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Elucidating the cellular and molecular mechanisms that govern filovirus pathogenesis within ferrets with emphasis on Marburg virus
No full textRecently, the ferret has gained attention as a novel animal model for studying filoviruses. Ferrets are highly susceptible to several orthoebolaviruses, including Ebola virus (EBOV), yet refractory to infection with orthomarburgviruses, namely Marburg virus (MARV) and Ravn virus. The fact that ferrets are uniformly susceptible to infection with most orthoebolaviruses but not orthomarburgviruses suggests that these viruses differ fundamentally in their pathogenic mechanisms.
This thesis explored two main hypotheses. Firstly, it was hypothesized that this lack of susceptibility by ferrets to lethal infection with orthomarburgviruses resulted from a block in glycoprotein (GP) mediated viral entry. The results demonstrate that while MARV-GP can mediate entry into ferret cells, the efficiency is lower than that of EBOV-GP, particularly during the early stages of infection. While MARV can replicate within ferret cells, replication is attenuated compared to EBOV. Lastly, rEBOV-mGP is uniformly lethal in ferrets. However, the onset of disease and viremia was delayed compared to EBOV. These data demonstrate that GP may represent one probable factor accounting for the lack of disease among MARV-challenged ferrets.
Secondly, it was hypothesized that this lack of susceptibility by ferrets to lethal infection with orthomarburgviruses but not orthoebolaviruses is the result of mechanistic differences in the innate immune evasion tactics of these two viruses. The results demonstrated that inhibition of type I IFN production using drugs has a negligible impact on the replication of MARV within ferret cells. In contrast, inhibition of type I IFN signalling using drugs targeting the JAK/STAT pathway positively enhanced viral replication of MARV within ferret cells. Together, these data emphasize the potential contribution of MARV VP40 toward the viral replication of MARV within ferret cells. Challenge with guinea pig-adapted Marburg virus (GPA-MARV) resulted in uniform lethality among ferrets, whereas challenge with mouse-adapted (MA)-MARV resulted in only partial lethality. High levels of viral replication, a dysregulated immune response and hematological perturbations in biochemistry and blood counts were also observed among GPA-MARV-challenged ferrets. Lastly, several genome mutations appeared following challenge with GPA-MARV. This is the first report of a lethal orthomarburgvirus ferret model, and these data provide insight into the pathogenesis of orthomarburgviruses.February 202
Management practices to improve the sustainability and profitability of cow-calf operations across Canada
No full textIncreasing demand for food with higher environmental standards is shaping agricultural activities toward more sustainable food systems. The objective of this research was to estimate whole-farm greenhouse gas (GHG) emissions while concurrently examining the profitability of cow-calf operations with varying management practices across Canada. Twenty-five benchmark farms with similar environmental conditions and production practices were developed using data from 115 cow-calf operations. Greenhouse gas emissions including methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2) were estimated using the Holos whole-farm model. Emission intensity was calculated as net GHG emissions (kg of CO2 equivalent) divided by total liveweight (LW, kg) sold. Farm emission intensity ranged between 18.3 and 35.1 kg CO2 equivalent/ kg LW. Both emissions and profitability varied widely across farms with those in the Western provinces reporting generally higher emission intensity, due to higher enteric CH4 emissions. Farms that utilized tame grass and legume species reported lower enteric CH4 emissions, while those that utilized extended grazing practices had lower manure CH4 emissions. Growing annual grain crops for export was associated with higher net farm incomes. Modelling of future farm scenarios was conducted to assess impact of changes in on-farm management practices including grazing standing corn, adoption of rotational grazing, use of artificial insemination, creep feeding, shortened calving intervals, and improved watering systems on GHG emissions and economic outcomes. The impact of the changes in management practices was not consistent across all farms, resulting in a small (0.004%) increase to 4% reduction in GHG emissions while improving whole farm net cash income by 3 to 41 % and cow-calf enterprise profitability by 2 to 130%. Therefore, consideration of existing farm practices and the local environment is essential when considering changes in management to improve economic sustainability and reduce GHG emissions.Canfax Research Services
University of ManitobaFebruary 202
Multiplex immunofluorescence studies to characterize early cellular dynamics in laser-ablated non-tumor mouse brain
No full textIntroduction: Laser Interstitial Thermal Therapy (LITT) is a minimally invasive, hyperthermia-based laser cytoreductive method used in the treatment of several severe conditions, including inoperable brain tumors, treatment-resistant epilepsy, and radiation necrosis. Laser-induced heat causes damage to the tissue and alters the brain-tissue microenvironment (TME) at the local treatment site and beyond. The regional effects include activation of resident brain cells, release of mediators of inflammation, and immune cell infiltration, which may activate immune responses. Immunomodulatory responses to LITT in the brain microenvironment are largely unknown. One hurdle is the lack of affordable and efficient imaging protocols that enable the simultaneous spatial visualization of multiple immunoreactive cellular targets in the brain. Here, we describe a flexible and affordable multiplex immunofluorescence (mIF) staining method in our established LITT mouse model. In the post-LITT mouse brain, mIF revealed laser ablation-induced complex spatial responses by the resident brain and innate immune cells.
