Le Fonds d'investissement de Montréal

monographi

La Coopérative d’habitation des Cantons de l’Est

Recherche réalisée grâce aux contributions de la Chaire de coopération Guy-Bernier et du Conseil de recherches en sciences humaines du Canada

Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy

In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models. Furthermore, the effect of CK1delta/epsilon inhibition strongly depends on endogenous PER2 protein levels, which differs depending on both the molecular cause of the circadian disruption and the patient\u27s lighting environment. To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. Our results reveal the importance of photosensitivity in the clinical efficacy of clock-modulating drugs, and enable precision medicine for circadian disruption

Whole genome sequencing and phylogenetic analysis of \u3ci\u3eBluetongue virus\u3c/i\u3e serotype 2 strains isolated in the Americas including a novel strain from the western United States

Bluetongue is a potentially fatal arboviral disease of domestic and wild ruminants that is characterized by widespread edema and tissue necrosis. Bluetongue virus (BTV) serotypes 10, 11, 13, and 17 occur throughout much of the United States, whereas serotype 2 (BTV-2) was previously only detected in the southeastern United States. Since 1998, 10 other BTV serotypes have also been isolated from ruminants in the southeastern United States. In 2010, BTV-2 was identified in California for the first time, and preliminary sequence analysis indicated that the virus isolate was closely related to BTV strains circulating in the southeastern United States. In the current study, the whole genome sequence of the California strain of BTV-2 was compared with those of other BTV-2 strains in the Americas. The results of the analysis suggest co-circulation of genetically distinct viruses in the southeastern United States, and further suggest that the 2010 western isolate is closely related to southeastern strains of BTV. Although it remains uncertain as to how this novel virus was translocated to California, the findings of the current study underscore the need for ongoing surveillance of this economically important livestock disease

Three dimensional characterization and archiving system

This system (3D-ICAS) is being developed as a remote system to perform rapid in situ analysis of hazardous organics and radionuclide contamination on structural materials. It is in the final phase of a 3-phase program to support Decontamination and Decommissioning (D&D) operations. Accurate physical characterization of surfaces and radioactive and organic contamination is a critical D&D task. Surface characterization includes identification of dangerous inorganic materials such as asbestos and transite. 3D-ICAS robotically conveys a multisensor probe near the surfaces to be inspected, using coherent laser radar tracking, which also provides 3D facility maps. High-speed automated organic analysis is provided by means of gas chromatograph-mass spectrometer sensor which can process a sample without contact in one minute. Volatile organics are extracted directly from contaminated surfaces without sample removal; multiple stage focusing is used for high time resolution. Additional discrimination is obtained through a final stage time-of-flight mass spectrometer. The radionuclide sensors combines {alpha}, {beta}, and {gamma} counting with energy discrimination of the {alpha} channel; this quantifies isotopes of U, Pu, Th, Tc, Np, and Am in one minute. The Molecular Vibrational Spectrometry sensor is used to characterize substrate material such as concrete, transite, wood, or asbestos; this can be used to provide estimates of the depth of contamination. The 3D-ICAS will be available for real-time monitoring immediately after each 1 to 2 minute sample period. After surface mapping, 3-D displays will be provided showing contours of detected contaminant concentrations. Permanent measurement and contaminant level archiving will be provided, assuring data integrity and allowing regulatory review before and after D&D operations

Targeted exercises can improve biomechanical markers in individuals with knee osteoarthritis: A secondary analysis from a cluster randomized controlled trial

Background: It is not clear whether exercise therapy significantly improves knee biomechanics during gait in osteoarthritis (OA) patients. This study aimed to determine whether targeted exercises based on a knee kinesiography exam improve biomechanical markers (BMs) compared with conventional primary care (CPC) management. Methods: This was a secondary analysis of a cluster randomized controlled trial in which patients were assigned to one of three groups: (1) Control (CPC), (2) Exercise, and (3) Exercise&Education. Fourteen known BMs in knee OA patients were assessed. The primary outcome was the global evolution ratio (GER), which was calculated as the sum of improved BMs over the sum of deteriorated BMs 6 months after baseline assessment. GER scores were categorized with three different sets of cut-off values into clinical levels: (a) Deteriorated, (b) Stabilized, and (c) Improved. Ordinal logistic regressions were performed on the per-protocol population to determine whether there was a relationship between group assignment and GER levels. Results: Of the 221 eligible participants, 163 were included. Two different regression models showed that patients from Group 3 (Exercise&Education) were 2.5-times more likely to be in an upper GER level (i.e., Stabilized or Improved) than patients from the control group (both odds ratio (OR) > 2.46, Wald Χ2(1) ≥ 7.268, P ≤ 0.01). They also reported significantly more improvement in pain and function (Knee Injury and Osteoarthritis Outcome Score, both P ≤ 0.01). Conclusions: Results suggest that targeted exercises can improve biomechanical markers in knee OA patients compared with CPC treatment. Further studies are needed to confirm these findings and refine the biomechanical markers to address to maximize patients’ clinical outcomes

