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Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies. We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects. We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively. Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.

OBJECTIVE:--To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery. RESEARCH DESIGN AND METHODS--The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery. RESULTS:--A total of 597 mothers had an OGTT at 28 weeks' gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy (P < 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P < 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P < 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up. CONCLUSIONS:--Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women.

Determinants of Incident Hyperglycemia 6 Years After Delivery in Young Rural Indian Mothers The Pune Maternal Nutrition Study (PMNS) Smita R. Kulkarni , MSC 1 , Caroline H.D. Fall , DM, FRCPCH 2 , Niranjan V. Joshi , MD, DNB 1 , Himangi G. Lubree , MSC 1 , Vaishali U. Deshpande , MSC 1 , Rashmi V. Pasarkar , MSC 1 , Dattatray S. Bhat , MSC 1 , Sadanand S. Naik , PHD 1 and Chittaranjan S. Yajnik , MD, FRCP 1 1 Kamalnayan Bajaj Diabetology Research Centre, KEM Hospital and Research Centre, Pune, India 2 MRC Epidemiology Resource Centre, University of Southampton, Southampton, U.K Address correspondence and reprint requests to Dr. Chittaranjan Sakerlal Yajnik, MD, FRCP, KEM Hospital and Research Center, 6th Floor, Banoo Coyaji Building, Sardar Mudliar Road, Rasta Peth, Pune 411011, India. E-mail: diabetes{at}vsnl.com Abstract OBJECTIVE —To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery. RESEARCH DESIGN AND METHODS —The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery. RESULTS —A total of 597 mothers had an OGTT at 28 weeks’ gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy ( P < 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P < 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P < 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up. CONCLUSIONS —Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women. GDM, gestational diabetes mellitus IFG, impaired fasting glycemia IGT, impaired glucose tolerance OGTT, oral glucose tolerance test PMNS, Pune Maternal Nutrition Study SES, socio-economic status TLC, total leukocyte count Footnotes Published ahead of print at http://care.diabetesjournals.org on 9 July 2007. DOI: 10.2337/dc07-0329. Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0329 . A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted June 30, 2007. Received February 16, 2007. DIABETES CARE

Background Laparoscopic cholecystectomy has changed the surgical management of cholelithiasis and has become the mainstay of the management of uncomplicated gallstone disease. Adequate postoperative pain relief leading to early ambulation is imperative for patient satisfaction and early discharge of the patient. The use of ultrasound in anesthetic practice has ushered in a new era of ultrasound-guided blocks for postoperative analgesia, replacing the conventional methods. This study compares two modalities of postoperative pain relief, namely the oblique subcostal transversus abdominis plane block and the newer erector spinae plane block for patients undergoing laparoscopic cholecystectomy. Results Sixty patients between the age group 18 to 75 of ASA grades I, II, and III were enrolled in the study. The erector spinae plane block group showed lower numerical rating scores up to 12 h, a longer time period for the requirement of first rescue analgesic, and lower total analgesic consumption postoperatively compared to the oblique subcostal transversus abdominis plane block group. Both blocks were found to have minimal side effects. Conclusions The erector spinae plane block is superior to the oblique subcostal transversus abdominis plane block in that it affords lower pain scores and a longer duration of analgesia and reduces the total analgesic consumption after laparoscopic cholecystectomy. Trial registration Clinical Trials Registry of India/CTRI/2020/10/028603/ registered on 23 October 2020 http://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=47807&EncHid=18303.55562&modid=1&compid=19

The free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/μL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001). The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.

Background: Limited information is available on the aetiology and semen profiles of male infertility in Indian population. Aim: The aim of this study is to study the clinical and semen characteristics of men attending the infertility clinic and also to understand the impact of World Health Organization (WHO) 2010 reference values on the diagnosis of male infertility. Setting and Design: A retrospective study evaluating the medical case records (January 2005 to December 2015, [n = 1906]) of men attending infertility clinic in Mumbai, India. Materials and Methods: The aetiology was classified based on the andrology evaluation and other investigations. Semen profiles were compared during the years 2005-2010 and 2011-2015 using WHO 1999 and WHO 2010 criteria, respectively. Statistical Analysis: The Chi-square and Mann-Whitney U tests were performed using Open Source Epidemiological software and Social science calculators. Results: The aetiology of male infertility was determined in 62% of the men; while the cause remained undetermined in 38%. Varicocele (25%), urogenital infections (10%), sexual dysfunctions (8%) and vas aplasia (8%) were identified as major aetiologies in our cohort. Men with sexual dysfunctions and vas aplasia were significantly higher during the years 2011-2015 as compared to 2005-2010. Men having normozoospermia (10%) and azoospermia (3%) were increased, whereas those having oligoasthenozoospermia (17%) were reduced in 2011-2015 as compared to 2005-2010. According to WHO 1999 criteria , 12-15% of men showed abnormal semen profiles. The semen parameters of these men became normal on using WHO 2010 reference values. Conclusions: Varicocele is the most common aetiology in infertile men. Idiopathic infertility was seen in a higher proportion among the infertile men.

Trophoblast antigen 2 (Trop2) is a transmembrane glycoprotein upregulated in multiple solid tumours. Trop2-based passive immunotherapies are in clinical trials, while Trop2 targeting CAR-T cell-based therapies are also reported. Information about its T- and B-cell epitopes is needed for it to be pursued as an active immunotherapeutic target. This study focused on identification of immunodominant epitopes in the Trop2 extracellular domain (ECD) that can mount an efficient anti-Trop2 antibody response. In silico analysis using various B-cell epitope prediction tools was carried out to identify linear and conformational B-cell epitopes in the ECD of Trop2. Three linear peptide immunogens were shortlisted and synthesized. Along with linear peptides, truncated Trop2 ECD that possesses combination of linear and conformational epitopes was also selected. Recombinant protein immunogen was produced in 293-F suspension culture system and affinity purified. Antisera against different immunogens were characterized by ELISA and Western blotting. Two anti-peptide antisera detected recombinant and ectopically expressed Trop2 protein; however, they were unable to recognize the endogenous Trop2 protein expressed by cancer cells. Antibodies against truncated Trop2 ECD could bind to the endogenous Trop2 expressed on the surface of cancer cells. In addition to their high avidity, these polyclonal anti-sera against truncated Trop2 protein also mediated antibody-dependent cell-mediated cytotoxicity (ADCC). In summary, our comparative analysis demonstrated the utility of truncated Trop2 ECD as a promising candidate to be pursued as an active immunotherapeutic molecule against Trop2-positive cancer cells.

Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/μL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (≥70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART.