78 results on '"Lagacé M"'
Search Results
2. La tumeur rhabdoïde maligne cutanée : un diagnostic rare, mais possiblement fatal
- Author
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Lagacé, M., primary, Smilga, A.S., additional, and Schreiber, A., additional
- Published
- 2022
- Full Text
- View/download PDF
3. C.3 Childhood Absence Epilepsy: Prevalence of neuropsychiatric comorbidities and predictors of treatment resistance
- Author
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Lagacé, M, primary, Michoulas, A, additional, Demos, M, additional, and Connolly, M, additional
- Published
- 2022
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4. P.102 Childhood Absence Epilepsy: Prevalence of treatment resistance and neuropsychiatric comorbidity.
- Author
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Lagacé, M, primary, Nicholas, A, additional, and Connolly, M, additional
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- 2021
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5. LO52: Distraction in the ED using Virtual reality for Intravenous Needs in Children to Improve comfort- DEVINCI - a pilot RCT
- Author
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Trottier, E. D., primary, Osmanlliu, E., additional, Bailey, B., additional, Lagacé, M., additional, Certain, M., additional, Khadra, C., additional, Sanchez, M., additional, Thériault, C., additional, Paquin, D., additional, Cotes-Turpin, C., additional, and Le May, S., additional
- Published
- 2020
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6. PCN26 COMPARATIVE EFFECTIVENESS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATIONS (ALLO-HSCT) FROM DIFFERENT GRAFT SOURCES IN ACUTE MYELOID LEUKEMIA (AML): RESULTS OF A SYSTEMATIC LITERATURE REVIEW
- Author
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Tomaras, D., primary, Dolph, M., additional, Caudrelier, P., additional, Dumont-Lagacé, M., additional, and Forsythe, A., additional
- Published
- 2019
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7. PCN290 ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATIONS (ALLO-HSCT) ARE ASSOCIATED WITH POOR QUALITY OF LIFE (QOL) AND ECONOMIC BURDEN DUE TO GRAFT-VERSUS-HOST DISEASE (GVHD) COMPLICATIONS: RESULTS OF A SYSTEMATIC LITERATURE REVIEW (SLR)
- Author
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Tomaras, D., primary, Dolph, M., additional, Caudrelier, P., additional, Dumont-Lagacé, M., additional, and Forsythe, A., additional
- Published
- 2019
- Full Text
- View/download PDF
8. PCN291 ACUTE GRAFT VERSUS HOST DISEASE (GVHD), CHRONIC GVHD AND NON-RELAPSE MORTALITY (NRM) ASSOCIATED WITH MISMATCHED ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT): A SYSTEMATIC REVIEW
- Author
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Tomaras, D., primary, Dolph, M., additional, Caudrelier, P., additional, Dumont-Lagacé, M., additional, and Forsythe, A., additional
- Published
- 2019
- Full Text
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9. Intranasal fentanyl and inhaled nitrous oxide for fracture reduction: The FAN observational study
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Hoeffe, J., primary, Doyon Trottier, E., additional, Bailey, B., additional, Shellshear, D., additional, Lagacé, M., additional, Sutter, C., additional, Grimard, G., additional, Cook, R., additional, and Babl, F.E., additional
- Published
- 2017
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10. Treating and Reducing Anxiety and Pain in the Paediatric Emergency Department (The Trapped 2 Survey): Time for Action – A Pediatric Emergency Research Canada (Perc) Project
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Trottier, ED, primary, Gravel, J, additional, Ali, S, additional, Meckler, G, additional, Blanchet, M, additional, Stang, A, additional, Porter, R, additional, Lemay, S, additional, Dubrovsky, A S, additional, Chan, M, additional, Jain, R, additional, Principi, T, additional, Joubert, G, additional, Kam, A, additional, Thull-Freedman, J, additional, Neto, G, additional, and Lagacé, M, additional
- Published
- 2016
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11. The Fan Study: Intranasal Fentanyl and Inhaled Nitrous Oxide for Fracture Reduction
- Author
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Hoeffe, J, primary, Trottier, ED, additional, Bailey, B, additional, Shellshear, D, additional, Lagacé, M, additional, Sutter, C, additional, Grimard, G, additional, Cook, R, additional, and Babl, FE, additional
- Published
- 2016
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12. MP005: Treating and Reducing Anxiety and Pain PEDs (TRAPPED 2): time for action - a PERC project
- Author
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Trottier, E. D., primary, Ali, S., additional, Meckler, G., additional, Blachet, M., additional, Stang, A.S., additional, Porter, R., additional, Le May, S., additional, Dubrovsky, A., additional, Chan, M., additional, Jain, R., additional, Principi, T., additional, Joubert, G., additional, Kam, A.J., additional, Thull-Freedman, J., additional, Neto, G., additional, Lagacé, M., additional, and Gravel, J., additional
- Published
- 2016
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13. P030: The FAN study: intranasal fentanyl and inhaled nitrous oxide for fracture reduction
- Author
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Hoeffe, J., primary, Trottier, E. D., additional, Bailey, B., additional, Shellshear, D., additional, Lagacé, M., additional, Sutter, C., additional, Grimard, G., additional, Cook, R., additional, and Babl, F., additional
- Published
- 2016
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14. Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.
- Author
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Cisbani, G, Drouin-Ouellet, Janelle, Gibrat, C, Saint-Pierre, M, Lagacé, M, Badrinarayanan, S, Lavallée-Bourget, M H, Charest, J, Chabrat, A, Boivin, L, Lebel, M, Bousquet, M, Lévesque, M, Cicchetti, F, Cisbani, G, Drouin-Ouellet, Janelle, Gibrat, C, Saint-Pierre, M, Lagacé, M, Badrinarayanan, S, Lavallée-Bourget, M H, Charest, J, Chabrat, A, Boivin, L, Lebel, M, Bousquet, M, Lévesque, M, and Cicchetti, F
- Abstract
The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.
- Published
- 2015
15. Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease
- Author
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Cisbani, G., primary, Drouin-Ouellet, J., additional, Gibrat, C., additional, Saint-Pierre, M., additional, Lagacé, M., additional, Badrinarayanan, S., additional, Lavallée-Bourget, M.H., additional, Charest, J., additional, Chabrat, A., additional, Boivin, L., additional, Lebel, M., additional, Bousquet, M., additional, Lévesque, M., additional, and Cicchetti, F., additional
- Published
- 2015
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16. 155: Impact of a Volunteer Program for Research in a Pediatric Emergency Department
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Lespérance, AJ, primary, Lagacé, M, additional, Cook, R, additional, and Gravel, J, additional
- Published
- 2015
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17. New Lithium Metal Polymer Solid State Battery for an Ultrahigh Energy: Nano C-LiFePO4 versus Nano Li1.2V3O8
- Author
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Hovington, P., primary, Lagacé, M., additional, Guerfi, A., additional, Bouchard, P., additional, Mauger, A., additional, Julien, C. M., additional, Armand, M., additional, and Zaghib, K., additional
- Published
- 2015
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18. Occupational Participation Among Older Adults During the COVID-19 Pandemic.
