Publications by authors named "Paul C LaStayo"

72 Publications

Longitudinal study of knee load avoidant movement behavior after total knee arthroplasty with recommendations for future retraining interventions.

Knee 2021 Apr 16;30:90-99. Epub 2021 Apr 16.

University of Montana, School of Physical Therapy & Rehabilitation Science, Missoula, MT, United States. Electronic address:

Background: This study aimed to evaluate clinical and biomechanical changes in self-report survey, quadriceps strength and gait analysis over 3- and 6-months post-total knee arthroplasty (TKA) and confirm the immediate effects of two forms of kinetic biofeedback on improving inter-limb biomechanics during a physically demanding decline walking task.

Methods: Thirty patients with unilateral TKA underwent testing at 3- and 6-months following surgery. All underwent self-report survey, quadriceps strength and gait analysis testing. Patients were assigned to one of two types of biofeedback [vertical ground reaction force (vGRF), knee extensor moment (KEM)].

Results: No decrease in gait asymmetry was observed in non-biofeedback trials over time (p > 0.05), despite significant improvements in self-report physical function (p < 0.01, Cohen d = 0.44), pain interference (p = 0.01, Cohen d = 0.68), numeric knee pain (p = 0.01, Cohen d = 0.74) and quadriceps strength (p = 0.01, Cohen d = 0.49) outcomes. KEM biofeedback induced significant decrease in total support moment (p = 0.05, Cohen f = 0.14) and knee extensor moment (p = 0.05, Cohen f = 0.21) asymmetry compared to using vGRF biofeedback at 6-months. vGRF biofeedback demonstrated significant decrease in hip flexion kinematic asymmetry compared to KEM biofeedback (p = 0.05, Cohen f = 0.18) at 6-months.

Conclusion: Gait compensation remained similar from 3- to 6-months during a task requiring greater knee demand compared to overground walking post-TKA, despite improvements in self-report survey and quadriceps strength. Single session gait symmetry training at 6-month supports findings at 3-month testing that motor learning is possible. KEM biofeedback is more effective at immediately improving joint kinetic loading compared to vGRF biofeedback post-TKA.
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http://dx.doi.org/10.1016/j.knee.2021.03.014DOI Listing
April 2021

Exercise and lung cancer surgery: A systematic review of randomized-controlled trials.

Crit Rev Oncol Hematol 2020 Dec 13;156:103086. Epub 2020 Sep 13.

Huntsman Cancer Institute, Population Sciences, Salt Lake City, UT, United States; Department of Population Health Sciences, University of Utah, Salt Lake City, UT, United States. Electronic address:

Lung cancer patients undergoing surgery are often left physically deconditioned and/or with functional deficits. Exercise interventions may improve pulmonary and physical function before and after lung resection. We conducted a systematic review of randomized-controlled trials (RCTs) testing the impact of pre-, post-, and combined pre-and-post surgery exercise interventions on physical and pulmonary function in lung cancer patients. Exercise pre-surgery seems to substantially improve physical and pulmonary function, which are factors associated with improved ability to undergo surgery while reducing post-surgery complications. Evidence is inconsistent for post-surgery interventions, reporting no or moderate effects. Results from pre-and-post surgery interventions are limited to one study. In conclusion, pre- and post-surgery exercise interventions, individually, have shown beneficial effects for lung cancer patients undergoing surgery. The impact of interventions combining both pre- and post-surgery exercise programs remains unknown. More evidence is needed on the ideal exercise setting, and timing across the lung cancer care continuum.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677203PMC
December 2020

Physical Function in the Hospital Is Associated With Patient-Centered Outcomes in an Inpatient Rehabilitation Facility.

Phys Ther 2020 08;100(8):1237-1248

Department of Physical Therapy and Athletic Training, University of Utah.

Objective: Poor knowledge of the relationships between physical function (PF) in the hospital and patient outcomes in an inpatient rehabilitation facility (IRF) limits the identification of patients most appropriate for discharge to an IRF. This study aimed to test for independent associations between PF measured via the AM-PAC "6-clicks" basic mobility short form in the hospital and outcomes in an IRF.

Methods: This was a retrospective cohort study. Primary data were collected from an acute hospital and IRF at 1 academic medical center. Associations were tested between PF at hospital admission or discharge and PF improvement in the IRF, discharge from the IRF to the community, and 30-day hospital events by estimating adjusted relative risk (aRR) using modified Poisson regression and the relative difference in IRF length of stay (LOS) using Gamma regression.

Results: A total of 1323 patients were included. Patients with moderately low, (aRR = 1.50; 95% CI = 1.15-1.93), moderately high (aRR = 1.52; 95% CI = 1.16-2.01), or high (aRR = 1.37; 95% CI = 1.02-1.85) PF at hospital discharge were more likely than those with very low PF to improve their PF while in the IRF. These same patients were more likely to discharge from IRF to the community and had significantly shorter IRF LOS. Hospital-measured PF did not differentiate risk for 30-day hospital events.

Conclusion: Patients with moderate-but not very low or very high-PF measured near the time of acute hospital discharge were likely to achieve meaningful PF improvement in an IRF. They also had a shorter IRF LOS so may be ideal candidates for discharge to IRF. Prospective studies with larger samples are necessary to test this assertion.

Impact: Providers in the hospital should identify patients with moderate PF near the time of hospital discharge as those who may benefit most from post-acute rehabilitation in an IRF.
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http://dx.doi.org/10.1093/ptj/pzaa073DOI Listing
August 2020

Clinically Integrated Physical Therapist Practice in Cancer Care: A New Comprehensive Approach.

Phys Ther 2020 03;100(3):543-553

Department of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 84108 (USA), and Huntsman Cancer Institute, University of Utah.

