NCube/papyrus huggingface dataset:
Effets d’un test de propulsion en fauteuil roulant sur l’intégrité tendineuse des muscles biceps et supra-épineux : étude d’imagerie musculosquelettique par ultrasonographie

Relevance. The completion of performance-based maximal cardiorespiratory fitness tests among manual wheelchair user is highly relevant to develop personalized cardiorespiratory fitness training programs and to assess their impacts over time. However, these tests could potentially increase risk exposure for the development of upper limb secondary musculoskeletal impairments specifically to the shoulder. Hence, finding an equilibrium between the need to measure aerobic fitness and the increased risk of developing secondary musculoskeletal impairments when completing performance-based  test is fundamental. Objective. To characterize the effect of the completion of a recently- developed treadmill-based progressive workload incremental test on the integrity of the  long head of the biceps and supraspinatus tendons using musculoskeletal ultrasound imaging biomarkers. Method. Fifteen manual wheelchair users living with a spinal cord injury completed the treadmill-based progressive workload incremental test. Ultrasound images of the long head of the biceps and supraspinatus tendons were recorded with a musculoskeletal ultrasound imaging device in the transversal and longitudinal planes before, immediately after, and 48 hours after the completion of the test using a standardized protocol. Geometric, luminosity, and texture-related ultrasound biomarkers of a region of interest have characterized tendon integrity. Results. The participants propelled an average of 10.2 ± 2.9 minutes with the majority (N = 13/15) reached at least the eighth stage of the test (speed = 0.8 m/s; slope = 3.6 ̊). None of the geometric, luminosity and texture biomarkers characterizing the integrity of the two tendons, measured in the longitudinal and transversal planes, changed significantly (p=0.063 to 1.000) between the three measurement times. Conclusion. The performance of the treadmill-based progressive workload propulsion test to assess aerobic capacity does not result in any observable deleterious change immediately after and 48 hrs after the performance of the test.

Keyphrases: Biceps, Tendon, Supraspinatus, Shoulder, Cardiorespiratory fitness, Wheelchair, Ultrasonography, Echography
Effet de la production thymique sur l’homéostasie du réservoir du VIH-1 chez des individus recevant une trithérapie antirétrovirale.

Antiretroviral therapy has prolonged the life expectancy of people living with the human immunodeficiency virus (HIV), but does not cure the infection. Indeed, latent virus persists in reservoirs, like CD4+ T cells, which is a major barrier to it’s complete elimination. It is well established that age has an impact on the clinical progression of the disease. However, the relationship between aging and viral persistence is still unknown. As age-associated reduction of thymic production has important consequences on lymphocyte homeostasis, we studied the association between aging, thymic activity avec HIV reservoirs. In infected individuals under antiretroviral therapy, we show that the inducible reservoir is significantly correlated with age. This association can be partially linked to the reduction of thymic production with age, causing a decrease in the frequency of CD8+ T cells. Furthermore, we highlight that individuals with atherosclerotic plaques, a sub-clinical factor highly associated with aging, have a bigger HIV reservoir. Finally, we show that restauration of thymic activity induced by the administration of recombinant growth hormone has a modest but significant beneficial effect on the size of total HIV reservoir. Overall, our results indicate that HIV reservoir evolves differently with age and that thymic involution contributes to viral persistence, which open the way to novel therapeutic approaches. In addition, they suggest that some viral reservoir measures could contribute to the evaluation of the risk of atherosclerotic plaques development.

Keyphrases: HIV, Persistence, Aging, Thymic production, Homeostasis, Cardiovascular diseases
Identification en thérapie cellulaire des patrons d’expression transcriptomique de cellules souches utilisées pour traiter la défaillance cardiaque afin d’en améliorer le potentiel thérapeutique

Ischemic cardiomyopathy and heart failure are the second annual cause of mortality in Canada. Despite rigorous prevention strategies and drug regimens preventing progression, no therapeutic modality can currently reverse the pathologic modifications of the disease. In the last quarter century, numerous advances in the field of regenerative medicine and cell therapy have demonstrated promising effects. COMPARE-AMI, a phase II randomized controlled trial (RCT), evaluated the effect of intracoronary injection of CD133+ cells in acute myocardial infarction following percutaneous intervention. IMPACTCABG, also a phase II RCT, evaluated the effect of intramyocardial injection of CD133+ hematopoietic stem cells in chronic ischemic cardiomyopathy at the time of surgical revascularization. That being said, we believe that the CD133+ cells used in therapy have shared transcriptomic signatures that are responsible for their clinical effects. By classifying patients into responders and non-responders according to an improvement in ejection fraction, we evaluated, a posteriori, those expression patterns. Autologous CD133+ cells of patients classified as responders expressed highly conserved transcriptomic signatures that could be responsible for the clinical outcomes of patients. Notably, these signatures were related to cardioprotective mechanisms including angiogenesis, stress response regulation and cell survival. In order to harness the full potential of stem cell therapy, we attempted to reproduce the identified phenotypes by pharmacological intervention with HSP90 inhibitors which are known to mimic some of these effets. Conditioned human mesenchymal stem cells (hMSC) activated ‘RISK’-type signaling pathways and augmented exosome and protein secretion relating to the response to cellular stress; this activation was unrelated to a switch of cell type. Furthermore, treated hMSC seemed to favour improved wound healing by paracrine activity and were more resistant to oxidative senescence. These encouraging results allow us to develop novel, more advance, strategies of ex vivo cell preconditioning before implantation, including of CD133+ cells. Ultimately, we hope that optimisation of cells through this mechanism and others will allow us to unleash the full potential of stem cell therapy.

