BET bromodomain inhibitors regulate keratinocyte plasticity.

Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing. Utilizing high-throughput phenotypic screening of primary keratinocytes, we identify such small molecules, including bromodomain and extra-terminal domain (BET) protein family inhibitors (BETi). BETi induce a sustained activated, migratory state in keratinocytes in vitro, increase activation markers in human epidermis ex vivo and enhance skin wound healing in vivo. Our findings suggest potential clinical utility of BETi in promoting keratinocyte re-epithelialization of skin wounds. Importantly, this novel property of BETi is exclusively observed after transient low-dose exposure, revealing new potential for this compound class.

Common Benign Melanocytic and Non-Melanocytic Skin Tumors among the Elderly: Results of the Graz Study on Health and Aging.

BACKGROUND AND OBJECTIVES: Benign skin tumors are the most common skin findings and contribute to the major reasons for consulting a dermatologist. However, the frequency of benign skin tumors concerning different body areas and their relationship with sun-related behavior have not been sufficiently characterized. We aimed to improve knowledge about the anatomic distribution of the most frequently occurring benign skin tumors among a healthy predominant elderly population. Furthermore, we investigated associations with sun-related habits. METHODS: In total, 100 participants, 37 men, and 63 women (mean age: 67.2 years; range: 46-86 years) were enrolled in the Graz Study on Health and Aging (GSHA) cohort. Full body images were investigated for melanocytic nevi, seborrheic keratoses, hemangiomas, dermatofibromas, and lentigines. Information on the phenotypic trait, sun exposure, use of sun-protective measures, and history of sunburns was collected in a questionnaire. RESULTS: Common melanocytic nevi were the most frequently encountered skin lesions. Male sex was associated with multiple common nevi on the abdomen and the presence of atypical nevi. High sun exposure in central European latitudes during adolescence was positively associated with multiple common nevi on the total body. Multiple common nevi and atypical nevi on the back correlated with frequent use of sunscreens with SPF during young adulthood and adolescence, respectively. CONCLUSION: Our study adds new knowledge about the most frequently occurring benign skin tumors, considering all visible body areas. This research may serve as a reference basis for following epidemiological studies.

A Standardized Treatment Pathway for Telehealth-Based Care of Chronic Wounds in Austria.

Chronic wounds present a significant healthcare challenge in Austria as well as in other countries. The interdisciplinary approach to wound treatment involving various caregivers, doctors, and relatives, poses challenges in documentation and information exchange. To overcome these barriers and promote patient-centered care, a new telehealth-supported treatment pathway for chronic wounds has been developed. The primary focus was to regularly update the status of the chronic wound by responding to predefined questions and transmitted images of the chronic wound. This was achieved by an interdisciplinary team of experts in chronic wound care, providing a new perspective for digital implementation in the healthcare system.

[Uncommon presentation of psoriasis vulgaris in an 11-year-old patient]. / Ungewöhnliche Präsentation einer Psoriasis vulgaris bei einem 11-jährigen Patienten.

Psoriasis vulgaris occurs with a prevalence of up to 2% in childhood and adolescence. In most cases, diagnosis can be made clinically. We report about a pediatric patient with psoriasis vulgaris who posed a diagnostic challenge due to uncharacteristic manifestation. The most important differential diagnoses of various forms of psoriasis vulgaris as well as actual treatment recommendations in childhood and adolescence are discussed.

Identification of Non-HLA antigens targeted by alloreactive antibodies in patients undergoing chronic hemodialysis.

The only treatment of end-stage renal disease patients undergoing chronic dialysis is kidney transplantation. However, about half of graft recipients encounter organ loss within ten years after renal transplantation. There is emerging evidence that the presence of alloreactive antibodies against non-HLA antigens in the serum of the recipient prior transplantation is associated with higher incidence of chronic rejection. However, the molecular identity of these antigens is largely unknown. To determine the most common non-HLA antigens, we tested lymphocytic extracts from 20 healthy volunteers with sera of 28 patients on the transplantation waiting list by Western blotting. There was a group of five proteins that was recognized by most sera. Using patient's own lymphocytes revealed that autoimmunity plays a minor role in this recognition. Two-dimensional Western blotting experiments followed by mass spectrometry identified the antigens as tubulin beta chain, vimentin, lamin-B1, and Rho GDP-dissociation inhibitor 2. A detailed analysis of vimentin expression revealed that the antigenic 60 kDa isoform is underrepresented in patient's lymphocytes in comparison to those of healthy volunteers. The study revealed that preformed alloreactive antibodies are directed against a small number of specific protein isoforms. Our findings could provide a basis for future improvement of donor-recipient matching.

Lymphocyte activation induces cell surface expression of an immunogenic vimentin isoform.

High titers of anti-vimentin antibodies after transplantation are known to be associated with poor long-term graft survival. Vimentin is an intracellular protein which is present in different isoforms in the cell. In a previous study with sera from hemodialysis patients on the kidney transplantation waiting list we could show that only a 49 kDa and a 60 kDa isoform are recognized by patients' anti-vimentin antibodies while the other isoforms remain undetected. However, it is still unclear whether antibodies against this intracellular protein can bind to intact cells. Here we show that vimentin can be present on the cell surface under certain conditions. Lymphocytes from healthy volunteers were used as a model for allogeneic cells. We could show by immunofluorescence microscopy, flow cytometry and Western blot experiments that concanavalin A (Con A) activated lymphocytes express a 49 kDa vimentin isoform on their cell surface while the 60 kDa isoform remains inaccessible from the outside. This expression is associated with an increased binding of sera from hemodialysis patients which were positive for anti-vimentin antibodies. These results suggest that cell activation enhances binding of anti-vimentin antibodies to intact cells which might contribute to chronic allograft nephropathy.