Prevalence and determinants of depression among elderly persons in a rural community from northern India.

Background. Globally, more than 350 million people of all ages suffer from depression. Elderly persons are more vulnerable to depression. We conducted this study to estimate the prevalence of depression, and to study the association of depression with sociodemographic and clinical variables among elderly persons in a rural community. Methods. We conducted a community-based cross-sectional study among 395 randomly selected elderly persons aged 60 years and above in a rural area of Ballabgarh, Haryana, India. The participants were screened by using the Geriatric Depression Scale, and diagnosis was confirmed by the Mini International Neuropsychiatric Interview. Multivariate analysis was done for independent predictors of depression. Results. The prevalence of depression was 11.4% (95% CI 8.6%–14.9%). Living in a nuclear family (adjusted odds ratio [AOR] 8.98, 95% CI 3.40–23.71), lack of physical activity (AOR 4.95, 95% CI 2.00–12.27), whole-time involvement in household work (AOR 4.47, 95% CI 1.18–16.93), presence of two or more chronic diseases (AOR 4.45, 95% CI 1.60–12.35), having no role in family decision-making (AOR 2.77, 95% CI 1.19–6.42), sleep problems in past one year (AOR 2.97, 95% CI 1.32–6.69) and bilateral hearing impairment (AOR 4.00, 95% CI 1.80–8.88) were factors associated with depression in elderly persons. Conclusions. Depression is common among elderly persons in rural areas. Individuals providing healthcare to elderly persons need to be trained to identify depression and take appropriate action; elderly persons with chronic diseases and hearing impairment deserve special attention. Natl Med J India 2016;29:129–35

Is CXCL10/CXCR3 axis overexpression a better indicator of leprosy type 1 reaction than inducible nitric oxide synthase.

Background & objectives: Leprosy type 1 reactions (T1R) are acute episodes of immune exacerbation that are a major cause of inflammation and nerve damage. T1R are diagnosed clinically and supported by histopathology. No laboratory marker is currently available that can accurately predict a T1R. Increased plasma and tissue expression of inducible nitric oxide synthase (i-NOS) and chemokine CXCL10 have been demonstrated in T1R. We studied the gene expression and immunoexpression of i-NOS, CXCL10 and its receptor CXCR3 in clinically and histopathologically confirmed patients with T1R and compared with non-reactional leprosy patients to understand which biomarker has better potential in distinguishing reaction from non-reaction. Methods: Gene expression of i-NOS, CXCL10 and CXCR3 was studied in 30 skin biopsies obtained from patients with borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) leprosy with and without T1R by real-time PCR. Further validation was done by immunhistochemical expression on 60 borderline leprosy biopsies with and without T1R. Results: Of the 120 patients histopathological evaluation confirmed T1R in 65 (54.2%) patients. CXCR3 gene expression was significantly (P<0.05) higher in BT- and BB-T1R patients compared to those without T1R. The CXCL10 gene expression was significantly higher (P<0.05) in BB leprosy with T1R but the difference was not significant in patients with BT with or without T1R. Immunoexpression for CXCR3 was significant in both BB-T1R and BB (P<0.001) and BT and BT-T1R (P<0.001). Immunoexpression of CXL10 was significant only in differentiating BB from BB-T1R leprosy (P<0.01) and not the BT cases. i-NOS immunoexpression was not useful in differentiating reactional from non-reactional leprosy. Interpretation & conclusions: Both CXCL10 and CXCR3 appeared to be useful in differentiating T1R reaction in borderline leprosy while CXCR3 alone differentiated BT from BT-T1R. CXCR3 may be a potentially useful immunohistochemical marker to predict an impending T1R.

A study exploring attributes and nature of the retracted literature on mental disorders.