Keyphrases: cell therapy, bone marrow-derived stem cells, ischemic heart disease, heart failure, transcriptomics, clinical research
Conception d’un modèle interprofessionnel d’interventions de soutien à l’adhésion au traitement par corset chez les adolescents atteints de scoliose idiopathique

Wearing a spinal brace between 20 to 23 hours a day is recognized as effective to prevent curve progression in adolescents with idiopathic scoliosis, but it generates important biopsychosocial consequences that disturb patients’ daily activities and that contribute to the generalized problem of brace nonadherence. Indeed, the observed time spent in-brace is approximately 12 hours a day. A thorough review of the literature could not yield any intervention to enhance brace adherence for this specific population. The purpose of this master’s thesis is to develop an interprofessional support intervention model to enhance brace adherence in adolescents with idiopathic scoliosis. To fulfill this purpose, we have conducted individual interviews with 9 professionals of various expertise in order to understand their perspectives and their potential strategies to support patients towards better brace adherence. The interviews were audiotaped, transcribed and coded. We proceeded to a thematic analysis of the interview transcripts, which resulted in the intervention model. During the interviews, participants mentioned adherence barriers to brace treatment and professional support barriers as well as functional, educational, motivational, psychological and interprofessional teamwork strategies for answering these issues. The model was reviewed by an expert panel of clinicians. The Interprofessional Adherence Support intervention model (IPAS) to brace treatment is three-tiered to provide different levels of intensity of support to patients (brace preparation, group workshops and one-on-one consultations) and has great potential for implementation in clinical practice.

Keyphrases: adolescence, idiopathic scoliosis, brace treatment, treatment nonadherence, intervention model, interprofessional teamwork, patient support, non-compliance
Associations entre les consommations d’alcool et de cannabis et les variations volumétriques chez l'adulte et lors de l’adolescence, et évaluation des différences sexuelles potentielles

Objectives: Structural differences associated with alcohol use disorders (AUD) and cannabis use disorders (CUD) are inconsistent in the literature, and researchers have difficulty identifying whether structural sex differences (SDs) observed in AUD and CUD patients occur. In addition, the longitudinal relationship between alcohol and cannabis use during adolescence and brain development is unclear. The first objective is to characterize the structural differences between AUD or CUD patients and their controls and to compare these case-control differences with those observed in other psychiatric disorders. The second objective is to assess the structural SDs in AUD and CUD patients compared to their controls. The third objective is to assess the relationship between alcohol and cannabis use and brain development during adolescence over a five-year period. Methods: Meta-analyses were performed on large samples for alcohol (k = 7, N = 798) and cannabis (k = 7, N = 447) use disorders based on the ENIGMA-Addiction working group dataset that includes adolescents and adults to a) compare structural differences in AUD and CUD patients compared to controls to those reported in other psychiatric conditions, and b) evaluate SSD in AUD and CUD by evaluating interaction terms and by performing sex-stratified analyses. The Neuroventure dataset (N = 130), a cohort of 13 year-old adolescents followed one a five-year period, was used to evaluate how adolescent binge-drinking and cannabis use were associated with SSD in brain structures and cognitive performance. The results on these two datasets are not directly compared since they do not focus on the same population of interest. Results: Reduced volumes were observed in AUD and CUD with effect sizes in general similar to those reported in the other compared psychiatric disorders. Male- and female-specific and non-sex specific case-control differences were also observed in AUD and CUD. Finally, reduced subcortical volumes and cortical thickness were associated with drug- and sex-specific parameters through adolescence. Conclusion: Although no causal direction was evaluated in the three articles, these results contribute to a better understanding of the impact of alcohol and cannabis misuse on the SSD occurring in the adult and adolescent brain, notably in the hippocampus. The observed sex differences are important to avoid generalizing the substance use-related structural abnormalities to both sexes.

