NCube/papyrus huggingface dataset:
Études génétiques de familles récessives d’ataxies et de paraplégies spastiques

Over the past years, genetics has undergone a phenomenal growth due to the development of new sequencing technologies. Indeed, whole exome sequencing in families led to the identification of new genes involved in many diseases. Neurosciences were also able to benefit from these discoveries, where several new genes have been identified in several neurological diseases. This thesis will covered two different movement disorders for which we have used traditional sequencing technology, in this case by Sanger sequencing, combined with whole exome sequencing for new gene discovery. The first movement disorder that is described is ataxia, which will be focused on autosomal recessive mode of inheritance. The first chapter will relate the new mutations found in French-Canadian with ataxia of Beauce. We will also discuss new mutations found in two other populations, confirming the involvement of the gene SYNE1 in worldwide cases of cerebellar ataxia. The second chapter will demonstrate that it is desirable to use whole exome sequencing in order to make a clinical diagnosis. Indeed, it has been possible to find the genetic cause for a family with two members with congenital cerebellar atrophy, which the predominant symptom is ataxia. Exome sequencing allowed the identification of mutations in the PMM2 gene, already known to cause a syndrome leading to glycosylation deficit of glycoprotein. For the second part, we will cover another movement disorder call hereditary spastic paraplegia (HSP). Chapter 3 relates the mutations found in the CYP7B1 gene in our cohort of HSP patients.

Keyphrases: Exome, Mutations, Ataxia, Spastic Paraplegia, Sequencing, Recessive
La néphrectomie partielle chez les patients atteints du cancer du rein de stade T1b

Objectives: To examine utilization rates of partial nephrectomy relative to radical nephrectomy for T1b renal cell carcinoma in contemporary years, to identify sociodemographic and disease characteristics associated with partial nephrectomy use, and to compare effectiveness of partial vs. radical nephrectomy with respect to cancer control outcomes. Materials and Methods: Using the Surveillance, Epidemiology, and End results database, 16,333 patients treated with partial or radical nephrectomy for T1bN0M0 renal cell carcinoma between 1988 and 2008 were identified. Logistic regression models were performed to identify determinants of partial nephrectomy. Subsequently, cumulative incidence rates of cancer-specific and other-cause mortality between partial and radical nephrectomy were assessed, within the matched cohort. Finally, we relied on competing-risks regression analyses for prediction of cancer-specific mortality, after adjusting for other-cause mortality, and vice-versa. Results: The utilization rate of partial nephrectomy increased from 1.2% in 1988 to 15.9% in 2008 (P<0.001). Younger individuals, smaller tumors, persons of black race, as well as men were more likely to be treated with partial nephrectomy in the current cohort (all P≤0.002). In the post-propensity cohort, the 5- and 10-year cancer-specific mortality rates were 4.4 and 6.1% for partial vs. 6.0 and 10.4% for radical nephrectomy, respectively (P=0.03). Following adjustment for other covariates, competing-risks regression analyses showed that nephrectomy type was not statistically significantly associated with cancer-specific mortality, even after adjusting for other-cause mortality (hazard ratio: 0.89, P=0.5). Conclusions: Despite a comparable cancer control outcome, consideration of partial over radical nephrectomy in T1b renal cell carcinoma individuals remains conservative in recent years.

Keyphrases: T1b, Competing-risk analyses, partial nephrectomy, renal cell carcinoma
Découverte de cellules souches potentielles de l’épithélium thymique