- Author
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Oostlander SA, Joanisse C, Mulvey MS, Fraser S, Lagacé M, Bélanger-Hardy L, Garcia L, Robitaille A, Gillis M, Courtemanche J, and O'Sullivan TL
- Abstract
Background . The COVID-19 pandemic led to abrupt occupational disruption for all people. However, some populations, like older adults, were disproportionately impacted particularly in the earlier waves. Purpose. The purpose of this study was to explore and understand how the occupational participation of community-dwelling older adults was experienced during the COVID-19 pandemic, using the Canadian Model of Occupational Participation (CanMOP) to contextualize findings. Method. Sixty-seven older adults participated in semi-structured interviews from September 2020 to May 2021, 37 of which also participated in a follow-up interview one-year later. Findings. Using reflexive thematic analysis, four themes were generated: (1) experiences of loss are complex and layered for older adults, (2) technology as a medium for occupational participation, (3) risk perception influences return to occupation, and (4) age-related challenges for older adults resuming volunteer work. Conclusion. Increasing frequency and severity of influenza pandemics and other disasters are a global concern, and OTs can use their skillsets to foster participation and expand occupational possibilities for older adults. The CanMOP was a helpful tool to understand the nuances underlying the participation of older adults in this context.
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- 2024
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19. [Words and views on old age, or how ageism undermines the care relationship].
- Author
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Lagacé M
- Subjects
- Humans, Aged, Nurse-Patient Relations, Aging psychology, Ageism psychology
- Abstract
Anxiety about ageing, as well as old age, is rooted in public discourse and has a negative impact on the quality of the relationship with the elderly, particularly in the context of care relationships with more vulnerable seniors. This text proposes a theoretical and empirical reflection on ageism, manifested as much in its hostile as in its compassionate forms., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
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20. Corrigendum to' UM171 expansion of cord blood improves donor availability and HLA matching for all patients, including minorities' [Transplantation and Cellular Therapy 28/7 (2022) 410-410.
- Author
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Dumont-Lagacé M, Feghaly A, Meunier MC, Finney M, Van't Hof W, Frenet EM, Sauvageau G, and Cohen S
- Published
- 2024
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21. Neonatal dysglycemia: a review of dysglycemia in relation to brain health and neurodevelopmental outcomes.
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Lagacé M and Tam EWY
- Abstract
Neonatal dysglycemia has been a longstanding interest of research in neonatology. Adverse outcomes from hypoglycemia were recognized early but are still being characterized. Premature infants additionally introduced and led the reflection on the importance of neonatal hyperglycemia. Cohorts of infants following neonatal encephalopathy provided further information about the impacts of hypoglycemia and, more recently, highlighted hyperglycemia as a central concern for this population. Innovative studies exposed the challenges of management of neonatal glycemic levels with a "u-shape" relationship between dysglycemia and adverse neurological outcomes. Lately, glycemic lability has been recognized as a key factor in adverse neurodevelopmental outcomes. Research and new technologies, such as MRI and continuous glucose monitoring, offered novel insight into neonatal dysglycemia. Combining clinical, physiological, and epidemiological data allowed the foundation of safe operational definitions, including initiation of treatment, to delineate neonatal hypoglycemia as ≤47 mg/dL, and >150-180 mg/dL for neonatal hyperglycemia. However, questions remain about the appropriate management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to continue to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes. IMPACT STATEMENT: Safe operational definitions guide the initiation of treatment of neonatal hypoglycemia and hyperglycemia. Innovative studies exposed the challenges of neonatal glycemia management with a "u-shaped" relationship between dysglycemia and adverse neurological outcomes. The importance of glycemic lability is also being recognized. However, questions remain about the optimal management of neonatal dysglycemia to optimize neurodevelopmental outcomes. Research collaborations and clinical trials with long-term follow-up and advanced use of evolving technologies will be necessary to progress the fascinating world of neonatal dysglycemia and neurodevelopment outcomes., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)
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- 2024
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22. Phototherapy causing a purpuric eruption in a neonate.
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Pelchat F, Lagacé M, and Vallée S
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- Humans, Infant, Newborn, Male, Female, Porphyrins, Phototherapy adverse effects, Purpura etiology, Purpura diagnosis, Jaundice, Neonatal therapy, Jaundice, Neonatal etiology, Jaundice, Neonatal diagnosis
- Abstract
Neonatal jaundice is a frequent condition in newborns and is commonly treated with phototherapy. We describe the case of a neonate with hemolytic disease of the newborn who developed a rarely described purpuric eruption. Laboratory testing revealed elevated porphyrins., (© 2024 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)
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- 2024
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23. Which interventions with youths counter ageism toward older adults? Results from a realist review.
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Bétrisey C, Carrier A, Cardinal JF, Lagacé M, Cohen AA, Beaulieu M, Baillargeon D, and Levasseur M
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- Humans, Adolescent, Intergenerational Relations, Child, Aged, Aging psychology, Ageism psychology, Stereotyping
- Abstract
Age-related social biases - ageism - are developed at an early age. Interventions to counter ageism have been identified but little is known about their mechanisms, particularly in children. This study aimed to provide a comprehensive understanding of which interventions in youths are most effective, under which circumstances, how, and with what outcomes. Using 46 keywords in 6 databases, a realist review identified 24 studies published between 2000 and 2022 targeting youths under 18. A content analysis of these studies led to the construction of a Context-Mechanisms-Outcomes explanatory model. Contextual facilitators triggering mechanisms for changing stereotypes, prejudices and discrimination were: 1) enhancing knowledge about aging and older adults by providing nuanced information, 2) improving the quality of intergenerational contacts, 3) increasing opportunities to apply previously acquired knowledge in intergenerational interactions, and 4) promoting reflective thinking about experiences with older adults. However, stereotypes and prejudices appeared to be resistant and changes difficult to generalize. Insufficiently advanced cognitive development in children or viewing healthy and socially engaged older adults as unrepresentative of their age group were obstacles that reduced intervention effectiveness. Future studies should explore how advancing age influences interventions as well as the characteristics of older adults involved.
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- 2024
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24. Not a Benign Vitamin: Infant with Vitamin A Toxicity and Acute Intracranial Hypertension.
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Lagacé M, Oskoui M, and Myers K
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- Infant, Humans, Vitamin A adverse effects, Vitamins adverse effects, Intracranial Hypertension chemically induced, Pseudotumor Cerebri
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- 2024
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25. Reactive Granulomatous Dermatitis: A Descriptive Study of 10 Patients.
