ABSTRACT
AIMS: Heart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A. METHODS AND RESULTS: Mice were irradiated and reconstituted with bone marrow cells. Mice lacking functional PPP1R15A, exhibited dilated cardiomyopathy and severe weight loss following irradiation, whilst wild-type mice were unaffected. This was associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in circulation. We provide evidence that the blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. We also show the relevance of GDF15 to lean mass and protein intake in patients with heart failure. CONCLUSION: Our data suggest that cardiac stress mediates a GDF15-dependent pathway that drives weight loss and worsens cardiac function. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.
ABSTRACT
INTRODUCTION: The COVID-19 pandemic has had a significant impact on medical education, with many institutions shifting to online learning to ensure the safety of students and staff. However, there has been a decline in in-person attendance at medical schools across the UK and worldwide following the relaxation of social distancing rules and the reinstation of in-person teaching. Importantly, this trend has been observed prior to the pandemic. While reflected within the literature, there is currently no systematic review describing these changes. We aim to find out how medical students' attendance is changing as documented within the literature and its impact on their educational outcomes. METHODS AND ANALYSIS: This systematic review will follow the guidelines of the Centre of Research and Dissemination, Meta-analyses of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We will search the major databases of Medline via Ovid, Embase via Ovid, Scopus, Web of Science, British Education Index via EBSCOhost and ERIC via EBSCOhost.Two reviewers will independently screen each paper and extract data, with a third reviewer for dispute resolution. All studies reporting on medical students from various universities, both graduate and undergraduate and describing changes in attendance and/or students' educational outcomes will be included. Risk of bias in individual studies will be assessed using the Newcastle-Ottawa Scale and confidence in cumulative evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research approach. A narrative synthesis of the findings from all included studies will be reported. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review of existing publicly available literature. We will subsequently aim to publish the results of this systematic review in a peer-reviewed journal.