No abstract

Overall, powered devices offer biomechanical and metabolic benefits over passive energy storage and return designs on level ground and perform as well as a passive model on inclines. The lower metabolic demand when using the powered device may delay fatigue for individuals with transtibial amputation when walking over level ground.

Sloped walking requires altered strategies for maintaining dynamic balance relative to level-ground walking, as evidenced by changes in sagittal-plane whole-body angular momentum (H) in able-bodied individuals. The ankle plantarflexor muscles are critical for regulating H, and functional loss of these muscles from transtibial amputation affects this regulation. However, it is unclear if a powered prosthesis, which more closely emulates intact ankle function than a passive energy-storage-and-return prosthesis, affects H differently during sloped walking. Therefore, our purpose was to investigate H in individuals with unilateral transtibial amputation when using powered and passive prostheses. Overall, the range of H was greater in people with a transtibial amputation relative to able-bodied individuals. On a −10° decline, individuals with amputation did not decrease H as much as able-bodied individuals, and had reduced prosthetic limb braking ground reaction forces and knee power absorption. On a +10° incline, individuals with amputation had a greater relative increase of H than able-bodied individuals, a more anterior placement of the prosthetic foot, and higher peak hip power generation. The powered prosthesis condition resulted in a smaller range of H during prosthetic stance relative to the passive condition, although it was still larger than able-bodied individuals. Our results suggest that prosthetic ankle power generation may help regulate dynamic balance during prosthetic stance, but alone is not sufficient for restoring H to that of able-bodied individuals on slopes. Contributions of knee extensor muscles and the biarticular gastrocnemius in regulating H on slopes should be further investigated.

BackgroundGiven the worldwide prevalence of NAFLD and NASH, there is a need to develop treatments to slow or reverse disease progression. GR-MD-02 (galactoarabino-rhamnogalaturonate) has been shown to reduce hepatic fibrosis in animal studies, and lower serum biomarkers of NASH fibrogenesis in humans. The primary aim of this study was to determine the difference between four-months of treatment with GR-MD-02 or placebo in liver inflammation and fibrosis as measured by iron-corrected T1 (cT1) mapping, a non-invasive magnetic resonance imaging (MRI) biomarker that correlates with the extent of hepatic fibro-inflammatory disease. The secondary aims were to determine change in liver stiffness as measured by magnetic resonance elastography (MRE) and shear-wave ultrasonic elastography (LSM), and to explore test-retest repeatability of the three biomarkers.Materials and methodsThirty subjects (13 females, 46–71 years) with NASH and advanced fibrosis were recruited. Subjects were randomized to receive 8 mg.kg-1 GR-MD-02 (via IV infusion) or placebo, administered biweekly over a 16-week period. Therapeutic efficacy was examined using cT1, MRE, and LSM. Statistical analyses on group differences in the biomarkers were performed using robust ANCOVA models adjusting for baseline measurement and additional covariates.ResultsThere was no significant difference in cT1 (p = 0.16) between GR-MD-02 and placebo groups following a 16-week intervention. There was also no significant difference in liver stiffness, measured by MRE (p = 0.80) or LSM (p = 0.63), between groups. Examination of repeatability of the cT1, MRE and LSM revealed coefficient of variations of 3.1%, 11% and 40% respectively.Conclusions8 mg.kg-1 of GR-MD-02 had no significant effect on non-invasive biomarkers of liver inflammation or fibrosis over a 4-month period. Histological confirmation was not available in this study. The high reproducibility of the primary outcome measure suggests that cT1 could be utilized for monitoring longitudinal change in patients with NASH.