University of Manitoba Scholarship

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This collection contains open access research publications authored or co-authored by University of Manitoba researchers. Content within this collection includes pre and post-print versions of articles and book chapters, conference proceedings and technical reports. MSpace is where faculty and students can deposit their research output to meet the open access requirements of grant funding agencies and other related mandates. Deposit is subject to copyright compliance, distribution license and other license restrictions that may be imposed on the work.

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Now showing 1 - 5 of 2141
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    Open Access
    Navigating MNE control and coordination: A critical review and directions for future research
    (Springer Science and Business Media LLC, 2023-03-08) Zeng, Rong
    Control and coordination efforts are at the heart of MNE functioning. Yet, our review reveals that the literature on MNE control and coordination lacks conceptual clarity, which may hamper the development of the field. In this critical review, we synthesize the literature over the past decade using a conceptual framework rooted in new internalization theory. Research remains fairly coarse regarding how various configurations and interactions of control and coordination mechanisms affect intended outcomes. We note a paucity of multilevel studies, direct investigations of microfoundations, and comparison studies between intra- and inter-MNE relationships. Insufficient attention has been paid to adaptation issues and the impact of external dynamics on the need for, and operationalization of, control and coordination mechanisms. These gaps are concerning, since external trends are changing the organizational landscape and MNE boundaries are becoming increasingly fuzzy. Going forward, a more nuanced conceptualization of outcomes is needed, one that specifies proximal outcomes which mediate the achievement of distant goals. We use our augmented conceptual framework to identify other key areas for future research. We also call for more research on how disruptive forces affect both the use and outcomes of organizational mechanisms aimed at achieving control and coordination.
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    Open Access
    Oxidized SOD1 accelerates cellular senescence in neural stem cells
    (2024-02-27) Guan, Teng; Guo, Ying; Zhou, Ting; Yu, Qiang; Sun, Jingyi; Sun, Baoliang; Zhang, Guohui; Kong, Jiming
    Abstract Background Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation. Once oxidized, it undergoes aberrant misfolding and gains toxic properties associated with age-related neurodegenerative disorders. The present study aims to examine the role of oxidized hSOD1 in the senescence of NSCs. Methods NSCs prepared from transgenic mice expressing the wild-type hSOD1 gene were maintained in culture through repeated passages. Extracellular vesicles (EVs) were isolated from culture media at each passage. To selectively knock down oxidized SOD1 in NSCs and EVs, we used a peptide-directed chaperone-mediated protein degradation system named CT4 that we developed recently. Results In NSCs expressing the hSOD1 from passage 5, we detected a significant increase of oxidized hSOD1 and an increased expression of biomarkers of cellular senescence, including upregulation of P53 and SA-β-Gal and cytoplasmic translocation of HMGB1. The removal of oxidized SOD1 remarkably increased the proliferation and stemness of the NSCs. Meanwhile, EVs derived from senescent NSCs carrying the wild-type hSOD1 contained high levels of oxidized hSOD1, which could accelerate the senescence of young NSCs and induce the death of cultured neurons. The removal of oxidized hSOD1 from the EVs abolished their senescence-inducing activity. Blocking oxidized SOD1 on EVs with the SOD1 binding domain of the CT4 peptide mitigated its toxicity to neurons. Conclusion Oxidized hSOD1 is a causal factor in the cellular senescence of NSCs. The removal of oxidized hSOD1 is a strategy to rejuvenate NSCs and to improve the quality of EVs derived from senescent cells.
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    Open Access
    The genetic architecture of youth anxiety: a study protocol
    (2024-02-23) McAusland, Laina; Burton, Christie L.; Bagnell, Alexa; Boylan, Khrista; Hatchard, Taylor; Lingley-Pottie, Patricia; Al Maruf, Abdullah; McGrath, Patrick; Newton, Amanda S.; Rowa, Karen; Schachar, Russell J.; Shaheen, S-M; Stewart, Sam; Arnold, Paul D.; Crosbie, Jennifer; Mattheisen, Manuel; Soreni, Noam; Stewart, S. E.; Meier, Sandra
    Abstract Background Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Methods The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10–19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. Discussion Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.
