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Drug repurposing is also termed as drug repositioning or therapeutic switching. This method is applied to identify the novel therapeutic agents from the existing FDA approved clinically used drug molecules. It is considered as an efficient approach to develop drug candidates with new pharmacological activities or therapeutic properties. As the drug discovery is a costly, time-consuming, laborious, and highly risk process, the novel approach of drug repositioning is employed to increases the success rate of drug development. This strategy is more advantageous over traditional drug discovery process in terms of reducing duration of drug development, low-cost, highly efficient and minimum risk of failure. In addition to this, World health organization declared Coronavirus disease (COVID-19) as pandemic globally on February 11, 2020. Currently, there is an urgent need to develop suitable therapeutic agents for the prevention of the outbreak of COVID-19. So, various investigations were carried out to design novel drug molecules by utilizing different approaches of drug repurposing to identify drug substances for treatment of COVID-19, which can act as significant inhibitors against viral proteins. It has been reported that COVID-19 can infect human respiratory system by entering into the alveoli of lung via respiratory tract. So, the infection occurs due to specific interaction or binding of spike protein with angiotensin converting enzyme-2 (ACE-2) receptor. Hence, drug repurposing strategy is utilized to identify suitable drugs by virtual screening of drug libraries. This approach helps to determine the binding interaction of drug candidates with target protein of coronavirus by using computational tools such as molecular similarity and homology modeling etc. For predicting the drug-receptor interactions and binding affinity, molecular docking study and binding free energy calculations are also performed. The methodologies involved in drug repurposing can be categorized into three groups such as drug-oriented, target-oriented and disease or therapy-oriented depending on the information available related to quality and quantity of the physico-chemical, biological, pharmacological, toxicological and pharmacokinetic property of drug molecules. This review focuses on drug repurposing strategy applied for existing drugs including Remdesivir, Favipiravir, Ribavirin, Baraticinib, Tocilizumab, Chloroquine, Hydroxychloroquine, Prulifloxacin, Carfilzomib, Bictegravir, Nelfinavir, Tegobuvir and Glucocorticoids etc to determine their effectiveness toward the treatment of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sahoo, Ravi Kumar, Sruti, Mahapatra, Banik and Borah.)

Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.

Background: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers., Methods: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection., Results: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection., Conclusion: Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic., Competing Interests: The authors have declared that no competing interests exist.

Introduction: COVID-19 is a pandemic affecting mainly respiratory and gastrointestinal system. Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) binds angiotensin converting enzyme 2 (ACE-2) of renin-angiotensin system (RAS) resulting in hypokalaemia. We hereby report the a of hypokalaemic paralysis induced by COVID-19., Case: A 56 years old male with no co-morbidities presented with fever (2days), weakness in bilateral lower limbs (1 day). His had severe hypokalaemia with serum potassium of 2.05 mEq/L. RT-PCR of nasopharyngeal swab for SARS-CoV- 19 was positive. He was diagnosed as a case of hypokalaemic paralysis induced by COVID-19 infection., Conclusion: We suggest that during this pandemic era if a COVID-19 patient presents with paralysis, hypokalaemia induced paralysis should be kept in the differential diagnosis., What Is Known: COVID-19 infection leads to hypokalemia., What Is New: Hypokalaemic paralysis as a manifestation of COVID-19., (© Journal of the Association of Physicians of India 2011.)

Development of coronary artery disease (CAD) is primarily due to the process of atherosclerosis, however the prognosis of CAD depends on pleiotropic effects of the genes located at 9p21.3 region. Genome wide association studies revealed association of variants in this region with CAD pathology. However, specific marker in predicting CAD development or progression is not yet identified. In the present study, 35 SNPs at 9p21.3 region, located in the cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) genes, were genotyped among 350 CAD cases and 480 controls from the southern Indian population of Hyderabad using fluidigm nanofluidic SNP genotyping system and the data were analyzed using PLINK and R softwares. Of the 35 SNPs analysed, only one SNP, rs7865618, was found to be highly significantly associated with CAD, even after correction for multiple testing (p = 0.008). The AG and GG genotypes of this SNP conferred 3.08 and 1.93 folds increased risk for CAD respectively. In particular, this SNP was significantly associated with severe anatomic (triple vessel disease p = 0.023) and phenotypic (acute coronary syndrome p = 0.007) categories of CAD. Pair wise SNP interaction analysis between the SNPs of 9p21.3 and 11q23.3 regions revealed significantly increased risk of three SNPs of 11q23.3 region that were not associated individually, in conjunction with rs7865618 of 9p21.3.

The progressive nature of type 2 diabetes mellitus (T2DM) renders the shifting of patients from oral drugs to insulin therapy an inevitability in most patients especially in those with long duration of diabetes. At the turn of the last millennium, neutral protamine Hagedorn (NPH) insulin was still the only long-acting insulin available for people with diabetes. The advent of the first truly long-acting basal insulin, i.e. insulin glargine 100 U/mL (Gla-100) brought to the table a remarkably long duration of action and a very minimal risk of hypoglycemia by due to less pronounced peaks in their action profile. Further, in trying to achieve fasting normoglycemia, Gla-100 has demonstrated remarkably more holistic glucose-lowering efficacy in several pivotal trials compared to other insulin formulations, such as premixed insulin and coformulations-apart from NPH insulin. This article delineates clinical data on the effectiveness of Gla-100 vs. other insulin formulations in the context of T2DM., (© Journal of the Association of Physicians of India 2011.)

