St Michaels Hospital Toronto
St Michaels Hospital Toronto
Mujib S.,University of Toronto |
Liu J.,University of Toronto |
Nur-Ur Rahman A.K.M.,University of Toronto |
Schwartz J.A.,University of Toronto |
And 4 more authors.
Journal of Virology | Year: 2017
Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. In this study, we determined the ability of 12 well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1 belonging to clades A, B, C, and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro. We further tested unique combinations of these antibodies to determine the optimal antibody cocktails to be tested in future clinical trials. We report that antibody binding to infected CD4 T cells is highly variable and correlates with ADCML and ADCC processes. Particularly, antibodies targeting the envelope glycan shield (2G12) and V1/V2 site (PG9, PG16, and PGT145) are best at recognizing HIV-1-infected CD4 T cells. However, only PG9 and PG16 and their combinations with other bnAbs sufficiently induced the elimination of HIV-1- infected CD4 T cells by ADCML, ADCC, or both. Notably, CD4 binding site antibodies VRC01, 3BNC117, and NIH45-46 G54W did not exhibit recognition of infected cells and were unable to induce their killing. Future trials geared toward the development of a cure for HIV/AIDS should incorporate V1/V2 antibodies for maximal clearance of infected cells. With the use of only primary immune cells, we conducted a comprehensive cross-clade physiological analysis to aid the direction of antibodies as therapeutics toward the development of a cure for HIV/AIDS. © 2017 American Society for Microbiology.
Baumhauer J.F.,University of Rochester |
Pinzur M.S.,Loyola University |
Daniels T.R.,St Michaels Hospital Toronto |
Lin S.S.,Rutgers University |
And 3 more authors.
Foot and Ankle International | Year: 2013
Background: Generally, autologous bone graft is felt to be an important treatment adjunct in the presence of structural deformity, surface irregularities, defects (due to trauma, surgery, or degenerative changes), or underlying comorbidities that predispose the patient to healing challenges. This study assessed the prognostic and predictive factors used in the clinical decision making for bone graft supplementation in foot and ankle fusion surgery. Methods: Utilizing standard survey research methodology, key-informant interviews, pretesting, and pilot testing; a survey was constructed. The survey consisted of a web-based 5-point Likert-type scale (never, seldom, sometimes, almost always, always) listing 14 clinical and 11 radiologic criteria that may influence the use of autologous bone grafting or other biologic augmentation in foot and ankle surgery. This survey was sent to Orthopaedic Foot and Ankle Surgeons in North America and Canada. Results: A total of 48 foot and ankle surgeons completed the blinded survey (73% response rate). More than 70% of responders felt bone graft was almost always (AA) or always (A) indicated in prior nonunion of the indicated joint (96%). Fewer than 50% of respondents felt poor soft tissue integrity (20%), prior foot and ankle infection (20%), and current foot and ankle infection (4%) needed bone graft. Radiologic factors marked as AA or A in over 70% of responders include radiographic evidence of nonunion (96%), avascular necrosis (87%), and others. Factors chosen as AA or A by fewer than 50% of surgeons include prior adjacent joint fusions (47%), intra-articular deformity (31%), and extra-articular deformity (13%). Conclusions: There was some uniformity of agreement on the number of both clinical and radiologic factors that prompt a surgeon to utilize autologous bone graft to try to avoid the complication of nonunion. Surgeons may wish to consider these factors when making a decision on the use of bone graft to supplement fusion. © The Author(s) 2013.
Cortinois A.A.,University of Toronto |
Glazier R.H.,Institute for Clinical Evaluative science |
Glazier R.H.,University of Toronto |
Glazier R.H.,St Michaels Hospital Toronto |
And 4 more authors.
American Journal of Preventive Medicine | Year: 2012
Background: Although access to information on health services is particularly important for recent immigrants, numerous studies have shown that their use of information and referral services is limited. This study explores the role played by 2-1-1 Toronto in supporting recent immigrants. Purpose: The study objectives were to (1) understand whether 2-1-1 Toronto is reaching and supporting recent immigrants and (2) gain a better appreciation of the information needs of this population group. Methods: A phone survey was conducted in 2005-2006 to collect information on 2-1-1 users' characteristics and levels of satisfaction. Survey data were compared (in 2006) with census data to assess their representativeness. To achieve Objective 2, semistructured qualitative interviews were conducted and analyzed in 2006-2007, with a subset of Spanish-speaking callers. Results: Recent immigrants were overrepresented among 2-1-1 callers. However, the survey population was substantially younger and had higher levels of formal education than the general population. Health-related queries represented almost one third of the total. The survey showed very high levels of satisfaction with the service. Many interviewees described their first experiences with the Canadian healthcare system negatively. Most of them had relied on disjointed, low-quality information sources. They trusted 2-1-1 but had discovered it late. Conclusions: Results are mixed in terms of 2-1-1's support to immigrants. A significant percentage of users do not take full advantage of the service. The service could become the information "entry point" for recent immigrants if it was able to reach them early in the resettlement process. Proactive, community-oriented work and a more creative use of technology could help. © 2012 American Journal of Preventive Medicine.
