Effect of a home-based exercise program on subsequent falls among community-dwelling older adults with cognitive frailty: A sub-group analysis of a randomized controlled trial.

Objectives: Cognitive frailty is characterized by concurrent physical frailty and mild cognitive impairment and is associated with increased risk of falls. Exercise is an evidence-based strategy to prevent falls, but whether exercise reduces falls in people with cognitive frailty is unknown. We examined the effects of home-based exercise on subsequent falls among community-dwelling older adults with cognitive frailty who have previously fallen.

Diabetes Associated With Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder characterized primarily by hearing impairment and diabetes. m.3243A>G, the most common phenotypic variant, causes a complex rewiring of the cell with discontinuous remodeling of both mitochondrial and nuclear genome expressions.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

Routine Spironolactone in Acute Myocardial Infarction.

Background: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain.

Methods: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo.

Regulatory T cells engineered with polyphenol-functionalized immunosuppressant nanocomplexes for rebuilding periodontal hard tissue under inflammation-challenged microenvironment.

Global aging heightens the risk of oral disorders, among which periodontitis is the major cause of tooth loss in the aging population. The regeneration of damaged periodontal hard tissue is highly challenging due to the existence of the refractory local inflammation. Owing to the potent anti-inflammatory capabilities, regulatory T cells hold great promise in immunotherapies for tissue regeneration.

New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.

Compact cell type-specific promoters are important tools for basic and preclinical research and clinical delivery of gene therapy. In this work, we designed novel MiniPromoters to target D1 and D2 type dopaminoceptive medium spiny neurons in the striatum by manually identifying candidate regulatory regions or employing the OnTarget webserver. We then empirically tested the designs in rAAV-PHP.

Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre.

Background: The findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes of multidisciplinary VUS Rounds, implemented at a neurological disease tertiary care centre, which aid in interpreting and communicating VUS identified in our neurogenetics patient population.

Methods: VUS Rounds brought together genetic counsellors, molecular geneticists and scientists to evaluate VUS against genomic and phenotypic evidence and assign an internal temperature classification of 'VUS Hot', 'True VUS' or 'VUS Cold', corresponding to potential pathogenicity.

Health Equity in the Care of Adult Critical Illness Survivors.

There is evidence that people who fare worse in recovery do so, not only because of their illness, but also because of social and structural determinants. For example, food insecurity and poor nutrition, unemployment, poverty, social isolation and loneliness, limited social support, and poor access to medical care represent marked obstacles to recovery. Those who experience social or structural disadvantage have a poor start to their critical illness journey and are more vulnerable to adverse material conditions that contribute to and worsen their health outcomes.

A framework for categorizing sources of uncertainty in in silico toxicology methods: Considerations for chemical toxicity predictions.

Improving regulatory confidence and acceptance of in silico toxicology methods for chemical risk assessment requires assessment of associated uncertainties. Therefore, there is a need to identify and systematically categorize sources of uncertainty relevant to the methods and their predictions. In the present study, we analyzed studies that have characterized sources of uncertainty across commonly applied in silico toxicology methods.

When New Experience Leads to New Knowledge: A Computational Framework for Formalizing Epistemically Transformative Experiences.

The discovery of a new kind of experience can teach an agent what that kind of experience is like. Such a discovery can be epistemically transformative, teaching an agent something they could not have learned without having that kind of experience. However, learning something new does not always require new experience.

Biomedical research grant resubmission: rates and factors related to success - a scoping review.

Objectives: Most first-time biomedical research grant applications are not funded. In the challenging research funding climate, resubmitting a grant application is a necessary task for scientists. Identifying which factors influence their decision to resubmit and the success of resubmissions will inform funders and applicants.

Structural variation in the pangenome of wild and domesticated barley.

Pangenomes are collections of annotated genome sequences of multiple individuals of a species. The structural variants uncovered by these datasets are a major asset to genetic analysis in crop plants. Here we report a pangenome of barley comprising long-read sequence assemblies of 76 wild and domesticated genomes and short-read sequence data of 1,315 genotypes.

Long-read sequencing for detection and subtyping of Prader-Willi and Angelman syndromes.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are imprinting disorders caused by genetic or epigenetic aberrations of 15q11.2-q13. Their clinical testing is often multitiered; diagnostic testing begins with methylation-specific multiplex ligation-dependent probe amplification or methylation-sensitive PCR and then proceeds to molecular subtyping to determine the mechanism and recurrence risk.

Prevention and Management of Cardiovascular Disease in Primary Care: A Comment on the PEER Simplified Lipid Guideline.

Background: In Canada, 2 guidelines provide guidance for the management of dyslipidemia. The Patients, Experience, Evidence, Research simplified lipid guidelines, intended for primary care practitioners, and the Canadian Cardiovascular Society guidelines, intended for all practitioners, are based on differing methodologies with distinct priorities and preferences. The disparate approaches may contribute to confusion among family practitioners and their co-managed patients, with the potential for compromised care, differing standards for training in the fundamentals of lipidology, and differing criteria that might be used in practice audits to evaluate quality of care.

'We listened and supported and depended on each other': a qualitative study of how leadership influences implementation of QI interventions.

Background: There is growing recognition in the literature of the 'Herculean' efforts required to bring about change in healthcare processes and systems. Leadership is recognised as a critical lever for implementation of quality improvement (QI) and other complex team-level interventions; however, the processes by which leaders facilitate change are not well understood. The aim of this study is to examine 'how' leadership influences implementation of QI interventions.

Impact of department chair gender on paid parental leave across American anaesthesiology residencies.

Background: Residency training and parenthood are conflicting pursuits for many residents, as both often occur during similar years of life. Online policy about paid parental leave for residents is important for not only mitigating this dilemma, but also ensuring that the associated health benefits can be fully capitalised on.

Purpose: Investigate the extent of advertised paid parental leave for anaesthesiology residencies in the USA and to explore whether this had an association with the gender of the department chair for these programmes.

Gender disparity in Canadian Institutes of Health Research funding within neurology.

Background: Despite efforts to advance equity, diversity and inclusion, women face gender-based barriers in research, including in neurology. Compared with men, women are less likely to hold leadership positions and be senior authors. Gender disparities in grant funding within neurology have yet to be investigated.

Role for Lumbar Cerebrospinal Fluid Drainage in High-risk Thoracic Endovascular Aortic Repair: A Narrative Review.

Lumbar cerebrospinal fluid (CSF) drainage is one of the few preventative and therapeutic practices that may reduce spinal cord ischemia in high-risk thoracic endovascular aortic aneurysm repair (TEVAR). Although this is part of clinical guidelines in open thoracoabdominal aortic repair, there are no randomized controlled trials that provide convincing evidence on the protection conferred by CSF drainage in high-risk TEVAR patients. This gap in knowledge obfuscates clinical decision making given the risk of significant complications of CSF drain insertion and management.