Chronobiology of high blood pressure

BIOCOS, the project aimed at studying BIOlogical systems in their COSmos, has obtained a great deal of expertise in the fields of blood pressure (BP) and heart rate (HR) monitoring and of marker rhythmometry for the purposes of screening, diagnosis, treatment, and prognosis. Prolonging the monitoring reduces the uncertainty in the estimation of circadian parameters; the current recommendation of BIOCOS requires monitoring for at least 7 days. The BIOCOS approach consists of a parametric and a non-parametric analysis of the data, in which the results from the individual subject are being compared with gender- and age-specified reference values in health. Chronobiological designs can offer important new information regarding the optimization of treatment by timing its administration as a function of circadian and other rhythms. New technological developments are needed to close the loop between the monitoring of blood pressure and the administration of antihypertensive drugs

Genetic Control of Canine Leishmaniasis: Genome-Wide Association Study and Genomic Selection Analysis

Background: the current disease model for leishmaniasis suggests that only a proportion of infected individuals develop clinical disease, while others are asymptomatically infected due to immune control of infection. The factors that determine whether individuals progress to clinical disease following Leishmania infection are unclear, although previous studies suggest a role for host genetics. Our hypothesis was that canine leishmaniasis is a complex disease with multiple loci responsible for the progression of the disease from Leishmania infection. Methodology/Principal Findings: genome-wide association and genomic selection approaches were applied to a population-based case-control dataset of 219 dogs from a single breed (Boxer) genotyped for ~170,000 SNPs. Firstly, we aimed to identify individual disease loci; secondly, we quantified the genetic component of the observed phenotypic variance; and thirdly, we tested whether genome-wide SNP data could accurately predict the disease. Conclusions/Significance: we estimated that a substantial proportion of the genome is affecting the trait and that its heritability could be as high as 60%. Using the genome-wide association approach, the strongest associations were on chromosomes 1, 4 and 20, although none of these were statistically significant at a genome-wide level and after correcting for genetic stratification and lifestyle. Amongst these associations, chromosome 4: 61.2-76.9 Mb maps to a locus that has previously been associated with host susceptibility to human and murine leishmaniasis, and genomic selection estimated markers in this region to have the greatest effect on the phenotype. We therefore propose these regions as candidates for replication studies. An important finding of this study was the significant predictive value from using the genomic information. We found that the phenotype could be predicted with an accuracy of ~0.29 in new samples and that the affection status was correctly predicted in 60% of dogs, significantly higher than expected by chance, and with satisfactory sensitivity-specificity values (AUC = 0.63)

Non-Photochemical Quenching in Cryptophyte Alga Rhodomonas salina Is Located in Chlorophyll a/c Antennae

Photosynthesis uses light as a source of energy but its excess can result in production of harmful oxygen radicals. To avoid any resulting damage, phototrophic organisms can employ a process known as non-photochemical quenching (NPQ), where excess light energy is safely dissipated as heat. The mechanism(s) of NPQ vary among different phototrophs. Here, we describe a new type of NPQ in the organism Rhodomonas salina, an alga belonging to the cryptophytes, part of the chromalveolate supergroup. Cryptophytes are exceptional among photosynthetic chromalveolates as they use both chlorophyll a/c proteins and phycobiliproteins for light harvesting. All our data demonstrates that NPQ in cryptophytes differs significantly from other chromalveolates – e.g. diatoms and it is also unique in comparison to NPQ in green algae and in higher plants: (1) there is no light induced xanthophyll cycle; (2) NPQ resembles the fast and flexible energetic quenching (qE) of higher plants, including its fast recovery; (3) a direct antennae protonation is involved in NPQ, similar to that found in higher plants. Further, fluorescence spectroscopy and biochemical characterization of isolated photosynthetic complexes suggest that NPQ in R. salina occurs in the chlorophyll a/c antennae but not in phycobiliproteins. All these results demonstrate that NPQ in cryptophytes represents a novel class of effective and flexible non-photochemical quenching

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Resistance to anti-discrimination law in Central and Eastern Europe – a post-Communist legacy?