Impact of a personalized care approach on 3D gait impairments in knee osteoarthritis patients (a cluster randomized controlled trial)

Purpose: Knee osteoarthritis (OA) often leads to gait kinematic impairments. The knee kinesiography exam, measuring three-dimensional (3D) knee kinematics during gait on a treadmill, allows to objectively identify gait impairments (GIs) in order to provide recommendations for a personalized care approach (targeted home-based exercises, bracing, etc.) to correct these impairments. A clinical trial showed that this approach can lead to significant improvement in function and pain reduction after 6 months compared to a control group. The aim of this study was to assess the impact of this personalized care approach (PCA) on 3D mechanical GIs in knee OA patients compared to a control group. Methods: Primary care physicians in this cluster randomized controlled trial in the Province of Quebec (Canada) were asked to recruit patients with a clinical diagnosis of knee OA. Patients were included if 1) knee OA was the main cause of their knee pain, 2) they rated their worst pain in the past 7 days ≥ 4 on a 0-10 pain intensity scale, 3) they had a Kellgren-Lawrence grade ≥ 2 on radiographs. Eligible patients from a same primary care clinic were randomized to the same group: 1- a control group (usual care), 2- a group with the PCA, and 3- a group with the PCA + an educational program. In all of the three groups, primary care physicians managed their patients according to their individual needs, but only physicians from groups 2- and 3- had access to the recommendations for the PCA. These were treatment recommendations (e.g. bracing, specific activities, etc.) and tailored home exercises targeting the GIs identified with the knee kinesiography results. Patients from group 3- also had a one-hour educational session on knee OA self-management and two follow-up group meetings with a therapist (to answer their questions, regulate the nature and intensity of their exercises, etc.). For all patients, we assessed the presence of 14 known GIs in knee OA at baseline and 6-month follow-up (see Table 1). If a GI changed from “Present” at baseline to “Absent” at 6 months, we considered it as improved. If it changed from “Absent” to “Present”, it was considered deteriorated. In order to summarize all GIs’ evolution in a single outcome, we calculated for each patient a global evolution ratio (GER) corresponding to the ratio of the sum of improved GIs over the sum of deteriorated GIs. The GER status was defined as “DETERIORATION” (≤0.5), “STABILIZATION” (0.5<GER<1.5), or “IMPROVEMENT” (≥1.5). Chi-square tests were used to assess between-group differences on the GER status. Results: 221 patients from 55 clinics participated. There were 61.1% women, the mean age was 63 years (95%CI: 62;64), and the mean BMI was 29.5 kg/m2 (95%CI: 28.7;30.2). There were no differences between groups at baseline on sociodemographic characteristics and patients were equally distributed between the three groups (1-Control: N=71; 2-PCA: N=72; 3-PCA+Education: N=78). There was a significant difference between the three groups on the GER status (p=0.03). Post-hoc analysis showed that both groups who received the PCA significantly differed from the control group (both p<0.05). As shown in Figure 1, the proportion of patients with an improved GER was higher in both groups with the PCA (Group 1: 28.2% vs Group 2: 37.5% and Group 3: 38.5%), and the proportion of patients with a deteriorated GER was lower (Group 1: 50.7% vs Group 2: 26.4% and Group 3: 30.8%) compared to the control group. There was no significant difference between the two groups with the PCA (p=0.75). Conclusions: Results suggest that a personalized care approach including tailored treatment recommendations (e.g. exercises, orthoses, etc.) to correct GIs can have a positive impact on 3D knee kinematics during gait after 6 months. Patients from both groups who had access to this PCA showed significantly less deterioration, and more stabilization and improvement of their gait impairments compared to the control group. There was no difference between groups 2- and 3-, suggesting that this approach may have an effect on gait impairments even without an additional education program. The proposed global evolution ratio showed interesting results but further analyses are needed to specifically identify which GIs’ evolutions have the most impact on patient outcomes