Intra- and inter-rater reliability and agreement of stimulus electrodiagnostic tests in post-COVID-19 patients.

Background. COVID-19 patients may present sequelae, such as neuromuscular electrophysiological disorders (NED), that can be assessed using the stimulus electrodiagnostic test (SET). However, little is known about the reliability and agreement of the SET in post-COVID-19 patients.Objective. We aimed to verify the intra-inter-rater reliability and agreement of SET measurements in the rectus femoris, vastus medialis, vastus lateralis, tibialis anterior, and gastrocnemius lateralis (GL) in post-COVID-19 participants.Methods. We designed an observational prospective study to evaluate 20 (10 males and 10 females) post-COVID-19 patients, age: 44.95 ± 11.07 years, weight: 87.99 ± 19.08 kg, height: 1.69 ± 0.09 m. Two independent raters took two evaluations using the SET on selected muscles. The intra-class correlation coefficient (ICC) and 95% limits of the agreement defined the quality and magnitude of the measures.Results. For intra-rater reliability, all measurements presented correlations classified as high or very high (ICC: 0.71-1.0). For inter-rater reliability, the rheobase, chronaxie, accommodation, and accommodation index presented high or very high correlations, except for the accommodation index of the GL (ICC = 0.65), which was moderate.Conclusion. The reliability of the SET obtained by independent raters was very high, except for the GL accommodation, which presented moderate ICC. Therefore, the SET is a reliable tool for evaluating NED in post-COVID-19 patients.

Targeting RNA:protein interactions with an integrative approach leads to the identification of potent YBX1 inhibitors.

RNA-protein interactions (RPIs) are promising targets for developing new molecules of therapeutic interest. Nevertheless, challenges arise from the lack of methods and feedback between computational and experimental techniques during the drug discovery process. Here, we tackle these challenges by developing a drug screening approach that integrates chemical, structural and cellular data from both advanced computational techniques and a method to score RPIs in cells for the development of small RPI inhibitors; and we demonstrate its robustness by targeting Y-box binding protein 1 (YB-1), a messenger RNA-binding protein involved in cancer progression and resistance to chemotherapy. This approach led to the identification of 22 hits validated by molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR) spectroscopy of which 11 were found to significantly interfere with the binding of messenger RNA (mRNA) to YB-1 in cells. One of our leads is an FDA-approved poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor. This work shows the potential of our integrative approach and paves the way for the rational development of RPI inhibitors.

Intra- and Inter-Rater Reliability and Agreement of Ultrasound Imaging of Muscle Architecture and Patellar Tendon in Post-COVID-19 Patients Who Had Experienced Moderate or Severe COVID-19 Infection.

COVID-19 is associated with musculoskeletal disorders. Ultrasound is a tool to assess muscle architecture and tendon measurements, offering an idea of the proportion of the consequences of the disease, since significant changes directly reflect the reduction in the ability to produce force and, consequently, in the functionality of the patient; however, its application in post-COVID-19 infection needs to be determined. We aimed to assess the intra- and inter-rater reliability of ultrasound measures of the architecture of the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM), gastrocnemius lateralis (GL), gastrocnemius medialis (GM), soleus (SO), and tibialis anterior (TA) muscles, as well as the patellar tendon (PT) cross-sectional area (CSA) in post-COVID-19 patients. An observational, prospective study with repeated measures was designed to evaluate 20 post-COVID-19 patients, who were measured for the pennation angle (θp), fascicular length (Lf), thickness, echogenicity of muscles, CSA and echogenicity of the PT. The intra-class correlation coefficient (ICC) and 95% limits of agreement were used. The intra-rater reliability presented high or very high correlations (ICC = 0.71-1.0) for most measures, except the θp of the TA, which was classified as moderate (ICC = 0.69). Observing the inter-rater reliability, all the evaluations of the PT, thickness and echogenicity of the muscles presented high or very high correlations. For the Lf, only the RF showed as low (ICC = 0.43), for the θp, RF (ICC = 0.68), GL (ICC = 0.70) and TA (ICC = 0.71) moderate and the SO (ICC = 0.40) low. The ultrasound reliability was acceptable for the muscle architecture, muscle and tendon echogenicity, and PT CSA, despite the low reliability for the Lf and θp of the RF and SO, respectively.