Comparing optimized exoskeleton assistance of the hip, knee, and ankle in single and multi-joint configurations.

Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints. In this study, we used a hip-knee-ankle exoskeleton emulator paired with human-in-the-loop optimization to find single-joint, two-joint, and whole-leg assistance that maximally reduced the metabolic cost of walking. Hip-only and ankle-only assistance reduced the metabolic cost of walking by 26 and 30% relative to walking in the device unassisted, confirming that both joints are good targets for assistance (N = 3). Knee-only assistance reduced the metabolic cost of walking by 13%, demonstrating that effective knee assistance is possible (N = 3). Two-joint assistance reduced the metabolic cost of walking by between 33 and 42%, with the largest improvements coming from hip-ankle assistance (N = 3). Assisting all three joints reduced the metabolic cost of walking by 50%, showing that at least half of the metabolic energy expended during walking can be saved through exoskeleton assistance (N = 4). Changes in kinematics and muscle activity indicate that single-joint assistance indirectly assisted muscles at other joints, such that the improvement from whole-leg assistance was smaller than the sum of its single-joint parts. Exoskeletons can assist the entire limb for maximum effect, but a single well-chosen joint can be more efficient when considering additional factors such as weight and cost.

Drug repositioning in epilepsy reveals novel antiseizure candidates.

Objective: Epilepsy treatment falls short in ~30% of cases. A better understanding of epilepsy pathophysiology can guide rational drug development in this difficult to treat condition. We tested a low-cost, drug-repositioning strategy to identify candidate epilepsy drugs that are already FDA-approved and might be immediately tested in epilepsy patients who require new therapies. Methods: Biopsies of spiking and nonspiking hippocampal brain tissue from six patients with unilateral mesial temporal lobe epilepsy were analyzed by RNA-Seq. These profiles were correlated with transcriptomes from cell lines treated with FDA-approved drugs, identifying compounds which were tested for therapeutic efficacy in a zebrafish seizure assay. Results: In spiking versus nonspiking biopsies, RNA-Seq identified 689 differentially expressed genes, 148 of which were previously cited in articles mentioning seizures or epilepsy. Differentially expressed genes were highly enriched for protein-protein interactions and formed three clusters with associated GO-terms including myelination, protein ubiquitination, and neuronal migration. Among the 184 compounds, a zebrafish seizure model tested the therapeutic efficacy of doxycycline, metformin, nifedipine, and pyrantel tartrate, with metformin, nifedipine, and pyrantel tartrate all showing efficacy. Interpretation: This proof-of-principle analysis suggests our powerful, rapid, cost-effective approach can likely be applied to other hard-to-treat diseases.