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Background: The need for effective and accepted method for opioid detoxification is ever increasing. Sublingual buprenorphine and oral clonidine have been effective in opioid detoxification. As often, there is a great variation in the dosage of buprenorphine and clonidine prescribed by the clinicians; hence, there is a felt need to find an effective dosage for a favorable outcome of opioid detoxification. Objective: The objective of this study was to compare the effectiveness of different doses of sublingual buprenorphine and clonidine in opioid detoxification. Materials and Methods: A total of 100 patients with the diagnosis of opioid dependence as per the international classification of diseases-10 criteria were recruited for this study. Participants were assigned randomly into four groups – low-dose clonidine, high-dose clonidine, low-dose sublingual buprenorphine, and high sublingual dose buprenorphine using a computer-generated random number table, resulting in 25, 26, 23, and 26 patients in each group, respectively. Results: The four groups had comparable scores on all the items of “stages of change readiness and treatment eagerness scale” for the assessment of motivation at baseline. Progressive decrease in withdrawal score was seen in all the groups on “clinical opiate withdrawal scale” and “subjective opiate withdrawal scale.” Conclusion: From the current study, we can infer that both low and high doses of buprenorphine and clonidine are comparable regarding controlling withdrawal. [ABSTRACT FROM AUTHOR]

Chronic iron overload results in heart and liver diseases and is a common cause of morbidity and mortality in patients with genetic hemochromatosis and secondary iron overload. We investigated the role of tissue inhibitor of metalloproteinase 3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking Timp3 (Timp3-/-) and wild-type (WT) mice to 12 wk of chronic iron overload. Whereas WT mice with iron overload developed diastolic dysfunction, iron-overloaded Timp3-/- mice showed worsened cardiac dysfunction coupled with systolic dysfunction. In the heart, loss of Timp3 was associated with increased myocardial fibrosis, greater Timp1, matrix metalloproteinase (Mmp)2, and Mmp9 expression, increased active MMP-2 levels, and gelatinase activity. Iron overload in Timp3-/- mice showed twofold higher iron accumulation in the liver compared with WT mice because of constituently lower levels of ferroportin. Loss of Timp3 enhanced the hepatic inflammatory response to iron overload, leading to greater neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL-1β and monocyte chemoattractant protein-1) was elevated to a greater extent in iron-overloaded Timp3-/- livers. Gelatin zymography demonstrated equivalent increases in MMP-2 and MMP-9 levels in WT and Timp3-/- iron-overloaded livers. Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and liver injury, suggesting that Timp3 is a key protective molecule against iron-mediated pathology. [ABSTRACT FROM AUTHOR]

The main purpose of the study was to find out the factors of residence area, income and education in geriatric mental state and their abilities. The study was conducted at Department of Psychiatry, Government Medical College and Hospital, Chandigarh. All the participants were administered: 1. HMSE and 2. EASI to assess their mental state and daily living activities. The result found gender, residence areas and income were not the strong significant influencing factors of cognitive function and their abilities. Many other factors may be involved in determining geriatric mental status and their abilities. [ABSTRACT FROM AUTHOR]

Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Depression is common among diabetes, and is associated with poor outcomes. However, the data on this important relationship are limited from India. Objective: The aim was to estimate the prevalence of depression in patients with diabetes and to determine the association of depression with age, sex, and other related parameters. Materials and Methods: The study was cross-sectional carried out in endocrinology clinic of tertiary care hospital in North India. Cases were patients with type 2 diabetes mellitus (T2DM) above 30 years of age. Depression was assessed using the patient health questionairre-9 (PHQ-9). The relationship with sociodemographic profile, duration of diabetes, hypertension and microvascular complications was also analyzed. Results: Seventy-three subjects (57.5% females) with mean age 50.8 ± 9.2 years were evaluated. The prevalence of depression was 41%. Severe depression (PHQ score ≥15) was present in 3 (4%) subjects, moderate depression (PHQ score ≥10) in 7 (10%) subjects, and mild depression was present in 20 (27%) of subjects. Depression was significantly more prevalent in rural subjects (57%) when compared to urban ones (31%, P = 0.049). Depression increased with presence of microvascular complications, fasting plasma glucose, hypertension, but the differences were not statistically significant. Conclusions: Our study demonstrates higher prevalence of depression in patients with type 2 diabetes. Apart from being belonging to the rural area, no other factor was significantly associated with depression. Therefore, depression should be assessed in each and every patient, irrespective of other factors. [ABSTRACT FROM AUTHOR]

