Effet du renforcement musculaire sur les niveaux d'effort des muscles de la cheville et de la hanche lors de la marche chez le sujet hémiparétique

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

Inhibitors of Pathogen Intercellular Signals as Selective Anti-Infective Compounds

Long-term antibiotic use generates pan-resistant super pathogens. Anti-infective compounds that selectively disrupt virulence pathways without affecting cell viability may be used to efficiently combat infections caused by these pathogens. A candidate target pathway is quorum sensing (QS), which many bacterial pathogens use to coordinately regulate virulence determinants. The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). Here, we identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function. These compounds provide a starting point for the design and development of selective anti-infectives that restrict human P. aeruginosa pathogenesis, and possibly other clinically significant pathogens

Implementation of increased physical therapy intensity for improving walking after stroke: Walk 'n Watch protocol for a multi-site stepped-wedge cluster randomized controlled trial

Clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Yet, practice is slow to change, evidenced by the little amount of walking activity in stroke rehabilitation units. Our recent study (n=75) found that a structured, progressive protocol integrated with typical daily physical therapy improved walking and quality of life measures over usual care. Research therapists progressed the intensity of exercise by using heart rate and step counters worn by the participants with stroke during therapy. To have the greatest impact, our next step is to undertake an implementation trial to change practice across stroke units where we enable the entire unit to use the protocol as part of standard of care. What is the effect of introducing structured, progressive exercise (termed the Walk 'n Watch protocol) to standard of care on the primary outcome of walking in adult participants with stroke over the hospital inpatient rehabilitation period? Secondary outcomes will be evaluated and include quality of life.Methods and sample size estimates: This national, multisite clinical trial will randomize 12 sites using a stepped-wedge design where each site will be randomized to deliver Usual Care initially for 4, 8, 12 or 16-months (three sites for each duration). Then, each site will switch to the Walk 'n Watch phase for the remaining duration of a total 20-month enrolment period. Each participant will be exposed to only one of Usual Care or Walk 'n Watch. The trial will enrol a total of 195 participants with stroke to achieve a power of 80% with a Type I error rate of 5%, allowing for 20% dropout. Participants will be medically stable adults post-stroke and able to take 5 steps with a maximum physical assistance from one therapist. The Walk 'n Watch protocol focuses on completing a minimum of 30-minutes of weight-bearing, walking-related activities (at the physical therapists' discretion) that progressively increases in intensity informed by activity trackers measuring heart rate and step number.Study outcome(s): The primary outcome will be the change in walking endurance, measured by the Six-Minute Walk Test, from Baseline (T1) to 4-weeks (T2). This change will be compared across Usual Care and Walk 'n Watch phases using a linear mixed-effects model. Additional physical, cognitive, and quality of life outcomes will be measured at T1, T2, and 12-months post-stroke (T3) by a blinded assessor. The implementation stepped-wedge cluster-randomized trial enables the protocol to be tested under real-world conditions, involving all clinicians on the unit. It will result in all sites and all clinicians on the unit to gain expertise in protocol delivery. Hence, a deliberate outcome of the trial is facilitating changes in best practice to improve outcomes for participants with stroke in the trial, and for the many participants with stroke admitted after the trial ends

Biomarkers of recovery after stroke.

Purpose of reviewA better understanding of the molecular events underlying stroke recovery might be useful to optimize restorative therapies. Measurement of these events, however, is generally inaccessible in humans, at least at the molecular level. Substitute measures, or biomarkers, that are accessible might provide deeper insights into spontaneous recovery in humans. This review considers advances in use of biomarkers to understand recovery from stroke, and to serve as a surrogate measure of stroke recovery, including in a clinical trial context.Recent findingsAmong the key recent findings is that measures of brain function and injury are the strongest predictors of treatment effect, moreso than behavioral measures are, despite the reliance on behavioral measures as study entry criteria. Functional neuroimaging studies have provided insights into therapeutic mechanism of action. In addition, measures of central nervous system function have been used to estimate individual therapy needs, findings that suggest the potential to tailor restorative therapies to the specific needs of individual patients.SummaryMany therapies are emerging as potentially useful to promote improved recovery after stroke. Continued advances in biomarkers are providing new insights into the neurobiology of both spontaneous and therapy-induced brain repair after stroke

Biomarkers of recovery after stroke.

