NCube/papyrus huggingface dataset:
L’expérience d’autosoins des femmes âgées atteintes d’un cancer du sein recevant des traitements de chimiothérapie en clinique ambulatoire

In recent years, the incidence of breast cancer diagnosis has increased among women aged 70 and over. During their care path, elderly women with breast cancer have a life context and needs different from those of younger women. In particular, they have to adapt to numerous changes with the so-called normal ageing process, namely the decrease of their functional autonomy. The presence of several co-morbidities and social isolation are factors that can influence their self-care. Self-care represents what the person does to preserve their biospsychosocial health. To our knowledge, they are very few studies on elderly women with breast cancer self-care behavior during their breast cancer. Based on the Orem (2003) self-care theory, this qualitative study aims at better understanding the elderly women experience in taking care. Individual interviews of 60 to 90 minutes with 5 women with breast cancer and at least 70 years old have been conducted. Thematic analysis has been carried out with the method of Miles and Huberman (2003).   Overall, results have allowed to better understanding the experience of elderly women self-care. During their care path, they had to fulfill some needs (self-care requirements) to optimize the quality of life and limit the impact of breast cancer. To this end, they were to: 1) maintain their autonomy in daily life activities and leisure, 2) assume their decision-making in the choice of treatment, 3) adapt to their disease and 4) maintain a positive self-image. Results showed that in order to meet the previous requirements, they had to rely on external support: 1) support from family members and relatives, 2) availability of the family doctor, and 3) availability of the pivot nurse. These resources enable women to implement self-care actions that enable them to meet their needs. The healthcare professionals, in particular the nurse in oncology, play an important role in the identification of self-care requirements and capacities and day-to-day measures from the beginning of the care path is essential to accompany the clientele in the execution of the actions of self-care.

Keyphrases: Breast cancer, Elderly women, Self-care
La collaboration interprofessionnelle lors de la prise en charge d'un polytraumatisé à l'urgence

Trauma is the leading cause of death among young adults in Quebec. Thus, the management of polytrauma in the emergency room is absolutely crucial to optimize care and prevent premature death. Unfortunately, several studies have highlighted important gaps in collaboration between the various professionals on the trauma team, creating a major challenge to the quality of care provided. This descriptive qualitative exploratory study aims to explore the experience of interprofessional collaboration (IPC), according to the point of view of health professionals, when treating a polytraumatic patient in the emergency room. More specifically, this study aims to determine the description that health professionals make of the concept of IPC in traumatology, as well as the identification of factors facilitating and limiting this collaboration. The conceptual framework to understand the interprofessional collaboration of Reeves, Lewin, Espin and Zwarenstein (2010) has served as a theoretical and structured basis for each step of this study. Individual interviews and a focus group were conducted among seven health professionals involved in the management of a polytrauma patient in the emergency room. In addition, two structured observations of the management of a polytraumatized patient were performed. Following a thematic analysis, the results show that for the participants of this study, the IPC describes itself as being the set of seven essential elements, including communication and having a common goal (the patient). The factors influencing IPC are multiple and fall into five broad categories: individual, relational, procedural, organizational and contextual. Individual factors, a category that is not part of the conceptual framework of Reeves and al. (2010), have emerged as being a major part of the IPC. In addition, the results of this study should provide a better understanding of the reality experienced by different health professionals when dealing with a polytrauma patient and appear to be the basis for future research on the development of an intervention aiming to consolidate the collaborative practices of health professionals working in this specific care context.

