A bistable prokaryotic differentiation system underlying development of conjugative transfer competence.

The mechanisms and impact of horizontal gene transfer processes to distribute gene functions with potential adaptive benefit among prokaryotes have been well documented. In contrast, little is known about the life-style of mobile elements mediating horizontal gene transfer, whereas this is the ultimate determinant for their transfer fitness. Here, we investigate the life-style of an integrative and conjugative element (ICE) within the genus Pseudomonas that is a model for a widespread family transmitting genes for xenobiotic compound metabolism and antibiotic resistances. Previous work showed bimodal ICE activation, but by using single cell time-lapse microscopy coupled to combinations of chromosomally integrated single copy ICE promoter-driven fluorescence reporters, RNA sequencing and mutant analysis, we now describe the complete regulon leading to the arisal of differentiated dedicated transfer competent cells. The regulon encompasses at least three regulatory nodes and five (possibly six) further conserved gene clusters on the ICE that all become expressed under stationary phase conditions. Time-lapse microscopy indicated expression of two regulatory nodes (i.e., bisR and alpA-bisDC) to precede that of the other clusters. Notably, expression of all clusters except of bisR was confined to the same cell subpopulation, and was dependent on the same key ICE regulatory factors. The ICE thus only transfers from a small fraction of cells in a population, with an estimated proportion of between 1.7-4%, which express various components of a dedicated transfer competence program imposed by the ICE, and form the centerpiece of ICE conjugation. The components mediating transfer competence are widely conserved, underscoring their selected fitness for efficient transfer of this class of mobile elements.

The Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index (EGFRISTI): a new tool for grading and managing skin adverse reactions to epidermal growth factor receptor inhibitors.

BACKGROUND: Skin toxicity is frequent and debilitating in oncologic patients treated with epidermal growth factor receptor inhibitors (EGFRIs). Grading and management of skin adverse events (AEs) are poorly standardized. MATERIALS AND METHODS: We developed a new score (EGFRISTI: Epidermal Growth Factor Receptor Inhibitor-Related Skin Toxicity Index) which is able to quantify and monitor all EGFRI-related dermatologic AEs over time. The utility of this tool was validated in 130 patients treated with 5 different EGFRIs including both monoclonal antibodies and tyrosine kinase inhibitors. RESULTS: The mean baseline EGFRISTI score was 26.9 (range: 6.0-64.5). Mild toxicity was found in 55 patients (42.3%), moderate toxicity in 43 (33.1%), and severe toxicity in 32 patients (24.6%). After the first-line toxicity treatment, an EGFRISTI score reduction of >75% was obtained in 31 patients (34.1%) and one of 50% in 40 patients (43.9%), while an improvement of <50% was observed in the remaining 20 subjects (22.0%). CONCLUSIONS: The EGFRISTI is a simple and reliable tool to quantify and express the severity of all clinical signs and symptoms of EGFRI skin toxicity with a single numerical value, to choose the most suitable therapy, and to measure its efficacy.

Drug- and virus- or bacteria-induced exanthems: the role of immunohistochemical staining for cytokines in differential diagnosis.

BACKGROUND: The differential clinical diagnosis between drug-induced exanthema (DIE) and virus- or bacteria-induced exanthema (VBIE) is frequently not easy because the serologic analysis for virus and bacteria and skin tests are not always exhaustive. In these cases, only the oral challenge test is nullifying. OBJECTIVES: This study wants to identify 1 or more structural changes and/or cytokine markers that might be helpful in discriminating the etiology and the possible correlation with the clinical features, type of the involved drug, blood and skin eosinophilia, and time of skin biopsy. METHODS: Involved non-sun-exposed skin biopsy specimens were obtained from 36 patients with DIE and 30 patients with VBIE. Blood investigations, skin tests, and oral rechallenge tests were carried out in all subjects. The histopathologic features and the immunohistochemical expression of a cytokine panel [fatty acid synthase-ligand, granzyme B, interleukin (IL) 2, IL-4, IL-5, IL-10, IL-13, interferon γ, perforin, tumor necrosis factor α] were analyzed. CONCLUSIONS: Finally, DIE and VBIE have distinct skin cytokine profile (IL-5 alone or in combination with granzyme B and perforin in DIEs was statistically more frequent than in VBIEs, mainly when skin biopsy was carried out within 2 days from clinical onset), which might be helpful in discriminating the etiology.

Atopic dermatitis in adults.

Atopic dermatitis (AD) is a chronically relapsing eczematous disease, more common in infants and children than in adults and very rare after midlife. The diagnosis of AD is not always easy in adults, especially when the extension of lesions is limited and their distribution atypical. The aim of this study was to investigate epidemiologic and clinical features of adult AD. The medical files of 332 consecutive AD patients were reviewed to ascertain family and personal history of atopy, age at onset, morphology and localization sites of AD lesions, serum total immunoglobulin E levels, skin prick-test and patch-test results. The present study has show that the disease is more frequent in females and during the third decade of life, starts after the 18th year in slightly fewer than half the patients (47.6%), is prevalently localized in the limb flexures, eyelids, and perioral region, but also in the forehead, cheeks, and anterolateral region of the neck, where it is mainly mild to moderate. AD is of the intrinsic type in 30.4% of cases. Positive patch-test reactions to chemical allergens have been observed in 23.8% of patients. These are very important, because they may influence the occupational choices and the development of hand dermatitis.