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.

Fixation effects on membranous and endochondral onlay bone graft revascularization and bone deposition.

Abstract: This paper investigates the relationship between bone resorption, the process of bone revascularization, and graft fixation. Vital staining techniques and microangiography were used to study the extent of graft revascularization of fixed and nonfixed endochondral (rib) and membranous (skull) onlay b

Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study

Abstract: Importance Self-harm behaviors, including suicidal ideation and past suicide attempts, are frequent in bariatric surgery candidates. It is unclear, however, whether these behaviors are mitigated or aggravated by surgery. Objective To compare the risk of self-harm behaviors before and after bariatric surgery. Design, Setting, and Participants In this population-based, self-matched, longitudinal cohort analysis, we studied 8815 adults from Ontario, Canada, who underwent bariatric surgery between April 1, 2006, and March 31, 2011. Follow-up for each patient was 3 years prior to surgery and 3 years after surgery. Main Outcomes and Measures Self-harm emergencies 3 years before and after surgery. Results The cohort included 8815 patients of whom 7176 (81.4%) were women, 7063 (80.1%) were 35 years or older, and 8681 (98.5%) were treated with gastric bypass. A total of 111 patients had 158 self-harm emergencies during follow-up. Overall, self-harm emergencies significantly increased after surgery (3.63 per 1000 patient-years) compared with before surgery (2.33 per 1000 patient-years), equaling a rate ratio (RR) of 1.54 (95% CI, 1.03-2.30; P = .007). Self-harm emergencies after surgery were higher than before surgery among patients older than 35 years (RR, 1.76; 95% CI, 1.05-2.94; P = .03), those with a low-income status (RR, 2.09; 95% CI, 1.20-3.65; P = .01), and those living in rural areas (RR, 6.49; 95% CI, 1.42-29.63; P = .02). The most common self-harm mechanism was an intentional overdose (115 [72.8%]). A total of 147 events (93.0%) occurred in patients diagnosed as having a mental health disorder during the 5 years before the surgery. Conclusions and Relevance In this study, the risk of self-harm emergencies increased after bariatric surgery, underscoring the need for screening for suicide risk during follow-up.

Isoform-specific antibodies reveal distinct subcellular localizations of C9orf72 in amyotrophic lateral sclerosis.

Abstract: Objective A noncoding hexanucleotide repeat expansion in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) It has been reported that the repeat expansion causes a downregulation of C9orf72 transcripts, suggesting that haploinsufficiency may contribute to disease pathogenesis Two protein isoforms are generated from three alternatively spliced transcripts of C9orf72; a long form (C9-L) and a short form (C9-S), and their function(s) are largely unknown owing to lack of specific antibodies Methods To investigate C9orf72 protein properties, we developed novel antibodies that recognize either C9-L or C9-S Multiple techniques, including Western blot, immunohistochemistry, and coimmunoprecipitation, were used to determine the expression levels and subcellular localizations of C9-L and C9-S Results Investigation of expression of C9-L and C9-S demonstrated distinct biochemical profiles, region-specific changes, and distinct subcellular localizations in ALS tissues In particular, C9-L antibody exhibited a diffuse cytoplasmic staining in neurons and labeled large speckles in cerebellar Purkinje cells In contrast, C9-S antibody gave very specific labeling of the nuclear membrane in healthy neurons, with apparent relocalization to the plasma membrane of diseased motor neurons in ALS Coimmunoprecipitation experiments revealed an interaction of the C9-isoforms with both Importin β1 and Ran-GTPase, components of the nuclear pore complex Interpretation Using these antibodies, we have shown that C9orf72 may be involved in nucleocytoplasmic shuttling and this may have relevance to pathophysiology of ALS/FTLD Our antibodies have provided improved detection of C9orf72 protein isoforms, which will help elucidate its physiological function and role in ALS/FTLD Ann Neurol 2015;78:568–583

Thrombelastography (TEG ® ): practical considerations on its clinical use in trauma resuscitation

Abstract: Thrombelastography is a laboratorial test that measures viscoelastic changes of the entire clotting process. There is growing interest in its clinical use in trauma resuscitation, particularly for managing acute coagulopathy of trauma and assisting decision making concerning transfusion. This review focuses on the clinical use of thrombelastography in trauma, with practical points to consider on its use in civilian and military settings. A search in the literature using the terms “thrombelastography AND trauma” was performed in PUBMED database. We focused the review on the main clinical aspects of this viscoelastic method in diagnosing and treating patients with acute coagulopathy of trauma during initial resuscitation. Thrombelastography is not a substitute for conventional laboratorial tests such as INR and aPTT but offers additional information and may guide blood transfusion. Thrombelastography can be used as a point of care test but requires multiple daily calibrations, should be performed by trained personnel and its technique requires standardization. While useful partial results may be available in minutes, the whole test may take as long as other conventional tests. The most important data provided by thrombelastography are clot strength and fibrinolysis. Clot strength measure can establish whether the bleeding is due to coagulopathy or not, and is the key information in thrombelastography-based transfusion algorithms. Thrombelastography is among the few tests that diagnose and quantify fibrinolysis and thus guide the use of anti-fibrinolytic drugs and blood products such as cryoprecipitate and fibrinogen concentrate. It may also diagnose platelet dysfunction and hypercoagulability and potentially prevent inappropriate transfusions of hemostatic blood products to non-coagulopathic patients. Thrombelastography has characteristics of an ideal coagulation test for use in early trauma resuscitation. It has limitations, but may prove useful as an additional test. Future studies should evaluate its potential to guide blood transfusion and the understanding of the mechanisms of trauma coagulopathy.

Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease.

Abstract: Fragmented sleep is a common and troubling symptom in ageing and Alzheimer’s disease; however, its neurobiological basis in many patients is unknown. In rodents, lesions of the hypothalamic ventrolateral preoptic nucleus cause fragmented sleep. We previously proposed that the intermediate nucleus in the human hypothalamus, which has a similar location and neurotransmitter profile, is the homologue of the ventrolateral preoptic nucleus, but physiological data in humans were lacking. We hypothesized that if the intermediate nucleus is important for human sleep, then intermediate nucleus cell loss may contribute to fragmentation and loss of sleep in ageing and Alzheimer’s disease. We studied 45 older adults (mean age at death 89.2 years; 71% female; 12 with Alzheimer’s disease) from the Rush Memory and Aging Project, a community-based study of ageing and dementia, who had at least 1 week of wrist actigraphy proximate to death. Upon death a median of 15.5 months later, we used immunohistochemistry and stereology to quantify the number of galanin-immunoreactive intermediate nucleus neurons in each individual, and related this to ante-mortem sleep fragmentation. Individuals with Alzheimer’s disease had fewer galaninergic intermediate nucleus neurons than those without (estimate −2872, standard error = 829, P = 0.001). Individuals with more galanin-immunoreactive intermediate nucleus neurons had less fragmented sleep, after adjusting for age and sex, and this association was strongest in those for whom the lag between actigraphy and death was <1 year (estimate −0.0013, standard error = 0.0005, P = 0.023). This association did not differ between individuals with and without Alzheimer’s disease, and similar associations were not seen for two other cell populations near the intermediate nucleus. These data are consistent with the intermediate nucleus being the human homologue of the ventrolateral preoptic nucleus. Moreover, they demonstrate that a paucity of galanin-immunoreactive intermediate nucleus neurons is accompanied by sleep fragmentation in older adults with and without Alzheimer’s disease.