- Author
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Lagacé M, Mainville L, and Dionne MC
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- Humans, Affect, Tumor Necrosis Factor Inhibitors, Oligopeptides, Dermatitis diagnosis, Autoimmune Diseases, Neoplasms
- Abstract
Background: Reactive granulomatous dermatitis (RGD) is a rare and misunderstood skin disorder. It includes interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: 2 entities of the same spectrum. Multiple associations are described with RGD in the literature, including autoimmune diseases, malignancy, and drugs., Objective: To report and describe the suspected associations with RGD at the time of diagnosis and in the following year., Methods: We retrieved and described cases of RGD confirmed by skin biopsy and clinicopathologic correlation. All patients were evaluated in the Centre Hospitalier Universitaire de Québec - Université Laval between January 2000 and December 2020. Collected data include the systemic diseases (autoimmune disease, malignancy) and suspected drugs, in addition to the clinical presentation and prescribed treatments., Results: Out of the 10 patients with RGD, 7 patients were known to have an autoimmune disease at the time of diagnosis. They either had inflammatory arthritis (3/10) or inflammatory bowel disease (4/10). There was a clinical suspicion of a possible association with a tumor necrosis factor (TNF) inhibitor in 2 of these 7 patients. Among the 3 patients with idiopathic RGD at the time of diagnosis, 1 patient developed a high-grade B-cell lymphoma 6 months later. There was no new association identified in the following year for patients with a known autoimmune condition., Conclusion: This descriptive study supports RGD and its previously described systemic associations, particularly autoimmune diseases, malignancy, and certain drugs (specifically TNF inhibitors). The majority of patients already had one of these associations identified at the time of histopathological diagnosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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26. Misclassified: identification of zoonotic transition biomarker candidates for influenza A viruses using deep neural network.
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Hatibi N, Dumont-Lagacé M, Alouani Z, El Fatimy R, Abik M, and Daouda T
- Abstract
Introduction: Zoonotic transition of Influenza A viruses is the cause of epidemics with high rates of morbidity and mortality. Predicting which viral strains are likely to transition from their genetic sequence could help in the prevention and response against these zoonotic strains. We hypothesized that features predictive of viral hosts could be leveraged to identify biomarkers of zoonotic viral transition. Methods: We trained deep learning models to predict viral hosts based on the virus mRNA or protein sequences. Our multi-host dataset contained 848,630 unique nucleotide sequences obtained from the NCBI Influenza Virus and Influenza Research Databases. Each sequence, representing one gene from one viral strain, was classified into one of the three host categories: Avian, Human, and Swine. Trained models were analyzed using various neural network interpretation methods to identify interesting candidates for zoonotic transition biomarkers. Results: Using mRNA sequences as input led to higher prediction accuracies than amino acids, suggesting that the codon sequence contains information relevant to viral hosts that is lost during protein translation. UMAP visualization of the latent space of our classifiers showed that viral sequences clustered according to their host of origin. Interestingly, sequences from pandemic zoonotic viral strains localized at the margins between hosts, while zoonotic sequences incapable of Human-to-Human transmission localized with non-zoonotic viruses from the same host. In addition, host prediction for pandemic zoonotic sequences had low prediction accuracy, which was not the case for the other zoonotic strains. This supports our hypothesis that ambiguously predicted viral sequences bear features associated with cross-species infectivity. Finally, we compared misclassified sequences to well-classified ones to extract interesting candidates for zoonotic transition biomarkers. While features varied significantly between pairs of species and viral genes, several codons were conserved in Swine-to-Human and Avian-to-Human misclassified sequences, and in particular in the NA, HA, and NP genes, suggesting their importance for zoonosis in Humans. Discussion: Analysis of viral sequences using neural network interpretation approaches revealed important genetic differences between zoonotic viruses with pandemic potential, compared to non-zoonotic viral strains or zoonotic viruses incapable of Human-to-Human transmission., Competing Interests: Author MD-L was employed by Piercing Star Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hatibi, Dumont-Lagacé, Alouani, El Fatimy, Abik and Daouda.)
- Published
- 2023
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27. Fostering Positive Views About Older Workers and Reducing Age Discrimination: A Retest of the Workplace Intergenerational Contact and Knowledge Sharing Model.
- Author
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Lagacé M, Van De Beeck L, Bergeron CD, and Rodrigues-Rouleau P
- Subjects
- Humans, Aged, Canada, Workplace psychology, Employment, Intention, Ageism psychology
- Abstract
Ageism toward older workers is prevalent in the labor market. The present study aimed to understand psychosocial mechanisms that may counteract this form of discrimination and help retain workers in the labor force. Using a sample of 500 Canadian younger and older workers, this study tested a model hypothesizing that intergenerational contacts and knowledge sharing practices can reduce ageist views about older adults and age-based discrimination against one's own group, and in turn, enhance work engagement and intentions to remain in the workplace. The final model shows that knowledge sharing practices mediate the relationship between intergroup contacts and positive views about older workers as well as age-based discrimination. It also suggests that low levels of age-based discrimination increase work engagement and intentions to remain in the organization for workers of all ages. Practice and policy implications are discussed.
- Published
- 2023
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28. Klf4 protects thymus integrity during late pregnancy.
- Author
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Depoërs L, Dumont-Lagacé M, Trinh VQ, Houques C, Côté C, Larouche JD, Brochu S, and Perreault C
- Subjects
- Female, Mice, Pregnancy, Animals, Epithelial Cells metabolism, Signal Transduction, Atrophy metabolism, Thymus Gland metabolism, Thymocytes metabolism
- Abstract
Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4
lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4-/- TECs revealed that Klf4 maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that Klf4 is essential for preserving TEC's integrity and mitigating thymic involution during late pregnancy., Competing Interests: Author MD-L was employed by the companies ExCell Thera, Inc. and Piercing Star Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Depoërs, Dumont-Lagacé, Trinh, Houques, Côté, Larouche, Brochu and Perreault.)- Published
- 2023
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29. An Examination of Mentors' Interpersonal Behaviors and Mentees' Motivation, Turnover Intentions, Engagement, and Well-Being.
- Author
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Firzly N, Chamandy M, Pelletier L, and Lagacé M
- Abstract
Using self-determination theory among a sample of student employees, the present cross-sectional study ( N = 358) examines how mentors' interpersonal behaviors relate to both motivation at work and motivation for a mentoring relationship and how these two contexts of motivation can differentially relate to mentees' work outcomes. Results revealed that mentors' need-supportive interpersonal behaviors were associated with greater autonomous motivation at work and in the mentoring relationship and, in turn, to greater well-being and work engagement, and to lower turnover intentions. In contrast, need-thwarting interpersonal behaviors were associated with greater controlled motivation at work and in the mentoring relationship and, in turn, to lower well-being and work engagement, and to greater turnover intentions. Overall, this study illustrates the impact of the mentor-mentee relationship on motivation for work and for the mentoring relationship and provided support for the contribution of both motivational contexts in the work-related outcomes of employees in the workplace., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)
- Published
- 2022
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30. The responsibility to care: lessons learned from emergency department workers' perspectives during the first wave of the COVID-19 pandemic in Canada.
