Activin A Induces Langerhans Cell Differentiation In Vitro and in Human Skin Explants

Langerhans cells (LC) represent a well characterized subset of dendritic cells located in the epidermis of skin and mucosae. In vivo, they originate from resident and blood-borne precursors in the presence of keratinocyte-derived TGFβ. Ιn vitro, LC can be generated from monocytes in the presence of GM-CSF, IL-4 and TGFβ. However, the signals that induce LC during an inflammatory reaction are not fully investigated. Here we report that Activin A, a TGFβ family member induced by pro-inflammatory cytokines and involved in skin morphogenesis and wound healing, induces the differentiation of human monocytes into LC in the absence of TGFβ. Activin A-induced LC are Langerin+, Birbeck granules+, E-cadherin+, CLA+ and CCR6+ and possess typical APC functions. In human skin explants, intradermal injection of Activin A increased the number of CD1a+ and Langerin+ cells in both the epidermis and dermis by promoting the differentiation of resident precursor cells. High levels of Activin A were present in the upper epidermal layers and in the dermis of Lichen Planus biopsies in association with a marked infiltration of CD1a+ and Langerin+ cells. This study reports that Activin A induces the differentiation of circulating CD14+ cells into LC. Since Activin A is abundantly produced during inflammatory conditions which are also characterized by increased numbers of LC, we propose that this cytokine represents a new pathway, alternative to TGFβ, responsible for LC differentiation during inflammatory/autoimmune conditions

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Progetto di vita e progettazione educative in dialogo: essere madre in contesti di detenzione

Il contributo intende presentare, secondo la logica ed i modelli della progettazione educativa, una riflessione in merito alle differenze di genere nei processi e contesti di pena con particolare attenzione alle madri con figli molto piccoli. Durante la detenzione lo spazio ed il tempo dei progetti devono essere riorganizzati, in virt\uf9 della pena (dimensione personale) e del luogo (dimensione sociale). In particolare si presenter\ue0 uno studio di caso per sostenere l\u2019evoluzione degli interventi educativi a sostegno delle norme specifiche del settore

Cyclodextrin-Based Nanosponges as a Nanotechnology Strategy for Imiquimod Delivery in Pathological Scarring Prevention and Treatment

International audienc

Indagine di prevalenza sulle infezioni correlate all\u2019assistenza in un Policlinico Universitario.

INTRODUZIONELe infezioni correlate all\u2019assistenza (ICA) rappresentano una delle pi\uf9 frequenti complicanze delle prestazioni ospedaliere e al contempo una delle sfide principali della sanit\ue0 pubblica del Paese. Al fine di delinearne al meglio l\u2019impatto, risultano fondamentali le attivit\ue0 di sorveglianza attiva attraverso indagini di prevalenza e incidenza.MATERIALI E METODI Dal 11 al 13 ottobre 2017, \ue8 stata condotta nelle degenze ordinarie del Policlinico Universitario un\u2019indagine di prevalenza puntuale sulle infezioni nosocomiali.Sono state acquisite informazioni sulla presenza fattori di rischio per l\u2019insorgenza di infezioni ospedaliere (interventi chirurgici nei 30 giorni antecedenti la rilevazione, provenienza da casa di cura, RSA o centri dialisi negli ultimi 90 giorni, isolamento di microrganismi MDR negli ultimi 90 giorni, presenza di un catetere urinario a permanenza, antibioticoterapia, tipologia di microrganismi isolati). Per la rilevazione \ue8 stato utilizzato un apposito software.RISULTATI Sono stati arruolati 1106 pazienti.Nel 2017, i pazienti con almeno una ICA sono stati 34, per un numero complessivo di 35 casi (62 casi nel 2016, 5,48% di prevalenza; p=0,025) mentre la prevalenza complessiva delle ICA \ue8 stata del 3,16%.La prevalenza per la tipologia di Specialit\ue0 secondo classificazione ECDC si \ue8 dimostrata pi\uf9 alta nell\u2019Area Medica (4,72%) con 22 casi di ICA rilevati. Pi\uf9 interessante appare il decremento, rispetto al 2016, osservato nei reparti di specialit\ue0 chirurgica (7,5% nel 2016 vs 1,78% nel 2017; p=0,002) e, anche se non significativo, in quelli della specialit\ue0 ginecologica (5,7% nel 2016 vs 2,3% nel 2017; p=0,247) e nelle terapie intensive (8,2% nel 2016 vs 4,35% nel 2016; p=0,231).Per quanto riguarda la tipologia di ICA, le infezioni del torrente ematico, con 11 casi, costituiscono la tipologia pi\uf9 frequente (0,99%), seguite dalle polmoniti con 9 casi (0,81%) e le Infezioni delle vie urinaria con 8 casi (0,72%).Rispetto al 2016, si nota un decremento significativo delle infezioni del sito chirurgico (6 casi nel 2017 vs 23 casi nel 2016; p=0,002) e, non significativo, delle infezioni delle vie urinarie (8 casi nel 2017 vs 16 casi nel 2016; p=0,113).CONCLUSIONILo studio, pur con i limiti propri delle indagini di prevalenza puntuale, sembra evidenziare l\u2019efficacia di alcune misure di prevenzione realizzate nel setting oggetto di sorveglianza. Informazioni pi\uf9 solide sul dato delle infezioni del sito chirurgico saranno acquisite con uno studio di incidenza che a rotazione interesser\ue0 tutti i reparti chirurgici dell\u2019Ospedale in programma per il periodo 2018 -2020