Context: Attitude of fresh graduates toward psychiatric patients is important to bridge the treatment gap due to mental illness. Psychiatry as a subject has been neglected in the undergraduates of MBBS. Aims: (1) To compare the attitude of medical students and interns in a medical college toward mental illness and psychiatry. (2) To assess the impact of psychiatric training on attitude toward the mentally ill person and mental illness. Settings and Design: Cross-sectional, single assessment study conducted at a tertiary hospital. Subjects and Methods: Participants consisted of medical students of 1st and 2nd year who didn't have any exposure to psychiatry and interns, who had completed their compulsory 2 week clinical posting in psychiatry. Participants were individually administered sociodemographic proforma, General Health Questionnaire-12 (GHQ-12), opinion about mental illness (OMI) scale, and attitude to psychiatry-29 (ATP-29) scale. Statistical Analysis: Standard descriptive statistics (mean, percentage), Chi-square test. Results: A total of 135 participants formed the study sample, with 48, 47, and 40 participants from 1st year, 2nd year and interns, respectively. Mean GHQ score was 14.03 for the entire sample. There was better outlook of interns toward psychiatry and patients with mental disorders in comparison to fresh graduate students in some areas. Overall, negative attitude toward mental illness and psychiatry was reflected. Conclusions: Exposure to psychiatry as per the current curriculum seems to have a limited influence in bringing a positive change in OMI and psychiatry. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is the most common cause of end-stage renal disease. Polymorphism in the tissue inhibitor of metalloproteinase-3 (TIMP3) gene, and the ECM-bound inhibitor of matrix metalloproteinases (MMPs), has been linked to diabetic nephropathy in humans. To elucidate the mechanism, we generated double mutant mice in which the TIMP3 gene was deleted in the genetic diabetic Akita mouse background. The aggravation of diabetic injury occurred in the absence of worsening of hypertension or hyperglycemia. In fact, myocardial TIMP3 levels were not affected in Akita hearts, and cardiac diastolic and systolic function remained unchanged in the double mutant mice. However, TIMP3 levels increased in Akita kidneys and deletion of TIMP3 exacerbated the diabetic renal injury in the Akita mouse, characterized by increased albuminuria, mesangial matrix expansion, and kidney hypertrophy. The progression of diabetic renal injury was accompanied by the upregulation of fibrotic and inflammatory markers, increased production of reactive oxygen species and NADPH oxidase activity, and elevated activity of TNF-α-converting enzyme (TACE) in the TIMP3-/-/Akita kidneys. Moreover, while the elevated phospho-Akt (S473 and T308) and phospho-ERK1/2 in the Akita mice was not detected in the TIMP3-/-/Akita kidneys, PKCβ1 (but not PKCα) was markedly elevated in the double mutant kidneys. Our data provide definitive evidence for a critical and selective role of TIMP3 in diabetic renal injury consistent with gene expression findings from human diabetic kidneys. [ABSTRACT FROM AUTHOR]

An epithelial-to-mesenchymal transition (EMT) phenotype with cancer stem cell-like properties is a critical feature of aggressive/metastatic tumors, but the mechanism(s) that promote it and its relation to metabolic stress remain unknown. Here we show that Collapsin Response Mediator Protein 2A (CRMP2A) is unexpectedly and reversibly induced in cancer cells in response to multiple metabolic stresses, including low glucose and hypoxia, and inhibits EMT/stemness. Loss of CRMP2A, when metabolic stress decreases (e.g., around blood vessels in vivo) or by gene deletion, induces extensive microtubule remodeling, increased glutamine utilization toward pyrimidine synthesis, and an EMT/stemness phenotype with increased migration, chemoresistance, tumor initiation capacity/growth, and metastatic potential. In a cohort of 27 prostate cancer patients with biopsies from primary tumors and distant metastases, CRMP2A expression decreases in the metastatic versus primary tumors. CRMP2A is an endogenous molecular brake on cancer EMT/stemness and its loss increases the aggressiveness and metastatic potential of tumors. [Display omitted] • CRMP2A is reversibly induced in response to diverse metabolic stressors • CRMP2A induction prevents acquisition of an energetically demanding EMT/stem cell state • Loss of CRMP2A when metabolic stress is reversed promotes EMT/stemness in cancer CRMP2A, a microtubule-associated protein, plays an unexpected role in the regulation of the EMT/stemness propensity of cancer cells. Boukouris et al. show how, in response to multiple metabolic stresses, changes in the relative levels of total and phosphorylated CRMP2A induce a reversible microtubule/cytoskeletal and metabolic remodeling, promoting EMT/stemness, migration, metastasis, and chemoresistance. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization Disability Assessment Schedule-2.0 (WHODAS 2.0) is a disability assessment instrument which is based on the conceptual framework of the International Classification of Functioning, Disability, and Health. It provides a global measure of disability and it has seven domains-specific scores. Objective: The present study aims to check the concordance among the patient, proxy, and clinician-rated versions of WHODAS 2.0 in India. Materials and Methods: This study was cross-sectional and comparative in nature. Sixty samples of patients with severe mental illness (SMI) were selected using a consecutive sampling procedure as per the International Classification of Diseases (ICD-10) criteria. Using patient, proxy, and clinician administrative version of WHODAS 2.0, the study was conducted at the outpatient department of Mental Health Institute and Department of Psychiatry, Government Medical College and Hospital Sector 32, Chandigarh, India. Patients diagnosed with SMI as per the ICD-10 aged above 18 years of age with a total duration of illness of at least more than 2 years were included. Those who refused to participate were excluded. The data were analyzed using the SPSS software. The normality of quantitative data was checked by the measures of Kolmogorov-Smirnov tests of normality. The continuous data were reported as mean ± standard deviation. The categorical variables were reported as counts and percentages. The group comparisons were made with the help of ANOVA test. Results: This study included 60 patients with SMI, and the results show that there was no significant difference found among the patient, proxy, and clinician's assessment for most items, but the mean score of the clinician-rated version score (68.733) was higher in comparison to patient- and proxy-rated versions of WHODAS 2.0. Conclusion: The overall inter-reliability of WHODAS 2.0 among the patients, proxy, and clinician was moderate. There was no significant difference among the patient, proxy, and clinician's assessments for most items. This highlights the fact that one does not have to rely on professionals' ratings for assessing the disability among patients with SMI. [ABSTRACT FROM AUTHOR]