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Abstract: LiFePO4 (LFP) particles were obtained by grinding ingot synthesized in the molten state. This process, followed by jet milling, and then wet milling, provides a simple way to obtain powders with controlled particle size in the range from macroscopic to 25nm. However, at this time, we find that these particles tend to agglomerate to form secondary particles of size ∼100nm. The particles obtained by this process are characterized by X-ray diffraction (XRD). In situ and ex situ scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The effect of milling was also investigated by analysis of physical properties using infrared spectroscopy (FTIR) and magnetic measurements. The electrochemical performance was evaluated in cells containing Li/1M LiPF6 in EC:DEC (1:1)/C-LiFePO4. After carbon coating, the LFP particles which are free of impurities, exhibit high-rate capability. Even with a limited amount of carbon (2wt.%) appropriate for commercial batteries, the capacity is 157mAhg−1 at 0.1C, 120mAhg−1 at 10C, without capacity fading after 60 cycles. [ABSTRACT FROM AUTHOR]

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.

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.)

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.)

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.)

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.

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.

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.)

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.

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.)

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.)

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).)

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.)

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.

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.

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.)

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.

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.)

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.

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.)

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.)

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.)

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.

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.)

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.)

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 (β 1 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 G z and G 12 pathways. The signalling cascade linking the β 1 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 G s and G 12 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.

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/m 2 , 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 × 10 5 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.)

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.)

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.)

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.

Ophiognomonia clavigignenti-juglandacearum endangers the survival of butternut (Juglans cinerea) throughout its native range. While screening for disease resistance, we found that artificial inoculations of 48 butternut seedlings with O. clavigignenti-juglandacearum induced the expression of external symptoms, but only after a period of dormancy. Before dormancy, compartmentalized tissues such as necrophylactic periderms (NPs) and xylem reaction zones (RZs) contributed to limiting pathogen invasion. Phenols were regularly detected in RZs, often in continuity with NPs during wound closure, and confocal microscopy revealed their presence in parenchyma cells, vessel plugs and cell walls. Vessels were blocked with tyloses and gels, particularly those present in RZs. Suberin was also detected in cells formed over the affected xylem by the callus at the inoculation point, in a few tylosis walls, and in longitudinal tubes that formed near NPs. Following dormancy, in all inoculated seedlings but one, defensive barriers were breached by O. clavigignenti-juglandacearum and then additional ones were produced in response to this new invasion. The results of this histopathological study indicate that trees inoculated in selection programs to test butternut canker resistance should go through at least one period of dormancy and that asymptomatic individuals should be dissected to better assess how they defend themselves against O. clavigignenti-juglandacearum.

Background/objectives: In 2013, the TRAPPED-1 survey reported inconsistent availability of pain and distress management strategies across all 15 Canadian paediatric emergency department (PEDs). The objective of the TRAPPED-2 study was to utilize a procedural pain quality improvement collaborative (QIC) and evaluate the number of newly introduced pain and distress-reducing strategies in Canadian PEDs over a 2-year period., Methods: A QIC was created to increase implementation of new strategies, through collaborative information sharing among PEDs. In 2015, 11 of the 15 Canadian PEDs participated in the TRAPPED QIC. At the end of the year, the TRAPPED-2 survey was electronically sent to a representative member at each of the 15 PEDs. The successful introduction of the chosen strategies by the QIC was assessed as well as the addition of new strategies per site. The number of new strategies introduced in the participating and nonparticipating QIC sites were described., Results: All 15 PEDs (100%) completed the TRAPPED-2 survey. Overall, 10/11 of QIC-participating sites implemented the strategy they had initially identified. All 15 Canadian PEDs implemented some new strategies during the study period; participants in the QIC reported a mean of 5.2 (1-11) new strategies compared to 2.5 (1-4) in the nonactively participating sites., Conclusion: While all PEDs introduced new strategies during the study, QIC-participating sites successfully introduced the majority of their previously identified new strategies in a short time period. Sharing deadlines and information between centres may have contributed to this success.

