👤 Anjon Audhya

The Patient-Reported Outcomes Measurement Information System (PROMIS) is a collection of generic patient-reported outcome instruments used to quantify disease impact on a variety of functional subdomains, including physical, cognitive, emotional, and other domains. The reliability and validity of the PROMIS Parent Proxy (PP) Physical Function-Upper Extremity (UE) item bank is not established in children with Duchenne muscular dystrophy (DMD). This study evaluated the psychometric properties and measurement quality of the PROMIS PP UE item bank v1.0 (29 items) in DMD using a Rasch psychometric analysis. The PROMIS PP UE item bank was completed by caregivers of children with DMD aged at least 8 years, under care at Nationwide Children's Hospital (Columbus, OH, United States). Rasch analysis was used to evaluate the psychometric performance of the measure and its items in DMD, based on several criteria, including item-trait interaction, individual items fit, Person Separation Index (PSI), individual persons fit, and response dependency. Rasch analysis was conducted on 206 observations. Several items had weak clinical utility in measuring upper extremity functioning in DMD. Additionally, the analysis identified specific response options that could be restructured to improve the reliability and precision of the items in evaluating upper extremity function in DMD. A new customized 21-item measure demonstrated overall good fit to Rasch model expectations ( The customized PROMIS PP UE measure conformed to Rasch assumptions, indicating that it can serve as a reliable option for caregiver-reported upper extremity assessment in DMD. Show less

The multivesicular body (MVB) sorting pathway provides a mechanism for delivering transmembrane proteins into the lumen of the lysosome/vacuole. Recent studies demonstrated that ubiquitin modification acts in cis as a signal for the sorting of cargoes into this pathway. Here, we present results from a genetic selection designed to identify mutants that missort MVB cargoes. This selection identified a point mutation in ubiquitin ligase Rsp5 (Rsp5-326). At the permissive temperature, this mutant is specifically defective for ubiquitination and sorting of the ubiquitin-dependent MVB cargo precursor carboxypeptidase S (pCPS), but not ligand-induced ubiquitination of Ste2. A previous study implicated Tul1 as the ubiquitin ligase responsible for MVB sorting of pCPS. However, we detected no defect in either the sorting or ubiquitination of pCPS in tul1 mutants. We had previously shown that Fab1 phosphatidylinositol 3-phosphate 5-kinase is also required for MVB sorting of pCPS, but not Ste2. However, our analyses reveal that fab1 mutants do not exhibit a defect in ubiquitination of pCPS. Thus, both Rsp5 and Fab1 play distinct and essential roles in the targeting of biosynthetic MVB cargoes. However, whereas Rsp5 seems to be responsible for cargo ubiquitination, the precise role for Fab1 remains to be elucidated. Show less