Chronic non-healing venous leg ulcers (VLUs) are widespread and debilitating, with high morbidity and associated costs; approximately $15 billion is spent annually on the care of VLUs in the US. Despite this, there is a paucity of treatments for VLUs, due to the lack of pathophysiologic insight into ulcer development as well as the lack of knowledge regarding biologic actions of existing VLU-targeted therapies. The bioengineered bilayered living cellular construct (BLCC) skin substitute is an FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or the BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA, and protein analyses. Ulcers treated with the BLCC skin substitute displayed three distinct transcriptomic patterns, suggesting that BLCC induced a shift from a non-healing to a healing tissue response involving modulation of inflammatory and growth factor signaling, keratinocyte activation, and attenuation of Wnt/β-catenin signaling. In these ways, BLCC application orchestrated a shift from the chronic non-healing ulcer microenvironment to a distinctive healing milieu resembling that of an acute, healing wound. Our findings provide in vivo evidence in patient VLU biopsies of pathways that can be targeted in the design of new therapies to promote healing of chronic VLUs.

Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue’s healing ability leading to development of DFUs.

Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells “meiomitosis” could impact chromosomal instability in melanoma and other cancers.

Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation.

IMPORTANCE Patients' perceptions of their physician can affect subjective and objective outcomes. Physician attire influences patients' perceptions of their physician and consequently may affect patient outcomes. OBJECTIVE To determine patient preferences for different types of dermatologist attire in dermatology medical, surgical, and wound care clinics. We hypothesized that patients in the dermatology medical setting would prefer professional attire, while patients in the dermatology surgical and wound care setting would prefer surgical scrubs. DESIGN, SETTING, AND PARTICIPANTS This study analyzed responses to a cross-sectional, anonymous survey by English-speaking dermatology patients (aged 18 years or older) at general, surgical, and wound care clinics in an academic center in Miami, Florida. Patients who could not read and understand the survey were excluded. Participants received pictures of a physician wearing business attire, professional attire, surgical attire, and casual attire, and responded by indicating which physician they preferred for each of 19 questions. Frequencies of responses were recorded, and χ 2 and regression tests were performed. MAIN OUTCOMES AND MEASURES Response frequencies. RESULTS Surveys were administered to 261 persons, and 255 participated and completed enough of the questions to be included in the outcome analyses (118 men, 121 women, 22 unknown [did not answer sex question]), mean (SD) age, 56.3 (18.6) years; about 49% of those who reported their sex were men; 56% were Hispanic; and 85% were white. Approximately 72% of respondents held a college degree or higher. About 63%, 24%, and 13% of respondents were medical, surgical, and wound care dermatology patients, respectively. Roughly 73%, 19%, 6%, and 2% of cumulative responses were for professional, surgical, business, and casual attire, respectively. Respondents who received a picture of a black male or black female physician were more likely to exclusively prefer professional attire: unadjusted odds ratios (ORs) 3.21 (95% CI, 1.39-7.42) and 2.78 (95% CI, 1.18-6.51), respectively, compared with respondents who received a picture of a white male physician. Nonwhite and unemployed respondents were less likely to prefer professional attire exclusively: ORs, 0.28 (95% CI, 0.1-0.83) and 0.28 (95% CI, 0.08-0.99), respectively. Respondents preferred professional attire in all clinic settings, though respondents in the dermatology surgery clinic were less likely to prefer professional attire compared with respondents in the medical dermatology clinic: race-adjusted OR, 0.74 (95% CI, 0.56-0.98). Wound care and medical dermatology respondents preferred professional attire comparably. CONCLUSIONS AND RELEVANCE In this study, most patients preferred professional attire for their dermatologists in most settings. It is possible that patients' perceptions of their physicians' knowledge and skill is influenced by the physicians' appearance, and these perceptions may affect outcomes.