AimsGenetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs in the absence of a mutation (i.e. genotype-negative HCM). Mitochondrial dysfunction is thought to be a key driver of pathological remodelling in HCM. Reports of mitochondrial respiratory function and specific disease-modifying treatment options in patients with HCM are scarce.Methods and resultsRespirometry was performed on septal myectomy tissue from patients with HCM (n = 59) to evaluate oxidative phosphorylation and fatty acid oxidation. Mitochondrial dysfunction was most notably reflected by impaired NADH-linked respiration. In genotype-negative patients, but not genotype-positive patients, NADH-linked respiration was markedly depressed in patients with an indexed septal thickness ≥10 compared with <10. Mitochondrial dysfunction was not explained by reduced abundance or fragmentation of mitochondria, as evaluated by transmission electron microscopy. Rather, improper organization of mitochondria relative to myofibrils (expressed as a percentage of disorganized mitochondria) was strongly associated with mitochondrial dysfunction. Pre-incubation with the cardiolipin-stabilizing drug elamipretide and raising mitochondrial NAD+ levels both boosted NADH-linked respiration.ConclusionMitochondrial dysfunction is explained by cardiomyocyte architecture disruption and is linked to septal hypertrophy in genotype-negative HCM. Despite severe myocardial remodelling mitochondria were responsive to treatments aimed at restoring respiratory function, eliciting the mitochondria as a drug target to prevent and ameliorate cardiac disease in HCM. Mitochondria-targeting therapy may particularly benefit genotype-negative patients with HCM, given the tight link between mitochondrial impairment and septal thickening in this subpopulation.
OBJECTIVE: We investigated smoking cessation rates in coronary heart disease (CHD) patients throughout Europe; current and as compared to earlier EUROASPIRE surveys, and we studied characteristics of successful quitters.METHODS: Analyses were done on 7998 patients from the EUROASPIRE-IV survey admitted for myocardial infarction, unstable angina and coronary revascularisation. Self-reported smoking status was validated by measuring carbon monoxide in exhaled air.RESULTS: Thirty-one percent of the patients reported being a smoker in the month preceding hospital admission for the recruiting event, varying from 15% in centres from Finland to 57% from centres in Cyprus. Smoking rates at the interview were also highly variable, ranging from 7% to 28%. The proportion of successful quitters was relatively low in centres with a low number of pre- event smokers. Overall, successful smoking cessation was associated with increasing age (OR 1.50; 95% CI 1.09-2.06) and higher levels of education (OR 1.38; 95% CI 1.08-1.75). Successful quitters more frequently reported that they had been advised (56% vs. 47%, p < .001) and to attend (81% vs. 75%, p < .01) a cardiac rehabilitation programme.CONCLUSION: Our study shows wide variation in cessation rates in a large contemporary European survey of CHD patients. Therefore, smoking cessation rates in patients with a CHD event should be interpreted in the light of pre-event smoking prevalence, and caution is needed when comparing cessation rates across Europe. Furthermore, we found that successful quitters reported more actions to make healthy lifestyle changes, including participating in a cardiac rehabilitation programme, as compared with persistent smokers.
This thesis presents an exploration of ‘how entrepreneurship education pedagogy can enhance undergraduate business students’ autonomous motivation for self-directed learning’. It has twin, equally valuable, purposes: to make an original theoretical contribution and to improve professional practice in this area. The work addresses the lack of pedagogical research in entrepreneurship education that focuses on learner development, with a specific aim at development of self-directed learning skills for lifelong learning. The research is approached with a concurrent, mixed methods design, comparing pre- and a post-EE, self-assessment survey results from 245 students, enrolled in a Young Enterprise venture creation programme, and a control group at a Dutch university. With the use of open-question surveys among the same population, during and after the EE modules, as well as from focus group discussions with a selection of participating students and teachers, explanation was sought for the observations drawn from the quantitative study. Significant relationships were found between students’ self-reported maturity of autonomy, self-efficacy, and motivation for learning, and in how these relate to self-directed learning readiness. Entrepreneurship education was found to significantly moderate the relationship between the learning characteristics and self-directed learning, and to strengthen of the students’ perceived readiness for self-directed learning. Explanation for the impact of EE were found to be related to the stage-wise, mixed pedagogy approach to learning, that combines authentic learning with a hierarchical approach to competence development, and supportive team dynamics. The research contributes to practice with a proposed conceptual framework for understanding how to prepare for self-directed learning readiness and a teaching-learning framework for its development in formal educational settings. It contributes to knowledge with its deeper understanding of how students experience learning in EE and how that affects their willingness to pursue learning opportunities.
MULTIFILE
