Disparity in cost of oral hypoglycemic agents available in Indian market

Background: Diabetes is one of the most common non-communicable disease worldwide, of which India has been crowned with the title of “diabetes capital of the world”. On an average a person spends 20% of his or her income for the treatment of diabetes per year. So, it’s become very important to conduct a complete cost disparity study among oral hypoglycemic agent available in the market. Information generated from the current analysis, will be helpful to doctors in choosing the right drug for their patient and for the health sector in successfully utilizing the available resources.Methods: The study was conducted in the department of pharmacology AIIMS, Patna 2019. Price of the drugs per tablet/capsule/vial were reviewed from “Current Index of Medical Specialties” January-April 2019 and “Drug Today” October-December, 2018 for analysis of different formulations of oral hypoglycemic agents.Results: The cost of total 16 drugs belonging to 6 different classes, available in 38 different formulations were analyzed. Total 44 different pharmaceutical companies were involved in the manufacture of oral hypoglycemic agents. Overall glibenclamide (5 mg) and bromocriptine (2.5 mg) showed maximum % price variation of 422.79 and 586.27 respectively. Dapagliflozin and canagliflozin both belonging to sodium glucose cotransporter-2 inhibitors shows minimum price variation of 9.86 and 0.9 respectively.Conclusions: The current study shows that there is a huge price variation among oral hypoglycemic agents manufactured by different companies and government needs to take essential steps to bring about the uniformity in the price

Making forecasting self-learning and adaptive -- Pilot forecasting rack

Retail sales and price projections are typically based on time series forecasting. For some product categories, the accuracy of demand forecasts achieved is low, negatively impacting inventory, transport, and replenishment planning. This paper presents our findings based on a proactive pilot exercise to explore ways to help retailers to improve forecast accuracy for such product categories. We evaluated opportunities for algorithmic interventions to improve forecast accuracy based on a sample product category, Knitwear. The Knitwear product category has a current demand forecast accuracy from non-AI models in the range of 60%. We explored how to improve the forecast accuracy using a rack approach. To generate forecasts, our decision model dynamically selects the best algorithm from an algorithm rack based on performance for a given state and context. Outcomes from our AI/ML forecasting model built using advanced feature engineering show an increase in the accuracy of demand forecast for Knitwear product category by 20%, taking the overall accuracy to 80%. Because our rack comprises algorithms that cater to a range of customer data sets, the forecasting model can be easily tailored for specific customer contexts

A questionnaire based comparative study on dry lab versus wet lab among second year medical undergraduates in a tertiary care hospital of Bihar

Background: Objective of the study was to identify whether there is any benefit of integrating dry lab/computer assisted lab (CAL) tool with conventional teaching/wet lab in experimental part of pharmacology.Methods: A questionnaire based study was conducted among 158 second year medical undergraduates in the department of pharmacology. The questionnaire was distributed among students with proper prior instructions in practical class. Students willing to participate in the study were included.Results: Total 94.9% were in the favour of replacing conventional teaching with CAL lab learning, 74.7% felt conventional lab to be more complex, 92.4% has the opinion of CAL lab result has less error along with that majority student felt it to be less time consuming, need lesser assistance and enhance learning. 67% student also felt real experimentation can’t be learned by CAL tool and 83.5% have their thought that CAL lab can never help them in exercising real experiment.Conclusions: Although there is no substitution of conventional teaching methods, in this new era of information and technology CAL lab can be the saviour to students in making better understanding and enhancing the performance without help of experimental animals

