Shared and unique common genetic determinants between pediatric and adult celiac disease

Table S1. Functional profiles of the top non-HLA association signals identified in Paediatric CD and Adult CD among north Indians. Table S2. Test of heterogeneity (Breslow-Day test) for associated SNPs in PaediatricCD and AdultCD groups. Table S3. cis-eQTL evaluation of associated SNPs. Table S4. GRAIL analysis revealed seven genes with significant (p <0.05) interaction with 39 known non-HLA coeliac disease loci. These seven genes are from four loci identified in this study. (DOCX 26 kb

How sustained is sustained viral response in patients with hepatitis C virus infection?

Abstract Background Sustained virological response (SVR) is achieved in a high proportion of patients with chronic hepatitis C infection, particularly those with genotype 2 or 3 HCV infection. However, data on long-term durability of virological response in patients who achieve SVR are limited. Aim To evaluate the long-term durability of virological response in patients who have achieved SVR with interferon-based combination therapy. Methods One hundred patients with chronic HCV infection who had obtained SVR after IFN and ribavirin combination therapy were followed up for up to 8 years with annual HCV RNA testing. Results During a followed up of 6 months to 8 years, 8 of 100 patients with initial SVR developed late relapse of HCV infection. Relapse was more common in patients who had cirrhosis (5/28 [18%] vs. (3/72 [4%] with no cirrhosis; p=0.037). Conclusion SVR is durable in most patients, but some patients do have late relapse; long term follow up may be particularly important in a subset of patients with HCV infection who have liver cirrhosis

Impact of “Sambhav” Program (Financial Assistance and Counselor Services) on Hepatitis C Pegylated Interferon Alpha Treatment Initiation in India

Abstract Background: Financial constraints, social taboos and beliefs in alternative medicine are common reasons for delaying or not considering treatment for hepatitis C in India. The present study was planned to analyze the impact of non-banking interest free loan facility in patients affected with hepatitis C virus (HCV) in North India. Methods: This one year observational, retrospective study was conducted in Department of Gastroenterology (January 2012-December 2013), Dayanand Medical College and Hospital Ludhiana, to evaluate the impact of program titled “Sambhav” (which provided non-banking financial assistance and counselor services) on treatment initiation and therapeutic compliance in HCV patients. Data of fully evaluated patients with chronic hepatitis, and/or cirrhosis due to HCV infection who were treated with Peginterferon alfa and ribavirin (RBV) combination during this duration (2012- 2013) was collected from patient medical records and analyzed. In the year 2012, eligible patients who were offered antiviral treatment paid for treatment themselves, while in 2013, ‘Sambhav’ program was launched and this provided interest free financing by non-banking financial company (NBFC) for the treatment of HCV in addition to free counselor services for disease management. The treatment initiation and compliance rates were compared between the patients (n = 585) enrolled in 2013 who were offered ‘Sambhav’ assistance and those enrolled in 2012 (n = 628) when ‘Sambhav’ was not available. Results: Introduction of Sambhav program improved the rates of treatment initiation (59% in 2013 vs. 51% in 2012, P=.004). Of the 585 eligible patients offered ‘Sambhav’ assistance in 2013, 233 patients (39.8%) applied but 106/233 (45.4%) received assistance. Antiviral therapy was started in 93/106 (87.7%) of these patients, while only 52 (42.5%) of 127 patients whose applications were rejected underwent treatment. Compliance to antiviral therapy also improved with the introduction of ‘Sambhav’ program (87.7% vs. 74.1%, P=.001). Conclusion: ‘Sambhav’ program had significant impact on the initiation of antiviral therapy by overcoming the financial hurdles. The free counselor services helped to mitigate social taboos and imparted adequate awareness about the disease to the patients. Initiatives like ‘Sambhav’ can be utilized for improving healthcare services in developing countries, especially for chronic diseases

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis

Background/Aims Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal

Variable Immunogenic Potential of Wheat: Prospective for Selection of Innocuous Varieties for Celiac Disease Patients via in vitro Approach

Celiac Disease (CD) is a multifactorial, autoimmune enteropathy activated by cereal proteins in genetically predisposed individuals carrying HLA DQ2/8 genes. A heterogenous gene combination of the cereal prolamins is documented in different wheat genotypes, which is suggestive of their variable immunogenic potential. In the current study, four wheat varieties (C591, C273, 9D, and K78) identified via in silico analysis were analyzed for immunogenicity by measuring T-cell proliferation rate and levels of inflammatory cytokines (Interferon-γ and Tumor Necrosis Factor-α). Peripheral Blood Mononuclear Cells and biopsy derived T-cell lines isolated from four CD patients in complete remission and two controls were stimulated and cultured in the presence of tissue transglutaminase activated pepsin-trypsin (PT) digest of total gliadin extract from test varieties. The immunogenicity was compared with PBW 621, one of the widely cultivated wheat varieties. Phytohaemagglutinin-p was taken as positive control, along with unstimulated cells as negative control. Rate of cell proliferation (0.318, 0.482; 0.369, 0.337), concentration of IFN- γ (107.4, 99.2; 117.9, 99.7 pg/ml), and TNF- α (453.8, 514.2; 463.8, 514.2 pg/ml) was minimum in cultures supplemented with wheat antigen from C273, when compared with other test varieties and unstimulated cells. Significant difference in toxicity levels among different wheat genotypes to stimulate celiac mucosal T-cells and PBMC's was observed; where C273 manifested least immunogenic response amongst the test varieties analyzed