Methods: We developed a customizable and affordable mIF detection protocol that uses standard histological and microscopy equipment to assess TME changes on single sections of formalin-fixed paraffin-embedded (FFPE) mouse brain tissues at day 6 post-LITT. This mIF imaging procedure provided a comprehensive spatial analysis of multiple cellular and molecular immunotargets in resident brain cell responses and immune cell profiles in individual tissue sections, as exemplified with a mouse brain microenvironment on day 6 post-LITT.
Results: We optimized mIF imaging methodology on LITT-treated mouse brain FFPE serial sections to visualize the spatial distribution of resident brain cell cellular activation states and the emergence and distribution of immune cell populations at the LITT site. Our mIF imaging protocol of mouse brain regions surrounding the LITT site revealed the activation of resident astrocytes and microglial cells and the presence of a diverse innate immune cell population in this region.
Conclusion: The combined use of LITT ablation treatment with multiplexed versus regular immunofluorescence offers a significant advancement and aids in our understanding of post-LITT repair and immune responses in the brain. We characterized the thermal ablation-induced modulation of resident brain cells and innate immune cell infiltrations.May 202
Residency training programs to support residents working in First Nations, Inuit, and Métis communities
Get PDFAbstract Background To gain culturally appropriate awareness of First Nations, Inuit and/or Métis Health, research suggests that programs focus on sending more trainees to First Nations, Inuit and/or Métis communities Working within this context provides experiences and knowledge that build upon classroom education and support trainees’ acquisition of skills to engage in culturally safe healthcare provision. This study examines residents' and faculty members' perceptions of how residency training programs can optimize First Nations, Inuit and/or Métis health training and support residents in gaining the knowledge, skills, and experiences for working in and with First Nations, Inuit and/or Métis communities. Methods A qualitative approach was used, guided by a relational lens for collecting data and a constructivist grounded theory for data interpretation. Theoretical sampling was used to recruit 35 participants from three main study sites across two western Canadian provinces. Recruitment, data collection, and analysis using constructivist grounded theory occurred concurrently to ensure appropriate depth of exploration. Results Our data analysis revealed five themes: Five themes were generated: Complexity of voluntourism as a concept; Diversity of knowledge representation required for developing curriculum; Effective models of care for First Nations, Inuit and/or Métis health; Essential traits that residents should have for working in First Nations, Inuit and/or Métis communities; and Building relationships and trust by engaging the community. Conclusions First Nations, Inuit and/or Métis Health should be prioritized within Canadian postgraduate medical education. Equipping trainees to provide holistic care, immersing in and learning from First Nations, Inuit and/or Métis communities is essential for developing the next generation of clinicians and preceptors. We present educational recommendations for residency programs to optimize First Nations, Inuit and/or Métis health educational experiences and provide residents with skills to provide effective and culturally safe care
Love, Manitoba: designing a staycation hotel
No full textTravel is a practice that many members of society feel a natural inclination towards. A new and sometimes foreign environment offers glimpses of an alternate life where reality can melt away. In the wake of the Covid-19 pandemic, this ability to travel freely was taken away from many who considered it to be a part of their routine. This practicum explored ways in which the local context of a location not typically seen as a destination, could be marketed as a desirable staycation by examining tourism trends and changes in response to the pandemic, how interior design principles such as adaptive reuse and experiential design can use history and site context to create an interior space that encapsulates qualities of a province, and how interior design used in a tourism context can create a memorable staycation experience for Manitoba residents.