Keyphrases: Neuroimagerie, Cannabis, Adolescents, Neuroimaging, Sex differences, Addiction, Alcohol, Adults
Identification de nouvelles cibles thérapeutiques dans la dysfonction primaire du greffon suite à une transplantation pulmonaire

Background: Primary graft dysfunction (PGD) after lung transplantation is the first cause of death in the perioperative phase. The PGD pathophysiology is not fully elucidated, but Ischemia/Reperfusion (I/R) injury might be an important factor. I/R and PGD both feature endothelial/ epithelial damage, lung edema and inflammation. Edema resorption then depends on the restoration of the alveolar functional integrity, especially the ability of alveolar epithelial cells to reabsorb Na+ (through ENaC channels) and fluid. We hypothesized that alveolar epithelial dysfunction (related to I/R), observed within donor grafts, then plays a key role in the development of PGD in lung recipients. Our goal was to identify novel biomarkers, associated with epithelial dysfunction within donor’s grafts, and then PGD development in recipients.  Methods: The impact of a protocol mimicking hypothermic ischemia and reperfusion was first tested on primary rat alveolar epithelial cell cultures. Then, the impact of I/R was studied in vivo using models of inflammatory stress induced by LPS infusion or after unilateral transplantation in pigs. Finally, lung biopsies from donor grafts were collected during lung transplantations. After defining PGD scores within the recipients, associated factors and alveolar alterations were finally analyzed. Results: In primary cell cultures, the protocol mimicking hypothermic I/R induced a decrease in tight junction proteins (ZO-1), transepithelial resistance, wound repair capacity as well as ENaC and CFTR channel expression. Treatment with a KvLQT1 K+ channel activator (R-L3) accelerated the repair rates and enhanced barrier integrity (ZO-1 staining) as well as ENaC and CFTR protein expressions. In the porcine models, an exacerbated inflammatory response was observed along with alveolar damage, lung edema and decreased ZO-1, ENaC and CFTR expressions. Our preliminary data using human samples collected during lung transplantations also indicate an inflammatory response and reduced ENaC, CFTR and ZO-1 expressions, already observed within lung grafts, submitted to longer cold ischemia duration, among lung recipients then developing a PGD.  Conclusion: Altogether these data support our hypothesis of an alveolar epithelial dysfunction, featuring an alteration of functionality and barrier integrity biomarkers (ENaC, CFTR and ZO-1), associated with I/R and DPG.

Keyphrases: Inflammation, Lung transplantation, Primary graft dysfunction, Ischemia/Reperfusion, Alveolar epithelium, Injury, Integrity, Ionic channels, Cellular and animal models, Translational research
Description de la pratique d’ergothérapeutes auprès des personnes présentant des symptômes comportementaux et psychologiques de la démence

The management of behavioural and psychological symptoms of dementia [BPSD] is a hot topic as dementia affects 7.1% of Canadians (Public Health Agency of Canada, 2017). Of these, approximately 40-60% experience symptoms such as wandering, aggression, verbal agitation, etc. (Public Health Agency of Canada, 2017). (MSSS, 2012).  Several recent publications, based on a consensus of experts, suggest good practices to be favoured regarding this problem (MSSS, 2014), however, implementation is poorly documented to date. The objectives of this master’s thesis are, first, to describe the practice of occupational therapists in Quebec with people with BPSD. The second objective is to describe how occupational therapists integrate evidence-based results into their practice with this clientele. A simultaneous mixed quote study (Briand & Larivière, 2014) was carried out. An online questionnaire addressing occupational therapist practice with individuals with BPSD was completed by 86 occupational therapists. As well, 12 occupational therapists participated in semi-structured interviews to provide additional information on the integration of evidence-based outcomes into their practice.  The results of the study highlight the importance that occupational therapists place on assessing functioning in activities of daily living through observation or role-playing. The preferred interventions mainly concern changes in the environment. The results indicate that the interventions advocated by the respondents are those that were considered least effective as indicated by the literature review. The results show that occupational therapists use interventions for which they perceive they are competent. Occupational therapists favour prior clinical experience and training to guide their practice over consulting scientific literature.  The results of this master’s thesis provide useful insights to guide the practice of occupational therapists in the management of BPSD. Understanding the factors influencing occupational therapists in their choice of preferred intervention allows us to propose solutions to optimize the integration of evidence-based results in practice.

