Carrying children, groceries, and water across varying terrain: Changes in gait and comfortable walking speed.

BACKGROUND: Carrying items of substantial weight and value in one's arms while traversing challenging terrain is a common task that requires considerable care. Carrying valuable (e.g., child) or variable (e.g., water) items, compared to stable ones (e.g., groceries) demands increased coordination, and is likely to lead to slower comfortable walking speed (CWS) and altered gait mechanics, especially on difficult terrain. RESEARCH QUESTION: How are gait parameters altered by carrying items of substantial weight and varying value and dynamics across more and less demanding terrain? METHODS: In two experiments, participants carried their child, an equally weighted sack of groceries, or an open bucket of water in the same manner across level floor and across uneven stairs of varying heights with gaps between them. Kinematics were assessed for both terrains; kinetics were measured for one step up and one step down on stairs. RESULTS: Mixed models ANOVAs with repeated measures revealed that CWS on uneven stairs was approximately 65 % of CWS for level floor, regardless of the item carried. Step-to-step coefficients of variation for step length and CWS were also greater. Water was carried most slowly, with shorter steps on level floor and reduced accelerations on uneven stairs. CWS with children and groceries did not differ. SIGNIFICANCE: Carrying items of weight and worth with varying dynamics across more and less challenging terrain illustrates the ecological complexity of walking. Terrain requiring greater flexibility, strength, and coordination reduced CWS substantially, a complexity-speed tradeoff. More variable, difficult to control items altered CWS and other gait patterns regardless of terrain difficulty, suggesting terrain and item dynamics contributed independently to gait adjustments. More valuable items were not carried more slowly than less valuable ones. Carrying tasks deserve greater attention in research and clinical assessment.

The γH2AX DSB marker may not be a suitable biodosimeter to measure the biological MRT valley dose.

PURPOSE: γH2AX biodosimetry has been proposed as an alternative dosimetry method for microbeam radiation therapy (MRT) because conventional dosimeters, such as ionization chambers, lack the spatial resolution required to accurately measure the MRT valley dose. Here we investigated whether γH2AX biodosimetry should be used to measure the biological valley dose of MRT-irradiated mammalian cells. MATERIALS AND METHODS: We irradiated human skin fibroblasts and mouse skin flaps with synchrotron MRT and broad beam (BB) radiation. BB doses of 1-5 Gy were used to generate a calibration curve in order to estimate the biological MRT valley dose using the γH2AX assay. RESULTS: Our key finding was that MRT induced a non-linear dose response compared to BB, where doses 2-3 times greater showed the same level of DNA DSB damage in the valley in cell and tissue studies. This indicates that γH2AX may not be an appropriate biodosimeter to estimate the biological valley doses of MRT-irradiated samples. We also established foci yields of 5.9 ± 0.04 and 27.4 ± 2.5  foci/cell/Gy in mouse skin tissue and human fibroblasts respectively, induced by BB. Using Monte Carlo simulations, a linear dose response was seen in cell and tissue studies and produced predicted peak-to-valley dose ratios (PVDRs) of ∼30 and ∼107 for human fibroblasts and mouse skin tissue respectively. CONCLUSIONS: Our report highlights novel MRT radiobiology, attempts to explain why γH2AX may not be an appropriate biodosimeter and suggests further studies aimed at revealing the biological and cellular communication mechanisms that drive the normal tissue sparing effect, which is characteristic of MRT.

The Effect of a Low-Cost Body Weight-Supported Treadmill Trainer on Walking Speed and Joint Motion.

Background and Objectives: Gait training with body weight-support has been shown to improve the walking speed of individuals with movement disorders. The AccesSportAmerica Gait Trainer is a low-cost, pre-market gait rehabilitation device that alters the stride characteristics of participants walking on a standard treadmill. The purpose of this study was to examine the biomechanical outcomes that training on this device has for people with brain injuries that affect motor functioning. It was hypothesized that there would be an increase in walking speed post-intervention, and that there would be an increase in step length and joint range-of-motion. Materials and Methods: An intervention study was conducted with 11 people with ambulatory difficulty caused by post-stroke hemiparesis (n = 7), traumatic brain injury (n = 3), and cerebral palsy (n = 1). The average time using the AccesSportAmerica Gait Trainer was 34.5 (SD = 6.0) minutes per session for 36.9 (SD = 21.8) sessions. Gait speed, step length and time, and joint flexion were measured during the 10 Meter Walk Test. Results: From pre- to post-intervention, there was a mean increase in walking speed of 0.19 m/s (SD = 0.06, p = 0.016, d = 0.40) and a decrease in step time of both affected and unaffected legs (affected: p = 0.011, d = 0.37; unaffected: p = 0.004, d = 0.67). There was no significant change in stride length or joint angles. Conclusions: The AccesSportAmerica Gait Trainer has the potential to improve the walking speed of people with ambulatory difficulty.

The Lighten Your Life Program: An Educational Support Group Intervention That Used a Mobile App for Managing Depressive Symptoms and Chronic Pain.

An educational support group, The Lighten Your Life Program, was developed for adult patients who self-reported depressive symptoms and had one or more comorbid chronic pain condition. Using a mixed methods, pilot design, the purpose of the current study was to test the feasibility of The Lighten Your Life Program, which combined depression education with in-person group support every 2 weeks. The Lighten Your Life Program also encouraged the use of Pacifica, a mobile application (app), as a self-management tool. Another aim was to explore what effect The Lighten Your Life Program had on decreasing depression severity. Statistically significant differences in Patient Health Questionnaire-9 scores were noted over time. Educational support group programs and the use of mobile apps, such as Pacifica, could be beneficial in helping individuals self-manage their depressive symptoms and chronic pain condition. [Journal of Psychosocial Nursing and Mental Health Services, 57(7), 39-47.].

A Functional Immune System Is Required for the Systemic Genotoxic Effects of Localized Irradiation.

PURPOSE: Nontargeted effects of ionizing radiation, by which unirradiated cells and tissues are also damaged, are a relatively new paradigm in radiobiology. We recently reported radiation-induced abscopal effects (RIAEs) in normal tissues; namely, DNA damage, apoptosis, and activation of the local and systemic immune responses in C57BL6/J mice after irradiation of a small region of the body. High-dose-rate, synchrotron-generated broad beam or multiplanar x-ray microbeam radiation therapy was used with various field sizes and doses. This study explores components of the immune system involved in the generation of these abscopal effects. METHODS AND MATERIALS: The following mice with various immune deficiencies were irradiated with the microbeam radiation therapy beam: (1) SCID/IL2γR-/- (NOD SCID gamma, NSG) mice, (2) wild-type C57BL6/J mice treated with an antibody-blocking macrophage colony-stimulating factor 1 receptor, which depletes and alters the function of macrophages, and (3) chemokine ligand 2/monocyte chemotactic protein 1 null mice. Complex DNA damage (ie, DNA double-strand breaks), oxidatively induced clustered DNA lesions, and apoptotic cells in tissues distant from the irradiation site were measured as RIAE endpoints and compared with those in wild-type C57BL6/J mice. RESULTS: Wild-type mice accumulated double-strand breaks, oxidatively induced clustered DNA lesions, and apoptosis, enforcing our RIAE model. However, these effects were completely or partially abrogated in mice with immune disruption, highlighting the pivotal role of the immune system in propagation of systemic genotoxic effects after localized irradiation. CONCLUSIONS: These results underline the importance of not only delineating the best strategies for tumor control but also mitigating systemic radiation toxicity.

Comparative toxicity of synchrotron and conventional radiation therapy based on total and partial body irradiation in a murine model.

Synchrotron radiation can facilitate novel radiation therapy modalities such as microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam radiation therapy (SBBR). Both of these modalities have unique physical properties that could be exploited for an improved therapeutic effect. While pre-clinical studies report promising normal tissue sparing phenomena, systematic toxicity data are still required. Our objective was to characterise the toxicity of SBBR and MRT and to calculate equivalent doses of conventional radiation therapy (CRT). A dose-escalation study was performed on C57BLJ/6 mice using total body and partial body irradiations. Dose-response curves and TD50 values were subsequently calculated using PROBIT analysis. For SBBR at dose-rates of 37 to 41 Gy/s, we found no evidence of a normal tissue sparing effect relative to CRT. Our findings also show that the MRT valley dose, rather than the peak dose, best correlates with CRT doses for acute toxicity. Importantly, longer-term weight tracking of irradiated animals revealed more pronounced growth impairment following MRT compared to both SBBR and CRT. Overall, this study provides the first in vivo dose-equivalence data between MRT, SBBR and CRT and presents systematic toxicity data for a range of organs that can be used as a reference point for future pre-clinical work.

Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition.

ADP-ribosyl-acceptor hydrolase 3 (ARH3) plays important roles in regulation of poly(ADP-ribosyl)ation, a reversible post-translational modification, and in maintenance of genomic integrity. ARH3 degrades poly(ADP-ribose) to protect cells from poly(ADP-ribose)-dependent cell death, reverses serine mono(ADP-ribosyl)ation, and hydrolyzes O-acetyl-ADP-ribose, a product of Sirtuin-catalyzed histone deacetylation. ARH3 preferentially hydrolyzes O-linkages attached to the anomeric C1″ of ADP-ribose; however, how ARH3 specifically recognizes and cleaves structurally diverse substrates remains unknown. Here, structures of full-length human ARH3 bound to ADP-ribose and Mg2+, coupled with computational modeling, reveal a dramatic conformational switch from closed to open states that enables specific substrate recognition. The glutamate flap, which blocks substrate entrance to Mg2+ in the unliganded closed state, is ejected from the active site when substrate is bound. This closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1″-O-linkage for cleavage while securing tightly 2″- and 3″-hydroxyls of ADP-ribose. Our collective data uncover an unprecedented structural plasticity of ARH3 that supports its specificity for the 1″-O-linkage in substrates and Mg2+-dependent catalysis.

The Chronic Knee Pain Program: A self-management model.

BACKGROUND: It is vital that patients take an active role in self-management of their chronic knee pain condition. The Chronic Knee Pain Program was developed to assist patients in managing their chronic condition and to improve their overall well-being. PURPOSE: The purpose of this pilot study was to determine the feasibility of a six-week self-management program and to explore whether it may assist in decreasing body mass index (BMI) and depression symptom severity and increase physical activity levels in obese adults with chronic knee pain. DESIGN: A one group, pre-test/post-test pilot study. SETTING: A pain management clinic in the northeastern United States. SAMPLE: Convenience sample of twelve adult patients with chronic knee pain and a BMI of 30 or greater were recruited, however, six participants completed the full program. RESULTS: This type of intervention has potential value to improve the lifestyles of those individuals with chronic knee pain, including improvements in BMI, depression symptom severity and physical activity levels. In this study there was a decrease in mean BMI overtime; 41.2 (at week 1), 40.8 (at week 6), and 40.7 (at week 10). CONCLUSIONS: The Chronic Knee Pain Program had a small sample size and high attrition rate, though yielded positive outcomes for some participants. Future research could focus on depression management, using conservative measures to help manage pain, and increasing pain coping skills. Implementing this program with a larger sample size is recommended to see if BMI, depression symptom severity and physical activity levels reach statistical significance.

Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses.

The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses. All radiation settings induced pronounced persistent systemic effects in mice, which resulted from even short exposures of a small irradiated area. OCDLs were elevated in a wide variety of unirradiated normal tissues. In out-of-field duodenum, there was a trend for elevated apoptotic cell death under most irradiation conditions; however, DSBs were elevated only after exposure to lower doses. These genotoxic events were accompanied by changes in plasma concentrations of macrophage-derived cytokine, eotaxin, IL10, TIMP1, VEGF, TGFß1, and TGFß2, along with changes in tissues in frequencies of macrophages, neutrophils, and T lymphocytes. Overall, our findings have implications for the planning of therapeutic and diagnostic radiation treatments to reduce the risk of radiation-related adverse systemic effects. Cancer Res; 77(22); 6389-99. ©2017 AACR.

Radiotherapy for Non-Small Cell Lung Cancer Induces DNA Damage Response in Both Irradiated and Out-of-field Normal Tissues.

PURPOSE: To study the response of irradiated and out-of-field normal tissues during localized curative intent radiotherapy. EXPERIMENTAL DESIGN: Sixteen patients with non-small cell lung carcinoma (NSCLC) received 60 Gy in 30 fractions of definitive thoracic radiotherapy with or without concurrent chemotherapy. Peripheral blood lymphocytes (PBL) and eyebrow hairs were sampled prior, during, and after radiotherapy. Clinical variables of radiotherapy dose/volume, patient age, and use of chemoradiotherapy were tested for association with γ-H2AX foci, a biomarker of DNA damage that underlies cellular response to irradiation. RESULTS: Radiotherapy induced an elevation of γ-H2AX foci in PBL, representing normal tissues in the irradiated volume, 1 hour after fraction one. The changes correlated directly with mean lung dose and inversely with age. γ-H2AX foci numbers returned to near baseline values in 24 hours and were not significantly different from controls at 4 weeks during radiotherapy or 12 weeks after treatment completion. In contrast, unirradiated hair follicles, a surrogate model for out-of-field normal tissues, exhibited delayed "abscopal" DNA damage response. γ-H2AX foci significantly increased at 24 hours post-fraction one and remained elevated during treatment, in a dose-independent manner. This observed abscopal effect was associated with changes in plasma levels of MDC/CCL22 and MIP-1α/CCL3 cytokines. No concordant changes in size and concentration of circulating plasma exosomes were observed. CONCLUSIONS: Both localized thoracic radiotherapy and chemoradiotherapy induce pronounced systemic DNA damage in normal tissues. Individual assessment of biologic response to dose delivered during radiotherapy may allow for therapeutic personalization for patients with NSCLC. Clin Cancer Res; 22(19); 4817-26. ©2016 AACRSee related commentary by Verma and Lin, p. 4763.

Do Gestational Age Dating Criteria Matter in Medically Indicated Late Preterm, Early-Term, and Full-Term Inductions of Labor?

OBJECTIVES: To assess short-term neonatal respiratory morbidity from inductions of labor (IOL) in well-dated (WD) pregnancies (dating ultrasound [US] <20 0/7 weeks) versus non-well-dated (NWD) pregnancies when applying National Institutes of Health/Society for Maternal-Fetal Medicine/American College of Obstetricians and Gynecologists delivery recommendations at ≥34 0/7 weeks. METHODS: Ours was a 1-year retrospective cohort of women with medically indicated IOL between 34 0/7 and 40 6/7 weeks with a live, cephalic, singleton gestation and no lethal anomaly. The primary outcome was a composite of neonatal respiratory morbidity (respiratory distress syndrome, transient tachypnea of the newborn, ventilator support, oxygen administration, and pneumonia). RESULTS: A total of 476 WD and 231 NWD women underwent IOL during the study period. The groups had similar maternal characteristics, indications for IOL, and mode of delivery. There was no difference in the rate of primary outcome (8.7% in NWD group vs 8.8% in WD group; P = 0.95). This finding persisted after control for parity, gestational age (GA) at first US, operator of the dating US, and exposure to antenatal corticosteroids and magnesium sulfate. When stratified by GA at delivery and GA at first US, these findings persisted even when the dating US was performed at >35 weeks. There were no differences in maternal or other neonatal outcomes between the WD and NWD pregnancies. CONCLUSIONS: In our cohort of medically indicated IOL, a dating US before 20 weeks was not associated with a difference in neonatal respiratory morbidity.

Análise da positividade da esquistossomose mansoni em Regionais de Saúde endêmicas em Pernambuco, 2005 a 2010* / Analysis of Schistosomiasis mansoni positivity in endemic Health Regions in the State of Pernambuco, Brazil, 2005-2010

Analisar a tendência da positividade da esquistossomose em exames coproscópicos na população de área endêmica do estado de Pernambuco, Brasil, de 2005 a 2010. Métodos: estudo ecológico de serie temporal, com dados secundários do Sistema de Informação do Programa de Controle da Esquistossomose, analisados por Regional de Saúde; foram avaliadas as tendências por regressão linear, considerando-se p<0,05 significativo. Resultados: Pernambuco apresentou média de 9,2 por cento de positividade; a Regional de Saúde III (Palmares) apresentou maior média de positividade (13,8 por cento), seguida das regionais II (Limoeiro: 9,9 por cento) e I (Recife: 7,8 por cento); a Regional V (Garanhuns) apresentou melhor média de tratamento (95,6 por cento), seguida da III (86,6 por cento); Pernambuco apresentou tendência decrescente na positividade para esquistossomose (p=0,005). Conclusão: em geral, há uma tendência decrescente da positividade de esquistossomose em Pernambuco, apesar da queda no número de exames; é importante manter e intensificar as intervenções de controle, com prioridades estratégicas focalizadas em localidades com elevadas prevalências...

To analyze Schistosomiasis positivity trends in stool tests in the population in endemic area of the state of Pernambuco, Brazil, 2005-2010. Methods: this was an ecological time series study using secondary data from the Schistosomiasis Control Program Information System, analyzed by Health Region. Trends were evaluated using linear regression and p<0.05 was considered significant. Results: Pernambuco had average positivity of 9.2 per cent; the 3rd Region (Palmares) had the highest average positivity (13.8 per cent), followed by the 2nd (Limoeiro: 9.9 per cent) and the 1st (Recife: 7.8 per cent); the 5th Region (Garanhuns) had best average treatment (95.6 per cent), followed by Palmares (86.6 per cent); Pernambuco showed a declining trend of Schistosomiasis positivity (p=0.005). Conclusion: in general, there has been a declining trend of Schistosomiasis positivity in Pernambuco, despite the reduction in the number of tests; it is important to maintain and intensify control interventions, with priority strategies focused on highest prevalence locations...

Individual muscle contributions to circular turning mechanics.

Turning is an activity of daily living that involves both the acceleration of the body center-of-mass (COM) towards the center of curvature and rotation of the pelvis towards the new heading. The purpose of this study was to understand which muscles contribute to turning using experimentation, musculoskeletal modeling and simulation. Ten healthy adults consented to walk around a 1-m radius circular path at their self-selected walking speed and then along a straight line at the same speed. Forward dynamics simulations of the individual subjects during the turning and straight-line walking tasks were generated to identify the contributions of individual muscle groups to the body mediolateral and anterior-posterior COM acceleration impulse and to the pelvis angular acceleration impulse. The stance leg gluteus medius and ankle plantarflexor muscles and the swing leg adductor muscles were the primary contributors to redirect the body's COM relative to straight-line walking. In some cases, contributions to mediolateral COM acceleration were modulated through changes in leg orientation rather than through changes in muscle force. While modulation of the muscle contributions generally occurred in both the inner and outer legs, greater changes were observed during inner single-leg support than during outer single-leg support. Total pelvis angular acceleration was minimal during the single-support phase, but the swing leg muscles contributed significantly to balancing the internal and external rotation of the pelvis. The understanding of which muscles contribute to turning the body during walking may help guide the development of more effective locomotor therapies for those with movement impairments.

Evaluation of outcomes after implementation of an induction-of-labor protocol.

OBJECTIVE: The purpose of this study was to determine whether adherence to an induction of labor (IOL) protocol decreases the rate of failed IOL (FIOL). STUDY DESIGN: We performed a 1-year retrospective chart review around the implementation of a hospital IOL protocol and compared maternal and neonatal outcomes from deliveries managed per protocol (n = 369) with those deliveries that were not (n = 230). Women at least 24 weeks' gestation with cervical dilation up to 2 cm who underwent an indicated IOL were included. Protocol-adherent (PA) inductions had amniotomy within 24 hours of starting oxytocin, intrauterine pressure catheter placement in latent labor, Montevideo units titrated to 200-300 or to adequate cervical change, and oxytocin administered for at least 12 hours after amniotomy before FIOL was diagnosed (defined as delivery by cesarean during latent labor as a result of failure to enter active labor). The primary outcome was the rate of FIOL. Control for possible confounders was made by stratification and multivariate modeling. RESULTS: FIOL rates were lowest in the PA group, which remained significant after stratification on parity and multivariate analysis (nulliparous women, 3.8% vs 9.8%; P = .043; multiparous women, 0% vs 6%; P < .0004). Median time to delivery was shortest in the PA group by 3.5 hours in nulliparous women (16.0 vs 19.5 hours, respectively; P = .0002) and 1.5 hours in multiparous women (10.75 vs 12.25 hours, respectively; P < .0001). There were no differences in infectious morbidity or neonatal outcomes between the groups. CONCLUSION: Adherence to a standardized IOL protocol is associated with a decreased rate of FIOL and length of labor.

Compensatory mechanisms of transtibial amputees during circular turning.

Turning plays a prominent role in daily living activities and requires the modulation of the ground reaction forces to accelerate the body's center-of-mass along the path of the turn. With the ankle plantarflexors being prominent contributors to the propulsive ground reaction forces, it is not clear how transtibial amputees perform turning tasks without these important muscles. The purpose of this study was to identify the compensatory mechanisms used by transtibial amputees during a simple turning task by analyzing the radial and anterior-posterior ground reaction impulses and sagittal, transverse and coronal joint work of the residual and intact legs. These quantities were analyzed with the residual leg on both the inside and outside of the turn and compared to non-amputees. The analysis showed that amputees and non-amputees use different joint strategies to turn. Amputees rely primarily on sagittal plane hip joint work to turn while non-amputees rely primarily on ankle work in the sagittal plane and hip joint work in the coronal plane. Differences in strategies are most likely due to the minimal power output provided by the passive prosthetic feet used by amputees and perhaps a desire to minimize the risk of falling. Understanding these differences in turning strategies will aid in developing effective rehabilitation therapies and prosthetic devices that improve amputee mobility.

The effects of prosthetic ankle dorsiflexion and energy return on below-knee amputee leg loading.

BACKGROUND: Prosthetic devices are intended to return lower limb amputees to their pre-amputation functional status. However, prosthetic devices designed for unilateral below-knee amputees have yet to completely restore the biomechanical functions normally provided by the ankle muscles, leading to gait asymmetries and increased reliance on their intact leg. In an effort to improve amputee gait, energy storage and return feet have been developed that store mechanical energy in elastic structures in early to mid-stance and return it in late stance. However, little is known regarding how ankle compliance and the level of energy return influences walking mechanics. The purpose of this study was to identify the influence of prosthetic ankle dorsiflexion and energy storage and return on leg loading during steady-state walking. METHODS: Compliant ankles with different stiffness levels were attached to a Seattle Lightfoot2 in different orientations (forward- and reverse-facing). FINDINGS: The ankles decreased residual leg vertical ground reaction forces in late stance, increased residual leg propulsive ground reaction force impulses and increased residual leg knee joint extensor moments. The reverse-facing ankles increased residual leg vertical ground reaction forces in early stance, and the compliant forward-facing ankle increased residual leg braking impulses. In contrast to previous studies, increased energy storage and return from compliant ankles did not decrease hip joint powers or the intact leg vertical ground reaction forces. INTERPRETATION: These results provide insight into the relationships between ankle dorsiflexion, energy storage and return, and leg loading, which may lead to more effective prosthetic devices to improve amputee gait.

The effect of prosthetic ankle energy storage and return properties on muscle activity in below-knee amputee walking.

In an effort to improve amputee gait, energy storage and return (ESAR) prosthetic feet have been developed to provide enhanced function by storing and returning mechanical energy through elastic structures. However, the effect of ESAR feet on muscle activity in amputee walking is not well understood. Previous studies have analyzed commercial prosthetic feet with a wide range of material properties and geometries, making it difficult to associate specific ESAR properties with changes in muscle activity. In contrast, prosthetic ankles offer a systematic way to manipulate ESAR properties while keeping the prosthetic heel and keel geometry intact. In the present study, ESAR ankles were added to a Seattle Lightfoot2 to carefully control the energy storage and return by altering the ankle stiffness and orientation in order to identify its effect on lower extremity muscle activity during below-knee amputee walking. A total of five foot conditions were analyzed: solid ankle (SA), stiff forward-facing ankle (FA), compliant FA, stiff reverse-facing ankle (RA) and compliant RA. The ESAR ankles decreased the activity of muscles that contribute to body forward propulsion and increased the activity of muscles that provide body support. The compliant ankles generally caused a greater change in muscle activity than the stiff ankles, but without a corresponding increase in energy return. Ankle orientation also had an effect, with RA generally causing a lower change in muscle activity than FA. These results highlight the influence of ESAR stiffness on muscle activity and the importance of prescribing appropriate prosthetic foot stiffness to improve rehabilitation outcomes.