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Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.

Recently, dupilumab, an anti-IL-4Rα antibody, has become available for the treatment of moderate-to-severe atopic dermatitis (AD).1-4 Baseline patient characteristics that can be used as predictors of response to dupilumab treatment in AD patients have not yet been identified.

Today it is clearly evident that genetic background constitutes an integral part of aging and longevity. Many studies on long-lived people have been conducted emphasizing the role of certain genes in long life. Classic case-control studies, genome-wide association studies, and high-throughput sequencing have permitted identification of a variety of genetic variants seemingly associated with longevity. Over the years, aging research has focused on the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway because of its evolutionarily conserved correlation with life-span extension in model animals. Indeed, many single-nucleotide polymorphisms (SNPs) associated with longevity were identified in genes encoding proteins that take part in this metabolic pathway. Closely related to this pathway is the Klotho gene. It encodes a type-I membrane protein expressed in two forms, membrane and secreted. The latter form suppresses oxidative stress and growth factor signaling and regulates ion channels and transporters. In particular, its over-expression seems to be able to suppress insulin/IGF-1 signaling extending life span. Thus, our aim was to assemble the results in the literature concerning the association between the functional variant of the Klotho "KL-VS" stretch, which contains six polymorphisms in linkage disequilibrium, and successful aging to quantify the possible effect of the variants. The results of our systematic review indicate that the Klotho KL-VS variant is associated with healthy aging.

Background Although the preventive efficacy of allergen immunotherapy (AIT) in the onset of new allergen sensitizations has been asserted by many reviews, position papers, and consensus conferences, the evidence available is from only 3 studies. The objective of this work was a systematic review to evaluate the preventive efficacy of AIT in the onset of new allergen sensitizations. The end-point was the risk difference (RD) in the onset of new allergen sensitizations between patients treated with AIT and pharmacotherapy. Methods Computerized bibliographic searches of MEDLINE, EMBASE, and the Cochrane Library (until November 30th, 2016) were done. Random-effects and fixed-effects model meta-analyses were performed. Randomized controlled trials or observational studies comparing children treated with AIT with house dust mite (HDM) to subjects who did not receive AIT, with a long-term observation period (at least 3 years including treatment and follow-up) have been included. Results Eight studies totaling 721 children (390 treated with AIT and 331 with pharmacotherapy) met the inclusion criteria. The risk of bias was high. Low evidence supports the conclusion that AIT prevents the onset of new allergen sensitizations, with 3 of 8 studies reporting a reduction in the onset of new sensitizations in patients treated with AIT vs pharmacotherapy. Our meta-analysis found no difference between AIT and pharmacotherapy, with high heterogeneity (RD, −0.10; 95% confidence interval [CI], −0.31 to 0.11; p = 0.32; I2 = 91.4%). Conclusion The data of this systematic review do not support a preventive effect in the onset of new allergen sensitizations, in children treated with AIT in comparison with those treated with pharmacotherapy.

Background. The amount of hepatology-related information available on the Internet has substantially increased, but little is known about the characteristics and quality of the websites. Aim. The aim of this study was to describe analytically and evaluate critically the information concerning three diseases of hepatological interest: chronic hepatitis, hemochromatosis and Caroli’s disease. Methods. In accordance with a validated method, the three search terms were entered into four English language search engines and the first five links of each were considered (a total of 60 sites). The characteristics of the websites were described and their quality was evaluated by three independent reviewers who assigned scores of 1–5 for accuracy, reliability and depth. The relationships between the site characteristics and quality scores were analysed by means of multiple logistic regression. Results. The overall rating score was sufficient (≥3) in 51% (95% confidence interval: 38–65%) of cases. The majority of the sites (73%) were aimed at patients rather than at physicians. Commercial sponsorship was significantly more frequent among the chronic hepatitis sites (45%) than among the hemochromatosis (15%) or Caroli’s disease sites (0%) (P=0.002); 61% of the commercial sites did not include a financial disclosure. The only variable that independently related to poor quality was the presence of commercial sponsorship (odds ratio 18.1; 95% confidence interval: 1.7–192.5). Conclusions. Hepatological websites are characterised by poor quality and are mainly aimed at patients. Quality is negatively affected by commercial interests, which are often undeclared. Guidelines for the certification and surveillance of websites relating to liver diseases are highly advisable.

Hyperthermia represents an interesting therapeutic strategy for the treatment of tumors. Moreover, it is able to regulate several aspects of the immune response. Fas (APO-1/CD95) and its ligand (FasL) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death, is implicated in diseases in which lymphocyte homeostasis is compromised, and plays an important role during cytotoxic and regulatory actions mediated by these cells. In this study we describe the effect of hyperthermia on activation of the fas-L gene in T lymphocytes. We show that hyperthermic treatment enhances Fas-L-mediated cytotoxicity, fas-L mRNA expression, and fas-L promoter activity in activated T cell lines. Our data indicate that hyperthermia enhances the transcriptional activity of AP-1 and NF-κB in activated T cells, and this correlates with an increased expression/nuclear translocation of these transcription factors. Moreover, we found that heat shock factor-1 is a transactivator of fas-L promoter in activated T cells, and the overexpression of a dominant negative form of heat shock factor-1 may attenuate the effect of hyperthermia on fas-L promoter activity. Furthermore, overexpression of dominant negative mutants of protein kinase Cε (PKCε) and PKCθ partially inhibited the promoter activation and, more importantly, could significantly reduce the enhancement mediated by hyperthermia, indicating that modulation of PKC activity may play an important role in this regulation. These results add novel information on the immunomodulatory action of heat, in particular in the context of its possible use as an adjuvant therapeutic strategy to consider for the treatment of cancer.

This work proposes a novel methodology based on the Business Process Modeling Notation (BPMN) standard capable of graphically modeling business rules. A set of new representation patterns allows business analysts to map processes described through BPMN into conditions and actions of business rules. Our approach exploits Domain Specific Language techniques in order to make the methodology independent from the programming language supported by the specific rule engine. Moreover, this work proposes a web graphical editor, instantiated on a specific sample scenario, where the selected rule engine is Drools, one of the most used open source products. The developed editor allows business analysts to graphically define business rules and to automatically generate executable code compliant with the selected rule engine. The case study and the resulting benchmarking show the effectiveness of the proposed methodology.

A dramatic increase in mean life span and life expectancy, coupled with a significant reduction in early mortality, has lead to a large increase in number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases associated with advancing age. Both innate and instructive immunity are implicated in almost all age-related diseases. The modifications of the immune system in the elderly are evaluated as a deterioration of the immune system, the so-called immunosenescence, which is thought to be mostly the result of the declining effectiveness of T cells and it is responsible for the increased susceptibility of elderly to infectious diseases. In addition, a low-grade systemic inflammation characterizes ageing and inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and inflammatory age-related diseases are initiated or worsened by systemic inflammation.

PERCUTANEOUS RADIOFREQUENCY THERMAL ABLATION 8 RFTA) OF SMALL HEPATOCELLUALR CARCINOMA: A PROSPECTIVE STUDY Data: 2004 Dettaglio tipologia d'Ateneo: 3a - Articoli su riviste ISI (anche on line)