TNFα-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury

TNFα-stimulated gene-6 (TSG6), a 30-kDa protein generated by activated macrophages, modulates inflammation; however, its mechanism of action and role in the activation of macrophages are not fully understood. Here we observed markedly augmented LPS-induced inflammatory lung injury and mortality in TSG6−/− mice compared with WT (TSG6+/+) mice. Treatment of mice with intratracheal instillation of TSG6 prevented LPS-induced lung injury and neutrophil sequestration, and increased survival in mice. We found that TSG6 inhibited the association of TLR4withMyD88, thereby suppressing NF-κB activation. TSG6 also prevented the expression of proinflammatory proteins (iNOS, IL-6, TNFα, IL-1β, and CXCL1) while increasing the expression of antiinflammatory proteins (CD206, Chi3l3, IL-4, and IL-10) in macrophages. This shift was associated with suppressed activation of proinflammatory transcription factors STAT1 and STAT3. In addition, we observed that LPS itself up-regulated the expression of TSG6 in TSG6+/+ mice, suggesting an autocrine role for TSG6 in transitioning macrophages. Thus, TSG6 functions by converting macrophages from a proinflammatory to an anti-inflammatory phenotype secondary to suppression of TLR4/NF-κB signaling and STAT1 and STAT3 activation

Regulation of Endothelial Barrier Integrity via Store-Operated Ca2+ entry

The edema genic factor thrombin increases the vascular permeability via disassembly of endothelial adherens junctions (AJs). VE-PTP stabilizes endothelial AJs through dephosphorylation of VE-cadherin. In the first part of my thesis, I investigated the role of STIM1 activation of store-operated Ca2+ entry (SOCE) in regulating adherens junction assembly. I observed that SOCE activated Pyk2 in human lung microvascular endothelial cells (ECs) and induced tyrosine phosphorylation of VE-PTP at Y1981. VE-PTP phosphorylation promoted Src binding to VE-PTP, Src activation, and subsequent VE-cadherin phosphorylation, and thereby increased the endothelial permeability. The increase in permeability was secondary to disassembly of AJs. In second part of my thesis, I focused on the intrinsic signaling mechanisms that mediate the reassembly of endothelial AJs. I showed that TAK1 activation downstream of SOCE signals the reassembly of endothelial AJs. I observed that STIM1 deficiency in ECs prevented thrombin-induced TAK1 phosphorylation (i.e., activation), indicating that SOCE is essential for thrombin-induced TAK1 activation. TAK1 inhibition, resulted in sustained permeability increase both in vitro and in intact lung microvessels in response to thrombin receptor protease-activated receptor 1 (PAR-1) activation. I also observed that thrombin-induced SOCE was augmented in TAK1 deficient ECs. Since EC-restricted TAK1 knockout mice are embryonically lethal, to study the in vivo role of EC-expressed TAK1, I generated tamoxifen-inducible EC-restricted TAK1 knockout (TAK1iΔEC) mice. Surprisingly, I observed that reduced expression of VE-cadherin and its associated β-catenin in lungs of TAK1iΔEC mice compared with their wild type littermates. In addition, the basal and PAR-1-mediated lung vascular permeability was augmented in TAK1iΔEC mice. Since, Glycogen-Synthase Kinase-3β (GSK-3β) regulates β-catenin expression by phosphorylation, I hypothesized that TAK1 activation promotes inactivation of GSK-3β to stabilize β-catenin. Therefore, I generated inducible EC-restricted GSK-3β knockout (GSK-3β iΔEC) mice and found that augmented β-catenin expression and inhibition of PAR-1-induced lung vascular permeability in GSK-3βiΔEC. These findings support the notion that TAK1 signaling in endothelial cells is required to maintain lung vascular barrier integrity. Thus, targeting the Pyk2 and TAK1 activation pathways may be potentially important strategies to combat vascular leak associated pulmonary edema in sepsis

Effective use of Cutting Parameters in Turning Process to Enhance Tool life

Machining is the process of removing the excess material from the work piece or unwanted material from the work piece using a cutting tool. The surface finish and tool life obtain in machining process depends upon the various factors like work material, tool material , tool geometry, machine conditions, coolant and feed rate , speed , depth of cut etc. The focus of present study deals with finding optimal controlled process parameters to obtain good surface finish as well as here predicted tool life. It also shows the effect of the process parameters; cutting speed, feed rate and depth of cut on tool life. Experiments design and conducted based on Taguchi method and corresponding surface roughness were noted. The most affecting factor on tool life are cutting speed and feed observed after the experimentation. Here it is also concluded that tool life decreases with increases of cutting speed and feed in machining process for CNMG tool and grey cast iron work material combination

