Master Abstract Document Canadian Student Health Research Forum (CSHRF) 2021 Hosted virtually by the University of Manitoba June 14 – 18, 2021 The design, synthesis, and application of new benzamides as antimicrobial molecules Monalisa Abas1, Rachel Willim1, Tabitha E. Wood1 1The University of Winnipeg Introduction: Antibiotic-resistant bacterial strains continue to rise, and new methods of antimicrobials are needed. A promising new target involves replication protein FtsZ. This protein, found only in prokaryotes, orchestrates the formation of a Z-ring. The Z-ring serves as the site of division, separating the singular bacterial cell into two identical daughter cells. This step is necessary in successful replication of bacteria. The most promising reports of potent FtsZ inhibitors are benzamides. Upon benzamide binding to FtsZ, the cell elongates, and replication is completely inhibited. This project aims to investigates the design and synthesis of a library of benzamide compounds. These compounds will be tested against a range of different bacteria to assess their inhibitory properties. The synthetic approach to benzamide synthesis may be achieved in many ways, however the Truce-Smiles rearrangement is of particular interest for its enhanced selectivity, reactivity and perfect atomeconomy. Additionally, the reaction achieves the formation of a new and highly desirable carbon-carbon bond. Methods: Ullmann coupling utilizes a copper catalyst and is used in the formation of the aniline starting material. Microwave-assisted TCT peptide coupling is used in the formation of the aryl benzamide intermediate by combing the starting aniline and a corresponding acid. The final synthesis involves the Truce-Smiles rearrangement. The rearrangement is achieved by directed ortho lithiation, lithium halogen exchange, or deprotonation. The compounds are characterization by standard methods of chromatography and spectroscopy. The compounds will be tested against a range of bacterial species. The broth microdilution method will be used to determine minimum inhibitory concentrations. Standard phase-contrast microscope techniques will be used to observe phenotypic changes upon benzamide binding. Results: The Ullmann coupling is reproducible with the aniline and pyridine-derivative aniline compounds. Additionally, the microwave-assisted amide synthesis has successfully synthesized the nitro-derived benzamide compound intermediates that have been proposed. Conclusion: The synthesis of the aniline starting material and nitro-derived benzamide compound intermediates have been successful thus far. These proposed methods of synthesis will continue to be used. Trends of COVID-19 incidence in Manitoba and public health measures: March 2020 to March 2021 Laila Aboulatta1, Kaarina Kowalec1,2, Sherif Eltonsy1,3 1College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Canada 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden 3The Children's Hospital Research Institute of Manitoba, Canada Introduction: The increasing spread of SARS-CoV-2 has prompted much of Canada to take unprecedented measures. Currently, there is no timeline to demonstrate the effectiveness of the implemented mitigation measures in controlling the burden of COVID-19. The aim of this report was to examine the impact of the implemented public health measures on the incidence of COVID-19 in Manitoba. Methods: Using the Manitoba Health, Senior and Active Living COVID-19 dataset, we examined the temporal trends of daily reported COVID-19 cases and the coinciding public health measures implemented from March 12, 2020 to March 1, 2021. Results: We developed a model that demonstrates the trend of COVID-19 incidence before, during and after the implementation of different mitigation measures. On March 20, 2020, the Premier of Manitoba declared a state of emergency to limit the viral spread. From March 13 to April 17, 2020, several mitigation strategies were applied including physical distancing, limiting gatherings, wearing masks, closure of universities, non-urgent medical care restriction, and non- essential travel limitations. Due to these restrictions, the daily cases decreased by 97% from 33 (April 1) to 1 (May 1, 2020). Between May 4 and July 17, 2020, the reported cases stabilized, and some restrictions were lifted. However, during the second wave in the Fall 2020, the number of cases increased by ~176% from 58 on October 7 to 160 on October 14, 2020. Since October 19, Manitoba had three-digit daily cases for 3 consecutive months, and the number peaked during November 4-27, 2020 (ranging from 227-593). Additional restrictions implemented included limiting social contacts to household members, non-essential items could not be purchased in-store, closing