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to "cytokine storm". This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed., Competing Interests: No conflicts of interest., (Copyright © 2020 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Though Convalescent plasma therapy (CPT) is being used for management of COVID-19, the evidence is still equivocal. So, we carried out this study to evaluate the currently available data to provide evidence about CPT in COVD-19 patients. RCTs and observational studies with sample size with more than 5 were included in the analysis. Out of 196 studies, 12 studies were selected for systematic review and meta-analysis was carried out for 6 studies having a control arm. For dichotomous values, risk ratio (RR) and 95% confidence interval was expressed., Main Outcomes: All-cause mortality, clinical improvement by day 7 and viral detection by day 7 were the defined outcome measures before starting of data extraction., Result: For 6 studies (2 RCTs and 4 observational studies) with 474 patients, the overall pooled RR for all-cause mortality was 0.61 (95%CI: 0.37 to 0.99. P= 0.04). Only RCTs and only observational studies for all-cause mortality showed pooled RR of 0.60 (95% CI: 0.33 to 1.10, P=0.10) and 0.48 (95% CI: 0.17 to 1.36, P= 0.17) respectively. There was risk of bias in the studies due to randomization process and confounding. Sensitivity analysis was carried out only for observational studies. The overall pooled RR for clinical improvement by day 7 and viral detection by day 7 were 1.12 (95%CI: 0.96 to 1.31, P=0.16) and 0.19 (95%CI: 0.09 to 0.60, P < 0.0001)., Conclusion and Relevance: Though the review suggests modest utility of CPT in reducing all-cause mortality, improving clinical outcome, and early viral clearance, it should be interpreted cautiously., (© Journal of the Association of Physicians of India 2011.)

Objective: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India., Methods: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included., Results: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets., Conclusion: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India., Competing Interests: Conflict of interest statement: Shunmugavelu Minakshisundaram was a study investigator and received an honorarium during the period in which the study was conducted. Anirban Majumdar is a consultant and/or speaker for Eli Lilly, Novo Nordisk India, Sanofi India Limited, and Wockhardt India Ltd. that market different insulin preparations. MC is a member of the speaker bureau for Sanofi, Eli Lilly, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, USV, IPCA, Biocon, and Cipla. SMJ has been associated with Sanofi, Novo, Eli Lilly, Novartis, Boehringer-Ingelheim, and AstraZeneca for various trials and educational initiatives. AR, Sagarika Mukherjee, Sanjeev Phatak, Shailesh Pitale, NA, ND, SJ, SL, Anuj Maheshwari, BMM, SR, PS, and SKS declared no conflict of interest. RG, Senthilnathan Mohanasundaram, Shalini Menon, DC, VK, CT are employees of Sanofi., (© The Author(s), 2020.)

Key Message: The new NB scope aids in better visualization of the scalp and blood collection and analysis at bed side., Objective: Caesarean section rates and inherent complications are on the rise all over the world. One way to avoid a caesarean is to measure fetal scalp blood lactate levels. The methods available to visualize fetal scalp, obtain the blood sample and perform the blood test are separate, cumbersome and expensive, needing a certain level of expertise. We propose a device that incorporates all the steps of obtaining a fetal scalp blood lactate into one sleek, easy to use device., Methods: The initial design, 3-D print and was tried on mannequin. After ethics committee approval, the prototype was experimented on patients in labour with singleton live fetus in cephalic presentation with no evidence of distress., Results: There were ( n  = 9) patients recruited. There were ( n  = 5) primigravida and ( n  = 4) multigravida all of whom were in active labour. Parity did not seem to influence ease of instrumentation. Of the ( n  = 9) mothers ( n  = 2) had meconium-stained liquor and the rest ( n  = 7) had clear liquor, meconium-stained liquor did not affect visualization. The mean time taken to collect the sample was 184.11(± 33.04) seconds., Conclusion: The Neeraj-Bhaskar (NB) scope is an easy to use, affordable device that can be used time and again to decide on cases where emergency caesarean section can be avoided due to fetal distress., Competing Interests: Conflict of InterestAll the authors do not have any conflict of interest. The manufactures also do not have any conflict of interest. Intellectual Property India No. 201741011937., (© Federation of Obstetric & Gynecological Societies of India 2020.)

Background: As future practitioners, undergraduate medical students have a key role in the antimicrobial stewardship program (ASP). However, at present, there are not much data about their knowledge and perception of antibiotic resistance and ASP., Methods: This was a cross-sectional questionnaire-based survey administered to the prefinal- and final-year undergraduate medical students of a tertiary care institution., Results: One hundred and ninety-seven students participated in our study constituting 70% response rate. The mean difference in knowledge score between prefinal- and final-year students was 0.77 (95% confidence interval: 0.30-1.24, P = 0.0016). Thirty-seven (39.7%) prefinal- and 57 (54.8%) final-year students knew the correct definition of antimicrobial stewardship. Majority of the participants, i.e., 66 (70.9%) prefinal-year and 80 (76.9%) final-year students perceived antibiotic resistance as a public health problem. Principal component analysis revealed the greater role of attitude-related questions., Conclusion: Good knowledge and positive attitude are paramount for the effective implementation of the antibiotic stewardship program. Our study revealed that the knowledge gap exists among the undergraduate students about the rational use of the antibiotic stewardship program. It was also revealed that the role of attitude plays a more significant role than knowledge for the proper understanding of the program. A sustained effort is required to make them aware of the rational use of antibiotics by incorporating the knowledge and practice of the ASP into their study curriculum., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Perspectives in Clinical Research.)

