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.

Induction of cyclin D1 overexpression by activated ras.

Abstract: Activated ras genes are known to alter control of cell proliferation. This is consistent with the fact that ras proteins are a key component of the biochemical pathway triggered by ligand-bound cell surface receptors that are tyrosine kinases. Although an important part of the ras signaling pathway has been recently uncovered, the molecular target(s) that mediates the effects of ras on cell cycle control remains unknown. Cyclins and cyclin-dependent kinases are key molecules in the control of cell cycle. Cyclin D1, in particular, is a critical target for proliferative signals in G1 and it has been shown that ectopic overexpression of this cyclin can significantly alter cell cycle regulation. Here we report that activated ras induces significant overexpression of cyclin D1 in epithelial cells derived from normal rat intestine and mouse mammary gland. A definitive causal role for activated ras in this overexpression is demonstrated by using intestinal cells transfected with an inducible ras expression vector. Treatment of the ras-transformed intestinal clones with anti-sense cyclin D1 oligonucleotides reduces their rate of cell proliferation indicating that the increment in cyclin D1 expression induced by activated ras is instrumental in the higher rate of cell proliferation conferred by the ras oncogene to the IEC cells. Based on these results we propose that, at least in certain cell types, cyclin D1 can be one of the mediators of the transforming action of activated ras.

The sequenced treatment alternatives to relieve depression (STAR*D) trial: a review.

Abstract: Objective:The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is the largest open-label, pragmatic trial that has been undertaken to examine the treatment of major depressive ...

Animal models in burn research

Abstract: Burn injury is a severe form of trauma affecting more than 2 million people in North America each year Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research

Barriers to Goals of Care Discussions With Seriously Ill Hospitalized Patients and Their Families: A Multicenter Survey of Clinicians

Abstract: Importance Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. Objective To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. Design, Setting, and Participants Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. Main Outcomes and Measures Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). Results Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member–related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members’ or patients’ difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members’ or patients’ difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients’ incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions—including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. Conclusions and Relevance Hospital-based clinicians perceive family member–related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

Association of temporal trends in risk factors and treatment uptake with coronary heart disease mortality, 1994-2005.

Abstract: Context Coronary heart disease (CHD) mortality has declined substantially in Canada since 1994. Objective To determine what proportion of this decline was associated with temporal trends in CHD risk factors and advancements in medical treatments. Design, Setting, and Patients Prospective analytic study of the Ontario, Canada, population aged 25 to 84 years between 1994 and 2005, using an updated version of the validated IMPACT model, which integrates data on population size, CHD mortality, risk factors, and treatment uptake changes. Relative risks and regression coefficients from the published literature quantified the relationship between CHD mortality and (1) evidence-based therapies in 8 distinct CHD subpopulations (acute myocardial infarction [AMI], acute coronary syndromes, secondary prevention post-AMI, chronic coronary artery disease, heart failure in the hospital vs in the community, and primary prevention for hyperlipidemia or hypertension) and (2) population trends in 6 risk factors (smoking, diabetes mellitus, systolic blood pressure, plasma cholesterol level, exercise, and obesity). Main Outcome Measures The number of deaths prevented or delayed in 2005; secondary outcome measures were improvements in medical treatments and trends in risk factors. Results Between 1994 and 2005, the age-adjusted CHD mortality rate in Ontario decreased by 35% from 191 to 125 deaths per 100 000 inhabitants, translating to an estimated 7585 fewer CHD deaths in 2005. Improvements in medical and surgical treatments were associated with 43% (range, 11% to 124%) of the total mortality decrease, most notably in AMI (8%; range, −5% to 40%), chronic stable coronary artery disease (17%; range, 7% to 35%), and heart failure occurring while in the community (10%; range, 6% to 31%). Trends in risk factors accounted for 3660 fewer CHD deaths prevented or delayed (48% of total; range, 28% to 64%), specifically, reductions in total cholesterol (23%; range, 10% to 33%) and systolic blood pressure (20%; range, 13% to 26%). Increasing diabetes prevalence and body mass index had an inverse relationship associated with higher CHD mortality of 6% (range, 4% to 8%) and 2% (range, 1% to 4%), respectively. Conclusion Between 1994 and 2005, there was a decrease in CHD mortality rates in Ontario that was associated primarily with trends in risk factors and improvements in medical treatments, each explaining about half of the decrease.