Carboxy-terminal blockade of sortilin binding enhances progranulin gene therapy, a potential treatment for frontotemporal dementia.

Unlabelled: Frontotemporal dementia is commonly caused by loss-of-function mutations in the progranulin gene. Potential therapies for this disorder have entered clinical trials, including progranulin gene therapy and drugs that reduce progranulin interactions with sortilin. Both approaches ameliorate functional and pathological abnormalities in mouse models of progranulin insufficiency.

Overcoming the Disparity in Mitral Valve Repair: A Sex-Based Analysis of Long-Term Outcomes.

Background: Sex disparities remain pervasive across most cardiovascular diseases and continue to demonstrate notably worse early and late outcomes for women, especially after surgical repair. This study aims to investigate outcomes of mitral valve (MV) repair by sex and identify opportunities for improvement.

Methods: A single center retrospective analysis of consecutive patients undergoing MV repair from May 2008 to February 2023 was conducted.

Regulation of extracellular progranulin in medial prefrontal cortex.

Progranulin is a secreted pro-protein that has anti-inflammatory and neurotrophic effects and is necessary for maintaining lysosomal function. Mutations in progranulin (GRN) are a major cause of frontotemporal dementia. Most pathogenic GRN mutations cause progranulin haploinsufficiency, so boosting progranulin levels is a promising therapeutic strategy.

Team Care for the Care Team: A Scoping Review of the Relational Dimensions of Collaboration in Healthcare Contexts.

Examining team care for the care team, this scoping literature review highlights the relational and compassionate dimensions of collaboration and teamwork that can alleviate healthcare worker suffering and promote well-being in challenging contexts of care. Its goal is to provide greater conceptual clarity about team care and examine the contextual dimensions regarding the needs and facilitators of team care. Analysis of the 48 retained texts identified three broad types of communicative practice that constitute team care: sharing; supporting; and leading with compassion.

New perspectives on the evolution of women's cooperation.

A holistic, evolutionary framework about human cooperation must incorporate information about women's cooperative behaviour. Yet, most empirical research on human cooperation has centered on men's behaviour or been derived from experimental studies conducted in western, industrialized populations. These bodies of data are unlikely to accurately represent human behavioural diversity.

Weak, but not strong, ties support coalition formation among wild female chimpanzees.

In social species, individuals may be able to overcome competitive constraints on cooperation by leveraging relationships with familiar, tolerant partners. While strong social ties have been linked to cooperation in several social mammals, it is unclear the extent to which weak social ties can support cooperation, particularly among non-kin. We tested the hypothesis that weakly affiliative social relationships support cooperative coalition formation using 10 years of behavioural data on wild female chimpanzees.

When Bothering is Part of Professional Practice: Interprofessional Collaboration and Institutional Influences in Primary Care.

In Western healthcare systems, increasing numbers of nurse practitioners are practicing in primary care organizations, and their integration onto interprofessional teams can be somewhat bumpy. In this article, we rely on the institutional theory of organizational communication to investigate the situated communication challenges faced by NPs as they integrate onto primary health care teams (RQ1), and how these local challenges manifested institutional features (RQ2). We analyze interview data from NPs, their physician partners, clinical nurses, and a network administrator for NPs at five family medicine clinics in Quebec, Canada.

The Socialization of Unpaid Family Caregivers: A Scoping Review.

As unpaid family caregiving of older adults becomes increasingly prevalent, it is imperative to understand how family caregivers are socialized and how they understand the caregiving role. This PRISMA-ScR-based scoping review examines the published literature between 1995-2019 on the socialization of potential and current unpaid family caregivers of older adults. Of 4,599 publications identified, 47 were included.

Hiatal hernia after robotic-assisted coronary artery bypass graft surgery.

Background: The aim of the present study is to determine the incidence/progression of hiatal hernia (HH) after robotic-assisted coronary artery bypass grafting (RA-CABG) surgery.

Methods: We reviewed the pre- and post-operative computed tomography (CT) of 491 patients who underwent RA-CABG between 2000 and 2017. Post-operative CT was acquired prospectively in a research protocol.

Aggression, glucocorticoids, and the chronic costs of status competition for wild male chimpanzees.

Across vertebrates, high social status affords preferential access to resources, and is expected to correlate positively with health and longevity. Increasing evidence, however, suggests that although dominant females generally enjoy reduced exposure to physiological and psychosocial stressors, dominant males do not. Here we test the hypothesis that costly mating competition by high-ranking males results in chronic, potentially harmful elevations in glucocorticoid production.

Dysregulation of PGC-1α-Dependent Transcriptional Programs in Neurological and Developmental Disorders: Therapeutic Challenges and Opportunities.

Substantial evidence indicates that mitochondrial impairment contributes to neuronal dysfunction and vulnerability in disease states, leading investigators to propose that the enhancement of mitochondrial function should be considered a strategy for neuroprotection. However, multiple attempts to improve mitochondrial function have failed to impact disease progression, suggesting that the biology underlying the normal regulation of mitochondrial pathways in neurons, and its dysfunction in disease, is more complex than initially thought. Here, we present the proteins and associated pathways involved in the transcriptional regulation of nuclear-encoded genes for mitochondrial function, with a focus on the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α).