- Author
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Lavoie B, Bourque CJ, Côté AJ, Rajagopal M, Clerc P, Bourdeau V, Ali S, Doyon-Trottier E, Castonguay V, Fontaine-Pagé É, Burstein B, Desaulniers P, Goldman RD, Thompson G, Berthelot S, Lagacé M, and Gaucher N
- Subjects
- Adult, Canada epidemiology, Emergency Service, Hospital, Fatigue, Female, Humans, Male, Pandemics, Burnout, Professional, COVID-19 epidemiology
- Abstract
Background: This study's objective was to examine emergency department (ED) workers' perspectives during the Canadian COVID-19 first wave., Methods: This qualitative study included workers from nine Canadian EDs who participated in 3 monthly video focus groups between April and July 2020 to explore (1) personal/professional experiences, (2) patient care and ED work, (3) relationships with teams, institutions and governing bodies. Framework analysis informed data collection and analysis., Results: Thirty-six focus groups and 15 interviews were conducted with 53 participants (including 24 physicians, 16 nurses). Median age was 37.5 years, 51% were female, 79% had more than 5 years' experience. Three main themes emerged. (1) Early in this pandemic, participants felt a responsibility to provide care to patients and solidarity toward their ED colleagues and team, while balancing many risks with their personal protection. (2) ED teams wanted to be engaged in decision-making, based on the best available scientific knowledge. Institutional decisions and clinical guidelines needed to be adapted to the specificity of each ED environment. (3) Working during the pandemic created new sources of moral distress and fatigue, including difficult clinical practices, distance with patients and families, frequent changes in information and added sources of fatigue. Although participants quickly adapted to a "new normal", they were concerned about long-term burnout. Participants who experienced high numbers of patient deaths felt especially unprepared., Interpretation: ED workers believe they have a responsibility to provide care through a pandemic. Trust in leadership is supported by managers who are present and responsive, transparent in their communication, and involve ED staff in the development and practice of policies and procedures. Such practices will help protect from burnout and ensure the workforce's long-term sustainability., (© 2022. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)
- Published
- 2022
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31. UM171 Expansion of Cord Blood Improves Donor Availability and HLA Matching For All Patients, Including Minorities.
- Author
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Dumont-Lagacé M, Feghaly A, Meunier MC, Finney M, Van't Hof W, Masson Frenet E, Sauvageau G, and Cohen S
- Subjects
- Adult, Ethnicity, Humans, Minority Groups, Retrospective Studies, Cord Blood Stem Cell Transplantation, Fetal Blood
- Abstract
Cord blood (CB) stem cell transplantation offers a greater tolerance to HLA mismatches compared to adult-derived stem cell transplants (i.e., bone marrow or peripheral blood stem cells). Indeed, 4/6 or 5/8 HLA-matched CB transplantations are regularly performed for patients lacking a matched unrelated donor. Unfortunately, most banked CB units contain a stem cell dose that is too small to treat adult patients, resulting in only 4% to 5% of available CB units offering an adequate cell dose for prompt engraftment for adult patients. Ex vivo stem cell expansion appears to be an attractive strategy to circumvent this cell dose issue, while also enabling the selection of better HLA-matched CB units. In this study, we retrospectively performed HLA matching simulations to assess how the minimal cell content requirements associated with UM171 CB expansion may improve usability of existing CB unit inventories and donor availability for patients of different races and ethnicities. We analyzed a dataset of 58,971 adults for whom a donor search was initiated through the National Marrow Donor Program Be The Match registry against 142,942 CB units from major U.S. public CB banks listed on the Be The Match registry. Our results show that by enabling selection of smaller CB units, UM171-expanded CB transplantation increases donor availability from 72% to 84% for all patients compared to single unmanipulated CB transplantation. Furthermore, the low cell dose criteria for UM171-expanded CB also increases donor availability compared to double CB transplantation, while enabling better HLA matching between donor and recipient. UM171 expanded CB appears particularly beneficial for racial and ethnic minority patients as CB availability increases from 53% to 78% for African Americans, from 66% to 85% for Hispanics, and from 68% to 84% for Asians and Pacific Islanders, compared to single unmanipulated CB transplantation. In addition, UM171 expansion dramatically improves usability of CB units currently in inventories, as only 4.3% and 0.6% of banked CBs have sufficient cell doses for a 70 kg and 100 kg patient, respectively. UM171 raises this proportion to 53.8% and 20.2%, respectively, making CB banks potentially more cost effective. In conclusion, UM171 expansion allows the use of smaller CB units while also improving access to transplantation for racial and ethnic minorities., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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32. Testing the Shielding Effect of Intergenerational Contact against Ageism in the Workplace: A Canadian Study.
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Lagacé M, Donizzetti AR, Van de Beeck L, Bergeron CD, Rodrigues-Rouleau P, and St-Amour A
- Subjects
- Adolescent, Adult, Aged, Attitude, Canada, Humans, Middle Aged, Surveys and Questionnaires, Workplace, Young Adult, Ageism prevention & control
- Abstract
Negative outcomes of ageism in the context of the Canadian labor market are well documented. Older workers remain the target of age-based stereotypes and attitudes on the part of employers. This study aims at assessing (1) the extent to which quality and quantity intergroup contacts between younger and older workers as well as knowledge-sharing practices reduce ageist attitudes, in turn (2) how a decrease in ageist attitudes increase the level of workers' engagement and intentions to remain in the organization. Data were collected from 603 Canadian workers (aged 18 to 68 years old) from private and public organizations using an online survey measuring concepts under study. Results of a path analysis suggest that intergroup contacts and knowledge-sharing practices are associated with positive attitudes about older workers. More so, positive attitudes about older workers generate higher levels of work engagement, which in turn are associated with stronger intentions to remain with the organization. However, positive attitudes about older workers had no effect on intentions to remain in the workplace. Results are discussed in light of the intergroup contact theory.
- Published
- 2022
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33. COVID-19 and the Elderly's Mental Illness: The Role of Risk Perception, Social Isolation, Loneliness and Ageism.
- Author
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Donizzetti AR and Lagacé M
- Subjects
- Aged, Female, Humans, Loneliness, Male, Pandemics, SARS-CoV-2, Social Isolation, Social Perception, Ageism, COVID-19 epidemiology, Mental Disorders epidemiology
- Abstract
For almost two years, populations around the globe faced precariousness and uncertainty as a result of the COVID-19 pandemic. Older adults were highly affected by the virus, and the policies meant to protect them have often resulted in ageist stereotypes and discrimination. For example, the public discourse around older adults had a paternalistic tone framing all older adults as "vulnerable". This study aimed to measure the extent to which perceived age discrimination in the context of the COVID-19 pandemic, as well as the sense of loneliness and social isolation, fear and perception of COVID-19 risks, had a negative effect on older adults' mental illness. To do so, a self-report questionnaire was administered to 1301 participants (average age: 77.25 years old, SD = 5.46; 56.10% females, 43.90% males). Descriptive and correlational analyses were performed, along with structural equation modelling. Results showed that perceived age discrimination in the context of the COVID-19 pandemic positively predicts loneliness and also indirectly predicts mental illness. In addition, loneliness is the strongest predictor of mental illness together with fear of COVID-19 and social isolation. Such results highlight the importance of implementing public policies and discourses that are non-discriminating, and that favour the inclusion of older people.
- Published
- 2022
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34. Impact of the 2016 Canadian Lipid Guidelines on Daily Practice at a Community Hospital.
