The effects of TGF-ß1 and IFN-α2b on decorin, decorin isoforms and type I collagen in hypertrophic scar dermal fibroblasts.

Hypertrophic scars (HTS) develop from an excessive synthesis of structural proteins like collagen and a decreased expression of proteoglycans such as decorin. Previous research has demonstrated that decorin expression is significantly down-regulated in HTS, deep dermal tissue, and thermally injured tissue, reducing its ability to regulate pro-fibrotic transforming growth factor-beta 1 (TGF-ß1) and normal fibrillogenesis. However, treatment of HTS fibroblasts with interferon-alpha 2b (IFN-α2b) has been shown to reduce excessive collagen synthesis and improve HTS by reducing serum TGF-ß1 levels. The expression of decorin isoforms in HTS is currently unknown and the effects of TGF-ß1 and IFN-α2b on decorin, decorin isoform expression and type 1 collagen are of great interest to our group. Dermal fibroblasts were treated with TGF-ß1 and/or IFN-α2b, for 48 h. The expression and secretion of decorin, decorin isoforms and type 1 collagen were quantified with reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and enzyme-linked immunosorbent assays. The mRNA expression of decorin and each isoform was significantly reduced in HTS fibroblasts relative to normal skin. TGF-ß1 decreased the mRNA expression of decorin and decorin isoforms, whereas IFN-α2b showed the opposite effect. IFN-α2b significantly inhibited TGF-ß1's effect on the mRNA expression of type I collagen alpha 1 in papillary dermal fibroblasts and overall showed relative effects of inhibiting TGF-ß1. These data support that a further investigation into the structural and functional roles of decorin isoforms in HTS pathogenesis is warranted and that IFN-α2b is an important agent in reducing fibrotic outcomes.

Effect of Radiotherapy on Sino-nasal Function in Nasopharynx Cancer Patients.

Introduction: Radiotherapy causes significant nasal comorbidity in nasopharynx cancer (NPC) patients. However, the literature addressing the sino-nasal quality of life (QoL) of those patients, especially on structural and functional changes after radiotherapy, is limited. Method: It is a case-control study with 14 NPC groups and 14 healthy control group. The sino-nasal QoL, including the olfactory threshold using Butanol Threshold Test (BTT), the olfactory identification level using the University of Pennsylvania Smell Identification Test (UPSIT), nasal symptoms using the sino-nasal outcome test (SNOT-22) questionnaire, nasal cross-sectional area, nasal flow, and nasal resistance using the acoustic rhinometry and rhinomanometry, were measured and compared. Result: The mean BTT score of the control group was higher than that of the NPC group (5.17 vs 2.71). The UPSIT score of the control group was higher than that of the NPC group (31.93 vs 25.14). The mean SNOT-22 score of control group was lower than that of the NPC group of (16.71 vs 37.71). All 3 results are statistically significant (P < .05). However, there is no statistical difference in nasal cross-sectional area, nasal flow, and nasal resistance between these 2 groups. Conclusion: In this study, we concluded that NPC patients who received radiotherapy suffered a worsening of sino-nasal functional changes, including the olfaction threshold, olfaction identification, and nasal symptoms. However, the sino-nasal structural changes on nasal cross-sectional area, nasal flow, and nasal resistance after radiation remain questionable.

Characteristics of Serum Exosomes after Burn Injury and Dermal Fibroblast Regulation by Exosomes In Vitro.

(1) Background: Exosomes (EXOs) have been considered a new target thought to be involved in and treat wound healing. More research is needed to fully understand EXO characteristics and the mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. (2) Methods: All EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After a confirmation of EXO uptake by dermal fibroblasts, we also explored the functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. (3) Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs both from burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. (4) Conclusions: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulates the fibroblasts in healing wounds, further studies will be required.

Serial Casting as an Effective Method for Burn Scar Contracture Rehabilitation: A Case Series.