Keyphrases: Collaboration, Étude qualitative, Polytraumatized patient, Qualitative study, Traumatology, Emergency services
L’expérience de parents d’adolescents ayant un trouble du spectre de l’autisme avec un handicap intellectuel à la suite d’une hospitalisation en pédopsychiatrie

Autism spectrum disorder (ASD) is a complex and chronic condition with a prevalence that is steadily increasing worldwide, including in Quebec. However, the services currently offered to support people with ASD are not adequate to address this growth. This thesis is an exploratory and descriptive qualitative study which aims to explore the experiences of parents of adolescents with ASD and intellectual disability (ID) across first, second and third line services, and following post-hospitalization in a child psychiatric unit. To facilitate data collection and analysis, the theoretical framework used was the Ecological Systems Theory by Bronfenbrenner (1979) adapted by Lefebvre and Levert (2006). A total of six semi-structured interviews were conducted with nine parents of adolescents between the ages of 12 and 17 with ASD and ID who have been inpatients in a child psychiatric unit. The primary finding is that the experiences of these parents are a series of disappointments, and the four emerging themes are 1) the expectations expressed, 2) the encountered difficulties, 3) the solutions put in place and 4) the feeling of failure. According to their account, the current services have not been able to meet their needs, despite the involvement of many health workers and professionals. In light of these findings, changes need to be made in the follow-up services offered to these families after the discharge of their adolescent children.

Keyphrases: Adolescent, Post-hospitalisation, Service, Autism Spectrum Disorder, Intellectual Disability, Adolescent, Parents’ Experience, Post-hospitalization (discharge), Child Psychiatry, Follow Up, Services, Qualitative Study
La conséquence de l’expression de hnRNP A1B sur la réponse cellulaire au stress

A first-line protective mechanism by which cells respond to an adverse environmental insult or stressor is the formation of stress granules (SGs). SGs are micron-sized, cytoplasmic structures that are highly dynamic and contain translationally arrested mRNAs and a broad range of proteins. Several lines of evidence suggest that the SG response is perturbed in amyotrophic lateral sclerosis (ALS). However, very little is known regarding the regulatory mechanisms of SG assembly and disassembly. One protein that could affect the recovery of cells from stress is the RNA binding protein hnRNP A1. This protein is highly abundant in motor neurons. The protein product of its alternatively spliced isoform, hnRNP A1B, is physiologically expressed at low levels. HnRNP A1B arises from the inclusion of exon 7B in the hnRNP A1 transcript. This leads to the retention of 52 amino acids in the protein’s prion-like domain. We have recently shown that hnRNP A1B is increased in ALS-affected tissues and that it has a higher propensity to aggregate compared to hnRNP A1 and this correlates with increased toxicity. The function of hnRNP A1B in SG dynamics has yet to be elucidated. We hypothesize that increased splicing of hnRNP A1 to hnRNP A1B contributes to cellular toxicity by: a) disrupting SG dynamics, and b) hnRNP A1B triggers formation of cytoplasmic inclusions. Our work indicates how hnRNP A1B affects the cellular stress response by altering SG dynamics.

Keyphrases: hnRNP A1, hnRNP A1B, processing bodies, amyotrophic lateral sclerosis, stress granules, stress response, protein aggregation, prion like domain
Processus de binding actif en mémoire de travail préservé chez des adultes autistes sans déficience intellectuelle

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by socio-communicative deficits, as well as restrictive interests and repetitive behaviors. Alterations in executive functions, including in working memory (WM), can also be found throughout the spectrum. WM is a temporary storage system allowing active conservation of information for a short period of time. The ability to associate different information together in WM, referred to as binding, is crucial for episodic memory and learning processes. There are two types of binding. Passive binding occurs when the association between two pieces of information is made unconsciously and automatically. Active binding requires a conscious effort to associate two pieces of information. These two types of binding rely on different neural substrates; passive binding is based on the functioning of the hippocampus, while active binding is based on the communication between the hippocampus and prefrontal cortex. Some studies have suggested impairments in WM tasks requiring intentional organisation of information in ASD. Other studies also suggested preserved capabilities in the passive form of binding in ASD. The objective of this project is to investigate the neural substrates underlying the two forms of binding in high functionning autistic adults, with more attention to the active form, using functional magnetic resonance imaging (fMRI). The study included 18 ASD participants and 18 controls (CT). All participants performed a WM task in an MRI scanner. The task consisted in the memorization of the association between three words and three spatial positions (defined by ellipses). At the behavioral level, both groups have a similar level of performance, which suggest that the active binding is preserved in autism. ASD participants showed higher levels of activation in the right frontal lobe (precentral gyrus),  and in the right parietal lobe (postcentral gyrus) during the maintenance phase. They also showed lower levels of activation in the right inferior frontal gyrus. This difference of levels of activation could mean that the two groups use their cerebral resources differently. At the anatomic level, ASD participants showed lower volume of grey matter in the limbic, temporal, occipital, frontal, occipital, frontal, cingulate and parietal regions.