The previously mentioned concepts will be studied and applied in the design of a small-scale boutique hotel. Natural elements of the site and provincial context combined with the strong sense of community that is often felt by residents and visitors of the city come together to inspire and influence the design at all points of the process. Maintaining inclusive design principles, and carefully designing a unique experience in which a combination of private spaces and public social spaces are desired, this hotel will experiment with a level of flexibility not typically associated with other projects of the same typology. The examined literature focuses on the concepts of memorable tourism experiences, experiential design, adaptive reuse, and visiting friends and relatives tourism. The conclusions derived from the study respond to the questions of a) how hospitality and experiential design strategies combine to encourage travel within Manitoba; b) how experiential design could be used to create a memorable staycation experience; and c) how can the memorable characteristics of a province and community influence the interior design of a physical space.February 202
Exploring the modulatory effects of aspirin on vaginal immunity
Get PDFIntroduction: Human cohort studies associate bacterial vaginosis (BV) with adverse reproductive health outcomes such as genital inflammation and increased HIV acquisition risk. We developed a bacterial challenge model to investigate BV-associated barrier disruption, elevated cytokine production, and increased T cell activation. Damping of genital inflammation needs to be part of a comprehensive HIV-prevention strategy along with pre-exposure prophylaxis (PrEP). Acetylsalicylic Acid (ASA) is an anti-inflammatory drug that is widely available, affordable, and accepted in Kenya. Human cohort studies in this region found that ASA modulates mucosal immunity by reducing HIV targets (CD4+CCR5+ T cells) in the female reproductive tract (FRT), but its broad impact on the vaginal mucosa is unknown. In this thesis, I addressed whether ASA could dampen BV-associated inflammation, CD4 T cell activation, and epithelial barrier disruption in vivo and whether these effects can lower HIV acquisition risk.
Methods: C57BL/6 mice were intravaginally challenged with BV-associated anaerobes Mobiluncus mulieris or Gardnerella vaginalis, with daily dosing of 32 mg/kg of ASA. In vivo assessment of vaginal epithelial layer function using Lucifer yellow dye, immunophenotyping of vaginal T cell subsets, and transcript-level analyses of FRT-draining lymph nodes by qPCR and RNAseq were performed to evaluate the therapeutic effects of ASA.
Results: ASA was found to have a potential to mitigate the disruption of vaginal epithelial barrier function associated with Mobiluncus mulieris challenge. Similarly, ASA was found to reduce neutrophil recruitment to the lamina propria of the FRT of Mobiluncus mulieris challenged mice. ASA treatment was found to alter pathways associated with cell activation and recruitment in the FRT-draining lymph nodes, and qPCR analysis of this compartment associated ASA with reduced TH17-associated cytokine transcripts. At the cellular level, ASA treatment was also found to counter the elevated frequency of TH17 cells in the FRT and lymph nodes associated with bacterial challenge.
Significance and Impact: Short-term ASA treatment significantly lowered key readouts of vaginal mucosal inflammation induced by BV-associated bacteria, such as the recruitment of TH17 cell subsets, pro-inflammatory cytokine production, and barrier disruption. Further testing is required to assess whether this translates to reduced HIV susceptibility.Research ManitobaFebruary 202
Designing behavioural nudges to encourage financial propriety of older adult proxies
Get PDFOlder adults sometimes request or require assistance with financial management tasks from close family or friends, and many of these tasks are now being completed online. Due to a lack of better mechanisms for granting a delegate access to their bank accounts, older adults commonly share their online banking passwords with their close others, opening the older adult up to a greater risk of financial abuse or other security or privacy violations. Through my research, I have explored the impact and value of two techniques for mitigating these risks: behavioural nudges and proxy accounts. The former are interface elements that guide the user without limiting their agency, and the latter is an access mechanism that provides accountability for, and limitations on, the account data and financial actions available to a delegate.
To investigate these techniques I designed and implemented a high-fidelity online banking prototype and used it to run a user study (n=21) in which older adults and close others were asked to perform a series of tasks in the prototype before discussing their perceptions of both the proxy accounts and nudges. Overall, my findings suggest that both older adults and close others greatly approve of the implementation of proxy accounts as this mechanism provides increased transparency, accountability, and legitimacy for the activities of close other delegates. Attitudes towards behavioural nudges were more neutral on average, with a wide range of opinions on their efficacy and desirability, but the findings also indicate that there is more work that can be done to investigate their efficacy in other contexts.
