University of Toronto

About: University of Toronto is a education organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 126067 authors who have published 294940 publications receiving 13536856 citations. The organization is also known as: UToronto & U of T.

VEGF inhibition and renal thrombotic microangiopathy.

Abstract: The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.

TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling

Abstract: Bone resorption and remodeling is an intricately controlled, physiological process that requires the function of osteoclasts. The processes governing both the differentiation and activation of osteoclasts involve signals induced by osteoprotegerin ligand (OPGL), a member of tumor necrosis factor (TNF) superfamily, and its cognate receptor RANK. The molecular mechanisms of the intracellular signal transduction remain to be elucidated. Here we report that mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function. Using in vitro assays, we demonstrate that TRAF6 is crucial not only in IL-1 and CD40 signaling but also, surprisingly, in LPS signaling. Furthermore, like TRAF2 and TRAF3, TRAF6 is essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling.

Quality End-of-Life Care: Patients' Perspectives

Abstract: ContextQuality end-of-life care is increasingly recognized as an ethical obligation of health care providers, both clinicians and organizations. However, this concept has not been examined from the perspective of patients.ObjectiveTo identify and describe elements of quality end-of-life care from the patient's perspective.DesignQualitative study using in-depth, open-ended, face-to-face interviews and content analysis.SettingToronto, Ontario.ParticipantsA total of 126 participants from 3 patient groups: dialysis patients (n = 48), people with human immunodeficiency virus infection (n = 40), and residents of a long-term care facility (n = 38).Outcome MeasuresParticipants' views on end-of-life issues.ResultsParticipants identified 5 domains of quality end-of-life care: receiving adequate pain and symptom management, avoiding inappropriate prolongation of dying, achieving a sense of control, relieving burden, and strengthening relationships with loved ones.ConclusionThese domains, which characterize patients' perspectives on end-of-life care, can serve as focal points for improving the quality of end-of-life care.

Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

Abstract: To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.