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Aim: To provide guidance for follow‐up and monitoring of children and adolescents identified as positive to islet autoantibodies (IA) in the general population screening for type 1 diabetes (T1D) in Italy. Methods: Detection of IA helps to diagnose pre‐symptomatic T1D, prevent diabetic ketoacidosis (DKA) and identify persons for new therapies to delay symptomatic diabetes. Italy recently became the first country to approve by law a general autoantibody screening program for T1D and celiac disease in all children and adolescents (age 1‐17yr). A pilot study is currently underway in four Italian regions addressing feasibility issues to be used in the scale up to nationwide screening. Meanwhile, a group of experts developed guidance recommendations for follow‐up and monitoring of identified IA positive persons. Results: Ten key components have been identified: establishment of a registry for children and adolescents at risk; close collaboration with the national network of family paediatricians; creation of T1D centers with expertise in follow‐up and monitoring; educational measures; assurance of solid IA tests; identification of appropriate metabolic tests; feed‐back feasibility and acceptability questionnaires; potential access to available therapeutic interventions; valuable outcome measures including DKA incidence; costs monitoring. Distinctive features of this program include single (in addition to multiple) IA antibody‐positive persons in follow‐up and the use of CGM to assess risk progression, rather than the cumbersome OGTT. Conclusion: It is expected that the proposed follow‐up and monitoring program will be effective, affordable and acceptable to children and families identified in general T1D screening in Italy. [ABSTRACT FROM AUTHOR]

Background: Tobacco consumption, incorrect nutrition and insufficient physical activity/sedentariness represent modifiable NCDs risk factors in Western countries. To evaluate recent lifestyle indicators in Italy, data from the national Health Examination Survey (HES), implemented in 2018–2019 within the CUORE Project, were assessed. Methods: Age–sex standardized results from random samples of Italian general population (35–74 years) were reported by sex, age-class, educational level and geographical area. From 2106 participants, 2090 were considered for smoking habit, 2016 for physical activity and 1578 for nutrition. Standardized questionnaires were used for smoking habit and physical activity, and the EPIC questionnaire for nutrition. Results: Total cigarette current smokers were 23% in men and 19% in women; sedentariness during leisure time was 34% in men and 45% in women and at work 45% and 47% in men and women, respectively. Prevalence of balanced eating behaviours for vegetables was 28% in men and 39% in women; and for fruits 50% and 52%, respectively; prevalence of correct lifestyle (not smoker, regular physical activity and following at least five correct eating behaviours) was 7% and 12% for men and women, respectively. Conclusions: In 2018–2019, levels of unhealthy lifestyles were found to be still epidemic and basically stable compared to 10 years earlier (slight smoking habit decrease, slight sedentariness increase and slight nutrition improvements); intersectoral strategies and monitoring need to be continued. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are two mechanisms involved in the pathogenesis of celiac disease (CD). Since the direct effect of gliadin on the intestinal epithelia is less studied, the aims of this study were the development of a specific cellular model based on the use of gliadin as a pro-inflammatory stimulus and the evaluation of the potential antioxidant and anti-inflammatory properties of extracts from different black rice in the framework of CD. The rice extracts were in vitro digested, characterized in terms of phenolic compounds and antioxidant capacity, and tested on Caco-2 cells to investigate their inhibitory effect on Reactive Oxygen Species, the NF-κB transcription and the CXC chemokines (sICAM-1, IL-8, and CXCL-10). In addition, the role of the extracts in modulating the activation of epithelial cells in CD was confirmed by applying the K562(S) agglutination test. The black rice extracts showed inhibitory effects on the production of the oxidative and the inflammatory mediators considered, with particular reference to lymphocyte-attracting CXCL-10 both before and after digestion. The presence of anthocyanins and their digestion metabolites may account for the observed anti-inflammatory activity after in vitro digestion. This work provided preliminary data supporting the use of black rice as a healthy food or ingredient of food supplements for celiacs. [ABSTRACT FROM AUTHOR]

Abstract Background The association between coeliac disease (CD) and neoplasms has been long established, but few data are available about the risk factors. The aim of this paper is to estimate the risk of developing a neoplasm among non diagnosed coeliac patients and to evaluate if this risk correlates with the age of patients at diagnosis of coeliac disease. Methods The study population consists of patients (n = 1968) diagnosed with CD at 20 Italian gastroenterology referral Centers between 1st January 1982 and 31st March 2005. Results The SIR for all cancers resulted to be 1.3; 95% CI = 1.0–1.7 p < 0.001. The specific SIRs for non Hodgkin lymphoma was 4.7; 95% CI = 2.9–7.3 p < 0.001, for the small bowel carcinoma 25; 95% CI = 8.5–51.4 p < 0.001, for non Hodgkin lymphoma 10; 95% CI = 2.7–25 p = 0.01, finally for the stomach carcinoma 3; 95% CI = 1.3–4.9 p < 0.08. The mean age at diagnosis of CD of patients that developed sooner or later a neoplasm was 47,6 ± 10.2 years versus 28.6 ± 18.2 years of patients who did not. Conclusion Coeliac patients have an increased risk of developing cancer in relation to the age of diagnosis of CD. This risk results higher for malignancies of the gastro-intestinal sites. An accurate screening for tumors should be performed in patients diagnosed with CD in adulthood and in advancing age.

A new mixture of selected sourdough lactobacilli and fungal proteases is used to eliminate the toxicity of wheat flour during long-time fermentation. It is considered as an efficient approach to eliminate gluten toxicity.

The prevention of necrotizing enterocolitis (NEC) is a primary goal in the care of preterm and low birth-weight infants. Donor-banked milk (DM)-feeding has been reported to have a protective effect towards NEC with respect to formula-feeding. All the meta-analysis published so far, have been focused on the protective effect of DM on the overall risk of NEC, none of them focused on the risk of the most severe cases on NEC only, that are those requiring surgery. We conducted a meta-analysis of available evidences on the risk of developing surgical cases of NEC in DM-fed preterm and/or low birth weight infants with respect to those formula-fed. A search for articles published between January 1960 and January 2018 and addressing the association between DM and surgical NEC was conducted via PubMed, Embase and Cochrane database. We included randomized controlled clinical trials, reporting primary data and involving preterm and/or low birth weight infants fed with preterm formula compared to DM, both as sole diet or complementing own mother's milk. Estimates were pooled using random-effects. Study quality was assessed by GRADE score and risk of bias by the Review Manager software tool. Four papers were included in the meta-analysis. DM did not exert a beneficial effect of DM on the risk of preventing surgical NEC with respect to formula (RR: 0.45; 95% CI: 0.19–1.09). This meta-analysis indicates that DM does not exert a clear protective effect, on the surgical cases of NEC with respect to preterm formula. Since DM feeding implies remarkable extra cost for the preparation, storage and delivery of the milk with respect to preterm formula, stronger evidences are required to recommend this type of feeding as a preventive strategy for surgical NEC. Mother's milk, when available, could represents the best choice. CRD42015020296 [ABSTRACT FROM AUTHOR]

The metabolic response to stress and infection is closely related to the corresponding requirements of energy and nutrients. On a general level, the response is driven by a complex endocrine network and related to the nature and severity of the insult. On an individual level, the effects of nutritional interventions are highly variable and a possible source of complications. This narrative review aims to discuss the metabolic changes in critically-ill children and the potential of developing personalized nutritional interventions. Through a literature search strategy, we have investigated the importance of blood glucose levels, the nutritional aspects of the different phases of acute stress response, and the reliability of the available tools to assess the energy expenditure. The dynamics of metabolism during stressful events reveal the difficult balance between risk of hypo- or hyperglycemia and under- or overfeeding. Within this context, individualized and accurate measurement of energy expenditure may help in defining the metabolic needs of patients. Given the variability of the metabolic response in critical conditions, randomized clinical studies in ill children are needed to evaluate the effect of individualized nutritional intervention on health outcomes. [ABSTRACT FROM AUTHOR]

A priority of the European Union is the control of risks possibly associated with chemical contaminants in food and undesirable substances in feed. Following an initial chapter describing the main contaminants detected in food and undesirable substances in feed in the EU, their main sources and the factors which affect their occurrence, the present review focuses on the “continous call for data” procedure that is a very effective system in place at EFSA to make possible the exposure assessment of specific contaminants and undesirable substances. Risk assessment of contaminants in food atances in feed is carried currently in the European Union by the CONTAM Panel of EFSA according to well defined methodologies and in collaboration with competent international organizations and with Member States. [ABSTRACT FROM PUBLISHER]

The human intestinal mucosal surface represents the first defense against pathogens and regulates the immune response through the combination of epithelial cell (EC) functions and immunological factors. ECs act as sensors of luminal stimuli and interact with the immune cells through signal-transduction pathways, thus representing the first barrier that HIV-1 virus encounters during infection. In particular, the HIV-1 Nef protein plays a crucial role in viral invasion and replication. Nef is expressed early during viral infection and interacts with numerous cellular proteins as a scaffold/adaptor. Nef is localized primarily to cellular membranes and affects several signaling cascades in infected cells modulating the expression of cell surface receptors critical for HIV-1 infection and transmission, also accompanied by the production of specific cytokines and progressive depletion of CD4C T cells. At the intestinal level, Nef contributes to affect the mucosal barrier by increasing epithelial permeability, that results in the translocation of microbial antigens and consequently in immune system activation. However, the pathological role of Nef in mucosal dysfunction has not been fully elucidated. Interestingly, Nef is secreted also within exosomes and contributes to regulate the intercellular communication exploiting the vesicular trafficking machinery of the host. This can be considered as a potential inter-kingdom communication pathway between virus and humans, where viral Nef contributes to modulate and post-transcriptionally regulate the host gene expression and immune response. In this mini-review we discuss the effects of HIV-1 Nef protein on intestinal epithelium and propose the existence of an inter-kingdom communication process mediated by exosomes. [ABSTRACT FROM AUTHOR]

To allow celiac patients to have meals out, a growing number of restaurants and pizzas houses that simultaneously provide gluten-free (GF) pizzas and wheat-based (WB) pizzas have recently been opened in Italy. In these restaurants, GF pizzas are prepared with GF raw materials, following procedures that minimize the risk of gluten cross-contact. Here, we evaluate the risk of gluten crosscontact of GF pizzas in relation to the preparation procedures, thus aiming at identifying a safe procedure for cooking GF pizzas. Our results show that, when specific requirements are complied with, the simultaneous cooking of GF and WB pizzas is a procedure as safe as having an oven dedicated to GF pizzas or the alternate cooking of GF and WB pizzas in the same oven. [ABSTRACT FROM AUTHOR]

Cactus pear (Opuntia ficus-indica L.) is widely distributed in the arid and semi-arid regions throughout the world. In the last decades, the interest towards vegetative crop increased, and cladodes are exploited for nutraceutical and health-promoting properties. This study aimed at investigating the capacity of selected lactic acid bacteria to increase the antioxidant and anti-inflammatory properties of cactus cladodes pulp, with the perspective of producing a functional ingredient, dietary supplement or pharmaceutical preparation. Preliminarily, the antioxidant activity was determined through in vitro assays. Further, it was confirmed through ex vivo analysis on intestinal Caco-2/TC7 cells, and the profile of flavonoids was characterized. Cactus cladode pulp was fermented with lactic acid bacteria, which were previously selected from plant materials. Chemically acidified suspension, without bacterial inoculum and incubated under the same conditions, was used as the control. Lactobacillus plantarum CIL6, POM1 and 1MR20, Lactobacillus brevis POM2 and POM4, Lactobacillus rossiae 2LC8 and Pediococcus pentosaceus CILSWE5 were the best growing strains. Fermentation of cladode pulp with L. brevis POM2 and POM4 allowed the highest concentration of γ-amino butyric acid. Lactic acid fermentation had preservative effects (P<0.05) on the levels of vitamin C and carotenoids. Two flavonoid derivatives (kaemferol and isorhamnetin) were identified in the ethyl acetate extracts, which were considered to be the major compounds responsible for the increased radical scavenging activity. After inducing oxidative stress by IL-1β, the increased antioxidant activity (P<0.05) of fermented cladode pulp was confirmed using Caco-2/TC7 cells. Fermented cladode pulp had also immune-modulatory effects towards Caco-2 cells. Compared to the control, fermented cladode pulp exhibited a significantly (P<0.05) higher inhibition of IL-8, TNFα and prostaglandins PGE2 synthesis. The highest functional effect was found using ethyl acetate extracts. In conclusion, fermentation, especially with L. plantarum strains and L. brevis POM4, enhanced the antioxidant and immune-modulation features of cladode pulp. [ABSTRACT FROM AUTHOR]

Objective: To review the evidence for the association of breast feeding, breastfeeding duration or the timing of gluten introduction and the later development of celiac disease (CD). Design: Systematic review. Methods: We searched MEDLINE, via PubMed, EMBASE and Web of Science, for studies published up to 31 August 2015 investigating the association of breastfeeding duration, breast feeding at the moment of gluten introduction or the timing of gluten introduction and the later development of CD. Prospective studies had to enrol infants/children at high risk of CD. For retrospective studies, participants had to be children or adults with CD. The paper quality was assessed by means of a GRADE score and the bias risk was assessed by the Newcastle-Ottawa Scale (for observational cohort studies) and Cochrane Collaboration's tool (for randomised trials). Results: Out of 149 retrieved papers, 48 were considered in depth and 16 were included in this review (9 were prospective and 2 were interventional). We found that neither duration of breastfeeding nor breastfeeding at time of gluten introduction nor the delayed introduction of gluten during weaning were effective in preventing later development of CD. Conclusions: Currently, there is no evidence on the optimal breastfeeding duration or the effects of avoiding early (<4 months of age) or late (≥6 or even at 12 months) gluten introduction in children at risk of CD. Accordingly, no specific general recommendations about gluten introduction or optimal breastfeeding duration can be presently provided on evidence-based criteria in order to prevent CD. [ABSTRACT FROM AUTHOR]

