Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Translation and Validation of the Chinese Diabetic Foot Ulcer Scale - Short Form

Background: The need to assess quality of life (QOL) in patients with a diabetic foot ulcer (DFU) has been well documented. However, no appropriate instrument was available for the Chinese population. Objective: The Diabetic Foot Ulcer Scale - Short Form (DFS-SF) is a reliable and valid 29-item instrument comprising six scales, which is used for assessing QOL in patients with DFU. This study aimed to translate the DFS-SF into Chinese and evaluate its psychometric performance. Methods: The Chinese DFS-SF went through the full linguistic validation process and was evaluated in 60 Hong Kong Chinese patients with current or healed DFU. Results: The internal consistency of all scales of the Chinese DFS-SF was consistently high (Cronbach's alpha ranged from 0.8 to 0.92). Item convergent and discriminant validity was satisfactory (median corrected item-scale correlation ranged from 0.63 to 0.84). Moreover, the instrument also demonstrated good construct validity when correlated with the SF-36. Sensitivity was shown between patients with healed DFU and those whose DFU was not healed, those with different types of foot ulcer, those with different Wagner grade, and those with differing episodes of DFU. Conclusions: The newly translated Chinese DFS-SF may be used to assess the impact of DFU in Chinese patients.Diabetic-foot-ulcer, Quality-of-life

Audit on the Hong Kong renal registry data accuracy: A single center perspective

Objective: The Hong Kong Renal Registry is a direct online computerized registry, and one of its functions is to serve as a clinical database for individual renal centers. Currently, we rely on clinical staff for data entry in our center. Integrity and accuracy of the data are important for analyzing patients on renal replacement therapy. The objective of this study was to perform an audit program on the accuracy of the renal registry data on existing renal replacement therapy patients. Methods: A total of 376 patients (268 peritoneal dialysis, 50 hemodialysis, and 58 post-transplanted patients) were on the renal replacement therapy registry of United Christian Hospital as of June 30, 2001. Approximately 10% of the patients (total 36 patients: 25 peritoneal dialysis, 5 hemodialysis, and 6 posttransplanted patients) were randomly selected for audit. We wanted to identify whether the data were being entered accurately, inaccurately, or not entered. Subgroup analyses on different registry categories and comparison between essential and nonessential data were performed. Results: We examined 3287 data items (2153 essential and 1134 nonessential). The overall rate of accurate data entry was 81%, the rate of inaccurate data entry was 4%, and missed data entry was 15%. The most frequent accurately entered data were "hemodialysis treatment" (96%) and "conservative treatment" (100%) under the category of "treatment/outcome"; the most frequent inaccurately entered data were "access complication" (17%) under the category of "complication." The most frequently missing essential data were "exit site infection" (40%) and "peritonitis" under the category of "complication." Conclusion: This audit program identifies the areas for improvement in data entry in the renal registry.link_to_subscribed_fulltex

S-Adenosylmethionine and Methylthioadenosine Inhibit Cellular FLICE Inhibitory Protein Expression and Induce Apoptosis in Colon Cancer Cells

S-Adenosylmethionine (SAMe) and its metabolite 5′-methylthioadenosine (MTA) inhibit mitogen-induced proliferative response in liver and colon cancer cells. SAMe and MTA are also proapoptotic in liver cancer cells by selectively inducing Bcl-xS expression. The aims of this work were to assess whether these agents are proapoptotic in colon cancer cells, and if so, to elucidate the molecular mechanisms. We found that both SAMe and MTA are proapoptotic in HT-29 and RKO cells in a dose- and time-dependent manner. Gene microarray uncovered down-regulation of cellular FLICE inhibitory protein (cFLIP). SAMe and MTA treatment led to a decrease in the mRNA and protein levels of both the long and short cFLIP isoforms. This required de novo RNA synthesis and was associated with activation of procaspase-8, Bid cleavage, and release of cytochrome c from the mitochondria. Inhibiting caspase 8 activity or overexpression of cFLIP protected against apoptosis, whereas supplementing with polyamines did not. SAMe and MTA treatment sensitized RKO cells to tumor necrosis factor α-related apoptosis-inducing ligand-induced apoptosis. Although SAMe and MTA are proapoptotic in colon cancer cells, they have no toxic effects in NCM460 cells, a normal colon epithelial cell line. In contrast to liver cancer cells, SAMe and MTA had no effect on Bcl-xS expression in colon cancer cells. In conclusion, SAMe and MTA are proapoptotic in colon cancer cells but not normal colon epithelial cells. One molecular mechanism identified is the inhibition of cFLIP expression. SAMe and MTA may be attractive agents in the chemoprevention and treatment of colon cancer

