Home-based versus centre-based cardiac rehabilitation: Abridged Cochrane systematic review and meta-analysis

Objective: To update the Cochrane review comparing the effects of home-based and supervised centre-based cardiac rehabilitation (CR) on mortality and morbidity, quality of life, and modifiable cardiac risk factors in patients with heart disease. Methods: Systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL were searched up to October 2014, without language restriction. Randomised trials comparing home-based and centre-based CR programmes in adults with myocardial infarction, angina, heart failure or who had undergone coronary revascularisation were included. Results: 17 studies with 2172 patients were included. No difference was seen between home-based and centre-based CR in terms of: mortality (relative risk (RR) 0.79, 95% CI 0.43 to 1.47); cardiac events; exercise capacity (mean difference (MD) −0.10, −0.29 to 0.08); total cholesterol (MD 0.07 mmol/L, −0.24 to 0.11); low-density lipoprotein cholesterol (MD −0.06 mmol/L, −0.27 to 0.15); triglycerides (MD −0.16 mmol/L, −0.38 to 0.07); systolic blood pressure (MD 0.2 mm Hg, −3.4 to 3.8); smoking (RR 0.98, 0.79 to 1.21); health-related quality of life and healthcare costs. Lower high-density lipoprotein cholesterol (MD −0.07 mmol/L, −0.11 to −0.03, p=0.001) and lower diastolic blood pressure (MD −1.9 mm Hg, −0.8 to −3.0, p=0.009) were observed in centre-based participants. Home-based CR was associated with slightly higher adherence (RR 1.04, 95% CI 1.01 to 1.07). Conclusions: Home-based and centre-based CR provide similar benefits in terms of clinical and health-related quality of life outcomes at equivalent cost for those with heart failure and following myocardial infarction and revascularisation

Home-based versus centre-based cardiac rehabilitation (Review)

This is the final version. Available from the Cochrane Collaboration via the DOI in this recordBACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based and technology-supported cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation, especially during the SARS-CoV-2 pandemic. This is an update of a review previously published in 2009, 2015, and 2017. OBJECTIVES: To compare the effect of home-based (which may include digital/telehealth interventions) and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease SEARCH METHODS: We updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 16 September 2022. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials that compared centre-based cardiac rehabilitation (e.g. hospital, sports/community centre) with home-based programmes (± digital/telehealth platforms) in adults with myocardial infarction, angina, heart failure, or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on predefined inclusion criteria. Disagreements were resolved through discussion or by involving a third review author. Two authors independently extracted outcome data and study characteristics and assessed risk of bias. Certainty of evidence was assessed using GRADE. MAIN RESULTS: We included three new trials in this update, bringing a total of 24 trials that have randomised a total of 3046 participants undergoing cardiac rehabilitation. A further nine studies were identified and are awaiting classification. Manual searching of trial registers until 16 September 2022 revealed a further 14 clinical trial registrations - these are ongoing. Participants had a history of acute myocardial infarction, revascularisation, or heart failure. Although there was little evidence of high risk of bias, a number of studies provided insufficient detail to enable assessment of potential risk of bias; in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported. No evidence of a difference was seen between home- and centre-based cardiac rehabilitation in our primary outcomes up to 12 months of follow-up: total mortality (risk ratio [RR] = 1.19, 95% confidence interval [CI] 0.65 to 2.16; participants = 1647; studies = 12/comparisons = 14; low-certainty evidence) or exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.24 to 0.04; participants = 2343; studies = 24/comparisons = 28; low-certainty evidence). The majority of evidence (N=71 / 77 comparisons of either total or domain scores) showed no significant difference in health-related quality of life up to 24 months follow-up between home- and centre-based cardiac rehabilitation. Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate-certainty evidence). There was a similar level of trial completion (RR 1.03, 95% CI 0.99 to 1.08; participants = 2638; studies = 22/comparisons = 26; low-certainty evidence) between home-based and centre-based participants. The cost per patient of centre- and home-based programmes was similar. AUTHORS' CONCLUSIONS: This update supports previous conclusions that home- (± digital/telehealth platforms) and centre-based forms of cardiac rehabilitation formally supported by healthcare staff seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction, or revascularisation, or with heart failure. This finding supports the continued expansion of healthcare professional supervised home-based cardiac rehabilitation programmes (± digital/telehealth platforms), especially important in the context of the ongoing global SARS-CoV-2 pandemic that has much limited patients in face-to-face access of hospital and community health services. Where settings are able to provide both supervised centre- and home-based programmes, consideration of the preference of the individual patient would seem appropriate. Although not included in the scope of this review, there is an increasing evidence base supporting the use of hybrid models that combine elements of both centre-based and home-based cardiac rehabilitation delivery. Further data are needed to determine: (1) whether the short-term effects of home/digital-telehealth and centre-based cardiac rehabilitation models of delivery can be confirmed in the longer term; (2) the relative clinical effectiveness and safety of home-based programmes for other heart patients, e.g. post-valve surgery and atrial fibrillation.National Institute for Health and Care Research (NIHR

Hyperspectral phasor analysis enables multiplexed 5D in vivo imaging

Time-lapse imaging of multiple labels is challenging for biological imaging as noise, photobleaching and phototoxicity compromise signal quality, while throughput can be limited by processing time. Here, we report software called Hyper-Spectral Phasors (HySP) for denoising and unmixing multiple spectrally overlapping fluorophores in a low signal-to-noise regime with fast analysis. We show that HySP enables unmixing of seven signals in time-lapse imaging of living zebrafish embryos

