Cardiac rehabilitation in Austria: long term health-related quality of life outcomes

<p>Abstract</p> <p>Background</p> <p>The goal of cardiac rehabilitation programs is not only to prolong life but also to improve physical functioning, symptoms, well-being, and health-related quality of life (HRQL). The aim of this study was to document the long-term effect of a 1-month inpatient cardiac rehabilitation intervention on HRQL in Austria.</p> <p>Methods</p> <p>Patients (N = 487, 64.7% male, age 60.9 ± 12.5 SD years) after myocardial infarction, with or without percutaneous interventions, coronary artery bypass grafting or valve surgery underwent inpatient cardiac rehabilitation and were included in this long-term observational study (two years follow-up). HRQL was measured with both the MacNew Heart Disease Quality of Life Instrument [MacNew] and EuroQoL-5D [EQ-5D].</p> <p>Results</p> <p>All MacNew scale scores improved significantly (p < 0.001) and exceeded the minimal important difference (0.5 MacNew points) by the end of rehabilitation. Although all MacNew scale scores deteriorated significantly over the two year follow-up period (p < .001), all MacNew scale scores still remained significantly higher than the pre-rehabilitation values. The mean improvement after two years in the MacNew social scale exceeded the minimal important difference while MacNew scale scores greater than the minimal important difference were reported by 40-49% of the patients.</p> <p>Two years after rehabilitation the mean improvement in the EQ-5D Visual Analogue Scale score was not significant with no significant change in the proportion of patients reporting problems at this time.</p> <p>Conclusion</p> <p>These findings provide a first indication that two years following inpatient cardiac rehabilitation in Austria, the long-term improvements in HRQL are statistically significant and clinically relevant for almost 50% of the patients. Future controlled randomized trials comparing different cardiac rehabilitation programs are needed.</p

Sialyl Residues Modulate LPS-Mediated Signaling through the Toll-Like Receptor 4 Complex

We previously reported that neuraminidase (NA) pretreatment of human PBMCs markedly increased their cytokine response to lipopolysaccharide (LPS). To study the mechanisms by which this occurs, we transfected HEK293T cells with plasmids encoding TLR4, CD14, and MD2 (three components of the LPS receptor complex), as well as a NFκB luciferase reporting system. Both TLR4 and MD2 encoded by the plasmids are α-2,6 sialylated. HEK293T cells transfected with TLR4/MD2/CD14 responded robustly to the addition of LPS; however, omission of the MD2 plasmid abrogated this response. Addition of culture supernatants from MD2 (sMD2)-transfected HEK293T cells, but not recombinant, non-glycosylated MD2 reconstituted this response. NA treatment of sMD2 enhanced the LPS response as did NA treatment of the TLR4/CD14-transfected cell supplemented with untreated sMD2, but optimal LPS-initiated responses were observed with NA-treated TLR4/CD14-transfected cells supplemented with NA-treated sMD2. We hypothesized that removal of negatively charged sialyl residues from glycans on the TLR4 complex would hasten the dimerization of TLR4 monomers required for signaling. Co-transfection of HEK293T cells with separate plasmids encoding either YFP- or FLAG-tagged TLR4, followed by treatment with NA and stimulation with LPS, led to an earlier and more robust time-dependent dimerization of TLR4 monomers on co-immunoprecipitation, compared to untreated cells. These findings were confirmed by fluorescence resonance energy transfer (FRET) analysis. Overexpression of human Neu1 increased LPS-initiated TLR4-mediated NFκB activation and a NA inhibitor suppressed its activation. We conclude that (1) sialyl residues on TLR4 modulate LPS responsiveness, perhaps by facilitating clustering of the homodimers, and that (2) sialic acid, and perhaps other glycosyl species, regulate MD2 activity required for LPS-mediated signaling. We speculate that endogenous sialidase activity mobilized during cell activation may play a role in this regulation

Genomic Structure of and Genome-Wide Recombination in the Saccharomyces cerevisiae S288C Progenitor Isolate EM93

The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces cerevisiae haploid laboratory strain, S288C. In this study, we generate a high-resolution overview of the genetic differences between EM93 and S288C. We show that EM93 is heterozygous for >45,000 polymorphisms, including large sequence polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We also find that many large sequence polymorphisms (LSPs) are associated with Ty-elements and sub-telomeric regions. We identified 2,965 genetic markers, which we then used to genotype 120 EM93 tetrads. In addition to deducing the structures of all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144 detectable recombination events, consisting of 87 crossover and 31 non-crossover gene conversion events. Of the 50 polymorphisms showing the highest levels of non-crossover gene conversions, only three deviated from parity, all of which were near heterozygous LSPs. We find that non-telomeric heterozygous LSPs significantly reduce meiotic recombination in adjacent intervals, while sub-telomeric LSPs have no discernable effect on recombination. We identified 203 recombination hotspots, relatively few of which are hot for both non-crossover gene conversions and crossovers. Strikingly, we find that recombination hotspots show limited conservation. Some novel hotspots are found adjacent to heterozygous LSPs that eliminate other hotspots, suggesting that hotspots may appear and disappear relatively rapidly

