Browsing by Author "Physical Therapy, School of Health and Rehabilitation Sciences"
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Item Become one with the force: optimising mechanotherapy through an understanding of mechanobiology(BMJ Journals, 2017-07) Warden, Stuart J; Thompson, William R; Physical Therapy, School of Health and Rehabilitation SciencesItem Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled, HRpQCT Study(Wolters Kluwer, 2021) Warden, Stuart J.; Wright, Christian S.; Fuchs, Robyn K.; Physical Therapy, School of Health and Rehabilitation SciencesPurpose Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 years) physical activity on trabecular microarchitectural properties and micro-finite element (μFE) analyses of estimated bone strength. Methods Female collegiate-level tennis players (n=15; age=20.3±0.9 yrs) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral computed tomography (HRpQCT). The distal tibia and tibial diaphysis in both legs were also assessed, and cross-country runners (n=15; age=20.8±1.2 yrs) included as controls. Results The distal radius of the racquet arm had 11.8% (95% confidence interval [CI], 7.9 to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than in the nonracquet arm (all p<0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI, 13.0 to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI, 6.7 to 12.6%) greater in the racquet vs. nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI, 1.7 to 7.1%) greater strength than the contralateral leg. Conclusion Chronically elevated physical activity enhances trabecular microarchitecture and μFE estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared to in the contralateral leg.Item Cell Mechanosensitivity to Extremely Low Magnitude Signals is Enabled by a LINCed Nucleus(Wiley, 2015-06) Uzer, Gunes; Thompson, William R.; Sen, Buer; Xie, Zhihui; Yen, Sherwin S.; Miller, Sean; Bas, Guniz; Styner, Maya; Rubin, Clinton T.; Judex, Stefan; Burridge, Keith; Rubin, Janet; Physical Therapy, School of Health and Rehabilitation SciencesA cell's ability to recognize and adapt to the physical environment is central to its survival and function, but how mechanical cues are perceived and transduced into intracellular signals remains unclear. In mesenchymal stem cells (MSCs), high-magnitude substrate strain (HMS, ≥2%) effectively suppresses adipogenesis via induction of focal adhesion (FA) kinase (FAK)/mTORC2/Akt signaling generated at FAs. Physiologic systems also rely on a persistent barrage of low-level signals to regulate behavior. Exposing MSC to extremely low-magnitude mechanical signals (LMS) suppresses adipocyte formation despite the virtual absence of substrate strain (<0.001%), suggesting that LMS-induced dynamic accelerations can generate force within the cell. Here, we show that MSC response to LMS is enabled through mechanical coupling between the cytoskeleton and the nucleus, in turn activating FAK and Akt signaling followed by FAK-dependent induction of RhoA. While LMS and HMS synergistically regulated FAK activity at the FAs, LMS-induced actin remodeling was concentrated at the perinuclear domain. Preventing nuclear-actin cytoskeleton mechanocoupling by disrupting linker of nucleoskeleton and cytoskeleton (LINC) complexes inhibited these LMS-induced signals as well as prevented LMS repression of adipogenic differentiation, highlighting that LINC connections are critical for sensing LMS. In contrast, FAK activation by HMS was unaffected by LINC decoupling, consistent with signal initiation at the FA mechanosome. These results indicate that the MSC responds to its dynamic physical environment not only with "outside-in" signaling initiated by substrate strain, but vibratory signals enacted through the LINC complex enable matrix independent "inside-inside" signaling.Item Change in Depression, Confidence, and Physical Function Among Older Adults With Mild Cognitive Impairment(Wolters Kluwer, 2019-09-01) Ellis, Jennifer L.; Altenburger, Peter; Lu, Yvonne; Physical Therapy, School of Health and Rehabilitation SciencesBackground and Purpose Nearly a quarter of those in the US over age 71 experience mild cognitive impairment (MCI). Persons with MCI (PwMCI) battle depression and progressive disengagement from daily activities, which contribute to participation restriction and activity limitation. Daily engagement in meaningful activity (DEMA) is a tailored intervention designed to benefit PwMCI and their caregivers through preserved engagement and supported adjustment to cognitive changes. This secondary analysis was guided by the International Classification of Functioning, Disability and Health (ICF) model. Aims were to (i) explore the extent to which change in self-rated activity performance and physical function can predict change in depressive symptoms, (ii) evaluate for difference in confidence and depressive symptoms at ICF levels of activity and participation, and (iii) quantify the impact of daily engagement at the ICF level of participation on physical function. Methods A secondary analysis was conducted using data from the parent study, which was a two-group randomized trial involving PwMCI and their informal caregivers participating in the Indiana Alzheimer Disease Center DEMA program. Quantitative analysis (dyads: DEMA N = 20, Information Support N = 20) examined outcomes at posttest and follow-up. Analysis employed linear regression to model the relationship between explanatory and dependent variables and independent t-test to examine for difference in confidence, depression, and