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Cartier LJ, Robin A, St-Cœur S, Lagacé M, Canales DD, and Douville P
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- Adult, Apolipoproteins B, Canada epidemiology, Hospitals, Community, Humans, Practice Guidelines as Topic, Dyslipidemias diagnosis, Dyslipidemias drug therapy, Dyslipidemias epidemiology, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
Objectives: The aim of this study was to determine the impact of the 2016 Canadian cardiovascular society guidelines for the management of dyslipidemia. More specifically, we assessed the use of 1) alternate lipid targets when triglyceride (TG) levels are high; and 2) nonfasting lipid testing., Methods: Lipid profiles and pharmacy data were obtained from patients with a history of myocardial infarction and from patients ≥40 years of age with a diagnosis of diabetes., Results: As TG increased to >1.5 mmol/L, percent within target for non-high-density lipoprotein cholesterol and apolipoprotein B 18 months after guideline release remained low in both patients with atherosclerotic cardiovascular disease (40%) and patients with diabetes in primary prevention (30%). Approximately 50% of patients were fasting when presenting for lipid testing. Use of high-intensity statin was suboptimal in both groups., Conclusions: The concept of alternate lipid targets may not be well understood by many physicians, leading to undertreatment of patients. Progress was made in the promotion of routine nonfasting lipid testing., (Copyright © 2021 Canadian Diabetes Association. All rights reserved.)
- Published
- 2022
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35. CAMAP: Artificial neural networks unveil the role of codon arrangement in modulating MHC-I peptides presentation.
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Daouda T, Dumont-Lagacé M, Feghaly A, Benslimane Y, Panes R, Courcelles M, Benhammadi M, Harrington L, Thibault P, Major F, Bengio Y, Gagnon É, Lemieux S, and Perreault C
- Subjects
- Algorithms, Amino Acid Sequence, Humans, Codon chemistry, Codon genetics, Codon metabolism, Computational Biology methods, Histocompatibility Antigens Class I chemistry, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I metabolism, Neural Networks, Computer
- Abstract
MHC-I associated peptides (MAPs) play a central role in the elimination of virus-infected and neoplastic cells by CD8 T cells. However, accurately predicting the MAP repertoire remains difficult, because only a fraction of the transcriptome generates MAPs. In this study, we investigated whether codon arrangement (usage and placement) regulates MAP biogenesis. We developed an artificial neural network called Codon Arrangement MAP Predictor (CAMAP), predicting MAP presentation solely from mRNA sequences flanking the MAP-coding codons (MCCs), while excluding the MCC per se. CAMAP predictions were significantly more accurate when using original codon sequences than shuffled codon sequences which reflect amino acid usage. Furthermore, predictions were independent of mRNA expression and MAP binding affinity to MHC-I molecules and applied to several cell types and species. Combining MAP ligand scores, transcript expression level and CAMAP scores was particularly useful to increase MAP prediction accuracy. Using an in vitro assay, we showed that varying the synonymous codons in the regions flanking the MCCs (without changing the amino acid sequence) resulted in significant modulation of MAP presentation at the cell surface. Taken together, our results demonstrate the role of codon arrangement in the regulation of MAP presentation and support integration of both translational and post-translational events in predictive algorithms to ameliorate modeling of the immunopeptidome., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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36. The "Vulnerability" Discourse in Times of Covid-19: Between Abandonment and Protection of Canadian Francophone Older Adults.
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Lagacé M, Doucet A, Dangoisse P, and Bergeron CD
- Subjects
- Aged, Canada, Humans, Pandemics, SARS-CoV-2, Ageism, COVID-19
- Abstract
The Covid-19 pandemic has been particularly difficult for older Canadians who have experienced age discrimination. As the media can provide a powerful channel for conveying stereotypes, the current study aimed to explore how Canadian Francophone older adults and the aging process were depicted by the media during the first wave of the Covid-19 pandemic, and to examine if and how the media discourse contributed to ageist attitudes and behaviors. A content analysis of two French Canadian media op-eds and comment pieces ( n = 85) published over the course of the first wave of the pandemic was conducted. Findings reveal that the aging process was mainly associated with words of decline, loss, and vulnerability. More so, older people were quasi-absent if not silent in the media discourse. Older adults were positioned as people to fight for and not as people to fight along with in the face of the pandemic. The findings from this study enhance the understanding of theories and concepts of the Theory of Social Representations and the Stereotype Content Model while outlining the importance of providing older people with a voice and a place in the shaping of public discourse around aging. Results also illustrate the transversality and influence of ageism in this linguistic minority context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lagacé, Doucet, Dangoisse and Bergeron.)
- Published
- 2021
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37. Let's Work Together: Assessing the Impact of Intergenerational Dynamics on Young Workers' Ageism Awareness and Job Satisfaction.
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Firzly N, Van de Beeck L, and Lagacé M
- Subjects
- Canada, Cross-Sectional Studies, Humans, Job Satisfaction, Workplace, Ageism
- Abstract
Previous studies suggest that intergroup contact has a positive effect on older workers' perception of ageism and satisfaction. This study aims at assessing such relationships amongst Canadian younger workers. Precisely, in light of the intergroup contact theory (ICT), it was first hypothesized that a positive perception of intergenerational workplace climate (IWC) and knowledge sharing practices (KSP) increase younger workers' awareness of ageist behaviors targeting older peers. Second, it was hypothesized that such awareness has a positive effect on young workers' level of satisfaction. Relying on a cross-sectional design composed of 612 participants, path analysis was conducted. Findings suggest that whereas KSP increases younger workers' awareness of ageist behaviors towards older workers, this is not the case for IWC. On the other hand, both IWC and KSP have a direct and positive impact on younger workers' level of satisfaction. Theoretical and practical implications of findings are discussed.
- Published
- 2021
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38. About me but without me? Older adult's perspectives on interpersonal communication during care transitions from hospital to seniors' residence.
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Lagacé M, Fraser S, Ranger MC, Moorjani-Houle D, and Ali N
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- Aged, 80 and over, Canada, Health Personnel, Hospitals, Humans, Communication, Patient Transfer
- Abstract
Background: Transitions in care can be stressful for an older adult. While communication protocols between health care professionals during transitions have been thoroughly studied, there is a need to better understand how older adults transitioning perceive interpersonal communication. Relying on Communication Accommodation Theory, the goal of this study is to explore Canadian older adults' perspectives of interpersonal communication during care transition from acute care in a hospital to a residence and assess if and how communication could improve health and well-being. Using a longitudinal exploratory design, 13 older adults (M
Age = 84 years) transitioning from acute hospital care to a residence were interviewed at three time points: (1) in the hospital, (2) upon arriving at the residence and (3) in the residence, 2-3 months later. A total of 30 interviews were analyzed using thematic content analysis. Five main themes emerged from participants' descriptions of their transition and communication with health care professionals: (1) Interpersonal Communication or Information, (2) Gratefulness & Burden, (3) Acceptance & Resilience, (4) Maintaining Autonomy and (5), Level of satisfaction. Most participants described being informed rather than being an active participant during the transition process. Most also accepted the transition and tried to reduce the burden on family notably by finding ways to maintain autonomy. A major finding of this study is the lack of interpersonal communication taking place during the transition process, which increased older adults' feeling of uncertainty about the future. Many were unclear on why this move was taking place and where they were going. Providing a space for older adults to communicate their perspectives could attenuate the negative outcomes stemming from stressful care transitions., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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39. COVID-19 and Quarantine, a Catalyst for Ageism.