of gyms and restaurants, with all of Manitoba placed in the highest response level (“critical”). Mitigation measures were extended through January 2021, and the number of cases dropped to 52 cases on March 1, 2021. Conclusion: This report provides estimates that physical distancing in conjunction with other containment measures can reduce the COVID-19 burden. Future studies into the extent of the implementation of the restrictions are necessary. Transplantation of young bone marrow stem cells can delay bone aging in mice Lina Abu-Nada1,4, Younan Liu2, Faez Al hamed2, Simon Tran2, Guylaine Ferland3, Vahab Soleimani1, Faleh Tamimi2, Monzur Murshed1,2,4 1Faculty of Medicine, McGill University, Montreal 2Faculty of Dentistry, McGill University, Montreal 3Faculty of Medicine, Université de Montréal, Montreal 4Shriners Hospital for Children, Montreal, Qc, Canada Background: Recent discoveries have shown that systemic manipulation such as parabiosis, blood exchange and young plasma transfer, can counteract many important symptoms of aging. This rejuvenation effect has been attributed to circulatory factors produced by several cells (haematopoietic or non-haematopoietic). However, the specific involvement of bone marrow (BM) or haematopoietic cells in producing these factors and their effects on bone remodeling is still unclear. Our objective is to develop a model of old mouse transplanted with young/old marrow cells through BM transplantation and assess the effects on the aging process, specifically in bone. Method: An aged mouse model with young/old BM/haematopoietic system has been created. In particular, aged C57BL/6 mice (18-month old) were total-body irradiated to eliminate their endogenous BM, and then transplanted with BM cells from either young (2-month) or old (18-month old) mice. Flow cytometry using a transplanted cell-specific marker (green fluorescent protein) confirmed BM cell engraftment. After six months of transplantation, mice were euthanized, and their long bones and vertebrae were collected and analyzed using micro CT, mechanical testing and histology. Results: A mouse model of “old mice transplanted with young/old BM cells” was successfully created with ~85% engraftment. Our results showed that rejuvenating the BM/hematopoietic system through young bone marrow transplantation reversed old age-associated low bone mass traits in mice. Specifically, young bone marrow transplantation improved bone trabecular microarchitecture both in tibiae and vertebrae of old mice and increased the number of osteoblasts and osteoclasts compared to old bone marrow transplantation. Conclusion: Young bone marrow cells may represent a future therapeutic strategy for osteoporosis. The findings of this study could radically alter our understanding of aging, and direct further examination of the cell signaling process involved in age- related diseases. Implementing SDM in interprofessional home care teams supporting caregivers of frail elderly facing housing decisions: a stepped wedge cluster randomised trial E. Lionel Adisso1, Louis-Paul Rivest1, Monica Taljaard2, France Légaré1 1Laval University, Quebec City, Quebec 2University of Ottawa, Ontario, Canada Introduction: One of the toughest decisions faced by cognitively impaired older adults with loss of autonomy (frail elderly) is whether to stay at home or move to a care facility. This study aims to evaluate the effect of the addition of a training programme in IP-SDM to the passive dissemination of a decision guide on the proportion of caregivers reporting an active role in the decision-making process about the housing of the frail elderly. Methods: A stepped wedge cluster randomised trial involving nine Integrated (University) Health and Social Service Centers (CISSS/CIUSSS) in the province of Quebec was conducted. Participants were home care teams working in recruited CISSS/CIUSSS, and caregivers of frail elderly (≥ 65 years) who were receiving care from a home care team. Participating CIUSSS/CISSS were randomised to one of four intervention periods. Eligible caregivers had made a housing decision for the frail elderly. The intervention, targeted IP home care teams, consisted of a 1.5-hour online tutorial and a 3.5-hour skills- building workshop in IP SDM. The comparator was a decision guide distributed passively at the beginning of the project. The primary outcome was the proportion of caregivers reporting an active role in the decision-making process. We performed intention-to-treat multilevel analysis and used a generalized linear mixed model. Results: Of the 339 caregivers, 167 were in the control periods and 172 in intervention periods. They were mostly female – 122 (73.1%) versus 117 (68.0%), more than 60 years old – 63.7 (IQR, 55.1