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Abstract: We explored use of the suction‐blister wound model in the assessment of not only epidermal regeneration but also pain, the microvascular response and bacteriology. The effects of topical zinc sulfate were studied to articulate the methodologies in this double‐blind trial. One epidermal suction blister (10 mm) was induced on each buttock in 30 healthy volunteers (15 females:15 males) and deroofed on day 0. The wounds were randomized to daily treatment with 1.4% zinc sulfate shower gel (n = 20), placebo (n = 20) or control (n = 20). Digital photography coupled with planimetry, transepidermal water loss (TEWL) measurement and optical coherence tomography (OCT) was benchmarked to the gold standard of histology of 60 full‐thickness wound biopsies on day 4. Pain increased after application of the shower gels. Microvessel density, determined from OCT images, increased from day 0 to day 2 in the three groups but increased more with the placebo than with the zinc shower gel (p = 0.003) or the control treatment (p = 0.002) and correlated (rS = 0.313, p = 0.015) with the inflammatory response on day 4, as determined by histology. Coagulase‐negative staphylococci were more common in wounds compared with skin (p = 0.002) and was reduced (p = 0.030) with zinc sulfate treatment. Planimetric analysis of digital wound images was not biased (p = 0.234) compared with histology, and TEWL measurements showed no correlation (rS = 0.052, p = 0.691) with epithelialization. Neoepidermal formation, determined by histology, did not differ (p = 0.290) among the groups. Zinc sulfate reduced (p = 0.031) the release of lactate dehydrogenase from cultured gel‐treated keratinocytes isolated from the blister roofs. Therefore, combination of the standardized suction‐blister wound model with noninvasive planimetry and OCT is a useful tool for assessing wound therapies. Zinc sulfate transiently dampened inflammation and reduced bacterial growth. [ABSTRACT FROM AUTHOR]

Interaction between tumour survival tactics and antitumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed by immunohistochemistry followed by automated image analysis in facial BCC, peritumoural skin and normal, buttock skin. Quantitative real-time PCR (qRT-PCR) was performed for FOXP3 and cytokines involved in T-reg attraction and T-cell activation. T-regs comprised 45% of CD4-cells surrounding BCC. FOXP3 was highly expressed in BCC, but absent in buttock skin. Unexpectedly, expression of FOXP3 was increased in peritumoural skin, with the FOXP3/CD3 fractions exceeding those of BCC (p = 0.0065). Transforming growth factor (TGF)-β and T-reg chemokine expression was increased in BCC and peritumoural skin, but not in buttock skin, with expression levels correlating with FOXP3 . T-regs are abundantly present both in BCC and in peritumoural skin, mediating an immunosuppressed microenvironment permissive for skin cancer. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is the most frequent form of cutaneous T-cell lymphoma. The disease often takes an indolent course, but in approximately one-third of the patients, the disease progresses to an aggressive malignancy with a poor prognosis. At the time of diagnosis, it is impossible to predict which patients develop severe disease and are in need of aggressive treatment. Accordingly, we investigated the prognostic potential of microRNAs (miRNAs) at the time of diagnosis in MF. Using a quantitative reverse transcription polymerase chain reaction platform, we analyzed miRNA expression in diagnostic skin biopsies from 154 Danish patients with early-stage MF. The patients were subdivided into a discovery cohort (n = 82) and an independent validation cohort (n = 72). The miRNA classifier was built using a LASSO (least absolute shrinkage and selection operator) Cox regression to predict progression-free survival (PFS). We developed a 3-miRNA classifier, based on miR-106b-5p, miR-148a-3p, and miR-338-3p, which successfully separated patients into high-risk and low-risk groups of disease progression. PFS was significantly different between these groups in both the discovery cohort and the validation cohort. The classifier was stronger than existing clinical prognostic factors and remained a strong independent prognostic tool after stratification and adjustment for these factors. Importantly, patients in the high-risk group had a significantly reduced overall survival. The 3-miRNA classifier is an effective tool to predict disease progression of early-stage MF at the time of diagnosis. The classifier adds significant prognostic value to existing clinical prognostic factors and may facilitate more individualized treatment of these patients. [ABSTRACT FROM AUTHOR]

HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3+ cells in lymphoid tissue, and the impact of Tregs on immunological reconstitution was determined.HIV-infected individuals on combination antiretroviral therapy for a minimum of 2 years were included. The study population included 14 immunological nonresponders (INR; CD4 T-cell count <200 cells/μL), 33 intermediate responders (CD4 T-cell count 200-500 cells/μL), 30 responders (CD4 T-cell count >500 cells/μL), and 34 healthy controls. Tregs, Treg subpopulations, and intracellular staining for interleukin 10 in peripheral blood were measured using flow cytometry. Foxp3+ cells in lymphoid tissue were evaluated using immunolabeling. The CD4 T-cell count was determined at inclusion and after 1 year of follow-up.INR displayed high percentage of Tregs and activated Tregs in peripheral blood accompanied by a high percentage of Tregs expressing interleukin 10, whereas numbers of Foxp3+ cells in lymphoid tissue were low. In contrast, responders resembled healthy controls. Finally, in INR, high level of Tregs in blood and Foxp3+ cells in lymphoid tissue were associated with higher level of immunological reconstitution after 1 year of follow-up.In conclusion, altered distribution of Tregs was found in INR. Interestingly, high level of Tregs predicted higher level of immunological reconstitution suggesting a role for Tregs in immunological reconstitution. [ABSTRACT FROM AUTHOR]

HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell counts in controllers and in LTNPs.Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17 cells, and CD3+CD8+CD161highTc17 cells in peripheral blood were measured using flow cytometry. Tregs in lymphoid tissue were determined in tonsil biopsies and evaluated using immunolabeling. The production of transforming growth factor beta (TGF-β), interleukin (IL)-10, and IL-17 upon stimulation with phytohemagglutinin in peripheral blood was determined by Luminex.All groups of HIV-infected patients displayed similar percentages of Tregs in both peripheral blood and lymphoid tissue. However, a larger percentage of Tregs in ECs and LTNPs were activated compared with that in controls, progressors, and viremic controllers. Further, ECs as the only group of HIV-infected patients, displayed elevated percentages of CD161+Th17 cells, preserved CD3+CD8+CD161highTc17 cells, and preserved IL-10 production.Overall, Treg percentage was similar in both blood and lymphoid tissue in all groups of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors. [ABSTRACT FROM AUTHOR]