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Barth N, Guyot J, Fraser SA, Lagacé M, Adam S, Gouttefarde P, Goethals L, Bechard L, Bongue B, Fundenberger H, and Célarier T
- Subjects
- Aged, Aging, France epidemiology, Humans, Pandemics, Quarantine, SARS-CoV-2, Ageism, COVID-19
- Abstract
In February 2021, France had more than 76,000 deaths due to COVID-19 and older adults were heavily affected. Most measures taken to reduce the impact of COVID-19 (quarantine, visit ban in nursing home, etc.) significantly influenced the lives of older adults. Yet they were rarely consulted about their implementation. Exclusion of and discrimination against older adults has been accentuated during the COVID-19 pandemic. While many articles discussing COVID-19 also mention ageism, few actually incorporate the perspectives and opinions of older adults. Our research aims to assess the ageism experienced by older adults during the COVID-19 pandemic. We conducted interviews with older adults (63-92 years, mean age = 76 years) in an urban area of France. Participants reported experiencing more ageism during the COVID-19 pandemic, including hostile and benevolent ageism from older adults' families. Despite reports of experiencing ageist attitudes and behaviors from others, however, older adults also identified positive signs of intergenerational solidarity during this COVID-19 crisis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barth, Guyot, Fraser, Lagacé, Adam, Gouttefarde, Goethals, Bechard, Bongue, Fundenberger and Célarier.)
- Published
- 2021
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40. Imaging appearance of ticks in tick paralysis.
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Halverson MR, Lagacé M, Smyth AE, Abu Sharar Z, and Sargent MA
- Subjects
- Animals, Humans, Tick Paralysis diagnostic imaging, Ticks
- Published
- 2021
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41. Child Neurology: Pheochromocytoma Unveiled by Reversible Cerebral Vasoconstriction Syndrome in a Child With Neurofibromatosis Type 1.
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Lagacé M, Graeber B, and Huh L
- Subjects
- Adolescent, Adrenal Gland Neoplasms complications, Follow-Up Studies, Humans, Male, Neurofibromatosis 1 complications, Pheochromocytoma complications, Syndrome, Vasoconstriction physiology, Vasospasm, Intracranial complications, Adrenal Gland Neoplasms diagnostic imaging, Neurofibromatosis 1 diagnostic imaging, Pheochromocytoma diagnostic imaging, Vasospasm, Intracranial diagnostic imaging
- Published
- 2021
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42. UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections.
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Dumont-Lagacé M, Li Q, Tanguay M, Chagraoui J, Kientega T, Cardin GB, Brasey A, Trofimov A, Carli C, Ahmad I, Bambace NM, Bernard L, Kiss TL, Roy J, Roy DC, Lemieux S, Perreault C, Rodier F, Dufresne SF, Busque L, Lachance S, Sauvageau G, Cohen S, and Delisle JS
- Subjects
- Fetal Blood, Humans, Retrospective Studies, T-Lymphocytes, Cord Blood Stem Cell Transplantation adverse effects, Graft vs Host Disease
- Abstract
Rapid T cell reconstitution following hematopoietic stem cell transplantation (HSCT) is essential for protection against infections and has been associated with lower incidence of chronic graft-versus-host disease (cGVHD), relapse, and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections, and TRM. Recently, results of a phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment (www.clinicaltrials.gov, NCT02668315). We assessed T cell reconstitution in patients who underwent transplantation with UM171-expanded CB grafts and retrospectively compared it to that of patients receiving unmanipulated CB transplants. While median T cell dose infused was at least 2 to 3 times lower than that of unmanipulated CB, numbers and phenotype of T cells at 3, 6, and 12 months post-transplant were similar between the 2 cohorts. T cell receptor sequencing analyses revealed that UM171 patients had greater T cell diversity and higher numbers of clonotypes at 12 months post-transplant. This was associated with higher counts of naive T cells and recent thymic emigrants, suggesting active thymopoiesis and correlating with the demonstration that UM171 expands common lymphoid progenitors in vitro. UM171 patients also showed rapid virus-specific T cell reactivity and significantly reduced incidence of severe infections. These results suggest that UM171 patients benefit from rapid T cell reconstitution, which likely contributes to the absence of moderate/severe cGVHD, infection-related mortality, and late TRM observed in this cohort., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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43. Distraction in the Emergency department using Virtual reality for INtravenous procedures in Children to Improve comfort (DEVINCI): a pilot pragmatic randomized controlled trial.
- Author
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Osmanlliu E, Trottier ED, Bailey B, Lagacé M, Certain M, Khadra C, Sanchez M, Thériault C, Paquin D, Côtes-Turpin C, and Le May S
- Subjects
- Child, Emergency Service, Hospital, Humans, Pain Management, Phlebotomy, Pain, Procedural prevention & control, Virtual Reality
- Abstract
Objectives: Intravenous (IV) procedures cause pain and distress in the pediatric emergency department (ED). We studied the feasibility and acceptability of virtual reality distraction for patient comfort during intravenous procedures., Methods: Children were randomized to a control (standard care) or intervention group (standard care + virtual reality). Thresholds for feasibility and acceptability (primary outcomes) were determined through a priori established criteria. The level of procedural pain (principal clinical outcome) and distress, as well as memory of pain at 24 h were collected and reported as medians (Q1, Q3) for each group., Results: 63 patients were enrolled, with a high rate of recruitment (78.8%) and game completion (90.3%). Patients, parents and, healthcare providers reported high satisfaction levels. There were no serious adverse events. Five of the 30 patients (16.7%) exposed to virtual reality reported mild side effects. Self-reported procedural pain (verbal numerical rating scale: 3 (1, 6)/10 vs 3 (1, 5.5)/10, p = 0.75) was similar between groups. Further exploratory clinical measures were reported for the intervention and control groups, respectively: self-rated distress during the procedure (Child Fear Scale: 1 (0, 2)/4 vs 2 (0, 3)/4); distress evaluated by proxy during the procedure (Procedure Behavior Check List: 8 (8, 9)/40 vs 10 (8, 15)/40); memory of pain at 24 h (VNRS: 2 (1, 3)/10 vs 4 (2, 6.5)/10)., Conclusion: The addition of virtual reality to standard care is feasible and acceptable for pain and distress management during IV procedures in the pediatric ED. Occasional mild, self-resolving side effects were observed in the intervention group. Self-reported pain during the procedure was similar between groups. CLINICALTRIALS., Gov Identifier: NCT03750578.
- Published
- 2021
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44. IFN-λ Enhances Constitutive Expression of MHC Class I Molecules on Thymic Epithelial Cells.
