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Zell am See, Austria

Maneek-Keber M.,National Institute of ChemistryLjubljana | Frank-Bertoncelj M.,University Medical Center LjubljanaLjubljana | Hafner-Bratkovie I.,National Institute of ChemistryLjubljana | Smole A.,National Institute of ChemistryLjubljana | And 9 more authors.
Science Signaling | Year: 2015

Oxidative stress produced in response to infection or sterile injury activates the innate immune response. We found that extracellular vesicles (EVs) isolated from the plasma of patients with rheumatoid arthritis or secreted from cells subjected to oxidative stress contained oxidized phospholipids that stimulated cells expressing Toll-like receptor 4 (TLR4) in a manner dependent on its co-receptor MD-2. EVs from healthy subjects or reconstituted synthetic EVs subjected to limited oxidation gained the ability to stimulate TLR4-expressing cells, whereas prolonged oxidation abrogated this property. Furthermore, we found that 15-lipoxygenase generated hydro(pero)xylated phospholipids that stimulated TLR4-expressing cells. Molecular modeling suggested that the mechanism of activation of TLR4 by oxidized phospholipids in EVs was structurally similar to that of the TLR4 ligand lipopolysaccharide (LPS). This was supported by experiments showing that EV-mediated stimulation of cells required MD-2, that mutations that block LPS binding to TLR4 abrogated the stimulatory effect of EVs, and that EVs induced TLR4 dimerization. On the other hand, analysis of gene expression profiles showed that genes encoding factors that resolve inflammation were more abundantly expressed in responses to EVs than in response to LPS. Together, these data suggest that EVs act as an oxidative stress-induced endogenous danger signal that underlies the pervasive role of TLR4 in inflammatory diseases. Source

Pieber K.,Medical University of Vienna | Herceg M.,Medical University of Vienna | Paternostro-Sluga T.,Medical University of Vienna | Pablik E.,Medical University of ViennaVienna | And 4 more authors.
BMC Musculoskeletal Disorders | Year: 2015

Abstract Background: The assessment of mobility is important in the acute care setting. Existing tests suffer from limitations. The aim of the study was to examine the inter-rater reliability, the validity, the sensitivity to change, and the internal consistency of an ICF based scale. Methods: In a prospective study inpatients in the acute care setting with restricted mobility aged above 50 years assigned to rehabilitative treatment were included. Assessment of subscales of the Functional Independence Measure (FIM) and the ICF based Basic Mobility Scale (BMS) were performed at admission and before discharge. Furthermore pain, length of stay in hospital, and post-discharge residential status were recorded. Inter-rater reliability, criterion-concurrent validity, sensitivity to change, and internal consistency were calculated. Furthermore, floor and ceiling effects were determined. Results: One hundred twenty-five patients (79 women/46 men) were included. The BMS showed an excellent inter-rater reliability for the total BMS (ICC BMS: 0.85 (95 % CI: 0.81-0.88). The criterion-concurrent validity was high to excellent (Spearman correlation coefficient: -0.91 in correlation to FIM) and the internal consistency was good (Cronbach's alpha 0.88). The BMS proved to be sensitive to improvements in mobility (Wilcoxon's signed rank test: p < 0.0001; The effect size for the BMS was 1.075 and the standardized response mean 1.10. At admission, the BMS was less vulnerable to floor effects. Conclusions: The BMS may be used as a reliable and valid tool for the assessment of mobility in the acute care setting. It is easy to apply, sensitive to change during the hospital stay and not vulnerable to floor and ceiling effects. © 2015 Pieber et al. Source

Gremmel T.,Dana-Farber Cancer Institute | Gremmel T.,Medical University of ViennaVienna | Michelson A.D.,Dana-Farber Cancer Institute | Frelinger A.L.,Dana-Farber Cancer Institute
Platelets | Year: 2016

Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether in vivo and thrombin receptor activating peptide (TRAP)-stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. In vivo and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. In vivo platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all p≤0.02). Patients with an acute coronary syndrome (ACS; n=125) had significantly higher levels of in vivo MPA than patients without ACS (n=437; p=0.01). In the overall study population (n=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA in vivo and in response to TRAP were similar in patients without and with subsequent ischemic events (all p>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n=459), stent implantation (n=205) or ACS (n=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, in vivo and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization. © 2015 Taylor & Francis, LLC. Source

Helbich M.,University Utrecht | Leitner M.,Louisiana State University | Kapusta N.D.,Medical University of ViennaVienna
British Journal of Psychiatry | Year: 2015

Background: Little is known about the effects of lithium intake through drinking water on suicide. This intake originates either from natural rock and soil elution and/or accumulation of lithium-based pharmaceuticals in ground water. Aims: To examine the interplay between natural lithium in drinking water, prescribed lithium-based pharmaceuticals and suicide in Austria. Method: Spatial Bayesian regressions for males, females and pooled suicide mortality rates were estimated. Results: Although the expected inverse association between lithium levels in drinking water and suicide mortality was confirmed for males and for total suicide rates, the relationship for females was not significant. The models do not indicate that lithium from prescriptions, assumed to accumulate in drinking water, is related to suicide risk patterns either as an individual effect or as a moderator of lithium levels in drinking water. Gender-specific differences in risk factors and local risk hot spots are confirmed. Conclusions: The findings do not support the hypotheses that lithium prescriptions have measureable protective effects on suicide or that they interact with lithium in drinking water. © The Royal College of Psychiatrists 2015. Source

Stattermayer A.F.,Medical University of Vienna | Traussnigg S.,Medical University of Vienna | Dienes H.-P.,Medical University of ViennaVienna | Aigner E.,Paracelsus Medical University | And 11 more authors.
Journal of Hepatology | Year: 2015

Background & Aims The earliest characteristic alterations of the liver pathology in Wilson disease (WD) include steatosis, which is sometimes indistinguishable from non-alcoholic fatty liver disease (NAFLD). Steatosis in WD may reflect copper-induced mitochondrial dysfunction. A genetic polymorphism in rs738409, in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), is strongly associated with appearance of in NAFLD. This study evaluated the role of PNPLA3 and hepatic copper content for development of steatosis in patients with WD. Methods Liver biopsies obtained at diagnosis and the PNPLA3 genotype were analyzed in 98 Caucasian patients with WD (male: 52 [53.1%]; mean age: 27.6 years [CI 95%: 24.8-30.4, range: 5.8-61.5]). Steatosis was graded as percentage of lipid containing hepatocytes by an expert hepatopathologist unaware of the results of genetic testing. Results Moderate/severe steatosis (>33% of hepatocytes) was observed in 28 patients (pediatric: n = 13/26 [50.0%], adult: n = 15/72 [20.8%]; p = 0.01). Forty-six patients (46.9%; pediatric: n = 7, adult: n = 39; p = 0.022) had cirrhosis. Multivariate logistic regression identified PNPLA3 G allele (OR: 2.469, CI 95%: 1.203-5.068; p = 0.014) and pediatric age (OR: 4.348; 1.577-11.905; p = 0.004) as independent variables associated with moderate/severe steatosis. In contrast, hepatic copper content did not impact on moderate/severe steatosis (OR: 1.000, CI 95%: 1.000-1.001; p = 0.297). Conclusions Steatosis is common in WD and the PNPLA3 G allele contributes to its pathogenesis. The role of hepatic copper concentration and ATP7B mutations in steatosis development deserve further investigations. © 2015 European Association for the Study of the Liver. Source

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