Post-communist Central and Eastern European (‘CEE’) legislators and judges have been resistant to equality and anti -discrimination law. This Article argues that these negative attitudes can be explained in part by the specific trajectory that EAL has taken in CEE during and after state socialism, which has differed from Western Europe. In the UK/EU, the formal guarantees of equal treatment and prohibitions of discrimination of the 1960s and 1970s were complemented by a more substantive understanding of equality in the 1990s and 2000s. This development was reversed in CEE—substantive equality, of a certain kind, preceded rather than followed formal equality and anti -discrimination guarantees. The State Socialist concern with equality was real, and yet the project was incomplete in several significant ways. It saw only socio-economic, but not socio-cultural inequalities (relating to dignity, identity or diversity). It was transformative with r egards to class, but not other discrimination grounds, especially not gender. While equality was a constitutionally enshrined principle, there was an absence of any corresponding enforceable anti discrimination right. Finally, the emphasis on the “natural ” differences between the sexes meant that sex/gender discrimination was not recognized as conflicting with women’s constitutional equality guarantees. Today, the lack of anti-discrimination legal guarantees has been remedied. However, equality and anti-discrimination law has been weakened by the fact that anti-discrimination rights have no indigenous history to draw upon, nor has substantive and transformative equality any fertile domestic conceptual ground within which to grow in relation to any protected characteristics other than class or socio -economic status.</p

The legal notion of gender equality in the Czech Republic

This article looks at the legal notion of gender equality in the Czech Republic as EU harmonization obligations meet with the socialist past. While the transition from state socialism to capitalism brought positive legal reforms - many incurred in the EU accession process - some of these new mechanisms, especially anti-discrimination and gender equality provisions, are mistrusted and misunderstood by legal actors. The article submits that the current notion of equality is influenced by the socialist past, and that both a continuity of conceptions between past and present about gender and equality, and attempts to distance the new capitalist order from its socialist predecessor impact it. © 2009 Elsevier Ltd. All rights reserved

Resistance to anti-discrimination law in Central and Eastern Europe – a post-Communist legacy?

Post-communist Central and Eastern European (‘CEE’) legislators and judges have been resistant to equality and anti -discrimination law. This Article argues that these negative attitudes can be explained in part by the specific trajectory that EAL has taken in CEE during and after state socialism, which has differed from Western Europe. In the UK/EU, the formal guarantees of equal treatment and prohibitions of discrimination of the 1960s and 1970s were complemented by a more substantive understanding of equality in the 1990s and 2000s. This development was reversed in CEE—substantive equality, of a certain kind, preceded rather than followed formal equality and anti -discrimination guarantees. The State Socialist concern with equality was real, and yet the project was incomplete in several significant ways. It saw only socio-economic, but not socio-cultural inequalities (relating to dignity, identity or diversity). It was transformative with r egards to class, but not other discrimination grounds, especially not gender. While equality was a constitutionally enshrined principle, there was an absence of any corresponding enforceable anti discrimination right. Finally, the emphasis on the “natural ” differences between the sexes meant that sex/gender discrimination was not recognized as conflicting with women’s constitutional equality guarantees. Today, the lack of anti-discrimination legal guarantees has been remedied. However, equality and anti-discrimination law has been weakened by the fact that anti-discrimination rights have no indigenous history to draw upon, nor has substantive and transformative equality any fertile domestic conceptual ground within which to grow in relation to any protected characteristics other than class or socio -economic status.</p

Women on company boards: Equality meets subsidiarity

This article explores the justifications for, and objections to, the proposed European Union ‘women on company boards’ Directive. It notes that Member State opposition to the measure had different emphases. The new, post-socialist Member States that intervened prominently questioned the Commission's understanding of the underlying social reality of gender inequality and the measure's focus on results, while the old Member States that intervened raised mainly the issue of subsidiarity and challenged the need for legislative action, and/or particularly the need for legislative action at EU level. The article further argues that the Commission weakened its case by emphasising economic rationales for the measure, and submits that a principled justification fits the proposal better. Finally, the article argues that subsidiarity-related arguments are available also to justify non-cross-border, non-economic projects, such as that of gender equality

Women on company boards: Equality meets subsidiarity

This article explores the justifications for, and objections to, the proposed European Union ‘women on company boards’ Directive. It notes that Member State opposition to the measure had different emphases. The new, post-socialist Member States that intervened prominently questioned the Commission's understanding of the underlying social reality of gender inequality and the measure's focus on results, while the old Member States that intervened raised mainly the issue of subsidiarity and challenged the need for legislative action, and/or particularly the need for legislative action at EU level. The article further argues that the Commission weakened its case by emphasising economic rationales for the measure, and submits that a principled justification fits the proposal better. Finally, the article argues that subsidiarity-related arguments are available also to justify non-cross-border, non-economic projects, such as that of gender equality