In recent years, hybrid systems are gaining considerable attention owing to their various biological applications in drug development. Generally, hybrid molecules are constructed from different molecular entities to generate a new functional molecule with improved biological activities. There already exist a large number of naturally occurring hybrid molecules based on both non-steroid and steroid frameworks synthesized by nature through mixed biosynthetic pathways such as, a) integration of the different biosynthetic pathways or b) Carbon- Carbon bond formation between different components derived through different biosynthetic pathways. Multicomponent reactions are a great way to generate efficient libraries of hybrid compounds with high diversity. Throughout the scientific history, the most common factors developing technologies are less energy consumption and avoiding the use of hazardous reagents. In this case, microwave energy plays a vital role in chemical transformations since it involves two very essential criteria of synthesis, minimizing energy consumption required for heating and time required for the reaction. This review summarizes the use of microwave energy in the synthesis of steroidal and non-steroidal hybrid molecules and the use of multicomponent reactions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polycyclic aromatic hydrocarbons (PAHs) are aromatic compounds with two or more fused benzene rings in their structural configurations. PAHs do not contain heteroatoms and substituents on the ring system. PAHs containing up to four rings are called light PAHs while those that contain more than four rings are considered as heavy PAHs. Heavy PAHs are more stable and more toxic than the light PAHs. Generally, the increase in the size and angularity of a PAH molecule results in an increase in hydrophobicity and electrochemical stability. Ring linkage patterns in PAHs may occur in such a way that the tertiary carbon atoms are centers of two or three interlinked rings. The examples of PAHs are naphthalene, anthracene, phenanthrene, acenaphthylene, acenaphthene, fluorene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, etc. PAHs can be produced either naturally or anthropogenically and have toxic properties. Due to the health risk posed by their exposure, there is a need to control the release of PAHs through air quality management. Refinery industries are required to monitor and regulate their discharges. There is an urgent need for the considerable efforts to be applied in the field of research to degrade and monitor potentially hazardous substances to control, predict and avoid negative effects of PAHs pollution., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The current management of COVID-19 is mostly limited to general supportive care and symptomatic treatment. Ivermectin is a broad-spectrum anti-parasitic drug used widely for the treatment of onchocerciasis and lymphatic filariasis. Apart from its anti-parasitic effect it also exhibits antiviral activity against a number of viruses both in vitro and in vivo. Hence, we conducted this systematic review and meta-analysis to assess the currently available data on the therapeutic potential of ivermectin for the treatment of COVID-19 as add on therapy. A total of 629 patients were included in the 4 studies and all were COVID-19 RT-PCR positive. Among them, 397 patients received ivermectin along with usual therapy. The random effect model showed the overall pooled OR to be 0.53 (95%CI: 0.29 to0.96) for the primary outcome (all-cause mortality) which was statistically significant (P=0.04). Similarly, the random effect model revealed that adding ivermectin led to significant clinical improvement compared to usual therapy (OR=1.98, 95% CI: 1.11 to 3.53, P=0.02).  However, this should be inferred cautiously as the quality of evidence is very low. Currently, many clinical trials are on-going, and definitive evidence for repurposing this drug for COVID-19 patients will emerge only in the future.

Background: Aza-steroids are an important class of compounds because of their numerous biological activities. The hetero steroids have different hydrogen bonding ability and hydrophobicity in comparison to steroids., Materials and Methods: Microwave-induced synthesis of a novel type of hybrid hetero-steroid amine conjugates, following Ugi-four component reactions of steroidal amines with alanine and valine methyl esters as amino acid residues is described. Specifically, hetero-steroid-amino acid conjugate based on D-ring fused hetero steroidal amine, hetero-steroid-amino acid conjugate based on A-ring hetero steroidal amine, and hetero-steroidamino acid conjugate based on B-ring hetero steroidal amine are synthesized., Results and Discussion: The yield of the products under microwave-induced process was considerably higher than that obtained by the conventional method. In contrast to the conventional method for the synthesis of these molecules, microwave-induced method has several advantages., Conclusion: These include rapid reaction, a superior yield of the product, minimum side reaction, and economical microwave-induced process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We explored genetic susceptibility profile of the South Indian women with a large set of SNPs and tested if the lack of association of type 2 diabetes genes with PCOS, recently observed in a number of studies, holds true for this Indian population and suggest probable universality of this phenomenon. A prioritized set of 92 SNPs that belong to important reproductive and metabolic pathway genes were genotyped on 250 PCOS cases and 299 ethnically matched controls, representing the southern Indian population of Hyderabad, using SEQUENOM MassARRAY iPLEX™ platform. These data were analyzed both for individual SNP association patterns as well as for gene-gene interactions, besides obtaining cumulative risk score and the ROC curve with the help of appropriate statistical packages such as PLINK, SNPAssoc of R-program, Haploview, GMDR and SPSS. The analysis of 72 of the 92 SNPs, after excluding 20 of those that showed either minor allele frequency < 1% and/or deviated from Hardy Weinberg Equilibrium (p < .001), suggested that only 13 were associated with PCOS at p ≤ .05, but none after correction for multiple testing. Further, neither any of the diabetic genes nor the interactions between diabetic and reproductive pathway genes were found to be significant even at p ≤ .05.The lack of association of any of the SNPs with PCOS and/or the gene-gene interactions among them may be because of the minor effects of each of them on the phenotype(OR < 2). Further, that none of the type 2 diabetes genes were associated with PCOS in the present study as well as in the earlier studies from different ethnic groups may indicate probable universality of this pattern. It is possible that there are still other genetic variants, novel as well as already known, which may confer greater risk than the ones considered in this study and further studies are warranted to ascertain this both in the present population as well as in other ethnic and/or geographic groups of the Indian subcontinent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Mercury is a pollutant of global concern. To protect human health and environment from mercury pollution, the Minamata Convention on mercury entered into force in 2017., Objectives: To support a future effectiveness evaluation of the convention, this study assesses worldwide and regional time trends of total mercury levels in human blood and breast milk across different population sub-groups in the last half-century prior to entry-into-force of the Minamata Convention. This study also provides an overview of the epidemiological literature showing evidence of associations between mercury exposure (in terms of total mercury levels in whole blood, cord blood, and breast milk) and human health., Methods: We searched electronic databases to identify articles published prior to June 14, 2017 and reported total mercury levels in any of three biological matrices (whole blood, cord blood, or breast milk) and/or associations with human health. Temporal trends of total mercury levels in the selected biological matrices across different population sub-groups were estimated using a linear fit of the log-transformed data. In parallel, statistical methods were employed to assess any possible effect of sources of inhomogeneity (i.e. study and population characteristics such as age, sex, ethnicity, source of exposure, sampling period, and geographical region) in the collected studies. Furthermore, a summary of significant and relevant associations between mercury exposure and human health conditions in children and adults was prepared., Findings: We found significant declines in total mercury levels in whole blood, cord blood, and breast milk between 1966 and 2015. A regional overview of total mercury levels in whole blood, cord blood, and breast milk suggests the highest levels in South America, followed by Africa or Asia whereas the population groups from Europe or North America displayed the lowest levels of total mercury in the selected biological matrices. We observed conclusive consistent associations of mercury exposure with selected health conditions, especially neurodevelopment and neurotoxicity in children and adults. For several other health conditions, reported findings in the collected studies do not support conclusive associations. We also found that several studies demonstrated significant associations between mercury exposure below the USEPA reference level and various health conditions., Conclusions: This study provides a worldwide and regional overview of trends in total mercury levels in human blood and breast milk and associated health risks prior to entry-into-force of the Minamata Convention and calls for further epidemiological investigations from across the globe to fully understand the health implications of mercury exposure., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Regrettably, before online publication the figure of Scheme 2 has been pasted twice as Scheme 1.