[Resident physicians' participation to the activities of the hospital hygiene unit in a teaching hospital: a pilot study]

INTRODUCTION: The Hospital Hygiene Unit ensures hospital patient safety, through surveillance and control of environmental conditions of risk. In this context, resident physicians in Hygiene and Preventive Medicine of the Catholic University of the Sacred Heart (UCSC) are required to attend the unit to acquire professional skills, for two months (four weeks in the first year of residency and four weeks in the second year). In the initial phase of the rotation, residents are acquainted with the organization and assigned activities. Ongoing meetings with the tutor take place to verify the progress of activities in which they are involved; verification of acquired skills is performed at the end of the period of attendance. The aim of the study was to evaluate resident doctors' opinions about their training experience, in order to assess the perceived quality and pursue continuous improvement of the training program. MATERIALS AND METHODS: A questionnaire was administered to resident physicians attending the first three years of residency; the survey consisted of 11 multiple choice questions on organization, attendance, training and overall satisfaction and 3 open-ended questions on strengths, weaknesses and proposals for improvement. RESULTS: Fourteen of 15 residents (93.3%) completed the questionnaire: seven were male, five were first-year residents, five were second-year and four were third-year residents. Overall, 78% gave a positive assessment of the quality of training; in particular, 11 of 14 residents reported that the experience was very relevant to their training in Hygiene and Preventive Medicine. Responses regarding the training organization were also mostly positive (75%), as were those regarding attendance (57%) and overall satisfaction (67%). Fifty percent reported difficulties in combining this internship with the other activities planned with their tutor. CONCLUSIONS: Positive opinions prevail in all areas of assessment, although there are some aspects that can be improved, including the possibility to extend the period of attendance. Overall, training activities at the Operative Unit of Hospital Hygiene are appreciated by resident physicians, who consider them an important opportunity for professional growth

Activin A induces Langerhans cells differentiation in epidermis-depleted skin explants.

<p>Langerin expression was evaluated in the dermal layer, separated from skin explants by dispase digestion and subsequently treated for 72 hrs after i.d. injection with 100 ng Activin A (magnification 100X, inset 400X.).</p

Dermal accumulation of Langerhans cells in lichen planus is associated to abundant production of Activin A.

<p>Sections from normal skin (NS) (<i>a</i> and <i>d</i>) and lichen planus (LP) (<i>b, c, e, f</i>) biopsies were stained for Langerin (<i>a</i>–<i>c</i>) and Activin A (<i>d–f</i>). In normal skin, Langerin⁺ cells are regularly distributed in basal and suprabasal layers and show multiple fine dendrites; no positive cells are detectable in the dermis (panel <i>a</i>). In LP biopsies, in addition to intraepidermal LC, accumulation of Langerin⁺ cells is observed in the dermis within the dense monuclear cell infiltrate (panel <i>b</i>). At high power view, Langerin⁺ cells show an ovoidal/dendritic shape (panel <i>c</i>) and are found surrounding Factor VIII⁺ dermal blood vessels (arrow head, inset in <i>c</i>). Serial sections from the same tissue blocks were stained for Activin A. Normal skin (panel <i>d</i>) showed weak intraepithelial reactivity (red arrow head); in the dermis, mast cells and occasional spindle cells were positive for Activin A (black arrow heads). In LP, Activin A was strongly induced in the superficial layers of epidermis; in the dermis, a diffuse reactivity can be observed in numerous cells within the inflammatory infiltrate (panel <i>e</i>). This cell population includes endothelial cells and a mixture of non-lymphoid mononuclear cells (panel <i>f</i>). Magnification 100x (<i>a, b, d, e</i>; scale bar 200 micron) and 400x (<i>c, f</i>; scale bar 50 micron).</p