Chow T.-f.F.,Li Ka Shing Knowledge Institute |
Youssef Y.M.,Li Ka Shing Knowledge Institute |
Lianidou E.,National and Kapodistrian University of Athens |
Romaschin A.D.,Li Ka Shing Knowledge Institute |
And 6 more authors.
Clinical Biochemistry | Year: 2010
Objective: We seek to identify the differentially expressed miRNAs in the clear cell subtype (ccRCC) of kidney cancer. Design and methods: We performed a miRNA microarray analysis to compare the miRNA expression levels between ccRCC tissues and their normal counterpart. The top dysregulated miRNAs were validated by quantitative RT-PCR analysis. Bioinformatics analysis was also performed. Results: A total of 33 dysregulated miRNAs were identified in ccRCC, including 21 upregulated miRNAs and many of these miRNAs have been reported to be dysregulated in other malignancies and have a potential role in cancer pathogenesis. The miRNAs showed a significant correlation with reported chromosomal aberration sites. We also utilized target prediction algorithms to identify gene targets. Preliminary analyses showed these targets can be directly involved in RCC pathogenesis. Conclusion: We identified miRNAs that are dysregulated in ccRCC and bioinformatics analysis suggests that these miRNAs may be involved in cancer pathogenesis and have the potential to be biomarkers. © 2009.
PubMed | University of Strathclyde, University of Nottingham, McMaster University, Klinische Forschergruppe and 25 more.
Type: | Journal: Frontiers in microbiology | Year: 2015
The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database (http://ipcd.ibis.ulaval.ca/). Here, we present our strategy and the results that emerged from the analysis of the first 389 genomes. With as yet unmatched resolution, our results confirm that P. aeruginosa strains can be divided into three major groups that are further divided into subgroups, some not previously reported in the literature. We also provide the first snapshot of P. aeruginosa strain diversity with respect to antibiotic resistance. Our approach will allow us to draw potential links between environmental strains and those implicated in human and animal infections, understand how patients become infected and how the infection evolves over time as well as identify prognostic markers for better evidence-based decisions on patient care.
PubMed | McMaster University, University of Toronto, St Michaels Hospital Toronto and Hospital Library
Type: | Journal: Clinical pediatrics | Year: 2015
This systematic review aims to identify existing social risk screening instruments applicable to hospitalized children (primary) and evaluate their content validity and methodological quality (secondary). Individual questions were abstracted and sorted by social risk theme. Content validity was evaluated by 13 hospital-based social workers. Methodological quality was assessed using the 108-item Consensus Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. A total of 1070 citations were evaluated and 146 articles were reviewed, which identified 44 unique instruments. No instrument was applicable to social risk in hospitalized children. Sixty-one percent of instruments focused on a single social risk theme and only 18% of instruments covered more than 5 themes. The 2 instruments with the highest combination of social worker endorsement and COSMIN scores each addressed only 1 social risk theme relevant to hospitalized children. A broad, content valid and methodologically strong social risk screening instrument for hospitalized children was not identified.
PubMed | St Michaels Hospital Toronto, Harvard University and Sunnybrook Research Institute
Type: | Journal: Frontiers in human neuroscience | Year: 2015
Neuropsychological tests of verbal fluency are very widely used to characterize impaired cognitive function. For clinical neuroscience studies and potential medical applications, measuring the brain activity that underlies such tests with functional magnetic resonance imaging (fMRI) is of significant interest-but a challenging proposition because overt speech can cause signal artifacts, which tend to worsen as the duration of speech tasks becomes longer. In a novel approach, we present the group brain activity of 12 subjects who performed a self-paced written version of phonemic fluency using fMRI-compatible tablet technology that recorded responses and provided task-related feedback on a projection screen display, over long-duration task blocks (60 s). As predicted, we observed robust activation in the left anterior inferior and medial frontal gyri, consistent with previously reported results of verbal fluency tasks which established the role of these areas in strategic word retrieval. In addition, the number of words produced in the late phase (last 30 s) of written phonemic fluency was significantly less (p < 0.05) than the number produced in the early phase (first 30 s). Activation during the late phase vs. the early phase was also assessed from the first 20 s and last 20 s of task performance, which eliminated the possibility that the sluggish hemodynamic response from the early phase would affect the activation estimates of the late phase. The last 20 s produced greater activation maps covering extended areas in bilateral precuneus, cuneus, middle temporal gyrus, insula, middle frontal gyrus and cingulate gyrus. Among these areas, greater activation was observed in the bilateral middle frontal gyrus (Brodmann area BA 9) and cingulate gyrus (BA 24, 32) likely as part of the initiation, maintenance, and shifting of attentional resources. Consistent with previous pertinent fMRI literature involving overt and covert verbal responses, these findings highlight the promise and practicality of fMRI of written phonemic fluency.