Two fluorescent aptasensor methods were developed for the detection of ATP in biochemical systems. The first method consisted of a label-free fluorescent "turn-on" approach using a guanine-rich ATP aptamer sequence and the DNA-binding agent berberine complex. In the presence of ATP, the ATP preferentially binds with its aptamer and conformationally changes into a G-quadruplex structure. The association of berberine with the G-quadruplex results in the enhancement of the fluorescence signal of the former. The detection limit of ATP was found to be 3.5 μM. Fluorescence, circular dichroism and melting temperature (T m ) experiments were carried out to confirm the binding specificity and structural changes. The second method employs the ratiometric fluorescent approach based on the Forster resonance energy transfer (FRET) for the detection of ATP using berberine along with a quencher (AuNRs, AgNPs) and a fluorophore (red quantum dots (RQDs), carbon dots (CDs)) labeled at 5' and 3' termini of the ATP-binding aptamer sequence. Upon addition of ATP and berberine, ATP specifically binds with its aptamer leading to the formation of G-quadruplex, and similarly, berberine also binds to the G-quadruplex. This leads to an enhancement of fluorescence of berberine while that of RQD and CDs were significantly quenched via FRET. The respective detection limits calculated were 3.6 μM and 3.8 μM, indicating these fluorescent aptasensor methods may be used for a wide variety of small molecules. Graphical abstract.

In this review, we briefly outlined salient features of pathophysiology and results of the genetic association studies hitherto conducted on type 2 diabetes. Primarily focusing on the current status of genomic research, we briefly discussed the limited progress made during the post-genomic era and tried to identify the limitations of the post-genomic research strategies. We suggested reanalysis of the existing genomic data through advanced statistical and computational methods and recommended integrated genomics-metabolomics approaches for future studies to facilitate understanding of the gene-environment interactions in the manifestation of the disease. We also propose a framework for research that may be apt for determining the effects of urbanization and changing lifestyles in the manifestation of complex genetic disorders like type 2 diabetes in the Indian populations and offset the confounding effects of both genetic and environmental factors in the natural way.

Purpose: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored., Methods: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Since trial registration was made mandatory in the country in June 2009, we selected two study periods as between January 2007 to May 2009 (Period I) and July 2009 to December 2011 (Period II). Seventy-five protocols were randomly selected using a computer-generated list for each study period, making a total of 150 protocols. Data on twelve key methodological characteristics were collected including clearly defined primary outcomes, randomization, blinding, use of control group, statistical methods, handling of withdrawals amongst others., Results: More than 3/4th of the trial applications in the two study periods were for new chemical entities and nearly 90% were pharmaceutical industry sponsored studies. Comparing the period before and after implementation of mandatory trial registration, description of clearly defined trial outcomes improved from nearly 42% to 80% (p<0.001), sample size justifications increased from 38% to 70% (p<0.001) and use of allocation concealment improved from 24% to 49% (p=0.001). Marked improvement was also noted for blinding, description of statistical methods and handling of withdrawals and dropouts. Remaining characteristics did not change significantly between the two study periods. The mean cumulative scores for the study protocols improved significantly from 7± 0.296 in the first period to 8.93± 0.346 (p<0.001) in the second period., Conclusions: Our study found a significant improvement in the methodological quality characteristics of the protocols particularly in elements related to minimization of bias and statistical methods, which could be attributed to mandatory trial registration. Overall, the significant improvement was limited to global clinical trials, and room for improvement was noted for two quality characteristics - proportion of randomized studies and trials adequately describing the generation of allocation sequence.