Guidelines and protocols for orthoses in burn scar contracture rehabilitation are limited. The current study aims to determine the optimal frequency of casting, potentially facilitating the development of a serial casting protocol. Previous literature supporting casting has low generalizability due to methodology limitations. Seven patients with burn scar contracted joints, who did not respond to traditional therapy, were recruited in this study. Patients were serially casted once, three times, or five times a week. Joint range of motion was maximized with stretching and exercise techniques before every new cast application. Across all patients, active range of motion increased from 65.8 ± 27.8° to 108.1 ± 23.3° with casting; or from 57.8 ± 16.2% to 96.7 ± 2.9% of normal. Similarly, scars improved from 9.5 ± 1.5 to 4.9 ± 1.4 on the Modified Vancouver Scar Scale score. This therapeutic effect was achieved within an average of 8.5 ± 3.7 d and 4.0 ± 2.2 new cast applications. Given the study findings, the procedures outlined could be used to develop a standardized serial casting protocol for burn scar contracture rehabilitation.

The dynamic changes of monocytes and cytokines during wound healing post-burn injury.

BACKGROUND: Burn injury is a sudden and traumatic injury that affects a large part of the population worldwide, who are placed at high risk of developing hypertrophic scars (HTS). HTS are a fibrotic scar resulting in painful contracted and raised scarring, affecting mobility in joints and work life, as well as cosmetically. The aim of this research was to enhance our understanding of the systematic response of monocytes and cytokines in wound healing after burn injury, in order to develop novel approaches to prevention and treatment of HTS. METHODS: Twenty-seven burn patients and thirteen healthy individuals were recruited in this study. Burn patients were stratified by burn total body surface area (TBSA). Peripheral blood samples were taken post-burn injury. Serum and peripheral blood mononuclear cells (PBMCs) were separated from the blood samples. This research investigated cytokines IL-6, IL-8, IL1RA, IL-10, and chemokine pathways SDF-1/CXCR4, MCP-1/CCR2, RANTES/CCR5 during the wound healing process in burn patients with varying severity of injuries by using enzyme-linked immunosorbent assays. PBMCs were stained for monocytes and the chemokine receptors by flow cytometry. Statistical analysis was done by one-way ANOVA with a Tukey correction, and regression analysis was performed using Pearson's Correlation analysis. RESULTS: The CD14+ CD16- monocyte subpopulation is larger in patients who developed HTS at 4-7 days. The CD14+ CD16+ monocyte subpopulation is smaller in the first week of injury, where it is similar after 8 days. Burn injury increased CXCR4, CCR2, and CCR5 expressions in CD14+ CD16+ monocytes. Increases in MCP-1 at 0-3 days after burn injury was positively correlated with burn severity. IL-6, IL-8, RANTES, and MCP-1 significantly increased with increasing burn severity. CONCLUSIONS: Monocytes and their chemokine receptors, as well as systemic levels of cytokines in wound healing of burn patients and scar development will require ongoing assessment to enhance our understanding of the abnormal wound healing after burn injury.

Seroprevalence of hepatitis B in previously undiagnosed patients: A community screening study.

BACKGROUND: Forty percent of hepatitis B carriers have no knowledge of their diagnosis. A prior study in British Columbia suggested high rates of hepatitis B among immigrants. The authors undertook a large-scale screening study to validate these rates. METHODS: Attendees at Asian health fairs without knowledge of their hepatitis B status participated. They completed a questionnaire, and blood was drawn for HBV serologies. Active HBV was defined as HBV surface antigen positive. RESULTS: Of 2,726 patients, 1,704 (62.5%) were female and 1,022 (37.5%) male. Mean age was 62.7 (SD 22.1) years, and mean time of residing in Canada was 27.5 (SD 15.3) years. Most patients originated from China (1,042 patients, 38.2%) and Hong Kong (871, 31.2%). Fifty-six patients tested positive (seroprevalence rate 2.05%, 95% CI 1.52%-2.59%). Most seropositive patients were from China (28 patients, 50.0%). Mean time of residence in Canada for seropositive patients (23.8 [SD 2.1] y) was less than seronegative patients (27.6 [SD 0.3] y) (p = 0.06). There was a trend towards association of seropositivity with time of residence in Canada (OR 0.98, 95% CI 0.96-1.00, p = 0.09). 8 (14.3%) seropositive patients did not have family doctors, compared with 128 (4.8%) seronegative patients. Lack of a family doctor was strongly associated with seropositivity (OR 3.31, 95% CI 1.32-7.25, χ2 = 10.42, p = 0.001). INTERPRETATION: The authors have shown that high risk immigrant populations may have seroprevalence rates as high as 2,700 per 100,000. Lack of a family physician was associated with seropositivity. These results should be used to design improved outreach programs.

The Biology of Extracellular Matrix Proteins in Hypertrophic Scarring.

Significance: Hypertrophic scars (HTS) are a fibroproliferative disorder that occur following deep dermal injury and affect up to 72% of burn patients. These scars result in discomfort, impaired mobility, disruption of normal function and cosmesis, and significant psychological distress. Currently, there are no satisfactory methods to treat or prevent HTS, as the cellular and molecular mechanisms are complex and incompletely understood. This review summarizes the biology of proteins in the dermal extracellular matrix (ECM), which are involved in wound healing and hypertrophic scarring. Recent Advances: New basic research continues toward understanding the diversity of cellular and molecular mechanisms of normal wound healing and hypertrophic scarring. Broadening the understanding of these mechanisms creates insight into novel methods for preventing and treating HTS. Critical Issues: Although there is an abundance of research conducted on collagen in the ECM and its relationship to HTS, there is a significant gap in understanding the role of proteoglycans and their specific isoforms in dermal fibrosis. Future Directions: Exploring the biological roles of ECM proteins and their unique isoforms in HTS, mature scars, and normal skin will further the understanding of abnormal wound healing and create a more robust understanding of what constitutes dermal fibrosis. Research into the biological roles of ECM protein isoforms and their regulation during wound healing warrants a more extensive investigation to identify their distinct biological functions in cellular processes and outcomes.

Molecular Features of Hypertrophic Scars After Thermal Injury: Is There a Biologic Basis for Laser Therapy?

Significance: Hypertrophic scars (HTS) and keloids are common after thermal injuries and other trauma to deep regions of dermis of the skin. These abnormal scars can cause contractures and the thick masses of scar tissue that result in functional and cosmetic impairment. Management of these dermal fibrotic conditions includes a wide range of medical and surgical treatments, which can be time consuming, only partially effective, and often uncomfortable for patients. Recent Advances: The molecular pathophysiology of HTS has become more understood over the past two decades, where thermal injury to the reticular dermis results in an inflammatory response, fibrogenic growth factor release, and the formation of a dermal scar with increased collagen and proteoglycan composition in an abnormal morphology. Lasers are becoming a widely used form of treatment for these types of scars; however, the evidence for the beneficial effects of laser treatments and the understanding of their mechanism of action are still evolving. Critical Issues: Paradoxically, laser delivery of thermal energy to the skin is suggested to improve scar remodeling and wound healing, yet HTS is a well-recognized complication of excessive thermal energy delivered by laser treatments. This review aims to examine the current evidence for the use of lasers for HTS, and to investigate the molecular mechanisms where re-injury of a burn scar from laser treatment could result in overall improvements in scar quality. Future Directions: Improved design of clinical trials for the treatment of scarring in the future will evolve from new methodology and models of HTS in animals and humans.

Fluorescent light energy modulates healing in skin grafted mouse model.

Skin grafting is often the only treatment for skin trauma when large areas of tissue are affected. This surgical intervention damages the deeper dermal layers of the skin with implications for wound healing and a risk of scar development. Photobiomodulation (PBM) therapy modulates biological processes in different tissues, with a positive effect on many cell types and pathways essential for wound healing. This study investigated the effect of fluorescent light energy (FLE) therapy, a novel type of PBM, on healing after skin grafting in a dermal fibrotic mouse model. Split-thickness human skin grafts were transplanted onto full-thickness excisional wounds on nude mice. Treated wounds were monitored, and excised xenografts were examined to assess healing and pathophysiological processes essential for developing chronic wounds or scarring. Results demonstrated that FLE treatment initially accelerated re-epithelialization and rete ridge formation, while later reduced neovascularization, collagen deposition, myofibroblast and mast cell accumulation, and connective tissue growth factor expression. While there was no visible difference in gross morphology, we found that FLE treatment promoted a balanced collagen remodeling. Collectively, these findings suggest that FLE has a conceivable effect at balancing healing after skin grafting, which reduces the risk of infections, chronic wound development, and fibrotic scarring.

Identification of short peptide sequences that activate human mast cells via Mas-related G-protein coupled receptor member X2.

Peptide based therapeutics are desirable owing to their high biological specificity. However, a number of these fail in clinical testing due to an adverse inflammatory response. Mast cells play a key role in directing the host response to drugs and related products. Although the role of FcεRI receptor is well known, Mas-related G-protein coupled receptor X2 (MRGPRX2) binding of endogenous peptides, and drugs will activate mast cells independent of FcεRI. Identifying peptides that activate mast cells through MRGPRX2, and their respective activation potency, can be used to reduce the failure rate of peptide therapeutics at clinical trial. Moreover, it will allow for peptide design where mast cell activation is actually desired. It was found that FRKKW and WNKWAL are two motifs that activate human LAD2 cells similar to PAMP-12 controls. Peptide activators of MRGPRX2 could be reduced to Xa-(Y)(n ≥ 3)-Xb where: Xa is an aromatic residue; Xb is a hydrophobic residue; and Y is a minimum 3 residue long sequence, containing a minimum of one positively charged residue with the remainder being uncharged residues. Artificial peptides WKKKW and FKKKF were constructed to test this structural functionality and were similar to PAMP-12 controls. Peptides with different activation potentials were found where FRKKW = WKKKW = FKKKF > PAMP-12 = WNKWAL > YKKKY > FRKKANKWALSR = FRKKWNKAALSR > KWKWK > FRKK = WNKWA > KYKYK > NKWALSR = YKKY = WNK. These sequences should be considered when designing peptide-based therapeutics. STATEMENT OF SIGNIFICANCE: Mast cells release immune regulating molecules upon activation that direct host's immune response. MRGPRX2 receptor provides an alternate pathway for mast cell activation that is independent of FcεRI receptor. It is thought that mast cell activation through MRGPRX2 plays a critical role in high failure rates of drugs in clinical trials. Identifying peptide sequences that activate mast cells through MRGPRX2 can serve two important purposes, namely, sequences to avoid when designing peptide therapeutics, and artificial peptides with different activation potentials for mast cells. Herein, we have identified a general amino acid sequence that induces mast cell activation through MRGPRX2. Furthermore, by modulating the identified sequence, artificial peptides have been designed which activate mast cells by varying degrees for therapeutic applications.

The Transition to Microsurgical Technique for Hepatic Artery Reconstruction in Pediatric Liver Transplantation.

BACKGROUND: Hepatic artery thrombosis represents a potentially fatal complication following liver transplantation. Rates of hepatic artery thrombosis are significantly higher in children, with mortality reported up to 80 percent. Microsurgical anastomosis has been shown to decrease the rate of hepatic artery thrombosis and now represents the standard of care at the authors' institution. In this article, the authors present the largest study of its type directly comparing rates of hepatic artery thrombosis with and without microsurgical reconstruction of the hepatic artery. METHODS: All pediatric patients who underwent primary orthotopic liver transplantation between 1989 and 2018 were included. Patients were divided into two cohorts: standard anastomosis with loupes, and microsurgical anastomosis under the operating microscope. The authors' primary outcome was the rate of hepatic artery thrombosis. Secondary outcomes were graft survival, patient survival, retransplantation rate, requirement for intraoperative blood products, and length of stay. RESULTS: Two hundred thirty-one children met criteria for inclusion. One hundred eighty cases were performed with loupe magnification and 51 cases were performed under the microscope. The hepatic artery thrombosis rate was lower, but not significantly so (p = 0.114), in the microsurgical group [n = 1 (2.0 percent)] compared with the standard cohort [n = 15 (8.3 percent)]. Survival analysis revealed a significant increase in graft survival with microsurgical anastomosis (p = 0.020), but not patient survival (p = 0.196). The retransplantation rate was significantly lower with microsurgical anastomosis (p = 0.021). CONCLUSIONS: Microsurgical anastomosis was associated with a clinically important decrease in hepatic artery thrombosis compared with standard loupe anastomosis. The graft survival rate was significantly higher in the microsurgical cohort, with a reduced retransplantation rate at 1 year. On this basis, the authors recommend microsurgical hepatic artery anastomosis in cases of pediatric liver transplantation. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Stimulation of toll-like receptor pathways by burn eschar tissue as a possible mechanism for hypertrophic scarring.

Hypertrophic scars (HTS) are a common complication following burn injuries with prolonged inflammation. They do not respond well to current treatment options including mechanical, biomolecular and surgical therapies. Toll-like receptor (TLR) 2 and 4 respond to microbes and damaged endogenous ligands to trigger pro-inflammatory pathways, and they are expressed more in HTS fibroblasts compared to normal skin fibroblasts. TLR2 responds to microbial lipoteichoic acid (LTA) while TLR4 responds to microbial lipopolysaccharide (LPS) and endogenous ligands. We investigated the role of burn tissue and small leucine-rich proteoglycans (decorin and biglycan) in the stimulation of TLR2 and TLR4 pathways using cells stably transfected with TLR2 or TLR4 linked to a reporter system. Normal skin (n = 5) was collected post-abdominoplasty, and burn eschar samples (n = 18) were collected from 18 patients between 0 and 14 days post-burn. We found that burn tissue stimulates TLR2 activity significantly more than normal tissue and contains significantly higher levels of LTA. Burn tissue was a stronger stimulator of TLR4 than was normal skin. Burn tissue samples' stimulation of TLR4 and TLR2 correlated. The time post-burn (0-14 days) of wound tissue sampling correlated positively but moderately with TLR2 and TLR4 simulation. In comparison to the dose-dependent effects of natural decorin or biglycan on TLR4 activation, their denatured forms exhibited stronger or weaker stimulation, respectively. They were not potent stimulators of TLR2. TLR2 and TLR4 stimulation is not limited to bacteria in wounds and likely involves multiple endogenous damage-associated molecular patterns. Insight into mechanisms of HTS will facilitate the development of future targeted therapies to modify wound progression and provide benefits to patients suffering with HTS and other fibroproliferative disorders.

Ischemic Colitis after Colonoscopy with Bisacodyl Bowel Preparation: A Report of Two Cases.