This study was aimed at assessing the retracted medical literature on mental disorders. Another aim was to test the hypothesis that the weak research infrastructure in certain countries and the rising pressure to publish in Asia due to the progress of science in that continent may have contributed to the increase in the number of retractions. A bibliometric search was carried out using the PubMed database. The data were analysed using SPSS version 21. The retraction rate for articles on mental disorders (number of retracted articles per 100,000 published articles on mental disorders) varied from a low of 3.56 (for 2005) to a high of 49.25 (for 2012). Of the 38 articles for which the reasons for retraction could be accessed, 10 (26.31%) were retracted for fraud. Overall, 0.0138% of all articles on the biomedical sciences were retracted. Of the articles on mental disorders, 0.0095% were retracted. There was a disproportionately greater number of retractions in the case of articles originating from low- and middle-income countries than high-income countries. Similarly, there was a disproportionately greater number of retractions in the case of articles originating in Asian countries than non-Asian countries.

Copy number polymorphism of glutathione-S-transferase genes (GSTM1 & GSTT1) in susceptibility to lung cancer in a high-risk population from north-east India.

Background & objectives: Genetic polymorphisms in glutathione-S-transferase genes (GSTM1 and GSTT1) have been studied intensively for their potential role in lung cancer susceptibility. However, most of the studies on association between the polymorphisms and lung cancer do not distinguish between genotypes with one or two copies of the genes. The present study investigates the gene dosage effects of GSTT1 and GSTM1 copy number and their environmental interactions to examine the association of lung cancer risk with trimodular genotypes of the GSTs in a high-risk population from north-east India. Methods: A total of 154 lung cancer cases and 154 age and sex matched controls from the high risk region of north-east India were analyzed by multiplex real-time PCR to determine the trimodal genotypes (+/+, +/- and -/-) in both the genes (GSTM1 and GSTT1). Results: No significant association and gene dosage effect of GSTM1 gene copy number with lung cancer risk (Ptrend=0.13) were found. However, absence of GSTT1 conferred 68 per cent (OR=0.32;95%CI=0.15-0.71;P=0.005) reduced risk compared to the two copy number of the gene. tThere was evidence of gene dosage effect of GSTT1 gene (Ptrend=0.006). Tobacco smoking was a major environmental risk factor to lung cancer (OR=3.03;95%CI=1.73-5.31;P<0.001). However, its interaction with null genotype of GSTT1 conferred significant reduced risk to lung cancer (OR=0.30;95%CI=0.10-0.91;P=0.03). Further in only tobacco smokers, null genotype was associated with increased reduced risk [0.03(0.001-0.78)0.03; Ptrend=0.006]. No effect modification of GSTM1 was observed with lung cancer risk by environmental risk factors. Interpretation & conclusions: The results suggest that absence of GSTT1 null genotype may be associated with a reduced risk of lung cancer and the effect remains unchanged after interaction with smoking.

Implication of DNA repair genes in prostate tumourigenesis in Indian males.

Background & objectives: Prostate cancer (CaP) is the fifth most common cancer among Indian men. Tumour protein p53 (TP53) gene increases the fidelity of DNA replication and homologous recombination by transcriptional transactivation of mismatch repair (MMR) genes. DNA repair thus has a potential role in molecular carcinogenesis of CaP. The aim of the present study was to identify mutations, and polymorphisms in TP53 gene and MMR protein expression in CaP in Indian male population. Methods: TP53 codon 72 polymorphism was analysed in 105 CaP, 120 benign prostatic hyperplasia (BPH) cases and 106 normal controls. Mutational analysis of TP53 was done in DNA extracted from formalin fixed paraffin embedded tissue of 80 CaP and 24 BPH cases. Expression of MMR proteins viz. hMLH1, hMSH2, hPMS1 and hPMS2 was studied in 80 CaP, 15 prostatic intraepithelial neoplasia (PIN) and 15 BPH cases. Results: A somatic C/A variation at the intronic boundary of exon 7 in TP53 gene was observed in one each biopsy samples from CaP and BPH. A significant association of codon 72 TP53 Pro/Pro genotype was observed with the risk of CaP (OR, 2.59, P=0.02) and BPH (OR, 6.27, P<0.001). Immunohistochemical analysis of MMR proteins showed maximum loss of hPMS1 expression in cases of CaP and PIN while no loss in expression of MMR proteins was observed in BPH cases. The study also identified a significant loss of hPMS2 protein in poorly differentiated tumours (Gleason score >7) than in well differentiated tumours (Gleason score 3-6) (P<0.05). Interpretation & conclusions: The results of the present study demonstrate that TP53 codon 72 polymorphism plays significant role in the pathogenesis and susceptibility to CaP and BPH. Also, an aberrant MMR protein expression could be involved in progression of prostate cancer through PIN, early CaP to aggressive CaP. The loss of hPMS2 protein expression may serve as a marker for progression of CaP.

