Rational Design of Protein-Specific Folding Modifiers.

Protein-folding can go wrong in vivo and in vitro, with significant consequences for the living organism and the pharmaceutical industry, respectively. Here we propose a design principle for small-peptide-based protein-specific folding modifiers. The principle is based on constructing a "xenonucleus", which is a prefolded peptide that mimics the folding nucleus of a protein. Using stopped-flow kinetics, NMR spectroscopy, Förster resonance energy transfer, single-molecule force measurements, and molecular dynamics simulations, we demonstrate that a xenonucleus can make the refolding of ubiquitin faster by 33 ± 5%, while variants of the same peptide have little or no effect. Our approach provides a novel method for constructing specific, genetically encodable folding catalysts for suitable proteins that have a well-defined contiguous folding nucleus.

Increasing Full Child Immunization Rates by Government Using an Innovative Computerized Immunization Due List in Rural India.

Increasing child vaccination coverage to 85% or more in rural India from the current level of 50% holds great promise for reducing infant and child mortality and improving health of children. We have tested a novel strategy called Rural Effective Affordable Comprehensive Health Care (REACH) in a rural population of more than 300 000 in Rajasthan and succeeded in achieving full immunization coverage of 88.7% among children aged 12 to 23 months in a short span of less than 2 years. The REACH strategy was first developed and successfully implemented in a demonstration project by SHARE INDIA in Medchal region of Andhra Pradesh, and was then replicated in Rajgarh block of Rajasthan in cooperation with Bhoruka Charitable Trust (private partners of Integrated Child Development Services and National Rural Health Mission health workers in Rajgarh). The success of the REACH strategy in both Andhra Pradesh and Rajasthan suggests that it could be successfully adopted as a model to enhance vaccination coverage dramatically in other areas of rural India.

Causality assessment: A brief insight into practices in pharmaceutical industry.

Healthcare industry is flooded with multitude of drugs, and the list is increasing day by day. Consumption of medications has enormously increased due to life style changes, having safer drugs is the need of the hour. Regulators and other authorities to have a check have put in stringent regulations and pharmacovigilance system in place. Eventhough there has been increase in adverse drug reactions (ADR) reporting in the last decade, causality assessment has been the greater challenge for academicians and even industry. Causality is crucial for risk benefit assessment, particularly when it involves post marketing safety signals. Pharmaceutical companies have put in efforts to have a standardized approach for causality assessment. This article will provide some insight into the approaches for causality assessment from a pharma industry perspective.

Study on relationship of total bilirubin with acute coronary syndrome (ACS) and associated risk factors

Background: Cardiovascular risk factors for ACS are on the rise in people of Indian origin and ACS is now the leading cause of death. More recent evidence suggests that bilirubin is a potent physiological antioxidant that may provide important protection against atherosclerosis and inflammation. Substantial evidence has documented that the development of CAD involves lipid oxidation and formation of oxygen radicals as atherosclerosis and inflammation are associated with formation of oxygen and peroxyl radicals. Keep of these points in mind, the present study was undertaken to find relation between Serum Bilirubin and Acute Coronary Syndrome.Methods: The present descriptive cross-sectional study conducted at A.J Institute of Medical Sciences and Research Centre, Mangaluru from October 2016 to April 2017. A detailed history, general physical examination, systemic examination and investigations was performed on all patients who fulfill the inclusion criterion and age >18yrs, both sexes who are admitted in CCU.Results: Hypertension had statistically significant correlation with ACS. All risk factors were more associated with STEMI compared to unstable angina or NSTEMI. On Correlation of LDL and Total leucocyte count with bilirubin both were statistically significant when compared to bilirubin levels.Conclusions: The study showed an inverse correlation of bilirubin with ACS, which in shows fact that bilirubin acts as an antioxidant and has cardioprotective action and patients with ACS have lower levels of bilirubin. This can use as a factor for screening individuals who have high risk for ACS and preventive strategies applied in them before the onset of overt ACS.

Assessment of prevalence of sexually transmissible infections among voluntary blood donors and its comparison with replacement donors at Hassan Institute of Medical Science, Hassan, Karnataka, India

Background: Hepatitis B virus, Hepatitis C virus and Human immunodeficiency virus (HIV) are important STDs which can be transmissible to the recipients of blood transfusion. The aim of the present study is to study the seroprevalence of HIV, HBV and HCV infection in the blood among voluntary and replacement donors in HIMS Hassan during 2010 to 2012.Methods: A retrospective study was conducted at blood bank of HIMS, Hassan for the years 2010 to 2012. The donors with Hemoglobin>12gm% for both sexes, weight >50 kg, no history of chronic illness, hepatitis, high risk behaviours were included in the study. All the blood samples collected were screened for HIV, HBV and HCV using ELISA kits. All the blood samples were sent to NACO (national AIDS control organization) and subjected to NAT (nucleic acid test) for detection of antigens. Results compared for both voluntary and replacement donors.Results: Total of 10938 blood donors screened. Majority of the donors were males 95.8% (10484) and belonged to voluntary group 72.8% (7971). The total prevalence of STDS were 0.61% (67). The prevalence of HBV, HCV and HIV was 0.47% (51), 0.04% (4) and 0.11% (12) respectively. Prevalence of STDs was higher among voluntary donors 0.57% (62) compared to replacement donors 0.05 % (5). Statistically significant difference was observed in HBV prevalence in voluntary and replacement donors.Conclusions: Most common STDs in blood donors was HBV followed by HIV and HCV. STDs were mainly seen in voluntary donors compared to replacement donors. Majority of the donors were males.

"MacCallum plaque of the heart": a medicolegal case

Mural endocardial lesions can be seen as MacCallum plaques in rheumatic heart disease. These plaques appear as map-like areas of thickened, roughened, and wrinkled part of the endocardium in the left atrium. Perhaps they are caused by regurgitant jets of blood flow, due to incompetence of the mitral valve. Although MacCallum plaques are one of the characteristic features in rheumatic heart disease, they are very uncommon in recent times. We hereby report a case of an adolescent female with RHD, who was working as a housemaid in a doctor's house for a few months, and suddenly developed respiratory tract infection and cardiac failure. She died on the fourth day of admission. A medicolegal autopsy was conducted, as her relatives accused her master of sexual assault. On autopsy it was seen that the mitral valves were narrowed, showing multiple vegetations. MacCallum plaque was seen in the dilated left atrium. Hence, it is presented here for educative purposes