BACKGROUND: Colonoscopy is widely used for the diagnosis and management of colorectal disease and requires adequate bowel preparation. Ischemic colitis is a form of intestinal ischemia that presents with abdominal pain, diarrhea, and hematochezia. Risk factors include advanced age, cardiovascular disease, and diabetes. Both colonoscopy and bisacodyl bowel preparation have been described as rare causes of ischemic colitis with less than 35 cases collectively in the literature. Our review found that of these cases, there exists significant heterogeneity within individual patient characteristics. The majority of the cases are managed conservatively without complications or sequela. Due to the risk of ischemic colitis, the FDA has withdrawn bisacodyl bowel preparations from use in the USA. Bisacodyl bowel preparations are still used in Canada. CASES: Here, we present two cases of ischemic colitis in previously healthy women aged 57 and 69 who underwent screening colonoscopy using bisacodyl bowel preparation. Both were treated conservatively without complications. CONCLUSION: Thus far, there has been one documented case of ischemic colitis following colonoscopy with bisacodyl bowel preparation; here, we present two additional cases with one case occurring without the presence of known risk factors for ischemic colitis. Our literature review finds that there is limited evidence surrounding bisacodyl as a causative agent of ischemic colitis. Cases often contain confounding variables such as the presence of known risk factors for ischemic colitis. Our report aims to highlight the need for a more comprehensive analysis evaluating the safety of bowel preparations as well as increasing the clinical awareness surrounding the rare risk of colonoscopy-induced ischemic colitis.

Skeletal Deformity in Patients With Unilateral Coronal Craniosynostosis: Perceptions of the General Public.

STUDY DESIGN: A two-alternative forced choice design was used to gather perceptual data regarding unicoronal synostosis (UCS). OBJECTIVE: Cranial vault remodeling aims at improving the aesthetic appearance of infants with UCS by reshaping the forehead and reducing the potential for psychosocial discrimination. People's perception of craniofacial deformity plays a role in the stigma of deformity. The purpose of this study is to examine the relationship between objective skull deformity in UCS patients and laypersons' perception of skull normality. METHODS: Forty layperson skull raters were recruited from the general public. Skull raters were asked to categorize 45 infant skull images as normal or abnormal. Twenty-one of the images were UCS skulls, and 24 were normal skulls. Skulls were displayed briefly on a computer to simulate a first impression scenario and generate a perceptual response. A χ 2 analysis and mixed-effects regression model were used to analyze the response data. RESULTS: Members of the general public were good at distinguishing between skull groups, χ 2 (1) = 281.97, P < .001. In addition, skull raters' responses were predicted by the severity of deformity in the UCS skulls (b = -0.10, z = -2.6, P = .010, CI: -0.18, -0.02). A skull with a deformity value of 2.8 mm (CI: 1.8, 4.1) was equally likely to be rated normal or abnormal. CONCLUSIONS: This is the first study to investigate the relationship between objective skull deformity in UCS and public perception. Laypersons were good at distinguishing the difference between normal and UCS skulls, and their perceptions of normality were predicted by the degree of skull deformity.

Test-retest validation of a cranial deformity index in unilateral coronal craniosynostosis.

Unilateral coronal craniosynostosis (UCS) affects many infants resulting in abnormalities affecting the forehead and orbits. As a result, the deformity caused by UCS is very noticeable and there are several surgical treatment options available to normalize the head shape. However, there is a lack of consistently used outcome measures, resulting in difficulty assessing surgical outcomes and on-going debate over optimal treatments. Current techniques to quantify deformity in UCS are cumbersome, provide limited information, or are based on subjective assessments. In this study, a cranial deformity index was developed to quantify abnormality at the frontal bones for UCS that is accessible, user-friendly, and generates objective surface distance measurements. The cranial deformity index is defined as the Euclidean distance at the point of the largest deviation between the deformed skull compared to a reference skull. In addition, the index was successfully used to quantify post-operative changes in a single case of UCS that underwent corrective surgery. The reproducibility of the index was assessed using test-retest reliability and was demonstrated to be highly reproducible (ICC = 0.93). A user-friendly measurement index that is based on open-source software may be a valuable tool for surgical teams. In addition, this information can augment the consultation experience for patients and their families.

Self-Assembling Peptide Nanoscaffold That Activates Human Mast Cells.

