Modeling techniques for analysing conformational transitions in hemocyanins by small-angle scattering of X-rays and neutrons.

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…

DHCR_OST-Cannabis_Alcohol_supplementary_2018-10-30_xyz151015746ed84_3-converted – Supplemental material for Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy—Data From the German Hepatitis C-Registry (DHC-R)

Supplemental material, DHCR_OST-Cannabis_Alcohol_supplementary_2018-10-30_xyz151015746ed84_3-converted for Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy—Data From the German Hepatitis C-Registry (DHC-R) by Stefan Christensen, Peter Buggisch, Stefan Mauss, Klaus HW Böker, Tobias Müller, Hartwig Klinker, Tim Zimmermann, Yvonne Serfert, Bernd Weber, Jens Reimer and Heiner Wedemeyer in Substance Abuse: Research and Treatment

Treatment outcomes in hepatitis C virus genotype 1a infected patients with and without baseline NS5A resistance‐associated substitutions

Background&aims The presence of baseline resistance-associated substitutions (RASs) reduced sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) genotype 1a infected patients treated with Elbasvir/Grazoprevir (EBR/GZR). This study aimed to evaluate the frequency of NS5A RASs and treatment outcomes in patients for whom EBR/GZR was intended. Methods We sequenced NS5A in 832 samples from German genotype1a-infected DAA-naive patients population-based, which were collected in the European Resistance Database. Treatment outcomes and clinical parameters were evaluated in 519 of these patients retrospectively. Results Overall, 6.5% of patients harbored EBR-specific NS5A RASs …

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci sh…

Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients

Background & aims AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyse the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real-world cohort. Methods A retrospective analysis of the DHC-R (Deutsches Hepatitis C-Register, German Hepatitis C-Registry) coh…

Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations

Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…

Alcohol and Cannabis Consumption Does Not Diminish Cure Rates in a Real-World Cohort of Chronic Hepatitis C Virus Infected Patients on Opioid Substitution Therapy-Data From the German Hepatitis C-Registry (DHC-R).

Background: The importance of alcohol and cannabis consumption for the effectiveness of treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) in people on opioid substitution therapy (OST) has not been investigated in detail. Methods: We investigated sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST (n = 739) and non-OST patients (n = 7008) in the German Hepatitis C-Registry (Deutsches Hepatitis C-Register, DHC-R), which is a national multicenter prospective non-interventional real-world registry. Non-OST patients comprised patients with former/current drug use (non-OST/DU; n = 1500) and patients never con…

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.

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Evolution of HCV patient characteristics and DAA regimens in the German Hepatitis C Registry (DHC-R) in 2014 and 2015

 The urgent need in HCV-infected patients with liver disease mandated the rapid implementation of IFN-free DAA combination therapies following their regulatory approval in 2014 and 2015 without full knowledge of the optimal combinations and regimens. Investigating the evolution of the DAA utilization patterns and treatment outcomes could provide learnings for future situations. This was an analysis of a prospective observational database from the German Hepatitis C Registry (DHC-R) covering a period from May 2014 to September 2015. Adult patients had evidence of chronic HCV GT1 or GT4 infection and were treated with an IFN-free combination regimen of simeprevir (SMV) + sofosbuvir (SOF) or o…

Caractérisation de transporteurs impliqués dans l´absorption et le transfert de composés carbonés et azotés au sein de la symbiose ectomycorhizienne entre Hebeloma cylindrosporum et Pinus pinaster

National audience; La mycorhize est une association entre les racines des plantes et les champignons; elle existerait chez 95 p. cent de toutes les plantes à fleurs et à graines. Chez la plante, elle augmente sa capacité d'absorber les minéraux essentiels et sa résistance aux maladies des racines. Celle-ci en échange alimente le champignon en glucides issus de la photosynthèse. Le transport des nutriments de la solution du sol aux racines de la plante est la résultante de trois composantes, l’une située à l’interface sol-champignon et les deux autres localisées à l’interface champignon-plante qui régulent également le transfert dans le sens plante-champignon. Pour mieux comprendre les inter…

Resistance-associated substitutions in patients with chronic hepatitis C virus genotype 4 infection

Data on the prevalence of resistance-associated substitutions (RASs) and their implications for treatment with direct-acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4-infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA-naive patients (5%) and the number of NS5A RASs was significantly highe…

Neuronal and Behavioral Correlates of Health Anxiety: Results of an Illness-Related Emotional Stroop Task

<b><i>Background:</i></b> Health anxiety (HA) is defined as the objectively unfounded fear or conviction of suffering from a severe illness. Predominant attention allocation to illness-related information is regarded as a central process in the development and maintenance of HA, yet little is known about the neuronal correlates of this attentional bias. <b><i>Methods:</i></b> An emotional Stroop task with body symptom, illness, and neutral words was employed to elicit emotional interference in healthy participants with high (HA+, n = 12) and low (HA–, n = 12) HA during functional magnetic resonance imaging. <b><i>Results:</i>…

Epigenetic dysregulation in the developing Down syndrome cortex

Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3–11 times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methyl…

Impact of socio-economic position on cancer stage at presentation: Findings from a large hospital-based study in Germany

We explored the relationship between socio-economic characteristics and cancer stage at presentation. Patients admitted to a university hospital for diagnosis and treatment of cancer provided data on their education, vocational training, income, employment, job, health insurance and postcode. Tumor stage was classified according to the Union International Contre le Cancer (UICC). To analyze disparities in the likelihood of late-stage (UICC III/IV vs. I/II) diagnoses, logistic regression models adjusting for age and gender were used. Out of 1,012 patients, 572 (59%) had late-stage cancer. Separately tested, increased odds of advanced disease were associated with post-compulsory education com…