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Achieving and maintaining a comfortable fit in a lower-limb prosthetic socket is an important goal to help ensure a successful rehabilitation. The purpose of this case study was to assess the performance of sockets with compliant features integrated into the socket wall to relieve in-socket pressure during transtibial amputee gait. Two sockets incorporating variably compliant areas over the fibula head and distal tibia were fabricated for a transtibial amputee. The two sockets were designed with different levels of compliance and were compared with a third more conventional socket without compliant areas. All three sockets were otherwise geometrically identical and were aligned identically to eliminate in-socket pressure differences due to alignment. The three sockets were fabricated using selective laser sintering, a form of solid freeform fabrication. The in-socket pressure measurements were acquired during normal walking. Tekscan F-Socket pressure sensors were attached to the amputee's residual limb rather than to the socket wall, which made it possible to measure pressures in the same location on the residual limb upon change of socket. A Vicon motion capture system was used to match in-socket pressures to the subject's gait cycle. The pressure measurements showed that the compliant socket peak pressures over the distal tibia and fibula head were similar for the two compliance levels and nearly 50% and 30% lower than the conventional socket pressures, respectively. This case study showed that selective laser sintering manufactured sockets with variably compliant regions holds great promise for reducing contact pressure in sensitive regions of the residual limb. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 hijacks the host cell transcriptional machinery to induce a phenotypic state amenable to its replication. Here we show that analysis of Master Regulator proteins representing mechanistic determinants of the gene expression signature induced by SARS-CoV-2 in infected cells revealed coordinated inactivation of Master Regulators enriched in physical interactions with SARS-CoV-2 proteins, suggesting their mechanistic role in maintaining a host cell state refractory to virus replication. To test their functional relevance, we measured SARS-CoV-2 replication in epithelial cells treated with drugs predicted to activate the entire repertoire of repressed Master Regulators, based on their experimentally elucidated, context-specific mechanism of action. Overall, 15 of the 18 drugs predicted to be effective by this methodology induced significant reduction of SARS-CoV-2 replication, without affecting cell viability. This model for host-directed pharmacological therapy is fully generalizable and can be deployed to identify drugs targeting host cell-based Master Regulator signatures induced by virtually any pathogen., (© 2022. The Author(s).)