Characterizing Knee Loading Patterns in People Post-Stroke

Post-stroke temporal gait asymmetry (TGA) could cause excess loading of the non-paretic leg which may cause musculoskeletal (MSK) issues in the knee. This thesis investigated knee loading during gait and its relationship to TGA post-stroke. Methods: Gait analysis was conducted in nine people post-stroke. Gait was classified as symmetric (TGS) or asymmetric and external knee adduction (KAM) and flexion moments (KFM) were calculated. Participants were compared to healthy older adults (n=109) on KAM and KFM. The proportion of individuals with increased loading was compared between the TGS and TGA groups. Results: Six and four participants exhibited increased loading of the non-paretic and paretic leg respectively. TGA and TGS groups did not differ in the proportion of individuals with increased loading. Conclusion: People post-stroke exhibited increased loading of the paretic and/or non-paretic leg but it was unrelated to TGA. Future work should investigate secondary MSK issues post-stroke in a longitudinal study

Reinforcement learning in large, structured action spaces: A simulation study of decision support for spinal cord injury rehabilitation

Reinforcement learning (RL) has helped improve decision-making in several applications. However, applying traditional RL is challenging in some applications, such as rehabilitation of people with a spinal cord injury (SCI). Among other factors, using RL in this domain is difficult because there are many possible treatments (i.e., large action space) and few patients (i.e., limited training data). Treatments for SCIs have natural groupings, so we propose two approaches to grouping treatments so that an RL agent can learn effectively from limited data. One relies on domain knowledge of SCI rehabilitation and the other learns similarities among treatments using an embedding technique. We then use Fitted Q Iteration to train an agent that learns optimal treatments. Through a simulation study designed to reflect the properties of SCI rehabilitation, we find that both methods can help improve the treatment decisions of physiotherapists, but the approach based on domain knowledge offers better performance. Our findings provide a "proof of concept" that RL can be used to help improve the treatment of those with an SCI and indicates that continued efforts to gather data and apply RL to this domain are worthwhile.Comment: 31 pages, 7 figure

Physical activity self-management interventions for adults with spinal cord injury: Part 1–A systematic review of the use and effectiveness of behavior change techniques

Objectives: To determine which behavior change techniques (BCTs) have been used within leisure time physical activity (LTPA) self-management interventions for persons with spinal cord injury (SCI), and which BCTs were effective for improving LTPA behavior and/or its antecedents. Design: Systematic review informed by the PRISMA guidelines. Methods: A comprehensive literature search was conducted using five databases. Study characteristics were extracted from included articles and intervention descriptions were coded using the BCT Taxonomy V.1. Effectiveness and maintenance of BCTs as well as the level of behavior change theory use in the design of interventions were examined within experimental studies. Results: Thirty-one unique studies were included, 16 of which had an experimental design. Across all 31 studies, a total of 222 BCTs were identified, representing 32 out of a possible 93 BCTs. The most commonly used BCTs related to the core components of self-management (i.e., education, training/rehearsal of psychological strategies, and social support). Examination of the 16 experimental studies revealed that the use of BCTs corresponding to core self-management components were related to significant improvements and maintenance of LTPA outcomes, regardless of the number of BCTs used. Conclusions: This review offers a glimpse into the mechanisms by which self-management interventions lead to behavior change; however, more research is needed to explore and evaluate other elements (e.g., theory use, tailoring, dose, mode of delivery, and provider) that may comprise effective LTPA self-management interventions for persons with SCI. PROSPERO registration number: CRD42016037531

Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.

Biological roles of obscurin and its close homolog Obsl1 (obscurin-like 1) have been enigmatic. While obscurin is highly expressed in striated muscles, Obsl1 is found ubiquitously. Accordingly, obscurin mutations have been linked to myopathies, whereas mutations in Obsl1 result in 3M-growth syndrome. To further study unique and redundant functions of these closely related proteins, we generated and characterized Obsl1 knockouts. Global Obsl1 knockouts are embryonically lethal. In contrast, skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization. To gain unbiased insights into changes to the muscle proteome, we analyzed tibialis anterior and soleus muscles by mass spectrometry, uncovering additional changes to the muscle metabolism. Our analyses suggest that all obscurin protein family members play functions for muscle membrane systems

A novel bilateral lower extremity mirror therapy intervention for individuals with stroke

Despite improvements made in stroke rehabilitation, motor impairment and gait deficits persist at discharge. New interventions are needed. Mirror therapy has promise as one element of a rehabilitation program. The primary objectives were to 1) describe a bilateral, lower extremity mirror therapy (LE-MT) device and training protocol and 2) investigate the feasibility of LE-MT. A LE-MT device was constructed to train bilateral LE movements for 30 min, 3 times/week for 4 weeks, as an adjunct to physiotherapy in three individuals post-stroke. Sessions were digitally recorded and reviewed to extract feasibility measures; repetitions, rests and session duration. Pre and post measures of gait and motor impairment were taken. Two participants completed 100% of the sessions and a third completed 83% due to a recurrence of pre-existing back pain. Repetitions increased and session duration was maintained. Number of rests decreased for two participants and increased for one participant. Participants reported fatigue and mild muscle soreness but also that the intervention was tolerable. Positive gait changes included increased velocity and decreased variability. LE motor impairment also improved. A bilateral LE-MT adjunct intervention for stroke is feasible and may have positive effects. A history of low back pain should be a precaution

A polyepitope DNA vaccine targeted to Her-2/ErbB-2 elicits a broad range of human and murine CTL effectors to protect against tumor challenge.

A cDNA vaccine (pVax1/pet-neu) was designed to encode 12 different Her-2/ErbB-2-derived, HLA-A*0201-restricted dominant and high-affinity heteroclitic cryptic epitopes. Vaccination with pVax1/pet-neu triggered multiple and ErbB-2-specific CTL responses in HLA-A*0201 transgenic HHD mice and in HLA-A*0201 healthy donors in vitro. Human and murine CTL specific for each one of the 12 ErbB-2 peptides recognized in vitro both human and murine tumor cells overexpressing endogenous ErbB-2. Furthermore, vaccination of HHD mice with pVax1/pet-neu significantly delayed the in vivo growth of challenged ErbB-2-expressing tumor (EL4/HHD/neu murine thymoma) more actively when compared with vaccination with the empty vector (pVax1) or vehicle alone. These data indicate that the pVax1/pet-neu cDNA vaccine coding for a poly-ErbB-2 epitope is able to generate simultaneous ErbB-2-specific antitumor responses against dominant and cryptic multiple epitopes