Skin Barrier Function: The Interplay of Physical, Chemical, and Immunologic Properties.

An intact barrier function of the skin is important in maintaining skin health. The regulation of the skin barrier depends on a multitude of molecular and immunological signaling pathways. By examining the regulation of a healthy skin barrier, including maintenance of the acid mantle and appropriate levels of ceramides, dermatologists can better formulate solutions to address issues that are related to a disrupted skin barrier. Conversely, by understanding specific skin barrier disruptions that are associated with specific conditions, such as atopic dermatitis or psoriasis, the development of new compounds could target signaling pathways to provide more effective relief for patients. We aim to review key factors mediating skin barrier regulation and inflammation, including skin acidity, interleukins, nuclear factor kappa B, and sirtuin 3. Furthermore, we will discuss current and emerging treatment options for skin barrier conditions.

Dermatologic care of patients with differences of sex development.

Background: Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex. Objective: Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD. Data sources: Published articles including case series and case reports on PubMed. Study selections: Selection was conducted by examining existing literature with a team of multidisciplinary specialists. Methods: Narrative review. Limitations: This article was not conducted as a systematic review. Results: In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common. Conclusion: Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.

Managing Dermatologic Effects of Gender-Affirming Therapy in Transgender Adolescents.

Transgender adolescents seek gender-affirming medical care to address gender identity and incongruence. Improved understanding of the dermatologic impact of gender-affirming medical care such as pubertal suppression, hormone therapy, and surgeries can enhance patient outcome. Pubertal suppression treats dysphoria associated with development of secondary sex characteristics, including androgen-driven acne. Gender-affirming hormone therapy influences acne and hair development in transgender adolescents. Dermatologists can help manage skin effects associated with chest binding and gender-affirming hormone therapy and surgery. Provision of patient-centered gender-affirming care in dermatologic and multidisciplinary settings is essential to improve skin and overall outcomes of gender-affirming therapy.

Indolium 1 Exerts Activity against Vemurafenib-Resistant Melanoma In Vivo.

The development of targeted therapies (BRAF/MEK inhibitors) and immunotherapy have had a major impact on the treatment of melanoma. However, the majority of patients with advanced melanomas succumb to their disease. The mechanisms of resistance to both targeted therapies and immunotherapies are numerous and have been well-described. These include the alternative activation of BRAF/MEK signaling, novel compensating mutations in additional oncogenes, and loss of neoantigens. There has been limited development of small molecules that target alternative pathways in melanoma in the last two decades. We have previously identified triphenylmethanes as a class that shows activity against a wide variety of tumors. We have synthesized a novel triphenylmethane, indolium 1, and demonstrated its efficacy against an aggressive vemurafenib-resistant melanoma in vivo. Indolium 1 has a novel mechanism of action against melanoma, in that it results in induction of the tumor-suppressor EPHA3. We believe that pre-IND studies are warranted for this novel compound, given its mechanism of action and ability to inhibit the growth of vemurafenib resistant melanoma in vivo.

Introduction of Mutant GNAQ into Endothelial Cells Induces a Vascular Malformation Phenotype with Therapeutic Response to Imatinib.

GNAQ is mutated in vascular and melanocytic lesions, including vascular malformations and nevi. No in vivo model of GNAQ activation in endothelial cells has previously been described. We introduce mutant GNAQ into a murine endothelial cell line, MS1. The resultant transduced cells exhibit a novel phenotype in vivo, with extensive vasoformative endothelial cells forming aberrant lumens similar to those seen in vascular malformations. ATAC-seq analysis reveals activation of c-Kit in the novel vascular malformations. We demonstrate that c-Kit is expressed in authentic human Sturge-Weber vascular malformations, indicating a novel druggable target for Sturge-Weber syndrome. Since c-Kit is targeted by the FDA-approved drug imatinib, we tested the ability of imatinib on the phenotype of the vascular malformations in vivo. Imatinib treated vascular malformations are significantly smaller and have decreased supporting stromal cells surrounding the lumen. Imatinib may be useful in the treatment of human vascular malformations that express c-Kit, including Sturge-Weber syndrome.

Treating Acne in Transgender Persons Receiving Testosterone: A Practical Guide.

