Doxorubicin-induced cardiotoxicity and risk factors.

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent to treat solid tumours and hematologic malignancies. Although useful in the treatment of cancers, the benefit of DOX is limited due to its cardiotoxic effect that is observed in a large number of patients. In the literature, there is evidence that the presence of various factors may increase the risk of developing DOX-induced cardiotoxicity.

Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001.

Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. Here we report results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL.

Discovery of STRO-002, a Novel Homogeneous ADC Targeting Folate Receptor Alpha, for the Treatment of Ovarian and Endometrial Cancers.

STRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) currently being investigated in the clinic as a treatment for ovarian and endometrial cancers. Here, we describe the discovery, optimization, and antitumor properties of STRO-002. STRO-002 was generated by conjugation of a novel cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to the nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within a high affinity anti-FolRα antibody using Sutro's XpressCF+, which resulted in a homogeneous ADC with a drug-antibody ratio (DAR) of 4.

Anthracycline-induced cardiotoxicity: targeting high-density lipoproteins to limit the damage?

Doxorubicin (DOX) is an anthracycline antibiotic frequently used against a wide range of cancers, including breast cancer. Although the drug is effective as a treatment against cancer, many patients develop heart failure (HF) months to years following their last treatment with DOX. The challenge in preventing DOX-induced cardiotoxicity is that symptoms present after damage has already occurred in the myocardium.

Impact of Gender on Clinical Evaluation of Trainees in the Intensive Care Unit.

Gender disparities in medical education are increasingly demonstrated, including in trainee assessment. This study aimed to evaluate whether gender differences exist in trainees' evaluation during intensive care unit (ICU) rotations, which has not been previously studied. We reviewed the in-training evaluation reports (ITERs) for trainees rotating through five academic ICUs at the University of Toronto over a 10-year period (2007-2017).

Evaluation of Communities That Care-Effects on Municipal Youth Crime Rates in Victoria, Australia: 2010-2019.

Internationally, youth crime is a significant social problem. Violent youth crime has been rising over the past decade in the state of Victoria, Australia. Communities That Care (CTC) is a coalition training process designed to prevent youth crime.

The age-old question: Thematic analysis of focus groups on physician experiences of aging in emergency medicine.

Objectives: Emergency medicine has a demanding work environment. Characteristics influencing longevity among older physicians in emergency medicine have been the subject of ongoing discussion. The American College of Emergency Physicians (ACEP) released a policy statement in 2009 suggesting accommodating emergency physicians in preretirement years.

Pond Acoustic Sampling Scheme: A draft protocol for rapid acoustic data collection in small waterbodies.

Freshwater conservation is vital to the maintenance of global biodiversity. Ponds are a critical, yet often under-recognized, part of this, contributing to overall ecosystem functioning and diversity. They provide habitats for a range of aquatic, terrestrial, and amphibious life, often including rare and declining species.

If You Build It They Will Come…and Stay: A Community-Based Family Medicine Program.

Introduction: In response to a government request to address physician shortages in underserved communities, the University of Toronto (U of T) established the Family Medicine Residency Program (FMRP) at the Royal Victoria Regional Health Centre (RVH) in Barrie, Ontario, Canada. Prior to establishing the FMRP, approximately 21% of Barrie residents did not have a family physician. This study investigated residents' training experiences, strengths and opportunities for improvement of a community FMRP, reasons why graduates choose to work in Barrie after graduation, and graduates' practice setting and location.

Quantitative 18F-FDG PET-CT scan characteristics correlate with tuberculosis treatment response.

Background: There is a growing interest in the use of F-18 FDG PET-CT to monitor tuberculosis (TB) treatment response. Tuberculosis lung lesions are often complex and diffuse, with dynamic changes during treatment and persisting metabolic activity after apparent clinical cure. This poses a challenge in quantifying scan-based markers of burden of disease and disease activity.

Targeting CD74 in multiple myeloma with the novel, site-specific antibody-drug conjugate STRO-001.

STRO-001 is a site-specific, predominantly single-species, fully human, aglycosylated anti-CD74 antibody-drug conjugate incorporating a non-cleavable linker-maytansinoid warhead with a drug-antibody ratio of 2 which was produced by a novel cell-free antibody synthesis platform. We examined the potential pharmacodynamics and anti-tumor effects of STRO-001 in multiple myeloma (MM). CD74 expression was assessed in MM cell lines and primary bone marrow (BM) MM biopsies.

Admission factors associated with international medical graduate certification success: a collaborative retrospective review of postgraduate medical education programs in Ontario.

