Indian suicide data: What do they mean? John Snowdon Indian Journal of Medical Research 2019 150(4):315-320

Is suicide prevention possible? Saxby Pridmore, William Pridmore Indian Journal of Medical Research 2019 150(4):321-323

Suicide in India: A preventable epidemic Srinagesh Mannekote Thippaiah, Muralidhara Shankarapura Nanjappa, Suresh Bada Math Indian Journal of Medical Research 2019 150(4):324-327

Looking into biological markers of suicidal behaviours Rakesh Kumar Chadda, Ankit Gupta Indian Journal of Medical Research 2019 150(4):328-331

Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India Mohammad Ashraf Ganie, Vishnu Vasudevan, Imtiyaz Ahmad Wani, Mohammad Salem Baba, Tasleem Arif, Aafia Rashid Indian Journal of Medical Research 2019 150(4):333-344 Polycystic ovary syndrome (PCOS) is a common endocrine disorder predominantly affecting women of reproductive age. Clinical manifestations are diverse including hyperandrogenism, anovulation, infertility and increased risk of metabolic diseases besides psychosocial dysfunction. This review provides information on the problem of PCOS in India, its pathophysiology, genetics and an overview of current management options to instigate further research in this field. Prevalence of PCOS in India ranges from 3.7 to 22.5 per cent depending on the population studied and the criteria used for diagnosis. Abnormalities in leptin-adiponectin (adipocyte biology), oxidative stress and autoimmunity are among the mechanisms studied regarding pathogenesis of PCOS. Many candidate gene studies have shown associations with PCOS in various studies. Studies have consistently demonstrated the relationship between the well-known manifestation of hyperandrogenism among Indian PCOS women and the metabolic morbidities including insulin resistance, glucose intolerance and cardiovascular risk. Management of individual components of PCOS can be achieved by medications or surgical methods, though further clarification regarding pathogenesis of PCOS is needed to sharpen our therapeutic armamentarium.

The human gut resistome: Current concepts & future prospects Shreya Singh, Nipun Verma, Neelam Taneja Indian Journal of Medical Research 2019 150(4):345-358 The human gut is home to a myriad of organisms. While some are harmless commensals, others are transient, pathogenic flora. The gut microbiome is composed of diverse bacterial flora, and apart from playing a major role in protecting from various infectious and non-infectious diseases, it plays an important role in resistance to antimicrobials. The collection of genes or genetic material that confers antimicrobial resistance constitutes the gut resistome, and it may involve the pathogens or commensals of the intestinal tract. The diversity of this gut resistome is influenced by various environmental factors including the diet and antibiotic exposure. This review highlights the recent concepts pertaining to the human gut resistome, factors affecting it, how it impacts human health and diseases, methods to study the resistome and potential therapeutic approaches.

Statins & risk of Clostridium difficile infection: A meta-analysis Karn Wijarnpreecha, Panadeekarn Panjawatanan, Charat Thongprayoon, Patompong Ungprasert Indian Journal of Medical Research 2019 150(4):359-364 Background & objectives: Clostridium difficile infection is one of the most common healthcare-associated infections worldwide. Recent epidemiologic studies have suggested that statin users may have a lower risk of C. difficile infection, although the results are inconsistent. This meta-analysis was conducted with the aim of summarizing all available data to assess the risk of C. difficile infection among statin users versus non-users. Methods: A literature review was performed using the MEDLINE and EMBASE databases from inception to October 2017. Cohort, case-control and cross-sectional studies that compared the risk of C. difficile infection among statin users versus non-users were included. Pooled odds ratio (OR) and 95 per cent confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Six case-control studies and two cross-sectional studies met the eligibility criteria and were included in this meta-analysis. The risk of C. difficile infection among statin users was significantly lower than non-users with the pooled OR of 0.74 (95% CI, 0.61-0.89). The statistical heterogeneity of this study was high (I[2]=90%). Interpretation & conclusions: This meta-analysis demonstrated a decreased risk of C. difficile infection among statin users versus non-users. Further studies are required to clarify the role of statins for prevention of C. difficile infection in clinical practice.