Design and analysis of a gap coupled split circular patch with elliptical slot filled with elliptical patch

107-113The paper presents radiation performance of a gap coupled split circular patch with elliptical slot filled with elliptical patch. Initially, a circular elliptical ring slot antenna is taken and it is modified step by step to achieve an end product with desired performance. The performance of designed antenna after each step is presented systematically. The simulated and measured results of proposed antenna are compared with that of a circular elliptical ring slot antenna. The gap between two gap-coupled semi circular elliptical ring structures and the length of major and minor axis of inserted inner elliptical patch are optimized to achieve best performance. It is observed that with proposed modifications in circular patch geometry, impedance bandwidth, gain and radiation efficiency of antenna are improved considerably. The resonance frequency of end product is lower than that of a circular elliptical ring slot antenna which indicates that for achieving identical resonance frequencies from circular elliptical ring slot antenna and modified circular patch geometry, effective patch size of modified antenna must be reduced. The outcome results into a further compact circular patch antenna with much improved performance

Appraisal of Inter-rater Agreement among Assessment Scales and Retrospective Analysis of Validated Reports of Cutaneous Adverse Drug Reactions at Tertiary Care Hospital in Eastern India

Introduction: Cutaneous Adverse Drug Reactions (CADRs) share significantly to Adverse Drug Reactions (ADRs) comprising 10%-30% of all ADR reporting in India. Multi Drug Therapy for Leprosy (MDT-L) and antimicrobials contribute remarkably to the overall CADRs burden. Aim: To show distinctive pictures of CADRs profile and to assess inter-rater agreement of assessment scales among study populations. Materials and Methods: A retrospective analysis was done for 245 CADRs reported from March 2018 to March 2020. Cohen kappa statistics was applied for inter-rater agreement study for causality (World Health Organisation-Uppsala Monitoring Cente {WHO-UMC} Scale and Naranjo’s Algorithm), severity (Hartwig and Siegel scale) and preventability assessment (Modified Schumock and Thornton scale). Results: CADRs contribute 45.54% of total ADRs reported during study period. Male (60.41%) and age group 21-40 years (22.45%) were predominant sex and age group, respectively. Multidrug therapy for leprosy (51.83%) was the most common offending agent and hyperpigmentation (20.82%), dryness (13.1%), and both (11%) were the most prevalent CADRs. Causality of WHO– UMC Scale was higher with ‘Possible’ than ‘Probable’. Whereas, ‘Probable’ was maximally found with Naranjo’s Algorithm. Severity assessment showed maximum ‘mild’ cases i.e., 66.53% (manual) and 69.8%% (app). Preventability assessment depicted mostly ‘Definite’, 66.53% (manual) and 85.71% (app). Inter-rater agreement study showed ‘Substantial agreement’ for WHO-UMC Scale (K=0.678) and Naranjo’s algorithm (K=0.820), when manual vs app ratings were compared. ‘Almost perfect’ for severity assessment (K=0.893) and ‘Moderate’ for preventability assessment (K=0.434) were noticed. ‘Fair’ agreement was observed when manual (WHO-UMC scale) vs manual (Naranjo’s algorithm) were compared with K=0.290 and also, in app (WHOUMC scale) vs app (Naranjo’s algorithm) with K=0.319. Conclusion: CADRs were most prevalent among ADRs which have a distinctive picture in eastern India. WHO- UMC scale and Naranjo’s algorithm concluded significant differences in causality with only ‘fair’ agreement between them. Severity and preventability assessment done by manually little varied in their results with pharmvigill app and is still more reliable and popular