Background: The failure rate on certification examinations of The College of Family Physicians of Canada (CFPC) and the Royal College of Physicians and Surgeons of Canada (RCPSC) is significantly higher for international medical graduates than for Canadian medical school graduates. The purpose of the current study was to generate evidence that supports or refutes the validity of hypotheses proposed to explain the lower success rates.

Methods: We conducted retrospective analyses of admissions and certification data to determine the factors associated with success of international medical graduate residents on the certification examinations.

Templation of a square grid copper(II) 4,4'-bipyridine network by a 3D PtS-related Cu(I)-Cu(II) 4,4'-bipyridine crystal.

Two cationic networks, [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) and [Cu(II)(4,4'bipy)2(H2O)2](2+) have been formed from a solution in which Cu(I) undergoes aerial oxidation. Whilst the topologies of the two networks are different the arrangement of Cu centres is almost identical, a structural feature which presumably allows for [Cu(I)Cu(II)(4,4'bipy)4(H2O)2](3+) to serve as a crystalline template for [Cu(II)(bipy)2(H2O)2](2+).

Identifying and Promoting Best Practices in Residency Application and Selection in a Complex Academic Health Network.

Medical education institutions have a social mandate to produce a diverse physician workforce that meets the public's needs. Recent reports have framed the admission process outcome of undergraduate and postgraduate medical education (UGME and PGME) programs as a key determinant of the collective contributions graduating cohorts will make to society, creating a sense of urgency around the issue of who gets accepted. The need for evidence-informed residency application and selection processes is growing because of the increasing size and diversity of the applicant pool and the need for equity, fairness, social accountability, and health human resource planning.

Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch.

Sprouting angiogenesis drives blood vessel growth in healthy and diseased tissues. Vegf and Dll4/Notch signalling cooperate in a negative feedback loop that specifies endothelial tip and stalk cells to ensure adequate vessel branching and function. Current concepts posit that endothelial cells default to the tip-cell phenotype when Notch is inactive.

Choosing psychiatry as a career: motivators and deterrents at a critical decision-making juncture.

Objective: To examine factors influencing the choice of psychiatry as a career between residency program application and ranking decision making.

Methods: Using an online questionnaire, applicants to the largest Canadian psychiatry residency program were surveyed about the impact of various factors on their ultimate decision to enter psychiatry residency training.

Results: Applicants reported that patient-related stigma was a motivator in considering psychiatry as a career, but that negative comments from colleagues, friends, and family about choosing psychiatry was a deterrent.

Functional consequences of Wnt-induced dishevelled 2 phosphorylation in canonical and noncanonical Wnt signaling.

Dishevelled (Dvl) proteins are intracellular effectors of Wnt signaling that have essential roles in both canonical and noncanonical Wnt pathways. It has long been known that Wnts stimulate Dvl phosphorylation, but relatively little is known about its functional significance. We have previously reported that both Wnt3a and Wnt5a induce Dvl2 phosphorylation that is associated with an electrophoretic mobility shift and loss of recognition by monoclonal antibody 10B5.

Tracking family medicine graduates. Where do they go, what services do they provide and whom do they see?

Background: There are continued concerns over an adequate supply of family physicians (FPs) practicing in Canada. While most resource planning has focused on intake into postgraduate education, less information is available on what postgraduate medical training yields. We therefore undertook a study of Family Medicine (FM) graduates from the University of Toronto (U of T) to determine the type of information for physician resource planning that may come from tracking FM graduates using health administrative data.

3d-Metal derivatives of the [Cu(I)(SO3)4]7- ion: structure and magnetism.

The Cu(SO(3))(4)(7-) anion, which consists of a tetrahedrally coordinated Cu(I) centre coordinated to four sulfur atoms, is able to act as a multidentate ligand in discrete and infinite supramolecular species. The slow oxidation of an aqueous solution of Na(7)Cu(SO(3))(4) yields a mixed oxidation state, 2D network of composition Na(5){[Cu(II)(H(2)O)][Cu(I)(SO(3))(4)]}·6H(2)O. The addition of Cu(II) and 2,2'-bipyridine to an aqueous Na(7)Cu(SO(3))(4) solution leads to the formation of a pentanuclear complex of composition {[Cu(II)(H(2)O)(bipy)](4)[Cu(I)(SO(3))(4)]}(+); a combination of hydrogen bonding and π-π stacking interactions leads to the generation of infinite parallel channels that are occupied by disordered nitrate anions and water molecules.