Evaluation of the indication of BRCA1/2 genetic tests in Iranian women and acceptance rate of risk-reducing surgeries in BRCA mutation carriers.

Background: A higher risk for breast and ovarian cancer has been reported in BRCA carriers and prophylactic surgeries are proposed to reduce this risk. This retrospective cohort study has evaluated the indication of BRCA1/2 genetic tests in Iranian women and the rate of women's acceptance of prophylactic surgeries recommended by the surgeon.

Methods: Medical records of 147 high-risk women according to NCCN clinical practice guidelines who referred for BRCA mutations testing were assessed.

Identification of Key Regions Mediating Human Melatonin Type 1 Receptor Functional Selectivity Revealed by Natural Variants.

Melatonin is a hormone mainly produced by the pineal gland and MT is one of the two G protein-coupled receptors (GPCRs) mediating its action. Despite an increasing number of available GPCR crystal structures, the molecular mechanism of activation of a large number of receptors, including MT, remains poorly understood. The purpose of this study is to elucidate the structural elements involved in the process of MT's activation using naturally occurring variants affecting its function.

What are your thoughts? Exploring age-related changes in episodic and semantic autobiographical content on an open-ended retrieval task.

Older adults display impairments in accessing episodic, but not semantic details, when specifically requested to construct autobiographical events. How aging affects access to autobiographical information under conditions of low retrieval constraint remains unclear. We examined the production of episodic and "non-episodic" details in young ( = 25) and older ( = 24) adults on a novel autobiographical narrative task free from constraints on the type of information to be retrieved (Thoughts task), compared with the standard autobiographical memory and picture description tasks.

Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications.

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition.

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.

Background: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication.

Objective: To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome.

Methods: Data are from the ESCAPE-NA1 Trial.

Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and Cardiac Arrhythmias.

The renin-angiotensin-aldosterone system (RAAS) plays a major role in cardiovascular health and disease. Short-term RAAS activation controls water and salt retention and causes vasoconstriction, which are beneficial for maintaining cardiac output in low blood pressure and early stage heart failure. However, prolonged RAAS activation is detrimental, leading to structural remodeling and cardiac dysfunction.

Axolotls' and Mices' Oral-Maxillofacial Trephining Wounds Heal Differently.

The Ambystoma maxicanum (axolotl) regenerates strikingly from wounds and amputations. Comparing its healing ability to non-regenerative species such as the mouse should help narrow in on mechanisms to improve human wound healing. Here, the tongue and intermandibular soft tissues of both mice (C57BL/6NCrl) and axolotls were wounded with a 2-2.

Does gut microbiota affect atrial rhythm? Causalities and speculations.

Dietary intake has been shown to change the composition of gut microbiota and some changes in microbiota (dysbiosis) have been linked to diabetes, hypertension, and obesity, which are established risk factors for atrial fibrillation (AF). In addition, intestinal dysbiosis generates microbiota-derived bioactive metabolites that might exert proarrhythmic actions. Although emerging preclinical investigations and clinical observational cohort studies suggest a possible role of gut dysbiosis in AF promotion, the exact mechanisms through which dysbiosis contributes to AF remain unclear.

Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression.

Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation.

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Chronic rhinosinusitis with nasal polyps affects approximately 2-4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal polyps.

Methods: SYNAPSE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial done at 93 centres, mainly hospitals, in 11 countries.

Canadian Rhinology Working Group consensus statement: biologic therapies for chronic rhinosinusitis.

Background: Recent evidence suggests that biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of chronic rhinosinusitis with nasal polyposis (CRSwNP). There remains a population in CRSwNP that despite medical therapy and endoscopic sinus surgery have persistent signs and symptoms of disease. Therefore, biologics, monoclonal antibody agents, could be beneficial therapeutic treatments for these patients.

Management of Pediatric Kidney Transplant Patients During the COVID-19 Pandemic: Guidance From the Canadian Society of Transplantation Pediatric Group.

Purpose Of The Program: To provide guidance on the management of pediatric kidney transplant patients during the COVID-19 pandemic.

Sources Of Information: Program-specific documents, preexisting, and related to COVID-19; documents from provincial, national, and international kidney transplant societies/agencies and organ procurement agencies; national and international webinars, including webinars that we hosted for input and feedback; with additional information from formal and informal review of published academic literature.

Methods: Challenges in the care of pediatric kidney transplant patients during the COVID-19 pandemic were highlighted within the Canadian Society of Transplantation (CST) Pediatric Group.

Patterns of lower limb muscular activity and joint moments during directional efforts using a static dynamometer.

Background: Strength and coordination of lower muscle groups typically identified in healthy subjects are two prerequisites to performing functional activities. These physical qualities can be impaired following a neurological insult. A static dynamometer apparatus that measures lower limb joint moments during directional efforts at the foot was developed to recruit different patterns of muscular activity.