NCube/papyrus huggingface dataset:
The effect of interference on reactivation of spatial memories in reconsolidation model by using an innovative experimental paradigm in healthy young adults at the behavioral level

Declarative memory is defined as our capacity to acquire facts and events that are subject to conscious recollection. After the encoding phase, new memories undergo offline transformations, which allow the initially labile traces to become fixed into the physical structure of the brain; a process called consolidation. There is also accumulating evidence that once a consolidated memory is reactivated or retrieved, the latter goes through a reconsolidation process during which it can be degraded, maintained or enhanced. In the present study, we sought to answer the following question: Are retrieved consolidated traces susceptible to disruption by the same type of information? Method: We developed a task based on work by Sonni et al. (Sonni and Spencer 2015), in which subjects were required to learn the location of 36 everyday objects images located on a computer screen. 40 healthy subjects (25.03 ± 3.66) participated in this study. Group 1: Interference (20 subjects); Group 2: control (20 subjects). Results: We found that the administration of the matrix B after recall of the first matrix (Group 1) interfered with reconsolidation of the memory, and thus significantly increase the amount of forgetting seen in the retest session on Day 3. In contrast we could not find any interference effect in the control group. Our results confirm the reconsolidation hypothesis for declarative memory, but further work is needed to identify whether the neural and neurophysiological substrates mediating reconsolidation are the same or different from those involved during consolidation.

Keyphrases: Reconsolidation, Recognition, Declarative memory, Interference
Génération de lignées de poissons-zèbres par génie génétique dans le cadre de l'étude du gène C9orf72

An intronic mutation in the gene C9orf72 is the most prevailing cause of Amyotrophic lateral sclerosis (ALS), an adult onset neurodegenerative disease of the motoneurons. Despite this, the function of C9orf72 remains uncertain. As animal models are an excellent way to study gene function and expression in vivo in complex systems, by using the CRISPR/Cas9 system we attempted to generate 3 lines of zebrafishes for which 12xhistidines or eGFP tags were inserted near either the N or C terminal of C9orf72. Surprisingly, these modifications were ill tolerated during the development, preventing us from obtaining F0 specimens able to pass on the inserted tag for any of our lines. To study the effects of a persistent knock-out of C9orf72 in the zebrafish, a line with deletions near the N-terminal, resulting in a functional knock-out of C9orf72, was obtained from the fishes injected for the 12xHistidine insertion. Preliminary results indicate a higher mortality rate and decrease mobility phenotypes. Additionally, two transgenic zebrafish lines expressing human C9orf72 alone or with eGFP were generated, using Tol2 in order to study C9orf72 localisation and the effect of its overexpression namely on morphology, development and the central nervous system. These lines, once validated and characterised will open new avenues to determine the role and subcellular localization of C9orf72, as well as for modeling ALS. Thus, it appears that the loss of an allele or haploinsufficiency of the C9orf72 gene is ill tolerated, but that transgenesis, by addition of a third allele, may allow for in vivo study of C9orf72.

Keyphrases: knock-out, CRISPR/Cas9, C9orf72, Amyotrophic lateral sclerosis, ALS, Zebrafish, knockout, Tol2
Étude de l’inflammation induite lors d’une hémorragie sous arachnoïdienne

Subarachnoid hemorrhage (SAH) is a devastating disease. Recently, neuroinflammation has been proposed as a key determinant of patient outcomes. However, more information is needed concerning cellular and molecular mechanisms induced by SAH and how this could affect patients’ outcomes. We propose the hypothesis that SAH induces inflammation and that this inflammation is associated with brain cell damage and possible worse patient outcomes. For the experimental component of this study, a blood injection model in the prechiasmatic cistern was used to induce SAH and study the degree of neuronal cell death or damage and the inflammatory burden in mice using immunofluorescence staining (NeuN, Fluoro-jade, F4/80), TUNEL and MPO. The clinical component studied the degree of systemic leukocytosis in two standard acute treatment groups after SAH—surgical clipping versus endovascular embolization—to evaluate if leukocytosis affects outcomes between the two groups. The study showed that there is evidence of neuronal damage and apoptosis in SAH mice at days 5 and 7. This could be due to inflammation by microglia/macrophages and/or neutrophils. The clinical statistical analysis demonstrated that leukocytosis was present initially after SAH, which peaked after the surgical intervention, but did not affect long-term clinical outcomes.  In conclusion, evidence of inflammation in the mouse model was confirmed by neuronal damage and the presence of inflammatory cell activation. Also, in patients, systemic leukocytosis is more important after surgery and could be an important player in the prognosis of SAH, but other inflammatory and clinical parameters should be considered.