Pharmaceuticals, personal care products (PPCPs), and artificial sweeteners (ASWs) are contaminants of emerging concern commonly found in the aquatic environments. In India, studies reporting environmental occurrence of these contaminants are scarce. In this study, we investigated the occurrence and distribution of 15 PPCPs and five ASWs in the river and groundwater (used untreated as drinking water) at several sites along the Ganges River. Based on the measured groundwater concentrations, we estimated the life-long human health risk from exposure to PPCPs through drinking. In addition, we estimated the risk of exposure to PPCPs and ASWs in the river water for aquatic organisms. The sum of detected PPCPs in the river water ranged between 54.7-826 ng/L, with higher concentrations in the severely anthropogenically influenced middle and lower reaches of the Ganges. The highest concentration among the PPCPs in the river water was of caffeine (743 ng/L). The sum of detected ASWs in river water ranged between 0.2-102 ng/L. Similar to PPCPs, the sum of ASWs in the river water was higher in the middle and lower reaches of the Ganges. In groundwater, the sum of detected PPCPs ranged between 34-293 ng/L, whereas of ASWs ranged between 0.5-25 ng/L. Negligible risk for humans was estimated from PPCPs in the drinking groundwater sources along the Ganges River, whereas moderate risks to PPCPs and ASWs (namely: caffeine, sulfamethoxazole, triclocarban, triclosan, and sucralose) were estimated for aquatic organisms in the Ganges River., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Neuronal voltage-gated potassium channels, K V 7s, are the molecular mediators of the M current and regulate membrane excitability in the central and peripheral neuronal systems. Herein, we report novel small molecule K V 7 openers that demonstrate anti-seizure activities in electroshock and pentylenetetrazol-induced seizure models without influencing Rotarod readouts in mice. The anti-seizure activity was determined to be proportional to the unbound concentration in the brain. K V 7 channels are also expressed in the bladder smooth muscle (detrusor) and activation of these channels may cause localized undesired effects. Therefore, the impact of individual K V 7 isoforms was investigated in human detrusor tissue using a panel of K V 7 openers with distinct activity profiles among K V 7 isoforms. KCNQ4 and KCNQ5 mRNA were highly expressed in detrusor tissue, yet a compound that has significantly reduced activity on homomeric K V 7.4 did not reduce detrusor contraction. This may suggest that the homomeric K V 7.4 channel plays a less significant role in bladder contraction and further investigation is needed., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background/aim: Optimal cutoff values are influenced by ethnicity, geography, lifestyles, and physical activity, and hence, there is a need for establishing population- and disease-specific cutoff values to screen individuals/populations. Therefore, the present study was carried out to determine the optimal cutoff values of anthropometric variables for coronary artery disease (CAD) for the population of southern Andhra Pradesh., Methods: One hundred sixty five patients with CAD and 87 controls were recruited, and 52 anthropometric variables were measured for them., Results: Higher means in 22 anthropometric variables covering circumferences, skinfold thickness (sft), and indices were observed in patients than those in controls. Receiver operator curve analysis revealed that 18 variables including circumference, sft, and fat measures with an area under curve ranging from 0.61 to 0.72 were found to have the ability of predicting the risk of CAD. A stepwise discriminant analysis showed 9 variables to correctly classify 87.4% of subjects into CAD and controls. In logistic regression analysis, among these 9 variables, only circumferences of abdomen and foot; sft of supratellar, thigh and calf; and sum of subscapular/suprailiac, waist-hip ratio and lean body mass were associated with CAD and explained 73.4% of its variation., Conclusions: Eighteen anthropometric variables were found to have the ability of predicting the risk of CAD. Longitudinal studies are needed to confirm the use of anthropometric variables in predicting the risk of CAD., (Copyright © 2018 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

We report two label-free fluorescent aptasensor methods for the detection of S. typhimurium. In the first method, we have used a ''turn off'' approach in which the aptamer is first intercalated with SYBR Green I (SG), leading to a greatly enhanced fluorescence signal. The addition of S. typhimurium (approximately 1530-96938 CFU/mL), which specifically binds with its aptamer and releases SG, leads to a linear decrease in fluorescence intensity. The lowest detection limit achieved with this approach was in the range of 733 CFU/mL. In the second method, a ''turn on'' approach was designed for S. typhimurium through the Förster resonance energy transfer (FRET) between Rhodamine B (RB) and gold nanoparticles (AuNPs). When the aptamer and AuNPs were mixed with RB, the fluorescence of RB was significantly quenched via FRET. The aptamer adsorbs to the AuNP surface to protect them from salt-induced aggregation, which leads to the fluorescence quenching of RB in presence of AuNPs. Upon the addition of S. typhimurium, S. typhimurium specifically binds with its aptamer and loses the capability to stabilize AuNPs. Thus, the salt easily induces the aggregation of AuNPs, resulting in the fluorescence recovery of the quenched RB. S. typhimurium concentrations ranging from 1530 to 96938 CFU/mL with the detection limit of 464 CFU/mL was achieved with this methodology. Given these data, some insights into the molecular interactions between the aptamer and the bacterial target are provided. These aptasensor methods also may be adapted for the detection of a wide variety of targets., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: This quasi-clinical trial compared the effects of Oral7 ® and salt-soda mouthwash on the development of dental caries, salivary gland function, radiation mucositis, xerostomia and EORTC QLQ H&N C35 scores in head and neck cancer patients who underwent radiotherapy., Methods: We included patients with histopathologically diagnosed head and neck cancers who had received radiation, with an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and age range of 15-60 years. Patients with prior radiotherapy and chemotherapy, edentulous status, total parotidectomy, sicca syndrome or on xerosis-induced medications were excluded. We assigned 15 patients each to the Oral7 ® and salt-soda groups., Results: There was no significant difference in the mean Decayed, Missing and Filling Teeth (DMFT) score between groups. Head and neck cancer patients who were on Oral7 ® had a significantly better quality of life than those on salt-soda in relation to the swallowing problems, social eating, mouth opening, xerostomia and illness scales. Patients who were on Oral7 ® had a significantly lower xerostomia score than patients on salt-soda mouthwash. Patients on Oral7 ® had a significantly lower mucositis score in week 5-7 compared to patients in the salt-soda group., Conclusion: Oral7 ® showed advantages over salt-soda solution in relation to reducing xerostomia, easing radiation-induced mucositis, and improving quality of life, despite the non-significant difference in the dental caries assessment., Competing Interests: Conflicts of Interest None

