The murine Pbx1-d lupus susceptibility allele accelerates mesenchymal stem cell differentiation and impairs their immunosuppressive function.

Pre­B cell leukemia homeobox 1 (Pbx1)-d is a dominant-negative splice isoform of the gene Pbx1 that corresponds to the NZM2410 lupus susceptibility locus Sle1a1. Pbx1 is required to maintain stem cell self-renewal, including that of mesenchymal stem cells (MSCs). MSCs have immunosuppressive functions that require stem cell maintenance. We tested the hypothesis that the expression of Pbx1-d favors MSC differentiation and impairs their immunosuppressive functions. We demonstrate that Sle1a1 MSCs express high levels of Pbx1-d as compared with congenic C57BL/6J (B6) MSCs. Sle1a1 MSCs grew faster and differentiated significantly more rapidly into osteoblasts than did B6 MSCs. This corresponded to a significant decrease in the expression of genes associated with stemness and an increase in the expression of genes associated with differentiation. Additionally, Sle1a1 MSCs express a gene expression profile associated with an enhanced innate immunity and inflammation. Suppression of Ig production from TLR-activated B6 B cells and IL-2 secretion from activated B6 CD4+ T cells was significantly impaired in Sle1a1 MSCs as compared with B6 MSCs. B6.Sle1a1 MSCs showed intermediate activity in suppressing lupus immunophenotypes in three different mouse models. Taken together, these data suggest that the expression of the lupus susceptibility allele Pbx1-d isoform impairs MSC functions, which may contribute to lupus pathogenesis both through a defective immunosuppression and the promotion of a proinflammatory environment.

The Accuracy of Transcutaneous Bilirubin as a Screening Test in Preterm Infants.

OBJECTIVE: To determine the accuracy of transcutaneous bilirubin (TcB) to predict total serum bilirubin (TSB) in preterm infants across gestational age (GA) ranges and to calculate the cost-effectiveness of TcB as the primary screening test of choice for neonatal jaundice in neonatal intensive care unit (NICU) settings. METHODS: Single-center retrospective study of infants aged ≤ seven days admitted to the NICU over a six-month period with a paired TSB and TcB, with or without phototherapy as part of their routine clinical care. Infants were divided into GA-specific groups as term, late preterm, moderate preterm, and very preterm. Measurement bias (bias=TSB-TcB) was calculated on the paired TSB and TcB values, and a Bland-Altman analysis was carried out. The impacts of additional infant-specific variables on the bias were assessed with univariate and multivariate linear regression techniques. The potential direct cost savings associated with the use of TcB as the primary screening test were calculated. RESULTS: A total of 263 paired TSB and TcB samples from 95 patients were included (130 paired samples from term (n=60), 75 from late preterm (n=21), 27 from moderate preterm (n=7), and 31 from very preterm (n=7)). The mean paired measurement bias across all the GA groups was -0.9 ± 2.9 mg/dL. The sensitivity and specificity of TcB in GA < 35 weeks were 92% and 62%, respectively. A conservative estimate of a one-third reduction in TSB measurement by using TcB as the primary screening test will have a direct cost saving of $3,148 over a six-month period. CONCLUSION: Our data suggest that TcB is a safe and potentially cost-effective screening test for jaundice across GA groups.

A Mobile Clinic Care Coordination Program: Enhancing Patient Care with Innovative Roles for Undergraduate Students.

The University of Florida Mobile Outreach Clinic's Care Coordination Program uses trained undergraduate volunteers to provide vital services; these include patient intake, recording vital signs, scribing first drafts of clinic notes, and making follow-up phone calls. The program and its benefits are replicable as demonstrated by our systematic implementation plan.