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PurposeDiarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disorder. Probiotics and synbiotics have been shown to improve symptoms of IBS, although mechanisms of action are currently not understood.MethodsWe investigated the effects of a 4-week oral synbiotic treatment (OMNi-BiOTiC® Stress Repair) in ten IBS-D patients on gastrointestinal mucosal and fecal microbiota, mucosa-associated immune cells, and fecal short-chain fatty acids. The upper and lower gastrointestinal tracts were compared before and after a 4-week synbiotic treatment using endoscopic evaluation to collect mucosal specimens for FACS analysis and mucosal 16S rRNA gene analysis. In stool samples, analysis for fecal SCFAs using GC–MS, fecal zonulin using ELISA, and fecal 16S rRNA gene analysis was performed.ResultsSynbiotics led to an increased microbial diversity in gastric (p = 0.008) and duodenal (p = 0.025) mucosal specimens. FACS analysis of mucosal immune cells showed a treatment-induced reduction of CD4+ T cells (60 vs. 55%, p = 0.042) in the ascending colon. Short-chain fatty acids (acetate 101 vs. 202 µmol/g; p = 0.007) and butyrate (27 vs. 40 µmol/g; p = 0.037) were elevated in fecal samples after treatment. Furthermore, treatment was accompanied by a reduction of fecal zonulin concentration (67 vs. 36 ng/ml; p = 0.035) and disease severity measured by IBS-SSS (237 vs. 54; p = 0.002).ConclusionsOur findings indicate that a short-course oral synbiotic trial may influence the human gastrointestinal tract in IBS-D patients on different levels which are region specific.Electronic supplementary materialThe online version of this article (10.1007/s00394-018-1826-7) contains supplementary material, which is available to authorized users.

Abstract-Mechanical impedance modulation is the key to natural, stable and efficient human locomotion. An improved understanding of this mechanism is necessary for the development of the next generation of intelligent prosthetic and orthotic devices. This paper documents the design methodologies that were employed to realize a knee perturbator that can experimentally estimate human knee impedance during gait through the application of angular velocity perturbations. The proposed experiment requires a light, transparent, wearable, and remotely actuated device that closely follows the movement of the biological joint. A genetic algorithm was used to design a polycentric hinge whose instantaneous center of rotation is optimized to be kinematically compatible with the human knee. A wafer disc clutch was designed to switch between a high transparency passive mode and a high impedance actuated mode. A remote actuation and transmission scheme was designed to enable high power output perturbations while minimizing the device's mass. Position and torque sensors were designed for device control and to provide data for post-processing and joint impedance estimation. Pending the fabrication and mechanical testing of the device, we expect this knee perturbator to be a valuable tool for experimental investigation of locomotive joint impedance modulation.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic. Cytokine release syndrome occurring in a minority of SARS-CoV-2 infections is associated with severe disease and high mortality. We profiled the composition, activation, and proliferation of T cells in 20 patients with severe or critical COVID-19 and 40 matched healthy controls by flow cytometry. Unsupervised hierarchical cluster analysis based on 18 T cell subsets resulted in separation of healthy controls and COVID-19 patients. Compared to healthy controls, patients suffering from severe and critical COVID-19 had increased frequencies of activated and proliferating CD38+Ki67+ CD4+ and CD8+ T cells, suggesting active antiviral T cell defense. Frequencies of CD38+Ki67+ Th1 and CD4+ cells correlated negatively with plasma IL-6. Thus, our data suggest that patients suffering from COVID-19 have a distinct T cell composition that is potentially modulated by IL-6.

Background: In autumn 2007, the Medical University of Graz (MUG) upgraded the status of general practice in medical training by integrating a compulsory fi ve-week clerkship in general practice surgeries in the sixth and last year of the curriculum. In cooperation with the Styrian Academy of General Practice (STAFAM), more than 200 general practitioners (GPs) had been accredited to introduce medical students to the specifi c tasks, problems and decision-making process in general practice. Between