Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H2O2 emission and production in healthy, older adults: A randomized controlled trial.

BACKGROUND AND AIMS: Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults. METHODS: We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers. RESULTS: We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial H2O2 emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59 ± 0.72 SE Fold, P = 0.04; METF production: 2.29 ± 0.53 SE Fold, P = 0.02). Furthermore, the change in H2O2 emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R2 = 0.5816, P = 0.0006; METF: R2 = 0.674, P = 0.0125). CONCLUSIONS: These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics. CLINICAL TRIAL REGISTRATION: NCT03107884, clinicaltrials.gov.

Impact of the COVID-19 pandemic on rural and urban cancer patients' experiences, health behaviors, and perceptions.

PURPOSE: The COVID-19 pandemic has disrupted many facets of life. We evaluated pandemic-related health care experiences, COVID-19 prevention behaviors and measures, health behaviors, and psychosocial outcomes among rural and urban cancer patients. METHODS: Among 1,472 adult cancer patients, who visited Huntsman Cancer Institute in the past 4 years and completed a COVID-19 survey (August-September 2020), we assessed the impact of the pandemic on medical appointments, prevention/health behaviors, and psychosocial factors, stratified by urbanicity. FINDINGS: Mean age was 61 years, with 52% female, 97% non-Hispanic White, and 27% were residing in rural areas. Rural versus urban patients were more likely to be older, not employed, uninsured, former/current smokers, consume alcohol, and have pandemic-related changes/cancellations in surgery appointments (all P<.05). Changes/cancellations in other health care access (eg, doctor's visits) were also common, particularly among urban patients. Urban versus rural patients were more likely to socially distance, use masks and hand sanitizer, and experience changes in exercise habits and in their daily lives (all P<.05). Less social interaction and financial stress were common among cancer patients but did not differ by urbanicity. CONCLUSIONS: These findings suggest that the COVID-19 pandemic had a substantial impact on cancer patients, with several challenges specific to rural patients. This comprehensive study provides unique insights into the first 6 months of COVID-19 pandemic-related experiences and continuity of care among rural and urban cancer patients predominantly from Utah. Further research is needed to better characterize the pandemic's short- and long-term effects on rural and urban cancer patients and appropriate interventions.

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

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 f2 = 0.14) and knee extensor moment (p = 0.05, Cohen f2 = 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 f2 = 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.

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

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.

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

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.

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

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.

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

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 (ß = 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.

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

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/m2) 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.

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

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.

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

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.

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

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. P 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 (P < .001) and lunge (P < .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 (P < .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.

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

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).

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

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 (MT ) (ß = 0.431; p < 0.001) and knee extensor moment (MK ) (ß = 0.493; p < 0.001) asymmetry. Again at 6 months, only quadriceps strength asymmetry was related to MT (ß = 0.432; p < 0.001) and MK (ß = 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.

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

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.

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

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 (MS) (mean differences [MD]=0.17; 95% CI=0.07, 0.22), knee extensor moment (MK) (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 MS (MD=0.24; 95% CI=0.13, 0.35), MK (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 MS (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.

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

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-ß 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 (CD68+CD11b+ and CD68+CD11b- 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.

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

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.

Eccentric versus traditional resistance exercise for older adult fallers in the community: a randomized trial within a multi-component fall reduction program.

BACKGROUND: Addressing muscle deficits within a multi-component exercise fall reduction program is a priority, especially for the highest risk older adults, i.e., those who have fallen previously. Eccentric resistance exercise with its high-force producing potential, at a low energetic cost, may be ideally-suited to address muscle impairments in this population. The purpose of this study was to compare the effects of resistance exercise via negative, eccentrically-induced, work (RENEW) versus traditional (TRAD) resistance exercise on mobility, balance confidence, muscle power and cross sectional area, as well as the number of days high fall risk older adults survived without a fall event over a 1 year period. METHODS: Randomized, two group, four time point (over 1 year) clinical trial testing RENEW versus TRAD as part of a 3 month multi-component exercise fall reduction program (MCEFRP). Primary outcomes of mobility, balance confidence, muscle power output and cross sectional area were analyzed using mixed effects modeling. The secondary outcomes of days to fall and days to near-fall were analyzed using survival analysis. RESULTS: The MCEFRP did have an effect on fall risk factors considered reversible with exercise interventions though there was no differential effect of RENEW versus TRAD (p = 0.896) on mobility, balance confidence, muscle power and cross sectional area. There were also no group differences in the number of days survived without a fall (p = 0.565) or near-fall (p = 0.678). Despite 100% of participants having at least one fall in the year prior to the MCEFRP, however, after 3 months of exercise and 9 months of follow-up <50% had experienced a fall or near fall. CONCLUSIONS: There were no differential effects of RENEW or TRAD as components of a MCEFRP on the primary or secondary outcomes. The two modes of resistance exercise had identical effects on fall risk and fall-free survival. TRIAL REGISTRATION: NCT01080196 ; March 2, 2010 (retrospectively registered).