Additionally I have identified a number of factors that should be considered when designing online banking systems to support delegation, with the goal of minimizing risk to older adults while still maintaining their agency and the level of support available to them. These findings, extensive literature review and synthesis, and my own design process were used to propose a design space for considering access mechanism and designing behavioural nudges in delegated banking contexts.The only funding I have received is via Dr. Latulipe's NSERC Discovery grants. I've included that information here. I received no direct funding myself.February 202
Staff and volunteer survey
Get PDFThe Centre on Aging conducted a study of COVID-19 vaccination decision-making in personal care homes (PCH) in Manitoba. This research project focused on residents who were not able to make their own decisions about being vaccinated, and the aim of this study was to learn more about the perspectives and experiences of employees, volunteers, and families and friends of residents regarding vaccination decision-making specifically related to the COVID-19 pandemic. Eligible participants had to be 18 years of age or older, someone who either worked or volunteered at a PCH during the pandemic, and/or a family member or friend of a PCH resident in Manitoba during the pandemic who was not able to provide their own consent to be vaccinated against COVID-19
The short-term effects of peer tutoring in first-year biology labs on students with and without ADHD
Get PDFPeer tutoring is an active learning strategy that has been implemented in many university-level courses. However, many studies that examine the effects of peer tutoring focus solely on the long-term impacts of peer tutoring on learning outcomes and student perceptions, without considering how peer tutoring may affect students with learning differences, such as attention-deficit/hyperactivity disorder (ADHD). Therefore, this study considers the short-term effects of peer tutoring on learning outcomes and perceptions related to understanding metabolic experiments and the ability to focus in students with different relationships with ADHD. Data was collected from students in BIOL 1020 labs at the University of Manitoba during the Fall 2024 semester through an experiment lab, peer tutoring lab, final lab exam, and demographic survey. The main results of this study revealed that peer tutoring had no significant effect on the learning outcomes of students who have different relationships with ADHD. However, peer tutoring did have a significant positive effect on all students’ perceived understanding of metabolic concepts, regardless of their relationship with ADHD. Peer tutoring also had no significant impact on students’ perceived ability to focus, regardless of their relationship with ADHD. The findings of this study not only provide useful information to educators who may want to implement peer tutoring in their labs, but also demonstrate how peer tutoring affects all students the same, and can therefore be considered an inclusive active learning strategy for students, regardless of their relationship with ADHD
'We're not making it as easy as we might': issues and opportunities Open Science mandates present to Canadian ethics officers and librarians supporting human ethics
Get PDFBackground: Open Science (OS) offers a grand challenge by demanding both cultural and structural change across the ecosystem to realize global benefit and research accountability. The regulatory function of ethics review for human participatory research (HPR) ensures protection of the participant throughout the entire research project. With OS mandates, the review process and its stakeholders are located at the centre of this challenge: upholding the values of OS while also defending participant autonomy and privacy, community stewardship and situational policy obligations, as well as evaluating and managing other risks. Data management plans (DMPs) reflect all these aspects in a project. Purpose: To explore the experiences of supporting research data management (RDM) and/or DMPs as part of ethics review process by ethics officers, chairs and librarians and/or staff. Methodology: Eight semi-structured, individual interviews were conducted and audio recorded by the author. Transcripts were analyzed using a critical realist approach to identify patterns of support considerations. Analysis/Findings: An inter-related grouping of themes arose from participant reflections in their organizations: time, capacity, personal v. system-constructed relationships. Time, and its consumption, was the determining factor in both providing access to support and demonstrating its value. Definitions of capacity extend beyond infrastructure limitations and availability to require a collective knowledge and awareness across all organizational levels. Relationships are the ‘engine’ of capacity, and in the absence of system-identified networks, the efficacy of support is dependent on the provider’s agency, leadership mobilization, and ‘known quantity’ within the organization. These themes, informed by the participant’s function and positionality within their organization, together contributed to an overall thematic perception of paralysis v. engagement with respect to data management plan adoption and utility, and an ‘us against the system’ dynamic. Data management topics of data sharing, deposit and sovereignty were issues of specific concern. Conclusions: To better meet the complex, interdisciplinary challenges of OS-related data management-ethics concerns, a movement from solo or isolated units of support, defined by process or discipline, to new matrixed system structures which facilitate role awareness, knowledge exchange, and common language should be encouraged