Barrett's esophagus in 2016: From pathophysiology to treatment

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett's esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE

Design of Approaches for Dependability and Initial Prototypes

The aim of CONNECT is to achieve universal interoperability between heterogeneous Networked Systems. For this, the non-functional properties required at each side of the connection going to be established must be fulfilled. By the one inclusive term "CONNECTability" we comprehend properties belonging to all four non-functional concerns of interest for CONNECT, namely dependability, performance, security and trust. We model such properties in conformance with a meta-model which establishes the relevant concepts and their relations. Then, building on the conceptual models proposed in the first year in Deliverable D5.1, in this document we present the approaches developed for assuring CONNECTability both at synthesis time and at runtime. The contributions include: the Dependability&Performance analysis Enabler, for which we release a modular architecture supporting stochastic verification and state-based analysis; incremental verification and event-based monitoring for runtime analysis; a model-based approach to interoperable trust management; the Security-by-Contract-with-Trust framework, which guarantees and enforces the expected trust levels and security policies

A little square revolution

During one of our editorial meetings, I realized that everybody was mixing up picture books with young adult fiction. I said it and Giulio Einaudi seized the moment – Why don’t you do it yourself, a picture books series? – So, I did it.These words are Bruno Munari’s, who directed the Tantibambini series from 1972 to 1978. Munari conceived a cutting-edge revolutionary template design: square-sized books, without hardcover, which kept production costs low; every cover had an oval colour spot for the author’s and illustrator’s names, and the title was written in a different type consistent with the book content, logotype and, especially, the first lines of the story. This was totally new.This article, after defining the Italian historical and publishing context of the late sixties, analyzes the paratext as an important space for dialogue with the readers. Exploring the achievements and the commercial failure of the project, the article also analyzes the ferocious critique of the series, written by Natalia Ginzburg, a fine intellectual, and the critical consciousness of Einaudi publisher. In the end, it presents a metamorphosis: a new collection started by another publisher which harked back to the shape and the idea of Munari’s project to narrate other stories

Gastroesophageal reflux symptoms among Italian university students: Epidemiology and dietary correlates using automatically recorded transactions

Background: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. Methods: A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. Results: We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. Discussion: The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. Conclusions: To our knowledge, this is the first study evaluating the prevalence of typical GERD-related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system

Additional file 1 of Gastroesophageal reflux symptoms among Italian university students: epidemiology and dietary correlates using automatically recorded transactions

Supplementary tables. (TEX 11 kb

Le '68 des enfants / The Children's '68

Sous la direction de Sophie Heywood et Cécile Boulaire / Edited by Sophie Heywood and Cécile Boulair

Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression

International audienceAbstract Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the −200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy – even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies