13th Annual Canadian Undergraduate Conference on Healthcare 2017: Medicine in the Modern World

The following are abstracts from the research competition at the 13th annual Canadian Undergraduate Conference on Healthcare. The conference was entitled “Medicine in the Modern World”, held on November 10th-12th, 2017 at Queen’s University. Abstracts are grouped under the categories of oral and poster presentations, with sub-categories based on the general field in which the abstract is found. For more information about the conference, please go to https://www.cucoh.com/.

[2] Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
[3] Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.[4] Women's College Research Institute, University of Toronto, Toronto, Canada.[5] Tisch Cancer Institute, Mount Sinai School of Medicine, New York, USA.
[6] Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Background: Pancreatic cancer is the fourth most common cause of mortality due to cancer globally.Pancreatic cancer has a poor prognosis and is usually diagnosed at later stages when tumor resection is not possible.Heritability for pancreatic cancer is relatively high and clinically significant.Methods: A group of 24 pancreatic cancer patients with young age at onset from a referral hospital in Tehran University of Medical Sciences were screened for mutations in 710 cancer relevant genes.
Results: Two patients had pathogenic mutations in known pancreatic cancer susceptibility genes, BRCA1/2.Two other patients also had potentially pathogenic mutations in two novel candidate genes including PARP4 and EXO1.Conclusion: BRCA1/2 genes are the most commonly mutated pancreatic cancer susceptibility genes and they should be considered in all pancreatic cancers cases with young age at onset or family history of cancer.PARP4 and EXO1 are also potential candidate genes for susceptibility to pancreatic cancer.Identifying the hereditary cases of pancreatic cancer will help in a known site for cancer genesis.The Hippo signaling pathway is important in regulating cell cycle and its chore is a phosphorylation cascade.LATS1 and LATS2 are putative tumor suppressors that are able to phosphorylate YAP.Unphosphorylated YAP is a transcription regulator that affects transcription of proliferation and survival genes.It is reported that Hippo signaling is disrupted in multiple cancers and that LATS1 levels decrease in OSE cells in malignancy.Therefore, we hypothesized that the loss of LATS1/2 contributes to the development of ovarian cancer.We unveiled that the loss of LATS1/2 in OSE cells increases proliferation.Also, deletion of LATS1/2 in OSE cells in vivo results in an aggressive ovarian cancer phenotype.By immunohistochemistry, we confirmed the histological subtype to be epithelial high-grade serous carcinoma, because tumors were positive for PAX8, WT1 and CK19.To suppress tumor growth, we treated mice with a YAP inhibitor.Verteporfin prevents YAP from interacting with transcription factors and therefore prevents transcription of targeted genes.We found that treating LATS1/2 deleted mice with verteporfin decreases tumor size.Finally, we showed that YAP is increased in human ovarian cancer cells by western blot.Our results suggest that dysregulations in the Hippo signaling pathway and especially in the phosphorylation cascade can cause OSE cell-derived ovarian cancer.

Oral Presentations in Physiology
Assessment of left ventricular function by cardiac MRI versus MUGA scans in breast cancer patients receiving trastuzumab: A prospective observational study Vinita Dhir, BSc Student [1], Andrew T. Yan, MD [2], Rosane Nisenbaum, PhD [3], Joanna Sloninko, MRT(N), MR(MR) [4], Kim A. Connelly,MBBS,PhD [2], Joseph Barfett, MD [4], Rashida Haq MD [1], Anish Kirpalani, MD [4], Kelvin KW Chan, MD, PhD [5], Teresa M. Petrella, MD [5], Christine Brezden-Masley, MD, PhD [1] [1] Division of Hematology/Oncology,St. Michael's Hospital,Toronto,ON,Canada,M5B 1W8 [2] Terrence Donnelly Heart Centre,St. Michael's Hospital,Toronto,ON,Canada,M5B 1W8 [3] Keenan Research Centre of the Li Ka Shing Knowledge Institute,St. Michael's Hospital,Toronto,ON,Canada,M5B 1W8 [4] Department of Medical Imaging,St. Michael's Hospital,Toronto,ON,Canada,M5B 1W8 [5] Sunnybrook Odette Cancer Centre, Toronto, ON, Canada, M4N 3M5 Purpose: Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab.The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied.Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume.Methods: This prospective longitudinal 2-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013.MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation.Results: 41 patients (age 51.7 ± 10.8 years) were enrolled.LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r=0.46,baseline;r=0.29,6 months;r=0.42,12 months;r=0.39,18 months;all p<0.05).Bland-Altman plots demonstrated wide agreement limits in LVEF (pooled agreement limits 3.0 ± 6.2).Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR.Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p<0.05), and LV systolic volume at 18 months (p<0.05).Conclusions: CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring.CMR is useful due to less radiation exposure and its accuracy of LV volume measurements.Changes in NT-BNP correlated with changes in LV volumes.Journal (2017): Volume 1, Issue 3 Page A8 of A28 DOI Link: https://doi.org/10.26685/urncst.15 [5] Lawrence S. Bloomberg Faculty of Nursing, University of Toronto,Toronto,Ontario,Canada,M5T 1P8 [6] Pediatrics, Surgery and Immunology, University of Alberta,Edmonton,Alberta,Canada,T6G 2R3 [7] Canadian National Transplant Research Program [8] Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada M5S 1V4 Aims: Subjective evaluation of disease outcomes and treatment from the patient's perspective has become increasingly important.Patient-reported outcome measures (PROMs) play a significant role in engaging patients in their healthcare and capturing their experiences.This review sought to identify PROMs used in the field of pediatric solid organ transplantation (Tx) and to analyse their health concepts, domains and psychometric properties.Methods: A systematic review of English language articles was performed on key databases (i.e., MEDLINE, EMBASE, CINAHL, PsychINFO) to identify publications utilizing PROMs in a pediatric Tx population.Screening and study selection were undertaken by two independent researchers.Methodological quality and psychometric properties of instruments validated within pediatric Tx were assessed using COSMIN.The systematic review was prospectively registered with PROS-PERO.

Williams et al. | URNCST
Results: The search yielded 3,670 articles with a final data set of 65 articles discussing 48 different PROMs.The PedsQL -Generic Core Scales (n=26) was the most frequently used PROM.PROMs were categorized according to their health concept: quality of life (n=16), psychological (n=23), physical (n=4), or social functioning (n=3), adherence behaviour (n=2).Seven PROMs were validated in a pediatric Tx population, with limited evidence for their psychometric properties.Conclusions: This systematic review identified PROMs used in the field of pediatric solid organ Tx.As the psychometric properties of PROMs were not adequately assessed within the specific patient population, more extensive validation and evaluation is necessary.This review helps guide methodological decision-making processes for integration of PROMs into clinical care.
"This is your brain on DHCA": Neurological activity in deep hypothermic circulatory arrest Alexander J. Puddifant, BSc Student [1,2], Michael McCartin, Jr, BS [1] [1] Aortic Institute at Yale-New Haven Hospital, Section of Cardiac Surgery, Department of Surgery, Yale University School of Medicine,New Haven,Connecticut,USA [2] Faculty of Science, University of Western Ontario, London, Ontario, Canada Deep hypothermic circulatory arrest (DHCA) is a commonly used technique for cerebral protection during surgical interventions involving the aortic arch.Although the effects of hypothermia on human organs and tissues have been extensively studied, what happens to the brain function as a result of cooling and rewarming is still not understood.We present a review with a particular focus on the current literature regarding DHCA and its effect on brain function assessed via intraoperative neuromonitoring.This presentation was originally featured as a continuing medical education (CME) accredited presentation at the August 2017 Aortic Institute Meeting of the Aortic Institute at Yale-New Haven Hospital at the Yale University School of Medicine in New Haven, Connecticut.

Dor David Abelman, HBHSc(c) [1] [1] Western University, Faculty of Health Sciences, School of Health Studies
To achieve true health equity, we must take into consideration one of Canada's deadliest categories of diseasecancers.Cancer incidence varies significantly across the country, with social determinants of health playing an important role.Aboriginal communities had worse outcomes of cancer and unique risk factors that should be considered in prevention programs.Some significant factors were food security, income, diet, land dispossession, alcohol use, smoking behaviour, and environmental pollution.There is much potential to reduce risk and improve disease outcomes.With improvements in health equity and education, Canadians can enjoy a significant reduction in cancer incidence and risk.Today more than ever we understand that social determinants of health are essential for keeping populations healthy and well.This review suggests that applying these principles to cancer, with an equity focus, can be the next big significant improvement to public health.Policy recommendations include: using culturally appropriate health education sources, working with priority population to understand their needs (and unique drivers of risky behaviour), and focusing on social determinants of health to address risk factors more effectively (ex/ food insecurity or pollution on reserve).

Advice and recommendations given to pregnant elite and high level recreational athletes in the sports community -A survey of coaches
Hiba Haidar Al-Bahrani, BSc Student [1], Karen Fleming, MD, MSC, CCFP [2] [1] Evaluative Clinical Scienes,Sunnybrook Health Sciences Center,Toronto,Ontario,Canada,M4N 3M5;Biomedical Sciences,University of Ottawa,Ottawa,Ontario,Canada,K1N 6N5 [2] Family Medicine and Obstetrics,Sunnybrook Health Sciences Center,Toronto,Ontario,Canada,M4N 3M5 Introduction: A study of pregnancy and reproductive outcomes in elite and high-level recreational athletes completed in summer/fall 2016 revealed athletes are not receiving adequate information or advice aligned with SOGC guidelines regarding exercise in the antenatal, perinatal and post-partum period.Elite and high-level recreational athletes revealed they often turned to coaches for recommendations in exercise in pregnancy.Objective: To identify the general knowledge of swimming coaches with regards to exercise in pregnancy, and determine whether advice given to pregnant elite and high-level recreational athletes align with Canadian guidelines.Study design: Retrospective cohort survey studydata will be collected through a link administered by email to Masters Swimming coaches using Qualtrics survey Subjects: Swimming coaches for Masters Swimming (n=300) who have coached pregnant swimmers Observation techniques: Participants were administered a survey of approximately 12 questions.Survey questions will ask about amount of pregnant swimmers, current knowledge of coaches concerning pregnancy, advice and recommendations coaches give their swimmers, and interest in receiving further information on exercise in pregnancy.Results: Preliminary data (n=14) shows coaches in Canada coach on average 5 pregnancy swimmers per year, and 87% of those coaches have been asked for advice on exercise in pregnancy by their swimmers, but feel only moderately comfortable (on a likert scale of 1-10) providing advice.Conclusion: All respondants were interested in receiving further information on exercise in pregnancy, demonstrating a clear absence in dissemation of knowledge of exercise physiology in pregnancy from those providing care, in any form, to pregnant athletes.This study warrants further research with an increased sample size.This study may lead to further attempts at educating trainers and coaches about the exercise and pregnancy guidelines.

This is your brain on neoliberalism: Ideology as pathology
Feodor Poukhovski-Sheremetyev, BA Candidate (2019) [1].[1] University of Alberta, Edmonton, AB, Canada, T6G 2R3 While the "biopsychosocial" approach has become increasingly ubiquitous in clinical psychology, the "social" aspect of this model rarely looks beyond immediate circumstances such as income and family situation.Conversely, the sociological field has spent well over a century examining how large-scale social factors can affect the psychology of the individual.This presentation seeks to marry these two lenses by examining how neoliberalism, the dominant socioeconomic ideology of our time, can have a profound negative effect on mental health.With current and future clinicians in mind, a brief introduction to the isolating tenets of neoliberalism will be followed by an examination of how this ideology produces distinct psychopathologies and damages the mental healthcare system itself.Developing an awareness of the ideology we live under and how it affects practice is critical for any clinician hoping to apply the biopsychosocial approach with greater efficacy and nuance.[1], Caitlin Miron, PhD Candidate [1], Anne Petitjean, PhD [1] [1] Department of Chemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6 Guanine quadruplex is an emerging area of supramolecular research with important implications for regulation of oncogenes.Guanine quadruplexes have been demonstrated to form in vitro from Hoogsteen bonding between four guanine base pairs from four strands of DNA.The four guanines form a planar tetrad which can stack on top of other similar tetrads to establish a quadruplex structure.Recent research demonstrated convincing evidence that g-quadruplex forms in vivo at key oncogene promoter regions.This current project and the Petitjean group are focused on designing chemical complexes which selectively binds to unique G-quadruplexes.Specifically, this project is focused on stabilizing the c-MYC g-quadruplex which inhibits expression of the c-MYC oncogene, and the human telomeric sequence, 22AG, the formation of which can inhibit telomere elongation which contributes to immortalization in cancer cells.Various biophysical analytical techniques have been employed to study the interactions of these synthesized ligands with G-quadruplexes.Circular dichroism titrations were performed to compare the interactions of different ligands with the c-MYC and 22AG quadruplexes.Any changes brought to the G-quadruplex conformation by ligand interaction could be confirmed in the CD spectra.Moreover, fluorescent intercalator displacement titrations (FID) were performed with the fluorescent agent, thiazole orange, to evaluate the binding constants of ligands to both G-quadruplexes and duplex DNA.Development of mathematical models based on FID results were used to explain and quantify the binding affinity and stoichiometry between ligand and DNA as well as the binding selectivity of the ligand for quadruplex over duplex DNA.

Mesenchymal stem cell transplantation reversed neuropathic pain in rats and mice
Kathleen Cheng, BSc Student [1] Chronic neuropathic pain (NP) due to disease or lesion of the somatosensory nervous system is one of the most common and most difficult-to-treat pain conditions.Mesenchymal stem cell transplantation (MSC-TP) has shown promise for treating NP but a number of critical parameters need to be determined before clinical trials.We investigated effects of the source of MSCs and route of administration in rats and mice.MSCs were isolated from the bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) from rats and human and characterized by functional differentiation and flow cytometry.Rats and mice with chronic constriction injury (CCI) of the sciatic nerve were transplanted either intravenously (IV) or intrathecally (IT) with BM-MSCs or AD-MSCs.The effects were evaluated by testing paw withdrawal thresholds in response to mechanical and thermal stimuli.MSCs, labeled with Dil dye, were traced after transplantation and immunohistochemistry was performed of the sciatic nerve and DRG.MSC-TP through either IT or IV significantly reversed NP in rats and mice.Similar results were observed between BM-MSCs and AD-MSCs and between human and rat MSCs.MSCs were traced to the injury site of the sciatic nerve after either IV or IT MSC-TP.Inflammation and nerve injury (Aδ and C fibers), induced by the CCI, were significantly reduced after MSC-TP.Signs of toxicity was not observed in any of the vital organs or functions.Thus, MSCs were remarkably efficacious in mitigating NP, promoting nerve repair, and modulating inflammatory processes surrounding the injured sciatic nerve, regardless the source and route of application.

Investigating associations between MTHFR and APOE genotypes and neurodegenerative disease phenotypes
Emily C. Evans, BMSc Student [1,2], Allison A. Dilliott,MSc Student [1,2], Sali M.K. Farhan, PhD [1,2], Mahdi Ghani, MD, PhD [3],Christine Sato,MSc [3], Eric Liang, BSc [1], Ming Zhang, PhD [3], Adam D. McIntyre, BSc [1], Henian Cao, MD [1], Lemuel Racacho, PhD [4,5], John F. Robinson [1], ONDRI Investigators, Michael J. Strong, MD, FRCP(C), FANN,FCAHS [1,6], Mario Masellis,MD,PhD,FRCPC [7],MD,FRS,FRSC,FRCPC [3,8], Dennis E. Bulman, PhD [4,9], Ekaterina Rogaeva, PhD [3],Sandra Black,OC,O.Ont.,MD,FRSC [7] A. Hegele,MD,FRCPC,FACP,FAHA,FCAHS [1,2] [1]  The Ontario Neurodegenerative Disease Research Initiative (ONDRI) characterizes five neurodegenerative diseases: Alzheimer's disease/mild cognitive impairment (AD/MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson's disease (PD), and vascular cognitive impairment (VCI).Genetic variants-including C526T and T388C in AP-OE and C677T in MTHFR-contribute to neurodegenerative disease risk.ApolipoproteinE (ApoE) exists in three isoforms-E2, E3, E4.The isoforms are encoded by the APOE gene, leading to six genotypes (E2/2; E3/2; E3/3; E4/2; E4/3; E4/4) based on combinations of alleles at C526T and T388C.The APOE E4 allele increases risk for AD/MCI.Its protein product does not efficiently clear amyloid ß (Aß) from the brain, accelerating Aß aggregate formation and contributing to neurodegeneration.MTHFR is a rate-limiting enzyme in homocysteine (Hcy) metabolism; the C677T variant has impaired function, causing increased blood Hcy levels, possibly leading to stroke and VCI.We investigated associations between APOE and MTHFR genotypes and the neurodegenerative diseases under study.APOE and MTHFR SNPs were genotyped via the ONDRISeq targeted next-generation sequencing panel and confirmed using TaqMan® allelic discrimination assays in 519 ONDRI participants, 192 APOE controls, and 110 MTHFR controls.Genotype and allele frequencies were compared between cohorts and controls.The APOE E4/4 genotype was significantly associated with AD/MCI when compared with FTD, ALS, PD, VCI, and control cohorts.In addition, the MTHFR C677T TT genotype was not more associated with VCI than other cohorts or controls.Future studies will analyze genomic data alongside clinical observations and neuroimaging to identify associations between genotypes and specific phenotypes.Helicobacter pylori (H.pylori) is a gram-negative bacterium that infects gastric epithelial cells leading to peptic ulcer disease and gastric cancer.Vacuolating Cytotoxin A (Vac A) is a bacterial virulence factor associated with a more severe disease outcome.VacA disrupts the host autophagy pathway and membrane trafficking, generating large vacuoles where the bacteria reside.Our laboratory determined that cells deficient in the lysosomal calcium channel TRPML1 phenocopy the effects of VacA, as they display large vacuoles and disrupted autophagy.This led to the hypothesis that VacA impairs TRPML1 activity.If this hypothesis is correct, we reasoned that the inhibition of TRPML1 by other means should mimic the effects of Va-cA.There is no commercial inhibitor of TRPML1, however, since TRPML1 is activated by PI(3,5)P2, it can be indirectly inhibited by blocking PIKfyve, the sole kinase responsible for synthethizing PI(3,5)P2.Therefore, I compared the effects of apilimod, a novel and specific PIKfyve inhibitor, with VacA on the gastric epithelial cell line, AGS.The cells were treated with Vac A, YM or apillimod.Vacuolation was determined by staining for the lysosomal marker, Lamp1, and autophagy was assessed by LC3 staining and Western blot.We found that apilimod treatment induced vacuolation in AGS cells.Alpillimod also dysregulated autophagy, increasing LC3-II levels.These results further support the hypothesis that VacA toxic effects are a consequence of inhibiting the TRPML1 channel.Elucidating the VacA mechanism of action will lead to the identification of new targets for H. pylori treatment.Inflammatory bowel disease (IBD) represents a group of complex incurable diseases characterized by chronic gastrointestinal inflammation.Growing evidence from animal and human studies indicate that vitamin D deficiency is an important environmental factor contributing to IBD pathogenesis.Although the exact mechanism is unknown, we hypothesize that vitamin D deficiency downregulates autophagy, a pathway consistently recognized as important in IBD.Previously in our laboratory, we have shown that a vitamin D deficient diet in mice causes a reduction in ATG16L1 and autophagy in the intestine.Therefore, to directly assess the impact of vitamin D on intestinal epithelial cells and autophagy, we employed mouse intestinal epithelial cells.MODE-K cells were incubated with increasing concentrations of active form of vitamin D and lysates assessed via western blotting for autophagy proteins, ATG16L1 and LC3II.Blots were also probed for the vitamin D receptor (VDR), which is a vitamin D responsive gene.A significant increase in expression of VDR was detected in cells incubated with increasing concentrations vitamin D, indicating a dose dependent relationship.A trend towards increased ATG16L1 was also detected in cells incubated with increasing concentrations of vitamin D. Taken together, our findings indicate that vitamin D regulates expression of the IBD susceptibility gene ATG16L1 providing a potential mechanism by which vitamin D deficiency influences IBD.Helicobacter pylori is a gram-negative bacterium that is known to play a role in the development of peptic ulcers and gastric cancer.The H. pylori vacuolating cytotoxin A (VacA) is a virulence factor associated with more severe disease outcomes.It is known to disrupt host autophagy and create large vacuoles which function as an intracellular niche, increasing intracellular H. pylori survival in the gastric epithelium.Interestingly, cells deficient in the mucolipin transient receptor potential 1 (TRPML-1) channel mimic the VacA phenotype; displaying large vacuoles and dysfunctional autophagy pathways.Recent work in the lab has shown that overexpression of TRPML-1 and treatment with the TRMPL-1 agonist ML-SA1 reverses Va-cA phenotype; indicating that VacA inhibits TRPML-1.To verify the results obtained with ML-SA1, I tested the ability of MK-683, another TRPML-1 agonist, to reverse the effects of VacA.Human AGS cells were incubated with either VacA+ or VacA-culture supernatant for four hours before being treated with MK-683, ML-SA1 or the drug vehicle DMSO.Immunostaining and western blot analysis of the autophagy marker LC3 showed that both TRPML-1 agonists restored functional autophagy.Additionally, staining of the lysosomal marker Lamp-1 revealed that MK-683 and ML-SA1 reduced the size and number of vacuoles.I found that two independent TRPML-1 agonists could reverse the effects of VacA and this study further supports the hypothesis that VacA acts by inhibiting the TRPML-1 channel.These findings suggest that activation of the TRPML-1 channel could be used to kill intracellular VacA+ H. pylori.

Poster Presentations in Biostatistics
Comparing AMSTAR and ROBIS in quality assessments of systematic reviews for drug treatments for Alzheimer's Disease.Sydney George, BSc Student [1], Mark Oremus, PhD Background and Objectives: Systematic reviews have been routinely used to evaluate drug treatments for Alzheimer's disease (AD).Policymakers use systematic reviews to help decide whether new drug treatments should be listed on provincial drug formularies.The methodological quality of systematic reviews is important, as policy decisions and current evidence for medical interventions should be based on high-quality reviews.The study aim was to identify all systematic reviews that evaluate the following AD medications: Donepezil, Rivastigmine, Galantamine and Memantine.Afterwards, each systematic review was rated using AMSTAR and ROBIS for methodological quality.Methods: The electronic databases EMBASE, PubMed, Medline, and Cochrane Library were searched using multiple search terms.Articles included were systematic reviews of randomized controlled trials for Donepezil, Rivastigmine, Memantine or Galantamine medications in AD patients.Results: 35 studies were identified that matched inclusion criteria.For the AMSTAR Scores (median = 0.81, 25th percentile = 0.63, 75th percentile = 0.83, IQR = 0.20).and ROBIS Scores, (median = 0.74, 25th percentile = 0.66, 75th percentile = 0.81, IQR= 0.15), the variance in index scores were similar, indicating a similarity in methodological quality for both assessment tools.The correlation coefficient was 0.90, indicating a strong positive linear relationship and consistency between AMSTAR and ROBIS high and low scores.

Conclusion:
The greater subjectivity and length of the ROBIS checklist required an assessor to spend more time answering questions.The variance index scores between AMSTAR and ROBIS didn't differ substantially.AMSTAR and ROBIS yielded similar quality assessments of systematic reviews.

AMPK regulates extravillous trophoblast invasion
Gurrattan K. Chandhoke, BHSc Student [1], Patrick J.A. Rodriguez, MSc [1,2] Anson Cheung, BHSc Student [1], Sandeep Raha, PhD [1,2] [1] Department of Pediatrics,McMaster University,Hamilton,ON,Canada L8N 3Z5 [2] The Graduate Program in Medical Sciences, McMaster University, 1200 Main Street W., Hamilton, ON, Canada L8N 3Z5 Background: The placenta is involved in transporting and exchanging gases, nutrients and waste products at the mother-fetus interface.Trophoblasts, the primary stem cell lineage in the placenta, play a crucial role in embryo implantation and in spiral artery remodeling during the early stages of pregnancy.Improper progression of these initial stages of pregnancy can lead to a series of adverse effects for both mother and fetus.At a cellular level, AMPK is involved in cellular energy homeostasis but may also contribute to the regulation of cell invasion; an important step in spiral artery remodeling.Hypothesis: We propose that AMPK function regulates the extravillous trophoblast cell invasion.Method/Results: By utilizing a transwell invasion assay, our results indicate that Metformin and AICAR increase trophoblast invasion while Compound C decreases the cells ability to invade over a 32 hour period.Reducing AMPK expression, via siRNA technology, results in reduced trophoblast invasion across all pharmacological treatments (Metformin, AICAR, Compound C) as well as the altered expression of genes linked to the trophoblast cell invasion, such as TIMP-1, TIMP-2, MMP-2 and MMP-9.Conclusion: AMPK is shown to play a role in altered trophoblast invasion through various invasion markers.
[2] Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5.
Duchenne muscular dystrophy (DMD) is a genetic disease characterized by reduced muscular function and premature death.Despite DMD being one of the most common and devastating forms of muscular dystrophy, a cure has not yet been developed.Our lab has proven that the system of Wnt7a and its receptor Fzd7 represents a mechanism for muscle regeneration.Local injection of Wnt7a in mdx mice (a model of DMD) results in an increase of the satellite cell population and myofiber hypertrophy.This data makes Wnt7a a potential solution for DMD.Nonetheless, Wnt7a is hydrophobic, making it incapable of traveling in the bloodstream as a systemic treatment.Therefore, our main goal is to establish an effective method of transportation for Wnt7a.To resolve this limitation, we are using exosomes, small vesicles responsible for intercellular communication.Recently, our lab made the exciting discovery that Wnt7a is also secreted through exosomes.breakthrough, we have begun to study the mechanism of exosomal secreted Wnt7a and comparing with the classical Wnt7a/Fzd7 signaling pathway.The short-term goal of my project was to evaluate the role of Fzd7 in the uptake of exosomal Wnt7a.To study the function of Fzd7, we started by comparing the uptake of exosomal Wnt7a by wild-type versus Fzd7 knockout primary myoblasts.Subsequently, using confocal microscopy and immunostaining we have proven that the uptake of exosomal Wnt7a is independent of Fzd7 binding.These results provided insights into a new mechanism for Wnt7a uptake and opened different avenues for DMD treatment.

Characterizing TβL1 SUMOylation in Dupuytren's disease
Kevin Ho, BSc Student [1,3], Ana Pena Diaz, MSc [3], David B. O'Gorman, PhD [1,2,3 Dupuytren's disease (DD) is a chronic, contractile fibrosis of the palmar fascia.Treatments are limited to surgical interventions, however disease recurrence rates are high and there is a need for novel therapeutic interventions.One molecular characteristic of DD is increased β-Catenin levels in fibroblasts that induce palmar fascia fibrosis (DD cells).The mechanism of β-Catenin nuclear translocation to transactivate gene expression and promote disease development are unclear.Recently, the conjugation of small ubiquitin-like modifiers (SUMO) to Transducin β-like 1 (TβL1) has been implicated in the nuclear localization of β-Catenin in cancer.We hypothesized that a similar mechanism promotes nuclear translocation of β-Catenin in DD, and there are higher levels of TβL1 SUMO-1 conjugation (SUMOylation) in DD cells relative to fibroblasts derived from non-fibrotic palmar fascia of healthy patients (CT cells).To test this hypothesis, primary DD and CT cells were isolated from three different patients and SUMOylated proteins were immunoprecipitated from cell lysates.Bound and unbound fractions were subsequently immunoblotted for TβL1 and TβL1 SUMOylation levels were quantified by densitometry analysis.To confirm our results, protein lysates from DD and CT cells were also immunoprecipitated with antibodies to TβL1 and subsequently immunoblotted for SUMOylated proteins.Our preliminary findings suggest a trend towards increased TβL1 SUMOylation in DD cells relative to the majority of CT cells assessed.These findings may provide further insights into the molecular basis behind increased β-Catenin levels in DD, and in the future SUMOylated TβL1 may serve as a potential therapeutic target for DD and other fibroses.

Cytoskeletal remodeling in macrophages:
The role of RhoA in Slit2-Robo1 signaling Nahid Iseyas, BSc Student [1], Vikrant Bhosle, MD, PhD [2], Lisa Robinson, MD, PhD, FRCP(C) [2,3] [1] Faculty of Arts and Science, University of Toronto, Toronto, ON,Canada,M5S 1A1 [2] Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada, M5G 0A4 [3] Departments of Pediatrics and Physiology, University of Toronto, Toronto, ON, Canada, M5S 1A1 Rationale: Slit2 is a glycoprotein that has been shown to play conserved roles as a neuronal repellent through interacting with its receptor Roundabout1 (Robo1).In the past, the Robinson group has shown that through Slit2-Robo1 signaling, members of the Rho family of small GTPases, Rac1/2 and Cdc42, are inactivated, inducing changes in the actin cytoskeleton of macrophages.However, this inactivation cannot fully account for all the cytoskeletal changes seen in the macrophages after treatment with Slit2.We recently found that another protein called RhoA, which is also involved in cytoskeletal remodeling, is activated once macrophages are treated with Slit2.Objective: To determine the molecular events involved in the signaling pathway of RhoA after Slit2 binds to Robo1.Methods: Using siRNAs, we knocked down the expression of RhoA in RAW 264.7 murine macrophages and treated them with Slit2, finding that the cell rounding effect of RhoA was inhibited.Furthermore, treatment of RAW macrophages with Slit2 and a specific inhibitor of Formin, a key actin polymerization factor in the RhoA pathway, inhibited the cell rounding effects of RhoA in macrophages, illustrating that Formin is involved in the Slit2-Robo1 signaling pathway.Conclusion: These results demonstrate a new signaling pathway for Slit2-Robo1 involving RhoA and several of its downstream effectors.Future studies will include testing more of the downstream effectors of RhoA and their relation to Slit2-Robo1.These pathways are particularly important in inflammatory diseases like atherosclerosis, where cytoskeletal changes of macrophages could significantly affect the progression of the disease.Conclusion: We found that LBW/premature children were more likely to develop SRNS, but do not have a difference in relapse-free duration with NBW children.This indicates that LBW/prematurity may be suggestive of an unfavourable course of NS.Physicians can use this information to follow patients closer from time of birth to ensure prompt assessment.

The effects of transcranial direct current stimulation (tDCS) on emotional processing strategies as assessed via the late positive potential electrocortical index
Tang F. (Bsc.Cand) [1], De la Salle S. (Phd Cand) [1], Jaworska N.(PhD) [1,2], Knott V. (Phd) [1,2] [1] University of Ottawa Institute of Health Research, Ottawa, ON, Canada, K1Z 7K4 [2] Royal Ottawa Mental Health Centre, Ottawa, ON, Canada, K1Z 7K4 Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that uses either anodal (excitatory) or cathodal (inhibitory) low current stimulation to modulate cortical excitability.This technique has shown promise in enhancing cognitive control and executive functioning by stimulating the left dorsolateral prefrontal cortex (DLPFC).In the current study, twenty minutes of excitatory, inhibitory or sham tDCS is applied to the left DLPFC.Few studies have assessed tDCS on emotional re-appraisal strategies, despite tDCS being studied as a potential treatment for mood disorders, which are characterized by emotional dysregulation.The Late Positive Potential (LPP) is an electrocortically-derived biomarker or event related potential, that has been found to be a reliable index of sustained attention to emotional stimuli (i.e. an index of emotional engagement).The LPP amplitude, which occurs 300 ms after emotional stimuli onset, will be analyzed to assess the response to negative or neutral images while different emotional regulation strategies are employed after the twenty minutes of excitatory, inhibitory or sham tDCS administration.Given that prefrontal stimulatory tDCS has been associated with enhancing cognitive regulation, it is expected that it will also modulate corresponding LPP amplitudes.Study design and Methods: 32 healthy participants (males and females with no psychiatric or major medical issues), aged 18-40 years, will be recruited and tested across three sessions.Each of the three sessions will include task-based electrophysiological recordings to measure and collect LPP data, after excitatory, inhibitory or sham tDCS stimulation has been applied.Electroencephalograms (EEG), will be used to measure electrophysiological activity, in which LPP event-related potentials will be extracted and analyzed.

Poster Presentations in Epidemiology
Rising fall-related death among seniors: Cause and effect of a policy change?Aayushi Joshi, BMSc Student [1], Fahra Rajabali, MSc [2], Kate Turcotte, MSc [3], Ian Pike, PhD [4] [1] Interdisciplinary Medical Sciences, Western University, London, Ontario, Canada N6A 3K7 [2] BC Injury and Prevention Unit, BC Children's Hospital,Vancouver,British Columbia,Canada,V6H 3V4 [3] BC Injury and Prevention Unit, BC Children's Hospital,Vancouver,British Columbia,Canada,V6H 3V4 [4] BC Injury and Prevention Unit, BC Children's Hospital,Vancouver,British Columbia,Canada,V6H 3V4 To classify deaths more accurately and consistently, the BC Coroners Service implemented a policy change in 2010 to support the identification of individuals whose death was related to a previous fall.These fall-related cases typically involved hospitalized elderly patients who eventually succumb to pneumonia.Prior to 2010, these deaths were classified as natural with pneumonia as the underlying cause of death; however, following the policy change the fall became the underlying cause of death and these cases were classified as accidental.The aim of this study was to determine how changes in reporting practice influence mortality statistics.BC Vital Statistics mortality data was analyzed from 2001-2015, for cases among seniors 65+ with ICD-10 fall codes W00-W19.Fall-related mortality rates among seniors aged 85 and over increased after 2010, peaked in 2012 at approximately 838 per 100,000 deaths, and decreased from 2012-2014.No significant difference in fall mortality rates for specified fall subcauses between 2007-2009 and 2012-2014 was found, suggesting that mortality rates post-2012 were approaching rates prior to 2010.A lack of documentation of the fall event was indicated by 69.8% of falls being classified as unspecified fall (n = 5,902).Time trends and key informant communication suggest there may be an unofficial reversion to previous reporting practice among certifiers in British Columbia.As such, further emphasis should be placed on accurately identifying the mechanism of death and implementation of educational interventions and quality assurance measures to allow development of targeted injury prevention initiatives and accurate mortality data.An evaluation of privatized healthcare in an urban Chicago eye institute Alexandra Bosco, BSc Student [1], Christina Morettin,BScH,OD,FAAO [2] [1] Queen's University, Kingston,Ontario,Canada [2] Illinois College of Optometry/Illinois Eye Institute, Chicago, Illinois, USA Purpose: This study aimed to look at vision and medical care outside of Canada in a privatized healthcare setting.Method: Surveys were distributed to patients waiting to be seen in the urgent and primary eye care clinics at the Illinois Eye Institute (IEI) over a 6 day period.Questions included patient demographics, level of insurance coverage for eye and medical exams, time since last eye and medical exams, and known chronic medical and ocular conditions.Results: Of the 275 patients surveyed, 234 were seen in IEI's primary eye care clinic, while 32 were in the urgent eye care clinic.The patient population was 64% female, with a mean age of 52.2 years (18 -89 years), and the majority identified as African-American (73%).67% of patients had full medical coverage, compared to 64% with full eye care coverage.Most patients had an eye exam within the last two years (86%) and a medical exam within the last year (78%).Of the patients surveyed, 40% had known ocular disease (most common glaucoma), and 54% had chronic medical conditions (most common diabetes).There was no statistical difference in last eye exam between primary care and urgent care eye exams (p=0.145).Conclusion: A high percentage (86%) of patients in an urban Chicago setting receive adequate eye care in a private healthcare setting.Providing adequate eye care services to reduce visual impairment and to provide early detection of systemic and ocular diseases is an important element of delivering primary health care.

Maple syrup urine disease: A retrospective chart review Jeeventh Kaur, BA Student [1], [2]; Laura Nagy, MSc [2]; Michal Inbar-Feigenberg, MD [2] [1] McGill University, Montreal, QC, Canada [2] Department of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada
Background: Maple syrup urine disease (MSUD) is a rare genetic disorder characterized by the accumulation of the branched-chain amino acids (BCAAs), resulting in the manifestation of phenotypes such as developmental impairment and metabolic decompensation when left untreated.In 2014, the Hospital for Sick Children (HSC) introduced a dried blood spot (DBS) home monitoring system to allow patients to track BCAA levels without the inconvenience of travelling to the hospital.
Objective: This study assesses the impacts of the implementation of DBS monitoring, as well as characterize parameters of the HSC MSUD population including age, biochemical control, and monitoring and hospitalization frequency.Methods: Retrospective chart review was conducted using data from all HSC MSUD patients followed between 1991-2017 (n=15).Results: Monitoring frequency was negatively correlated with average leucine level in the newborn period of 0-6 months (r=-0.74,p=0.037) and positively associated with the proportion of levels within target range (r=0.68,p=0.046).Correlation strength decreased with age.Monitoring frequency increased by an average of 159% per patient following DBS monitoring implementation (8.6 in 2014 to 22.3 in 2015).Younger patients were most likely to be admitted to the ICU for metabolic decompensation, with an average peak leucine level 9.65 times greater than the maximum recommended threshold of 300 μmol/L (2895 μmol/L).Conclusions: DBS monitoring has resulted in a sharp increase in monitoring frequency, which, in turn, is associated with a greater degree of biochemical control.Younger patients are most greatly impacted by changes in monitoring frequency and are most likely to be hospitalized.

Characterizing the natural progression of cirrhosis, portal hypertension, and timing of liver transplantation in children with biliary atresia: A competing risks analysis.
Simon C. Ling, MB, ChB, MRCP(UK) [1] and Sarah E. Jarvis, BSc [2] [1] Department of Paediatrics Division of Gastroenterology,Hepatology and Nutrition,Hospital for Sick Children,Toronto,Ontario,Canada [2] Department of Paediatrics Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada Background: Cirrhosis progresses through stages of increasing severity characterized by different clinical complications.We describe the course of cirrhosis in biliary atresia (BA) using a multistate model and hypothesize that this framework, previously only used in adult cirrhosis, will be applicable to this population.Methodology: We reviewed medical charts of 59 consecutive children diagnosed with BA between 2001-2012 to identify episodes of compensated cirrhosis (CC), clinically significant portal hypertension (CSPH), decompensated cirrhosis (DC), late decompensation (LD), liver transplantation and death.Data defining stages of cirrhosis were collected from time of Kasai hepatoportoenterostomy (KP) until death or last follow up, including variceal bleeding and ultrasound evidence of ascites, splenomegaly, or portosystemic collaterals.Results: At time of KP, 54% of patients were not cirrhotic and the rest CC.At final evaluation, 59% were transplanted and alive, 2% were not cirrhotic, 5% CC, 17% CSPH, 10% DC, 2% LD, and 5% were dead.The median duration (days) of stages was 88 for non-cirrhosis, 70 for CC, 775 for CSPH, 173 for DC, and 91 for LD.Among patients with cirrhosis at time of KP, 82% required transplantation, compared to 47% of patients with no cirrhosis at KP.Total duration of in-patient stay was greater in more advanced stages of cirrhosis.

Conclusion:
The description of cirrhosis in BA with a multistate model shows the high proportion of patients who pass through stages of decompensation to liver transplantation.The model reflects clinical severity measured by length of inpatient stay and prediction of need for transplantation.

Systematic review: Stimulant medications and induced suicidality in youth with ADHD
Feodor Poukhovski-Sheremetyev, BA Candidate ( 2019) [1], Karen Wang, MEd, MD, FRCPC [2], Nicholas H Neufeld,MD,MSc [2], Sefi Kronenberg,MD,PhD [2,3].[1] University of Alberta, Edmonton, AB, Canada, T6G 2R3 [2] Department of Psychiatry, University of Toronto, Toronto, ON, Canada, M5T 1R8 [3] SickKids, The Hospital for Sick Children, Toronto, ON, Canada, M5G 1X8 In 2015, Health Canada issued a warning linking stimulant medications with suicidal thoughts and behaviour in youth with ADHD.To the best of our knowledge, there are no peer-reviewed studies presenting such a correlation, and it is possible that the warning is based primarily on anecdotal evidence.In order to correct this gap in psychopharmacological knowledge, we are conducting the first systematic review of research associating suicidality, stimulants, and ADHD.Our preliminary findings have been unable to show a statistically significant association between pediatric suicidality and stimulant medications.That said, two major outcomes are still possible: the discovery of a positive correlation, or no detectable signal.The contribution of this study would be substantial in both cases, either supporting or challenging Health Canada's statements.Accurate pharmacological information is essential for effective treatment and minimizing risks to patients.

Association between maternal vitamin D status during pregnancy and antenatal and postpartum depression: A systematic review
Newsha Mahinpey, BSc Student [1], Nicole Letourneau, PhD [1], Fariba Aghajafari, PhD [1], Gerald Giesbrecht PhD [1], Nela Cosic, MD student [1] [1] Owerko Research Center, University of Calgary, Calgary, Alberta, Canada, T2N 1N4 A recent systematic review revealed a positive relationship between lower 25-hydroxyvitamin D (vitamin D) status and depression in adults (Ju et al).Vitamin D has also been implicated in antenatal depression and postpartum depression (PPD) in many studies; however, results have been inconsistent results due to the complexity of this association.The aim of this study is to systematically review current literature addressing associations between vitamin D and antenatal depression or PPD, and conduct a meta-analysis.Four electronic databases were searched for studies examining the association between vitamin D and PPD or antenatal depression with no date or language limits.Two independent authors reviewed titles and abstracts of the search results and selected studies for full review based on inclusion criteria.Data were extracted and a quality rating was done using the Newcastle-Ottawa Scale (NOS) on the selected studies.A total of 239 studies were identified and after the removal of duplicates 143 were reviewed for titles and abstracts.Ultimately, 21 eligible studies were assessed, and 14 of these were included in the review.When using the NOS, the quality assessment of the included studies ranged from moderate to high.Of the studies on PPD, 4 of the 7 showed an association between vitamin D and PPD.Five of 7 studies on antenatal depression showed an association with vitamin D status.Among these studies there was variation in adjusting for confounding factors.To date, the effect of vitamin D on PPD and antenatal depression remains inconclusive.Meta-analytic techniques to be employed on the existing data have the potential to provide clearer understanding of associations.Inflammatory Bowel Disease (IBD) are a group of intestinal disorders of which the two main diseases are ulcerative colitis and Crohn's disease.IBD is multifactorial, and while it is suspected that dietary components play an important role in the disease, there are limited data regarding the impact that specific dietary components have on clinical and endoscopic activity, and the patient-targeted dietary recommendations that are available are overly-restrictive and are very conflicting.In this study, we identified recurring links between certain dietary factors and specific IBD outcomes by conducting extensive literature searches and validating these findings by collecting primary patient data.The goal of the study was to use this knowledge to develop a clinical tool that would patients with accurate, safe, and explicit dietary recommendations.First, we conducted an extensive PubMed search, from which 71 articles met our inclusion criteria.The articles were assembled into a hierarchy based on the quality of the study and of the outcome measurements, to facilitate the comparison of papers that reported conflicting outcomes.Second, 69 Patients with IBD from two tertiary care centers in Toronto, Canada completed a 3-to 4-day food diary prior to their scheduled colonoscopies.Differences in nutrient composition associated with clinical and endoscopic activity were analyzed by generalized linear models in a univariate analysis, while accounting for disease type.The data from the literature search, substantiated by the primary patient data, were used to develop a concise food guide for patients which will be distributed at Mount Sinai Hospital.

Williams
A systematic review of international comparison studies on physical/sports activity participation and cultural consumption Katarina Vukovojac, BHSc Student [1], Brice Lefevre, PhD [2], Guillaume Routier, PhD [2] [1] Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Canada [2] School of Sport & Exercise Sciences, Université Claude Bernard Lyon 1, Lyon, France Background: Although complex, international comparisons are scientifically useful and necessary for a thorough understanding of leisure practices from one country to another.In Canada and France, the histories, cultures, sociopolitical structures, and demographics, albeit similar in some respect, remain distinct and tend to produce specific inequalities in sporting commitment.
Objective: The purpose of the review was to explore the theory, methodology, and quantitative results of international comparison studies relating to participation in physical sports activities (PSA) and cultural consumption in different national contexts.Methodology: A systematic electronic search was conducted using the following databases: SPORTdiscus, PsycINFO, and Sociological Abstracts.Specific inclusion criteria were outlined relating to publication date, language, and research design.The selection process involved a keyword search, title scan, abstract review, and a complete reading of the articles.Results: Of the 4922 reviewed studies relating to PSA participation comparisons, 6 were selected for inclusion.Of the 7515 reviewed studies relating to international comparisons on cultural consumption, 32 were selected for inclusion.Altogether 24 studies utilized international survey data comparison methods, 10 utilized cross-national survey data comparison methods, and 2 utilized a combination.No direct comparison studies between Canada and France were identified.Conclusion: An abundance of international survey data was identified in comparison to cross-national survey data, suggesting that international surveys are advantageous for PSA participation/cultural consumption comparison study purposes.The information and methods identified in the selected studies allow for a better future analysis of the various factors affecting PSA participation rates in Canada and France.

Poster Presentations in Immunology
Evaluation of TGFb and IFNb cytokine induced polarization of neutrophil-like HL60 cells Gillian Y. Liu [1], Laura H. Wells [1] [1] Department of Chemical Engineering, Queen's University, ON, Canada After cataract surgery, an intraocular lens (IOLs), commonly made of PMMA, is inserted to replace the removed natural lens.However, posterior capsular opacification (PCO) can occur as a complication of cataract surgery, also known as secondary cataracts.Neutrophils are the body's first response cells at a site of infection or intrusion by a foreign material.Neutrophils are found to polarize into one of two forms, N1 (pro-inflammatory) and N2 (anti-inflammatory).The purpose of the experiment is to evaluate TGFβ and IFNβ cytokine induced neutrophil polarization through measuring TNFα on ELISA, which is expressed at high levels in N1, and low levels in N2.
Introduction: Myelin-reactive T cells of T helper 1 (Th1) and Th17 types are thought to be pathogenic in MS.GM-CSF is a cytokine that is produced by pro-inflammatory Th1 and Th17 cells and has been understudied in MS.IL-11 is another cytokine that is poorly understood in the context of autoimmunity, but was recently shown to be the most highly up-regulated cytokine in the cerebral spinal fluid of MS patients.Objective: To conduct a broad-scale profiling of T cell cytokine production in response myelin antigens in MS patients using ELISPOT assays.Methods: Thus far, we have collected blood samples from MS patients (22 females, 4 males) and a limited number of healthy controls (4 females, 1 male).Peripheral blood mononuclear cells (PBMCs) were isolated from these samples and then were plated together with either myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), peptides encoding parts of these proteins, or control antigens on ELISPOT plates.Cytokine (IL-5, IL-10, IL-11, IL-17, TNFα, IFNγ, GMCSF) spots were developed after 48 hours of culture and detected using an ELISPOT reader.Results: To date, we have analyzed data for GM-CSF and IL-11 responses.For GM-CSF, we have observed a higher frequency of cytokine-producing cells in MS patients versus healthy controls in wells that were stimulated with MBP, a PLP peptide pool that encodes determinants in the second hydrophilic domain of the protein, and MP4 (a fusion protein of MBP and PLP hydrophilic domains).We also detected a higher frequency of GM-CSF spots in MS patients versus controls in the media control wells (contained PBMCs, but no antigen).For IL-11, we saw that IL-11 producing cells were present at a higher frequency in the media control wells in the MS patients versus healthy controls, but that this number did not appreciably increase with the myelin stimuli, with the exception of the MP4 wells.Conclusion: Patients have a higher frequency of GM-CSF and IL-11 producing cells in peripheral blood than healthy controls.GM-CSF-producing T cells are more reactive to MBP and PLP.

