Does cardiac resynchronization therapy restore peripheral circulatory homeostasis?

Aims: To evaluate whether peripheral circulatory ‘remodeling’ as measured by changes in vascular compliance and in markers of nitric oxide signaling contributes to patient response to cardiac resynchronization therapy (CRT)  Methods and results: Effects of CRT were evaluated in 33 patients pre- and 6 months post- procedure. Peak oxygen consumption (VO2 max), six-minute walk distance (6MWD), NYHA class, and quality of life score (QOL) were evaluated. Augmentation index (AIX) and its interactions with nitric oxide (NO) were evaluated by applanation tonometry. Platelet NO responsiveness and content of thioredoxin-interacting protein (TXNIP) were assessed. Plasma concentrationsof NT-proBNP, asymmetric and symmetric dimethylarginine (ADMA and SDMA), high sensitivity C-reactive protein, catecholamines and matrix metalloproteinases-2 and -9 were assessed. Despite significant improvement in 6MWD (p=0.005), NYHA class (p<0.001), QOL (p=0.001), and all echocardiographic parameters post CRT, there were no significant changesin AIx measurements, TXNIP content and platelet NO response. Significant falls in NTproBNP (p=0.008) and SDMA (p=0.013; independent of renal function) occurred. Falls in SDMA predicted reduction in hs-CRP (p=0.04) and increases in VO2max (p=0.04). There were no correlations between changes in echocardiographic parameters and those in vascular function.  Conclusions: These data suggest that the beneficial effects of CRT over 6 months are independent of any change in peripheral NO-related signaling. However there is evidence that suppression of inflammation occurs and its magnitude predicts extent of clinical improvement

Commissioning of inline ECE system within waveguide based ECRH transmission systems on ASDEX upgrade

A CW capable inline electron cyclotron emission (ECE) separation system for feedback control, featuring oversized corrugated waveguides, is commissioned on ASDEX upgrade (AUG). The system is based on a combination of a polarization independent, non-resonant, Mach-Zehnder diplexer equipped with dielectric plate beam splitters [2, 3] employed as corrugated oversized waveguide filter, and a resonant Fast Directional Switch, FADIS [4, 5, 6, 7] as ECE/ECCD separation system. This paper presents an overview of the system, the low power characterisation tests and first high power commissioning on AUG

Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6−/− mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6−/− and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6−/− mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6−/− mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K

Overview of data-synthesis in systematic reviews of studies on outcome prediction models

Background: Many prognostic models have been developed. Different types of models, i.e. prognostic factor and outcome prediction studies, serve different purposes, which should be reflected in how the results are summarized in reviews. Therefore we set out to investigate how authors of reviews synthesize and report the results of primary outcome prediction studies. Methods: Outcome prediction reviews published in MEDLINE between October 2005 and March 2011 were eligible and 127 Systematic reviews with the aim to summarize outcome prediction studies written in English were identified for inclusion. Characteristics of the reviews and the primary studies that were included were independently assessed by 2 review authors, using standardized forms. Results: After consensus meetings a total of 50 systematic reviews that met the inclusion criteria were included. The type of primary studies included (prognostic factor or outcome prediction) was unclear in two-thirds of the reviews. A minority of the reviews reported univariable or multivariable point estimates and measures of dispersion from the primary studies. Moreover, the variables considered for outcome prediction model development were often not reported, or were unclear. In most reviews there was no information about model performance. Quantitative analysis was performed in 10 reviews, and 49 reviews assessed the primary studies qualitatively. In both analyses types a range of different methods was used to present the results of the outcome prediction studies. Conclusions: Different methods are applied to synthesize primary study results but quantitative analysis is rarely performed. The description of its objectives and of the primary studies is suboptimal and performance parameters of the outcome prediction models are rarely mentioned. The poor reporting and the wide variety of data synthesis strategies are prone to influence the conclusions of outcome prediction reviews. Therefore, there is much room for improvement in reviews of outcome prediction studies. (aut.ref.