Keyphrases: IRM, Autistic spectrum disorder, Working memory, Active binding, MRI
Criblage génétique et caractérisation fonctionnelle des mutations dans le gène CHD2 associé à l’épilepsie dans un modèle de poisson zèbre

Epilepsy is one of the most common neurological diseases worldwide affecting more than 50 million people. Although medical research unravelled the genetic basis of some epilepsies, the majority of cases remains unexplained. A particular form of epileptic encephalopathies with photosensitivity has recently been associated with the CHD2 gene. In order to better understand the role of CHD2 in epilepsy, we screened epileptic patients for pathogenic variants and we characterized the functional effect of newly discovered genetic variations in a zebrafish model. Overall, we sequenced the CHD2 gene in a total of 1959 epileptic patients, including 95 photosensitive, and reported 37 new genetic variations potentially damaging in various types of epilepsy. We demonstrated in vitro that a silent mutation found in a photosensitive epileptic patient affects the splicing of the gene and leads to the introduction of a premature stop codon, suggesting a partial loss of function of the protein. We then showed in situ that the chd2 gene is expressed in the brain of zebrafish, and could be knocked down in this model using a Morpholino (MO). Zebrafish injected with MO presented a curved morphological phenotype, as well as a reduced lifetime. Then we showed that injection of the wild-type human CHD2 gene resulted in a significant rescue of this abnormal phenotype. Subsequently, we injected different mutant copies of the human CHD2 gene to characterize genetic variations identified in our cohort. Only one of these did not significantly save the phenotype. In order to study the effect of a complete inactivation of chd2, we established a stable line of zebrafish that do not express this gene, using the CRISPR-Cas9 technique. We are the first to knockout chd2 in zebrafish, and will continue using this transgenic line to better understand the role of this gene in epilepsy. Although our results are preliminary, we showed in a zebrafish model that a new genetic variation in CHD2 could cause epilepsy.

Keyphrases: CHD2, Morpholino, CRISPR-Cas9, epilepsy, epileptic encephalopathy, photosensitivity, zebrafish, genetic screening
L’haploinsuffisance de Syngap1 dans les neurones GABAergiques induit une hyperactivation de mTOR et des déficits cognitifs

Intellectual disability is characterized by significant impairments of cognitive and adaptative functions reaching a prevalence of 2 to 3 % worlwide. Numerous studies have linked intellectual disability with mutations in genes coding for protein active at the synapses. De novo mutations in the SYNGAP1 gene, coding for a GTPase-activating protein, causes moderate to severe intellectual disability. Syngap1 haploinsufficiency increases activity level of Ras-ERK-mTOR, causing excessive insertion of AMPA receptor at the postsynaptic membrane of excitatory neurons and affects spine morphology. In mice, cognitive deficits are in part due to alteration of the GABAergic circuitry. Syngap1 haploinsufficiency in GABAergic neurons originating from the medial ganglionic eminence reduces the number of perisomatic innervation formed by parvalbuminexpressing basket cells and reduces inhibitory synaptic activity. The downstream molecular mechanisms linking Syngap1 haploinsufficiency to GABAergic deficits are unknown. In this study, we show that mTOR is hyperactivated in parvalbumin-expressing basket cells in the prefrontal cortex under basal conditions and after neuronal stimulation in Tg(Nkx2.1-Cre); Syngap1flox/+ mice. Furthermore, we show that two mice models exhibiting mTOR hyperactivation in parvalbumin-expressing interneurons had contextual fear memory deficits. Lovastatin treatment failed to restore regular mTOR signaling and contextual fear memory in Tg(Nkx2.1-Cre); Syngap1flox/+ mice. Finally, we show that inducing Syngap1 haploinsufficiency specifically in parvabumin-postive interneurons after the second postnatal week does not cause fear memory deficits, thus suggesting that cognitive problems in adult mice may be due to alterations occurring during early brain development. Our results point to mTOR pathway as a signaling mechanism potentially linking Syngap1 haploinsufficiency and GABAergic deficits. In addition, our data suggest that treatment in the early postnatal period might be more effective to treat molecular and cognitive deficits caused by Syngap1 mutations.