The thymus undergoes a rapid degeneration with age termed thymic involution that causes a loss of function of the thymus with age. To this day, mechanisms of thymic maintenance are still unknown. This is why we aimed to identify thymic epithelial stem cells. Since stem cells are quiescent in many tissues in adults, our main objectives were to determine whether the thymic epithelium contains quiescent cells and study the proliferation kinetics of thymic epithelial cells in neonatal and adult mice. To this end, we used the transgenic mouse model H2B-GFP Tet-On, a label-retaining assay allowing us to identify cells that have not divided for a prolonged period of time, which are called label-retaining cells (LRC). First, we showed that in the adult thymus, females’ thymic epithelial cells (TECs) proliferated more actively than males’ TECs. We observed three main differences between neonatal and adult thymi: (1) cTECs and mTECs have similar proliferation rates in young, but mTECs cycled more actively in adult mice; (2) neonatal TECs have a higher turnover rate than adult’s TECs, and (3) we were able to detect LRC in adult mice, but not in neonatal mice. These LRC are contained in the cTEC compartment and express very low levels of senescence-associated proteins and show a high expression of genes important for thymic development and. These results show that the LRC identified in adult thymi are not senescent cells and therefore might represent the elusive thymic progenitor cells responsible for thymic maintenance and regeneration in adult mice.

Keyphrases: Label-retaining assay, Thymic epithelial cells, Thymic involution, Stem cells, Thymic development
Caractérisation du rôle et des mécanismes d’action des gènes Hoxa dans l’hématopoïèse adulte

In humans, a large percentage of myeloid and lymphoid leukemias exhibit aberrant Homeobox (Hox) genes expression, predominantly Hoxa genes. This aberrant expression is known to be caused by either translocations involving Hox genes or indirect activation of Hox genes. In addition, evidence now indicates a critical role for Hox genes in the initiation of leukemias. Clearly, understanding how Hox genes function in normal hematopoiesis is prerequisite to elucidate their involvement in leukemogenesis and this may eventually lead to new treatments for this disease. Attempts to determine the precise role(s) of Hox genes in normal hematopoiesis using single gene loss of function mutants have shown little success due to functional complementation by the remaining Hox genes. We previously showed that the Hoxa genes are much higher expressed in enriched hematopoietic stem cell (HSC) populations than the other members of the Hox gene family. Moreover, Hoxb cluster genes were found to be dispensable for HSCs long-term repopulation of irradiated mice. Thus, we hypothesize that Hoxa genes are critical for normal adult hematopoiesis. We have used a multi-gene knockout (KO for the entire Hoxa cluster) approach to thoroughly evaluate this issue.  In this thesis, we showed that HSC, primitive progenitors and B cell progenitors are particularly sensitive to the levels of Hoxa gene expression. Furthermore, a lower survival and a premature differentiation account for the loss HSC Hoxa-/- in bone marrow. Differential expression profiling by RNASeq revealed that Hoxa genes are capable of regulating a broad array of genes involved in various biological processes. Indeed, Hoxa genes regulate the expression of several genes coding for cytokine receptors. Furthermore, Hoxa genes modulate the expression of genes implicated in the regulation and formation of the niche architecture. The expression of several adhesion molecules is also modulated by the Hoxa genes, which can affect the relationship of HSC with the hematopoietic niche. Through their action on several biological processes such as apoptosis, cell cycle and niche interactions, Hoxa genes are necessary for maintenance of HSC and progenitors. Taken together, these results demonstrate that Hoxa genes are important regulators of adult hematopoiesis.

Keyphrases: Hox genes, hematopoiesis, hematopoietic stem cells, transcription factors
Évaluation clinique et biomécanique de deux différents types d’arthroplastie totale de genou

Various implants of total knee arthroplasty (TKA) are used in clinical practice and each presents specific biomechanical characteristics. No implant managed this day to reproduce perfectly the biomechanics of the natural knee. The objectives of this study are to compare the clinical and tridimensional (3D) biomechanical data of two different designs of TKA on the same patients and to compare the resulting 3D biomechanical data with those of asymptomatic knees. A cohort of fifteen patients with a traditional implant in one knee and an implant of new generation allowing a pivot in the contralateral knee was studied. The control group was composed of thirty-five asymptomatic knees. Assessment of 3D knee kinematics analysis was realized with the KneeKG (Emovi Inc. Canada) during treadmill gait. Clinical evaluation included range of motion as well as questionnaires of joint perception, KOOS, Womac and SF-12. Results showed some statistically significant differences in knee 3D kinematics of both TKAs in sagittal and frontal planes while comparison between TKAs and asymptomatic knees revealed several significant differences in all three planes. Clinical scores of both TKAs did not have significant difference. In our cohort of patients, TKA implant design had few measurable influences on kinematics during gait and on clinical results. TKA with these implants did not reproduce natural knee kinematics during gait. Significant research and development in new TKA designs are needed to improve clinical scores and reproduce natural knee kinematics.