Transgender persons who undergo masculinizing hormone therapy experience a wide array of dermatologic effects as they initiate and maintain testosterone therapy. Acne is one of the most common adverse effects for many transmasculine patients receiving testosterone. Acne can worsen body image and mental health, with significant impact on quality of life in transgender patients. Specific training and awareness are needed for a clinically and culturally competent encounter while providing care for the transgender patient. This article provides a practical guide for the treatment of testosterone-induced acne in transmasculine patients. Recommendations on creating a welcoming clinical setting, taking a gender-inclusive history, and conducting a patient-centered physical examination relevant to acne care are provided. Assessment of reproductive potential and the appropriate contraceptive methods before prescribing acne treatment with teratogenic potential in transmasculine patients are examined. Interactions between acne treatments with gender-affirming therapies are explored. For patients with severe or treatment-refractory acne, indications, contraindications, and barriers to isotretinoin prescription, such as the US iPLEDGE program, are examined. Multidisciplinary approaches to acne care, involving mental health, reproductive health, gender-affirming hormone therapy and surgeries, are adopted to guide isotretinoin treatment.

Mitochondrial Metabolism in Melanoma.

Melanoma and its associated alterations in cellular pathways have been growing areas of interest in research, especially as specific biological pathways are being elucidated. Some of these alterations include changes in the mitochondrial metabolism in melanoma. Many mitochondrial metabolic changes lead to differences in the survivability of cancer cells and confer resistance to targeted therapies. While extensive work has gone into characterizing mechanisms of resistance, the role of mitochondrial adaptation as a mode of resistance is not completely understood. In this review, we wish to explore mitochondrial metabolism in melanoma and how it impacts modes of resistance. There are several genes that play a major role in melanoma mitochondrial metabolism which require a full understanding to optimally target melanoma. These include BRAF, CRAF, SOX2, MCL1, TRAP1, RHOA, SRF, SIRT3, PTEN, and AKT1. We will be discussing the role of these genes in melanoma in greater detail. An enhanced understanding of mitochondrial metabolism and these modes of resistance may result in novel combinatorial and sequential therapies that may lead to greater therapeutic benefit.

Choriocarcinoma metastatic to the skin: A rare occurrence associated with dismal outcome.

Germ cell tumors (GCTs) are a histologically heterogeneous group of tumors that arise from the primitive germ cell of the embryonic gonad. Choriocarcinoma is a variant of GCTs that is prone to hematogenous metastasis to the liver, lung, and brain. Cutaneous metastasis in choriocarcinoma is rarely encountered with only a few cases reported in literature. We report the case of a 28-year-old male presenting with lower back pain that, upon further work-up, was diagnosed with pure choriocarcinoma of the testes. Around 9 months after his initial presentation, he developed a cutaneous back lesion. Microscopic examination confirmed the presence of choriocarcinoma composed of mononuclear cytotrophoblasts which interweave with multinucleated syncytiotrophoblasts. The patient passed away 3 weeks after the onset of cutaneous metastasis.

Attitudes and barriers towards using complementary and alternative medicine among university students in Jordan.

BACKGROUND: Perceptions towards Complementary and Alternative Medicine (CAM) are highly variable but are improving globally. However, studies conducted in Jordan about CAM are insufficient. This study aims to explore the attitudes and barriers towards using CAM among university students in Jordan. DESIGN AND METHODS: This cross-sectional study was conducted at the University of Jordan. A self-administered paper questionnaire was distributed to 475 students from the Faculties of Medicine, Pharmacy and Engineering of all academic years. Descriptive and multivariate data analysis was done using SPSS v.20. RESULTS: Seventy percent of all the participants have used at least one type of CAM. Younger female pharmacy students were most likely to use CAM. There were significant differences between students of different academic years regarding their opinions on CAM (p < 0.024). The percentage of medical students who believed that combining CAM with modern medicine would improve the overall treatment quality was significantly lower than the other two faculties (p < 0.001). Of the students who never used CAM, 39% did not do because they doubted its effectiveness. CONCLUSION: There is a need for including CAM in the universities' curriculum as mandatory courses for health faculties and elective courses for other disciplines.