Engineering biomaterials to manipulate the immune response to elicit specific therapeutic outcomes is a burgeoning field of research. Mast cells play a distinct and central role in the innate immune response, and are characterized by their rapid release of a myriad of proinflammatory mediators in response to stimulation. These mediators are central to protective actions such as wound healing, angiogenesis, and host defense against pathogens and animal venoms. Considering that mast cells are widely distributed in tissues that interface with the external environment, and are loaded with large amounts of preformed protective compounds, they are ideal targets for novel immunotherapies. Here we report that, by using an engineered nanoscaffold, human mast cells can be contact activated in cell and primary human skin tissue culture using a specific receptor-ligand mechanism. The IgE independent PAMP-12 peptide activates human mast cells through the recently identified Mas-related G-protein coupled receptor member X2 (MRGPRX2) receptor. The PAMP-12 motif was conjugated, via a glycine spacer, with the self-assembling peptide (RADA)4 and mixed with unmodified (RADA)4 to form a nanofiber matrix; mast cell activation was influenced directly by this ratio. Moreover, conjugating the PAMP-12 motif within the matrix was shown to only activate local, tissue-resident mast cells. The result of ex vivo human skin tissue tests confirmed that the engineered nanoscaffold successfully activated skin-resident mast cells by contact. Thus, this nanoscaffold design may provide a new platform to modulate localized mast cell functions thereby facilitating their protective role in the skin.

Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis.

Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels. This pathway is activated at physiological intensities of light that penetrate the skin on a sunny day. Daily exposure of differentiated adipocytes to blue light resulted in decreased lipid droplet size, increased basal lipolytic rate and alterations in adiponectin and leptin secretion. Our results suggest that scWAT function may be directly under the influence of ambient sunlight exposure and may have important implications for our current understanding of adipocyte biology. (150 words).

Biological Principles of Scar and Contracture.

Hypertrophic scar and contracture in burn patients is a complex process. Contributing factors include critical injury depth and activation of key cell subpopulations, including deep dermal fibroblasts, myofibroblasts, fibrocytes, and T-helper cells, which cause scarring rather than regeneration. These cells influence each other via cellular profibrotic and antifibrotic signals, which help to determine the outcome. These cells also both modify and interact with extracellular matrix of the wound, ultimately forming hypertrophic scar. Current treatments reduce hypertrophic scar formation or improve remodeling by targeting these pathways and signals.

Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.

BACKGROUND & AIMS: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB). METHODS: LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data. RESULTS: Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively. CONCLUSIONS: TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks. LAY SUMMARY: The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

Butane Hash Oil Burns: A 7-Year Perspective on a Growing Problem.

With the legalization of marijuana in four states, and decriminalization in many others, marijuana is becoming easier to obtain. The authors have experienced an increase in burn injuries related to the production of butane hash oil (BHO; a concentrated tetrahydrocannabinol product produced by the distillation of marijuana plant products with pressurized butane). This article updates our experience and highlights the increasing public health problem associated with these burns. Charts of patients who presented to the burn center with suspicion of BHO-related injuries between January 2007 and December 2014 were examined. Data collected included demographics, injury characteristics, treatment utilized, and outcomes. Charts of 101 patients were identified as having BHO-related burn injury. The mean age of these patients was 30.5 ± 10.6 years (mean ± standard deviation, range: 2-55 years) and 93.1% were male. Patients sustained a mean of 26.8 ± 24.1% TBSA burn with 14.3 ± 25.1% third degree burns. Three patients died as the result of their injuries. Patients required a mean of 12 ± 48.4 ventilator days, and 27.1 ± 59.4 days in the hospital. The number of patients presenting with these burns increased over the past 7 years. BHO burns occur most commonly in February (12 patients), on Wednesday (19 patients), and between 18:00 and 06:00 (58 patients). There has been a sharp increase in the number of patients presenting with burn-associated BHO production in the region over the past 7 years. The authors as burn care providers need to increase public awareness of this issue and aid in the development of legislation to help prevent these burns before it becomes a public health crisis.