Browsing by Author "Department of Physical Therapy, School of Health and Rehabilitation Sciences"
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Item Achilles tendon material properties are greater in the jump leg of jumping athletes(ISMNI, 2016-06) Bayliss, Amy J.; Weatherholt, Alyssa M.; Crandall, Trent T.; Farmer, Danielle L.; McConnell, Jethro C.; Crossley, K. M.; Warden, Stuart J.; Department of Physical Therapy, School of Health and Rehabilitation SciencesPurpose: The Achilles tendon (AT) must adapt to meet changes in demands. This study explored AT adaptation by comparing properties within the jump and non-jump legs of jumping athletes. Non-jumping control athletes were included to control limb dominance effects. Methods: AT properties were assessed in the preferred (jump) and non-preferred (lead) jumping legs of male collegiate-level long and/or high jump (jumpers; n=10) and cross-country (controls; n=10) athletes. Cross-sectional area (CSA), elongation, and force during isometric contractions were used to estimate the morphological, mechanical and material properties of the ATs bilaterally. Results: Jumpers exposed their ATs to more force and stress than controls (all p≤0.03). AT force and stress were also greater in the jump leg of both jumpers and controls than in the lead leg (all p<0.05). Jumpers had 17.8% greater AT stiffness and 24.4% greater Young’s modulus in their jump leg compared to lead leg (all p<0.05). There were no jump versus lead leg differences in AT stiffness or Young’s modulus within controls (all p>0.05). Conclusion: ATs chronically exposed to elevated mechanical loading were found to exhibit greater mechanical (stiffness) and material (Young’s modulus) properties.Item Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage(Wiley, 2016-06) Uzer, Gunes; Fuchs, Robyn K.; Rubin, Janet; Thompson, William R.; Department of Physical Therapy, School of Health and Rehabilitation SciencesNumerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on “outside-in” signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis.Item Estradiol improves right ventricular function in rats with severe angioproliferative pulmonary hypertension: effects of endogenous and exogenous sex hormones(American Physiological Society, 2015-05) Frump, Andrea L.; Goss, Kara N.; Vayl, Alexandra; Albrecht, Marjorie; Fisher, Amanda; Tursunova, Roziya; Fierst, John; Whitson, Jordan; Cucci, Anthony R.; Brown, M. Beth; Lahm, Tim; Department of Physical Therapy, School of Health and Rehabilitation SciencesEstrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2’s RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg−1·day−1). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH.Item Health benefits of seated speed, resistance, and power training for an individual with spastic quadriplegic cerebral palsy: A case report(IOS Press, 2015-09-06) Gannotti, Mary E.; Fuchs, Robyn Kimberly; Roberts, Dawn E.; Hobbs, Nedda; Cannon, Ian M.; Department of Physical Therapy, School of Health and Rehabilitation SciencesChildren with moderate to severe cerebral palsy are at risk for low bone mass for chronological age, which compounds risk in adulthood for progressive deformity and chronic pain. Physical activity and exercise can be a key component to optimizing bone health. In this case report we present a young adult male with non-ambulatory, spastic quadriplegia CP whom began a seated speed, resistance, and power training exercise program at age 14.5 years. Exercise program continued into adulthood as part of an active lifestyle. The individual had a history of failure to thrive, bowel and bladder incontinence, reduced bone mineral density (BMD) for age, and spinal deformity at the time exercise was initiated. Participation in the exercise program began once a week for 1.5-2 hours/session, and progressed to 3-5 times per week after two years. This exercise program is now a component of his habitual lifestyle. Over the 6 years he was followed, lumbar spine and total hip BMD Z-scores did not worsen, which may be viewed as a positive outcome given his level of gross motor impairment. Additionally, the individual reported less back pain, improved bowel and bladder control, increased energy level, and never sustained an exercise related injury. Findings from this case report suggest a regular program of seated speed, resistance, power training may promote overall well-being, are safe, and should be considered as a mechanism for optimizing bone health.Item High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension(APS, 2017) Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J.; Presson, Robert G.; Petrache, Irina; Kline, Jeffrey A.; Lahm, Tim; Department of Physical Therapy, School of Health and Rehabilitation SciencesExercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT’s superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.Item Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial(Elsevier, 2015-12) Becker, Clemens; Lord, Stephen R.; Studenski, Stephanie A.; Warden, Stuart J.; Fielding, Roger A.; Recknor, Christopher P.; Hochberg, Marc C.; Ferrari, Serge L.; Blain, Hubert; Binder, Ellen F.; Rolland, Yves; Poiraudeau, Serge; Benson, Charles T.; Myers, Stephen L.; Hu, Leijun; Ahmad, Qasim I.; Pacuch, Kelli R.; Gomez, Elisa V.; Benichau, Olivier; Department of Physical Therapy, School of Health and Rehabilitation SciencesBackground Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low muscle strength and power. Methods In this proof-of-concept, randomised, placebo-controlled, double-blind, parallel, multicentre, phase 2 study, we recruited patients aged 75 years or older who had fallen in the past year from 21 investigator sites across Argentina, Australia, France, Germany, Sweden, and the USA. Eligible patients had low performance on hand grip strength and chair rise tests, tested with the procedure described by Guralnik and colleagues. Participants were stratified by country, age, hand grip strength, and performance on the chair rise test, and were randomly assigned (1:1) by a computer-generated random sequence to receive subcutaneous injections of placebo or 315 mg LY at weeks 0 (randomisation visit), 4, 8, 12, 16, and 20, followed by 16 weeks observation. The primary outcome was change in aLBM from baseline to 24 weeks. We measured physical performance as secondary outcomes (four-step stair climbing time, usual gait speed, and time to rise five times from a chair without arms, or with arms for participants unable to do it without arms) and exploratory outcomes (12-step stair climbing test, 6-min walking distance, fast gait speed, hand grip strength, and isometric leg extension strength). Efficacy analyses included all randomly assigned patients who received at least one dose and had a baseline and at least one subsequent measure. The primary analysis and all other tests of treatment effect (except physical performance tests) were done at a two-sided alpha level of 0·05. Tests of treatment effect on physical performance tests were done at a pre-specified two-sided alpha level of 0·1. This trial is registered with ClinicalTrials.gov, number NCT01604408. Findings Between June 19, 2012, and Dec 12, 2013, we screened 365 patients. 99 were randomly assigned to receive placebo and 102 to receive LY. Treatment was completed in 85 (86%) of patients given placebo and in 82 (80%) given LY. At 24 weeks, the least-squares mean change in aLBM was −0·123 kg (95% CI −0·287 to 0·040) in the placebo group and 0·303 kg (0·135 to 0·470) in the LY group, a difference of 0·43 kg (95% CI 0·192 to 0·660; p<0·0001). Stair climbing time (four-step and 12-step tests), chair rise with arms, and fast gait speed improved significantly from baseline to week 24 with differences between LY and placebo of respectively −0·46 s (p=0·093), −1·28 s (p=0·011), −4·15 s (p=0·054), and 0·05 m/s (p=0·088). No effect was detected for other performance-based measures. Injection site reactions were recorded in nine (9%) patients given placebo and in 31 (30%) patients given LY (p<0·0001), and were generally mild, and led to treatment discontinuation in two patients given LY. Interpretation Our findings show LY treatment increases lean mass and might improve functional measures of muscle power. Although additional studies are needed to confirm these results, our data suggest LY should be tested for its potential ability to reduce the risk of falls or physical dependency in older weak fallers.Item Physical activity when young provides lifelong benefits to cortical bone size and strength in men(National Academy of Sciences, 2014-04-08) Warden, Stuart J.; Mantila Roosa, Sara M.; Kersh, Mariana E.; Hurd, Andrea L.; Fleisig, Glenn S.; Pandy, Marcus G.; Fuchs, Robyn K.; Department of Physical Therapy, School of Health and Rehabilitation SciencesThe skeleton shows greatest plasticity to physical activity-related mechanical loads during youth but is more at risk for failure during aging. Do the skeletal benefits of physical activity during youth persist with aging? To address this question, we used a uniquely controlled cross-sectional study design in which we compared the throwing-to-nonthrowing arm differences in humeral diaphysis bone properties in professional baseball players at different stages of their careers (n = 103) with dominant-to-nondominant arm differences in controls (n = 94). Throwing-related physical activity introduced extreme loading to the humeral diaphysis and nearly doubled its strength. Once throwing activities ceased, the cortical bone mass, area, and thickness benefits of physical activity during youth were gradually lost because of greater medullary expansion and cortical trabecularization. However, half of the bone size (total cross-sectional area) and one-third of the bone strength (polar moment of inertia) benefits of throwing-related physical activity during youth were maintained lifelong. In players who continued throwing during aging, some cortical bone mass and more strength benefits of the physical activity during youth were maintained as a result of less medullary expansion and cortical trabecularization. These data indicate that the old adage of “use it or lose it” is not entirely applicable to the skeleton and that physical activity during youth should be encouraged for lifelong bone health, with the focus being optimization of bone size and strength rather than the current paradigm of increasing mass. The data also indicate that physical activity should be encouraged during aging to reduce skeletal structural decay.Item Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease(Plos, 2016-08-03) Avin, Keith G.; Chen, Neal X.; Organ, Jason M.; Zarse, Chad; O'Neil, Kalisha; Conway, Richard G.; Konrad, Robert J.; Bacallao, Robert L.; Allen, Matthew R.; Moe, Sharon M.; Department of Physical Therapy, School of Health and Rehabilitation SciencesSkeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD.Item Successful treatment of a guitarist with a finger joint injury using instrument-assisted soft tissue mobilization: a case report(Taylor & Francis, 2015-12) Loghmani, M. Terry; Bayliss, Amy J.; Clayton, Greg; Gundeck, Evelina; Department of Physical Therapy, School of Health and Rehabilitation SciencesFinger injuries are common and can greatly affect a musician's quality of life. A 55-year-old man, who had injured the proximal interphalangeal joint of the left index finger 6 months prior to any intervention, was treated with a manual therapy approach incorporating instrument-assisted soft tissue mobilization (IASTM). Initial examination findings included self-reported pain and functional limitations and physical impairments that significantly impeded his ability to play the acoustic guitar. He was treated once a week for 6 weeks with IASTM, joint mobilization, therapeutic exercise, and ice massage. Additionally, a home exercise program and self-care instructions were provided. The patient gained positive outcomes with improvements in pain (Numerical Pain Rating Scale while playing the guitar: initial 5/10, discharge 1/10) and function (Disability Arm Shoulder Hand Sports-Performing Arts Optional Module: initial 75; discharge 6·25), each reaching a minimum clinically important difference. Importantly, he was able to play the guitar with minimal to no pain as desired. Physical measures also improved, including an immediate gain in finger range of motion with IASTM alone. Manual therapy approaches integrating IASTM may provide an effective conservative treatment strategy for patients with finger/hand conditions in the performing arts and other patient populations.Item Tibial Bone Strength is Enhanced in the Jump Leg of Collegiate-Level Jumping Athletes: A Within-Subject Controlled Cross-Sectional Study(Springer, 2016-02) Weatherholt, Alyssa M.; Warden, Stuart J.; Department of Physical Therapy, School of Health and Rehabilitation SciencesAn efficient method of studying skeletal adaptation to mechanical loading is to assess side-to-side differences (i.e., asymmetry) within individuals who unilaterally exercise one side of the body. Within-subject controlled study designs have been used to explore skeletal mechanoadaptation at upper extremity sites; however, there is no established model in the lower extremities. The current study assessed tibial diaphysis and distal tibia asymmetry in collegiate-level jumping athletes (N = 12). To account for normal crossed asymmetry, data in jumping athletes were compared to asymmetry in a cohort of athletic controls not routinely exposed to elevated unilateral lower extremity loading (N = 11). Jumpers exhibited side-to-side differences between their jump and lead legs at both the tibial diaphysis and distal tibia, with differences at the former site persisting following comparison to dominant-to-nondominant leg differences in controls. In particular, jump-to-lead leg differences for cortical area and thickness at the tibial diaphysis in jumpers were 3.6% (95% CI 0.5-6.8%) and 3.5% (95% CI 0.4-6.6%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Similarly, jump-to-lead leg differences in jumpers for tibial diaphysis maximum second moment of area and polar moment of inertia were 7.2% (95% CI 1.2-13.2%) and 5.7% (95% CI 1.7-9.8%) greater than dominant-to-nondominant differences in controls, respectively (all p < 0.05). Assessment of region-specific differences of the tibial diaphysis in jumpers indicated that the jump leg had greater pericortical radii on the medial and posterior sides and greater radial cortical thickness posteromedially when compared to the lead leg. These data suggest that athletes who perform repetitive and forceful unilateral jumping may be a useful and efficient within-subject controlled model for studying lower extremity skeletal mechanoadaptation.