NCube/papyrus huggingface dataset:
L’entérotoxine STb d’Escherichia coli déloge la claudine-1 des jonctions serrées

Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ) proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability we treated human colon cells (T84) with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40 (a non-ionic, non-denaturing detergent)-containing solution we investigated the distribution of claudin-1, a major TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble) and the cytoplasmic (NP40- soluble) location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24h, cells grown in low Ca++-containing medium (5 μM) treated with STb, showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from low to physiological Ca++-containing medium (1,8 mM) increased the dislodgement rate of claudin-1, as comparable delocalization was observed after 6h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compare to the low Ca++-containing medium. Using anti- phosphoserine and anti-phosphothreonine antibodies we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

Keyphrases: soluble, insoluble, phosphorylation/déphosphorylation, Escherichia coli, Tight junction, soluble, insoluble, diarrhea, phosphorylation/dephosphorylation, Escherichia coli, secretion, STb toxine
Métrologie de la douleur animale : validation de méthodes sur un modèle arthrosique chez le rat

Animal models of osteoarthritis pain have been used for decades in rats to test the analgesia response of numerous compounds. Study methodology, in particular the pain assessment methods, is quite variable, making the comparison between each project difficult and sometimes simply impossible. In order to improve the translation of new therapies from the preclinical research to the clinical field, this study proposed to establish the reliability and concurrent validity of a panel of pain assessment methods. The concurrent validation was performed in the most popular osteoarthritis rat model, i.e. using the intra-articular injection of monosodium iodoacetate (MIA). The repeatability and inter-observer reliability of various pain assessment methods were evaluated, and the most reliable acclimatization protocol was determined. Then, the most reliable methods were tested comparatively in the rat MIA osteoarthritis model for their sensitivity in detecting painful changes related to the MIA injection. Their responsiveness to treatment, i.e. an intra-articular injection of lidocaine, was also assessed. A complete pain evaluation protocol and reliable acclimatization period, combining reflexive and spontaneous behavior measures as well as operant testing, successfully demonstrated the pain related changes of the MIA injection. Operant testing was the most responsive to the analgesic effect of lidocaine. This study established the most reliable and sensitive methods of pain assessment and optimized acclimatization protocol. Moreover it defined the operant testing as a highly relevant tool to demonstrate the affective component of pain in rodent.

Keyphrases: Validation, Animal model, Osteoarthritis, Operant testing, Monosodium iodoacetate, Acclimatization, Pain metrology
Experiences of participants in the field of food insecurity through the lens of Bourdieu's cultural capital : practical and theoretical explorations

Using qualitative semi-structured interview data, this thesis examines the resources used by food insecure Montrealers through the lens of Pierre Bourdieu’s concept of cultural capital. Respondents were chosen among users of alternative community food security organizations and all were food insecure. Inductive and deductive analyses were performed. Sixteen indicators of embodied cultural capital and three indicators of each of institutionalized and objectified cultural capital were found to be related to the strategies respondents used to try to improve their situation of food insecurity. This research demonstrates that cultural capital plays a role in the strategies employed by food insecure Montrealers, including the participation in community-based organizations. In addition, a lack of appropriate capital can serve as a barrier to participation in certain strategies. Further examination of these barriers could help to deepen understanding of the appropriateness and effectiveness of the current community strategies to face food insecurity.

Keyphrases: Food security, Social theory, Cultural capital, Pierre Bourdieu, Food insecurity, Recherche qualitative
Genetic association study of plasma creatine kinase levels in the Montreal Heart Institute Hospital Cohort

Statins (HMG-CoA reductase inhibitors) have been shown to reduce LDL-cholesterol and are undoubtedly the mainstay in the treatment of hyperlipidemia. Approximately 10 percent of statin users suffer from adverse side effects, the most common being muscle myopathy. Muscle myopathy is often accompanied by elevated levels of plasma creatine kinase (CK). Oftentimes, patients are taken off statins after their CK levels surpass a reference threshold. We looked at CK levels in the MHI Biobank, which have recently been genotyped in over 6000 participants with the Illumina ExomChip. Prior studies have found significant association between plasma CK levels and genetic variants and we aimed to replicate these findings using a genome wide association and a SKAT burden test for rare variants. We were able to replicate findings in the CKM gene (rs11559024, p=1.59x10-23) and LILRB5 gene (rs12975366, p=1.44x10-23) in chromosome 19. We hope that these results will eventually be utilized in clinical statin care by aiding in the prediction of personalized reference CK levels based on genetic information for patients using statins.