Keyphrases: KneeKG, Total knee arthroplasty, Kinematics, KneeKG, Gait analysis, Biomechanics
Élaboration de critères de design pour un outil de communication médecin-patient

Today’s medical system is using an increasing number of information technologies to help healthcare professionals in their daily practice. Commonly known as HIT (Health Information Technologies), they create new forms of doctor-patient interaction and complexify the therapeutic approach called “patient centered approach”. Their use promises to improve the efficiency of the healthcare system and the overall satisfaction of the patient by improving his understanding of his illness, yet they can also become communication barriers during a consultation and even a source of conflict when used outside a clinical context. This research project aims at studying the design criteria for a Health Information tool that can help improve the doctor-patient relationship. The study uses a user-centered approach and therefore, focuses on understanding the needs and expectations of both doctors and patients. The study of the theoretical and "on the field" therapeutic approach shows that the pressurized time of the consultation, the many communication barriers and the low level of information remembered by patients are problems that can be solved by a HIT. A virtual vulgarization tool that uses multimedia such as 3D animations, 3D models and drawings can considerably help the doctor-patient relationship.

Keyphrases: TIS, eHealth, HIT, user centered design, doctor-patient relationship, doctor-patient communication, eHealth
Coordonner les transports et l'urbanisme dans un contexte urbain concret : le TOD comme instrument d'action publique, le cas de Sainte-Therese, QC

The concept of transit-oriented development (TOD) is usually defined as a reproducible combination of certain physical and spacial characteristics. This definition does not however allow for a full understanding of how this general concept can be relevant for coordinating land-use and transportation in a given urban context. Our research seeks to address this issue and proposes to study TOD as an urban policy instrument, the choice, the production and the usage of which is defined by the goals, the resources and the constraints in a particular territorial context. This exploratory research is based on a case study of the TOD implementation in Sainte-Therese (Quebec). In order to understand how the different interests at play were aligned, and what resulted thereof, we consulted written sources and conducted semi-directed interviews with people who were actively involved in the TOD implementation. The results of our study confirm the relevance of this analytical approach to study TOD. One of the virtues of TOD as a policy instrument is that it allows to aggregate various, even potentially contradictory, interests at play. However, it does not offer a universally applicable formula: the TOD implementation is to a great extent conducted incrementally, according to local conditions. This process does not necessarily require the invention of a new public policy framework and can largely be done with the help of existing tools. Nevertheless, in order to fully make use of those tools in the course of TOD implementation, the organizational leadership in land-use and transportation agencies is crucial.

Keyphrases: TOD, Transit-oriented development, Coordination urbanisme-transport, Land-use and transportation coordination, Policy instrument, Montreal metropolitan region
Fiabilité et changement minimal détectable de mesures obtenues à partir d'images enregistrées par ultrasonographie afin de caractériser l'intégrité du tendon d'Achille

Background: Quantifying the integrity of the Achilles tendon (AT) represents a challenge in rehabilitation. The adoption of quantitative measurements of the AT, extracted from an ultrasound image (QUS) could remedy this shortcoming. Objectives: 1) To assess the test-retest reliability and accuracy of QUS measurements of the AT; 2) To determine the best protocol of QUS measurements to use in clinical practice. Methods: A total of 23 ATs with symptoms of mid-portion Achilles tendinopathy and 63 asymptomatic ATs were evaluated. For each AT, 8 images were recorded (2visits* 2 evaluators* 2 images). Different types of QUS measurements were taken: geometric (thickness, width, area), derived from a gray-level histogram and derived from a co-occurrence marix. A generalizability study quantified the reliability and accuracy of each QUS measurement whereas a decision study highlighted the best protocols for measuring use. Results: The geometric measurements showed excellent reliability and accuracy. The measures derived from the gray-level histogram showed poor reliability and accuracy. The measurements derived from a co-occurrence matrix have shown moderate to excellent reliability and a variable precision. In clinical practice, it is recommended averaging the results of three images collected by an assessor during a single visit. Conclusions: The use of geometric QUS measures allows to quantify the integrity of the AT in clinical practice and in research. Further studies on QUS measurements derived from a matrix of co-occurrence are needed.

