Langzeit-Monitoring der Auswirkungen einer Umstellung auf den biologischen Landbau (MBUIL V), Abschlussbericht

Auf einem Ackerbaubetrieb im Marchfeld in Niederösterreich wird seit dem Jahr 2003 eine umfassende Langzeituntersuchung zur Dokumentation und Entwicklung des biologischen Landbaus und agrarökologischer Begleitmaßnahmen durchgeführt (www.mubil.boku.ac.at). In der Projektphase MUBIL V wurden im Jahr 2014 spezifische Themen aus dem Gesamtmonitoring ausgewählt und fortgeführt. Die Untersuchungen fanden auf Betriebs-, Schlag- und Parzellenebene statt. Die Ziele des Projektes waren: (a) Wissenschaftlich abgesicherte Erkenntnisse über das Ausmaß und die Geschwindigkeit von Veränderungen der pflanzenbaulichen Entwicklung mit der längerfristigen biologischen Bewirtschaftung zu erhalten. (b) Erkenntnisse über die Auswirkungen unterschiedliche Düngungssysteme viehloser und viehhaltender biologischer Bewirtschaftung mithilfe pflanzenbaulicher Untersuchungen über vergleichende Versuchsanstellungen zu erlangen. (c) Erkenntnisse über die Wirkungen von Blühstreifen mit unterschiedlichen Ansaatmischungen und Pflegemaßnahmen auf die Wildbienen zu dokumentieren

PI3Kγ Protects from Myocardial Ischemia and Reperfusion Injury through a Kinase-Independent Pathway

BACKGROUND: PI3Kgamma functions in the immune compartment to promote inflammation in response to G-protein-coupled receptor (GPCR) agonists and PI3Kgamma also acts within the heart itself both as a negative regulator of cardiac contractility and as a pro-survival factor. Thus, PI3Kgamma has the potential to both promote and limit M I/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Complete PI3Kgamma-/- mutant mice, catalytically inactive PI3KgammaKD/KD (KD) knock-in mice, and control wild type (WT) mice were subjected to in vivo myocardial ischemia and reperfusion (M I/R) injury. Additionally, bone-marrow chimeric mice were constructed to elucidate the contribution of the inflammatory response to cardiac damage. PI3Kgamma-/- mice exhibited a significantly increased infarction size following reperfusion. Mechanistically, PI3Kgamma is required for activation of the Reperfusion Injury Salvage Kinase (RISK) pathway (AKT/ERK1/2) and regulates phospholamban phosphorylation in the acute injury response. Using bone marrow chimeras, the cardioprotective role of PI3Kgamma was mapped to non-haematopoietic cells. Importantly, this massive increase in M I/R injury in PI3Kgamma-/- mice was rescued in PI3Kgamma kinase-dead (PI3KgammaKD/KD) knock-in mice. However, PI3KgammaKD/KD mice exhibited a cardiac injury similar to wild type animals, suggesting that specific blockade of PI3Kgamma catalytic activity has no beneficial effects. CONCLUSIONS/SIGNIFICANCE: Our data show that PI3Kgamma is cardioprotective during M I/R injury independent of its catalytic kinase activity and that loss of PI3Kgamma function in the hematopoietic compartment does not affect disease outcome. Thus, clinical development of specific PI3Kgamma blockers should proceed with caution

The additional value of patient-reported health status in predicting 1-year mortality after invasive coronary procedures: A report from the Euro Heart Survey on Coronary Revascularisation

Objective: Self-perceived health status may be helpful in identifying patients at high risk for adverse outcomes. The Euro Heart Survey on Coronary Revascularization (EHS-CR) provided an opportunity to explore whether impaired health status was a predictor of 1-year mortality in patients with coronary artery disease (CAD) undergoing angiographic procedures. Methods: Data from the EHS-CR that included 5619 patients from 31 member countries of the European Society of Cardiology were used. Inclusion criteria for the current study were completion of a self-report measure of health status, the EuroQol Questionnaire (EQ-5D) at discharge and information on 1-year follow-up, resulting in a study population of 3786 patients. Results: The 1-year mortality was 3.2% (n = 120). Survivors reported fewer problems on the five dimensions of the EQ-5D as compared with non-survivors. A broad range of potential confounders were adjusted for, which reached a p<0.10 in the unadjusted analyses. In the adjusted analyses, problems with self-care (OR 3.45; 95% CI 2.14 to 5.59) and a low rating (≤ 60) on health status (OR 2.41; 95% CI 1.47 to 3.94) were the most powerful independent predictors of mortality, among the 22 clinical variables included in the analysis. Furthermore, patients who reported no problems on all five dimensions had significantly lower 1-year mortality rates (OR 0.47; 95% CI 0.28 to 0.81). Conclusions: This analysis shows that impaired health status is associated with a 2-3-fold increased risk of all-cause mortality in patients with CAD, independent of other conventional risk factors. These results highlight the importance of including patients' subjective experience of their own health status in the evaluation strategy to optimise risk stratification and management in clinical practice

In vivo cardiac role of migfilin during experimental pressure overload

Aims Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca2+-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. Methods and results To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. Conclusions Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC

Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma

Purpose: Patients with primary cutaneous melanoma with a Breslow thickness greater than or equal to 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome, Since interferon alfa-2a (IFN alpha 2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFN alpha 2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor