HCY), 0.62 (CRP), 0.57 (MMP9), 0.60 (SELE) and 0.53 (SELP) and for poor outcome at 90-day (mRS: 3-6) were 0.60 (HCY), 0.62 (CRP), 0.54 (MMP9), 0.67 (SELE) and 0.54 (SELP). In multivariable model including age, ICH volume, IVH and GCS at admission, serum SELE (p=0.004) significant for poor outcome with improved AUROC (0.86) and HCY (p=0.04), CRP (p=0.003) & MMP9 (p=0.02) for mortality with least Akaike's Information Criterion-(AIC) (1060.5).ConclusionsOur findings suggest that the serum SELE is a significant predictor of poor outcome and HCY, CRP & MMP9 for Mortality in patients with ICH in the north Indian population.     

Evaluation of existing and candidate measures of obesity for detection of insulin resistance and cardiometabolic risk among Asian Indians: Development of two clinically useful models

BackgroundThe optimal measure of obesity continues to be debated. The objective of this study was to evaluate existing and candidate measures of obesity for detecting the presence of cardiometabolic risk and insulin resistance among Asian Indians.MethodsAnthropometry, detailed body composition analysis, blood pressure, lipids, fasting blood glucose and fasting serum insulin were measured in a cross-sectional study involving 507 subjects from North India.ResultsIn females, all indices of obesity, except waist-to-hip ratio (WHR) and total body fat (TBF) to waist circumference (WC) ratio and in men, all indices of obesity including fat mass index and WHR, were significantly associated with insulin resistance and cardiovascular risk factors (p < 0.05). Using stepwise logistic regression, two models were developed excluding WC and WHR, respectively. In model 1, subscapular skinfold thickness, WHR and age in males, and waist circumference to square of height ratio (WS²R) and age in females; and in model 2, subscapular skinfold thickness, WS²R and visceral adiposity index in males, and TBF to WC ratio, WS²R and age in females showed strong and significant association with the presence of cardiovascular risk factors or insulin resistance.ConclusionsThe clinical models for measurement of obesity developed by us would help in detecting cardiometabolic risk in Asian Indians.     

Cholecystectomy Concomitant with Laparoscopic Gastric Bypass: A Trend Analysis of the Nationwide Inpatient Sample from 2001 to 2008

Background  

Gallstone formation is common in obese patients, particularly during rapid weight loss. Whether a concomitant cholecystectomy should be performed during laparoscopic gastric bypass surgery is still contentious. We aimed to analyze trends in concomitant cholecystectomy and laparoscopic gastric bypass surgery (2001–2008), to identify factors associated with concomitant cholecystectomy, and to compare short-term outcomes after laparoscopic gastric bypass with and without concomitant cholecystectomy.     

WriteSim TCExam - An open source text simulation environment for training novice researchers in scientific writing

Background  

The ability to write clearly and effectively is of central importance to the scientific enterprise. Encouraged by the success of simulation environments in other biomedical sciences, we developed WriteSim TCExam, an open-source, Web-based, textual simulation environment for teaching effective writing techniques to novice researchers. We shortlisted and modified an existing open source application - TCExam to serve as a textual simulation environment. After testing usability internally in our team, we conducted formal field usability studies with novice researchers. These were followed by formal surveys with researchers fitting the role of administrators and users (novice researchers)     

Rapamycin, an mTOR inhibitor, disrupts triglyceride metabolism in guinea pigs

This study was designed to define some of the mechanisms by which rapamycin (RAPA), an mTOR inhibitor, induces hypertriglyceridemia when used as an immunosuppressive or antiproliferative agent and to determine whether low doses result in less undesirable side effects. Thirty male guinea pigs (n=10 per group) were randomly assigned to control (no RAPA), low-RAPA (0.08 mg/d), or high-RAPA (0.85 mg/d) treatment for 3 weeks. Rapamycin treatment resulted in more than a 2-fold increase in plasma triglycerides (TG) (P<.01), whereas no differences were observed in plasma cholesterol between RAPA and control groups. Low-RAPA treatment resulted in lower concentrations of cholesterol in the aorta (28.6%) and lower hepatic acyl-CoA cholesteryl acyltransferase activity compared to control and high-RAPA groups (P<.01). In addition, acyl-CoA cholesteryl acyltransferase activity was positively correlated with aortic cholesterol (r=0.43, P<.05). In contrast, aortic TG concentrations were higher in RAPA-treated guinea pigs than in control (P<.01). Very low density lipoprotein and low-density lipoprotein particles isolated from guinea pigs treated with RAPA were larger in size and contained more TG molecules than particles from control animals. Interestingly, plasma free fatty acids and fasting plasma glucose were 65% and 72% higher in the high-RAPA group than in control (P<.01). Tumor necrosis factor-alpha concentrations in the aorta were 3.6- and 10.4-fold higher in the low-RAPA and high-RAPA groups than in control guinea pigs (P<.01). These results suggest that RAPA interferes with TG metabolism by altering the insulin signaling pathway, inducing increased secretion of very low density lipoprotein and promoting deposition of TG in the aorta. Low RAPA was found to decrease cholesterol accumulation in tissue (liver and aorta) compared to high RAPA, suggesting that lower doses could be less detrimental to transplant patients.     

Maintenance of the LDL cholesterol:HDL cholesterol ratio in an elderly population given a dietary cholesterol challenge

We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.     

Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study

Results:Median AEC was 0 cells/mm³ in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm³, AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT.Conclusions:This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers.