Follow-up and monitoring programme in children identified in early-stage type 1 diabetes during screening in the general population of Italy.

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.

A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease.

Intestinal handling of dietary proteins usually prevents local inflammatory and immune responses and promotes oral tolerance. However, in ~ 1% of the world population, gluten proteins from wheat and related cereals trigger an HLA DQ2/8-restricted TH1 immune and antibody response leading to celiac disease. Prior epithelial stress and innate immune activation are essential for breaking oral tolerance to the gluten component gliadin. How gliadin subverts host intestinal mucosal defenses remains elusive. Here, we show that the α-gliadin-derived LGQQQPFPPQQPY peptide (P31-43) inhibits the function of cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel pivotal for epithelial adaptation to cell-autonomous or environmental stress. P31-43 binds to, and reduces ATPase activity of, the nucleotide-binding domain-1 (NBD1) of CFTR, thus impairing CFTR function. This generates epithelial stress, tissue transglutaminase and inflammasome activation, NF-κB nuclear translocation and IL-15 production, that all can be prevented by potentiators of CFTR channel gating. The CFTR potentiator VX-770 attenuates gliadin-induced inflammation and promotes a tolerogenic response in gluten-sensitive mice and cells from celiac patients. Our results unveil a primordial role for CFTR as a central hub orchestrating gliadin activities and identify a novel therapeutic option for celiac disease.

Protein and growth during the first year of life: a systematic review and meta-analysis.

Dietary protein intake in the first year of life might influence later growth. We conducted a systematic review to investigate the growth effects of interventions based on infant formula composition providing different amounts of protein within the first year of life of healthy term infants; in the absence of other comparable information over the investigated period, a meta-analysis further compared weight or length gain at 120 days from high- (>2.0 g/100 kcal) and low-protein (≤2.0 g/100 kcal) content formula groups. Twelve papers (n = 2275) were included and five of them (n = 677) contributed to the meta-analysis. Most studies compared a high-protein formula, a low-protein formula, and breastfeeding. Evidence from the systematic review was inconclusive due to heterogeneity in design and treatments. In the presence of modest heterogeneity but in the absence of publication bias, the weighted mean difference for weight gain at 120 days was -0.02 g/day (95% CI: -1.41, 1.45); with higher heterogeneity, the weighted MD estimate of length gain at 120 days was 0.004 cm/month (95% CI: -0.26, 0.27). Although limited and underpowered, evidence from the meta-analysis does not support the assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first months of life. Prospero registration number: CRD42017058535. IMPACT: The optimal amount of dietary protein that should be given to healthy full-term infants early in life is still debated. Despite heterogeneity in study design, treatments, and outcomes, this systematic review showed that there is no clear-cut effect on the growth of different amounts of protein intake from formulas or complementary feeding. Evidence from the meta-analysis based on the five articles enrolling infants <1 month of life does not support the previous assumption that high- vs. low-protein content formulas during exclusive milk-feeding lead to different growth outcomes in the first 4 months of life.

Front-of-pack (FOP) labelling systems to improve the quality of nutrition information to prevent obesity: NutrInform Battery vs Nutri-Score.

Many systems for classifying food products to adequately predict lower all-cause morbidity and mortality have been proposed as front-of-pack (FOP) nutritional labels. Although the efforts and advances that these systems represent for public health must be appreciated, as scientists involved in nutrition research and belonging to diverse Italian nutrition scientific societies, we would like to draw stakeholders' attention to the fact that some FOP labels risk being not correctly informative to consumers' awareness of nutritional food quality. The European Commission has explicitly called for such a nutrition information system to be part of the European "strategy on nutrition, overweight and obesity-related issues" to "facilitate consumer understanding of the contribution or importance of the food to the energy and nutrient content of a diet". Some European countries have adopted the popular French proposal Nutri-Score. However, many critical limits and inadequacies have been identified in this system. As an alternative, we endorse a new enriched informative label-the NutrInform Battery-promoted by the Italian Ministry of Health and deeply studied by the Center for Study and Research on Obesity, Milan University. Therefore, the present position paper limits comparing these two FOP nutritional labels, focusing on the evidence suggesting that the NutrInform Battery can help consumers better than the Nutri-Score system to understand nutritional information, potentially improving dietary choices. LEVEL OF EVIDENCE: II. Evidence was obtained from well-designed controlled trials without randomization.

Personalized nutrition approach in pediatrics: a narrative review.

Dietary habits represent the main determinant of health. Although extensive research has been conducted to modify unhealthy dietary behaviors across the lifespan, obesity and obesity-associated comorbidities are increasingly observed worldwide. Individually tailored interventions are nowadays considered a promising frontier for nutritional research. In this narrative review, the technologies of importance in a pediatric clinical setting are discussed. The first determinant of the dietary balance is represented by energy intakes matching individual needs. Most emerging studies highlight the opportunity to reconsider the widely used prediction equations of resting energy expenditure. Artificial Neural Network approaches may help to disentangle the role of single contributors to energy expenditure. Artificial intelligence is also useful in the prediction of the glycemic response, based on the individual microbiome. Other factors further concurring to define individually tailored nutritional needs are metabolomics and nutrigenomic. Since most available data come from studies in adult groups, new efforts should now be addressed to integrate all these aspects to develop comprehensive and-above all-effective interventions for children. IMPACT: Personalized dietary advice, specific to individuals, should be more effective in the prevention of chronic diseases than general recommendations about diet. Artificial Neural Networks algorithms are technologies of importance in a pediatric setting that may help practitioners to provide personalized nutrition. Other approaches to personalized nutrition, while promising in adults and for basic research, are still far from practical application in pediatrics.

Food and feed chemical contaminants in the European Union: Regulatory, scientific, and technical issues concerning chemical contaminants occurrence, risk assessment, and risk management in the European Union.

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.

Two wheat decapeptides prevent gliadin-dependent maturation of human dendritic cells.

Celiac disease (CD) is a small intestinal enteropathy, triggered in susceptible individuals by the ingestion of dietary gluten. Dendritic cells (DC) are instrumental in the generation and regulation of immune responses and oversee intestinal immune homeostasis promoting and maintaining oral tolerance to food antigens. The aim of this study was to monitor the effect of peptic-tryptic digest of gliadin (PT-gliadin) on the maturation of human monocyte-derived DC and the impact of pDAV and pRPQ decapeptides in the modulation of PT-gliadin-induced phenotypic and functional DC maturation. Immature DC (iDC) were challenged in vitro with PT-gliadin. In some experiments iDC were pre-treated with pDAV or pRPQ and after 2h PT-gliadin was added to the cultures. We found that PT-gliadin up-regulates the expression of the maturation markers HLA-DR, CD83, CD80 and CD86. The functional consequence of PT-gliadin treatment of iDC is a significant increase in IL-12, TNF-alpha production as well as in their T cell stimulatory capacity. On the contrary, the digest of zein had no effect on DC maturation. Interestingly, we found that pre-treatment of iDC with pDAV or pRPQ decapeptides significantly prevents the functional maturation of DC induced by PT-gliadin. On the other hand, pDAV and pRPQ did not revert the PT-gliadin-induced phenotypic maturation of DC. Here we report, for the first time, that naturally occurring peptides are able to prevent the gliadin-dependent DC maturation. This finding could have implication for CD, raising the perspective of a potential therapeutic strategy alternative to a gluten free diet.

Low risk of colon cancer in patients with celiac disease.

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.

Diversity of oat varieties in eliciting the early inflammatory events in celiac disease.

PURPOSE: Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic-tryptic digests of the proteins of the oat cultivars. METHODS: K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42-44 in T84 cells were the early gliadin-dependent events studied. RESULTS: The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti-gliadin antibodies. CONCLUSION: We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety.

Use of fungal proteases and selected sourdough lactic acid bacteria for making wheat bread with an intermediate content of gluten.

This study was aimed at combining the highest degradation of gluten during wheat flour fermentation with good structural and sensory features of the related bread. As estimated by R5-ELISA, the degree of degradation of immune reactive gluten was ca. 28%. Two-dimensional electrophoresis and RP-FPLC analyses showed marked variations of the protein fractions compared to the untreated flour. The comparison was also extended to in vitro effect of the peptic/tryptic-digests towards K562 and T84 cells. The flour with the intermediate content of gluten (ICG) was used for bread making, and compared to whole gluten (WG) bread. The chemical, structural and sensory features of the ICG bread approached those of the bread made with WG flour. The protein digestibility of the ICG bread was higher than that from WG flour. Also the nutritional quality, as estimated by different indexes, was the highest for ICG bread.

Adherence to Mediterranean Diet and Health Outcomes in Adolescents: An Umbrella Review.

CONTEXT: Proper nutrition represents 1 of the domains of adolescents' well-being. In this context, the Mediterranean diet (MD), as a healthy, traditional, and sustainable dietary pattern, plays a crucial role in promoting adequate growth and preventing chronic noncommunicable diseases. OBJECTIVE: The currently available evidence on the effects of adherence to the MD (AMD) in association with several physical health outcomes in adolescence is summarized in this review. DATA SOURCES: Five electronic databases were searched. STUDY SELECTION: Systematic reviews with or without meta-analysis of observational studies and randomized clinical trials, published in English during 2013-2022, and that assessed the health impact of AMD among adolescents were eligible. DATA EXTRACTION: Details on study design, methods, population, assessment of dietary patterns, health outcomes, and main results were extracted. RESULTS: The search yielded 59 references after removal of duplicates. Applying PICOS criteria, 4 systematic reviews and 3 meta-analyses ultimately were included in this review. The AMD was evaluated in association with overweight/obesity and adiposity in 2 studies, musculoskeletal health in another 2, inflammation in 1 study, and cardiometabolic health in 1 study. The seventh review examined all mentioned health outcomes (overweight and obesity, musculoskeletal health, inflammation, and cardiometabolic health) in relation to AMD. CONCLUSIONS: Overall, this umbrella review showed limited evidence and a lack of consistency about the relation between AMD and health outcomes of interest in adolescence, indicating the need for more studies to better understand it. SYSTEMIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023428712.

Analysis of suspected adverse reactions to food supplements containing beehive products: an update from the Italian Phytovigilance System.

INTRODUCTION: Beehive products are widely used in food supplements; however, their composition variability and allergenic components have raised some concerns. This work aims to provide information about the beehive products safety profile by evaluating the suspected adverse reactions (ARs). METHODS: The suspected report of ARs collected within the Italian Phytovigilance System (IPS) were evaluated. The clinical and demographic characteristics of the cases were described, and the causality assessment performed. RESULTS: 61 reports were analysed, mainly concerned women. Serious events were reported in 17 forms (28%). The ARs (n=116) referred to respiratory (25.0%), skin (24.1%), and gastrointestinal disorders (21.5%). Label warnings for atopic subjects were present only in 7 food supplements. The causality assessment was mostly probable (54.1%). CONCLUSIONS: Present findings outline relevant information about the safety issues of beehive product consumption, especially in atopic or allergic subjects, and strengthen the importance of IPS to point out safety signals.

Adherence to Mediterranean Diet and its main determinants in a sample of Italian adults: results from the ARIANNA cross-sectional survey.

Introduction: Over the last years, many Mediterranean countries, including Italy, have witnessed a shift away from the Mediterranean Diet, thus contributing to the high rates of overweight and obesity. The survey "Adherence to Mediterranean Diet in Italy (ARIANNA)" aimed to evaluate the Adherence to Mediterranean Diet (AMD) and its main determinants in the Italian population. Materials and methods: This study started on March 2023 and was addressed to adults aged ≥17 years, born and resident in Italy, proficient in Italian. Data are collected electronically through a voluntary, anonymous and self-administered questionnaire on the project website. Univariate and then multivariate logistic regressions were performed to evaluate associations between AMD and demographic characteristics, socio-economic status, health status, and lifestyle. Results: On a total of 3,732 completed questionnaires, the 87.70% of the respondents was female and the 71.28% was 17-40 years old. The 83.82% of the respondents had medium AMD, 11.33% low and only 4.85% high. The multivariate analysis revealed that being male (p < 0.001), aged >40 years (p < 0.05), workers (p ≤ 0.001), and unemployed (p < 0.05), determined the probability of having a lower AMD. Vegans and vegetarian's diets positively contributed to a higher AMD (p < 0.001). Discussion: These results highlighted a medium AMD in the Italian adult participants and suggested the necessity to implement tailored public health intervention strategies to improve food habits.

Nutrition, Physical Activity and Smoking Habit in the Italian General Adult Population: CUORE Project Health Examination Survey 2018-2019.

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.

Tackling the challenge of cardiovascular diseases and diabetes across Europe: a joint action by more than 300 public health professionals. Commentary.

Cardiovascular diseases (CVD) and diabetes pose significant health challenges in Europe, affecting millions and burdening healthcare systems. The recent EU4Health Programme places reducing the burden of non-communicable diseases (NCD) at the forefront, through a Joint Action focused on CVD and diabetes (JACARDI, Joint Action on CARdiovascular diseases and DIabetes). This initiative unites 21 European countries, including Ukraine, and over 300 experts. Employing an innovative approach and standardised methodology, JACARDI implements 142 pilot projects covering the entire "patient" journey. Particular focus will be given to improvement of data availability and quality. Additionally, JACARDI will emphasise transversal and intersectional aspects, such as health equity, determinants of health, and social, cultural, and ethnic diversity, while pioneering gender-transformative leadership. Committed to evidence-based interventions, JACARDI aims to harmonise strategies and disseminate knowledge for enhanced CVD and diabetes prevention and management. The goal is to identify effective strategies for wider implementation, fostering cross-national collaboration and fortifying Europe's health resilience.

Potential new mechanisms of placental damage in celiac disease: anti-transglutaminase antibodies impair human endometrial angiogenesis.

Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion and characterized by circulating anti-transglutaminase type 2 (anti-TG2) autoantibodies. An epidemiological link between maternal CD and increased risk of pregnancy failure has been established; however, the mechanism underlying this association is still poorly understood. Because proper endometrial angiogenesis and decidualization are prerequisites for placental development, we investigated the effect of anti-TG2 antibodies on the process of endometrial angiogenesis. Binding of anti-TG2 antibodies to human endometrial endothelial cells (HEECs) was evaluated by ELISA. Angiogenesis was studied in vitro on HEECs and in vivo in a murine model. In particular, we investigated the effect of anti-TG2 antibodies on HEEC matrix metalloprotease-2 (MMP-2) activity by gelatin zymography, cytoskeletal organization and membrane properties by confocal microscopy, and activation of extracellular signal-regulated kinases (ERKs) and focal adhesion kinase (FAK) by Western blot analysis. Anti-TG2 antibodies bound to HEECs and decreased newly formed vessels both in vitro and in vivo. Anti-TG2 antibodies impaired angiogenesis by inhibiting the activation of MMP-2, disarranging cytoskeleton fibers, changing the physical and mechanical properties of cell membranes, and inhibiting the intracellular phosphorylation of FAK and ERK. Anti-TG2 antibodies inhibit endometrial angiogenesis affecting the TG2-dependent migration of HEECs and extracellular matrix degradation, which are necessary to form new vessels. Our results identify pathogenic mechanisms of placental damage in CD.

Endoscopic submucosal dissection in the treatment of gastric submucosal tumors: results from a retrospective cohort study.

BACKGROUND: A submucosal tumor (SMT) of the stomach, which is an occasional finding during routine upper gastrointestinal endoscopy, may pose diagnostic and therapeutic challenges. METHODS: To assess whether endoscopic submucosal dissection (ESD) is a feasible approach to definitively cure SMTs, the authors performed a retrospective cohort study with two endoscopic italian centers. RESULTS: The study consisted of 20 patients with SMTs who underwent ESD. The patients underwent ESD and were followed up by endoscopy. We analyzed complete resection rate, frequency of complications, and survival. The overall rate of R0 resection was 90 % (18/20), with two endoscopic failures, one for a submucosal tumor and one for a neoplasm deeply infiltrating the proper muscle layer. The median procedure time was 119.1 min (range 40-240 min). The median size of the resected specimens was 29 mm (range 15-60 mm). Perforation occurred in 3 patients; all were treated conservatively. There were no cases of severe bleeding. Based on histopathological findings, 6 cases of ectopic pancreas, 1 of ectopic spleen, 3 of leiomyoma, and 10 of gastrointestinal stromal tumor (GIST) were diagnosed. Complete resection was obtained in all GIST cases. Among the 10 GIST cases treated by ESD, no death occurred: the 5-year disease-specific survival rate was 100 %. CONCLUSIONS: The high success rate of 90 % and the low incidence of complications should indicate ESD is the correct diagnostic and definitive treatment in selected patients.

Role of Portion Size in the Context of a Healthy, Balanced Diet: A Case Study of European Countries.

Over the past decades, a generalised increase in food portion sizes has probably contributed to the growing global obesity epidemic. Increasing awareness of appropriate portion sizes could contribute to reversing this trend through better control of calorie intake. In this study, a comparison of standard portion sizes in European countries for various food categories shows a wide variability of their importance for food, nutrient, and energy consumption according to government and institutional websites. On the other hand, the overall averages appear to be largely in line with the values indicated by the Italian Society of Human Nutrition, which is the most comprehensive and detailed document among those evaluated. The exceptions are milk and yoghurt, for which the reference portions in Europe are generally higher, and vegetables and legumes, for which portions are smaller than those reported in the Italian document. Moreover, the portion sizes of staple foods (e.g., pasta and potatoes) vary according to different food traditions. It is reasonable to consider that the creation of harmonised standard reference portions common to the European countries, based on international guidelines and scientific evidence, would significantly contribute to consumers' nutritional education and ability to make informed choices for a healthy diet.

Adherence to Mediterranean diet in Italy (ARIANNA) cross-sectional survey: study protocol.

INTRODUCTION: There is evidence, although limited, that the Italian population has been no longer following a Mediterranean dietary pattern. The ARIANNA (Adherence to the Mediterranean Diet in Italy) project consists of a survey-based cross-sectional study with the objective of gaining a greater knowledge of adherence to the Mediterranean Diet and its main determinants in different age groups of the Italian population. METHODS/ANALYSIS: The ARIANNA study will involve males and females aged ≥7 years, born and resident in Italy, and proficient in Italian. The voluntary enrolment will be in the period between March 2023 and May 2023. The data, which will include sociodemographic factors and dietary habits, will be collected through a web-based questionnaire. Adherence to the Mediterranean Diet will be assessed through the use of two validated score systems: the Mediterranean Diet Quality Index in children and adolescents for participants aged ≤16 years and the Mediterranean Diet Serving Score for participants aged ≥17 years. A review of the scientific literature will be carried out to collect historical data on adherence to the Mediterranean dietary pattern in the Italian population, which will be compared with those collected within this project. ETHICS AND DISSEMINATION: The ARIANNA study has been approved by the Ethics Committee of Istituto Superiore di Sanità. The results will be disseminated through peer-reviewed papers, leaflets and documents for the general public. A report will be presented to the national policy makers, to give them the tools to implement appropriate intervention to improve, in necessary, the adherence to Mediterranean dietary pattern in Italy.