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous semi-volatile organic pollutants. Their environmental occurrence is of global concern as some of them are carcinogens, mutagens, and teratogens. In this study, concentrations and distributions of 16 priority PAHs (∑PAHs) were measured in air, atmospheric deposition, and surface water at various locations in Himalayan, Middle, and Lower Reaches of the Ganges River, covering a spatial transect of 2500km, during two seasons (pre-monsoon and monsoon). The concentration of ∑PAHs ranged between 2.2 and 182.2ngm -3 in air, between 186 and 8810ngm -2 day -1 in atmospheric deposition, and between 0.05 and 65.9ngL -1 in surface water. Air concentrations were strongly correlated with human population density. In the Middle and Lower Reaches of the Ganges River, atmospheric PAHs were mainly attributed to fossil fuel combustion sources. In the Himalayan Reach the influence of forest fire or biomass combustion was evident during the dry pre-monsoon season. Seasonality in concentrations of PAHs in river water was evident in the Himalayan Reach of the river, as a probable consequence of climate-modulated secondary source intensity (i.e. releases from glacier melting). Seasonality faded in the Middle and Lower Reaches of the Ganges where water contamination is expected to mainly reflect anthropogenic primary sources. Ambient air concentrations were used to calculate the probabilistic incremental lifetime cancer risk (ILCR). It was expectedly found to be higher in the Middle and Lower Reaches compared to the Himalayan Reach. The strong correlation between population density and air concentrations suggests population density may be used as a surrogate variable to assess human health risk in data-sparse regions such as the Ganges River basin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy., (Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The mathematical models reported in the literature so far have been found using Center of Sums (CoS) defuzzification method only. It appears that no one has found models using Center of Area (CoA) or Center of Gravity (CoG) defuzzification method. Although there have been some works reported to deal with modeling of fuzzy controllers via Centroid method, all of them have in fact used CoS method only. In this paper, for the first time mathematical models of the simplest Mamdani type fuzzy Proportional Integral (PI)/Proportional Derivative (PD) controllers via CoG defuzzification are presented. L-type and Γ-type membership functions over different Universes of Discourse (UoDs) are considered for the input variables. L-type, Π-type and Γ-type membership functions are considered for the output variable. Three linear fuzzy control rules relating all four input fuzzy sets to three output fuzzy sets are chosen. Two triangular norms namely Algebraic Product (AP) and Minimum (Min), Maximum (Max) triangular co-norm, and two inference methods, Larsen Product (LP) and Mamdani Minimum (MM), are used. Properties of the models are studied. Stability analysis of closed-loop systems containing one of these controller models in the loop is done using the Small Gain theorem. Since digital controllers are implemented using digital processors, computational and memory requirements of these fuzzy controllers and conventional (nonfuzzy) controllers are compared. A rough estimate of the computational time taken by the digital computer while implementing any of these discrete-time fuzzy controllers is given. Two nonlinear plants are considered to show the superiority of the simplest fuzzy controller obtained using CoA or CoG defuzzification method over the simplest fuzzy controller obtained using CoS method and reported recently. Real-time implementation of one of the developed controller models is done on coupled tank experimental setup to show the feasibility of the developed model., (Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: Dietary intake of phytonutrients present in fruits and vegetables, such as carotenoids, is associated with a lower risk of obesity and related traits, but the impact of genetic variation on these associations is poorly understood, especially in children. Objective: We estimated common genetic influences on serum carotenoid concentrations and obesity-related traits in Mexican American (MA) children. Design: Obesity-related data were obtained from 670 nondiabetic MA children, aged 6-17 y. Serum α- and β-carotenoid concentrations were measured in ∼570 (α-carotene in 565 and β-carotene in 572) of these children with the use of an ultraperformance liquid chromatography-photodiode array. We determined heritabilities for both carotenoids and examined their genetic relation with 10 obesity-related traits [body mass index (BMI), waist circumference (WC), high-density lipoprotein (HDL) cholesterol, triglycerides, fat mass (FM), systolic and diastolic blood pressure, fasting insulin and glucose, and homeostasis model assessment of insulin resistance] by using family data and a variance components approach. For these analyses, carotenoid values were inverse normalized, and all traits were adjusted for significant covariate effects of age and sex. Results: Carotenoid concentrations were highly heritable and significant [α-carotene: heritability ( h 2 ) = 0.81, P = 6.7 × 10 -11 ; β-carotene: h 2 = 0.90, P = 3.5 × 10 -15 ]. After adjusting for multiple comparisons, we found significant ( P ≤ 0.05) negative phenotypic correlations between carotenoid concentrations and the following traits: BMI, WC, FM, and triglycerides (range: α-carotene = -0.19 to -0.12; β-carotene = -0.24 to -0.13) and positive correlations with HDL cholesterol (α-carotene = 0.17; β-carotene = 0.24). However, when the phenotypic correlations were partitioned into genetic and environmental correlations, we found marginally significant ( P = 0.051) genetic correlations only between β-carotene and BMI (-0.27), WC (-0.30), and HDL cholesterol (0.31) after accounting for multiple comparisons. None of the environmental correlations were significant. Conclusions: The findings from this study suggest that the serum carotenoid concentrations were under strong additive genetic influences based on variance components analyses, and that the common genetic factors may influence β-carotene and obesity and lipid traits in MA children., (© 2017 American Society for Nutrition.)

