Non-alcoholic steatohepatitis (NASH) is the leading cause of cirrhosis worldwide and the most rapidly growing indication for liver transplantation. Macrophages are the important cellular component in the inflammatory milieu in NASH. Inflammatory and pro-fibrotic mediators produced by macrophages causes significant tissue injury in many inflammatory diseases. Therefore, inhibition of the inflammatory macrophages would be a promising approach to attenuate NASH. In this study, we studied the implication of SYK pathway in NASH, and investigated PLGA nanoparticles-based delivery of SYK pathway inhibitor as an effective and promising therapeutic approach for the treatment of NASH. We found positive correlation between SYK expression with the pathogenesis of NASH and alcoholic hepatitis in patients. Importantly, SYK expression was significantly induced in M1-differentiated inflammatory macrophages. To inhibit SYK pathway specifically, we used a small-molecule inhibitor R406 that blocks Fc-receptor signaling pathway and reduces immune complex-mediated inflammation. R406 dose-dependently inhibited nitric-oxide release and M1-specific markers in M1-differentiated macrophages. Thereafter, we synthesized PLGA nanoparticles to deliver R406 to increase the drug pharmacokinetics for the efficient treatment of NASH. We investigated the therapeutic efficacy of R406-PLGA in-vitro in differentiated macrophages, and in-vivo in Methionine-Choline-deficient (MCD)-diet induced NASH mouse model. R406-PLGA inhibited M1-specific differentiation markers in RAW and bone-marrow-derived macrophages. In-vivo, R406 and more strongly R406-PLGA ameliorated fibrosis, inflammation and steatosis in mice. R406 and more significantly R406-PLGA reduced ALT, AST, cholesterol and triglyceride plasma levels. These results suggest that delivery of SYK inhibitor using PLGA nanoparticles can be a potential therapeutic approach for the treatment of Non-alcoholic steatohepatitis.

Aim:This systematic literature review was conducted to identify, evaluate, and characterize the variety, quality, and intent of the health economics and outcomes research studies being conducted in India.Materials and Methods:Studies published in English language between 1999 and 2012 were retrieved from Embase and PubMed databases using relevant search strategies. Two researchers independently reviewed the studies as per Cochrane methodology; information on the type of research and the outcomes were extracted. Quality of reporting was assessed for model-based health economic studies using a published 100-point Quality of Health Economic Studies (QHES) instrument.Results:Of 546 studies screened, 132 were included in the review. The broad study categories were cost-effectiveness analyses [(CEA) 54 studies], cost analyses (19 studies), and burden of illness [(BOI) 18 studies]. The outcomes evaluated were direct and indirect costs, and incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and disability-adjusted life years (DALYs). Direct medical costs assessed cost of medicines, monitoring costs, consultation and hospital charges, along with direct non-medical costs (travel and food for patients and care givers). Loss of productivity and loss of income of patients and care givers were identified as the components of indirect cost. Overall, 33 studies assessed the quality of life (QoL), and the WHO Quality of Life-BREF (WHOQOL-BREF) was the most commonly used instrument. Quality assessment for modeling studies showed that most studies were of high quality [mean (range) QHES score to be 75.5 (34-93)].Conclusions:This review identified various patterns of pharmacoeconomic studies and good-quality CEA studies. However, there is a need for better assessment of utilization of healthcare resources in India.

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Background Biocontrol is an effective strategy in the integrated management of plant diseases, now more as a necessity than choice, in the present era of environmental and health awareness. Microbial diversity is a wonder by nature that inspires to explore and accordingly, the diversity analysis of the isolated microbes revealed their morphological and molecular differences. The DNA provides a common platform to store the microbial information in the form of databases in public domain that can be used by anyone from anywhere. Results Exploration for native microbes in the present study resulted in isolation of different isolates of Trichoderma and Bacillus. The microbes were identified using morphological traits and molecular markers and the key conserved 18S and 16S gene sequences submitted with the appropriate repositories. Nucleotide analysis indicated a close phylogenetic relationship between BIK 2 and BIK 3 (Bacillus isolates) and within all the 5 Trichoderma isolates. The percent disease reduction of Rhizoctonia solani and Xanthomonas oryzae pv. oryzae (Xoo) was more in plants treated with consortia of the Trichoderma (61.13%) and Bacillus (53.59%) isolates, respectively. Screening of plant growth promotion activities, percentage increase in root (41.00%) and shoot length (44.77%) were found to be maximum in Trichoderma consortia treated plants. Conclusions Three Bacillus and one Trichoderma strains, viz., B. velezensis, B. subtilis and B. paralicheniformis and Trichoderma asperellum, were identified and found to be effective against R. solani and Xoo pathogens of rice. In vitro and in vivo studies indicated that TAIK1 and BIK3 were found to be the most potential isolates among others isolated. Ability to improve plant growth was more pronounced by consortia of microbes.

Oncology is a highly researched therapeutic area with an ever expanding armamentarium of drugs entering the market. It is unique in how the heterogeneity of tumor, patient and treatment factors is critical in determining outcomes of interventions. When it comes to decision making in the clinic, the practicing physician often seeks answers in populations with obvious deviations from the ideal selected populations included in the pivotal phase III randomized controlled trials (RCTs). While the randomized nature of the RCT ensures its high internal validity by removing bias, their ‘controlled’ nature casts a doubt on their generalizability to the real world population. It is for this reason that trials done in a naturalistic setting post the marketing authorization of a drug are increasingly required. This article discusses the importance of non interventional drug studies in oncology as an important tool in testing the external validity of controlled trial results and its value in generation of new hypothesis. It also discusses the limitations of such studies while outlining the steps in their effective conduct.