Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS

In Situ Synchrotron X-Ray Diffraction Stress Analysis During Laser Surface Line Hardening of Samples with Specific Geometric Features

Multiple in situ X-ray diffraction experiments of temperature controlled laser line hardening processes have been carried out at the German Electron Synchrotron (DESY) in Hamburg, Germany. During the process, the local strain and stress evolution were monitored using synchrotron radiation with a time resolution of 50 Hz with a spatial resolution of less than Ø1 mm. To quantify sample geometry effects on the stress formation and hence the residual stress state in the process zone, different samples with geometric features made of steel grade AISI 4140 were line hardened by means of a high-power diode laser unit using a maximum control temperature of 950 °C at constant laser feed of 0.8 m/min. A specially designed process chamber was used in the experiment, allowing the control of the inert gas atmosphere to avoid surface oxidization. The symmetric application of four fast micro-strip line detectors allows for the real-time measurement of several diffraction lines hkl during the heat treatment process. The thermal and elastic strains were separated and time resolved stress analysis was carried out using a conventional X-ray stress analysis approach. The results were carefully discussed using data obtained by numerical process simulation by finite element method (FEM). It could be shown and explained that geometric features (radii) in the process zone of laser surface line hardening lead to a decrease of resulting residual stresses transverse to the processed workpiece zone

The effects of an acute serotonergic challenge on brain-gut responses in irritable bowel syndrome patients and controls

Summary Background : Serotonin, a key denominator of the brain-gut axis is involved in the regulation of gastrointestinal function as well as cognition, mood and hypothalamic-pituitary-adrenal axis-mediated neuroendocrine responses. Aim : To assess the effects of an acutely increased serotonergic activity, using a 20 mg intravenous citalopram challenge test on visceral perception, affective memory performance, mood and neuroendocrine responses, respectively, in diarrhoea-predominant irritable bowel syndrome patients and controls. Methods : In a randomized, double-blind crossover design, 14 diarrhoea-predominant irritable bowel syndrome patients and 14 matched controls were studied under citalopram and placebo conditions, respectively. Visceral perception was scored in response to rectal distensions. Affective memory performance, mood, levels of adrenocorticotropic hormone, cortisol, prolactin and biochemical parameters of serotonergic metabolism were simultaneously assessed. Results : Visceral perception did not significantly differ between the citalopram and placebo condition. Citalopram administration enhanced affective memory performance because of a bias towards positive material but no significant changes in mood. Citalopram significantly increased plasma serotonin, adrenocorticotropic hormone and cortisol levels compared with placebo. Citalopram did not differentially affect the patient or control group. Conclusions : We have provided evidence that acutely increased serotonergic activity influences neuroendocrine responses and cognition in diarrhoea-predominant irritable bowel syndrome and controls without a significant effect on visceral perception

Arsenic burden from cooked rice in the populations of arsenic affected and nonaffected areas and Kolkata city in west-Bengal, India

Arsenic contamination of rice irrigated with contaminated groundwater contributes to the additional arsenic burden of the population where rice is the staple food. In an arsenic contaminated area, an experimental field-based study done on nine fields elucidated significant positive correlation between arsenic in irrigation water and soil, irrigation water and rice, and also soil and rice both for Boro (groundwater) and Aman (rainwater) rice. Speciation studies showed that for both Boro (cooked) and Aman (raw) rice from contaminated area, 90% of total recovered arsenic was inorganic. In arsenic contaminated, uncontaminated villages, and Kolkata city, daily quantities of arsenic ingested by adult population from cooked rice diet are equivalent to 6.5, 1.8, and 2.3 L, respectively, of drinking water containing WHO guideline value. In contaminated area, daily intake only from cooked Boro rice for 34.6% of the samples exceeded the WHO recommended MTDI value (2 mu g In-As day(-1) kg(-1) body wt), whereas daily intake from Aman rice was below MTDI value as was rice from uncontaminated areas and Kolkata city. Our study indicated that employing traditional rice cooking method as followed in Bengal delta and using water having arsenic <3 mu g L(-1) for cooking, actual exposure to arsenic from rice would be much less

Short-Term Outcomes of Tricuspid Edge-to-Edge Repair in Clinical Practice

Background: Severe tricuspid regurgitation (TR) is known to be associated with substantial morbidity and mortality. Objectives: The authors sought to study the acute outcomes of subjects treated by tricuspid transcatheter edge-to-edge repair with the TriClip system (Abbott) in a contemporary, real-world setting. Methods: The bRIGHT (An Observational Real-World Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip™ Device) postapproval study is a prospective, single-arm, open-label, multicenter, postmarket registry conducted at 26 sites in Europe. Echocardiographic assessment was performed at a core laboratory. Results: Enrolled subjects were elderly (79 ± 7 years of age) with significant comorbidities. Eighty-eight percent had baseline massive or torrential TR, and 80% of subjects were in NYHA functional class III or IV. Successful device implantation occurred in 99% of subjects, and TR was reduced to ≤moderate at 30 days in 77%. Associated significant improvements in NYHA functional class (I/II, 20% to 79%; P &lt; 0.0001) and Kansas City Cardiomyopathy Questionnaire score (19 ± 23 points improvement; P &lt; 0.0001) were observed at 30 days. With baseline TR grade removed as a variable, smaller right atrial volume and smaller tethering distance at baseline were independent predictors of TR reduction to ≤moderate at discharge (OR: 0.679; 95% CI: 0.537-0.858; P = 0.0012; OR: 0.722; 95% CI: 0.564-0.924; P = 0.0097). Fourteen subjects (2.5%) experienced a major adverse event at 30 days. Conclusions: Transcatheter tricuspid valve repair was found to be safe and effective in treating significant TR in a diverse, real-world population. (An Observational Real-World Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip™ Device [bRIGHT]; NCT04483089