Objective: To investigate the occurrence and clinical characteristics of dapsone-related adverse drug reactions (ADRs) among leprosy patients who underwent multidrug therapy (MDT) from 2010 to 2013 in the western region of Nepal., Methods: A retrospective review was carried out in the rehabilitation center. Data were collected from the record files of the hospital., Results: From 2010 to 2013, there were 18 patients reported to have dapsone ADRs, with an occurrence rate of 0.82% in the 4-year duration. The maximum incidence of ADRs (1.043%) was in 2010 and the minimum incidence of ADRs (0.26%) was in 2013. Among two types of bacterial infections, 94.44% were of multibacillary and 5.56% were of paucibacillary type. The age range of patients with dapsone ADRs was 11-68 years. The male-to-female ratio was 1.25. The onset of dapsone ADRs after taking MDT was within a minimum of 3 weeks and a maximum of 21 weeks. There were 14 (77.77%) patients who presented with jaundice, 8 (44.44%) with exfoliative dermatitis, 5 (27.77%) with hemolytic anemia and 4 (22.22%) with fever and headache. The rare side effects (5.5%) found were agranulocytosis or toxic epidermal necrolysis. Three patients were cured; some were still on the treatment. Four patients died with dapsone ADRs., Conclusion: The common dapsone ADRs present in leprosy patients were jaundice, exfoliative dermatitis and hemolytic anemia in MDT-treated patients. Patients could be cured by managing the dapsone ADRs effectively on time. Some patients may die of dapsone ADRs if clinicians fail to manage the side effects on time., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Given the characteristic atherogenic dyslipidemia of south Indian population and crucial role of APOA1, APOC3, APOA4 and APOA5 genes clustered in 11q23.3 chromosomal region in regulating lipoprotein metabolism and cholesterol homeostasis, a large number of recently identified variants are to be explored for their role in regulating the serum lipid parameters among south Indians., Methods: Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of the 11q23.3 chromosomal region were genotyped on 516 individuals from Hyderabad, India, and its vicinity and aged >45 years., Results: The linear regression analysis of the individual lipid traits viz., TC, LDLC, HDLC, VLDL and TG with each of the 78 SNPs that confirm to HWE and with minor allele frequency > 1%, suggests 23 of those to be significantly associated (p ≤ 0.05) with at least one of these quantitative traits. Most importantly, the variant rs632153 is involved in elevating TC, LDLC, TG and VLDLs and probably playing a crucial role in the manifestation of dyslipidemia. Additionally, another three SNPs rs633389, rs2187126 and rs1263163 are found risk conferring to dyslipidemia by elevating LDLC and TC levels in the present population. Further, the ROC (receiver operating curve) analysis for the risk scores and dyslipidemia status yielded a significant area under curve (AUC) = 0.675, suggesting high discriminative power of the risk variants towards the condition. The interaction analysis suggests rs10488699-rs2187126 pair of the BUD13 gene to confer significant risk (Interaction odds ratio = 14.38, P = 7.17 × 10 5 ) towards dyslipidemia by elevating the TC levels (β = 37.13, p = 6.614 × 10 5 ). On the other hand, the interaction between variants of APOA1 gene and BUD13 and/or ZPR1 regulatory genes at this region are associated with elevated TG and VLDL., Conclusion: The variants at 11q23.3 chromosomal region seem to determine the quantitative lipid traits and in turn dyslipidemia in the population of Hyderabad. Particularly, the variants rs632153, rs633389, rs2187126 and rs1263163 might be risk conferring to dyslipidemia by elevating LDLC and TC levels, while the variants of APOC3 and APOA1 genes might be the genetic determinants of elevated triglycerides in the present population.

Semecarpus anacardium L. is a tree species which produces secondary metabolites of medicinal importance. Roots of the plant have been traditionally used in folk medicines. Different strains of Agrobacterium rhizogenes (A4, ATCC15834 and LBA 9402) were used for induction of hairy roots in in vitro grown tissues of the plant. Hairy root initiation was observed after 25-30 days of infection. Optimum transformation frequency of 61% was achieved on leaf explants with ATCC15834 strain. Infection time of 30 min resulted in greater transformation frequency compared to 10 and 20 min, respectively. The hairy roots cultured in growth regulator-free semi-solid woody plant medium differentiated into callus. Whole shoots infected with ATCC 15834 were found to produce more transformants upon co-cultivation for 4 (65%) and 5 (67%) days. Induction of hairy roots in stem explants infected with ATCC 15834 was lower (52%) compared to leaves (62%) after 4 days of co-cultivation. In A4 and LBA9402 strains transformation efficiency was 49 ± 2.8% and 36 ± 5.7% in shoots after 4 days of co-cultivation. Transformation frequency was higher in ATCC15834 strain, irrespective of explants. The hairy roots of S. anacardium elongated slowly upon transfer to half-strength liquid medium. After 3-4 passages in liquid medium slender hairy roots started differentiating which were separated from the original explants. Visible growth of the roots was observed in hormone-free liquid medium after 2-3 months of culturing. Polymerase chain reaction with gene-specific primers from rol A, B and C genes confirms the positive transformation events.

Introduction: Catheter based Interventional procedures have become an indispensable treatment option for patients contraindicated for surgical heart valve replacement . The broad spectrum of disease that affect the mitral valve have increased the need for a transcatheter mitral valve replacement (TMVR) device. As complex as the mitral valve anatomy is, so are challenges in the development of a TMVR device. Areas covered: This review article analyses the challenges in the development of the TMVR device from an engineering perspective of material and device design. The major sections in this paper discusses the engineering challenges in the development of TMVR device, material & design considerations, surface coating, present and future of TMVR, delivery catheter specifications and commercial prospects of the TMVR. This article highlights the current status in the development of each of the devices based on the outcome clinical trials and case studies. The literature analysis was carried out using the keywords search. Expert commentary: This section concludes with the need for collaborative efforts from the medical and engineering expertise for the successful development of TMVR device. Overcoming the anatomical challenges with engineering innovations would create new frontier in TMVR technologies.

Background: Genetic predisposition to the clinical categories of coronary artery disease (anatomical viz., insignificant, single, double, and triple vessel diseases and phenotypic severity categories viz., angina, acute coronary syndrome, and myocardial infarction) is poorly understood. Particularly, the apolipoprotein genes clustered at 11q23.3 chromosomal region play a vital role in cholesterol homeostasis, and a large number of SNPs identified in this region need to be explored for their association with the clinical categories of CAD., Methods: Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of 11q23.3 chromosomal region were genotyped on 508 CAD cases and 516 ethnicity matched controls, enrolled from Hyderabad, India, and its vicinity., Results: The association analysis suggests 19 and 15 SNPs to be significantly associated (p ≤ 0.05) with at least one of the anatomical and/or phenotypic severity categories, respectively. Overall, the six SNPs rs17440396:G>A, rs6589566:A>G, rs2849165:G>A, rs10488699:G>A, rs1263163:G>A, and rs1263171:G>A were significant even after correction for multiple testing. Three of these (rs17440396:G>A, rs6589566:A>G, and rs2849165:G>A) that belong to BUD13, ZPR1, and APOA5-APOA4 intergenic regions, respectively, were found to be associated across the anatomical categories of CAD. However, no particular trend in the genotypic odds ratios with the increasing severity was apparent. The association analysis of the variants with phenotypic severity categories suggests that a high degree of phenotypic severity could be a result of more number of risk alleles. While the risk score analysis suggests high discriminative power of the variants towards the individual clinical categories of CAD, the complex network of interactions seen between the intronic variants of BUD13 and ZPR1 regulatory genes and intergenic variants of APOA5-APOA4 suggests pleiotropic effects of regulatory genes in the manifestation of these CAD categories., Conclusion: The complex network of interactions observed in the present study between the regulatory and protein-coding genes suggests their role in the manifestation of distinct clinical categories of CAD, which needs to be functionally validated.

