Medical University of Graz

About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.

TGF-β directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury

Abstract: TGF-β is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-β pathway is described, which rapidly promoted internalization of the αβγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-β applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which—together with patch-clamp and flow cytometry studies—identified ENaC as the target of TGF-β. TGF-β rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of βENaC, the subunit responsible for cell-surface stability of the αβγENaC complex. ENaC internalization was dependent on oxidation of βENaC Cys43. Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove βENaC internalization, which was inhibited by a TGF-β neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-β signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-β–dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

Body composition for health and performance: a survey of body composition assessment practice carried out by the Ad Hoc Research Working Group on Body Composition, Health and Performance under the auspices of the IOC Medical Commission

Abstract: Background Successful performers in weight-sensitive sports are characterised by low body mass (BM) and fat content. This often requires chronic energy restriction and acute weight loss practices. Aim To evaluate current use of body composition (BC) assessment methods and identify problems and solutions with current BC approaches. Methods A 40-item survey was developed, including demographic and content questions related to BC assessment. The survey was electronically distributed among international sporting organisations. Frequencies and χ 2 analyses were computed. Results 216 responses were received, from 33 countries, representing various institutions, sports and competitive levels. Of the sample, 86% of respondents currently assess BC, most frequently using skinfolds (International Society for the Advancement of Kinanthropometry (ISAK): 50%; non-ISAK, conventional: 40%; both: 28%), dual energy X-ray absorptiometry (38%), bioelectrical impedance (29%), air displacement plethysmography (17%) and hydrostatic weighing (10%). Of those using skinfolds, more at the international level used ISAK, whereas conventional approaches were more reported at regional/national level (p=0.006). The sport dietitian/nutritionist (57%) and physiologist/sports scientist (54%) were most frequently the professionals assessing BC, followed by MDs and athletic trainers, with some reporting coaches (5%). 36% of 116 respondents assessed hydration status and more (64%) did so at international than regional/national level (36%, p=0.028). Of 125 participants answering the question of whether they thought that BC assessment raised problems, 69% said ‘yes’, with most providing ideas for solutions. Conclusions Results show high use of BC assessment but also a lack of standardisation and widespread perception of problems related to BM and BC in sport. Future work should emphasise standardisation with appropriate training opportunities and more research on BC and performance.

EAACI guidelines on allergen immunotherapy: Executive statement

Abstract: The allergist's community has recently celebrated 100 year of Allergen Immunotherapy (AIT) Unfortunately the implemention of this treatment is still impaired by some challenges With the diversity of definitions, methodology and different allergen products used, research studies have produced conflicting outcomes This has resulted in confusion about the benefits and risks of AIT amongst policymakers and professionals, as well as in the variable availability of AIT products, regulation and reimbursement policies globally In 2015 EAACI initiated the AIT Guidelines project as part of the Presidential plan in order to settle the controversies This article is protected by copyright All rights reserved

A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis

Abstract: Background Systemic sclerosis is a multisystemic connective tissue disease with marked involvement of the skin and joints for which few effective evidence based therapies are available. To further investigate the efficacy of extracorporeal photochemotherapy on early aggresive cutaneous disease, a randomized, double-blind, placebo-controlled trial was performed. Objective Our aim was to evaluate the efficacy of photopheresis in the treatment of patients with systemic sclerosis (scleroderma). Methods This randomized, double-blind, placebo-controlled clinical trial was conducted at 16 investigational sites in the United States, Canada, and Europe. Sixty-four patients with typical clinical and histologic findings of scleroderma, of less than 2 years' duration, were studied. Patients did not receive any other concomitant treatment for scleroderma. Patients were randomized to receive either active or sham photopheresis treatment on two consecutive days monthly for 12 months. Severity of skin (skin scores assessed in 22 body regions) and joint involvement (60 joints examined for contractures) were assessed on a monthly basis. Results A statistically significant improvement in skin scores as compared with baseline was observed at 6 months (P = .0024) and 12 months (P = .008) among those who received active photopheresis, but not among those who received sham photopheresis. Comparison of skin scores between the two study arms did not achieve statistical significance because of the small sample size of the study arms. Joint involvement was also significantly improved after 6 months (P = .002) and 12 months (P = .001) of active photopheresis when compared with baseline. Limitations The study lacks sufficient statistical power to reveal a significant difference in skin and joint manifestations between the active and sham photopheresis arms. Conclusion Photopheresis induced significant improvement of skin and joint involvement in patients with scleroderma of recent onset; however, any effect when compared with sham treatment and a possible placebo effect may be modest.

Deep Sequencing Reveals Highly Complex Dynamics of Human Cytomegalovirus Genotypes in Transplant Patients over Time

Abstract: In lung transplant patients undergoing immunosuppression, more than one human cytomegalovirus (HCMV) genotype may emerge during follow-up, and this could be critical for the outcome of HCMV infection. Up to now, many cases of infection with multiple HCMV genotypes were probably overlooked due to the limitations of the current genotyping approaches. We have now analyzed mixed-genotype infections in 17 clinical samples from 9 lung transplant patients using the highly sensitive ultradeep-pyrosequencing (UDPS) technology. UDPS genotyping was performed at three variable HCMV genes, coding for glycoprotein N (gN), glycoprotein O (gO), and UL139. Simultaneous analysis of a mean of 10,430 sequence reads per amplicon allowed the relative amounts of distinct genotypes in the samples to be determined down to 0.1% to 1% abundance. Complex mixtures of up to six different HCMV genotypes per sample were observed. In all samples, no more than two major genotypes accounted for at least 88% of the HCMV DNA load, and these were often accompanied by up to four low-abundance genotypes at frequencies of 0.1% to 8.6%. No evidence for the emergence of new genotypes or sequence changes over time was observed. However, analysis of different samples withdrawn from the same patients at different time points revealed that the relative levels of replication of the individual HCMV genotypes changed within a mixed-genotype population upon reemergence of the virus. Our data show for the first time that, similar to what has been hypothesized for the murine model, HCMV reactivation in humans seems to occur stochastically.