Best practice recommendations in cancer care increasingly call for integrated rehabilitation services to address physical impairments and disability. These recommendations have languished primarily due to a lack of pragmatic, generalizable intervention models. This perspective paper proposes a clinically integrated physical therapist (CI-PT) model that enables flexible and scalable services for screening, triage, and intervention addressing functional mobility. The model is based on (1) a CI-PT embedded in cancer care provider clinics, and (2) rehabilitation across the care continuum determined by the patient's level of functional mobility. The CI-PT model includes regular screening of functional mobility in provider clinics via a patient-reported mobility measure-the Activity Measure for Post-Acute Care, a brief physical therapy evaluation tailored to the specific functional needs of the individual-and a tailored, skilled physical therapist intervention based on functional level. The CI-PT model provides a pragmatic, barrier-free, patient-centric, data-driven approach to integrating rehabilitation as part of standard care for survivors of cancer. The model standardizes CI-PT practice and may be sufficiently agile to provide targeted interventions in widely varying cancer settings and populations. Therefore, it may be ideal for wide implementation among outpatient oncological settings. Implementation of this model requires a shared approach to care that includes physical therapists, rehabilitation administrators, cancer care providers, and cancer center administrators.
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http://dx.doi.org/10.1093/ptj/pzz169DOI Listing
March 2020

Preoperative quadriceps weakness preferentially predicts postoperative aberrant movement patterns during high-demand mobility following total knee arthroplasty.

Knee 2019 Jan 29;26(1):79-87. Epub 2018 Dec 29.

University of Utah, Department of Orthopaedics, 590 Wakara Way, Salt Lake City, UT 84108, USA. Electronic address:

Background: Nearly all patients with total knee arthroplasty show aberrant movement patterns during tasks requiring greater joint demand compared to matched peers. Greater movement compensation leads to increased loading onto other joints, decreased functional capacity and limited reserve for independence later in life. Understanding how preoperative predictors contribute to postoperative aberrant movement patterns is needed to make better decisions for patients considering total knee arthroplasty.

Methods: Forty-seven patients were tested preoperatively and six months following primary total knee arthroplasty. Demographic (age, sex, body mass), self-reported (knee pain, perception of physical performance, physical activity level), physical performance (quadriceps strength, lower limb power and timed stair climbing) and surgical metrics were collected as predictor variables. Three-dimensional models based on joint mechanic asymmetry during a decline walking task were collected at six months postoperatively. Decline walking is a preferred means to assess the surgical knee's contribution to limb performance during high-demand tasks. Bootstrap inclusion fraction was employed to compare the stability of each predictor variable prior to the final regression model.

Results: Preoperative quadriceps strength (β = 0.33; p = 0.04) showed a significant relationship with knee extensor angular impulse during loading phase. No other predictor variable had any meaningful relationship with aberrant movement patterns (p > 0.05).

Conclusion: Our findings highlight patients' preoperative quadriceps strength as a meaningful predictor of postoperative performance. Preoperative quadriceps strength should be addressed when considering the knee's ability to contribute to higher demanding mobility tasks following surgery.
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http://dx.doi.org/10.1016/j.knee.2018.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377852PMC
January 2019

Precision-Exercise-Prescription in patients with lung cancer undergoing surgery: rationale and design of the PEP study trial.

BMJ Open 2018 12 16;8(12):e024672. Epub 2018 Dec 16.

Department of Surgery, University of Utah, Salt Lake City, Utah, USA.

Introduction: Lung cancer is a significant burden on societies worldwide, and the most common cause of death in patients with cancer overall. Exercise intervention studies in patients with lung cancer have consistently shown benefits with respect to physical and emotional functioning. However, to date, exercise training has not been consistently implemented into clinical practice given that interventions have been costly and not aligned with clinical care.

Methods/design: The Precision-Exercise-Prescription (PEP) study is a prospective randomised controlled trial comparing the effectiveness and feasibility of a personalised intervention exercise programme among patients with lung cancer undergoing surgery. Two-hundred patients who are diagnosed with stage primary or secondary lung cancer and are eligible to undergo surgical treatment at Huntsman Cancer Institute comprise the target population. Patients are randomised to either the (1) outpatient precision-exercise intervention group or (2) delayed intervention group. The intervention approach uses Motivation and Problem Solving, a hybrid behavioural treatment based on motivational interviewing and practical problem solving. The dosage of the exercise intervention is personalised based on the individual's Activity Measure for Post-Acute-Care outpatient basic mobility score, and incorporates four exercise modes: mobility, callisthenics, aerobic and resistance. Exercise is implemented by physical therapists at study visits from presurgery until 6 months postsurgery. The primary endpoint is the level of physical function assessed by 6 min walk distance at 2 months postsurgery. Secondary outcomes include patient-reported outcomes (eg, quality of life, fatigue and self-efficacy) and other clinical outcomes, including length of stay, complications, readmission, pulmonary function and treatment-related costs up to 6 months postsurgery.

Ethics/dissemination: The PEP study will test the clinical effectiveness and feasibility of a personalised exercise intervention in patients with lung cancer undergoing surgery. Outcomes of this clinical trial will be presented at national and international conferences and symposia and will be published in international, peer-reviewed journals. Ethics approval was obtained at the University of Utah (IRB 00104671).

Trial Registration Number: NCT03306992.
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http://dx.doi.org/10.1136/bmjopen-2018-024672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303592PMC
December 2018

Basic science and clinical use of eccentric contractions: History and uncertainties.

J Sport Health Sci 2018 Jul 20;7(3):265-274. Epub 2018 Jun 20.

Department of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 86011, USA.

The peculiar attributes of muscles that are stretched when active have been noted for nearly a century. Understandably, the focus of muscle physiology has been primarily on shortening and isometric contractions, as eloquently revealed by A.V. Hill and subsequently by his students. When the sliding filament theory was introduced by A.F. Huxley and H.E. Huxley, it was a relatively simple task to link Hill's mechanical observations to the actions of the cross bridges during these shortening and isometric contractions. In contrast, lengthening or eccentric contractions have remained somewhat enigmatic. Dismissed as necessarily causing muscle damage, eccentric contractions have been much more difficult to fit into the cross-bridge theory. The relatively recent discovery of the giant elastic sarcomeric filament titin has thrust a previously missing element into any discussion of muscle function, in particular during active stretch. Indeed, the unexpected contribution of giant elastic proteins to muscle contractile function is highlighted by recent discoveries that twitchin-actin interactions are responsible for the "catch" property of invertebrate muscle. In this review, we examine several current theories that have been proposed to account for the properties of muscle during eccentric contraction. We ask how well each of these explains existing data and how an elastic filament can be incorporated into the sliding filament model. Finally, we review the increasing body of evidence for the benefits of including eccentric contractions into a program of muscle rehabilitation and strengthening.
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http://dx.doi.org/10.1016/j.jshs.2018.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189250PMC
July 2018

Comparison of 2 Forms of Kinetic Biofeedback on the Immediate Correction of Knee Extensor Moment Asymmetry Following Total Knee Arthroplasty During Decline Walking.

