SDF-1-CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1-SLIT2 interactions in mice.

AIMS/HYPOTHESIS: We had previously reported that stromal cell-derived factor 1 (SDF-1) mediates chemorepulsion of diabetogenic T cell adhesion to islet microvascular endothelium through unknown mechanisms in NOD mice. Here we report that SDF-1-mediated chemorepulsion occurs through slit homologue (SLIT)2-roundabout, axon guidance receptor, homologue 1 (Drosophila) (ROBO1) interactions. METHODS: C-X-C receptor (CXCR)4 and ROBO1 protein expression was measured in mouse and human T cells. Parallel plate flow chamber adhesion and detachment studies were performed to examine the molecular importance of ROBO1 and SLIT2 for SDF-1-mediated T cell chemorepulsion. Diabetogenic splenocyte transfer was performed in NOD/LtSz Rag1(-/-) mice to examine the effect of the SDF-1 mimetic CTCE-0214 on adoptive transfer of diabetes. RESULTS: CXCR4 and ROBO1 protein expression was elevated in diabetic NOD/ShiLtJ T cells over time and coincided with the onset of hyperglycaemia. CXCR4 and ROBO1 expression was also increased in human type 1 diabetic T cells, with ROBO1 expression maximal at less than 1 year post diagnosis. Cell detachment studies revealed that immunoneutralisation of ROBO1 prevented SDF-1-mediated chemorepulsion of NOD T cell firm adhesion to TNFα-stimulated islet endothelial cells. SDF-1 increased NOD T cell adhesion to recombinant adhesion molecules, a phenomenon that was reversed by recombinant SLIT2. Finally, we found that an SDF-1 peptide mimetic prevented NOD T cell adhesion in vitro and significantly delayed adoptive transfer of autoimmune diabetes in vivo. CONCLUSIONS/INTERPRETATION: These data reveal a novel molecular pathway, which regulates diabetogenic T cell recruitment and may be useful in modulating autoimmune diabetes.

Population Density and Triage of Pediatric Firearm Injuries in a Rural Trauma System.

BACKGROUND: Rural pediatric firearm injuries require regional pediatric and trauma expertise. We evaluated county-level population density associations with transport, hospital interventions, and patient outcomes at a Level I pediatric trauma center serving a rural, statewide catchment area. MATERIAL AND METHODS: The trauma registry of the only in-state pediatric trauma center was reviewed for firearm injuries in patients < 18 between 1/2013 and 3/2020. County-level population density was classified according to the United States Office of Management and Budget definitions for rural, micropolitan, and metropolitan areas. RESULTS: 364 patients were identified, including 7 patients who were re-injured. Mean age was 11.3 ± 4.5 y and patients were 79.4% male. 59.3% were transferred from a referring hospital. Median injury severity score was 5 (IQR 1-10); 88.0% required trauma center admission, and 48.2% required operative intervention. 7.4% were injured in a rural county, 46.4% in a micropolitan county, and 46.2% in a metropolitan county. Patients from rural counties were more likely to be unintentionally injured (72.0%) than those from micropolitan (54.4%) or metropolitan counties (44.0%, P = .04). While need for inpatient admission and length of stay were similar, those transported from rural counties had significantly longer transport times (P < .01) and less frequent need for operative intervention (P = .03), as well as trends toward lower injury severity (P = .08) and mortality (P = .06). CONCLUSION: Management of pediatric firearm injury is a unique challenge with significant regional variability. Opportunities exist for outreach, telehealth, and decision support to ensure equitable distribution of resources in rural trauma systems. LEVEL OF EVIDENCE: Epidemiological, Level III.

Complete Genome Sequence of Citrobacter freundii Myophage Mijalis.

Citrobacter freundii is responsible for various opportunistic nosocomial infections. Phage therapies against C. freundii may prove useful in human medicine for treatment of infections caused by the ubiquitous bacteria. Here, we announce the complete genome sequence of the C. freundii Felix O1-like myophage Mijalis and present its features.

Complete Genome Sequence of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Myophage Miro.

Klebsiella pneumoniae is a Gram-negative pathogen frequently associated with antibiotic-resistant nosocomial infections. Bacteriophage therapy against K. pneumoniae may be possible to combat these infections. The following describes the complete genome sequence and key features of the pseudo-T-even K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae myophage Miro.