Expert Consensus Statement on Proficiency Standards for Dermoscopy Education in Primary Care.

BACKGROUND: Primary care providers (PCPs) frequently address dermatologic concerns and perform skin examinations during clinical encounters. For PCPs who evaluate concerning skin lesions, dermoscopy (a noninvasive skin visualization technique) has been shown to increase the sensitivity for skin cancer diagnosis compared with unassisted clinical examinations. Because no formal consensus existed on the fundamental knowledge and skills that PCPs should have with respect to dermoscopy for skin cancer detection, the objective of this study was to develop an expert consensus statement on proficiency standards for PCPs learning or using dermoscopy. METHODS: A 2-phase modified Delphi method was used to develop 2 proficiency standards. In the study's first phase, a focus group of PCPs and dermatologists generated a list of dermoscopic diagnoses and associated features. In the second phase, a larger panel evaluated the proposed list and determined whether each diagnosis was reflective of a foundational or intermediate proficiency or neither. RESULTS: Of the 35 initial panelists, 5 PCPs were lost to follow-up or withdrew; 30 completed the fifth and last round. The final consensus-based list contained 39 dermoscopic diagnoses and associated features. CONCLUSIONS: This consensus statement will inform the development of PCP-targeted dermoscopy training initiatives designed to support early cancer detection.

Assessing human metal accumulations in an urban superfund site.

Butte, Montana is part of the largest superfund site in the continental United States. Open-pit mining continues in close proximity to Butte's urban population. This study seeks to establish baseline metal concentrations in the hair and blood of individuals living in Butte, MT and possible routes of exposure. Volunteers from Butte (n=116) and Bozeman (n=86) were recruited to submit hair and blood samples and asked to complete a lifestyle survey. Elemental analysis of hair and blood samples was performed by ICP-MS. Three air monitors were stationed in Butte to collect particulate and filters were analyzed by ICP-MS. Soil samples from the yards of Butte volunteers were quantified by ICP-MS. Hair analysis revealed concentrations of Al, As, Cd, Cu, Mn, Mo, and U to be statistically elevated in Butte's population. Blood analysis revealed that the concentration of As was also statistically elevated in the Butte population. Multiple regression analysis was performed for the elements As, Cu, and Mn for hair and blood samples. Soil samples revealed detectable levels of As, Pb, Cu, Mn, and Cd, with As and Cu levels being higher than expected in some of the samples. Air sampling revealed consistently elevated As and Mn levels in the larger particulate sampled as compared to average U.S. ambient air data.

Cutting Edge: Selective Oral ROCK2 Inhibitor Reduces Clinical Scores in Patients with Psoriasis Vulgaris and Normalizes Skin Pathology via Concurrent Regulation of IL-17 and IL-10.

Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.

Identification of integrin beta subunit mutations that alter heterodimer function in situ.

We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila betaPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to support the development of adult animals, including mutations in the ADMIDAS site and in a cytoplasmic NPXY motif. Many mutations in the I-like domain reduce integrin expression specifically when betaPS is combined with activating alphaPS2 cytoplasmic mutations, indicating that integrins in the extended conformation are unstable relative to the inactive, bent heterodimers. Interestingly, the screen has identified alleles that show gain-of-function characteristics in cell culture, but have negative effects on animal development or viability. This is illustrated by the allele mys(b58); available structural models suggest that the molecular lesion of mys(b58), V409>D, should promote the "open" conformation of the beta subunit I-like domain. This expectation is supported by the finding that alphaPS2betaPS (V409>D) promotes adhesion and spreading of S2 cells more effectively than does wild-type alphaPS2betaPS, even when betaPS is paired with alphaPS2 containing activating cytoplasmic mutations. Finally, comparisons with the sequence of human beta8 suggest that evolution has targeted the "mys(b58)" residue as a means of affecting integrin activity.