Use of thiopurines in inflammatory bowel disease : an update

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.Peer reviewe

An Investigation of Genome-Wide Studies Reported Susceptibility Loci for Ulcerative Colitis Shows Limited Replication in North Indians

Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci

Treatment of chronic hepatitis C genotype 1 early responders with 36 week pegylated interferon and ribavirin therapy

Introduction. Standard treatment for patients with chronic hepatitis C genotype 1 (CHC G-1) infection includes pegylated interferon plus ribavirin (PEG-RBV) for 48 weeks. Shorter treatment regimen would be more acceptable due to lower cost and fewer side-effects. We aimed to compare the efficacy of 36 week PEG-RBV therapy with standard 48 week therapy in CHC G-1 patients who achieve complete early virological response (cEVR).Material and methods. Consecutive treatment-naïve patients with CHC G-1 were treated with pegylated interferon a2b (1.5 μg/kg/week) or α2a (180 μg/week) and weight based ribavirin. Patients who achieved cEVR at 12 weeks [undetectable HCV RNA irrespective of RVR (rapid virological response)] were randomized into- group A (48 weeks therapy) and group B (36 weeks therapy). Primary end-point was achievement of sustained virological response (SVR) at 24 weeks of follow up.Results. Out of the total 166 patients started on treatment, 112 (69.3%) achieved cEVR, and were randomized into group A (n = 59) and group B (n = 53). Fifty-five (93.2%) patients in group A and 50 (94.3%) in group B completed therapy. The overall SVR rate in group A was 79.6% (47/59) and group B was 84.9% (45/53) (p = 0.622). SVR rates in the two groups were comparable in all patient sub-groups according to factors like viral load (≤ or > 400,000 IU/mL), RVR (achieved/not achieved), age (≤ or > 40 years), body mass index (≤ or > 27) and cirrhosis (present/absent).Conclusion. In CHC G-1 patients who achieve cEVR, 36 weeks PEG-RBV therapy is as effective as standard 48 weeks therapy, irrespective of other host or virological factors

A preliminary report on physical activity patterns among children aged 8–14 years to predict risk of cardiovascular diseases in Malwa region of Punjab

Objective: To determine the pattern of physical activity specific to age and gender among young Indian school going girls and boys aged 8-14 years. Design: Cross-sectional study. Setting: Private and government sponsored schools in Patiala and Mansa District of Punjab, India. Participants: Two hundred thirty four school going girls and boys aged 8–14 years. Methodology: A structured questionnaire recorded the various forms of daily physical activity, sedentary activity as well as physical activity level of all the participants. The energy expenditure was also calculated using the standard metabolic equivalent index. Results: There is a significant difference between mean weights of participants belonging to different physical activity levels (p < .04). In comparison to boys, the girl participants have significant lower values of physical activity duration as well as total metabolic equivalent expenditure (p < .05). The total duration of moderate/vigorous physical activity declined in both girls and boys as the age increased. Conclusion: Physical activity among children in Northern regions of India is on decline as their age increases especially among girls. It is important to determine physical activity duration in early age groups and motivate children for daily physical activity. Keywords: Daily physical activity, MET expenditure, Cardio vascular risk factors, Gender, Growth factor

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Not AvailableA field experiment was conducted during the kharif season of 2007 at Agronomy Research Farm, Chaudhary Charan Singh Haryana Agricultural University, Hisar to study the effect of crop geometry and nitrogen levels on growth and yield of newly develop pearl millet hybrid HHB197. Four spacing patterns viz., 45 x 12, 45 x 16, 60 x 12 and 60 x 16 cm and five nitrogen levels viz., control, 40, 80, 120 and 160 kg N ha-1 tested in factorial randomized block design (FRBD) with three replications. Plant growth in terms of height, dry matter accumulation plant-1, leaf area plant-1 increased significantly with increase in spacing at most of the stages of observations. Similarly, yield attributing characters like effective tillers plant-1, 1000 grain weight, length of earhead and girth of earhead increased significantly with increase in spacing.Not Availabl