Investigating the repolarization capacity of macrophages and its implications in wound repair
Nirob Saha, BSc Student [1,2],Karun Tandon,MSc [2,3],Ehab Ayaub,PhD [2,3],Pavithra Partasarathy,MSc [2,3], Nafis Wazed, BSc [1,2], Kjetil Ask, PhD [1,2,3] [1] Department of Biochemistry and Biomedical Science,McMaster University,Hamilton,Ontario,Canada L8S 4L8 [2] McMaster Immunology Research Center,McMaster University,Hamilton,Ontario,Canada L8S 4L8 [3] Firestone Institute for Respiratory Health,Saint Joseph's Healthcare,Hamilton,Ontario,Canada,L8N 4A6 Despite being part of multiple disease pathogeneses, fibrosis has been evolutionarily conserved, as the production of scar tissue is imperative in the wound healing process.Wound healing can be separated into two phases, beginning with an initial inflammatory phase aimed towards removing the injury, and a later fibrotic phase characterized with extracellular matrix deposition and scar formation.Although fibrosis is generally reversible, when the balance between inflammation and fibrogenesis is dysregulated, or when injury becomes chronic, pathological scarring can occur.A range of macrophage subpopulations have been associated with different aspects of the wound healing process.The inflammatory phase is flush with classically activated macrophages (CAM/M1).Then during the later fibrosis phase, the macrophage population becomes alternatively active (AAM/M2), which are shown to promote fibrosis.We have found that mature M2 macrophages have the capaci- ty to downregulate their M2 phenotype towards a more M1-like phenotype when repolarized with M1-inducing cytokines.We anticipate that this repolarized macrophage population may have an effect on fibroblast to myofibroblast differentiation and collagen production, providing a potential therapeutic route to decrease the progression of fibrogenesis.Although previous research has utilized variety of pathways to inhibit fibrogenesis, we have directed our view towards macrophage polarization, as macrophages are a crucial factor in both immunity and the wound healing process.

Poster Presentations in Neuroscience
Novel derivatives of kainic acid as inhibitors of neuroinflammation Morgan Alford, BSc Hons Student [1],Frederic Menard,PhD [2], Andis Klegeris, PhD [1] [1] Department of Biology, University of British Columbia, Kelowna, BC, Canada V1V 1V7 [2] Department of Chemistry, University of British Columbia, Kelowna, BC, Canada V1V 1V7 Alzheimer's disease (AD) is a neurodegenerative disorder that presents in patients as progressive cognitive decline, invariably resulting in dementia.This manifestation causes severe emotional and financial hardship for AD patients and their families.The diseased brain is characterized by the presence of neuritic plaques and tangles.When microglia, the immune cells of the central nervous system, interact with these pathological structures, the microglia become activated.Chronic microglial activation leads to the continuous secretion of pro-inflammatory mediators, which at high concentrations are damaging to neurons.The goal of this project was to assess the therapeutic potential of two novel kainic acid chemical derivatives as treatments of AD.The first objective was to determine how these derivatives affect activated microglial functions that negatively impact neuronal cell viability.After treatment with either of the derivatives, microglia were activated and their conditioned media was transferred onto neurons.Neurotoxicity of microglia treated with either of the two derivatives was significantly reduced compared to stimulated untreated cells.The second objective was to determine whether these derivatives alter the microglial secretion of pro-inflammatory mediators.Analysis of the microglia-conditioned media confirmed that treatment with either of the kainic acid derivatives caused a downregulation of the potentially harmful monocyte chemoattractant protein-1, reactive nitrogen species and reactive oxygen species.AD currently affects 40 million people worldwide.This number is predicted to double by the year 2030 as there is currently no effective treatment.This project unveils potential therapeutic strategies, which could impact the lives of AD patients and their families.

Influence of transcranial direct current stimulation on the posterior parietal cortex in action execution, action observation and action imagination S. Latter, BSc Student [1], T. Welsh [2]
[1] Faculty of Kinesiology and Physical Education,University of Toronto,Toronto,ON,Canada,M5S 2W6 [2] Center for Motor Control, University of Toronto, Toronto, ON, Canada, M5S 2W6 Rehabilitation approaches typically incorporate protocols in which the patient executes a series of movements (physical practice).Physical practice can be limited, however, due to fatigue, pain, and other symptoms.For this reason, action observation (observational learning) and imagination (motor imagery) are being considered and incorporated into rehabilitation protocols because these approaches show benefits to performance without the need for executing movements.To maximize the potential of these approaches, a deeper understanding of the neuro-cognitive mechanisms involved in action execution, imagination and perception is needed.The present study was designed to investigate the role of the posterior parietal cortex (PPC) in these tasks.To this end, participants completed action execution, perception, and imagination tasks before and after receiving transcranial direct current stimulation (TDCS) to the PPC.TDCS is a technique that can modulate (increase of decrease) activity in a targeted cortical region.Participants received anodal, cathodal or sham tDCS on different testing days.During each visit, participants executed, imagined and perceived cyclical aiming movements of the hand before and after tDCS (for 20 minutes while they rested).The primary outcome measure was movement time of the executed, perceived and imagined movements and it was found that performance on the tasks was altered following tDCS.These results will be discussed with respect to the role that the PPC plays in motor behavior.Future work will explore the role of PPC in motor adaption or (re)learning following, as well as the potential use of these tasks for better assessing and understanding movement disorders.Qualitative analysis of spontaneous movements has been validated as a method of predicting the onset of neurodevelopmental disorders.Spontaneous movement are early involuntary movements that begin during fetal development and continue into infancy.Spontaneous movements have been associated with the cortical subplate, a transient zone in the brain that is heavily involved in neurodevelopment.Thus far, literature has focused on determining the accuracy of utilizing qualitative analysis of spontaneous movements a predictor.The aim of this study is to elucidate the quantitative phenotypes of spontaneous movement in healthy, full-term infants.This proof-of-concept pilot study details the trial methodology conducted over 24 healthy full-term infants.Kinematic data for one infant undergoes frequency and velocity analysis to demonstrate potential methods of data manipulation in future investigation.The protocol generated from this pilot study will inform further work in the predictive capacity of spontaneous movements.

Poster Presentations in Oncology
Efficacy of recombinant wild type vaccinia virus Maltseva M., BSc Student [1] The research is aimed for the identification and characterization of cancer killing therapeutic viruses based on selective replication of viruses in cancer cells and their subsequent spread within the tumour while leaving healthy tissues unharmed.The remarkable parallels between cancer propagation and viral infection within mammalian cells has led to the development of oncolytic viruses which are becoming a likely tool for cancer immunotherapies.It has been shown that oncolytic viruses infect and in some cases destroy tumour cells and additionally induce anti-tumour immune response.In this research, we will be testing out the efficacy and cytotoxicity of the recombinant strains of the wild type vaccinia virus in leukemia cells.The screening of L1210, HL60, Hela S3 and 786-0 cell lines will indicate which recombinant viruses are more effective and ensuing the subsequent testing in vivo using L1210 and at t=0, t=6 to observe the vaccine's affect on other organs and it's cytotoxicity.In turn allowing us to conduct a safety-bio distribution profile and potential modification of the recombinant viruses though the application of immune checkpoint inhibitors.

