Exercise-based cardiac rehabilitation improves exercise capacity and health-related quality of life in people with atrial fibrillation: A systematic review and meta-analysis of randomised and non-randomised trials

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective The aim of this study was to undertake a contemporary review of the impact of exercise-based cardiac rehabilitation (CR) targeted at patients with atrial fibrillation (AF). Methods We conducted searches of PubMED, EMBASE and the Cochrane Library of Controlled Trials (up until 30 November 2017) using key terms related to exercise-based CR and AF. Randomised and non-randomised controlled trials were included if they compared the effects of an exercise-based CR intervention to a no exercise or usual care control group. Meta-analyses of outcomes were conducted where appropriate. Results The nine randomised trials included 959 (483 exercise-based CR vs 476 controls) patients with various types of AF. Compared with control, pooled analysis showed no difference in all-cause mortality (risk ratio (RR) 1.08, 95% CI 0.77 to 1.53, p=0.64) following exercise-based CR. However, there were improvements in health-related quality of life (mean SF-36 mental component score (MCS): 4.00, 95% CI 0.26 to 7.74; p=0.04 and mean SF-36 physical component score: 1.82, 95% CI 0.06 to 3.59; p=0.04) and exercise capacity (mean peak VO2: 1.59 ml/kg/min, 95% CI 0.11 to 3.08; p=0.04; mean 6 min walk test: 46.9 m, 95% CI 26.4 to 67.4; p<0.001) with exercise-based CR. Improvements were also seen in AF symptom burden and markers of cardiac function. Conclusions Exercise capacity, cardiac function, symptom burden and health-related quality of life were improved with exercise-based CR in the short term (up to 6 months) targeted at patients with AF. However, high-quality multicentre randomised trials are needed to clarify the impact of exercise-based CR on key patient and health system outcomes (including health-related quality of life, mortality, hospitalisation and costs) and how these effects may vary across AF subtypes.National Institute for Health Research (NIHR

Protection against LPS-induced cartilage inflammation and degradation provided by a biological extract of Mentha spicata

<p>Abstract</p> <p>Background</p> <p>A variety of mint [<it>Mentha spicata</it>] has been bred which over-expresses Rosmarinic acid (RA) by approximately 20-fold. RA has demonstrated significant anti-inflammatory activity <it>in vitro </it>and in small rodents; thus it was hypothesized that this plant would demonstrate significant anti-inflammatory activity <it>in vitro</it>. The objectives of this study were: a) to develop an <it>in vitro </it>extraction procedure which mimics digestion and hepatic metabolism, b) to compare anti-inflammatory properties of High-Rosmarinic-Acid <it>Mentha spicata </it>(HRAM) with wild-type control <it>M. spicata </it>(CM), and c) to quantify the relative contributions of RA and three of its hepatic metabolites [ferulic acid (FA), caffeic acid (CA), coumaric acid (CO)] to anti-inflammatory activity of HRAM.</p> <p>Methods</p> <p>HRAM and CM were incubated in simulated gastric and intestinal fluid, liver microsomes (from male rat) and NADPH. Concentrations of RA, CA, CO, and FA in simulated digest of HRAM (HRAM_sim) and CM (CM_sim) were determined (HPLC) and compared with concentrations in aqueous extracts of HRAM and CM. Cartilage explants (porcine) were cultured with LPS (0 or 3 μg/mL) and test article [HRAM_sim(0, 8, 40, 80, 240, or 400 μg/mL), or CM_sim(0, 1, 5 or 10 mg/mL), or RA (0.640 μg/mL), or CA (0.384 μg/mL), or CO (0.057 μg/mL) or FA (0.038 μg/mL)] for 96 h. Media samples were analyzed for prostaglandin E₂(PGE₂), interleukin 1β (IL-1), glycosaminoglycan (GAG), nitric oxide (NO) and cell viability (differential live-dead cell staining).</p> <p>Results</p> <p>RA concentration of HRAM_simand CM_simwas 49.3 and 0.4 μg/mL, respectively. CA, FA and CO were identified in HRAM_simbut not in aqueous extract of HRAM. HRAM_sim(≥ 8 μg/mL) inhibited LPS-induced PGE₂and NO; HRAM_sim(≥ 80 μg/mL) inhibited LPS-induced GAG release. RA inhibited LPS-induced GAG release. No anti-inflammatory or chondroprotective effects of RA metabolites on cartilage explants were identified.</p> <p>Conclusions</p> <p>Our biological extraction procedure produces a substance which is similar in composition to post-hepatic products. HRAM_simis an effective inhibitor of LPS-induced inflammation in cartilage explants, and effects are primarily independent of RA. Further research is needed to identify bioactive phytochemical(s) in HRAM_sim.</p

Contrasting Effects of Energy Transfer in Determining Efficiency Improvements in Ternary Polymer Solar Cells

