Proteoglycan 4 (PRG4) treatment improves skin wound healing in a porcine model.

Proteoglycan 4 (PRG4) is a boundary lubricant originally identified in articular cartilage and has been since shown to have immunomodulation and antifibrotic properties. Previously, we have demonstrated that recombinant human (rh)PRG4 treatment accelerates auricular cartilage injury closure through an inhibition of the fibrotic response, and promotion of tissue regeneration in mice. The purpose of the current study was to examine the effects of rhPRG4 treatment (vs. a DMSO carried control) on full-thickness skin wound healing in a preclinical porcine model. Our findings suggest that while rhPRG4 did not significantly accelerate nor impede full-thickness skin wound closure, it did improve repair quality by decreasing molecular markers of fibrosis and increasing re-vascularization. We also demonstrated that rhPRG4 treatment increased dermal adipose tissue during the healing process specifically by retaining adipocytes in the wound area but did not inhibit lipolysis. Overall, the results of the current study have demonstrated that rhPRG4 acts as antifibrotic agent and regulates dermal adipose tissue during the healing processes resulting in a tissue with a trajectory that more resembles the native skin vs. a fibrotic patch. This study provides strong rationale to examine if rhPRG4 can improve regeneration in human wounds.

Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.

The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling molecules that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.

Profiling Chromatin Accessibility at Single-cell Resolution.

How distinct transcriptional programs are enacted to generate cellular heterogeneity and plasticity, and enable complex fate decisions are important open questions. One key regulator is the cell's epigenome state that drives distinct transcriptional programs by regulating chromatin accessibility. Genome-wide chromatin accessibility measurements can impart insights into regulatory sequences (in)accessible to DNA-binding proteins at a single-cell resolution. This review outlines molecular methods and bioinformatic tools for capturing cell-to-cell chromatin variation using single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) in a scalable fashion. It also covers joint profiling of chromatin with transcriptome/proteome measurements, computational strategies to integrate multi-omic measurements, and predictive bioinformatic tools to infer chromatin accessibility from single-cell transcriptomic datasets. Methodological refinements that increase power for cell discovery through robust chromatin coverage and integrate measurements from multiple modalities will further expand our understanding of gene regulation during homeostasis and disease.

Epidemiological analysis of pediatric burns in the Dominican Republic reveals a demographic profile at significant risk for electrical burns.

OBJECTIVE: Pediatric burns are preventable with legislative and infrastructural changes. Although retrospective audits of many low- and middle-income countries have aided preventative efforts, the epidemiological status of burns in the Caribbean is not known. This study characterizes pediatric burns in the Dominican Republic (DR) and compares these to age-matched North American records captured by the National Burn Repository. METHODS: A retrospective audit of 1600 patients admitted to the Unidad de Niños Quemados Dra. Thelma Rosario Hospital, the island's only major pediatric burn center, between January 2010 to March 2017 was performed. Epidemiological variables analyzed included age, gender, burn mechanism, year, month, city, admission duration, nationality, mortality, and %TBSA. RESULTS: Pediatric burn patients in the DR sustained larger burns (8.2% vs. 6.5% TBSA) and spent more days in the hospital (10 vs. 6 days). Females were overrepresented (M:F=1:1.5) and mortality amongst admitted patients was 4-fold higher (2.8% vs. 0.7%). Electrical burns were significantly overrepresented in DR (21%) compared to age-matched North American patients (2%). Although electrical burns were smaller (4% TBSA), compared to scald (14% TBSA), and flame (19% TBSA), these burns preferred hands and had a high mortality rate (3%). No significant seasonality in burn mechanisms were observed. Finally, we report geographical and age group differences in the distribution of burn mechanisms and highlight particularly vulnerable subpopulations. CONCLUSION: This investigation identifies a demographical profile where electrical burns account for a significant percentage of the burn population. This provides a basis for concentrating preventative efforts in vulnerable populations.

Burns from illegal cannabis oil manufacturing: a case series.

BACKGROUND: The increasing consideration of cannabis legalization in Canada and the United States has motivated physicians to assess its prospective impact on the health care system. Health care providers in the burns community are concerned about injuries sustained as a result of the illegal manufacturing of cannabis oil because it involves highly flammable reagents. METHODS: We report a retrospective case series of patients with cannabis oil burns (identified by evidence of combustion during cannabis oil manufacturing) treated from April 2012 to March 2014 at the Foothills Medical Centre in Calgary, Alberta, Canada. We compare the characteristics of these patients with those of patients admitted over the same period with any burns. RESULTS: We found that 12 (out of 161 patients) admitted over the review period sustained burns from cannabis oil manufacturing. Compared with patients in the total burn group, patients with cannabis oil burns were younger (75% and 48% were younger than 41 years in the group with cannabis oil burns and the total burn group, respectively), were more likely to be male (83% in the group with cannabis oil burns v. 74% in the total burn group) and sustained burns over a larger percentage of their total body surface area (24% v. 9%). Patients with cannabis oil burns also required extensive surgical management (skin grafting in 75% of cases) and spent a substantial amount of time (mean 32 d) in the burn unit. INTERPRETATION: Burns from illegal cannabis oil manufacturing are large, require extensive management and involve younger patients than burns in general. Given that the frequency of cannabis oil burns may increase in Canada after legalization, Canadian burn centres are encouraged to monitor and report on cases with this injury mechanism.

Burn clinical trials: A systematic review of registration and publications.

BACKGROUND: Randomized controlled clinical trials (CTs) are gold standard tools for assessing interventions. Although burn CTs have improved care, their status, publication frequency, and publication quality are not known. OBJECTIVES: (1) Characterize burn CTs by analyzing location, completion status, temporal trend, and funding sources. (2) Assess quality of trial reporting. DATA SOURCES: CT records were obtained from ClinicalTrials.gov and WHO's CT Registry (searched May 2017). Publications were obtained from PubMed, Google Scholar, OVID MEDLINE, and ClinicalTrials.gov (searched June 2017). PUBLICATION APPRAISAL: 23-item rubric adapted from CONSORT and ICH E3 guidelines. RESULTS: 738 burn CTs were identified globally, of which majority were publically-funded (77%), ongoing (52%), and assessed behavioral, pharmacological, device-based, dietary-based, and biological/procedural interventions. Amongst the ended trials, 69 (28%) published their findings. Significantly fewer industry-funded trials published findings (14% vs 33% publically-funded). Quality of reporting was suboptimal, and most underreported categories were trial phase, severity, and sample size estimation. LIMITATIONS: Incomplete, outdated, and non-registered CTs which are difficult to track. CONCLUSIONS: Burn trials are proliferating in number, location, and interventions assessed. Only a small proportion are published and quality of reporting is suboptimal. IMPLICATIONS OF KEY FINDINGS: Burn researchers should aim to register and report on all clinical trials regardless of outcome. Superior a priori design can reduce precocious termination and mandatory reporting of data fields can improve quality of reporting. Systematic review registration number: CRD42017068549.