Track 1

Track1

1.1. An Evaluation of Recently Emerging Therapeutics in Triple-Negative Breast Cancer.
Ammar Salkini* (1)
(1) Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON

Triple-negative breast cancer (TNBC) is a highly metastatic type of breast cancer and a significant contributor to cancer mortality in women. Many TNBC drugs that successfully produce antitumor effects in-vitro fail to produce significant, long-lasting effects at the clinical level. This is because they do not effectively suppress the growth of cancer stem cells (CSCs), which have the capacity to differentiate into metastatic tumors. Moreover, it has been shown that in TNBC, CSCs are able to modify their metabolomic signature to escape the toxic effects of these drugs; their modified metabolomic signature is causally associated with increased metastasis. Therefore, successful therapies must have the ability to selectively inhibit CSC growth and its metastatic-metabolomic signature (MMS). This study will evaluate the potency of five recently proposed TNBC treatments—which all successfully decreased tumor development in-vitro—to inhibit (TNBC-specific) genes involved in CSC survival and MMS. TNBC cell-lines and/or patient-derived xenografts were treated with five different treatments: DCC-2036, 9Gy proton-irradiation, miR302b+cisplatin, DFX+doxorubicin, and BKM120. Genome-wide mRNA profiling (using either RNA-seq or microarray) was performed on control and treated groups. Data was obtained from NCBI-GEO datasets. We assessed the differential expression of genes associated with CSC growth and MMS in TNBC tumors. Statistical analysis was performed to validate significance of results. So far, bioinformatics analysis was performed on only the DCC-2036 treatment group. Analysis revealed significant activation of CSC TNBC biomarkers—such as ADHL, CD44, CCR5, and SNAI1—and of genes associated with MMS—such as PPARGC1A, HK1, PFKB1 and PFKB4. The profiles of the remaining groups are currently being analyzed. Our data suggests that although DCC-2036 has been shown to reduce global tumor proliferation in-vitro, it failed to inhibit CSC-related genes in-vitro and will likely fail to suppress CSC survival and metastasis in-vivo. Finally, the outline of this study provides a useful rationale of predicting the efficacy of emerging TNBC drugs.

Keywords:TNBC, CSC rebound, metastasis, drug resistance, gene enrichment.

1.2. Review of literature to examine maternal and infant health outcomes from exposure to PBDE during pregnancy.
Myeesha Begum* (1), Prem Kumarathasan (1, 2), James Gomes (1)
(1) Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON.
(2) Environmental Health Science and Research Bureau, HECSB, Health Canada, Ottawa, ON

Background: Polybrominated diphenyl ethers (PBDE) are persistent organic pollutants found in the environment. They exhibit endocrine disrupting properties and in-utero exposure to these chemicals can cause adverse maternal and infant health outcomes. Objective: The objective is to examine the level of exposure to PBDE during pregnancy and determine its impact on maternal and infant health outcomes. The alterations in the expression of biomarkers from exposure to PBDE are evaluated as indicators of adverse health effects. Methods: A literature review was conducted using: PubMed, Ovid, EMBASE, Scopus, and Web of Science.The search strategy included search terms (polybrominated diphenyl ether*), (gestational* OR pregnan* OR maternal* ), AND (infant* OR newborn* OR neonate*) published between January 2005 and February 2021. Inclusion criteria were English articles, pregnant women between the ages 15 and 49, singleton births criteria, no previous medical history that may affect endocrine action. Results: The search produced a total of 1395 articles. A total of 49 articles (44 human observational and 5 review) were selected for further scrutiny. The studies focused on PBDE exposure in relation to thyroid and sex hormone disruption, maternal adverse effects included gestational hypertension, gestational diabetes (GDM) and pre-eclampsia and infant health impacts included low birth weight, head circumference, apgar score, fetal growth restriction (FGR) and more. The alterations in biomarkers were noted for its effect on maternal and infant health. Conclusion: Four articles that reported on GDM and three on FGR showed consistent results in increased odds of GDM and FGR with increased concentration of PBDE exposure. There is inconclusive evidence of adverse maternal and infant health but there is indication that PBDE could have negative effects on maternal and infant health.The findings also indicated alterations in the biomarker profile. This study warrants further research on the impact of PBDE on maternal and infant health.

Keywords:polybrominated diphenyl ether, gestational*, pregnan*,maternal* and infant

1.3. Self-Managed Abortion: Dispelling Myths and Creating a Path for Increased Abortion Access.
Laura O’Connor* (1)
(1) Faculty of Social Sciences, University of Ottawa, Ottawa, Ontario, Canada.

This article seeks to explore the current risks and objections to self-managed abortions, and the ways in which self-managed abortion(s) could expand abortion access in Canada. This article argues that the Government of Canada, in alignment with its policy commitments to reproductive freedom, should alter its current medication abortion recommendations to include an approval of self-assessed and self-managed medication abortions. I will begin my argument with an explanation of “self-assessed and self-managed abortion” and dispel misconceptions as to what this may look like. I will then provide a thorough analysis of current Health Canada policies on medication abortion provision, and WHO’s position on self-managed abortion, to provide a policy-focussed context for my argument. I then analyze current public health understandings of the risks associated with self-managed abortions and the degree of expertise needed to safely administer Mifegymiso (medication abortion). I then seek to understand current gaps in abortion access in Canada, working from a reproductive justice theoretical framework and a right-to-health perspective, to ultimately identify the ways in which self-managed abortion could address these gaps in access. I will conclude this article with a call to action on the part of Health Canada to provide an update to current Mifegymiso prescription information, allowing for Mifegymiso to be self-managed by the patient.

Keywords:Abortion, reproductive justice, right to health, mifegymiso, public health

1.4. Specialized Pro-Resolving Lipid Mediators as a Novel Therapy for Pneumonia- Associated Inflammation to Decrease Risk of Severe Cardiac Events.
Cameron Stotts* (1)
(1) Faculty of Medicine – Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON.

This article seeks to explore the current risks and objections to self-managed abortions, and the ways in which self-managed abortion(s) could expand abortion access in Canada. This article argues that the Government of Canada, in alignment with its policy commitments to reproductive freedom, should alter its current medication abortion recommendations to include an approval of self-assessed and self-managed medication abortions. I will begin my argument with an explanation of “self-assessed and self-managed abortion” and dispel misconceptions as to what this may look like. I will then provide a thorough analysis of current Health Canada policies on medication abortion provision, and WHO’s position on self-managed abortion, to provide a policy-focussed context for my argument. I then analyze current public health understandings of the risks associated with self-managed abortions and the degree of expertise needed to safely administer Mifegymiso (medication abortion). I then seek to understand current gaps in abortion access in Canada, working from a reproductive justice theoretical framework and a right-to-health perspective, to ultimately identify the ways in which self-managed abortion could address these gaps in access. I will conclude this article with a call to action on the part of Health Canada to provide an update to current Mifegymiso prescription information, allowing for Mifegymiso to be self-managed by the patient.

Keywords:Pneumonia, atherosclerosis, specialized pro-resolving lipid mediators, resolution, cardiovascular disease

1.5. Efficient, Remote Heart-Rate Detection using Video Information.
Mariam Jabara* (1)
(1) School of Electrical Engineering and Computer Science, University of Ottawa, Ottawa

Introduction: Remote monitoring of patient vital signs is becoming of more interest as the demand for long-term health information and telemedicine expands. With such, the need to develop an accurate, computationally efficient and robust method to detect cardiac pulse is imperative for the integration of remote vital sign monitoring. Many algorithms involved in non-contact pulse detection involve various parameters, the values of which may greatly impact the results produced by the software. As a result, there also exists the need for a tool to allow researchers to explore various combinations of parameters, without having to alter the source code. Objectives: In this study, we propose a computationally efficient research tool that detects heart rate at a clinical level of accuracy from video information and allows its users to alter key parameters involved in the heart-rate detection algorithm. Methods: The proposed tool leverages the Fast Fourier Transform (FFT) algorithm to detect heart rate from video input signals. A proof of concept for heart-rate accuracy is demonstrated, along with experiments that explore the effects of video resolution and region of skin examined on the heart-rate estimation. Results: The results of the preliminary experiments suggest that our tool detects cardiac pulse from video information with clinically acceptable accuracy, and provides consistent results even for videos in low-resolution (270p). Conclusion: Our preliminary findings indicate that the Fast Fourier Transform alone is sufficient to produce clinically acceptable results in heart-rate estimation, leading the way for more efficient and scalable implementations of remote vital sign monitoring.

Keywords:heart-rate detection, Fast Fourier Transform, remote monitoring, video processing

1.6. Modulating Human Skeletal Muscle Satellite Cell Division with WNT7A and EGF.
Maria Madana* (1,2), Morten Ritso (1,2), Ricardo Carmona (1,2), Michael Rudnicki (1,2)
(1) Regenerative Medicine, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada
(2) Cellular and Molecular Medicine, University of Ottawa, Roger Guindon Hall, 455 Smyth Road, Ottawa, Ontario, Canada

Introduction: Skeletal muscle stem cells, referred to as satellite cells, are characterized by Pax7 expression. Our lab discovered that in mice, satellite cells express the Wnt-receptor Frizzled 7, and that its ligand WNT7A stimulates symmetric expansion of satellite cells by giving rise to two daughter satellite stem cells. On the other hand, epidermal growth factor (EGF) stimulation of satellite cells activates the EGF receptor and induces an asymmetric division, generating one daughter satellite stem cell and one committed myogenic precursor cell. We also discovered that a lack of dystrophin protein in Duchenne Muscular Dystrophy (DMD) reduces the number of asymmetric divisions, which reduces the number of myogenic progenitors that are needed for proper muscle regeneration. Objective: Confirm the aforementioned discoveries in a human in vitro model by using induced pluripotent stem cells (hiPSCs) generated from healthy and DMD patient cells differentiated into the myogenic lineage to create satellite-like cells and perform WNT7A/EGF treatment on these cells. Methods: hiPSC colonies were treated with a GSK3 inhibitor to drive mesoderm specification. From day 12 of differentiation, cells were treated with either WNT7A or EGF. On days 21, 35 and 50, myogenic differentiation was assayed through immunofluorescence (IF) analysis. Array scanner analysis of IF staining was used to quantify myogenic cell numbers and investigate population dynamics. Additionally, myogenic gene and protein expression was assessed within the differentiating cell populations. Results: Myogenic markers were expressed in the differentiating cell cultures. The proportions of cells expressing different myogenic factors were affected by the different treatments. Gene expression analysis demonstrated an upregulation of early myogenic markers following WNT7A treatment and late myogenic markers with EGF treatment. Conclusion: This project studied and confirmed previous findings of the regeneration mechanisms that drive the pathological etiology of DMD in a human in vitro model.

Keywords: Induced pluripotent stem cells, WNT7A, EGF, Duchenne Muscular Dystrophy, Translational Evidence

1.7. Exploring the experiences of healthcare leaders from diverse professional backgrounds.
Alannah Mulholland* (1) Stella Ng (2,3), Ryan Brydges (2,3), Emilia Kangasjarvi (2,3), Betty Onyura (2,3), Susan Lieff (2,3), Beverly Bulmer (2,3)
(1)Faculty of Medicine, University of Ottawa, Ottawa, ON
(2)Centre for Faculty Development, Faculty of Medicine, University of Toronto, Toronto, ON
(3)AERO Research Group, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON

Introduction: While high-level leadership roles in hospitals have traditionally been fulfilled by physicians and nurses, the professional profiles of healthcare leaders has grown increasingly diverse in recent years. Various health disciplines offer valuable perspectives to the visions, strategies, and daily operations of hospitals. However, literature on these other professions in the hospital leadership space is sparse and research in other domains has shown that diversifying membership does not necessarily address equity and inclusion. Objective: To understand the experiences of senior leadership executives that come from professional backgrounds other than medicine and nursing in order to inform supports and improve structures. Methods: We conducted a phenomenographically informed qualitative study, interviewing 14 participants. Inclusion criteria included 1) holding a senior leadership position in an Ontario hospital and 2) having a professional background outside of nursing or medicine. One-hour semi-structured in-depth interviews were held with each participant, which were transcribed and inductively coded. Results: Common identities and journeys to leadership were identified as three overlapping categories: the emancipatory journey of the champion leader, the unexpected journey of the discovered leader, and the practical journey of the utilitarian leader. Participants had diverging perspectives on the importance of clinical knowledge, and felt their individual expertise contributed to their success. Generally, participants with healthcare experience tended to disregard their previous identity, while those possessing business backgrounds embraced theirs. Conclusion: If health sciences genuinely value professional diversity, opportunities to support experiences of professionals with non-health and various health backgrounds in hospital settings need attention. Mentorship supports focusing on individuals are required, but this alone is not sufficient. To promote unique and diverse perspectives in healthcare leadership spaces, cultural and structural changes must lead the way. Leadership programs may need to attend not only to developing diverse teams but also to genuinely embracing this diversity in hospital settings.​

Keywords:leadership, healthcare, phenomenography, qualitative, professionals

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