Improvement of adult female acne with a novel weekly estradiol loaded peel off mask. A split face, placebo controlled study.

BACKGROUND: Adult female acne is characterized by a relapsing eruption of acne in individuals who are 25 years or older. It usually shows slower response to the traditional adolescent acne treatments. Usually, androgens promote acne by stimulating sebum production, while estrogens have the opposite effect by reducing sebum output when present in adequate quantities. Estradiol is the female sex hormone with the highest absolute serum levels and the highest estrogenic activity during a woman's reproductive years. Peel-off facial masks were suggested to intensify the effect of the added active ingredient through forming an occlusive film after drying. OBJECTIVES: to study the safety and efficacy of weekly topical estradiol 0.05% in the treatment of adult acne in females. METHODS: Twenty female patients with adult acne were subjected to once weekly application of estradiol 0.05% and placebo masks to either side of the face for 8 weeks. Acne lesion count was performed at baseline, at each visit and 8 weeks after end of treatment. RESULTS: At the end of the treatment period, the treated side showed significant improvement of comedones, papules and pustules. Although, lesions count increased 2 months after stopping treatment, they were still significantly less on the estradiol side compared to placebo. No side effects were reported. LIMITATIONS: The limited number of patients studied and the limited follow-up period. The estradiol effect was not studied on cellular and molecular levels. CONCLUSIONS: Topical estradiol peel off mask can be a promising convenient, safe and effective treatment for adult acne in women.

Urine scRNAseq reveals new insights into the bladder tumor immune microenvironment.

Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.

Natural Killer Cell Dysfunction In Human Bladder Cancer Is Caused By Tissue-Specific Suppression of SLAMF6 Signaling.

NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors. Rather, TME-specific TGF-ß and metabolic perturbations such as hypoxia directly suppressed NK cell function. Specifically, an oxygen-dependent reduction in signaling through SLAMF6 was mechanistically responsible for poor NK cell function, as tumor-infiltrating NK cells cultured ex vivo under normoxic conditions exhibited complete restoration of function, while deletion of SLAMF6 abrogated NK cell cytolytic function even under normoxic conditions. Collectively, this work highlights the role of tissue-specific factors in dictating NK cell function, and implicates SLAMF6 signaling as a rational target for immuno-modulation to improve NK cell function in bladder cancer.

The effectiveness of biosecurity interventions in reducing the transmission of bacteria from livestock to humans at the farm level: A systematic literature review.

Zoonotic bacterial infections are a health hazard for people who are in regular contact with livestock at the farm level. Improved biosecurity can limit zoonotic pathogen transmission within farms. The aim of this review was to summarize the effectiveness of farm-level biosecurity interventions in reducing bacterial transmission from animals to people who lived, worked in or visited farms. A systematic literature review was conducted using Embase, Ovid Medline and Agris databases, which were searched on 7th of July 2019, limited to English language papers but with no time exclusion criteria. A narrative synthesis was undertaken utilizing the Centre for Reviews and Dissemination approach, reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias within and across the included studies was performed using established checklists. Out of 869 studies retrieved through database searches, 11 studies were selected. In addition, three studies were found through study reference lists. Fourteen studies were therefore included in this review. Biosecurity interventions were grouped into five categories: hand washing, sanitization and hygienic measures (six studies); personal protective equipment (five studies); vaccination (two studies); other interventions (e.g. air ventilation flap) (four studies); and routine farm activities (two studies). Across studies that investigated odds of human colonization or infection (three studies), odds were seen to both be increased and decreased through use of tested biosecurity measures. Large confidence intervals that often crossed the threshold of an odds ratio equal to 1 were found. Most of the studies' overall risk of bias was 'medium risk' (11 studies), with selection bias domains generally being scored 'medium risk.' Biosecurity interventions are potentially beneficial in reducing bacterial transmission from animals to humans. However, more high-quality evidence is needed to increase certainty in which interventions, in which contexts, are most effective from the human health perspective.