Characterization of the GREB1 interactome in human ovarian cancer cells
Lisa Oliviero, HBSc Student [1,3],Laura Forrest,MD/PhD Candidate [2,3],Barbara Vanderhyden,PhD [2,3] [1]  The use of exogenous estrogen, such as in hormone replacement therapy, increases the risk of ovarian cancer.Our lab has demonstrated in a mouse model of ovarian cancer that estrogen treatment resulted in early onset of tumors and significantly decreased survival time.A microarray analysis of the tumors shows that estrogen upregulated 197 genes, with GREB1 (Growth regulation by estrogen in breast cancer 1) being highly increased.GREB1 is a critical meditator of estrogenstimulated proliferation and involved in estrogen receptor 1 (ESR1)-related transcription.Estrogen upregulates GREB1 in ovarian cancer through ESR1, though preliminary data in other hormone-stimulated tissues suggest that GREB1 can be upregulated through progesterone receptors (PR).Therefore, we hypothesize that steroid-hormone responsive GREB1 participates in both ESR1 and PR pathways in human ovarian cancer cells.We have characterized a panel of human ovarian cancer cell lines for their response to steroid hormones and identified a subset that upregulated GREB1 upon estrogen or progesterone treatment, with significant increases determined in ovarian cancer cell lines ES-2 and PEO1.To shed light on the function of GREB1 in ovarian cancer, we are currently identifying its binding partners using Biotinylation Identification (Bio-ID), a method used to identify robust and transient protein-protein interactions in living cells.Although how GREB1 functions in ovarian cancer is unknown, we have shown that both estrogen and progesterone can increase GREB1 expression and identification of its interacting proteins will help to further elucidate its role in hormone-induced actions.

Immunofluorescent image analysis of tumour hypoxia microenvironments
Mark Zaidi, BSc Student [1,2], Dan Cojocari, PhD [1],Trevor McKee,PhD [3], Brad Wouters, PhD [1] [1] Princess Margaret Cancer Centre,University Health Network,Toronto,Ontario [2] Ryerson University, Toronto, Ontario [3] STTARR facility, University Health Network, Toronto, Ontario Solid tumour's hypoxic environment is known to cause dramatic changes in tumor cell phenotypes, such as increased metastasis, radiation resistance, and overall poor survival of patients.Thus, understanding the root causes and molecular mechanisms of tumour hypoxia formation can help target these malignant phenotypes, improve the efficacy of hypoxia-targeted drugs, and extend patient survival.The current study aims to develop an immunofluorescence image analysis pipeline to accurately quantify the oxygen and proliferation gradients as a function of distance from the nearest perfused blood vessel.Pancreatic cancer xenografts were grown subcutaneously in mice, then excised and embedded in OCT.Serial slices of the tumor were stained with immunofluorescent markers DAPI (nucleus), EF5 (hypoxia), EdU (proliferation), CD31 (vessels), and Hoechst (perfusion), and subsequently imaged.The slices were digitally registered to one another in MATLAB.Image analysis was performed using Definiens, an object-oriented machine learning software.Vessels that were actively supplying oxygen were detected based on morphology and CD31 stain intensity, and each cell in the tumor slice was assigned a "distance to the nearest vessel" value.Mean intensities of the hypoxia and proliferation markers were quantified on a per cell basis, and plotted against their distance to the nearest vessel.Analysis shows an increase in hypoxia and a decrease in proliferation the further a cell is from a vessel.This pipeline could be validated and used in clinical scenarios, such as assessing the patient tumour hypoxic status, which ultimately could be used to improve the efficacy of hypoxia-targeting drugs or radiation treatment.

Poster Presentations in Social Sciences
Risk of bias assessment of randomized controlled trials in high-impact rheumatology journals and general medical journals: A systematic review Lazar Joksimovic, BSc Student [1], Robert Koucheki, BSc Student [1], Sahar Alimirzaie BSc Student [1], Paymun Pezeshkpour, BSc Student [1], Kathleen Cheng, BSc Student [1], Iris Ma, BSc Student [1] [1] Faculty of Arts & Science, University of Toronto, Toronto, Ontario, Canada This systematic review investigates the risk of bias in randomized controlled trials (RCTs) published in high-impact rheumatology journals and general medical journals.We also aim to identify factors associated with high risk of bias.Using Ovid MEDLINE (1946MEDLINE ( -2016)), RCTs in the top 3 high-impact rheumatology journals containing RCTs published in the year 2015, were systematically identified and critically appraised for the risk of bias prevalence.To perform the critical appraisal, relevant extracted RCTs were assessed in all domains of bias as defined by the Cochrane Collaboration.A comparison to rheumatology articles from three high-impact general medical journals was performed.Of the 138 records that were screened from rheumatology-specific journals, 113 RCTs met all inclusion criteria and were critically appraised.In total, 32.2% of domains had an unclear risk, 18.6% had a high risk and 50.2% had a low risk of bias.In comparison, rheumatology articles from general medical journals had a higher prevalence of unclear risk (39.0%), lower prevalence of high risk (14.3%) and a lower proportion of low risk domains (46.8%).Similar to our previous study in ophthalmology, more than half of RCTs contained at least one high risk of bias domain, a finding that highlights the need for greater awareness of this issue in the medical scientific community.Given the influence that bias can have on study results, it is necessary that authors and peer reviewers of RCTs closely adhere to published guidelines formulated by the Cochrane Collaboration as a way of minimizing risk of bias.
"The case of the castle": A study abroad strategy of experiential learning and its implications for medical education Grace S. Yin, BA 2019 [1] [1] Department of Experiential Learning, Queen's University, Kingston,Ontario,Canada,K7L 3N6 , Morris Freedman, MD, Faculty of Arts and Science, University of Toronto, Toronto, ON, Canada, M5S 1A1 [2] Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada, M5G 0A4 [3] Departments of Paediatrics and Physiology, University of Toronto, Toronto, ON, Canada, M5S 1A1 Biochemistry, Schulich School of Medicine and Dentistry -Western University, London, ON, Canada, N6G 1H3 [2] Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada, M5G 0A4 [3] Departments of Paediatrics and Physiology, University of Toronto, Toronto, ON, Canada, M5S 1A1 [2] [1] School of Public Health and Health Systems, Department of Applied Health Sciences, University of Waterloo, Waterloo, ON, N2L 3G1 [2] School of Public Health and Health Systems, Department of Applied Health Sciences, University of Waterloo, Waterloo, ON, N2L 3G1 Williams et al. | URNCST Journal (2017): Volume 1, Issue 3 Page A13 of A28 DOI Link: https://doi.org/10.26685/urncst.15 collected and analyzed.Testing is planned to commence in Waterloo, London, Thunder Bay, Windsor, and Corner Brook.Conclusion: Educational and advocacy projects driven by undergraduate and graduate students may impact the community by potentially improving outcomes and informing children about new career options.Risk of chronic kidney disease following acute kidney injury during diabetic ketoacidosis in children with type 1 diabetesMehima Kang, BSc Student[1], Rebecca Ronsley, MD[2], Cherry Mammen, MD, FRCPC [3], Constadina Panagiotopoulos, MD, FRCPC [2][1] Department of Life Sciences, Queen's University,Kingston, Ontario, Canada  [2]  Division ofDiabetes & Metabolism, British Columbia's Children's Hospital, Vancouver, BC, Canada  [3]  Division of Nephrology, British Columbia's Children's Hospital, Vancouver, BC, Canada    Background: A recent study demonstrated that 64% of children hospitalized for diabetic ketoacidosis (DKA) presented with acute kidney injury (AKI).Other pediatric populations show AKI to confer an increased risk for chronic kidney disease ( spontaneous movement in full-term infants Matthew Yau, BHSc Student[1], Victoria Galea, PhD [2][1] Faculty of Health Sciences, McMaster University, Hamilton, Ontario, L8S 4L8[1] School of RehabilitationScience, McMaster University, Hamilton, Ontario, L8S 4L8

Williams et al. | URNCST Journal (2017): Volume 1, Issue 3 Page A10 of A28 DOI Link: https://doi.org/10.26685/urncst.15 Conference Poster Presentation Abstracts Poster Presentations in Biochemistry Biophysical studies of novel DNA guanine quadruplex binders with eventual anticancer applications Mickey Chen, BSc Student
Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, N6A 5B7 [2] Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, N6A 5B7 [3] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada, M5S 1A1 [4] Department of Microbiology and Immunology, Faculty of Medicine, Department of Biochemistry, University of Ottawa, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Science Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Cana-Department of Pediatrics, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada, K1N 6N5