Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Breast cancer. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

The role of the cerebellum in cognition and behavior: A selective review

Abstract: The cerebellum has traditionally been seen primarily to coordinate voluntary movement, but evidence is accumulating that it may play a role in cognition and behavior as well. This is a selective review of studies assessing potential cognitive deficits and personality changes associated with cerebellar disease. Preliminary studies of the role of the cerebellum in schizophrenia, dementia, and other psychiatric disorders are also discussed. Efforts to understand the neurological substrates of behavior should consider the role of the cerebellum.

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications and Summary of Clinical Trials

Abstract: Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor. The CANVAS trial (Canagliflozin Cardiovascular Assessment Study) subsequently reported a reduction in 3-point major adverse cardiovascular events and HF hospitalization risk. Although SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, and decreases in blood pressure, arterial stiffness, and afterload as well, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients who have HF with and without T2D. Accordingly, in this review, we summarize the key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence that support the rationale for the use of SGLT2 inhibitors in patients with HF who have T2D. Because these favorable effects presumably occur independent of blood glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

The origins of vertebrate adaptive immunity

Abstract: The vertebrate adaptive immune system is defined by antigen-binding receptors of diverse specificity and the cells that express them. But how did this system evolve? Here, our current understanding of the evolutionary acquisition of the factors required to generate such receptor variation and cellular complexity is discussed. Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been thought to occur by the acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of pre-existing systems are the main source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity.

Obstructive Sleep Apnea and Risk of Cardiovascular Events and All-Cause Mortality: A Decade-Long Historical Cohort Study

Abstract: Background: Obstructive sleep apnea (OSA) has been reported to be a risk factor for cardiovascular (CV) disease. Although the apnea-hypopnea index (AHI) is the most commonly used measure of OSA, other less well studied OSA-related variables may be more pathophysiologically relevant and offer better prediction. The objective of this study was to evaluate the relationship between OSA-related variables and risk of CV events. Methods and Findings: A historical cohort study was conducted using clinical database and health administrative data. Adults referred for suspected OSA who underwent diagnostic polysomnography at the sleep laboratory at St Michael’s Hospital (Toronto, Canada) between 1994 and 2010 were followed through provincial health administrative data (Ontario, Canada) until May 2011 to examine the occurrence of a composite outcome (myocardial infarction, stroke, congestive heart failure, revascularization procedures, or death from any cause). Cox regression models were used to investigate the association between baseline OSA-related variables and composite outcome controlling for traditional risk factors. The results were expressed as hazard ratios (HRs) and 95% CIs; for continuous variables, HRs compare the 75th and 25th percentiles. Over a median follow-up of 68 months, 1,172 (11.5%) of 10,149 participants experienced our composite outcome. In a fully adjusted model, other than AHI OSA-related variables were significant independent predictors: time spent with oxygen saturation ,90% (9 minutes versus 0; HR=1.50, 95% CI 1.25–1.79), sleep time (4.9 versus 6.4 hours; HR=1.20, 95% CI 1.12–1.27), awakenings (35 versus 18; HR=1.06, 95% CI 1.02–1.10), periodic leg movements (13 versus 0/ hour; HR=1.05, 95% CI 1.03–1.07), heart rate (70 versus 56 beats per minute [bpm]; HR=1.28, 95% CI 1.19–1.37), and daytime sleepiness (HR=1.13, 95% CI 1.01–1.28).The main study limitation was lack of information about continuous positive airway pressure (CPAP) adherence. Conclusion: OSA-related factors other than AHI were shown as important predictors of composite CV outcome and should be considered in future studies and clinical practice. Please see later in the article for the Editors’ Summary.