Keyphrases: Inflammation, Subarachnoid hemorrhage (SAH), Leukocytosis
Implication des ROS dans la régulation des dynamiques calciques locales de l’endothélium

The endothelium is essential for vascular homeostasis through its important role in the regulation of vascular tone. This regulation is exerted via endothelial intracellular calcium dynamics. Disturbance in endothelial calcium homeostasis leads to endothelial dysfunction which is associated with several cardiovascular pathologies, including hypertension and atherosclerosis. Therefore, it is essential to strengthen our understanding of endothelial calcium dynamics involved in the regulation of vascular tone. In arteries, communication between endothelial cells and smooth muscle cells is possible via fenestrations through the internal elastic lamina. The structure allowing this communication is called myoendothelial projection (MEP). The calcium pulsar is an endothelial calcium transient that is localized within these MEPs. Pulsars have been characterized and results from the spontaneous release of calcium from the endoplasmic reticulum upon the activation of inositol 1,4,5-trisphosphate receptors (IP3R). Electron microscopy images has shown the presence of mitochondria at the cleft of MEPs. Mitochondria have an important role in the calcium homeostasis and constitute an important intracellular source of calcium. In addition, they are involved in cellular homeostasis with their production of reactive oxygen species (ROS). IP3R’s sensitivity to ROS imply that mitochondrial ROS (mROS) could be part of a precise and local regulation mechanism for pulsars by modulating IP3Rs activity. The main objective of our study was to evaluate the impact of mROS on endothelial calcium dynamics. Our study has shown that mROS chelation, with MitoTEMPO, significantly reduced pulsar’s frequency. Furthermore, our work shows that an inhibitor of the mitochondria electron transport chain (antimycin A) stimulates mROS production and therfore significantly increases the frequency of calcium dynamics. Our work highlighted the link between mROS and calcium pulsars, that is mitochondrial ROS are a pulsar’s regulation mechanism. Regulation of calcium pulsars and endothelial calcium homeostasis is essential for the maintenance of endothelial functions. Our results unveils a potential new avenue in the development of new therapies in the prevention of endothelial dysfunction and, ultimately, of cardiovascular diseases, such as hypertension associated with endothelial dysfunction.

Keyphrases: Calcium, Endothelium, Oxidative stress, Artery, Mitochondria, Reactive oxygen species (ROS)
Développement d’un système d’imagerie haute vitesse pour la surveillance en continue de cultures cardiaques

Current scientific knowledge allows the differentiation of stem cells into cardiac cells. However, the protocols that allow this process have variable yields, which results in cultures with variable characteristics. In turn, this limits the potential to generate replacement tissues, such as the biopacemaker. In this context, a differentiation protocol for mouse embryonic stem cell was established. To optimise these cultures, a monitoring tool combined with a feedback approach was developed. The working principle of this tool relies on the cellular pattern variations during contraction, captured by digital lenseless imaging under partially coherent illumination. The system allows cell culture directly on the device, which can be placed into an incubator. It also allows the control of substrate rigidity and of an electrical stimulation system. It is possible to capture images at speeds up to 300 frames per seconds and high-resolution images at 4 megapixels. These images in turn inform regarding the spatial organisation of the tissue as well as its contractile properties, from a characteristic signal obtained from the high-speed videos. The device has been validated with three different cardiomyocyte types: neonatal rat and two lines of human cardiomyocytes derives from induced pluripotent stem cell (hIPSc). The developed system thus allows the observation, the evaluation of contractile properties and the monitoring of cardiomyocyte cultures, which make it a promising tool for optimisation in cardiac tissue engineering.