physical function. Results and Discussion At posttest, change in self-rated performance predicted change in depressive symptoms. Those in the DEMA group who engaged in activity at the ICF level of participation demonstrated a significant increase in confidence and physical function. Although not significant, the control group posttest results showed a mean decrease in confidence. Conclusions Results demonstrate a positive impact of DEMA on depressive symptoms, confidence, and physical function. Change in occupational performance predicted change in depressive symptoms. Confidence significantly improved among those who engaged at the ICF participation level. A larger, randomized controlled longitudinal trial is needed to better assess the impact of DEMA on physical function, activity, participation restriction and quality of life.Item Changes in Walking Spatiotemporal Parameters After Therapeutic Yoga in People with Chronic Stroke(Iris, 2019) Miller, Kristine K.; Altenburger, Peter; Dierks, Tracy; Mason, Arianne; Van Puymbroeck, Marieke; Schmid, Arlene A.; Physical Therapy, School of Health and Rehabilitation SciencesWalking limitations after stroke can contribute to long-term functional impairments. Walking characteristics such as spatiotemporal step parameters may be associated with these persistent walking limitations. The purpose of this study was to investigate changes in specific spatiotemporal walking parameters such as: walking speed; step length; swing time; step parameter symmetry; and double support time in adults with stroke who were participating in a therapeutic yoga intervention. The therapeutic yoga intervention was offered as a post-rehabilitation wellness activity 2 times per week for 8 weeks and was led by a yoga therapist. Spatiotemporal walking data were collected using the GAITRite Walkway System on a sub sample (n=24) of participants in a randomized controlled trial testing the efficacy of therapeutic yoga for improving balance in adults with chronic stroke. These data demonstrated that therapeutic yoga may have a positive impact on some spatiotemporal walking characteristics such as comfortable walking speed, step length, and double support time, while other spatiotemporal walking characteristics did not change (step parameter symmetry) or change at a significant level (sustained walking speed). The clinical relevance of this study is that participation in therapeutic yoga as a post-rehabilitation wellness activity may have a positive impact on walking characteristics in adults with chronic stroke.Item Fibroblast Growth Factor 23 Does Not Directly Influence Skeletal Muscle Cell Proliferation and Differentiation or Ex Vivo Muscle Contractility(American Physiological Society, 2018-10-01) Avin, Keith G.; Vallejo, Julian A.; Chen, Neal X.; Wang, Kun; Touchberry, Chad D.; Brotto, Marco; Dallas, Sarah L.; Moe, Sharon M.; Wacker, Michael J.; Physical Therapy, School of Health and Rehabilitation SciencesSkeletal muscle dysfunction accompanies the clinical disorders of chronic kidney disease (CKD) and hereditary hypophosphatemic rickets. In both disorders, fibroblast growth factor 23 (FGF23), a bone-derived hormone regulating phosphate and vitamin D metabolism, becomes chronically elevated. FGF23 has been shown to play a direct role in cardiac muscle dysfunction; however, it is unknown whether FGF23 signaling can also directly induce skeletal muscle dysfunction. We found expression of potential FGF23 receptors ( Fgfr1-4) and α-Klotho in muscles of two animal models (CD-1 and Cy/+ rat, a naturally occurring rat model of chronic kidney disease-mineral bone disorder) as well as C2C12 myoblasts and myotubes. C2C12 proliferation, myogenic gene expression, oxidative stress marker 8-OHdG, intracellular Ca2+ ([Ca2+]i), and ex vivo contractility of extensor digitorum longus (EDL) or soleus muscles were assessed after treatment with various amounts of FGF23. FGF23 (2-100 ng/ml) did not alter C2C12 proliferation, expression of myogenic genes, or oxidative stress after 24- to 72-h treatment. Acute or prolonged FGF23 treatment up to 6 days did not alter C2C12 [Ca2+]i handling, nor did acute treatment with FGF23 (9-100 ng/ml) affect EDL and soleus muscle contractility. In conclusion, although skeletal muscles express the receptors involved in FGF23-mediated signaling, in vitro FGF23 treatments failed to directly alter skeletal muscle development or function under the conditions tested. We hypothesize that other endogenous substances may be required to act in concert with FGF23 or apart from FGF23 to promote muscle dysfunction in hereditary hypophosphatemic rickets and CKD.Item From Hospital to Home to Participation: A Position Paper on Transition Planning Poststroke(Elsevier, 2019-06) Miller, Kristine K.; Lin, Susan H.; Neville, Marsha; Physical Therapy, School of Health and Rehabilitation SciencesBased on a review of the evidence, members of the American Congress of Rehabilitation Medicine Stroke Group’s Movement Interventions Task Force offer these 5 recommendations to help improve transitions of care for patients and their caregivers: (1) improving communication processes; (2) using transition specialists; (3) implementing a patient-centered discharge checklist; (4) using standardized outcome measures; and (5) establishing partnerships with community wellness programs. Because of changes in health care policy, there are incentives to improve transitions during stroke rehabilitation. Although transition management programs often include multidisciplinary teams, medication management, caregiver education, and