Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.

CAR (CARSKNKDC) is a wound-homing peptide that recognises angiogenic neovessels. Here we discover that systemically administered CAR peptide has inherent ability to promote wound healing: wounds close and re-epithelialise faster in CAR-treated male mice. CAR promotes keratinocyte migration in vitro. The heparan sulfate proteoglycan syndecan-4 regulates cell migration and is crucial for wound healing. We report that syndecan-4 expression is restricted to epidermis and blood vessels in mice skin wounds. Syndecan-4 regulates binding and internalisation of CAR peptide and CAR-mediated cytoskeletal remodelling. CAR induces syndecan-4-dependent activation of the small GTPase ARF6, via the guanine nucleotide exchange factor cytohesin-2, and promotes syndecan-4-, ARF6- and Cytohesin-2-mediated keratinocyte migration. Finally, we show that genetic ablation of syndecan-4 in male mice eliminates CAR-induced wound re-epithelialisation following systemic administration. We propose that CAR peptide activates syndecan-4 functions to selectively promote re-epithelialisation. Thus, CAR peptide provides a therapeutic approach to enhance wound healing in mice; systemic, yet target organ- and cell-specific.

Connecting the dots: combined control of endocytic recycling and degradation.

Endocytosis is an essential process where proteins and lipids are internalised from the plasma membrane in membrane-bound carriers, such as clathrin-coated vesicles. Once internalised into the cell these vesicles fuse with the endocytic network where their contents are sorted towards degradation in the lysosome or recycling to their origin. Initially, it was thought that cargo recycling is a passive process, but in recent years the identification and characterisation of specialised recycling complexes has established a hitherto unthought-of level of complexity that actively opposes degradation. This review will summarise recent developments regarding the composition and regulation of the recycling machineries and their relationship with the degradative pathways of the endosome.

Frequency of venous thromboembolism in 6513 patients with COVID-19: a retrospective study.

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appear to be at increased risk for venous thromboembolism (VTE), especially if they become critically ill with COVID-19. Some centers have reported very high rates of thrombosis despite anticoagulant prophylaxis. The electronic health record (EHR) of a New Orleans-based health system was searched for all patients with polymerase chain reaction-confirmed SARS-CoV-2 infection who were either admitted to hospital or treated and discharged from an emergency department between 1 March 2020 and 1 May 2020. From this cohort, patients with confirmed VTE (either during or after their hospital encounter) were identified by administrative query of the EHR.: Between 1 March 2020 and 1 May 2020, 6153 patients with COVID-19 were identified; 2748 of these patients were admitted, while 3405 received care exclusively through the emergency department. In total, 637 patients required mechanical ventilation and 206 required renal replacement therapy. Within the hospitalized cohort, the overall mortality rate was 24.5% and VTE occurred in 86 patients (3.1%). In the 637 patients who required mechanical ventilation at some point during their hospital stay, 45 developed VTE (7.2%). After a median follow-up of 14.6 days, VTE had been diagnosed in 3 of the 2075 admitted who were discharged alive (0.14%). Among 6153 patients with COVID-19 who were hospitalized or treated in emergency departments, we did not find evidence of unusually high VTE risk. Pending further evidence from prospective, controlled trials, our findings support a traditional approach to primary VTE prevention in patients with COVID-19.

Preventive resin restorations: practice and billing patterns of pediatric dentists.

PURPOSE: The purpose of this study was to determine practice patterns of pediatric dentists for preventive resin restorations (PRRs) and if they believe a code should be added to the American Dental Association's current dental terminology (CDT) for the PRR. METHODS: A 16-question survey sent to 475 pediatric dentists randomly selected from the American Academy of Pediatric Dentistry database, addressed demographics, treatment planning, techniques in preparation and restoration, billing practices, and perceptions about the need for a CDT code for PRRs. RESULTS: Two hundred thirty-eight (50%) surveys were returned, revealing that 72% of respondents perform PRRs and 64% feel that a PRR code should be added to the CDT Fifty-two percent believe not having a CDT code could cause dentists to perform more invasive dentistry to comply with billing requirements that Class I restorations be in dentin. PRRs are commonly treatment planned for deep pits and fissures with questionable decoy not entering dentin. Up to 50% of respondents could be erroneously billing for PRRs. CONCLUSIONS: Most pediatric dentists perform preventive resin restorations in their office and believe that a code for the procedure needs to be added to the current dental terminology.