Keyphrases: Imagerie continue, Real-time Imaging, Lenseless imaging, Cardiac Tissue Engineering
High frequency CMUT for continuous monitoring of red blood cells aggregation

Research has demonstrated that Capacitive Micro machined Ultrasonic Transducer (CMUT) can be an alternative to piezoelectric transducers in different domains including medical ultrasound imaging. Previous work showed advantages of CMUT in terms of high frequency production, sensitivity, its compatibility with complementary metal–oxide–semiconductor technology and its low cost of fabrication. This work will show preliminary work toward fabricating an ultrasound transducer using CMUTs to continuously measure Red Blood Cells aggregation. CMUTs cells were designed and simulated to obtain specific resonant frequencies and dimension that fulfill that purpose using finite element modeling with COMSOL Multiphysics. Ultrasound simulations (Field II software) were used to characterize the emitted and received US beams to design the cells geometrical distribution.  Fabrication was done using multilayered photolithography and depositions. Eight masks were designed for each deposition layer. The masks were designed to have four groups of CMUTs, one emitting and receiving at 40MHz, a second emitting at 30 MHz and receiving at 40 MHz, a third one emitting at 20 MHz and receiving at 30 MHz, and a last one emitting at 10 MHz and receiving at 30 MHz. The frequency changes with the radius of each CMUT cell but the thickness dimensions are the same for all the cells, the membranes and insulation layers thicknesses are 0.3 µm and the vacuum gap is 0.1 µm. The CMUT arrays were fabricated using sacrificial release layer technology in Polytechnic LMF Lab.

Keyphrases: Capacitive Micro machined Ultrasonic Transducer, Red Blood Cells aggregation, Complementary metal-oxide-semiconductor
L'étude des antimicrobiens comme modulateurs du système de sécrétion de type VI de vibrio cholerae

Vibrio cholerae is a Gamma proteobacterium, colonizing marine aquatic environments, rivers and estuaries. V. cholerae is the etiological agent of cholera, a disease still considered as a major public health problem, which causes severe watery diarrhea. This bacterium has multiple virulence factors, including cholera toxin and toxin coregulated pilus, which are responsible for the typical symptoms of the disease. However, V. cholerae has accessory virulence factors, including the Type VI Secretion System (T6SS). The T6SS is a versatile weapon allowing bacteria to inject effectors into neighboring eukaryotic or prokaryotic cells. T6SS is involved in virulence in humans as well as in interbacterial competition. During its lifestyle, V. cholerae is in close contact with many antimicrobial molecules produced by the host immune system or the gut microbiota but also from aquatic environment where antibiotics are often found in sub-lethal concentrations. These antimicrobial molecules are known to modulate virulence genes of pathogenic bacteria. Thus, our research is based on the hypothesis that low doses of antimicrobials would have the ability to modulate Vibrio cholerae T6SS. In order to determine the impact of antimicrobials on the T6SS, proteomic analyzes by mass spectrometry and by Western blot directed against T6SS proteins have been carried out on bacteria grown with different antimicrobials at sub-lethal concentrations. Then, the bactericidal activities of Vibrio cholerae T6SS has been studied by inter bacterial competition using Escherichia coli as a prey. Finally, we evaluated the ability of T6SS to provide Vibrio cholerae antimicrobial resistance. Our results demonstrated that the presence of antimicrobials during bacterial growth can modulate the abundance of T6SS proteins in the bacterial cells and secreted. However, we were unable to clearly demonstrate that this modulation affected interbacterial competition involving Vibrio cholerae. Finally, we found no evidence that the T6SS is involved in antimicrobial resistance.

