The αvβ6 integrin plays a role in compromised epidermal wound healing

The alphavbeta6 integrin is an exclusively epithelial integrin that is highly expressed during fetal development. In adult tissue, alphavbeta6 integrin is expressed during inflammation, carcinogenesis, and in wound healing. We previously reported that alphavbeta6 integrin is highly expressed in poorly healing human wounds and its over-expression is associated with chronic wounds in a mouse model. The objective of this study was to investigate the role of alphavbeta6 integrin in compromised wound healing induced by hydrocortisone treatment or aging by using young and old mice deficient in or overexpressing the beta6 integrin subunit in the epidermis. Untreated aged beta6 integrin-deficient (beta6-/-) animals showed a significant delay in wound healing when compared to their age-matched controls or younger beta6-/- mice. The most significant delay was observed at the stages where granulation tissue deposition was occurring. Hydrocortisone treatment significantly delayed wound healing in wild-type and beta6 integrin-deficient mice in comparison with the untreated controls. However, hydrocortisone treatment in beta6 integrin overexpressing animals did not cause a significant delay in wound healing. The results of this study suggest that alphavbeta6 integrin plays an important role in wound healing in animals compromised by either age or stress mimicked by hydrocortisone.     

Reproducibility of Two Four-Point Clinical Severity Scores for Lateral Canthal Lines (Crow''s Feet)

BACKGROUND: Several clinical scoring systems have been used to evaluate the efficacy of botulinum toxin A in the treatment of hyperkinetic wrinkles. So far very few have been investigated for their reproducibility. OBJECTIVE: The aim of this study was to investigate the reproducibility of two clinical four-point scales for lateral canthal lines (crow's feet), at rest and at maximum smile. MATERIAL AND METHODS: Based on standardized photographs, a consensus atlas depicting the different severity grades [from 0 (none) to 3 (severe)] was developed. After training based on the atlas, 49 photographs at rest and 48 at maximum smile were graded by the same group of investigators on 2 consecutive days (n=9 on Day 1; n=8 on Day 2). The scores were compared for reproducibility using kappa statistics. RESULTS: Overall, reproducibility was good for both scales. Interobserver reproducibility showed an agreement of 0.6 at rest and 0.58 at maximum smile (unweighted kappa). Intraobserver reproducibility showed an agreement between 0.47 and 0.86 at rest and between 0.62 and 0.81 at maximum smile (unweighted kappa). Using weighted kappa analysis, the agreement ranged between 0.63 and 0.91 at rest and between 0.71 and 0.85 at maximum smile. CONCLUSION: The clinical scales using scores of 0 to 3 for crow's feet, both at rest and at maximum smile, show a good inter- and intraobserver reproducibility. The use of these scores in clinical trials can be recommended.     

Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.