Keyphrases: statin, creatine kinase, myopathy
Trajectoires développementales des dimensions du profil de dysrégulation (CBCL-DE) – agressivité, anxiété et inattention : éléments prédicteurs de diplomation au secondaire chez les garçons

The objective of this study was to investigate the relationship between belonging to the Achenbach’s dysregulation profile (CBCL-DP) and the odds of having a high school diploma among boys at the age of 24. Two phases of analyzes were conducted from a sample of 1,037 boys assessed at 7 repetitions between the ages of 6 and 15. The first set of analyzes used a semi-parametric design to identify four developmental trajectories for each dimension. From the lowest level of severity measured at the age of 6, the trajectories obtained for the physical aggression dimension are: low, low-decreasing, high-decreasing and chronic; for the anxiety dimension: low, moderate, high and high-decreasing; and finally for the inattention dimension: low, low-increasing, high-decreasing, and high-raising. It was found that for one dimension, boys can follow a path independently from the severity of the two other dimensions. The second phase of analysis showed that belonging to either of the developmental trajectories of the CBCL-DP decrease the odds of obtaining a high-school diploma beyond the fact of belonging to the path of the other dimensions. These results suggest considering the longitudinal development of each dimension of the profile in combination with the total score obtained with the CBCL. In addition, future work should examine whether early work on self-regulation skills can generate an impact on the development of these three dimensions, for example by reducing the severity of symptoms. This longitudinal perspective could support children who show early onset of difficulties upon the aggressive, anxious and inattentive spheres in their school achievement.

Keyphrases: CBCL, Emotional dysregulation, Longitudinal study, High-school diplomation
Etude des facteurs associés à la détresse psychologique lors de la transition des ainés vers la retraite

Rationale : Retirement is an important step in seniors’ life. It is a period characterized by several changes such as the end of role of worker, a considerable decrease in income, and a change in the way of living that may affect the psychological well-being of retirees. According to Atchley, the risk of psychological distress increases when the transition to retirement leads to discontinuity in internal and external resources which are available to individuals before and after retirement. Objectives : To examine the evolution of internal and external resources of individuals before and after retirement and to estimate the influence of the evolution of these factors on psychological distress of retirees. Methods : Data come from the Canadian National Population Health Survey, a longitudinal population-based survey conducted by Statistics Canada. The sample was made up of 426 retirees aged 55 and over at the time of retirement. Psychological distress was measured by Kessler’s K6. Independent variables included the sense of control (internal factor), stress, social network and social support (external factors). Data were analyzed by linear regression analysis. Results : Psychological distress of retirees increases according to their level of distress before retirement and to the financial and general stress experienced after retirement. It decreases according to their sense of control felt after retirement and to the change in their social network and sense of control before and after retirement. Conclusion : Contrary to what was predicted by the model of Atchley, discontinuity of internal and external resources is not necessarily a risk factor for distress of retirees since their situation after retirement can also affect their mental health.

Keyphrases: Transition, Psychological distress, Internal factors, External factors, Seniors, Transition, Retirement
La régénération axonale suivant l'axotomie du nerf sciatique et stimulation électrique directe et transcutanée chez la souris

Direct electrical stimulation (DES) for one hour increases the rate of peripheral nerve regeneration in rats after nerve repair. Clinically, this would lengthen surgery time, increasing risks of perioperative complications. Purpose: This study examines whether transcutaneous electrical stimulation (TCES) is as effective at improving peripheral nerve regeneration as direct electrical stimulation. Methods: The right sciatic nerve was axotomized in 28 mice. End-to-end microsuture repair was undertaken. Four groups were studied: (1) sham; (2) suture only; (3) suture and DES; (4) suture and TCES. Stimulation was applied for 1 hour, at 20 Hz. The mice were studied for a total of 12 weeks. Hind-limb recovery was evaluated at weeks 0, 1, 2 and then every 2 weeks by walking-track analysis. Results: Post recovery kinematic showed significantly improved functional sciatic index and foot-base angles at weeks 8, 10 and 12 for both DES and TCES groups. Conclusions: 12 weeks after sciatic nerve axotomy, functional recovery was improved significantly in both DES and TCES groups. Therefore, TCES is as beneficial in promoting nerve regeneration and functional muscle reinnervation as is DES.

Keyphrases: motoneurone, axotomy, nerve injury, electrical stimulation, nerve repair, axonal regeneration, functional recuperation, motoneuron, kinematics
Expression des histones déméthylases dans les cellules hématopoïétiques humaines et les leucémies aiguës

