Usefulness of Faecal Markers in Cow’s Milk Protein Immunomediated Reactions

Cow’s milk protein allergy (CMPA) affects children most commonly than adults, with symptoms usually developing before 1 year of age and within 1 week after the intake of cow’s milk. Food allergies can be divided into: IgE mediated and non-IgE mediated. Some reactions may include both mechanisms (mixed type). The most studied faecal Mar-kers, so far, are calprotectin, Tumor necrosis factor-alpha (TNF-α), beta-defensin and eosinophil cationic protein (ECP). Calprotectin belongs to the S-100 family of calcium-binding proteins and seems to be involved in the regulation of inflammation. Faecal calprotectin (FC) values are significantly higher in infants suspected of having CMPA than in a comparison group of healthy infants. Moreover, there is a significant decrease in FC in infants with CMPA after a period of dietary antigen elimination, although levels use to remain higher than in age- and diet-matched comparisons. TNF-α is a cytokine involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. TNF-α expression in the epithelial cells and mononuclear cells in the lamina propria is markedly increased in FPIES patients. TNF-α is also increased in the stools of patients with gastrointestinal milk allergy after milk challenge. Defensins are small (~29 to 42 amino acid) cationic arginine and cysteine rich, amphipathic peptides with a molecular weight of 3–5 kDa. They can be classified into three groups: α-, β- and θ-defensins. Among them, only α- and β-defensins are expressed in humans. Defensins display various functions, including antimicrobial activity and also act as chemoattractant. They contribute to host immunity and to maintain the balance between pathogens and normal flora. Beta-defensins values detected in infants with a previous diagnosis of CMPA prior to the oral food challenge, and during each provocation do not seem to show significant changes. ECP is a single-chain, zinc-containing protein with a molecular weight ranging from 16 to 22 kDa and is one of the most important proteins in the granules of eosinophil granulocytes. Infants with atopic eczema exhibit a specific faecal protein pattern characterized by an increase in both ECP and TNF-α. The faecal concentration of ECP enhances particularly in patients with immediate-type reactions to the cow’s milk challenge whereas faecal TNF-α enhances in those with delayed-type reactions, confirming the different pathogenesis (IgE mediated and non-IgE mediated) of these two types of reactions

La tecnologia del Gene Editing nella didattica esperienziale per studenti delle scuole secondarie di secondo grado

Le moderne tecnologie di Gene Editing, come il sistema CRISPR, si sono diffuse in tutti i laboratori del mondo, alimentando al contempo speranze e timori per le sue applicazioni. Poiché queste tecnologie sono destinate ad avere un enorme impatto sulle nostre vite, è fondamentale comunicare e suscitare un dibattito, soprattutto tra i più giovani. Per avvicinare gli studenti delle scuole secondarie di secondo grado ai grandi temi scientifici e far sperimentare loro l’utilizzo di nuove tecnologie per comprenderne le potenzialità, negli ultimi anni abbiamo messo a punto un corso di Gene Editing. La risposta degli studenti a questo tipo di corso dimostra l’efficacia della sperimentazione nell’informare e suscitare una discussione su queste tematiche. In questo articolo riportiamo e commentiamo i risultati dello studio

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis

Hydrolyzed protein formula for allergy prevention in preterm infants: follow-up analysis of a randomized, triple-blind, placebo-controlled study

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors. Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors. Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age. Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found. Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed

Complementary feeding in preterm infants: a position paper by Italian neonatal, paediatric and paediatric gastroenterology joint societies

Nutrition in the first 1000 days of life is essential to ensure appropriate growth rates, prevent adverse short- and long-term outcomes, and allow physiologic neurocognitive development. Appropriate management of early nutritional needs is particularly crucial for preterm infants. Although the impact of early nutrition on health outcomes in preterm infants is well established, evidence-based recommendations on complementary feeding for preterm neonates and especially extremely low birth weight and extremely low gestational age neonates are still lacking. In the present position paper we performed a narrative review to summarize current evidence regarding complementary feeding in preterm neonates and draw recommendation shared by joint societies (SIP, SIN and SIGENP) for paediatricians, healthcare providers and families with the final aim to reduce the variability of attitude and timing among professionals

Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid-β-induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular networks and platelet function. However, not much is known about peripheral vascular inflammation and how pro-inflammatory circulating cells/mediators could affect peripheral vessels' function. This study aimed to evaluate whether IL-17Ab treatment could also impact peripheral AD features, such as systemic inflammation, peripheral vascular dysfunction, and related pro-thrombotic state in a non-genetic mouse model of AD. Mice were injected intracerebroventricularly with Aβ1-42 peptide (3 μg/3 μl). To evaluate the systemic/peripheral protective profile of IL-17Ab, we used an intranasal administration of IL-17Ab (1 μg/10 μl) at 5, 12, and 19 days after Aβ1-42 injection. Circulating Th17/Treg cells and related cyto-chemokines, haematological parameters, vascular/endothelial reactivity, platelets and coagulation function in mice were evaluated. IL-17Ab treatment ameliorates the systemic/peripheral inflammation, immunological perturbance, vascular/endothelial impairment and pro-thrombotic state, suggesting a key role for this cytokine in fostering inflammatory processes that characterize the multifaced aspects of AD. </p

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Comparative efficacy of methods for surfactant administration: a network meta-analysis

Objectives To compare surfactant administration via thin catheters, laryngeal mask, nebulisation, pharyngeal instillation, intubation and surfactant administration followed by immediate extubation (InSurE) and no surfactant administration. Design Network meta-analysis. Setting Medline, Scopus, CENTRAL, Web of Science, Google-scholar and Clinicaltrials.gov databases were systematically searched from inception to 15 February 2020. Patients Preterm neonates with respiratory distress syndrome. Interventions Less invasive surfactant administration. Main outcome measures The primary outcomes were mortality, mechanical ventilation and bronchopulmonary dysplasia. Results Overall, 16 randomised controlled trials (RCTs) and 20 observational studies were included (N=13 234). For the InSurE group, the median risk of mortality, mechanical ventilation and bronchopulmonary dysplasia were 7.8%, 42.1% and 10%, respectively. Compared with InSurE, administration via thin catheter was associated with significantly lower rates of mortality (OR: 0.64, 95% CI: 0.54 to 0.76), mechanical ventilation (OR: 0.43, 95% CI: 0.29 to 0.63), bronchopulmonary dysplasia (OR: 0.57, 95% CI: 0.44 to 0.73), periventricular leukomalacia (OR: 0.66, 95% CI: 0.53 to 0.82) with moderate quality of evidence and necrotising enterocolitis (OR: 0.67, 95% CI: 0.41 to 0.9, low quality of evidence). No significant differences were observed by comparing InSurE with administration via laryngeal mask, nebulisation or pharyngeal instillation. In RCTs, thin catheter administration lowered the rates of mechanical ventilation (OR: 0.39, 95% CI: 0.26 to 0.60) but not the incidence of the remaining outcomes. Conclusion Among preterm infants, surfactant administration via thin catheters was associated with lower likelihood of mortality, need for mechanical ventilation and bronchopulmonary dysplasia compared with InSurE. Further research is needed to reach firm conclusions about the efficacy of alternative minimally invasive techniques of surfactant administration

Macronutrients and Micronutrients in Parenteral Nutrition for Preterm Newborns: A Narrative Review

Preterm neonates display a high risk of postnatal malnutrition, especially at very low gestational ages, because nutritional stores are less in younger preterm infants. For this reason nutrition and growth in early life play a pivotal role in the establishment of the long-term health of premature infants. Nutritional care for preterm neonates remains a challenge in clinical practice. According to the recent and latest recommendations from ESPGHAN, at birth, water intake of 70&ndash;80 mL/kg/day is suggested, progressively increasing to 150 mL/kg/day by the end of the first week of life, along with a calorie intake of 120 kcal/kg/day and a minimum protein intake of 2.5&ndash;3 g/kg/day. Regarding glucose intake, an infusion rate of 3&ndash;5 mg/kg/min is recommended, but VLBW and ELBW preterm neonates may require up to 12 mg/kg/min. In preterm infants, lipid emulsions can be started immediately after birth at a dosage of 0.5&ndash;1 g/kg/day. However, some authors have recently shown that it is not always possible to achieve optimal and recommended nutrition, due to the complexity of the daily management of premature infants, especially if extremely preterm. It would be desirable if multicenter randomized controlled trials were designed to explore the effect of early nutrition and growth on long-term health

Lung Ultrasound: A New Tool in the Management of Congenital Lung Malformation

 This study was aimed to evaluate effectiveness of lung ultrasound (LUS) in the management of congenital pulmonary airway malformation and pulmonary sequestration in NICUs