Department of Physical Therapy Articles
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Item Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship(Karger, 2021-04) Wilson, Thad E.; Narra, Seetharam; Metzler-Wilson, Kristen; Schneider, Artur; Bullens, Kelsey A.; Holt, Ian S.; Physical Therapy, School of Health and Human SciencesBradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.Item Mechanical stimulation of human dermal fibroblasts regulates pro-inflammatory cytokines: potential insight into soft tissue manual therapies(BMC, 2020-08-27) 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 Human SciencesSoft 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.Item Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity(Nature, 2020-11-17) Yi, Xin; Wright, Laura E.; Pagnotti, Gabriel M.; Uzer, Gunes; Powell, Katherine M.; Wallace, Joseph M.; Sankar, Uma; Rubin, Clinton T.; Mohammad, Khalid; Guise, Theresa A.; Thompson, William R.; Physical Therapy, School of Health and Human SciencesExercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression. We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration. Low-magnitude, high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration (LIV). LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH, IL-11, and RANKL. Furthermore, paracrine signals from mechanically stimulated cancer cells, reduced osteoclast differentiation and resorptive capacity. Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion. LIV increased cell stiffness; an effect dependent on the LINC complex. These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells, where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.Item Tester and testing procedure influence clinically determined gait speed(Elsevier, 2019-10-01) Warden, Stuart J.; Kemp, Allie C.; Liu, Ziyue; Moe, Sharon M.; Physical Therapy, School of Health and Human SciencesBackground: There is a clinical need to be able to reliably detect meaningful changes (0.1 to 0.2 m/s) in usual gait speed (UGS) considering reduced gait speed is associated with morbidity and mortality. Research question: What is the impact of tester on UGS assessment, and the influence of test repetition (trial 1 vs. 2), timing method (manual stopwatch vs. automated timing), and starting condition (stationary vs. dynamic start) on the ability to detect changes in UGS and fast gait speed (FGS)? Methods: UGS and FGS was assessed in 725 participants on a 8-m course with infrared timing gates positioned at 0, 2, 4 and 6 m. Testing was performed by one of 13 testers trained by a single researcher. Time to walk 4-m from a stationary start (i.e. from 0-m to 4-m) was measured manually using a stopwatch and automatically via the timing gates at 0-m and 4-m. Time taken to walk 4-m with a dynamic start was measured during the same trial by recording the time to walk between the timing gates at 2-m and 6-m (i.e. after 2-m acceleration). Results: Testers differed for UGS measured using manual vs. automated timing (p=0.02), with five and two testers recording slower and faster UGS using manual timing, respectively. 95% limits of agreement for trial 1 vs. 2, manual vs. automated timing, and dynamic vs. stationary start ranged from ±0.15 m/s to ±0.20 m/s, coinciding with the range for a clinically meaningful change. Limits of agreement for FGS were larger ranging from ±0.26 m/s to ±0.35 m/s. Significance: Repeat testing of UGS should performed by the same tester or using an automated timing method to control for tester effects. Test protocol should remain constant both between and within participants as protocol deviations may result in detection of an artificial clinically meaningful change.Item Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)(American Society of Nephrology, 2019-10-01) Avin, Keith G.; Allen, Matthew R.; Chen, Neal X.; Srinivasan, Shruthi; O’Neill, Kalisha D.; Troutman, Ashley D.; Mast, Garrison; Swallow, Elizabeth A.; Brown, Mary Beth; Wallace, Joseph M.; Zimmers, Teresa A.; Warden, Stuart J.; Moe, Sharon M.; Physical Therapy, School of Health and Human SciencesBackground Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality. Methods We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2–3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics. Results Wheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index. Conclusions Voluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.Item 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 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 Post-Rehabilitation Adapted-Yoga at the YMCA for Adults with Acquired Brain Injury: A Feasibility and Pilot Study(Juniper, 2020) Miller, Kristine K.; Burris, Richard; Nuest, Hilary; Mason, Arianne; Schmid, Arlene A.; Hanna, Carol; Barringer, Monica; Physical Therapy, School of Health and Rehabilitation SciencesBackground & purpose: Adults with acquired brain injury (ABI) (stroke and traumatic brain injury) experience long-term physical performance deficits for which participation in post-rehabilitation exercise is recommended. Community-based adapted-yoga has potential as an exercise modality to promote post-rehabilitation exercise and physical function improvements. The purpose of this study was to examine the feasibility and benefit of adapted-yoga at the local YMCA for post-rehabilitation adults with ABI. Methods: Participants were recruited by referral from clinical therapists in outpatient rehabilitation centers to participate in adapted-yoga 2x/week for 8 weeks at the YMCA. Referral tracking, yoga attendance, safety, and intervention fidelity were assessed for feasibility. Participants completed pre and post-yoga assessments of balance (trunk impairment scale [TIS], berg balance scale [BBS], dynamic gait index [DGI]) and walking (10-meter walk test [10MWT] and six-minute walk test [6MWT]) and 8 weeks of adapted-yoga class. Results: Thirty-two people were referred to the YMCA adapted-yoga program by clinical therapists with 17 (53%) of referred persons enrolling in the program. Intervention fidelity was 87% with the standardized adapted-yoga protocol, and the average number of classes attended was 12.82+3.7. Balance (TIS, p<0.001; BBS, p<0.001; DGI, p<0.001), and walking distance (6MWT, p= 0.028) all significantly improved after 8-weeks of yoga. Balance confidence did not improve significantly and walking speed did not change. Discussion & Conclusion: Clinician referral to community-based programs may be a feasible mechanism to engage persons in post-rehabilitation community-based exercise. Adapted-yoga may beneficially impact balance and walking performance in post-rehabilitation adults with ABI.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 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.