Keyphrases: Mesure quantitative, Achilles tendon, Musculoskeletal, Physiotherapy, Precision, Quantitative, Measurement, Rehabilitation, Reliability, Tendinopathy, Ultrasound
Différentes approches dans le traitement de la dépression post-infarctus du myocarde : effet de la desvenlafaxine et des probiotiques

Several studies have highlighted that disruption of the cardiovascular functions is a major risk of developing depressive disorder in humans. 15-30% of the general population develops major depression within 6 to 8 months after a myocardial infarction. To better understand the underlying mechanisms and identify therapeutic pathways, we use a rat model of post-myocardial infarction developed in our laboratory.  We have observed in these animals an increased apoptosis in the limbic system, which starts in the first minutes following reperfusion and peaks 3 days post-reperfusion. As a result, a depression-like phenotype and learning impairments appear 2 weeks after the myocardial infarction, which will persist up to 4 months after the infarct. We hypothesize that the observed apoptosis and the resulting depressive-like behavior are mediated by the inflammatory response induced after myocardial infarction. Indeed, depression-like behavior is prevented by the administration of an inhibitor of the pro-inflammatory cytokines, (pentoxifillyne, celecoxib), as well as by probiotics. In this thesis, we show that desvenlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI) prevents death by apoptosis in the limbic system. Desvenlafaxine also helps to improve the depressive-like behavior in these rats as well as the learning impairments, even if the treatment is administered during the first 2 weeks post-reperfusion. Finally, we have discovered that vagotomy prevents the probiotics effect over the apoptosis appearing after myocardial infarction, highlighting the importance of the vagus nerve in the beneficial effects of probiotics.  In conclusion, several interventions are effective in limiting the consequences of myocardial infarction on the limbic system and also key to prevent the apparition of secondary psychological disorders.

Keyphrases: Desvenlafaxine, Rat, Cytokines, Myocardial infarction, Probiotics, Apoptosis, Vagus nerve, Limbic system, Learning disorders
Age-related eye disease and cognitive function

Objective: To examine the extent of cognitive impairment in patients with age-related macular degeneration (AMD), glaucoma, or Fuchs corneal dystrophy as compared to a control group of older adults with good vision. Design: Cross-sectional hospital-based study. Participants: 420 people (113 with AMD, 66 with Fuchs, 130 with glaucoma, and 111 controls). Methods: Patients were recruited from the ophthalmology clinic of Maisonneuve-Rosemont Hospital (Montreal, Canada) from September 2009 until September 2013. Patients with AMD and Fuchs had to have visual acuity in the better eye of worse than 20/40 while patients with glaucoma had to have visual field deficit in their worse eye of at least -4dB. Control patients who had normal visual acuity and visual field were recruited from the same clinic. Cognitive status was measured using the Mini-Mental State Exam (MMSE) Blind Version. Visual acuity, contrast sensitivity, and visual field were assessed, and the medical record was reviewed. Linear regression was used. Main Outcome Measures: Mini-Mental State Exam (MMSE) Blind Version Results: The three eye diseases were associated with of cognitive impairment. Compared to controls, patients with age-related eye disease had lower MMSE Blind scores (p < 0.05). Scores were between 0.7-0.8 units lower than the control group. Better education was associated with better cognition (p < 0.001). Conclusions: Our results suggest that eye diseases are associated with cognitive impairment. It is important to further explore the impact of eye disease on cognitive function in this population in order to develop interventions that would help affected older adults maintaintheir independence.