follow-up care management, there is a lack of a comprehensive and standardized approach to implement transition management protocols during poststroke rehabilitation. This article uses the Transitions of Care (TOC) model to conceptualize how to facilitate a comprehensive patient-centered hand off at discharge to maximize patient functioning and health. Specifically, this article reviews current guidelines and provides an evidence summary of several commonly cited approaches (Early Supported Discharge, planned predischarge home visits, discharge checklists) to manage TOC, followed by a description of documented barriers to effective transitions. Patient-centered and standardized transition management may improve community integration, activities of daily living performance, and quality of life for stroke survivors while also decreasing hospital readmission rates during the transition from hospital to home to community.Item Internships in Kinesiology: Reconsidering Best Practices(Human Kinetics, 2018) Urtel, Mark; Michaliszyn, Sara F.; Stiemsma, Craig; Physical Therapy, School of Health and Rehabilitation SciencesThe purpose of this paper is to summarize the 2018 American Kinesiology Association preworkshop on best practices in internships. This preworkshop contained 2 keynote speakers, 5 ignite sessions, and 6 round-table discussions looking at the status of internships in departments of kinesiology, nationally. It is clear that kinesiology does not have a common practice for implementing internships. Given the many variables in respect to offering an internship, such as curricular mandates, faculty workload policy, community partner availability, program outcomes, student learning objectives, and assessment tools, this is not surprising. Perhaps we should rethink the notion that there is a set of best practices that guide internship development and consider the possibility that internships will look different at various institutions for valid reasons.Item LARG GEF and ARHGAP18 orchestrate RhoA activity to control mesenchymal stem cell lineage(Elsevier, 2018-02) Thompson, William R.; Yen, Sherwin S.; Uzer, Gunes; Xie, Zhihui; Sen, Buer; Styner, Maya; Burridge, Keith; Rubin, Janet; Physical Therapy, School of Health and Rehabilitation SciencesThe quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure. To understand the basis of force-driven RhoA activation, we considered critical GEFs (activators) and GAPs (inactivators) on bone marrow MSC lineage fate. Knockdown of LARG accelerated adipogenesis and repressed basal RhoA activity. Importantly, mechanical activation of RhoA was almost entirely inhibited following LARG depletion, and the ability of strain to inhibit adipogenesis was impaired. Knockdown of ARHGAP18 increased basal RhoA activity and actin stress fiber formation, but did not enhance mechanical strain activation of RhoA. ARHGAP18 null MSCs exhibited suppressed adipogenesis assessed by Oil-Red-O staining and Western blot of adipogenic markers. Furthermore, ARHGAP18 knockdown enhanced osteogenic commitment, confirmed by alkaline phosphatase staining and qPCR of Sp7, Alpl, and Bglap genes. This suggests that ARHGAP18 conveys tonic inhibition of MSC cytoskeletal assembly, returning RhoA to an “off state” and affecting cell lineage in the static state. In contrast, LARG is recruited during dynamic mechanical strain, and is necessary for mechanical suppression of adipogenesis. In summary, mechanical activation of RhoA in mesenchymal progenitors is dependent on LARG, while ARHGAP18 limits RhoA delineated cytoskeletal structure in static cultures. Thus, on and off GTP exchangers work through RhoA to influence MSC fate and responses to static and dynamic physical factors in the microenvironment.Item Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies(BMC, 2020) Anloague, Aric; Mahoney, Aaron; Ogunbekun, Oladipupo; Hiland, Taylor A.; Thompson, William R.; Larsen, Bryan; Loghmani, M. Terry; Hum, Julia M.; Lowery, Jonathan W.; Physical Therapy, School of Health and Rehabilitation SciencesObjective Soft tissue manual therapies are commonly utilized by osteopathic physicians, chiropractors, physical therapists and massage therapists. These techniques are predicated on subjecting tissues to biophysical mechanical stimulation but the cellular and molecular mechanism(s) mediating these effects are poorly understood. Previous studies established an in vitro model system for examining mechanical stimulation of dermal fibroblasts and established that cyclical strain, intended to mimic overuse injury, induces secretion of numerous pro-inflammatory cytokines. Moreover, mechanical strain intended to mimic soft tissue manual therapy reduces strain-induced secretion of pro-inflammatory cytokines. Here, we sought to partially confirm and extend these reports and provide independent corroboration of prior results. Results Using cultures of primary human dermal fibroblasts, we confirm cyclical mechanical strain increases levels of IL-6 and adding long-duration stretch, intended to mimic therapeutic soft tissue stimulation, after cyclical strain results in lower IL-6 levels. We also extend the prior work, reporting that long-duration stretch results in lower levels of IL-8. Although there are important limitations to this experimental model, these findings provide supportive evidence that therapeutic soft tissue stimulation may reduce levels of pro-inflammatory cytokines. Future work is required to address these open questions and advance the mechanistic understanding of therapeutic soft tissue stimulation.