Predictive simulation of post-stroke gait with functional electrical stimulation.

Post-stroke patients present various gait abnormalities such as drop foot, stiff-knee gait (SKG), and knee hyperextension. Functional electrical stimulation (FES) improves drop foot gait although the mechanistic basis for this effect is not well understood. To answer this question, we evaluated the gait of a post-stroke patient walking with and without FES by inverse dynamics analysis and compared the results to an optimal control framework. The effect of FES and cause-effect relationship of changes in knee and ankle muscle strength were investigated; personalized muscle-tendon parameters allowed the prediction of pathologic gait. We also predicted healthy gait patterns at different speeds to simulate the subject walking without impairment. The passive moment of the knee played an important role in the estimation of muscle force with knee hyperextension, which was decreased during FES and knee extensor strengthening. Weakening the knee extensors and strengthening the flexors improved SKG. During FES, weak ankle plantarflexors and strong ankle dorsiflexors resulted in increased ankle dorsiflexion, which reduced drop foot. FES also improved gait speed and reduced circumduction. These findings provide insight into compensatory strategies adopted by post-stroke patients that can guide the design of individualized rehabilitation and treatment programs.

Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita-Baylis-Hillman adducts from isatin derivatives.

Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita-Baylis-Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita-Baylis-Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available.

Predictive simulation of diabetic gait: Individual contribution of ankle stiffness and muscle weakening.

Diabetic neuropathic individuals present massive muscle strength reduction at the ankle plantar- and dorsiflexors and increased joint stiffness. Our aim is to investigate the adaptation strategies to these musculoskeletal alterations during walking by means of predictive simulations. We used a seven segment planar musculoskeletal model actuated by eight Hill-type muscles in each leg. The effect of all passive tissue in muscles and other joint structures was modeled by net passive joint moment curves. The predictive simulations were generated by solving an optimal control problem that minimized a cost function, including effort and tracking terms, using direct collocation and a commercial optimal control package. We simulate four conditions to represent the weakening of the distal muscles triceps sural (TS) and tibialis anterior (TA), and five conditions to represent the effect of increasing nonlinear ankle stiffness in flexion. The weakening of the distal muscles leads to a delayed action of the TS and a progressive decrease of the gastrocnemius peak force in the push-off phase. This distal deficit is compensated by a larger hip flexion moment resulting from an increase in the iliopsoas muscle force in this phase, known as the hip strategy. The adaptation mechanisms observed in response to an increase in ankle stiffness include the hip strategy and the exploitation of the passive joint structures as springs, which store energy during midstance and release it during push-off, reducing TS force and power in this phase and leading to a consistent decrease in the overall muscle force levels.