Search results for: Maude Beaudoin

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Beaudoin Marie-Joelle, Poirier Nathalie

Abstract:

Introduction: Children with autism spectrum disorder (ASD) tend to lack socio-emotional skills (e.g., emotional regulation and theory of mind). Eisenberg’s theoretical model on emotion-related socialization behaviors suggests that mothers of children with ASD could play a central role in fostering the acquisition of socio-emotional skills by engaging in frequent educational conversations about emotions. Although, mothers’ perceptions of their own emotional skills and their child’s personality traits and social deficits could mitigate the benefit of their educative role. Objective: Our study aims to explore the association between mother-child conversations about emotions and the socio-emotional skills of their children when accounting for the moderating role of the mothers’ perceptions. Forty-nine mothers completed five questionnaires about emotionally related conversations, self-openness to emotions, and perceptions of personality and socio-emotional skills of their children with ASD. Results: Regression analyses showed that frequent mother-child conversations about emotions predicted better emotional regulation and theory of mind skills in children with ASD (p < 0.01). The children’s theory of mind was moderated by mothers’ perceptions of their own emotional openness (p < 0.05) and their perceptions of their children’s openness to experience (p < 0.01) and conscientiousness (p < 0.05). Conclusion: Mothers likely play an important role in the socio-emotional education of children with ASD. Further, mothers may be most helpful when they perceive that their interventions improve their child’s behaviors. Our findings corroborate those of the Eisenberg model, which claims that mother-child conversations about emotions predict socio-emotional development skills in children with ASD. Our results also help clarify the moderating role of mothers’ perceptions, which could mitigate their willingness to engage in educational conversations about emotions with their children. Therefore, in special needs' children education, school professionals could collaborate with mothers to increase the frequency of emotion-related conversations in ASD's students with emotion dysregulation or theory of mind problems.

Keywords: autism, parental socialization of emotion, emotional regulation, theory of mind

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Authors: Luna Sequier, Florian Forelli, Maude Traulle, Amaury Vandebrouck, Pascal Duffiet, Louis Ratte, Jean Mazeas

Abstract:

The study's objective is to compare the muscular activity of the flexor knee muscle in patients who underwent an anterior cruciate ligament reconstruction with hamstring autograft and the individuals who have not undergone surgery. Methods: The participants were divided into two groups: a healthy group and an experimental group who had undergone an anterior cruciate ligament reconstruction with a hamstring graft. All participants had to perform a knee flexion strength test on an isokinetic dynamometer. The medial Gastrocnemius, lateral Gastrocnemius, Biceps femoris, and medial Hamstring muscle activity were measured during this test. Each group’s mean muscle activity was tested with statistical analysis, and a muscle activity ratio of gastrocnemius and hamstring muscles was calculated Results: The results showed a significant difference in activity of the medial gastrocnemius (p = 0,004901), the biceps femoris (p = 5,394.10-6), and the semitendinosus muscles (p = 1,822.10-6), with a higher Biceps femoris and Semitendinosus activity for the experimental group. It is however noticeable that inter-subject differences were important. Conclusion: This study has shown a difference in the gastrocnemius and hamstring muscle activity between patients who underwent an anterior cruciate ligament reconstruction surgery and healthy participants. With further results, this could show a modification of muscle activity patterns after surgery which could lead to compensatory behaviors at a return to sport and eventually explain a higher injury risk for our patients.

Keywords: anterior cruciate ligament, electromyography, muscle activity, physiotherapy

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Authors: John Acord, Ankita Batla, Kiran Khepar, Maude Schmidt, Charlotte Allen, Russ Bradford

Abstract:

Objectives: Despite the availability oftreatment options, Parkinson’s disease (PD) continues to impact heavily on a patient’s quality of life (QoL), as many symptoms that bother the patient remain unexplored and untreated in clinical settings. The aims of this research were to understand the burden of PDsymptoms from a patient perspective, particularly those which are the most persistent and debilitating, and to determine if current treatments and treatment algorithms adequately focus on their resolution. Methods: A13-question, online, patient-reported survey was created based on the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)and symptoms listed on Parkinson’s Disease Patient Advocacy Groups websites, and then validated by 10 Parkinson’s patients. In the survey, patients were asked to choose both their most common and their most bothersome symptoms, whether they had received treatment for those and, if so, had it been effective in resolving those symptoms. Results: The most bothersome symptoms reported by the 111 participants who completed the survey were sleep problems (61%), feeling tired (56%), slowness of movements (54%), and pain in some parts of the body (49%). However, while 86% of patients reported receiving dopamine or dopamine like drugs to treat their PD, far fewer reported receiving targeted therapies for additional symptoms. For example, of the patients who reported having sleep problems, only 33% received some form of treatment for this symptom. This was also true for feeling tired (30% received treatment for this symptom), slowness of movements (62% received treatment for this symptom), and pain in some parts of the body (61% received treatment for this symptom). Additionally, 65% of patients reported that the symptoms they experienced were not adequately controlled by the treatments they received, and 9% reported that their current treatments had no effect on their symptoms whatsoever. Conclusion: The survey outcomes highlight that the majority of patients involved in the study received treatment focused on their disease, however, symptom-based treatments were less well represented. Consequently, patient-reported symptoms such as sleep problems and feeling tired tended to receive more fragmented intervention than ‘classical’ PD symptoms, such as slowness of movement, even though they were reported as being amongst the most bothersome symptoms for patients. This research highlights the need to explore symptom burden from the patient’s perspective and offer Customised treatment/support for both motor and non-motor symptoms maximize patients’ quality of life.

Keywords: survey, patient reported symptom burden, unmet needs, parkinson's disease

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

Abstract:

Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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