Background & Objectives: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India., Methods: A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform., Results: None of the 15 SNPs were found to be significantly associated with PCOS after Bonferroni correction for multiple testing, either in the univariate or multivariate context. The cumulative effect of risk alleles observed with reference to T2DM was also not seen with reference to PCOS., Interpretation & Conclusions: The nine T2DM genes considered in this exploratory study might not be the primary susceptibility factors for PCOS among Indian women. Our results supplement the lack of evidence of the association of T2DM genes with PCOS among the Chinese and Caucasians hinting at the possible universality of this pattern. Specifically designed comprehensive studies that include women with T2DM and PCOS are required to explore the precise role of the diabetes genes.

Objective: To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats., Methods: The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test., Results: The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats., Conclusion: Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.

Aim: Self-medication is widely practiced with varying dimensions in India. This practice has many implications, especially among medical and paramedical students having some knowledge and good exposure to drugs. We conducted a two-period observational study to evaluate the change in knowledge and practice of self-medication, over 5 years of time period, among medical and paramedical students from different parts of India., Materials and Methods: A structured questionnaire was administered to medical (MBBS), dental (BDS), and paramedical students, who come to attend pan India annual cultural, literary, and sports event at New Delhi. The study was conducted in two phases (2007 and 2012) in different respondents of same categories (medical and paramedical) of students. Three-hundred and thirty students from 39 colleges in 2007 and 356 students from 38 colleges in 2012 participated in the study., Results: The prevalence of self-medication remained high in both 2007 and 2012 (74.6% and 69.4%), although no significant difference was observed between the two phases (P = 0.14%). Oral antibacterial agents, oral anti-inflammatory agents, and antipyretics were the most common group of drugs used in both phases of study. A significant increase was observed in number of students who took complete course of oral antibiotics (28.3-38.3%, P = 0.01)., Conclusion: The prevalence of self-medication among undergraduate students remains unaltered over the span of 5 years. Nevertheless, there was a better sensitization toward appropriate antibiotic usage and the practice of responsible self-medication needs to be promoted among future healthcare providers.

Aims: To evaluate the accuracy of dies made from dual arch impressions using different sectional dual arch trays, combinations of elastomeric impression materials, and the sequence of pour of dies., Subjects and Methods: The dual arch impression materials were grouped into three groups depending on the combination of impression materials used and each group is subdivided into four subgroups. A sample size of 8 in each subgroup yielding a total 96 impressions will be made into three groups of 32 each (Group I, II, and III). Group I constitute impressions made using monophase (M) impression material, Group II constitute impressions made using combination of heavy body and light body (HL), and Group III constitute impressions made using combination of putty and light body (PL). Dies obtained were evaluated with a travelling microscope to measure the buccolingual width of the tooth at the margin by using the sharp corners of the notches as reference points., Statistical Analysis Used: Descriptive analysis namely mean and standard deviation, one-way analysis of variance test., Results: The results obtained in this study indicate that though not statistically significant, the metal dual arch trays performed better when compared to the plastic trays in reproducing die dimensions., Conclusions: From the results obtained, dies poured from combination of heavy body and light body impressions using plastic or metal dual arch trays showed least variation in bucco-lingual dimension from master model.

Purpose: To identify clinico-radiological distinguishing features in various types of spinal arteriovenous malformations (AVM) with an aim to define the role of surgical intervention., Materials and Methods: Hero's modified Di Chiro classification differentiated four types of spinal AVMs on digital subtraction angiogram (DSA) in 74 patients: I. Dural arteriovenous fistulae (n = 35, 47.3%); II. Glomus/intramedullary (n = 13, 17.6%); III. Juvenile/metameric (n = 4, 5.4%); and, IV. Ventral perimedullary fistula (n = 21, 28.4%). A patient with extradural AVM remained unclassified. Demographic profiles, DSA features and reason for surgical referral were recorded. Statistical comparison of discrete variables like gender, spinal cord level, presentation and outcome was made using Chi-square test; and, continuous variables like age, feeder number, duration of symptoms and number of staged embolizations by one way analysis of variance with Boneferoni post hoc comparison. Embolization alone (n = 39, 52.7%), surgery alone (n = 16, 21.6%), and combined approach (n = 4, 5.4%) were the treatments offered (15 were treated elsewhere)., Results: Type I-AVM occurred in significantly older population than other types (P = 0.01). Mean duration of symptoms was 13.18 ± 12.8 months. Thoracic cord involvement predominated in type-I and III AVMs (P = 0.01). Number of feeding arteries were 1 in 59.7%; 2 in 29.0%; and, multiple in 11.3% patients, respectively. Staged embolization procedures in type-III AVM were significant (P < 0.01). Surgical referral was required due to: Vessel tortuosity/insufficient parent vessel caliber (n = 7); residual AVM (n = 4); low flow AVM (n = 3); and, multiple feeders (n = 2). Check DSA (n = 34) revealed complete AVM obliteration in 26 and minor residual lesion in eight patients. Neurological status improved in 26 and stabilized in 25 patients., Conclusions: Differentiating between Type I-IV AVMs has a significant bearing on their management. Surgical intervention should be considered as an important adjunct/alternative to therapeutic embolization.

Background & Objectives: The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India., Methods: A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform., Results: The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology., Interpretation & Conclusions: A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.

This consensus statement focuses on the window of opportunity, which exists while treating patients with diabetic kidney disease and anemia.