Purpose of reviewA better understanding of the molecular events underlying stroke recovery might be useful to optimize restorative therapies. Measurement of these events, however, is generally inaccessible in humans, at least at the molecular level. Substitute measures, or biomarkers, that are accessible might provide deeper insights into spontaneous recovery in humans. This review considers advances in use of biomarkers to understand recovery from stroke, and to serve as a surrogate measure of stroke recovery, including in a clinical trial context.Recent findingsAmong the key recent findings is that measures of brain function and injury are the strongest predictors of treatment effect, moreso than behavioral measures are, despite the reliance on behavioral measures as study entry criteria. Functional neuroimaging studies have provided insights into therapeutic mechanism of action. In addition, measures of central nervous system function have been used to estimate individual therapy needs, findings that suggest the potential to tailor restorative therapies to the specific needs of individual patients.SummaryMany therapies are emerging as potentially useful to promote improved recovery after stroke. Continued advances in biomarkers are providing new insights into the neurobiology of both spontaneous and therapy-induced brain repair after stroke

Comparison of error-amplification and haptic-guidance training techniques for learning of a timing-based motor task by healthy individuals.

Performance errors drive motor learning for many tasks. Some researchers have suggested that reducing performance errors with haptic guidance can benefit learning by demonstrating correct movements, while others have suggested that artificially increasing errors will force faster and more complete learning. This study compared the effect of these two techniques--haptic guidance and error amplification--as healthy subjects learned to play a computerized pinball-like game. The game required learning to press a button using wrist movement at the correct time to make a flipper hit a falling ball to a randomly positioned target. Errors were decreased or increased using a robotic device that retarded or accelerated wrist movement, based on sensed movement initiation timing errors. After training with either error amplification or haptic guidance, subjects significantly reduced their timing errors and generalized learning to untrained targets. However, for a subset of more skilled subjects, training with amplified errors produced significantly greater learning than training with the reduced errors associated with haptic guidance, while for a subset of less skilled subjects, training with haptic guidance seemed to benefit learning more. These results suggest that both techniques help enhanced performance of a timing task, but learning is optimized if training subjects with the appropriate technique based on their baseline skill level

Neural circuits activated by error amplification and haptic guidance training techniques during performance of a timing-based motor task by healthy individuals

To promote motor learning, robotic devices have been used to improve subjects’ performance by guiding desired movements (haptic guidance—HG) or by artificially increasing movement errors to foster a more rapid learning (error amplification—EA). To better understand the neurophysiological basis of motor learning, a few studies have evaluated brain regions activated during EA/HG, but none has compared both approaches. The goal of this study was to investigate using fMRI which brain networks were activated during a single training session of HG/EA in healthy adults learning to play a computerized pinball-like timing task. Subjects had to trigger a robotic device by flexing their wrist at the correct timing to activate a virtual flipper and hit a falling ball towards randomly positioned targets. During training with HG/EA, subjects’ timing errors were decreased/increased, respectively, by the robotic device to delay or accelerate their wrist movement. The results showed that at the beginning of the training period with HG/EA, an error-detection network, including cerebellum and angular gyrus, was activated, consistent with subjects recognizing discrepancies between their intended actions and the actual movement timing. At the end of the training period, an error-detection network was still present for EA, while a memory consolidation/automatization network (caudate head and parahippocampal gyrus) was activated for HG. The results indicate that training movement with various kinds of robotic input relies on different brain networks. Better understanding the neurophysiological underpinnings of brain processes during HG/EA could prove useful for optimizing rehabilitative movement training for people with different patterns of brain damage