Objective: To compare the fasting and non-fasting lipid profile including ApoB in a cohort of patients from a community setting. Our purpose was to determine the proportion of results that could be explained by the known biological variation in the fasting state and to examine the additional impact of non-fasting on these same lipid parameters., Methods: 1093 adult outpatients with fasting lipid requests were recruited from February to September 2016 at the blood collection sites of the Moncton Hospital. Participants were asked to come back in the next 3-4days after having eaten a regular breakfast to have their blood drawn for a non-fasting lipid profile., Results: 91.6% of patients in this study had a change in total cholesterol that fell within the biological variation expected for this parameter. Similar results were seen for HDL-C (94.3%) non-HDL-C (88.8%) and ApoB (93.0%). A smaller number of patients fell within the biological variation expected for TG (78.8%) and LDL-C (74.6%). An average TG increase of 0.3mmol/L was observed in fed patients no matter the level of fasting TG. A gradual widening in the range of change in TG concentration was observed as fasting TG increased. Similar results were seen in diabetic patients., Conclusion: Outside of LDL-C and TG, little changes were seen in lipid parameters in the postprandial state. A large part of these changes could be explained by the biological variation. We observed a gradual widening in the range of increase in TG for patients with higher fasting TG. Non-HDL-C and ApoB should be the treatment target of choice for patients in the non-fasting state., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Thymic aging precedes that of other organs and is initiated by the gradual loss of thymic epithelial cells (TECs). Based on in vitro culture and transplantation assays, recent studies have reported on the presence of thymic epithelial progenitor cells (TEPCs) in young adult mice. However, the physiological role and properties of TEPC populations reported to date remain unclear. Using an in vivo label-retention assay, we previously identified a population of quiescent but non-senescent TECs. The goals of this study were therefore (i) to evaluate the contribution of these quiescent TECs to thymic regeneration following irradiation-induced acute thymic injury and (ii) to characterize their phenotypic and molecular profiles using flow cytometry, immunohistology, and transcriptome sequencing. We report that while UEA1 + cells cycle the most in steady state, they are greatly affected by irradiation, leading to cell loss and proliferative arrest following acute thymic involution. On the opposite, the UEA1 - subset of quiescent TECs is radioresistant and proliferate in situ following acute thymic involution, thereby contributing to thymic regeneration in 28- to 30-week-old mice. UEA1 - quiescent TECs display an undifferentiated phenotype (co-expression of K8 and K5 cytokeratins) and express high levels of genes that regulate stem cell activity in different tissues (e.g., Podxl and Ptprz1 ). In addition, two features suggest that UEA1 - quiescent TECs occupy discrete stromal niches: (i) their preferential location in clusters adjacent to the cortico-medullary junction and (ii) their high expression of genes involved in cross talk with mesenchymal cells. The ability of UEA1 - quiescent TECs to participate to TEC regeneration qualifies them as in vivo progenitor cells particularly relevant in the context of regeneration following acute thymic injury.

Objectives: To evaluate the effects of triglyceride (TG) and glycated hemoglobin (A1C) concentrations in the percentage of patients with diabetes who are within target (WT) for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (ApoB), as defined by the Canadian Lipid Guidelines, in a cohort of outpatients presenting at a 350-bed community hospital., Methods: Laboratory samples from 1919 patients, 18 years or older, who had A1C levels of 6.5% or above were used. Fasting lipid profiles were retrieved, and ApoB was measured., Results: We found no significant difference in the percentage of those WT for LDL-C as TG increased from normal to intermediate and high levels. For non-HDL-C, we saw a substantial decrease in the percentage of patients WT as TG levels increased from normal (61%) to intermediate (30.4%) and high levels (14.0%). ApoB showed a similar pattern to non-HDL-C: decreasing from normal (68.8%) to intermediate (40.7%) and high levels (21.0%). No significant difference was seen in the percentage of patients WT for the 3 lipid parameters studied with the increase in A1C levels., Conclusions: As TG increases, we saw discordance in the percentage of patients WT for LDL-C in relation to non-HDL-C and ApoB. Alternative targets to LDL-C should preferentially be used when the TG concentration is elevated., (Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.)

Purpose of the Study: Newspapers are an important source of information. The discourses within the media can influence public attitudes and support or discourage stereotypical portrayals of older individuals. This study critically examined discourses within a Canadian newspaper in terms of stereotypical depictions of age-related health conditions and assistive technology devices (ATDs)., Design and Methods: Four years (2009-2013) of Globe and Mail articles were searched for terms relevant to the research question. A total of 65 articles were retained, and a critical discourse analysis (CDA) of the texts was conducted. The articles were coded for stereotypes associated with age-related health conditions and ATDs, consequences of the stereotyping, and context (overall setting or background) of the discourse., Results: The primary code list included 4 contexts, 13 stereotypes, and 9 consequences of stereotyping. CDA revealed discourses relating to (a) maintaining autonomy in a stereotypical world, (b) ATDs as obstacles in employment, (c) barriers to help seeking for age-related conditions, and (d) people in power setting the stage for discrimination., Implications: Our findings indicate that discourses in the Canadian media include stereotypes associated with age-related health conditions. Further, depictions of health conditions and ATDs may exacerbate existing stereotypes about older individuals, limit the options available to them, lead to a reduction in help seeking, and lower ATD use. Education about the realities of age-related health changes and ATDs is needed in order to diminish stereotypes and encourage ATD uptake and use., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs. These effects were exquisitely TEC-subset specific. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.