J Orthop Sports Phys Ther 2019 Feb 20;49(2):105-111. Epub 2018 Aug 20.

Background: Individuals with total knee arthroplasty (TKA) display interlimb knee extensor moment (KEM) asymmetry during level walking that is exacerbated as task demands are increased. Studies using biofeedback to correct interlimb KEM asymmetry following TKA have reported mixed results.

Objective: To compare the immediate effect of 2 forms of real-time kinetic biofeedback-vertical ground reaction force (vGRF) or KEM-on improving interlimb peak KEM symmetry during the weight-acceptance phase of decline walking in persons who have undergone TKA.

Methods: In this cross-sectional, controlled laboratory study, 30 participants (17 men; mean ± SD age, 61.9 ± 8.5 years; body mass index, 28.4 ± 3.7 kg/m) were allocated to either a vGRF or KEM real-time biofeedback group. Peak KEM interlimb asymmetry was obtained during both nonbiofeedback and biofeedback decline walking trials 3 months following TKA.

Results: Significant interlimb asymmetry in peak KEM was observed in both groups during the nonbiofeedback condition (KEM, P = .02; vGRF, P<.01). The KEM biofeedback group demonstrated an immediate improvement in peak KEM asymmetry (P = .42). No change in peak KEM asymmetry was observed in the vGRF biofeedback group (P = .01).

Conclusion: Knee extensor moment biofeedback has an immediate effect on improving peak KEM asymmetry 3 months post TKA. J Orthop Sports Phys Ther 2019;49(2):105-111. Epub 20 Aug 2018. doi:10.2519/jospt.2019.7800.
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http://dx.doi.org/10.2519/jospt.2019.7800DOI Listing
February 2019

The Positive Benefits of Negative Movement Patterns Following Total Knee Arthroplasty.

Geriatr Orthop Surg Rehabil 2018 26;9:2151458518757796. Epub 2018 Mar 26.

Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA.

Introduction: Eccentric (negative) resistance exercise of the legs using specialized machines has been reported to be useful and often superior to standard exercise following total knee arthroplasty (TKA). Movements that utilize body mass and gravity as a mode of eccentric resistance exercise in a more pragmatic rehabilitation paradigm may also be useful in reversing chronic muscle impairments observed years following surgery. This study explores whether an eccentrically biased, body mass resistance exercise induces greater magnitude of sagittal plane extensor angular impulse of the support torque and individual net joint torque contributions during both squatting and lunging movement patterns 6 weeks following TKA.

Methods: Cross-sectional laboratory-based study design including 10 patients following primary unilateral TKA (6.5 ± 0.8 weeks.). All patients completed 3 trials of the squat and lunge movement pattern under both a concentric and an eccentric condition. Extensor angular impulse of the support torque and net joint torque contributions were calculated by integrating the joint torque versus time curves. A Two-way analysis of covariance was conducted and contracts of clinical interest were computed using Wald posttest. Values for all pairwise comparisons were adjusted for multiplicity using Bonferroni multiple comparison procedure.

Results: The eccentric condition, compared to the concentric condition, displayed larger magnitude of extensor angular impulse during both the squat ( < .001) and lunge ( < .001) movement patterns for the support torques. Similarly, the eccentric condition, compared to the concentric condition, displayed larger magnitude of extensor angular impulse of the hip, knee, and ankle ( < .001) during both movement patterns.

Conclusion: Eccentrically biased, body mass movement exercises can produce higher levels of extensor angular impulse on the surgical limb in patients early after TKA. Patients in this study were able to tolerate the higher extensor angular impulse demands and performed the eccentrically biased conditions (without specialized machines) that could be beneficial in postoperative rehabilitation.
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http://dx.doi.org/10.1177/2151458518757796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881975PMC
March 2018

Quadriceps weakness preferentially predicts detrimental gait compensations among common impairments after total knee arthroplasty.

J Orthop Res 2018 09 24;36(9):2355-2363. Epub 2018 Apr 24.

Department of Physical Therapy & Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, Utah 84108.

Patients with total knee arthroplasty (TKA) have large deficits in physical performance in comparison to their healthy age-matched peers. Limb asymmetry stemming from less relative load borne by the surgical limb during daily mobility is associated with diminished performance and worsens with greater mobility demands. How common targets of postoperative care, such as muscle weakness, lower limb extension power, residual knee pain, and poor balance confidence can influence asymmetrical limb loading remains unclear. Forty-six patients with unilateral TKA underwent testing of impairments and motion analysis during 10° decline walking at 3 and 6 months postoperatively. At 3 months, only quadriceps femoris strength asymmetry was found to be significantly related to both total support moment (M ) (β = 0.431; p < 0.001) and knee extensor moment (M ) (β = 0.493; p < 0.001) asymmetry. Again at 6 months, only quadriceps strength asymmetry was related to M (β = 0.432; p < 0.001) and M (β = 0.534; p < 0.001) asymmetry. Quadriceps strength significantly improved over time in both limbs, however, deficits between limbs remained. Persistent quadriceps weakness is a key factor associated with walking compensation patterns that are limiting the capacity for greater physical performance of patients with TKA. The pronounced asymmetry in limb and knee loading at 3 months remains unchanged until at least 6 months after surgery, and its association with quadriceps strength asymmetry does not substantially change over time. While other factors may also prompt gait compensations, emphasis on improved quadriceps strength should be a focus of efforts to resolve gait compensations and enhance physical performance outcomes. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2355-2363, 2018.
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http://dx.doi.org/10.1002/jor.23894DOI Listing
September 2018

Clinical Efficacy of Jump Training Augmented With Body Weight Support After ACL Reconstruction: A Randomized Controlled Trial.

Am J Sports Med 2018 06 20;46(7):1650-1660. Epub 2018 Mar 20.

School of Physical Therapy and Rehabilitation Science, University of Montana, Missoula, Montana, USA.

Background: Limited knee flexion and increased muscle co-contraction during jump landing are believed to diminish outcomes after anterior cruciate ligament (ACL) reconstruction. The efficacy of jump training to improve patients' mechanical and neuromuscular deficits is understudied.

Hypothesis: Jump training will improve functional, mechanical, and neuromuscular outcomes and higher repetition training augmented by body weight support will result in better retention of gains.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: Thirty athletes (18 months after surgery) were screened, and 19 with mechanical deficits and limited clinical outcomes were enrolled in the trial. Testing included the International Knee Documentation Committee (IKDC) questionnaire, leg landing mechanics via motion analysis, knee joint effusion using a stroke test, and a surface electromyography-generated co-contraction index during a single-legged landing. Participants were randomly assigned to 1 of 2 groups: jump training with normal body weight (JTBW) and high-repetition jump training with body weight support (JTBWS). Knee effusion grading throughout training was used to assess joint tolerance. Changes in outcomes over time were analyzed with mixed-effects modeling. Immediate outcomes were compared with retention testing at 8 weeks after training by use of 2-way analyses of variance with effects of time and group.

Results: Significant effects of time were found during the training phase for all outcome measures, but no effects of group or sex were found. IKDC score (pooled; mean ± SD) increased from 76 ± 12 to 87 ± 8 ( P < .001). Knee flexion during single-legged landing increased from 57° ± 11° to 73° ± 9° ( P < .001). Average co-contraction index decreased from 37 ± 15 to 19 ± 6 ( P < .001). All measures were retained over the retention period in both groups. The relative risk of knee effusion of the JTBW group versus the JTBWS group was 4.2 (95% CI, 2.25-7.71; P < .001).

Conclusion: Jump training mitigated some risk factors for second injury and osteoarthritis in patients after ACL reconstruction. Training made lasting improvements in physical function measures as well as mechanical and neuromuscular coordination deficits. Higher repetitions used with body weight support did not improve retention but substantially reduced risk for effusion.

Clinical Relevance: Jump training is an efficacious intervention for athletes with poor outcomes after ACL reconstruction, and training with body weight support lessens the risk for excessive joint stress during practice. Registration: NCT02148172 ( ClinicalTrials.gov identifier).
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http://dx.doi.org/10.1177/0363546518759052DOI Listing
June 2018

Visual knee-kinetic biofeedback technique normalizes gait abnormalities during high-demand mobility after total knee arthroplasty.

Knee 2018 Jan 2;25(1):73-82. Epub 2018 Jan 2.

University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States. Electronic address:

Background: Abnormal knee mechanics frequently follow total knee arthroplasty (TKA) surgery with these deficits amplifying as task demands increase. Knee-kinetic biofeedback could provide a means of attenuating gait abnormalities. The purposes of this study were as follows: (1) to describe the gait characteristic differences between patients with TKA and non-TKA adults during level (low-demand) and decline (high-demand) walking; and (2) where differences existed, to determine the impact of knee-kinetic biofeedback on normalizing these abnormalities.

Methods: Twenty participants six months following a primary TKA and 15 non-TKA peers underwent gait analysis testing during level and decline walking. Knee-kinetic biofeedback was implemented to patients with TKA to correct abnormal gait characteristics if observed.

Results: Patients with TKA had lower knee extensor angular impulse (p<0.001), vGRF (p=0.001) and knee flexion motion (p=0.005) compared to the non-TKA group during decline walking without biofeedback. Patients with TKA normalized their knee extensor angular impulse (p=0.991) and peak vGRF (p=0.299) during decline walking when exposed to biofeedback. No between-group differences were observed during level walking. Groups were similar in age, gender, body mass index, physical activity level, pain interference and depression scores (p>0.05).

Conclusion: Patients with TKA demonstrate abnormal gait characteristics during a high-demand walking task when compared to non-TKA peers. Our findings indicate that knee-kinetic biofeedback can induce immediate improvements in gait characteristics during a high-demand walking task. There may be a potential role for the use of visual knee-kinetic biofeedback techniques to improve gait abnormalities during high-demand tasks following TKA.
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http://dx.doi.org/10.1016/j.knee.2017.11.010DOI Listing
January 2018

Joint mechanical asymmetries during low- and high-demand mobility tasks: Comparison between total knee arthroplasty and healthy-matched peers.

Gait Posture 2018 02 21;60:104-110. Epub 2017 Nov 21.

University of Utah, Department of Orthopaedics, Salt Lake City, UT, United States; University of Utah, Department of Physical Therapy & Athletic Training, Salt Lake City, UT, United States.

Chronic inter-limb joint mechanical asymmetry has been reported following total knee arthroplasty (TKA) during low-demand mobility tasks such as level walking. However, no study has compared the inter-limb asymmetry during a high-demand mobility task such as decline walking. The objective of this cross-sectional study was to compare inter-limb asymmetry differences during both level and decline walking tasks at six months following TKA compared to asymmetry present in an age, gender, body mass index and activity level matched healthy cohort. Kinetic and kinematic gait analysis was conducted on 42 patients with TKA and 15 healthy-matched peers. Our inter-limb asymmetry results demonstrated significantly (p<0.05) greater combined limb support moment (M) (mean differences [MD]=0.17; 95% CI=0.07, 0.22), knee extensor moment (M) (MD=0.05; 95% CI=0.02, 0.09) and vertical ground reaction force (vGRF) (MD=0.03; 95% CI=0.01, 0.08) differences during decline walking compared to level walking in patients with TKA. Greater M (MD=0.24; 95% CI=0.13, 0.35), M (MD=0.08; 95% CI=0.03, 0.18), vGRF (MD=0.04; 95% CI=0.01, 0.08) and knee joint angle (MD=2.4; 95% CI=0.37, 3.80) differences were present in patients with TKA compared to healthy-matched peers during decline walking. Greater M (MD=0.13; 95% CI=0.05, 0.20) and plantarflexor moment (MD=0.06; 95% CI=0.04, 0.16) differences were present in patients with TKA compared to healthy-matched peers during level walking. Post-TKA inter-limb asymmetry during level walking worsens as the physical demands of the task are increased. Thus, even patients with good self-reported outcomes after TKA exhibit substantial deficits in their mobility reserves that could limit their independence and community mobility as they age.
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http://dx.doi.org/10.1016/j.gaitpost.2017.11.017DOI Listing
February 2018

Aging-related effects of bed rest followed by eccentric exercise rehabilitation on skeletal muscle macrophages and insulin sensitivity.

Exp Gerontol 2018 07 10;107:37-49. Epub 2017 Jul 10.