Downregulation of apolipoprotein A-IV in plasma & impaired reverse cholesterol transport in individuals with recent acts of deliberate self-harm Boby Mathew, Krishnamachari Srinivasan, Johnson Pradeep, Tinku Thomas, Shakuntala Kandikuppa Murthy, Amit Kumar Mandal Indian Journal of Medical Research 2019 150(4):365-375 Background & objectives: The major limiting factor in the prevention of suicide is the limited knowledge on molecular insights in individuals at risk. Identification of peripheral protein markers which can classify individuals at high-risk of suicide might aid in early diagnosis and effective medical intervention. The aim of the present study was, therefore, to analyze the differential regulation of plasma proteins in individuals with deliberate self-harm compared to controls. Methods: Using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption-ionization mass spectrometry, differentially expressed plasma proteins were identified in study participants with deliberate self-harm compared to age- and gender-matched controls. The finding was validated using mass spectrometry-based isotope-labelled relative quantification and Western blot analysis in a new set of individuals with deliberate self-harm and controls. Results: The plasma proteomic analysis showed that apolipoprotein A-IV (Apo A-IV ) was downregulated by 2.63-fold (confidence interval: 1.52-4.54) in individuals with deliberate self-harm (n=10) compared to matched controls, which was consistent in mass spectrometry-based relative quantification and Western blot analysis performed in an independent set of individuals with deliberate self-harm (n=18). In addition, plasma levels of total cholesterol, esterified cholesterol and high-density lipoprotein (HDL) were observed to be significantly lower individuals with deliberate self-harm compared to controls. Interpretation & conclusions: Apo A-IV, which plays a crucial role in the esterification of free cholesterol, was found to be downregulated with concomitantly decreased levels of HDL, esterified cholesterol and total cholesterol in individuals with deliberate self-harm compared to matched controls. The present findings might provide a link between the differential regulation of plasma proteins and the previously reported results on altered cholesterol levels in individuals with deliberate self-harm.

Comparison of laboratory-developed test & validated assay of programmed death ligand-1 immunohistochemistry in non-small-cell lung carcinoma Aruna Nambirajan, Nuzhat Husain, Saumya Shukla, Sunil Kumar, Deepali Jain Indian Journal of Medical Research 2019 150(4):376-384 Background & objectives: Inhibitors of immune checkpoint regulators, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), improve outcome in advanced non-small-cell lung carcinoma (NSCLC). Tumours expressing PD-L1 protein are more likely to benefit from this targeted therapy. Multiple concurrent clinical trials evaluating different anti-PD-1/PD-L1 therapies have validated five different immunohistochemistry (IHC) assays using varied antibody clones and staining conditions. This study was aimed at identification of a single harmonized PD-L1 assay for tumour tissue conservation and cost-effectiveness in patients with NSCLC. Methods: The performance of low-cost, manual, laboratory-developed technique (LDT) PD-L1 IHC assay using the easily available SP142 clone was compared with trial validated Ventana SP263 IHC performed on automated Ventana staining platform on tumour sections of NSCLCs. Results: Eighty cases of NSCLC were included. SP263 and SP142 stained both tumour cells and immune cells. The concordance rate of tumour cell staining was about 76 per cent, with SP263 detecting more tumour cells in 16 per cent of cases. The concordance rate of immune cell staining was only 61 per cent, with SP142 detecting more immune cells in 24 per cent of cases. The sensitivity, specificity, positive and negative predictive values of manual SP142 LDT assay against gold standard SP263 Ventana assay were 70, 94, 86 and 86 per cent, respectively, at positivity thresholds of ≥1 per cent tumour cell staining. Interpretation & conclusions: The study findings suggested that LDT using SP142 clone showed only moderate concordance with SP263 Ventana assay, and the two assays were not interchangeable. More such validation studies need to be done to generate information that can complement patient therapy in cases of NSCLC.

Evaluation of haemoglobin cut-off for mild anaemia in Asians - analysis of multiple rounds of two national nutrition surveys Jithin Sam Varghese, Tinku Thomas, Anura V Kurpad Indian Journal of Medical Research 2019 150(4):385-389 Background & objectives: The haemoglobin (Hb) cut-off is a single value for all populations. It is possible that different populations might have slightly different cut-off values; but, this needs to be evaluated in healthy populations with low possibility of inadequate dietary intakes of haematopoietic nutrients. This study was conducted to assess the existence of race-specific Hb cut-offs for mild anaemia in healthy populations and their potential implications. Methods: In this study the Hb distributions of healthy White, Black, Mexican and Hispanic and Asian non-pregnant women obtained from nine rounds of the National Health and Nutrition Examination Survey (NHANES) and two rounds of National Diet and Nutrition Survey (NDNS), was examined to check the existence of race-specific Hb cut-off for mild anaemia, by standard statistical methods. Results: The mean Hb of Blacks, Mexicans and Hispanics and Asians were lower than Whites, consistent with previous literature. The Hb cut-off for mild anaemia in Asians was lower at 11.22 g/dl. Interpretation & conclusions: Using the Hb cut-off derived in this study in place of the World Health Organization, cut-off of 12 g/dl would result in a 17.9 per cent decrease in the prevalence of anaemia in India. This points to the need for re-examining race-specific cut-off for mild anaemia and points to the need for alternative methods, perhaps linked to risk of unhealthy outcomes.