Keyphrases: Vibrio cholerae, Peptides antimicrobiens, Modulation, Virulence, Type VI secretion system, Antibiotics, Antimicrobial peptides
Analyse tridimensionnelle du rachis suite à une chirurgie de modulation de croissance chez les patients atteints de scoliose idiopathique de l’adolescent

Adolescent idiopathic scoliosis is a three-dimensional deformation of the spine. It usually develops during the adolescent growth spurt. A surgical intervention is needed to correct severe curves to prevent long-term progression of the deformity. Conventional surgeries are invasive and involves fusion of the spine thus limiting mobility and growth of the spine. Anterior Vertebral Body Growth Modulation (AVBGM) is a fusionless surgery that aims to progressively correct scoliosis by modulating the remaining vertebral growth. The results of three studies on AVBGM are presented in this thesis. In the first study, a three-dimensional analysis of the spine immediately after AVBGM surgery is presented. We conclude that AVBGM offers a significant correction in the coronal and transverse planes immediately post-op. Although the correction was achieved through an anterior compression approach, there was no impact on the kyphosis of the patient. The second study is a threedimensional analysis of the spine at 2-year follow-up to evaluate the impact of growth on the correction of the spine. This study confirmed that the rate of correction is of about 1 ° per instrumented level during the first year and the correction is then maintained at 2 years. Patients were satisfied with their management despite a decrease in function. We also demonstrate a need for a stronger cable as multiple broken cables were suspected. The last study presents a predictive model of the correction obtained by AVBGM based on a machine learning algorithm. We aim to create a tool which will assist orthopedists in their choice of candidates for the ABVGM. We concluded that postoperative reduction of the Cobb angle following AVBGM can be predicted by training a data-driven model, combining preoperative anatomical and patient data with known postoperative outcomes. To conclude, this thesis demonstrates the clear role of AVBGM in the management of idiopathic scoliosis, and also introduces a predictive model which aims to be a future tool in decision-making regarding the selection of candidates for AVBGM.

Keyphrases: Adolescent idiopathic scoliosis, Juvenile idiopathic scoliosis, Anterior Vertebral Body Tethering, Anterior Vertebral Body Growth Modulation, Predictive model
Impact de la prise de statines sur les bienfaits cognitifs associés à l’entraînement de type aérobie chez les aînés

Studies suggest that aerobic training (AER) has benefits on cognition in older adults by improving cardiorespiratory fitness. Other studies underline that statins could limit the physiological benefits of AER. Statins could thus have an effect on the cognitive benefits associated with AER. This hypothesis was tested in 144 sedentary participants (> 60 y.o.; 106 non-users, 38 statins users) who took part in randomized controlled trials. Participants were either part of an AER group (n=75) or a control group (CON) (n=69). Cognition was assessed using the Stroop Test. Analyses were performed on z-score changes from pre to post intervention of Stroop reaction time (RT) and number of errors. Age, Education, BMI, Charlson Comorbidity Index, Sex, Protocol and Handgrip strength were used as covariates. Two-factor ANCOVA (Statins/Non-Statins * AER/CON) was applied on dependent variables. A moderation test was done whenever there was a significant interaction to explore the specific effects of statins on the cognitive changes associated with AER. ANCOVA showed an interaction between intervention and statins on the switching condition RT (F [1, 140] = 5,659, p <0,01). The intervention effect on switching RT was moderated by statins: Intervention effect on switching RT was only significant for participants who were not taking statins (Effect = 0,1678; p <0,01). No interaction was found on the number of errors. Results suggest that statins could limit the cognitive benefits of AER on the Stroop test’s switching condition in some patients. Future studies including a larger number of participants using statins could confirm these results.

Keyphrases: Cognition, Aging, Aerobic Training, Cognitive Aging, Executive Functions, Older adults
Effets d'une manipulation vertébrale sur la sommation temporelle de la douleur

Spinal pain is considered the most important, costly and common chronic disease. Many conservative therapies including spinal manipulation, practised mainly in chiropractic and physiotherapy, demonstrate efficacy like other conventional treatments for back pain. Several studies have examined the effects of the vertebral manipulation on both clinical and experimental pain. However, the mechanism behind hypoalgesia is unknown. One of the hypotheses rose to explain the effectiveness of the spinal manipulation is that it may modulate pain through spinal mechanisms underlying temporal summation and central sensitization, two phenomena involved in the development and maintenance of chronic pain.  The results presented in the first paper allowed to reproduce the transient hypoalgesic effects on temporal summation reported in the literature for experimental chest pain. In the second paper, mechanically assisted vertebral manipulation could not reproduce the results obtained in the first study on pain ratings. Moreover, expected neuromuscular responses to the mechanically assisted vertebral manipulation were obtained while the nociceptive flexion reflex was unaffected, thus suggesting that stimulation modalities and manipulation nature may influence hypoalgesic effects. The two experiments of this dissertation partially explain the mechanism of spinal manipulation on pain and may be relevant for the future experiments studying this therapy mechanism used by a considerable number of participants.

