Cardiac cachexia in early literature: a review of research prior to Medline

Cachexia has been known to physicians since ancient Greek times as a 'signum mali ominis' in various diseases indicating end stage disease and poor quality of life. Cardiac cachexia is recently receiving growing attention as modern treatment options prevent early death from cardiac events and more patients live with chronic compensated heart failure. Nevertheless, observation and clinical documentation of this condition go back as long as medical science itself. Pioneering studies on the reasons and mechanisms of cachexia were performed several decades ago. These studies provide fundamental insights and guidance towards a better understanding of cachexia. This review presents an overview of early thoughts and milestone studies on metabolic abnormalities and cachexia in chronic heart failure

Natura 2000 and the regulation of agricultural ammonia emissions

This article provides a comparative analysis of the regulation of ammonia emissions, primarily from livestock installations, in Denmark, Germany and the Netherlands. It discusses the challenges of regulating agricultural ammonia emissions in view of the rulings of the Court of Justice of the European Union (cjeu) on Art. 6(3) of the Habitats Directive. It is argued that the need to ensure certainty concerning the absence of significant effects on Natura 2000 sites is challenged by the uncertainties regarding both the state of individual habitat types and the potential impact of individual projects. A more integrated or programmatic approach may provide an alternative approach to individual assessments, but it is necessary to ensure that additional loads from new or enlarged livestock installations are permitted in areas with high ammonia loads only where it is certain that a programmatic approach will ensure that there are no harmful effects. This might be an almost impossible task

Nucleosomes in serum as a marker for cell death

The concentration of nucleosomes is elevated in blood of patients with diseases which are associated with enhanced cell death. In order to detect these circulating nucleosomes, we used the Cell Death Detection-ELISA(Plus) (CDDE) from Roche Diagnostics (Mannheim, Germany) (details at http:\textbackslash{}\textbackslash{}biochem.roche.com). For its application in liquid materials we performed various modifications: we introduced a standard curve with nucleosome-rich material, which enabled direct quantification and improved comparability of the values within (CVinterassay:3.0-4.1%) and between several runs (CVinterassay:8.6-13.5%), and tested the analytical specificity of the ELISA. Because of the fast elimination of nucleosomes from circulation and their limited stability, we compared plasma and serum matrix and investigated in detail the pre-analytical handling of serum samples which can considerably influence the test results. Careless venipuncture producing hemolysis, delayed centrifugation and bacterial contamination of the blood samples led to false-positive results; delayed stabilization with EDTA and insufficient storage conditions resulted in false-negative values. At temperatures of -20 degreesC, serum samples which were treated with 10 mM EDTA were stable for at least 6 months. In order to avoid possible interfering factors, we recommend a schedule for the pre-analytical handling of the samples. As the first stage, the possible clinical application was investigated in the sera of 310 persons. Patients with solid tumors (n = 220; mean = 361 Arbitrary Units (AU)) had considerably higher values than healthy persons (n = 50; mean = 30 AU; P = 0.0001) and patients with inflammatory diseases (n = 40; mean = 296 AU; p = 0.096). Within the group of patients with tumors, those in advanced stages (UICC 4) showed significantly higher values than those in early stages (UICC 1-3) (P = 0.0004)

Efficiency of choice set generation methods for bicycle routes

The current study analyses the efficiency of choice set generation methods for bicycle routes and proposes the extension of cost functions to bicycle-oriented factors not limited to distance and time. Three choice set generation methods for route choice were examined in their ability to generate relevant and heterogeneous routes: doubly stochastic generation function, breadth first search on link elimination, and branch & bound algorithm. Efficiency of the methods was evaluated for a high-resolution network by comparing the performances with four multiattribute cost functions accounting for scenic routes, dedicated cycle lanes, and road type. Data consisted of 778 bicycle trips traced by GPS and carried out by 139 persons living in the Greater Copenhagen Area, in Denmark. Results suggest that both the breadth first search on link elimination and the doubly stochastic generation function generated realistic routes, while the former outperformed in computation cost and the latter produced more heterogeneous routes

Methylation of the imprinted GNAS1 gene in cell-free plasma DNA : equal steady-state quantities of methylated and unmethylated DNA in plasma

Background Genomic DNA sequences in cell-free plasma are biomarkers of cancer prognosis, where characteristic changes in methylation of tumour suppressor or oncogene DNA regions are indicative of changes in gene activity. Also, cell-free fetal DNA can be distinguished, by its methylation status, from the maternal DNA in the plasma of pregnant women, hence providing DNA biomarkers for the proposed minimally-invasive diagnosis of fetal aneuploidies, including Down's syndrome. However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes. Methods We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-of-origin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing. Results Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers. Conclusions Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults