Background and Purpose-We compared the test-retest reliability, validity, and responsiveness of the Dynamic Gait Index, the 4-item Dynamic Gait Index, and the Functional Gait Assessment for assessment of walking in patients with stroke. Methods-Forty-five outpatients participating in the validity and responsiveness study were tested using the 3 walking measures as well as the 10-m walk test, Barthel Index, and Postural Assessment Scale for Stroke Patients. We tested them during the first week, then again after 2 months and 5 months of therapy. Another 48 chronic patients completed the 3 measures twice, 1 week apart, in the test-retest reliability study. Results-Thirty-five participants completed 3 time-point assessments. The Functional Gait Assessment showed the least floor and ceiling effects, indicating it has the best discriminative ability for patients with stroke with high walking function. We found the 3 measures were highly correlated with each other, indicating excellent concurrent validity, and all measures at the first week of therapy were moderately to highly correlated with the Barthel Index scores at 5 months, indicating good predictive validity. Responsiveness of the 3 measures was moderate during a 5-month period, and all showed good test-retest reliability. The minimal detectable changes between tests indicate acceptable random error. Conclusions-All 3 measures showed sufficient validity, responsiveness, and reliability for assessment of walking function in patients with stroke undergoing rehabilitation, but the Functional Gait Assessment is recommended for its psychometric properties.
The COVID-19 pandemic caused by SARS-CoV-2 is a health threat worldwide. Viral main protease (Mpro, also called 3C-like protease, 3CLpro) is a therapeutic target for drug discovery. Herein, we report that GC376, a broad-spectrum inhibitor targeting Mpro in the picornavirus-like supercluster, is potent inhibitor for the Mpro encoded by SARS-CoV-2 with half-maximum inhibitory concentration (IC50) of 26.4±1.1 nM. In this study, we also show that GC376 inhibits SARS-CoV-2 replication with a half-maximum effective concentration (EC50) of 0.91±0.03 μM. Only a small portion of SARS-CoV-2-Mpro was covalently modified in the excess of GC376 as evaluated by mass spectrometry analysis; indicating that improved inhibitors are needed. Subsequently, molecular docking analysis revealing the recognition and binding groups of GC376 within the active site of SARS-CoV-2 Mpro provides important new information for the optimization of GC376. Given that sufficient safety and efficacy data are available for GC376 as an investigational veterinary drug, expedited development of GC376, or its optimized analogues, for treatment of SARS-CoV-2 infection in human is recommended.
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