Crystallizable, high-mobility conjugated polymers have been employed as secondary donor materials in ternary polymer solar cells in order to improve device efficiency by broadening their spectral response range and enhancing charge dissociation and transport. We demonstrate contrasting effects of two crystallizable polymers, namely PffBT4T-2OD and PDPP2TBT, in determining the efficiency improvements in PTB7-Th:PC71BM host blends. A notable power conversion efficient of 11% can be obtained by introducing 10% PffBT4T-2OD (relative to PTB7-Th), while the efficiency of PDPP2TBT-incorporated ternary devices decreased dramatically despite an enhancement in hole mobility and light absorption. Blend morphology studies suggest that both PffBT4T-2OD and PDPP2TBT are well dissolved within the host PTB7-Th phase and facilitate an increased degree of phase separation between polymer and fullerene domains. Whilst negligible charge transfer was determined in binary blends of each polymer mixture, effective energy transfer was identified from PffBT4T-2OD to PTB7-Th that contributes to an improvement in ternary blend device efficiency. In contrast, energy transfer from PTB7-Th to PDPP2TBT worsened the efficiency of the ternary device due to inefficient charge dissociation between PDPP2TBT and PC71BM

The Milliarcsecond Structure of Radio Galaxies and Quasars

Hybrid maps of the nuclei of radio galaxies and quasars show a variety of morphologies. Among compact sources, two structures are common: an asymmetric, “core-jet” morphology (eg, 3C 273), and an “equal double” morphology with two separated, similar components (eg, CTD 93). The nuclei of extended, double radio galaxies generally have a core-jet morphology with the jet directed toward one of the outer components

Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria

Refined saddle-point preconditioners for discretized Stokes problems

This paper is concerned with the implementation of efficient solution algorithms for elliptic problems with constraints. We establish theory which shows that including a simple scaling within well-established block diagonal preconditioners for Stokes problems can result in significantly faster convergence when applying the preconditioned MINRES method. The codes used in the numerical studies are available online

Exercise-based cardiac rehabilitation improves exercise capacity and health-related quality of life in people with atrial fibrillation: a systematic review and meta-analysis of randomised and non-randomised trials.

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective The aim of this study was to undertake a contemporary review of the impact of exercise-based cardiac rehabilitation (CR) targeted at patients with atrial fibrillation (AF). Methods We conducted searches of PubMED, EMBASE and the Cochrane Library of Controlled Trials (up until 30 November 2017) using key terms related to exercise-based CR and AF. Randomised and non-randomised controlled trials were included if they compared the effects of an exercise-based CR intervention to a no exercise or usual care control group. Meta-analyses of outcomes were conducted where appropriate. Results The nine randomised trials included 959 (483 exercise-based CR vs 476 controls) patients with various types of AF. Compared with control, pooled analysis showed no difference in all-cause mortality (risk ratio (RR) 1.08, 95% CI 0.77 to 1.53, p=0.64) following exercise-based CR. However, there were improvements in health-related quality of life (mean SF-36 mental component score (MCS): 4.00, 95% CI 0.26 to 7.74; p=0.04 and mean SF-36 physical component score: 1.82, 95% CI 0.06 to 3.59; p=0.04) and exercise capacity (mean peak VO2: 1.59 ml/kg/min, 95% CI 0.11 to 3.08; p=0.04; mean 6 min walk test: 46.9 m, 95% CI 26.4 to 67.4; p<0.001) with exercise-based CR. Improvements were also seen in AF symptom burden and markers of cardiac function. Conclusions Exercise capacity, cardiac function, symptom burden and health-related quality of life were improved with exercise-based CR in the short term (up to 6 months) targeted at patients with AF. However, high-quality multicentre randomised trials are needed to clarify the impact of exercise-based CR on key patient and health system outcomes (including health-related quality of life, mortality, hospitalisation and costs) and how these effects may vary across AF subtypes.National Institute for Health Research (NIHR

SCA8 CAG/CTG Expansions, a Tale of Two TOXICities: A Unique or Common Case?

International audienc

Shifting suitability for malaria vectors across Africa with warming climates

<p>Abstract</p> <p>Background</p> <p>Climates are changing rapidly, producing warm climate conditions globally not previously observed in modern history. Malaria is of great concern as a cause of human mortality and morbidity, particularly across Africa, thanks in large part to the presence there of a particularly competent suite of mosquito vector species.</p> <p>Methods</p> <p>I derive spatially explicit estimates of human populations living in regions newly suitable climatically for populations of two key <it>Anopheles gambiae </it>vector complex species in Africa over the coming 50 years, based on ecological niche model projections over two global climate models, two scenarios of climate change, and detailed spatial summaries of human population distributions.</p> <p>Results</p> <p>For both species, under all scenarios, given the changing spatial distribution of appropriate conditions and the current population distribution, the models predict a reduction of 11.3–30.2% in the percentage of the overall population living in areas climatically suitable for these vector species in coming decades, but reductions and increases are focused in different regions: malaria vector suitability is likely to decrease in West Africa, but increase in eastern and southern Africa.</p> <p>Conclusion</p> <p>Climate change effects on African malaria vectors shift their distributional potential from west to east and south, which has implications for overall numbers of people exposed to these vector species. Although the total is reduced, malaria is likely to pose novel public health problems in areas where it has not previously been common.</p