Objective. Celiac disease (CD) has strongly been established as associated with some site-specific gastrointestinal malignancies. On the contrary, according to the few reports available, the risk of colon carcinoma in CD patients has been described similar to that of general population. In this cohort study, we describe the risk of colon carcinoma in a group of Italian celiac patients. Materials and methods. The study population included all CD patients diagnosed at the Collaborating Centers of the Italian Registry of CD between 1st January 1982 and 31st December 2006. Upon diagnosis of CD and upon at every subsequent clinical control, the Collaborating Centers filled in a validated form for each CD patient reporting information about demographic data, possible occurrence of a neoplasm and adherence to a gluten-free diet. Results. Out of 1757 celiac patients enrolled, 6 developed a colon carcinoma during the follow-up period (mean: 18.1 years). The standardized incidence ratio (SIR) resulted 0.29 (95% CI = 0.07-0.45). Stratifying the risk for the dietary gluten intake, the SIR dropped to 0.07 (95% CI = 0.009-0.27) for CD patients with a strict adherence to a gluten-free diet. Conclusion. We confirm the previous finding that there is low risk to develop a colon cancer in celiac patients. [ABSTRACT FROM AUTHOR]

Celiac Disease (CD) is a chronic inflammatory enteropathy, triggered in genetically susceptible individuals by dietary gluten. Gluten is able to elicit proliferation of specific T cells and secretion of inflammatory cytokines in the small intestine. In this study we investigated the possibility that p10-mer, a decapeptide from durum wheat (QQPQDAVQPF), which was previously shown to prevent the activation of celiac peripheral lymphocytes, may exert an inhibitory effect on peptic-tryptic digested gliadin (PT-Gly)-stimulated intestinal carcinoma CACO-2 cells. In these cells, incubated with PT-Gly or p31-43 α-gliadin derived peptide in the presence or in the absence of p10-mer, IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation were measured by immunoblotting, Cyclooxigenase 2 (COX-2) activity by PGE-2 release assay, and production of cytokines in the cell supernatants by ELISA. Our results showed that pre-treatment of CACO-2 cells with p10-mer significantly inhibited IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation, as well as COX-2 activity (i.e. PGE-2 release) and production of the IL-6 and IL-8 pro-inflammatory cytokines, induced by gliadin peptides. These findings demonstrate the inhibitory effect of the p10-mer peptide on inflammatory response in CACO-2 cells. The results of the present study show that this p10-mer peptide can modulate "in vitro" the inflammatory response induced by gliadin peptides, allowing to move towards new therapeutic strategies. Turning off the inflammatory response, may in fact represent a key target in the immunotherapy of celiac disease. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: The cytosolic phospolypase A2 (cPLA2) - dependent release of arachidonic acid (AA) from the intra-epithelial lymphocytes plays a pivotal role in arming lymphocytes to cytolysis in the immune response of celiac disease. However, little is known about the role of enterocytes in releasing AA. Docosahexaenoic acid (DHA) is a long chain polyunsaturated fatty acid that counteracts many of the proinflammatory effect of AA. The aims of the present work were to evaluate if: 1) intestinal epithelial cells have a role in the celiac inflammation, releasing AA, and 2) if DHA is able to modulate the celiac inflammation, down-regulating the release of AA. Methods: A human intestinal epithelial cell line (Caco-2) was exposed to gliadin peptides (PT-gl) (500 μg/ml) and DHA (2 μg/ml), both alone and simultaneously up to 24 h. Results: The exposure of those cells to PT-gl alone resulted in an increased AA release, cycloxygenase-2 expression, cPLA2 activity and prostaglandin E2 and interleukin-8 release in culture medium, whereas the simultaneous exposure of the cells to DHA and PT-gl prevented the above-mentioned increases. Conclusions: These results suggest that intestinal epithelial cells sustain the celiac inflammation, releasing AA when stimulated with gliadin and that DHA inhibits the AA release by these cells. [Copyright &y& Elsevier]