Keyphrases: fibres C, Wind-Up, rachialgie, temporal summation of pain, spinal manipulation, C fibres, mechanically assisted spinal manipulation, spine, vertebral, manual therapy, back pain, chiropractic
Mise en place d'un protocole de remplacement articulaire de la hanche et du genou avec une durée de séjour postopératoire réduite et évaluation des risques et bénéfices pour les patients

Context Total hip replacement (THR) and total knee replacement (TKR) in a fast track surgery setting (less than 24 h) are becoming a new trend in orthopedics. However, the reduced length of stay should not affect the safety and efficiency of the surgical procedure. The aim of this study is to evaluate the implementation of a fast track surgery program. We hypothesized that the THR and TKR fast track protocol would present a similar or inferior complication rate compared to the standard procedure without increasing the cost of care.  Method: We compared an experimental group of 120 patients hospitalized less than 24 hours (21TKR, 93 THR) to a retrospective control group (by medical file revue) of 150 patients hospitalized more than 24 hours (35 TKR, 115 THR). Undesirable events (up to one year after the procedure following the Clavien-Dindo scale), pain, surgical data, length of stay and  quality of life (HOOS, KOOS, SF-36) were compared between groups. The failures to discharge in less than 24 hours were listed and a comparison of hospitalisation cost was described. Results:  Six patients from the experimental group abandoned before their surgery. Among the experimental group, 7 patients failed to discharge in less than 24 hours. The length of stay significantly decreased of 2,8 days for the THR and 3,9 days for the TKR for the experimental group (THR 0,1 versus 2,9 and 4,9 versus 1,0 for the TKR p0,001).  We demonstrated a statistically significant decrease rate of complication graded 1 or 2 per patient in the experimental group (0,76vs 3,00 p0,001). No significant differences were found for higher grade the complications. The estimation of cost reduction brought by the fast track protocol were 1489,34$ per subject for THR and 4206,45$ for TKR. Conclusion: The fast track hip and knee surgery program implantation has permitted a reduction in the length of stay while reducing the rate of postoperative undesirable events and a reduction in costs. The program implementation to a larger group of patients could improve the quality of care and promote substantial economic savings.

Keyphrases: complications, Fast track, TKR, THR, Length of stay, Costs
Développement et validation d’un outil d’évaluation de la compétence chirurgicale pour l’évidement cervical

Objectives: To develop and validate a new tool assessing surgical competency for Otolaryngology – Head & Neck Surgery (OTL-HNS) residents learning neck dissection. Methods: A systematic review of literature was done to list methods developed to assess surgical competency in OTL-HNS. The surgical procedures for which these tools were developed were catalogued. A lack of evaluation tools specific to oncologic procedures in OTLHNS was identified, which includes neck dissection. A modified Delphi method was used to develop a list of steps deemed essential to a group of experts in order to complete a neck dissection. This list was combined to the general list of the Objective Structured Assessment of Technical Skills (OSATS) tool to develop a tool specific to neck dissection. This tool was validated in the operating room with the collaboration of the OTL-HNS oncology team of Université de Montréal and of the residents of this program. Results: A total of twenty-nine evaluations were completed throughout the 2016-2017 academic year. Acceptability ranked high for both residents and staff, with a single discrepancy in responses regarding a potential formative as opposed to summative use of the tool. Validation study results demonstrated significantly higher checklist scores for senior residents as opposed to junior residents, as well as a significant score progression over time (p<0,05). Trends in scores on the task-specific tool correlated highly to results obtained on a validated global rating scale (p<0,05). Conclusion: The first tool assessing surgical competency in OTL-HNS residents for neck dissection was successfully developed and validated.

Keyphrases: simulation, otorhinolaryngology, residency, competency, evaluation tool, reliability, validity, surgery, neck dissection, medical education