Keyphrases: Syngap1, mTOR, cognition, Intellectual disability, GABAergic interneurons, behavior, lovastatin
Le rôle de la 12/15-Lipoxygénase dans la pathogenèse de l'arthrose

Osteoarthritis (OA) is the most common rheumatic disease in the world. It is recognized as a multifactorial disease affecting different tissues of the joint. It is known that 12/15- lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators and is involved in several inflammatory and degenerative diseases. However, its involvement in the pathophysiology of OA is not yet established. Hence, in this project, we have investigated the role of 12/15-LOX in the pathogenesis of OA. First, we demonstrated that 12/15-LOX is overexpressed in the cartilage of wild-type (WT) mice during the development of OA induced by age or by the destabilization of the medical meniscus (DMM)-induced OA. The increase in protein expression of 12/15-LOX, obtained by immunohistochemistry, is accompanied by an increase in expression at the mRNA level. Subsequently, our histological work demonstrated that the deletion of the 12/15-LOX gene accelerated cartilage erosion with age and after DMM surgery. We have also shown that there is an increase in the expression of catabolic mediators (ADAMTS5 and MMP-13) and inflammatory mediators (iNOS and mPGES-1), as well as degradation products of type II collagen (C1, 2C) and aggrecan (VDIPEN) in 12/15-LOX - / - mice compared to WT. We subsequently demonstrated that the presence of 12/15-LOX metabolites 13-HODE, 15-HETE and LXA4 decreased the level of MMP-13, PGE2 and NO following stimulation of cartilage explants with IL-α. However, the metabolite LXA4 produced a better inhibition of catabolic and inflammatory responses in cartilage. Finally, our results suggest that LXA4 has protective effects in vivo, as it reduces the severity of cartilage degradation induced by DMM following its peritoneal injection in WT mice. Together, these data indicate that 12/15-LOX has an important role in the pathogenesis of OA. Activation of the 12/15-LOX pathway and its metabolites may represent a promising avenue in the development of new therapies for osteoarthritis.

Keyphrases: Osteoarthritis, Cartilage, 12/15-LOX, 13-HODE, 15-HETE, MMP-13, ADAMTS5, iNOS, mPGES-1, C1,2C, VIDIPEN
Effet de l’activation du récepteur mGluR2 par LY-354,740 sur les dyskinésies chez le modèle parkinsonien de rat lésé à la 6-hydroxydopamine