Jenkins D.J.A.,St Michaels Hospital Toronto |
Jenkins D.J.A.,University of Toronto |
Kendall C.W.C.,St Michaels Hospital Toronto |
Kendall C.W.C.,University of Toronto |
And 17 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - Fat intake, especially monounsaturated fatty acid (MUFA), has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control, yet the exact sources have not been clearly defined. Therefore, we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA 1c in type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 117 type 2 diabetic subjects were randomized to one of three treatments for 3months. Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts (75 g/day),muffins, or half portions of both. The primary outcome was change in HbA 1c. RESULTS - The relative increase in MUFAs was 8.7% energy on the full-nut dose compared with muffins. Using an intention-to-treat analysis (n = 117), full-nut dose (mean intake 73 g/day) reduced HbA 1c (20.21% absolute HbA 1c units, 95% CI 20.30 to 20.11, P < 0.001) with no change after half-nut dose or muffin. Full-nut dose was significantly different from half-nut dose (P = 0.004) and muffin (P = 0.001), but no difference was seen between half-nut dose and muffins. LDL cholesterol also decreased significantly after full-nut dose compared with muffin. The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from the other treatments. Apolipoprotein (apo) B and the apoB:apoA1 ratio behaved similarly. Nut intake related negatively to changes in HbA 1c (r =20.20, P = 0.033) and LDL cholesterol (r = 20.24, P = 0.011). CONCLUSIONS - Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes. © 2011 by the American Diabetes Association.
Jessri M.,University of Toronto |
Nishi S.K.,University of Toronto |
Nishi S.K.,St Michaels Hospital Toronto |
L'Abbe M.R.,University of Toronto
BMC Public Health | Year: 2016
Background: Health Canada's Surveillance Tool (HCST) Tier System was developed in 2014 with the aim of assessing the adherence of dietary intakes with Eating Well with Canada's Food Guide (EWCFG). HCST uses a Tier system to categorize all foods into one of four Tiers based on thresholds for total fat, saturated fat, sodium, and sugar, with Tier 4 reflecting the unhealthiest and Tier 1 the healthiest foods. This study presents the first application of the HCST to examine (i) the dietary patterns of Canadian children, and (ii) the applicability and relevance of HCST as a measure of diet quality. Methods: Data were from the nationally-representative, cross-sectional Canadian Community Health Survey 2.2. A total of 13,749 participants aged 2-18 years who had complete lifestyle and 24-hour dietary recall data were examined. Results: Dietary patterns of Canadian children and adolescents demonstrated a high prevalence of Tier 4 foods within the sub-groups of processed meats and potatoes. On average, 23-31 % of daily calories were derived from "other" foods and beverages not recommended in EWCFG. However, the majority of food choices fell within the Tier 2 and 3 classifications due to lenient criteria used by the HCST for classifying foods. Adherence to the recommendations presented in the HCST was associated with closer compliance to meeting nutrient Dietary Reference Intake recommendations, however it did not relate to reduced obesity as assessed by body mass index (p > 0.05). Conclusions: EWCFG recommendations are currently not being met by most children and adolescents. Future nutrient profiling systems need to incorporate both positive and negative nutrients and an overall score. In addition, a wider range of nutrient thresholds should be considered for HCST to better capture product differences, prevent categorization of most foods as Tiers 2-3 and provide incentives for product reformulation. © 2016 Jessri et al.
Baribeau D.,University of Toronto |
Ramji N.,University of Toronto |
Slater M.,St Michaels Hospital Toronto |
Weyman K.,University of Toronto
Clinical Teacher | Year: 2016
Background: Promoting advocacy and social responsibility is a requirement of medical education. This article describes a brief clinical educational initiative to foster advocacy amongst medical students, and explores student attitudes towards homelessness. Methods: A compulsory clinical experience in homeless health was integrated into the family medicine clerkship curriculum for a subset (n = 30) of all third-year medical students (n = 254) at the University of Toronto in 2012/13. This programme consisted of four half-days, in which students provided primary care within a shelter setting under supervision from a physician. The experience was paired with a supportive and reflective debriefing session, and feedback was collected from participating students. Surveys on attitudes towards homelessness were also administered to all third-year students before and after their rotation in family medicine. Students provided primary care within a shelter setting under supervision from a physician Results: Student feedback indicated that the programme was very well received; however, some students described feeling overwhelmed at times when working with this vulnerable population. On attitude surveys, female sex, age, earlier month of survey administration and interest in certain specialties was associated with more positive attitudes towards homelessness. Discussion: A brief clinical experience outside of a traditional health care setting in which students are exposed to the day-to-day reality of advocating for vulnerable populations can meaningfully contribute to a comprehensive advocacy curriculum. We suggest this programme could be feasibility adapted to other settings and populations. The importance of supportive and reflective mentorship and diverse clinical settings are highlighted. © 2016 John Wiley & Sons Ltd.