Genetic effects of multiple asthma loci identified by genomewide association studies on asthma and spirometric indices

Background: Genomewide association study (GWAS) published by GABRIEL consortium identified 10 asthma-associated loci. However, their relationship with lung functions is unclear. This study investigated the association between asthma traits and single-nucleotide polymorphisms (SNPs) of these GWAS loci. Methods: Rs3894194 and rs9273349 were not genotyped due to unavailable TaqMan assays. Genetic associations of remaining eight SNPs were investigated in 903 school-age asthmatics and 1205 non-allergic controls. Four significant SNPs were then replicated in 479 adult asthmatics and 746 adult controls, and 1341 Chinese preschool children. Meta-analyses were performed by combining data from school-age children and adults. Generalized multifactor dimensionality reduction (GMDR) was used to analyze their interactions for asthma traits. Results: Childhood asthma was associated with GSDMB_rs2305480 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57–0.83). IL13_rs1295686 was associated with all asthma (OR 1.64, 95% CI 1.16–2.32) and early-onset asthma (OR 1.92, 95% CI 1.20–3.06) in adults, whereas GSDMB_rs2305480 was only associated with early-onset asthma (OR 0.69, 95% CI 0.49–0.96). According to meta-analyses, the minor allele of rs2305480 was inversely associated with FEV1, FVC, and FEV1/FVC (p \u3c 0.01). GMDR analyses revealed 2-locus models of SLC22A5 with SMAD3 to modulate FEVt/FVC in both preschool children and adults, with IL13 to determine FVC in both school-age children and adults, and with IL2RB to modulate FEV1/FVC in school-age children. Conclusions: IL13 and GSDMB are replicated as asthma genes. Rs2305480 of GSDMB is also associated with low FEV1, FVC, and FEV1/FVC among asthmatics. Moreover, SLC22A5, IL13, SMAD3, and GSDMB interact to modulate spirometric indices

Epidemiology and Relative Severity of Influenza Subtypes in Singapore in the Post-Pandemic Period from 2009 to 2010

10.1093/cid/cix694CLINICAL INFECTIOUS DISEASES65111905-191

Health-related quality of life among patients with moderate-to-severe plaque psoriasis in Taiwan

Background/Objectives: Plaque psoriasis is a debilitating condition that significantly affects patient well-being. Limited data are available regarding the effect of psoriasis and treatment on health-related quality of life (HRQoL) and work ability among Taiwanese patients.To document and compare HRQoL, treatment satisfaction, and work disability among Taiwanese patients with current and past moderate-to-severe plaque psoriasis. Methods: This was a multicenter, non-interventional, cross-sectional study of adult patients with moderate-to-severe plaque psoriasis. During a single clinic visit, each patient was assessed for body surface area (BSA) involvement, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), Euro Quality of Life-5 Dimensions (EQ-5D), 10-level satisfaction scale for psoriasis treatment, and Working Productivity and Activity Impairment (WPAI). Multivariate regression was used to identify factors associated with HRQoL and work disability. Results: A total of 305 patients were included within the analysis. The mean PASI score was 11.83, and the mean BSA involvement was 20.90%. The mean EQ-5D score was 65.68 and the mean DLQI score was 12.55. Fewer than half of patients (45.68%) indicated they were satisfied with the standard therapy they were currently receiving. Among employed patients, the mean reduction in on-the-job effectiveness was 32.09% and the mean reduction in overall productivity was 33.48%. The regression analysis indicated that patients with more severe psoriasis defined by PASI scores show a greater impact in quality of life and impairment in work disability; and that patients who were satisfied with current standard treatment had a better quality of life. Conclusion: The effect of psoriasis on HRQoL among patients with psoriasis in Taiwan is substantial, with fewer than half of patients reporting satisfaction with therapeutic options. Keywords: DLQI, EQ-5D, Health-related quality of life, Psoriasis, WPA