The importance of chromatin modifiers in regulation of hematopoiesis and hematologic malignancies is illustrated by the Mixed-Lineage Leukemia (MLL) histone methyltransferase, which is essential to maintain hematopoietic stem cells (HSC) and whose corresponding gene, MLL, is rearranged in over 70% of infant leukemia. The recently discovered histone demethylases (HDM) are also involved in HSC fate and in hematologic malignancies. The purpose of this project is to study the expression of HDM in normal and leukemic hematopoietic cells to identify potential regulators of their fate. We performed a comprehensive gene expression profile of HDM by qRTPCR and transcriptome sequencing (RNA-seq) in cord blood cells (CD34+ cells enriched in HSC and differentiated cells) and in acute myeloid leukemia (AML) cells with MLL rearrangement. Both techniques revealed differential expression of HDM between these cell populations. KDM5B and KDM1A are overexpressed in CD34+ cells compared to differentiated cells. Moreover, KDM4A and PADI2 are overexpressed in leukemic cells compared to normal cells. Functional studies will determine whether modulation of these candidates can be used in HSC expansion strategies or as anti-leukemic drug target. We have also developed and validated a new diagnostic test to detect mutations of GATA2, a gene encoding a key transcription factor involved in hematopoiesis and in AML. This work highlights the importance of nuclear factors in the regulation of normal and leukemic hematopoiesis.

Keyphrases: GATA2, Epigenetic, Histone demethylases, Hematopoietic stem cells, Self-renewal, Cord blood, Myeloid leukemia, MonoMAC syndrome
Modulation de l'expression de Sirt-1 induite par l'endothéline-1 dans les cellules musculaires lisses vasculaires

Cardiovascular diseases (CVD) are associated with several vascular dysfunctions such as heart failure and hypertension. These phenomena cause increased synthesis of endothelin-1 (ET-1), a neuropeptide, synthesized by endothelial cells which has vasoconstrictor action on vascular smooth muscle cells (VSMC). Overexpression of this vasopeptide leads eventually to hypertension (HTA). This usually happen after atherosclerosis or restenosis, leading to proliferation and migration of VSMC from media to intima.  It was shown that during atherosclerosis, the protein sirtuin-1 (Sirt-1), a member of protein histone deacetylases (HDAC), has an anti-atherosclerotic effect due to its ability to diminish proliferation and migration of VSMC. It has also been observed that during hypertension, Sirt-1 was poorly expressed in VSMC. Its role in vascular pathophysiology remains sparsely studied, therefore it’s essential to explore it. In the present study we investigated the expression of Sirt-1 in VSMC isolated from the ascending aorta of rats, in response to ET-1 stimulation. We observed that Sirt-1 expression decreases after 1 hour of stimulation by ET-1 via ETA receptors. In summary, these results suggest that the ability of ET-1 to attenuate Sirt-1 expression in VSMC, may be a potential mechanism for promoting CVD.

Keyphrases: Hypertension artérielle, Cardiovascular diseases, Endothelin-1, Vascular smooth muscle cell, Hypertension, histone deacetylase, Sirtuin-1
L'impact de l'infiltration lymphocytaire sur le pronostic de l'adénocarcinome du pancréas

The main objective of this project was to determine the prognostic significance of T-lymphocytes densities in pancreatic adenocarcinoma.  Using tissue microarrays, CD3+, CD4+, CD8+, CD45RO+, and FOXP3 T-cells were quantified by immunohistochemistry in the intratumoral (T) and peritumoral (PT) compartments of 111 specimens.  An immune score (IS) based on T CD4+ and PT CD8+ counts and T/PT CD3+ ratio grouped patients into IS---, IS+/- and IS+++ if none, 1 or 2, or all 3 of the favorable immune features were present, respectively. Patients have different overall survival (OS) depending on their IS status. Patients IS--- have a median OS of 14 months and of 19 months and 29 months for those IS+/- and IS+++ respectively (log-rank p=0.01). By multivariate analysis, IS was independently associated with survival as were the histological grade and adjuvant therapy.  An immune score that combines specific T-cell location and density may have prognostic value in patients with resected pancreatic adenocarcinoma, independently from current pathologic features.

Keyphrases: lymphocytes infiltrants, tumour-infiltrating lymphocytes, T-lymphocytes, pancreatic neoplasms, immunotherapy, immune score, prognosis, tumour antigen
Approches thérapeutiques de la carcinose péritonéale d’origine appendiculaire récidivante

Background: Additional treatment in patients presenting recurrent peritoneal carcinomatosis (PC) has been much overlooked in the literature. The aim of this study is to assess the effects of additional treatment in patients with recurrent disease despite a first CRS with HIPEC. Methods: Since 2003, data from all patients with PC arising from the appendix treated in our center were prospectively collected. Treatment of primary disease consisted in CRS followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin. When recurrent disease occurred, second CRS followed by HIPEC with mitomycin C were offered to patients meeting some selection criteria. Results: A total of 58 patients underwent CRS followed by HIPEC with oxaliplatin. During follow-up, 22 patients developed recurrent disease (39%). Peritoneum was the most common site of treatment failure. In the entire series, histologic grades and completeness of CRS were significant independent predictors of disease-free survival. Among patients with recurrent disease (n=22), eight patients underwent second CRS followed by HIPEC with mitomycin C, one patient received a CRS alone, and thirteen patients had unresectable disease. Mean overall survival for patients who received a second treatment (n=8) was 28 months. Morbidity and mortality rates following second CRS and HIPEC were 25% and 0%, respectively. Conclusions: CRS followed by HIPEC remains a possible intervention in patients with recurrent disease, but some selection criteria should be applied in order to maximise survival and minimise morbidity and mortality of this approach.