Keyphrases: Occupational therapy, Evidence-based practice, Professional practice, Behavioural and psychological symptoms of dementia
Identification des besoins décisionnels des couples porteurs de maladies héréditaires rares

A national carrier screening program for four recessive diseases (Leigh syndrome, autosomal recessive spastic ataxia of Charlevoix-Saguenay, hereditary motor and sensory neuropathy with or without agenesis of the corpus callosum and hereditary tyrosinemia type 1) known to be relatively more prevalent in some parts of Quebec province is available since 2018. Carrier couples face an important decision-making process regarding their familial planning that can become a significant source of discomfort and potential regrets. Our study aimed to describe the decisional needs of couples carriers of one of the four recessive disorders according to the Ottawa Decision Support Framework. A qualitative descriptive study was conducted, and qualitative individual and joint couple interviews were performed among 39 carrier individuals and 11 health and social care professionals. Decisional needs reported by the participants of this study included decisional conflict, roles in decision-making, decisional stages, dynamics of the decision-making process and available support. Decision-making process of all four disorders, but particularly autosomal recessive spastic ataxia of Charlevoix-Saguenay French-Canadian and hereditary tyrosinemia type 1 carriers, was associated with increased decisional conflict. Considering these results, patient decision aids will be designed to meet the needs of carrier couples.

Keyphrases: Decisional need, Decision making, Patient decision aid, Decision support, Genetic counseling, Reproductive decision
Perméabilité et endothélialisation in vivo d’une prothèse vasculaire de petit diamètre électrofilée avec membrane bioactive

Cardiovascular diseases present a growing burden of morbidity and mortality worldwide [1, 2]. Despite significant advances in medical and endovascular treatments of these pathologies, the need of revascularization by arterial bypass is increasing. Actual synthetic vascular conduits perform well when used on large-diameter arteries, but small-diameter conduits (<6 mm) still show unacceptably low medium- and long-term permeability rates [3-11]. Two hypotheses can explain this phenomenon – the inability of synthetic bypasses to create a neo-endothelium and compliance mismatch between the graft and the native artery [12-18]. The goal of this study was to create and evaluate the performance of a novel small-diameter vascular conduit with superior endothelialization properties and a compliance similar to native vessels. This study presents two distinct aspects : the in vitro elaboration and evaluation of an electrospun, small-diameter (5 mm) vascular conduit made up of a scaffold of polyurethane/polycaprolactone (PU/PCL) combined with a chondroitin sulfate (CS) bioactive coating by a team specialized in biomaterials, and the elaboration and evaluation of an in vivo trial testing the performance of the novel vascular graft in a large animal model by a second team. The experimental conduits (eVG-CS) showed an in vitro compliance 10-times superior to their commercially-available expanded polytetrafluoroethylene (ePTFE) counterparts, while remaining stable after aging trials. However, in vivo evaluation, as bilateral interposition carotid bypasses in sheep, showed the novel bypasses to be inferior to ePTFE controls in terms of permeability and by the absence of significant endothelialization. The in vivo inferiority of these novel bioactive electrospun grafts despite favorable in vitro results was attributed to the low porosity of the grafts and to the inability of the CS coating to promote the endothelialization process. Establishment of a more porous graft with a different bioactive coating represents the future of the evaluation of this promising PU/PCL structure.

Keyphrases: polyurethane, polycaprolactone, compliance, Cardiovascular, Bypass, Electrospinning, Chondroitin
Predictive carboplatin treatment response models for epithelial ovarian cancer : comparison of 2D, 3D and in-vivo models

Epithelial ovarian adenocarcinoma (EOC) is the most lethal gynecological cancer. The drug discovery pipeline is heavily based on preclinical models. Typically, 2D cell line (CL)-based models are used to screen compounds followed by validation in animal models to generate the evidence needed to design clinical trials. This process incurs a high cost to the research pipeline and still results in high drug attrition rates. This may in part reflect the poor translation of preclinical to clinical results and points to deficiencies in modeling. Previous work from our laboratory shows that the sensitivity of our EOC CLs to carboplatin therapy varies between 2D and 3D in vitro models, however it is unclear how these differences align with the in vivo response. We hypothesize that 3D models will more closely reflect therapeutic in vivo response. The objective of this study was to characterize the carboplatin sensitivity of EOC CLs in 2D and 3D-spheroids and compare them to in vivo response using mouse xenografts. We injected mice with 6 different EOC CLs that were treated with 3 different carboplatin concentrations. Tumor volume measurements and immunofluorescence viability stains were used to categorize CLs by their sensitivity. The same CLs were seeded in low attachment plates to form, and thereafter treat, spheroids. Flow cytometry analysis was used to classify CLs by their 50% inhibitory response (IC50). The 2D response (IC50) for these CLs has previously been published. Our results show that therapeutic response changes significantly for a single CL between different systems, and the 3D model was most concordant with the in vivo model. Our ultra-resistant CL in 2D became more sensitive in 3D/mouse models. In contrast, the highly 2D sensitive CL became more resistant in our xenograft/spheroid models. The results are important to consider when investing time/funds in drug screening and therapeutic response prediction studies.

Keyphrases: Preclinical models, Ovarian cancer, Mouse xenografts, Spheroids, Carboplatin, Carboplatin