Epithelial mesenchymal transition in urothelial carcinoma: Twist in the tale.

Context: Epithelial to mesenchymal transition (EMT) is a process involving conversion of cells from an epithelial to mesenchymal phenotype. The role of candidate genes promoting EMT and favoring a promigratory phenotype has been demonstrated in epithelial cancer. Existing scientific research has not yielded a clinically relevant biomarker with predictive capacity beyond grade and stage in bladder cancer. Aim: The purpose of this study is to evaluate the immunohistochemical expression pattern of a panel of epithelial and mesenchymal markers in paraffin-embedded archival material of primary urothelial carcinoma as evidence of EMT. Materials and Methods: Immunohistochemical expression of transcription factor twist, epithelial (E-cadherin, cytokeratin) and mesenchymal (vimentin, N-cadherin) markers was analyzed on archival paraffin-embedded tissue samples from 48 patients with diagnosis of primary urothelial carcinoma of bladder. Statistical Analysis: Karl Pearson's χ2 test was used to evaluate the association between the expression of immunohistochemical markers and various clinico-pathologic variables. Non-parametric Kendall's tau-b statistics was used to determine the correlation between categorical variables. Results and Conclusion: The study demonstrated statistically significant association of cytokeratin, E-cadherin, vimentin, and twist with stage and grade of bladder cancer. Since these markers form part of the spectrum of changes associated with EMT, the study establishes proof of concept of the existence of this process in vivo. A significant negative correlation was noted between the expression of twist and E-cadherin. Exploiting its role as a transcriptional repressor of E-cadherin, twist may prove to be a useful candidate for targeted therapy in urologic oncology.

Expression of androgen receptor in breast cancer & its correlation with other steroid receptors & growth factors.

Background & objectives: Breast cancer is the second most common malignancy in Indian women. Among the members of the steroid receptor superfamily the role of estrogen and progesterone receptors (ER and PR) is well established in breast cancer in predicting the prognosis and management of therapy, however, little is known about the clinical significance of androgen receptor (AR) in breast carcinogenesis. The present study was aimed to evaluate the expression of AR in breast cancer and to elucidate its clinical significance by correlating it with clinicopathological parameters, other steroid receptors (ER and PR) and growth factors receptors (EGFR and CD105). Methods: Expression of AR, ER, PR, epidermal growth factor receptor (EGFR) and endoglin (CD105) was studied in 100 cases of breast cancer by immunohistochemistry (IHC). Risk ratio (RR) along with 95% confidence interval (CI) was estimated to assess the strength of association between the markers and clinicopathological characteristics. Categorical principal component analysis (CATPCA) was applied to obtain new sets of linearly combined expression, for their further evaluation with clinicopathological characteristics (n=100). Results: In 31 cases presenting with locally advanced breast cancer (LABC), the expression of AR, ER, PR, EGFR and CD105 was associated with response to neoadjuvant chemotherapy (NACT). The results indicated the association of AR+ (P=0.001) and AR+/EGFR- (P=0.001) with the therapeutic response to NACT in LABC patients. The AR expression exhibited maximum sensitivity, specificity and likelihood ratio of positive and negative test. The present results showed the benefit of adding AR, EGFR and CD105 to the existing panel of markers to be able to predict response to therapy. Interpretation & conclusions: More studies on the expression profiles of AR+, AR+/CD105+ and AR+/EGFR- in larger set of breast cancer patients may possibly help in confirming their predictive role for therapeutic response in LABC patients.