L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective symptomatic treatment for Parkinson’s disease (PD). However, with long term administration, L-DOPA use is associated with the development of motor complications such as dyskinesia. Dyskinesia causes significant morbidity to as many as 50-95% of patients with advanced PD and treatment options are few. Recently, studies have indicated that serotonin 2A receptor (5-HT2AR) blockade has an anti-dyskinetic effect. 5-HT2A receptors interact tightly with metabotropic glutamate receptor 2 (mGluR2); at the downstream signalling level, 5-HT2AR blockade has an effect similar to mGluR2 activation. Based on this, we hypothesised that mGluR2 activation would effectively alleviate dyskinesia in PD. In the present studies, we investigated the effect of the mGluR2 orthosteric agonist LY-354,740 at alleviating established, and preventing the development of, L-DOPA-induced dyskinesia (LID) in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Rats were rendered hemi-parkinsonian by stereotaxic injection of 6-OHDA into the right medial forebrain bundle. Following a recovery period, degree of parkinsonism was assessed using the cylinder test and two studies were then performed. In the first set of experiments, rats were primed with chronic L-DOPA administration to induce abnormal involuntary movements (AIMs), after which L-DOPA was administered, in combination with LY-354,740 (vehicle, 0.1, 1 and 10 mg/kg). The effect of LY-354,740 on L-DOPA anti-parkinsonian action was subsequently determined by the cylinder test. In the second set of experiments, which sought to determine the effect of LY-354,740 at preventing the development of dyskinesia, hemi-parkinsonian rats were administered a daily dose of LY-354,740 (0.1 or 1 mg/kg) or vehicle, started concurrently with L-DOPA for 22 days and dyskinesia severity was monitored. After a 3-day washout period, an acute challenge of L-DOPA was administered and ALO AIMs severity was assessed to determine if dyskinesia development had indeed been reduced. In the first set of experiments, we found LY-354,740 0.1 mg/kg, in combination with L-DOPA, significantly reduced AIMs amplitude and duration by 21% and 18%, respectively (P < 0.0001) without impairing L-DOPA anti-parkinsonian effect. LY-354,740 0.1 mg/kg also attenuated the priming process leading to the development of dyskinesia when started concurrently with L-DOPA, when compared to the L-DOPA/vehicle group. Our results suggest that selective mGluR2 activation through orthosteric activation is an effective and promising therapeutic strategy to alleviate the severity of established, and attenuate the development of dyskinesia.

Keyphrases: mGluR2, LY-354,740, L-DOPA, Parkinson’s disease, dyskinesia
Rôle du récepteur TRPV1 dans l'induction du récepteur B1 des kinines dans un modèle de douleur neuropathique

The kinin B1 receptor (B1R) and the TRPV1 (transient receptor potential vanilloid 1) are two membrane receptors which play an essential role in the development of neuropathic pain (NP). We hypothesize that they act concurrently and interact directly or indirectly through pro-inflammatory cytokines (TNFα and IL-1β). The aim of this study was to evaluate in a model of NP the kind of interaction between these receptors by measuring the impact of a treatment with an antagonist of B1R (SSR240612, 10 mg/kg i.p.)  or TRPV1 (SB366791, 1 mg/kg i.p.) on the behavioural nociceptive responses, the expression (mRNA by qRT-PCR) and the distribution (immunofluorescence) of B1R, TRPV1 and the two cytokines in the spinal cord. Sprague-Dawley rats were subjected to a unilateral partial sciatic nerve ligation (PSNL) and the antagonists were administered daily for a week starting 14 days after surgery. Both antagonists were able to block thermal hyperalgesia on the ipsilateral and contralateral side of the PSNL. The mechanical and cold allodynia were transiently inhibited by the TRPV1 antagonist, but remained unaffected by the B1R antagonist. Whereas SSR240612 reversed astrogliosis and blocked B1R and TRPV1 gene overexpression in the spinal cord, SB366791 further enhanced the expression of B1R and astrogliosis. Both antagonists also enhanced the mRNA levels of IL-1β without affecting those of TNFα. B1R and IL-1β were found colocalised on astrocytes while TRPV1 was exclusively expressed in peptidergic and non peptidergic primary sensory fibers. These data provide support for an indirect interaction between B1R and TRPV1 through possibly the release of IL-1β from astrocytes. IL-1β would be responsible to maintain allodynia and to cause the upregulation of B1R. This study highlights the possibility that the exclusive inhibition of TRPV1 can be shadowed by the increase expression and pronociceptive function of B1R in NP. Hence, it is suggested that a combined treatment with B1R and TRPV1 inhibitors can afford a better therapeutic perspective.

Keyphrases: TRPV1, Astrocytes, Neuropathic pain, Kinin receptors, Allodynia, Hyperalgesia, Astrogliosis, Pro-inflammatory cytokines, Spinal cord, Primary sensory fibers