Keyphrases: Peritoneal neoplasms, Appendiceal neoplasms, Hyperthermic intraperitoneal chemotherapy, Oxaliplatin, Recurrent disease
Syndrome du QT long: étude clinique à l’Institut Cardiologique de Montréal et recherche de nouvelles variantes causales par séquençage à haut débit

Long QT syndrome (LQTS) is a channelopathy, causing syncope and sudden death. Genetic testing of individuals identifies genetic variants in up to 50-70% of cases, suggesting that additional genes may be involved. We have identified 50 patients with a diagnosis of LQTS at MHI, and recruited 12 patients reported negative for clinical testing of mutations in LQTS for a whole-exome next generation DNA sequencing approach in order to identify new variants and candidate genes. We have developed a stepwise analytic approach that focuses on (1) the known LQTS genes, (2) the genes in loci identified in genome-wide association studies of QT-interval, and (3) the loci showing variants across multiple patients. Our approach identified new variants in (1) KCNJ2, ANK2 and AKAP9, and (2) in NOS1AP. We identify 2 patients with a very similar phenotype with a homozygous variant in TECRL, an novel candidate gene with an unknown role in LQTS.

Keyphrases: Long QT, Sequencing, Phenotype, Variants, Genotype
Le remplacement valvulaire aortique chez le jeune adulte

In young adults, the ideal aortic valve substitute remains unknown. Mechanical prostheses are durable. However, their use requires lifelong anticoagulation. Recent reports suggest an excess in long-term mortality in patients following mechanical aortic valve replacement (AVR). Furthermore, many patients are of childbearing age when the surgery is indicated. Pregnancy in patients with mechanical prostheses is associated with an increased thromboembolic event. Those are better prevented by warfarin comparatively to heparin. However, warfarin is associated with fetal malformations. Bioprostheses avoid anticoagulation. Nevertheless, young adults experience a more rapid prosthetic valve deterioration, which exposes young patients to a significantly higher risk of early reoperation. The aim of this thesis is to assess long term outcomes following AVR in young adults. For this project, two different studies were completed. The first study examines the long-term survival and complications following isolated AVR in young adults. Long-term survival was lower than what was expected in a sex- and gender-matched Quebec general population. There was a low but constant occurrence of valve dysfunction and reintervention after AVR in this population. The goal of the second study was to assess cardiac, maternal and fetal complications during and after pregnancy in women with mechanical or biological AVR. Based on our results, we concluded that pregnancies in those women carried a significant risk of cardiac and maternal adverse outcomes, particularly with mechanical prostheses.

Keyphrases: valve, adult, aortic, replacement, mechanical, prosthesis, young, cardiac, surgery
L'effet de l'entrainement avec le ballon d'exercice pendant la grossesse sur l'accouchement

Abstract Introduction: The training with a birth ball during pregnancy has positive effects on labor. However, the dose-response to achieve a reduction in the length of phases 1 (dilatation-active phase) and 2 (expulsion) of labor, a decrease of epidurals and cesarean sections is unknown. Purpose: The purpose of the study was to determine if an association is present between the level of training with a birth ball during pregnancy and labor outcomes in natural settings. Methods: This quasi-experimental study was conducted with a convenient sample composed of 32 pregnant women who participated in one to 28 supervised exercise classes during the pregnancy (the Ballon Forme program), with the option of performing additional birth ball exercises at home. A questionnaire and a logbook were completed by the participants, with the assistance of a nurse for the medical information. Results: A long training time is significantly associated with a shorter labor duration, and this remained the case when the total labor time (r= -0.408; p= 0.031) or specific stages of labor were considered [phase 1 (r= -0.372; p= 0.043, and phase 2 (r= -0.415; p= 0.028]. Longer training times is more specifically linked to a reduced second phase in women who gave birth for the first time, and high levels of class attendance is more associated with faster deliveries than home exercises. No adverse effects on labor parameters or the baby’s health were noted with higher amounts of training. In fact, a very low number of cesarean sections (6%), epidurals (47%) and instrumental deliveries (forceps or vacuum: 13%) characterize this sample of trained women. Conclusion: Exercise with a birth ball is a promising way for women to exercise during pregnancy, and a higher involvement in the practice led to faster deliveries and without any complications for the baby. The implementation of this program could help to significantly reduce health costs in Quebec by promoting natural childbirth. Future research should examine in depth this specific exercise modality for pregnant women.

Keyphrases: Training, Exercise, Birth ball, Pregnancy, Labor, Swiss ball, Birthing ball, Labour