- Author
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Benhammadi M, Mathé J, Dumont-Lagacé M, Kobayashi KS, Gaboury L, Brochu S, and Perreault C
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, Female, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Thymocytes immunology, Interferon Lambda, Epithelial Cells immunology, Histocompatibility Antigens Class I immunology, Interferons immunology, Receptors, Interferon immunology, Thymus Gland immunology
- Abstract
Regulation of MHC class I (MHC I) expression has been studied almost exclusively in hematolymphoid cells. We report that thymic epithelial cells (TECs), particularly the medullary TECs, constitutively express up to 100-fold more cell surface MHC I proteins than epithelial cells (ECs) from the skin, colon, and lung. Differential abundance of cell surface MHC I in primary ECs is regulated via transcription of MHC I and of genes implicated in the generation of MHC I-binding peptides. Superior MHC I expression in TECs is unaffected by deletion of Ifnar1 or Ifngr1 , but is lessened by deletion of Aire , Ifnlr1 , Stat1 , or Nlrc5 , and is driven mainly by type III IFN produced by medullary TECs. Ifnlr1
-/- mice show impaired negative selection of CD8 thymocytes and, at 9 mo of age, present autoimmune manifestations. Our study shows unanticipated variation in MHC I expression by ECs from various sites and provides compelling evidence that superior expression of MHC I in TECs is crucial for proper thymocyte education., (Copyright © 2020 by The American Association of Immunologists, Inc.)- Published
- 2020
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45. Ageism and COVID-19: what does our society's response say about us?
- Author
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Fraser S, Lagacé M, Bongué B, Ndeye N, Guyot J, Bechard L, Garcia L, Taler V, Adam S, Beaulieu M, Bergeron CD, Boudjemadi V, Desmette D, Donizzetti AR, Éthier S, Garon S, Gillis M, Levasseur M, Lortie-Lussier M, Marier P, Robitaille A, Sawchuk K, Lafontaine C, and Tougas F
- Subjects
- Aged, Betacoronavirus, COVID-19, Humans, Needs Assessment, Public Opinion, SARS-CoV-2, Social Perception, Ageism prevention & control, Ageism psychology, Ageism trends, Aging ethics, Aging psychology, Coronavirus Infections epidemiology, Coronavirus Infections psychology, Intergenerational Relations, Pandemics, Pneumonia, Viral epidemiology, Pneumonia, Viral psychology, Residential Facilities standards
- Abstract
The goal of this commentary is to highlight the ageism that has emerged during the COVID-19 pandemic. Over 20 international researchers in the field of ageing have contributed to this document. This commentary discusses how older people are misrepresented and undervalued in the current public discourse surrounding the pandemic. It points to issues in documenting the deaths of older adults, the lack of preparation for such a crisis in long-term care homes, how some 'protective' policies can be considered patronising and how the initial perception of the public was that the virus was really an older adult problem. This commentary also calls attention to important intergenerational solidarity that has occurred during this crisis to ensure support and social-inclusion of older adults, even at a distance. Our hope is that with this commentary we can contribute to the discourse on older adults during this pandemic and diminish the ageist attitudes that have circulated., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
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46. Signal profiling of the β 1 AR reveals coupling to novel signalling pathways and distinct phenotypic responses mediated by β 1 AR and β 2 AR.
- Author
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Lukasheva V, Devost D, Le Gouill C, Namkung Y, Martin RD, Longpré JM, Amraei M, Shinjo Y, Hogue M, Lagacé M, Breton B, Aoki J, Tanny JC, Laporte SA, Pineyro G, Inoue A, Bouvier M, and Hébert TE
- Subjects
- Biosensing Techniques methods, CRISPR-Cas Systems, Calcium metabolism, Gene Editing, HEK293 Cells, Humans, Ligands, Phenotype, Receptors, Adrenergic, beta-1 genetics, Receptors, Adrenergic, beta-2 genetics, Signal Transduction, GTP-Binding Protein alpha Subunits, G12-G13 metabolism, GTP-Binding Protein alpha Subunits, Gs metabolism, Receptors, Adrenergic, beta-1 metabolism, Receptors, Adrenergic, beta-2 metabolism
- Abstract
A comprehensive understanding of signalling downstream of GPCRs requires a broad approach to capture novel signalling modalities in addition to established pathways. Here, using an array of sixteen validated BRET-based biosensors, we analyzed the ability of seven different β-adrenergic ligands to engage five distinct signalling pathways downstream of the β
1 -adrenergic receptor (β1 AR). In addition to generating signalling signatures and capturing functional selectivity for the different ligands toward these pathways, we also revealed coupling to signalling pathways that have not previously been ascribed to the βAR. These include coupling to Gz and G12 pathways. The signalling cascade linking the β1 AR to calcium mobilization was also characterized using a combination of BRET-based biosensors and CRISPR-engineered HEK 293 cells lacking the Gαs subunit or with pharmacological or genetically engineered pathway inhibitors. We show that both Gs and G12 are required for the full calcium response. Our work highlights the power of combining signal profiling with genome editing approaches to capture the full complement of GPCR signalling activities in a given cell type and to probe their underlying mechanisms.- Published
- 2020
- Full Text
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47. Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study.
- Author
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Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, Roy DC, Barabé F, Ahmad I, Bambace N, Bernard L, Kiss T, Bouchard P, Caudrelier P, Landais S, Larochelle F, Chagraoui J, Lehnertz B, Corneau S, Tomellini E, van Kampen JJA, Cornelissen JJ, Dumont-Lagacé M, Tanguay M, Li Q, Lemieux S, Zandstra PW, and Sauvageau G
- Subjects
- Adolescent, Adult, Cell Self Renewal drug effects, Cells, Cultured drug effects, Cells, Cultured transplantation, Cord Blood Stem Cell Transplantation adverse effects, Disease-Free Survival, Feasibility Studies, Febrile Neutropenia etiology, Female, Graft Survival, Graft vs Host Disease etiology, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cells cytology, Humans, Infant, Newborn, Male, Middle Aged, Proportional Hazards Models, Treatment Outcome, Young Adult, Cord Blood Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cells drug effects, Indoles pharmacology, Pyrimidines pharmacology
- Abstract
Background: Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to expand cord blood stem cells and enhance multilineage blood cell reconstitution in mice. We aimed to investigate the safety and feasibility of single UM171-expanded cord blood transplantation in patients with haematological malignancies who do not have a suitable HLA-matched donor., Methods: This single-arm, open-label, phase 1-2 safety and feasibility study was done at two hospitals in Canada. The study had two parts. In part 1, patients received two cord blood units (one expanded with UM171 and one unmanipulated cord blood) until UM171-expanded cord blood demonstrated engraftment. Once engraftment was documented we initiated part 2, reported here, in which patients received a single UM171-expanded cord blood unit with a dose de-escalation design to determine the minimal cord blood unit cell dose that achieved prompt engraftment. Eligible patients were aged 3-64 years, weighed 12 kg or more, had a haematological malignancy with an indication for allogeneic hematopoietic stem cell transplant and did not have a suitable HLA-matched donor, and a had a Karnofsky performance status score of 70% or more. Five clinical sites were planned to participate in the study; however, only two study sites opened, both of which only treated adult patients, thus no paediatric patients (aged <18 years) were recruited. Patients aged younger than 50 years without comorbidities received a myeloablative conditioning regimen (cyclophosphamide 120 mg/kg, fludarabine 75 mg/m