Physician-assisted suicide: a review of the literature concerning practical and clinical implications for UK doctors

BACKGROUND: A bill to legalize physician-assisted suicide in the UK recently made significant progress in the British House of Lords and will be reintroduced in the future. Until now there has been little discussion of the clinical implications of physician-assisted suicide for the UK. This paper describes problematical issues that became apparent from a review of the medical and psychiatric literature as to the potential effects of legalized physician-assisted suicide. DISCUSSION: Most deaths by physician-assisted suicide are likely to occur for the illness of cancer and in the elderly. GPs will deal with most requests for assisted suicide. The UK is likely to have proportionately more PAS deaths than Oregon due to the bill's wider application to individuals with more severe physical disabilities. Evidence from other countries has shown that coercion and unconscious motivations on the part of patients and doctors in the form of transference and countertransference contribute to the misapplication of physician-assisted suicide. Depression influences requests for hastened death in terminally ill patients, but is often under-recognized or dismissed by doctors, some of whom proceed with assisted death anyway. Psychiatric evaluations, though helpful, do not solve these problems. Safeguards that are incorporated into physician-assisted suicide criteria probably decrease but do not prevent its misapplication. SUMMARY: The UK is likely to face significant clinical problems arising from physician-assisted suicide if it is legalized. Terminally ill patients with mental illness, especially depression, are particularly vulnerable to the misapplication of physician-assisted suicide despite guidelines and safeguards

Comparing population health in the United States and Canada

<p>Abstract</p> <p>Background</p> <p>The objective of the paper is to compare population health in the United States (US) and Canada. Although the two countries are very similar in many ways, there are potentially important differences in the levels of social and economic inequality and the organization and financing of and access to health care in the two countries.</p> <p>Methods</p> <p>Data are from the Joint Canada/United States Survey of Health 2002/03. The Health Utilities Index Mark 3 (HUI3) was used to measure overall health-related quality of life (HRQL). Mean HUI3 scores were compared, adjusting for major determinants of health, including body mass index, smoking, education, gender, race, and income. In addition, estimates of life expectancy were compared. Finally, mean HUI3 scores by age and gender and Canadian and US life tables were used to estimate health-adjusted life expectancy (HALE).</p> <p>Results</p> <p>Life expectancy in Canada is higher than in the US. For those < 40 years, there were no differences in HRQL between the US and Canada. For the 40+ group, HRQL appears to be higher in Canada. The results comparing the white-only population in both countries were very similar. For a 19-year-old, HALE was 52.0 years in Canada and 49.3 in the US.</p> <p>Conclusions</p> <p>The population of Canada appears to be substantially healthier than the US population with respect to life expectancy, HRQL, and HALE. Factors that account for the difference may include access to health care over the full life span (universal health insurance) and lower levels of social and economic inequality, especially among the elderly.</p

Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being

Biomass and morphology of fine roots in temperate broad-leaved forests differing in tree species diversity: is there evidence of below-ground overyielding?

Biodiversity effects on ecosystem functioning in forests have only recently attracted increasing attention. The vast majority of studies in forests have focused on above-ground responses to differences in tree species diversity, while systematic analyses of the effects of biodiversity on root systems are virtually non-existent. By investigating the fine root systems in 12 temperate deciduous forest stands in Central Europe, we tested the hypotheses that (1) stand fine root biomass increases with tree diversity, and (2) ‘below-ground overyielding’ of species-rich stands in terms of fine root biomass is the consequence of spatial niche segregation of the roots of different species. The selected stands represent a gradient in tree species diversity on similar bedrock from almost pure beech forests to medium-diverse forests built by beech, ash, and lime, and highly-diverse stands dominated by beech, ash, lime, maple, and hornbeam. We investigated fine root biomass and necromass at 24 profiles per stand and analyzed species differences in fine root morphology by microscopic analysis. Fine root biomass ranged from 440 to 480 g m−2 in the species-poor to species-rich stands, with 63–77% being concentrated in the upper 20 cm of the soil. In contradiction to our two hypotheses, the differences in tree species diversity affected neither stand fine root biomass nor vertical root distribution patterns. Fine root morphology showed marked distinctions between species, but these root morphological differences did not lead to significant differences in fine root surface area or root tip number on a stand area basis. Moreover, differences in species composition of the stands did not alter fine root morphology of the species. We conclude that ‘below-ground overyielding’ in terms of fine root biomass does not occur in the species-rich stands, which is most likely caused by the absence of significant spatial segregation of the root systems of these late-successional species