Evaluating the impact of physical frailty during ageing in wild chimpanzees ().

While declining physical performance is an expected consequence of ageing, human clinical research has placed increasing emphasis on physical frailty as a predictor of death and disability in the elderly. We examined non-invasive measures approximating frailty in a richly sampled longitudinal dataset on wild chimpanzees. Using urinary creatinine to assess lean body mass, we found moderate but significant declines in physical condition with age in both sexes.

Starch or Saline After Cardiac Surgery: A Double-Blinded Randomized Controlled Trial.

Background: Despite decades of investigation, the balance of clinical risks and benefits of fluid supplementation with starch remain unresolved. Patient-centered outcomes have not been well explored in a "real-world" trial in cardiac surgery.

Objective: We sought to compare a starch-based fluid strategy with a saline-based fluid strategy in the cardiac surgery patient.

Biallelic MADD variants cause a phenotypic spectrum ranging from developmental delay to a multisystem disorder.

In pleiotropic diseases, multiple organ systems are affected causing a variety of clinical manifestations. Here, we report a pleiotropic disorder with a unique constellation of neurological, endocrine, exocrine, and haematological findings that is caused by biallelic MADD variants. MADD, the mitogen-activated protein kinase (MAPK) activating death domain protein, regulates various cellular functions, such as vesicle trafficking, activity of the Rab3 and Rab27 small GTPases, tumour necrosis factor-α (TNF-α)-induced signalling and prevention of cell death.

Hybrid arch frozen elephant trunk repair: evidence from the Canadian Thoracic Aortic Collaborative.

Background: The frozen elephant trunk (FET) technique has become an increasingly popular strategy for aortic reconstruction in the setting of extensive thoracic aortic aneurysms or dissections. The objective of this study is to report on the Canadian experience with the FET technique in both the elective and emergent settings.

Methods: A total of 167 consecutive patients (mean age 65±13 years, 30% female, 25% re-operation) underwent elective (70%) and non-elective (30%) aortic arch reconstruction with the FET technique between May 2008 and October 2019 in six centers of the Canadian Thoracic Aortic Collaborative (CTAC).

Wild chimpanzees exhibit humanlike aging of glucocorticoid regulation.

Cortisol, a key product of the stress response, has critical influences on degenerative aging in humans. In turn, cortisol production is affected by senescence of the hypothalamic-pituitary-adrenal (HPA) axis, leading to progressive dysregulation and increased cortisol exposure. These processes have been studied extensively in industrialized settings, but few comparative data are available from humans and closely related species living in natural environments, where stressors are very different.

Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass Grafting: Comparative Effectiveness Analysis With Long-Term Follow-up.

Background Hybrid coronary revascularization (HCR) involves the integration of coronary artery bypass grafting (CABG) and percutaneous coronary intervention to treat multivessel coronary artery disease. Our objective was to perform a comparative analysis with long-term follow-up between HCR and conventional off-pump CABG. Methods and Results We compared all double off-pump CABG (n=216) and HCR (n=147; robotic-assisted minimally invasive direct CABG of the left internal thoracic artery to the left anterior descending artery and percutaneous coronary intervention to one of the non-left anterior descending vessels) performed at a single institution between March 2004 and November 2015.

Human-like adrenal development in wild chimpanzees: A longitudinal study of urinary dehydroepiandrosterone-sulfate and cortisol.

The development of the adrenal cortex varies considerably across primates, being most conspicuous in humans, where a functional zona reticularis-the site of dehydroepiandrosterone-sulfate (DHEA/S) production-does not develop until middle childhood (5-8 years). Prior reports suggest that a human-like adrenarche, associated with a sharp prepubertal increase in DHEA/S, may only occur in the genus Pan. However, the timing and variability in adrenarche in chimpanzees remain poorly described, owing to the lack of longitudinal data, or data from wild populations.

Communication and Interprofessional Collaboration in Primary Care: From Ideal to Reality in Practice.

To improve patient-centered care, many health care systems are mandating interprofessional collaboration (IPC). However, in many primary care contexts, IPC is still nascent and fraught with tension. Communication is thought to be a key determinant of IPC, but few studies empirically examine IP communication practices.

Seno-destructive smooth muscle cells in the ascending aorta of patients with bicuspid aortic valve disease.

Background: Ascending aortic aneurysms constitute an important hazard for individuals with a bicuspid aortic valve (BAV). However, the processes that degrade the aortic wall in BAV disease remain poorly understood.

Methods: We undertook in situ analysis of ascending aortas from 68 patients, seeking potentially damaging cellular senescence cascades.

FGF-23 Deficiency Impairs Hippocampal-Dependent Cognitive Function.

Fibroblast growth factor receptor (FGFR) and α-Klotho transduce FGF-23 signaling in renal tubules to maintain systemic phosphate/vitamin D homeostasis. Mice deficient for either the ligand, FGF-23, or the co-receptor, Klotho, are phenocopies with both showing rapid and premature development of multiple aging-like abnormalities. Such similarity in phenotype, suggests that FGF-23 and Klotho have co-dependent systemic functions.