Keyphrases: Cognition, Eye disease, Aging
Effets électrophysiologiques d’une thérapie cognitivo-comportementale pour traiter le syndrome de Gilles de la Tourette et le trouble de tics chroniques

Gilles de la Tourette syndrome and chronic tic disorder are two neuropsychiatric condition involving motor and/or phonic tics. In the DSM, these two conditions are characterized as “tic disorders”. Patients with such diagnoses face numerous comorbidities, and also show multiple neuropsychological impairments, especially concerning inhibition and motor processing. Tic symptoms, as well as general condition, can be improved with a cognitive-behavioural therapy (CBT). To this end, we recorded, during a stimulus-response compatibility task, event-related potentials and lateralized readiness potentials in 20 patients with tic disorder and 20 healthy controls. Patients and controls were paired on age, sex and hand dominance. Our result revealed a delay in stimulus-locked lateralized readiness potential (LRP) onset latency, higher response-locked LRP peak amplitude and a frontal overactivation related to stimulus inhibition in GTS and CTD patients. Following CBT, stimulus-locked LRP onset latency and response-locked LRP peak amplitude were normalized, but the frontal overactivation related to inhibition processing remained unchanged. These results suggest that CBT induces a modification of pre-motor processes such as response selection and preparation, as well as motor processes like response execution, but does not affect cortical activation related to stimulus inhibition. Since we found a reduction in tic symptoms, as well as a normalization of stimulus-locked LRP onset latency and response-locked LRP peak amplitude, and because LRPs are partly generated by the supplementary motor area, we suggest that CBT leads to a modification of this structure’s functioning.

Keyphrases: Tics, Tourette syndrome, Tics, Event-related potentials, Lateralized readiness potentials, Electrophysiology, Cognitive-behavioural therapy
Abdominal aortic aneurysm follow-up after endovascular repair in a canine model with non-invasive vascular elastography

Surgical treatment of abdominal aortic aneurysms is increasingly being replaced by EVAR using SGs. However, the efficacy of this less invasive approach is jeopardized by the incidence of persistent flow within the aneurysm, called endoleaks leading to aneurysm rupture if not properly detected. Hence, a life-long surveillance by computed tomography (CT) angiography on an annual basis is increasing the cost of EVAR, exposing the patient to ionizing radiation and nephrotoxic contrast agent.  The mechanism of aneurysm rupture secondary to endoleak is related to a pressurization of the aneurysm sac close to the systemic pressure. There is a relation between sac shrinkage or expansion and sac pressurization. The residual pressurization of AAA will induce sac pulsatility and blood circulation in the sac thus preventing sac thrombosis and aneurysm healing. NIVE using the LSME may become a complementary follow-up imaging technique for EVAR. NIVE has the capability of providing important information on the thrombus organization within the aneurysm sac and on the detection of endoleaks.  The characterization of the thrombus organization was not possible in a previous NIVE study. A limitation was the absence of CT examinations as gold standard for endoleak diagnosis. In the current study, we aimed to apply and optimize NIVE of AAA after EVAR with SG in a canine model to detect endoleaks and characterize thrombus organization.  SGs were implanted in a group of 18 dogs with an aneurysm created in the abdominal aorta. Type I endoleak was created in 4 aneurysms, type II in 13 aneurysms and no endoleak in 1 aneurysm. DUS and NIVE examinations were performed at baseline, 1-week, 1-month, 3-month and 6-month follow-up after EVAR. Angiography, CT-scan and macroscopic tissue slides were performed at sacrifice. Strain values were computed using the LSME. Areas of endoleak, solid thrombus (organized) and fresh thrombus (non-organized) were identified and segmented by comparing the results of CT scan and macroscopic tissue slides. Strain values in areas with endoleak, organized and fresh thrombi were compared.  Strain values were significantly different between endoleak and organized or fresh thrombus areas and between organized and fresh thrombus areas. All endoleaks were clearly characterized on elastography examinations. No correlation was found between strain values and type of endoleak, sac pressure, endoleak size and aneurysm size.

Keyphrases: Thrombus, Aorta, Abdominal aortic aneurysm, Endovascular repair, Computed tomography, Endoleak, Thrombus