Decriminalization and medical students attitudes to same sex behaviour.

The Supreme Court of India, decriminalized same-sex activities in 2018 but the Indian medical curriculum has not been updated and inclusive of the sexual minorities despite the change. This study explores the attitude of medical students towards same-gender attraction and how it has shaped and reshaped in an ever-changing social environment. Medical students of four reputed Indian medical colleges were asked to self-administer an 18-item questionnaire anonymously. Internal consistency of the questionnaire statements was high. Of 729 initial responses, 84 were omitted for giving incomplete responses and 3 were omitted for not being Indian. A total of 642 responses was included in the analysis. More than 80% of the students believed homosexuality is a sexual orientation whereas only 15% believed it is an acquired behaviour and only 1.9% considered it an illness. However, more than 95%of students agreed that homosexuality is not an illness. Although the overall attitude of Indian medical students has changed since decriminalization, urgent work on the medical curriculum is needed to change some negative attitudes so that patients receive appropriate care.

The Hippo kinase LATS2 impairs pancreatic ß-cell survival in diabetes through the mTORC1-autophagy axis.

Diabetes results from a decline in functional pancreatic ß-cells, but the molecular mechanisms underlying the pathological ß-cell failure are poorly understood. Here we report that large-tumor suppressor 2 (LATS2), a core component of the Hippo signaling pathway, is activated under diabetic conditions and induces ß-cell apoptosis and impaired function. LATS2 deficiency in ß-cells and primary isolated human islets as well as ß-cell specific LATS2 ablation in mice improves ß-cell viability, insulin secretion and ß-cell mass and ameliorates diabetes development. LATS2 activates mechanistic target of rapamycin complex 1 (mTORC1), a physiological suppressor of autophagy, in ß-cells and genetic and pharmacological inhibition of mTORC1 counteracts the pro-apoptotic action of activated LATS2. We further show a direct interplay between Hippo and autophagy, in which LATS2 is an autophagy substrate. On the other hand, LATS2 regulates ß-cell apoptosis triggered by impaired autophagy suggesting an existence of a stress-sensitive multicomponent cellular loop coordinating ß-cell compensation and survival. Our data reveal an important role for LATS2 in pancreatic ß-cell turnover and suggest LATS2 as a potential therapeutic target to improve pancreatic ß-cell survival and function in diabetes.

Inhibition of PHLPP1/2 phosphatases rescues pancreatic ß-cells in diabetes.

Pancreatic ß-cell failure is the key pathogenic element of the complex metabolic deterioration in type 2 diabetes (T2D); its underlying pathomechanism is still elusive. Here, we identify pleckstrin homology domain leucine-rich repeat protein phosphatases 1 and 2 (PHLPP1/2) as phosphatases whose upregulation leads to ß-cell failure in diabetes. PHLPP levels are highly elevated in metabolically stressed human and rodent diabetic ß-cells. Sustained hyper-activation of mechanistic target of rapamycin complex 1 (mTORC1) is the primary mechanism of the PHLPP upregulation linking chronic metabolic stress to ultimate ß-cell death. PHLPPs directly dephosphorylate and regulate activities of ß-cell survival-dependent kinases AKT and MST1, constituting a regulatory triangle loop to control ß-cell apoptosis. Genetic inhibition of PHLPPs markedly improves ß-cell survival and function in experimental models of diabetes in vitro, in vivo, and in primary human T2D islets. Our study presents PHLPPs as targets for functional regenerative therapy of pancreatic ß cells in diabetes.

Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients.

The aim of this study was to investigate the impact of Supervised and Home-based resistance exercise on the Kynurenine pathway in patients with pancreatic cancer who underwent surgery and chemotherapy. In the SUPPORT study, adult pancreatic cancer patients were randomized to intervention programs of 6-month (1) a Supervised moderate-to-high-intensity progressive resistance training or (2) unsupervised Home-based resistance training, or (3) to a standard care patient Control group. Serum levels of kynurenine, tryptophan and IL-6 were assessed for 32 participants before, after 3 months and after 6 months of exercise intervention. Group differences were investigated using analysis-of-covariance. Patients in the Supervised training group showed decreased levels of serum kynurenine and kynurenine/tryptophan ratio (p = 0.07; p = 0.01 respectively) as well as increased Tryptophan levels (p = 0.05) in comparison to Home-based and Control group over time. The Home-based exercise group had significant increased kynurenine and kynurenine/tryptophan ratio levels. IL-6 levels decreased over the first three months for both intervention groups as well as the Control group (Supervised: p < 0.01, Home-based: p < 0.010, Control group: p < 0.01). Supervised resistance exercise might positively regulate the Kynurenine pathway and downregulate the kynurenine/tryptophan (indicative of IDO/TDO enzyme) levels, hence modulating the immune system.

No Evidence for Effect of Exercise on Transcriptome of NK Cells in Breast Cancer Patients Undergoing Adjuvant Therapy: Results From a Pilot Study.

BACKGROUND: Mobilization and activation of natural killer cells (NK cells) have been hypothesized to contribute to observed protective effects of exercise on cancer development and progression. Some evidence exists for acute effects of aerobic exercise on NK cell mobilization and function, i.e., alteration of the gene expression profile of NK cells. Yet, the chronic effects of exercise training, and effects of other modalities than endurance exercise are still understudied. Here, we investigated the chronic effects of a 12-week resistance exercise program on NK cell gene expression in breast cancer patients undergoing adjuvant chemo- or radiotherapy. METHODS: Breast cancer patients were randomly assigned to either a 12-week resistance exercise program or a relaxation control group concomitant to adjuvant therapy. In a subsample of 19 participants, RNA was extracted from magnet bead isolated NK cells and subsequently analyzed for differential gene expression using microarray Illumina HumanHT-12 v4 before and after the intervention. RESULTS: After chronic exercise intervention several genes showed higher differential expression compared to the control group. However, after correction for multiple testing, baseline-adjusted analyses of covariance indicated no significant differences between the intervention and the control group with regard to the gene expression profile. DISCUSSION: Our findings suggest that 12-week resistance-exercise did not alter the gene expression profile of NK cells in breast cancer patients undergoing adjuvant therapy on the long term. Further studies with larger sample sizes and specifically designed to investigate whether exercise-induced changes in NK cell function are attributed to acute effects are warranted.