Objective: Although the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood-brain barrier (BBB), which have been suggested to contribute to their pathophysiology. We investigated whether similar changes are also present in HD., Methods: We used 3- and 7-Tesla magnetic resonance imaging as well as postmortem tissue analyses to assess blood vessel impairments in HD patients. Our findings were further investigated in the R6/2 mouse model using in situ cerebral perfusion, histological analysis, Western blotting, as well as transmission and scanning electron microscopy., Results: We found mutant huntingtin protein (mHtt) aggregates to be present in all major components of the neurovascular unit of both R6/2 mice and HD patients. This was accompanied by an increase in blood vessel density, a reduction in blood vessel diameter, as well as BBB leakage in the striatum of R6/2 mice, which correlated with a reduced expression of tight junction-associated proteins and increased numbers of transcytotic vesicles, which occasionally contained mHtt aggregates. We confirmed the existence of similar vascular and BBB changes in HD patients., Interpretation: Taken together, our results provide evidence for alterations in the cerebral vasculature in HD leading to BBB leakage, both in the R6/2 mouse model and in HD patients, a phenomenon that may, in turn, have important pathophysiological implications., (© 2015 American Neurological Association.)

One-year-old white spruce (Picea glauca) seedlings were studied in microgravity conditions in the International Space Station (ISS) and compared with seedlings grown on Earth. Leaf growth was clearly stimulated in space whereas data suggest a similar trend for the shoots. Needles on the current shoots of ground-based seedlings were more inclined towards the stem base than those of seedlings grown in the ISS. Amyloplasts sedimented in specialized cells of shoots and roots in seedlings grown on Earth while they were distributed at random in similar cells of seedlings tested in the ISS. In shoots, such amyloplasts were found in starch sheath cells located between leaf traces and cortical cells whereas in roots they were constituents of columella cells of the cap. Nuclei were regularly observed just above the sedimented amyloplasts in both organs. It was also frequent to detect vacuoles with phenolic compounds and endoplasmic reticulum (ER) close to the sedimented amyloplasts. The ER was mainly observed just under these amyloplasts. Thus, when amyloplasts sediment, the pressure exerted on the ER, the organelle that can for instance secrete proteins destined for the plasma membrane, might influence their functioning and play a role in signaling pathways involved in gravity-sensing white spruce cells., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Background: Public representations of ageing can influence how individuals perceive their own experience of ageing. Results of studies on the OECD (Organisation for Economic Co-operation and Development)'s governmental messages on older workers suggest that they are mainly constructed around economic productivity and personal responsibility., Objective: The goal of this study is to examine how the Canadian government frames issues around ageing, work and older workers. Canada is facing a rapidly ageing workforce, hence the importance of examining how the government discusses ageing at work., Method: A thematic content analysis was conducted on a total of 154 government web pages., Results: Results revealed that predominant themes revolve around economic challenges resulting from an ageing workforce. Older workers are depicted as a key component for the (economic) management of an ageing workforce. More specifically, older workers who intend to continue working are highly valued in the government's messages which present them as productive citizens and role models for "ageing well"., Conclusion: Canada's response to the challenges of an ageing workforce echoes the underlying standards of positive ageing models, which may generate, perhaps inadvertently, a new form of ageism by creating intra-and intergenerational divides in the workplace.