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    Open Access
    The effectiveness of sodium-glucose co-transporter 2 inhibitors on cardiorenal outcomes: an updated systematic review and meta-analysis
    (2024-02-15) Ali, Muhammad U.; Mancini, G. B. J.; Fitzpatrick-Lewis, Donna; Connelly, Kim A.; O’Meara, Eileen; Zieroth, Shelley; Sherifali, Diana
    Abstract Background The 2022 Canadian Cardiovascular Society (CCS) cardiorenal guideline provided clinical recommendations on sodium-glucose co-transport 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) use. Since then, additional trials of relevance for SGLT2i have been published. This update re-evaluates the clinical recommendations for using SGLTi and their indirect comparison with existing evidence on GLP-1RA as compared to the standard of care to reduce cardiorenal morbidity and mortality. Methods We updated our existing search and screening of the literature from September 2021 to April 2023 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. We conducted risk of bias assessment, data extraction and updated our meta-analysis of studies with similar interventions and components. The certainty of the evidence was determined using GRADE. Results Evidence from three new trials and additional results from an updated existing trial on SGLT2i met our inclusion criteria after an updated search. Across all the included studies, the total sample size was 151,023 adults, with 90,943 in SGLT2i trials and 60,080 in GLP-1 RA trials. The mean age ranged from 59.9 to 68.4 years. Compared with standard care, the use of SGLT2i and GLP-1 RA showed significant reductions in the outcomes of cardiovascular (CV) mortality (14% & 13%), any-cause mortality (12% & 12%), major adverse CV events (MACE) (11% & 14%), heart failure (HF) hospitalization (30% & 9%), CV death or HF hospitalization (23% & 11%), and kidney composite outcome (32% & 22%). In participants with T2D, both classes demonstrated significant cardiorenal protection. But, only GLP-1RA showed a reduction in non-fatal stroke (16%) and only SGLT2i showed a reduction in HF hospitalization (30%) in this population of people living with T2D. Conclusions This updated and comprehensive meta-analysis substantiates and strengthens the clinical recommendations of the CCS cardiorenal guidelines.
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    Open Access
    Developing a set of emergency department performance measures to evaluate delirium care quality for older adults: a modified e-Delphi study
    (2024-02-15) Filiatreault, Sarah; Kreindler, Sara A.; Grimshaw, Jeremy M.; Chochinov, Alecs; Doupe, Malcolm B.
    Abstract Background Older adults are at high risk of developing delirium in the emergency department (ED); however, it is under-recognized in routine clinical care. Lack of detection and treatment is associated with poor outcomes, such as mortality. Performance measures (PMs) are needed to identify variations in quality care to help guide improvement strategies. The purpose of this study is to gain consensus on a set of quality statements and PMs that can be used to evaluate delirium care quality for older ED patients. Methods A 3-round modified e-Delphi study was conducted with ED clinical experts. In each round, participants rated quality statements according to the concepts of importance and actionability, then their associated PMs according to the concept of necessity (1–9 Likert scales), with the ability to comment on each. Consensus and stability were evaluated using a priori criteria using descriptive statistics. Qualitative data was examined to identify themes within and across quality statements and PMs, which went through a participant validation exercise in the final round. Results Twenty-two experts participated, 95.5% were from west or central Canada. From 10 quality statements and 24 PMs, consensus was achieved for six quality statements and 22 PMs. Qualitative data supported justification for including three quality statements and one PM that achieved consensus slightly below a priori criteria. Three overarching themes emerged from the qualitative data related to quality statement actionability. Nine quality statements, nine structure PMs, and 14 process PMs are included in the final set, addressing four areas of delirium care: screening, diagnosis, risk reduction and management. Conclusion Results provide a set of quality statements and PMs that are important, actionable, and necessary to a diverse group of clinical experts. To our knowledge, this is the first known study to develop a de novo set of guideline-based quality statements and PMs to evaluate the quality of delirium care older adults receive in the ED setting.