Department of Physical Therapy and Athletic Training, University of Utah, 520 Wakara Way, Salt Lake City, UT 84018, USA; Department of Nutrition and Integrative Physiology, University of Utah, 250 S. 1850 E, RM 214, Salt Lake City, UT 84112, USA. Electronic address:

The pro- and anti-inflammatory macrophages are associated with insulin sensitivity and skeletal muscle regeneration. Infiltrating macrophages in skeletal muscle during a period of physical inactivity and subsequent reloading/rehabilitation in older adults is unknown, but may provide insight into mechanisms related to the development of metabolic disease and changes in muscle cell size. The purpose of this study was to determine if skeletal muscle macrophage infiltration is modulated differently between young and older adults after bed rest and exercise rehabilitation and if these responses are related to muscle and insulin sensitivity changes. 14 young and 9 older adults underwent 5-days of bed rest followed by 8-weeks of lower limb eccentric exercise rehabilitation (REHAB). Dual-energy X-ray absorptiometry, magnetic resonance imaging and myofiber analysis were used to identify muscle morphology and CLIX-IR and CLIX-β were used to assess insulin sensitivity. Skeletal muscle macrophages, CD68 (pan), CD11b (M1), CD163 (M2), CD206 (M2), were characterized using immunohistochemistry and gene expression. Insulin sensitivity, independent of age, decreased ~38% following bed rest and was restored following REHAB. We found robust age-related differences in muscle atrophy during bed rest, yet older and younger adults equally hypertrophied during REHAB. Interestingly, there were age-related differences in macrophage content (CD68CD11b and CD68CD11b cells) but both young and old similarly increased macrophages with REHAB. Satellite cell changes during rehab corresponded to macrophage content changes. Muscle tissue resident macrophages and gene expression, were not associated with changes in insulin sensitivity following bed rest and REHAB. These data suggest that muscle macrophages are modulated as a result of exercise rehabilitation following bed rest and may more associated with muscle regrowth/hypertrophy rather than insulin sensitivity in young or older adults. This trial was registered at clinicaltrials.gov as NCT01669590.
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http://dx.doi.org/10.1016/j.exger.2017.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762440PMC
July 2018

Chronic eccentric arm cycling improves maximum upper-body strength and power.

Eur J Appl Physiol 2017 Jul 17;117(7):1473-1483. Epub 2017 May 17.

Department of Physical Therapy, University of Utah, Salt Lake City, UT, 84108, USA.

Introduction: Eccentric leg cycling (cycle ergometry adapted to impose muscle lengthening contractions) offers an effective exercise for restoring lower-body muscular function, maintaining health, and improving performance in clinical and athletic populations.

Purpose: We extended this model to the upper body and evaluated the effectiveness of a 7-week eccentric arm cycling (ECC) intervention to improve upper-body muscular function. We also explored whether ECC would alter arterial function.

Methods: Participants performed ECC (n = 9) or concentric arm cycling (CON; n = 8) 3×/week while training intensity increased (5-20 min, 60-70% upper-body peak heart rate). Maximum elbow extensor strength, upper-body concentric power, and peripheral and central arterial stiffness were assessed before and after training.

Results: During training, heart rates and perceived exertion did not differ between groups (~68% upper-body peak heart rate, ~12 Borg units, both P > 0.05), whereas power during ECC was ~2× that for CON (122 ± 43 vs. 59 ± 20 W, P < 0.01). Muscle soreness for ECC was greater than CON (P = 0.02), however, soreness was minimal for both groups (<0.50 cm). Following training, ECC exhibited greater changes in elbow extensor strength (16 ± 10 vs. 1 ± 9%, P = 0.01) and upper-body power (6 ± 8 vs. -3 ± 7%, P < 0.01) compared to CON. Peripheral and central arterial stiffness did not change for either group (both P > 0.05).

Conclusion: Upper-body eccentric exercise improved dynamic muscular function while training at low exertion levels. Results occurred with minimal soreness and without compromising arterial function. ECC findings parallel eccentric leg cycling findings and indicate that eccentric cycle ergometry offers a robust model for enhancing upper-body muscular function. ECC could have applications in rehabilitation and sport training.
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http://dx.doi.org/10.1007/s00421-017-3642-9DOI Listing
July 2017

Neuromuscular Electrical Stimulation Combined with Protein Ingestion Preserves Thigh Muscle Mass But Not Muscle Function in Healthy Older Adults During 5 Days of Bed Rest.

Rejuvenation Res 2017 Dec 19;20(6):449-461. Epub 2017 Jun 19.

1 Department of Physical Therapy and Athletic Training, University of Utah , Salt Lake City, Utah.

Short-term bed rest in older adults is characterized by significant loss in leg lean mass and strength posing significant health consequences. The purpose of this study was to determine in healthy older adults if the daily combination of neuromuscular electrical stimulation and protein supplementation (NMES+PRO) would protect muscle mass and function after 5 days of bed rest. Twenty healthy older adults (∼70 years) were subjected to 5 days of continuous bed rest and were randomized into one of two groups: NMES+PRO (n = 10) or control (CON) (n = 10). The NMES+PRO group received bilateral NMES to quadriceps (40 minutes/session, 3 × /day; morning, afternoon, and evening) followed by an interventional protein supplement (17 g). The CON group received an isocaloric equivalent beverage. Before and after bed rest, vastus lateralis biopsies occurred before and after acute essential amino acid (EAA) ingestion for purposes of acutely stimulating mechanistic target of rapamycin (mTORC1) signaling, a major regulator of muscle protein synthesis, in response to bed rest and NMES+PRO. Baseline (pre and post bed rest) muscle samples were also used to assess myofiber characteristics and gene expression of muscle atrophy markers. Thigh lean mass and muscle function were measured before and after bed rest. Five days of bed rest reduced thigh lean mass, muscle function, myofiber cross-sectional area, satellite cell content, blunted EAA-induced mTORC1 signaling, and increased myostatin and MAFbx mRNA expression. Interestingly, NMES+PRO during bed rest maintained thigh lean mass, but not muscle function. Thigh muscle preservation during bed rest with NMES+PRO may partly be explained by attenuation of myostatin and MAFbx mRNA expression rather than restoration of nutrient-induced mTORC1 signaling. We conclude that the combination of NMES and protein supplementation thrice a day may be an effective therapeutic tool to use to preserve thigh muscle mass during periods of short-term hospitalization in older adults. However this combined intervention was not effective to prevent the loss in muscle function.
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http://dx.doi.org/10.1089/rej.2017.1942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731550PMC
December 2017

Asymmetries Identified in Sit-to-Stand Task Explain Physical Function After Hip Fracture.

J Geriatr Phys Ther 2018 Oct/Dec;41(4):210-217

Department of Physical Therapy, College of Health, University of Utah, Salt Lake City, Utah.

Background: Several known demographic and functional characteristics combine to predict physical function after hip fracture. Long-term weight-bearing asymmetries, evident during functional movements after hip fracture, contribute to limited mobility and large asymmetries in muscle function are linked to a high rate of injurious falls. Although postfracture mobility is commonly measured as whole body movement, a force-plate imbedded chair can identify individual limb contributions to an important task like moving from a sitting to standing position. The modified Physical Performance Test (mPPT) and stair climb test (SCT) are reliable, valid measures of function that predict independence after hip fracture. The purpose of this study was to determine to what extent asymmetry during a sit-to-stand task (STST) predicts function (mPPT, 12-step SCT), above and beyond other known predictors.

Methods: Thirty-one independent community-dwelling older adults, recently discharged from usual care physical therapy (mean [standard deviation], 77.7 [10.5] years, 10 male), within 2 to 8 months postfracture, volunteered for this study. Participants performed an STST on a force-plate-imbedded chair designed to identify individual limb contributions during an STST. Asymmetry magnitude during the STST was determined for each individual. In addition, mPPT and SCT were assessed and regression analyses were performed to determine the contribution of asymmetry to the variance in these physical function scores beyond other factors predicting function.

Results: Demographic factors (sex, time since fracture, repair type, and body mass index) were not significantly related to function in this sample. Age, gait speed, knee extension strength, balance confidence, and functional self-report were each significantly related to both mPPT (r = 0.43-0.86) and SCT (r = 0.40-0.83), and were retained in the regression model. Included variables accounted for 83.4% of the variance in mPPT score, and asymmetry during the STST did not significantly contribute to explaining variability in mPPT (P = .23). Variables in the regression model accounted for 78.0% of the variance in SCT score, and STST asymmetry explained 7.1% (P < .005) of the variance in SCT score.

Discussion: In this small sample, asymmetry contributed significantly to explaining the variability in SCT performance, but not mPPT score. The SCT requires greater unilateral strength and control than the battery of items that comprise the mPPT. This contributes to the disproportionate number of falls occurring during stair ambulation (>10% of all fall-related deaths), relative to the minimal time typically involved in stair negotiation. Our results indicate potential benefit to identifying injured limb asymmetries as they predict function in challenging, high-risk functional tasks after hip fracture.

Conclusion: Although gait speed is the best explanator of physical function in older adults after hip fracture, lower extremity asymmetry during an STST provides a unique contribution to explaining high-level ambulatory performance after hip fracture. Efforts to reduce weight-bearing asymmetry during rehabilitation following hip fracture may improve function and recovery.
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http://dx.doi.org/10.1519/JPT.0000000000000122DOI Listing
September 2019

Stance time variability during stair stepping before and after total knee arthroplasty: A pilot study.

Hum Mov Sci 2016 Feb 17;45:53-62. Epub 2015 Nov 17.

Department of Bioengineering, University of Utah, Salt Lake City, UT, USA; Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA; Department of Orthopedics, University of Utah, Salt Lake City, UT, USA; Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.

The main objectives of this pilot study were to: (1) investigate stance time variability (STV) during stair stepping in older adults with osteoarthritis (OA) before and after total knee arthroplasty (TKA), and compare to an age- and sex-matched group of healthy controls with native knees and (2) evaluate the relationship between quadriceps strength and STV during stair stepping before and after TKA. A prospective, observational, pilot study was carried out on 13 individuals (15% male, mean age 62.71±6.84years) before and after TKA using an instrumented stairway, patient-reported outcomes, timed stair stepping test, and quadriceps strength measures. At 6-months post-operatively, STV during stair descent was significantly greater in the TKA-GROUP compared to the CONTROL-GROUP, but was not significantly different at 12-months compared to controls. There were no significant differences in STV for stair ascent between the pre- and post-operative visits, or compared to controls. There was a trend toward significance for the relationship between quadriceps strength and STV during stair ascent (P=0.059) and descent (P=0.073). Variability during stair stepping may provide an important, short-term rehabilitation target for individuals following TKA and may represent another parameter to predict declines in functional mobility.
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http://dx.doi.org/10.1016/j.humov.2015.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688059PMC
February 2016

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

J Physiol 2015 Sep 31;593(18):4259-73. Epub 2015 Jul 31.

Department of Physical Therapy, University of Utah, Salt Lake City, UT, USA.

Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.
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http://dx.doi.org/10.1113/JP270699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594296PMC
September 2015

Low Physical Function in Maintenance Hemodialysis Patients Is Independent of Muscle Mass and Comorbidity.

J Ren Nutr 2015 Jul 30;25(4):371-5. Epub 2015 Mar 30.

Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah; Veterans Affairs Salt Lake City Healthcare System, Renal Section, Salt Lake City, Utah. Electronic address:

Objectives: It is unknown whether muscle wasting accounts for impaired physical function in adults on maintenance hemodialysis (MHD).

Design: Observational study.

Setting: Outpatient dialysis units and a fall clinic.

Subjects: One hundred eight MHD and 122 elderly nonhemodialysis (non-HD) participants.

Exposure Variable: Mid-thigh muscle area was measured by magnetic resonance imaging.

Main Outcome Measure: Physical function was measured by distance walked in 6 minutes.

Results: Compared with non-HD elderly participants, MHD participants were younger (49.2 ± 15.8 vs. 75.3 ± 7.1 years; P < .001) and had higher mid-thigh muscle area (106.2 ± 26.8 vs. 96.1 ± 21.1 cm2; P = .002). However, the distance walked in 6 minutes was lower in MHD participants (322.9 ± 110.4 vs. 409.0 ± 128.3 m; P < .001). In multiple regression analysis adjusted for demographics, comorbid conditions, and mid-thigh muscle area, MHD patients walked significantly less distance (-117 m; 95% confidence interval: -177 to -56 m; P < .001) than the non-HD elderly.

Conclusions: Even when compared with elderly non-HD participants, younger MHD participants have poorer physical function that was not explained by muscle mass or comorbid conditions. We speculate that the uremic milieu may impair muscle function independent of muscle mass. The mechanism of impaired muscle function in uremia needs to be established in future studies.
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http://dx.doi.org/10.1053/j.jrn.2015.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469499PMC
July 2015

Effects of practice on variability of muscle force.

Percept Mot Skills 2015 Apr 23;120(2):475-90. Epub 2015 Mar 23.

1 University of Utah.

The motor skill required to decrease the variability in muscle force steadiness can be challenging. The purposes of this study were to determine whether muscle force steadiness improved following repeated trials and whether the number of trials varied for healthy younger adults, healthy older adults, and older adults who have fallen to obtain stable muscle force steadiness measures. Sixty participants performed 30 concentric and eccentric contractions of the knee extensors on an isokinetic dynamometer. Each group had significant improvements in muscle force steadiness and obtained stable measures within six to nine trials. Healthy younger and older adults, and older adults who have fallen, can improve muscle force steadiness. These findings provide a framework for methodological approaches when testing steadiness in varying populations.
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http://dx.doi.org/10.2466/26.PMS.120v12x4DOI Listing
April 2015

Exercise and medication effects on persons with Parkinson disease across the domains of disability: a randomized clinical trial.

J Neurol Phys Ther 2015 Apr;39(2):85-92

Department of Physical Therapy (L.E.D., K.B.F., R.L.M., P.C.L.), University of Utah, Salt Lake City; and Department of Medicine (O.A.), Division of Gerontology and Geriatric Medicine, University of Maryland School of Medicine, and Veterans Affairs Geriatric Research, Education and Clinical Center and Research Development Service, Baltimore.

Background And Purpose: Hypokinesia and bradykinesia as movement deficits of Parkinson disease are thought to be mediated by both basal ganglia dysfunction and a loss of muscle mass and strength commensurate with aging and decreased levels of physical activity. For these reasons, we sought to utilize resistance training as a means to increase muscle force and minimize hypokinesia and bradykinesia in persons with Parkinson disease and examine the effects of exercise and medication on Body Structure and Function (muscle force production and muscle cross-sectional area), Activity (mobility), and Participation (Health Status) outcomes.

Methods: Forty-two participants were enrolled in a 12-week randomized clinical trial that compared 2 active exercise interventions: a standard care control group (Active Control) and an experimental group that underwent Resistance Exercise via Negative Eccentric Work (RENEW).

Results: Participants in both groups improved in muscle force production and mobility as a result of exercise and medication (P < 0.02). There were no significant interaction or between-group differences and no significant changes in muscle cross-sectional area or health status were observed. Effect sizes for exercise and medication combined exceeded the effect sizes of either intervention in isolation.

Discussion And Conclusions: Taken together, these results point to the complementary effects of exercise and medication on the Body Structure and Function and Activity outcomes but little effect on Participation outcomes.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A92).
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http://dx.doi.org/10.1097/NPT.0000000000000086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366306PMC
April 2015

The Association Between Knee Extensor Force Steadiness, Force Accuracy, and Mobility in Older Adults Who Have Fallen.

J Geriatr Phys Ther 2016 Jan-Mar;39(1):1-7

1Department of Physical Therapy, University of Utah, Salt Lake City, Utah. 2DPT Program, Rocky Mountain University of Health Professions, Provo, Utah. 3Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado.

Background: Older adults often experience limited mobility, lower extremity muscle weakness, and increased fall risk. Furthermore, when older adults perform tasks that require control of submaximal force, impairments in their ability to maintain steady and accurate force output have been reported. Such problems may be related to deteriorating levels of mobility, particularly in older adults who have fallen.

Purpose: The purpose of this study was to determine whether an association exists between muscle force steadiness (MFS) or muscle force accuracy (MFA) of the knee extensors and mobility in older adults who have fallen.

Methods: Twenty older adults ((Equation is included in full-text article.)= 77.5 ± 7 years, 5 males and 15 females) with 2 or more comorbid conditions and who experienced a fall in the past year underwent assessment of maximal voluntary isometric contraction of the knee extensors. A submaximal target force of 50% of their maximal voluntary isometric contraction was used to determine concentric and eccentric (ECC) steadiness (the fluctuations in force production) and accuracy (the average distance of the mean force from the target force) measures. Mobility was indicated by the 6-minute walk test, the Timed Up and Go, stair ascent, and stair descent tests. Correlation analysis was used to assess the relationship between measures of muscle force control and mobility.

Results: The correlations between muscle force steadiness and mobility were not significant (P > .05) for either contraction type. However, MFA during ECC contractions only was correlated significantly with all measures of mobility-6 minute walk test (r = -0.48; P = .03), Timed Up and Go (r = 0.68; P = .01), stair ascent (r = 0.60; P = .01), and stair descent (r = 0.75; P < .01).

Conclusion: The identification of the relationship between ECC MFA and mobility in older adults who have fallen is novel. Although the correlations are not causal, these relationships suggest that inaccurate force output during ECC contractions of the knee extensors is linked to impaired mobility.
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http://dx.doi.org/10.1519/JPT.0000000000000044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540703PMC
September 2016

Blood pressure, salivary cortisol, and inflammatory cytokine outcomes in senior female cancer survivors enrolled in a tai chi chih randomized controlled trial.

J Cancer Surviv 2015 Mar 28;9(1):115-25. Epub 2014 Aug 28.

Program on Integrative Medicine, Department of Physical Medicine & Rehabilitation, University of North Carolina at Chapel Hill, CB# 7200, Chapel Hill, NC, 27599-7200, USA,

Purpose: Older cancer survivors are a vulnerable population due to an increased risk for chronic diseases (e.g., cardiovascular disease) compounded with treatment late-effects and declines in physical functioning. Therefore, interventions that reduce chronic disease risk factors (i.e., blood pressure, chronic inflammation, and cortisol) are important in this population. Tai chi chih (TCC) is a mind-body exercise associated with reductions in chronic disease risk factors, but has not been examined with older cancer survivors. In a feasibility randomized controlled trial of TCC, we examined secondary outcomes of blood pressure, salivary cortisol, and inflammatory cytokines (interleukin (IL)-6, IL-12, tumor necrosis factor-α, IL-10, IL-4) due to their implications in chronic diseases.

Methods: Sixty-three senior female cancer survivors (M age = 67 years, SD = 7.15) with physical functioning limitations (SF-12 physical functioning ≤80 or role-physical ≤72) were randomized to 12-weeks (60-min, three times a week) of TCC or Health Education control (HEC) classes. Resting blood pressure, 1-day salivary cortisol samples, and fasting plasma samples for cytokine multiplex assays were collected at baseline and 1-week post-intervention.

Results: Controlling for baseline values, the TCC group had significantly lower systolic blood pressure (SBP, p = 0.002) and cortisol area-under-curve (AUC, p = 0.02) at post-intervention than the HEC group. There was no intervention effect on inflammatory cytokines (p's > 0.05).

Conclusions: This TCC feasibility trial was associated with significant reductions in SBP and cortisol AUC in senior female cancer survivors. Larger, definitive trials are needed to confirm these findings.

Implications For Cancer Survivors: Senior survivors' have an increased risk for chronic diseases; however, TCC interventions may help reduce associated risk factors.
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http://dx.doi.org/10.1007/s11764-014-0395-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344390PMC
March 2015

Revisiting the positive aspects of negative work.

J Exp Biol 2014 Jul;217(Pt 14):2434-6

University of Utah

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http://dx.doi.org/10.1242/jeb.092247DOI Listing
July 2014

Muscle force and movement variability before and after total knee arthroplasty: A review.

World J Orthop 2014 Apr 18;5(2):69-79. Epub 2014 Apr 18.

Jessica W Smith, Paul C LaStayo, Department of Bioengineering, University of Utah, Salt Lake City, UT 84108-1290, United States.

Variability in muscle force output and movement variability are important aspects of identifying individuals with mobility deficits, central nervous system impairments, and future risk of falling. This has been investigated in elderly healthy and impaired adults, as well as in adults with osteoarthritis (OA), but the question of whether the same correlations also apply to those who have undergone a surgical intervention such as total knee arthroplasty (TKA) is still being investigated. While there is a growing body of literature identifying potential rehabilitation targets for individuals who have undergone TKA, it is important to first understand the underlying post-operative impairments to more efficiently target functional deficits that may lead to improved long-term outcomes. The purpose of this article is to review the potential role of muscle force output and movement variability in TKA recipients. The narrative review relies on existing literature in elderly healthy and impaired individuals, as well as in those with OA before and following TKA. The variables that may predict long-term functional abilities and deficits are discussed in the context of existing literature in healthy older adults and older adults with OA and following TKA, as well as the role future research in this field may play in providing evidence-based data for improved rehabilitation targets.
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http://dx.doi.org/10.5312/wjo.v5.i2.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017309PMC
April 2014

Intermuscular fat: a review of the consequences and causes.

Int J Endocrinol 2014 8;2014:309570. Epub 2014 Jan 8.

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, 10 North Green Street, BT/18/GRECC, Baltimore, MD 21201, USA ; Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, USA.

Muscle's structural composition is an important factor underlying muscle strength and physical function in older adults. There is an increasing amount of research to support the clear disassociation between the loss of muscle lean tissue mass and strength with aging. This disassociation implies that factors in addition to lean muscle mass are responsible for the decreases in strength and function seen with aging. Intermuscular adipose tissue (IMAT) is a significant predictor of both muscle function and mobility function in older adults and across a wide variety of comorbid conditions such as stroke, spinal cord injury, diabetes, and COPD. IMAT is also implicated in metabolic dysfunction such as insulin resistance. The purpose of this narrative review is to provide a review of the implications of increased IMAT levels in metabolic, muscle, and mobility function. Potential treatment options to mitigate increasing levels of IMAT will also be discussed.
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http://dx.doi.org/10.1155/2014/309570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3910392PMC
June 2014

Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: a cross-sectional comparison.

J Gerontol A Biol Sci Med Sci 2014 Aug 13;69(8):1040-8. Epub 2014 Feb 13.

Department of Physical Therapy.

Background And Objectives: Reduced lean mass and physical function is a characteristic of frailty. However, it is currently unknown if proteolysis through the E3 ubiquitin ligases and the autophagic lysosomal pathway is dysregulated in inactive frail older women. The purpose of this study was to determine the expression of key markers of ubiquitin-mediated and autophagic lysosomal proteolysis in inactive (N = 7) compared with active (N = 7) older women.

Methods: Strength, mobility, leg lean mass, and physical activity assessment were used to characterize activity levels and frailty in older women. Vastus lateralis biopsies were collected after an overnight fast and were assessed for gene and protein targets related to E3 ubiquitin ligases and the autophagic lysosomal system.

Results: We found that AMP-activated protein kinase alpha (Thr172) was increased (p = .045), and forkhead box O3A (FOXO3A) gene expression (p = .047) was lower in inactive frail older women. Foxo3a (Ser253), Beclin1 (Ser93/96), and class III phosphatidylinositol-3-kinase (VPS34) protein expression were not different between the groups (p > .05). Neural precursor cell-expressed developmentally downregulated protein 4, muscle ring finger 1, muscle atrophy F-box, and the autophagy/mitophagy gene expression markers, Beclin1, autophagy-related-7, BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), dynamin-related protein 1, and Parkinson protein 2 (PARKIN) were lower in inactive frail older women (p < .05). Autophagy/mitophagy markers were positively correlated with the 6-minute walk and leg lean mass (p < .05).

Conclusions: We conclude that physical inactivity in frail older women is associated with a downregulation of ubiquitin-mediated and autophagic lysosomal skeletal muscle gene expression, perhaps related to low muscle mass and poor physical function.
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http://dx.doi.org/10.1093/gerona/glu004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111292PMC
August 2014

Muscle force steadiness in older adults before and after total knee arthroplasty.

J Arthroplasty 2014 Jun 2;29(6):1143-8. Epub 2013 Dec 2.

Department of Bioengineering, University of Utah; Department of Physical Therapy, University of Utah; Department of Orthopedics and University Orthopedics Center, University of Utah; Department of Exercise Science, University of Utah.

The ability to control submaximal muscle forces has been shown to be associated with age-related decreases in physical function, such as increased tendency to fall. This study compared quadriceps muscle force steadiness (MFS) in individuals with knee OA before and after total knee arthroplasty (TKA) to an age-matched group of controls. Lower extremity MFS was measured in 13 subjects with knee OA before and at six months after TKA (TKA-GROUP) and compared to an age-matched control group (CONTROL-GROUP). MFS was significantly more impaired in the TKA-GROUP at the pre-operative, but not post-operative visit, and significantly improved between the pre-operative and post-operative visits. Further research is warranted to evaluate the relation between this MFS measurement and physical functional performance in those at high risk for falling.
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http://dx.doi.org/10.1016/j.arth.2013.11.023DOI Listing
June 2014