Background: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown., Methods: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields., Results: In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field., Conclusion: We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Progress in our understanding of thymic epithelial cell (TEC) renewal and homeostasis is hindered by the lack of markers for TEC progenitors. Stem and progenitor cell populations display remarkable diversity in their proliferative behavior. In some but not all tissues, stemness is associated with quiescence. The primary goal of our study was to discover whether quiescent cells were present in neonatal and adult TECs. To this end, we used a transgenic label-retaining cell (LRC) assay in which a histone H2B-GFP fusion protein is expressed under the control of the reverse tetracycline-controlled transactivator and the tetracycline operator minimal promoter. In adult mice, we found that both cortical and medullary TECs (cTECs and mTECs) proliferated more actively in females than males. Moreover, we observed three main differences between neonatal and adult TECs: 1) neonatal TECs proliferated more actively than adult TECs; 2) whereas cTECs and mTECs had similar turnover rates in young mice, the turnover of mTECs was more rapid than that of cTECs in adults; and 3) although no LRCs could be detected in young mice, LRCs were detectable after a 16-wk chase in adults. In female mice, LRCs were found almost exclusively among cTECs and expressed relatively low levels of p16INK4a, p19ARF, and Serpine1, and high levels of Bmi1, Foxn1, Trp63, and Wnt4. We conclude that LRCs in adult TECs are not senescent postmitotic cells and may represent the elusive progenitors responsible for TEC maintenance in the adult thymus.

Both physiological and psychological stress cause thymic atrophy via glucocorticoïd (GC)-dependent apoptosis of double-positive (DP) thymocytes. Given the pervasiveness of stress, GC-induced thymic atrophy is arguably the most common type of acquired immunodeficiency. We recently reported that interleukin-21 (IL-21) has a unique ability to expand the small subset of DP thymocytes (CD69(+)) which are ongoing positive selection, and that administration of IL-21 increases thymic output in aged mice. The goal of this study was to evaluate whether IL-21 could mitigate GC-induced thymic atrophy. In contrast to double-negative (DN) and single-positive (SP) thymocytes, most DP thymocytes (CD69(-)) do not constitutively express the IL-21 receptor (IL-21R). Accordingly, CD69(-) DP thymocytes from PBS-treated mice were unresponsive to IL-21 administration. However, following GC injection, surviving CD69(-) DP thymocytes up-regulated IL-21R and responded to IL-21 treatment as evidenced by enhancement of Bcl6 expression and phosphorylation of STAT1, STAT3 and STAT5. Consequently, IL-21 administration to GC-treated mice accelerated thymic recovery by expanding considerably DP thymocytes and, to a lesser extent, DN thymocytes. However, IL-21-induced expansion of DN/DP thymocytes did not alter the diversity of the intrathymic or peripheral T-cell receptor (TCR) repertoire. We conclude that IL-21 dramatically accelerates recovery from GC-induced thymic atrophy.

In order to gain novel insights into thymus biology, we analysed the whole transcriptome of cortical and medullary thymic epithelial cells (cTECs and mTECs) and of skin epithelial cells (ECs). Consistent with their ability to express ectopic genes, mTECs expressed more genes than other cell populations. Out of a total of 15,069 genes expressed in TECs, 25% were differentially expressed by at least 5-fold in cTECs vs. mTECs. Genes expressed at higher levels in cTECs than mTECs regulate numerous cell functions including cell differentiation, cell movement and microtubule dynamics. Many positive regulators of the cell cycle were overexpressed in skin ECs relative to TECs. Our RNA-seq data provide novel systems-level insights into the transcriptional landscape of TECs, highlight substantial divergences in the transcriptome of TEC subsets and suggest that cell cycle progression is differentially regulated in TECs and skin ECs.

Somalis currently constitute the largest Sub-Saharan community in Canada and as such have greatly contributed to the transformation of the immigrant population of this country. Although there is a growing body of research on the Somali community in Canada, the question of how the first generation of Somali Canadians experiences aging and transmits its values and attitudes in this regard to younger generations has yet to be explored. The goal of the present study is precisely to understand how male and female Somali seniors living in Canada perceive and experience aging from a cross-cultural perspective. A total of 17 Somali elders (9 women and 8 men) took part in two focus group discussions. Results of the interpretative content analysis revealed that, regardless of the cultural context, both Somali men and women foster quite a positive view of the notion of aging. However, as Somali migrants, men were more critical than women in regards to the challenges of aging in Canada. Results are discussed in light of previous studies on aging, ageism and culture.

The aim of this exploratory study was to better understand interpersonal communication between frail elders and caregivers in the context of long-term care giving. In addition, in light of the Communication Accommodation Theory, the goal was to determine the extent to which communication can be a transmitter of ageism, particularly of implicit ageism. A total of 26 semi-structured interviews were conducted among elders and caregivers of a Quebec long-term care facility. Results suggest a close convergence between the perception of seniors and caregivers in regards to a quasi total absence of daily communication and moreover, in regards to the highly instrumental nature of this same communication. Finally, results of the content analysis also suggest that implicit ageism is indeed reflected in interpersonal communication between frail elders and caregivers.