2 , and 12 Gy total body irradiation) and patients aged older than 50 years and those with comorbidities received a less myeloablative conditioning regimen (cyclophosphamide 50 mg/kg, thiotepa 10 mg/kg, fludarabine 150 mg/m2 , and 4 Gy total body irradiation). Patients were infused with the 7-day UM171-expanded CD34-positive cells and the lymphocyte-containing CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety of the transplant, kinetics of hematopoietic reconstitution (time to neutrophil and platelet engraftment) of UM171-expanded cord blood, and minimal pre-expansion cord blood unit cell dose that achieved prompt engraftment. We analysed feasibility in all enrolled patients and all other primary outcomes were analysed per protocol, in all patients who received single UM171-expanded cord blood transplantation. This trial has been completed and was registered with ClinicalTrials.gov, NCT02668315., Findings: Between Feb 17, 2016, and Nov 11, 2018, we enrolled 27 patients, four of whom received two cord blood units for safety purposes in part 1 of the study. 23 patients were subsequently enrolled in part 2 to receive a single UM171-expanded cord blood transplant and 22 patients received a single UM171-expanded cord blood transplantation. At data cutoff (Dec 31, 2018), median follow-up was 18 months (IQR 12-22). The minimal cord blood unit cell dose at thaw that achieved prompt engraftment as a single cord transplant after UM171 expansion was 0·52 × 105 CD34-positive cells. We successfully expanded 26 (96%) of 27 cord blood units with UM171. Among the 22 patients who received single UM171-expanded cord blood transplantation, median time to engraftment of 100 neutrophils per μL was 9·5 days (IQR 8-12), median time to engraftment of 500 neutrophils per μL was 18 days (12·5-20·0), and no graft failure occurred. Median time to platelet recovery was 42 days (IQR 35-47). The most common non-haematological adverse events were grade 3 febrile neutropenia (16 [73%] of 22 patients) and bacteraemia (nine [41%]). No unexpected adverse events were observed. One (5%) of 22 patients died due to treatment-related diffuse alveolar haemorrhage., Interpretation: Our preliminary findings suggest that UM171 cord blood stem cell expansion is feasible, safe, and allows for the use of small single cords without compromising engraftment. UM171-expanded cord blood might have the potential to overcome the disadvantages of other cord blood transplants while maintaining the benefits of low risk of chronic GVHD and relapse, and warrants further investigation in randomised trials., Funding: Canadian Institutes of Health Research, Canadian Cancer Society and Stem Cell Network., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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48. Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration.
- Author
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Dumont-Lagacé M, Daouda T, Depoërs L, Zumer J, Benslimane Y, Brochu S, Harrington L, Lemieux S, and Perreault C
- Subjects
- Animals, Epithelial Cells cytology, Female, Mice, Pregnancy, Thymocytes cytology, Epithelial Cells immunology, Postpartum Period immunology, Regeneration immunology, Thymocytes immunology, Thymus Gland physiology
- Abstract
During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1 , its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition., (Copyright © 2020 Dumont-Lagacé, Daouda, Depoërs, Zumer, Benslimane, Brochu, Harrington, Lemieux and Perreault.)
- Published
- 2020
- Full Text
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49. Febrile seizures and increased stress sensitivity in children: How it relates to seizure characteristics.
- Author
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Thébault-Dagher F, Lafontaine MP, Knoth IS, Deguire F, Sheppard E, Cook R, Lagacé M, Gravel J, Lupien S, and Lippé S
- Subjects
- Case-Control Studies, Child, Preschool, Comorbidity, Electroencephalography adverse effects, Female, Humans, Infant, Male, Hydrocortisone metabolism, Seizures, Febrile epidemiology, Stress, Psychological epidemiology, Stress, Psychological metabolism
- Abstract
Background: Studies suggest that the relationship between seizures and stress starts early in life. However, evidence of long-term altered stress reactivity following early-life seizures is lacking. Our objectives were to assess alterations in stress hormone reactivity in children with past febrile seizures (FS) and investigate how these alterations relate to clinical characteristics., Method: This case-control study compared a convenience sample of children with simple FS (n = 24), complex FS (n = 18), and matched healthy controls (n = 42). Stress was induced by electrode placement for an electroencephalography (EEG) exam. Salivary cortisol to stress, using three samples collected before and after the stressor, was compared between groups and sex. The relationship between stress reactivity and clinical characteristics (i.e., FS duration, age at first FS, time since the last FS) was investigated., Results: Cortisol reactivity to stress was significantly different depending on study groups, F(1, 78) = 6.415, p = 0.003, η
2 = 0.141, but not sex nor was there a significant interaction between group and sex (p ≥ 0.581). Participants with simple FS showed higher cortisol reactivity to stress (M = 14.936, Standard deviation (SD) = 26.852) compared with those with complex FS (M = -4.663, SD = 18.649, p = 0.015) and controls (M = -3.817, SD = 18.907, p = 0.003). There was no significant difference between participants with complex FS and controls (p > 0.999). Stress reactivity was not linked to clinical characteristics.p = 0.141, but not sex nor was there a significant interaction between group and sex (p ≥ 0.581). Participants with simple FS showed higher cortisol reactivity to stress (M = 14.936, Standard deviation (SD) = 26.852) compared with those with complex FS (M = -4.663, SD = 18.649, p = 0.015) and controls (M = -3.817, SD = 18.907, p = 0.003). There was no significant difference between participants with complex FS and controls (p > 0.999). Stress reactivity was not linked to clinical characteristics., Conclusions: Children with past simple FS showed greater changes in salivary cortisol following stress, suggesting enhanced stress sensitivity. As similar results were not found in a population with complex FS, our study shows that stress alterations are not caused by seizure severity. Future studies are needed to investigate whether stress sensitivity may be premorbid to simple FS and may contribute to simple FS incidence., (Copyright © 2019 Elsevier Inc. All rights reserved.)- Published
- 2019
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50. In Situ Scanning Electron Microscopy Detection of Carbide Nature of Dendrites in Li-Polymer Batteries.
- Author
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Golozar M, Hovington P, Paolella A, Bessette S, Lagacé M, Bouchard P, Demers H, Gauvin R, and Zaghib K
- Abstract
Li metal batteries suffer from dendrite formation which causes short circuit of the battery. Therefore, it is important to understand the chemical composition and growth mechanism of dendrites that limit battery efficiency and cycle life. In this study, in situ scanning electron microscopy was employed to monitor the cycling behavior of all-solid Li metal batteries with LiFePO
4 cathodes. Chemical analyses of the dendrites were conducted using a windowless energy dispersive spectroscopy detector, which showed that the dendrites are not metallic lithium as universally recognized. Our results revealed the carbide nature of the dendrites with a hollow morphology and hardness greater than that of pure lithium. These carbide-based dendrites were able to perforate through the polymer, which was confirmed by milling the polymer using focused ion beam. It was also shown that applying pressure on the battery can suppress growth of the dendrites.- Published
- 2018
- Full Text
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