Meiosis-Specific Loading of the Centromere-Specific Histone CENH3 in Arabidopsis thaliana

Centromere behavior is specialized in meiosis I, so that sister chromatids of homologous chromosomes are pulled toward the same side of the spindle (through kinetochore mono-orientation) and chromosome number is reduced. Factors required for mono-orientation have been identified in yeast. However, comparatively little is known about how meiotic centromere behavior is specialized in animals and plants that typically have large tandem repeat centromeres. Kinetochores are nucleated by the centromere-specific histone CENH3. Unlike conventional histone H3s, CENH3 is rapidly evolving, particularly in its N-terminal tail domain. Here we describe chimeric variants of CENH3 with alterations in the N-terminal tail that are specifically defective in meiosis. Arabidopsis thaliana cenh3 mutants expressing a GFP-tagged chimeric protein containing the H3 N-terminal tail and the CENH3 C-terminus (termed GFP-tailswap) are sterile because of random meiotic chromosome segregation. These defects result from the specific depletion of GFP-tailswap protein from meiotic kinetochores, which contrasts with its normal localization in mitotic cells. Loss of the GFP-tailswap CENH3 variant in meiosis affects recruitment of the essential kinetochore protein MIS12. Our findings suggest that CENH3 loading dynamics might be regulated differently in mitosis and meiosis. As further support for our hypothesis, we show that GFP-tailswap protein is recruited back to centromeres in a subset of pollen grains in GFP-tailswap once they resume haploid mitosis. Meiotic recruitment of the GFP-tailswap CENH3 variant is not restored by removal of the meiosis-specific cohesin subunit REC8. Our results reveal the existence of a specialized loading pathway for CENH3 during meiosis that is likely to involve the hypervariable N-terminal tail. Meiosis-specific CENH3 dynamics may play a role in modulating meiotic centromere behavior

Regulation of Glucose Homeostasis by KSR1 and MARK2

Protein scaffolds control the intensity and duration of signaling and dictate the specificity of signaling through MAP kinase pathways. KSR1 is a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. Relative to wild-type mice, ksr1-/- mice are modestly glucose intolerant, but show a normal response to exogenous insulin. However, ksr1-/- mice also demonstrate a three-fold increase in serum insulin levels in response to a glucose challenge, suggesting a role for KSR1 in insulin secretion. The kinase MARK2 is closely related to C-TAK1, a known regulator of KSR1. Mice lacking MARK2 have an increased rate of glucose disposal in response to exogenous insulin, increased glucose tolerance, and are resistant to diet-induced obesity. mark2-/-ksr1-/- (DKO) mice were compared to wild type, mark2-/-, and ksr1-/- mice for their ability to regulate glucose homeostasis. Here we show that disruption of KSR1 in mark2-/- mice reverses the increased sensitivity to exogenous insulin resulting from MARK2 deletion. DKO mice respond to exogenous insulin similarly to wild type and ksr1-/- mice. These data suggest a model whereby MARK2 negatively regulates insulin sensitivity in peripheral tissue through inhibition of KSR1. Consistent with this model, we found that MARK2 binds and phosphorylates KSR1 on Ser392. Phosphorylation of Ser392 is a critical regulator of KSR1 stability, subcellular location, and ERK activation. These data reveal an unexpected role for the molecular scaffold KSR1 in insulin-regulated glucose metabolism

Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics

In humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In a placebo-controlled design, we tested 20 healthy male volunteers to investigate these behavioural and neurophysiological modulations using magnetoencephalography. As an index of the individuals' characteristics, we used the empathy quotient (EQ), the autism spectrum quotient (AQ), and the systemising quotient (SQ). Only during the perception of another person's angry face was a higher SQ a significant predictor of OT-induced prosocial change, both in the behavioural and neurophysiological indicators. In addition, a lower EQ was only a significant predictor of OT-induced prosocial changes in the neurophysiological indicators during the perception of angry faces. Both on the behavioural and the neurophysiological level, the effects of OT were specific for anger and correlated with a higher SQ

Coffee, Alcohol, Smoking, Physical Activity and QT Interval Duration: Results from the Third National Health and Nutrition Examination Survey

Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration.We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview.In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (-0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (-0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (-2.9 to 5.2) and 1.7 ms (-2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was -0.8 ms (-3.0 to 1.4).Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity

Arrhythmogenic right ventricular cardiomyopathy/dysplasia

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator. Young age, family history of juvenile sudden death, QRS dispersion ≥ 40 ms, T-wave inversion, left ventricular involvement, ventricular tachycardia, syncope and previous cardiac arrest are the major risk factors for adverse prognosis. Preparticipation screening for sport eligibility has been proven to be effective in detecting asymptomatic patients and sport disqualification has been life-saving, substantially declining sudden death in young athletes

Novel facultative Methylocella strains are active methane consumers at terrestrial natural gas seeps

Natural gas seeps contribute to global climate change by releasing substantial amounts of the potent greenhouse gas methane and other climate-active gases including ethane and propane to the atmosphere. However, methanotrophs, bacteria capable of utilising methane as the sole source of carbon and energy, play a significant role in reducing the emissions of methane from many environments. Methylocella-like facultative methanotrophs are a unique group of bacteria that grow on other components of natural gas (i.e. ethane and propane) in addition to methane but a little is known about the distribution and activity of Methylocella in the environment. The purposes of this study were to identify bacteria involved in cycling methane emitted from natural gas seeps and, most importantly, to investigate if Methylocella-like facultative methanotrophs were active utilisers of natural gas at seep sites