The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unreponsive to standard heart failure therapy

Phospholamban (PLN) plays a role in cardiomyocyte calcium handling as primary inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The p.(Arg14del) pathogenic variant in the PLN gene results in a high risk of developing dilated or arrhythmogenic cardiomyopathy with heart failure. There is no established treatment other than standard heart failure therapy or heart transplantation. In this study, we generated a novel mouse model with the PLN-R14del pathogenic variant, performed detailed phenotyping, and tested the efficacy of established heart failure therapies eplerenone or metoprolol. Heterozygous PLN-R14del mice demonstrated increased susceptibility to ex vivo induced arrhythmias, and cardiomyopathy at 18 months of age, which was not accelerated by isoproterenol infusion. Homozygous PLN-R14del mice exhibited an accelerated phenotype including cardiac dilatation, contractile dysfunction, decreased ECG potentials, high susceptibility to ex vivo induced arrhythmias, myocardial fibrosis, PLN protein aggregation, and early mortality. Neither eplerenone nor metoprolol administration improved cardiac function or survival. In conclusion, our novel PLN-R14del mouse model exhibits most features of human disease. Administration of standard heart failure therapy did not rescue the phenotype, underscoring the need for better understanding of the pathophysiology of PLN-R14del-associated cardiomyopathy. This model provides a great opportunity to study the pathophysiology, and to screen for potential therapeutic treatments

Author Correction:The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy (Scientific Reports, (2020), 10, 1, (9819), 10.1038/s41598-020-66656-9)

The title in the original version of this Article contained a typographical error of ‘unresponsive’. The error has now been corrected in the PDF and HTML versions of the Article

The effectiveness of injury prevention programs to modify risk factors for non-contact anterior cruciate ligament and hamstring injuries in uninjured team sports athletes: A systematic review

Background Hamstring strain and anterior cruciate ligament injuries are, respectively, the most prevalent and serious non-contact occurring injuries in team sports. Specific biomechanical and neuromuscular variables have been used to estimate the risk of incurring a non-contact injury in athletes. Objective The aim of this study was to systematically review the evidences for the effectiveness of injury prevention protocols to modify biomechanical and neuromuscular anterior cruciate and/or hamstring injuries associated risk factors in uninjured team sport athletes. Data Sources PubMed, Science Direct, Web of Science, Cochrane Libraries, U.S. National Institutes of Health clinicaltrials.gov, Sport Discuss and Google Scholar databases were searched for relevant journal articles published until March 2015. A manual review of relevant articles, authors, and journals, including bibliographies was performed from identified articles. Main Results Nineteen studies were included in this review. Four assessment categories: i) landing, ii) side cutting, iii) stop-jump, and iv) muscle strength outcomes, were used to analyze the effectiveness of the preventive protocols. Eight studies using multifaceted interventions supported by video and/or technical feedback showed improvement in landing and/or stop-jump biomechanics, while no effects were observed on side-cutting maneuver. Additionally, multifaceted programs including hamstring eccentric exercises increased hamstring strength, hamstring to quadriceps functional ratio and/or promoted a shift of optimal knee flexion peak torque toward a more open angle position. Conclusions Multifaceted programs, supported by proper video and/or technical feedback, including eccentric hamstring exercises would positively modify the biomechanical and or neuromuscular anterior cruciate and/or hamstring injury risk factors

Culturally grounded indicators of resilience in social-ecological systems

International audiencen AbstrAct: Measuring progress toward sustainability goals is a multifaceted task. International , regional, and national organizations and agencies seek to promote resilience and capacity for adaptation at local levels. However, their measurement systems may be poorly aligned with local contexts, cultures, and needs. Understanding how to build effective, culturally grounded measurement systems is a fundamental step toward supporting adaptive management and resilience in the face of environmental, social, and economic change. To identify patterns and inform future efforts, we review seven case studies and one framework regarding the development of culturally grounded indicator sets. Additionally, we explore ways to bridge locally relevant indicators and those of use at national and international levels. The process of identifying and setting criteria for appropriate indicators of resilience in social-ecological systems needs further documentation , discussion, and refinement, particularly regarding capturing feedbacks between biological and social-cultural elements of systems. n Indigenous and other place-based, local communities increasingly face an assortment of externally codified development and sustainability goals, regional commitments, and national policies and actions that are designed, in part, to foster adaptation and resilience at the local level. Resilience refers to the capacity of a system to absorb shocks and disturbances and to catalyze renewal, adaptation, transformation, and innovation (Béneét al. 2013). Identifying and setting criteria for the underlying factors that confer resilience to a community are the first steps toward effectively aligning external sustainability-seeking processes, often associated with resourcing mechanisms, with locally relevant and locally embraced approaches to sustaining environmental health and community well-being in the face of environmental, social, and economic change (Fazey et al. 2011; Folke et al. 2003)

Author Correction: The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy (vol 10, 9819, 2020): The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy

An amendment to this paper has been published and can be accessed via a link at the top of the paper