Abnormal Wnt and PI3Kinase Signaling in the Malformed Intestine of lama5 Deficient Mice

Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin α5 gene deficiency and the physiological phenotype. We show that laminin α5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelial and muscle differentiation. Conversely, adhesion to laminin-511 may serve as a potent regulator of known interconnected PI3K/Akt and Wnt signaling pathways. Thus deregulated adhesion to laminin-511 may be instrumental in diseases such as human pathologies of the gut where laminin-511 is abnormally expressed as it is shown here

Perspective: Striking a Balance between Planetary and Human Health-Is There a Path Forward?

The global adoption of predominantly plant-based, sustainable, healthy diets will help reduce the risk of obesity-and malnutrition-related noncommunicable diseases while protecting the future health of our planet. This review examines the benefits and limitations of different types of plant-based diets in terms of health and nutrition, affordability and accessibility, cultural (ethical and religious) acceptability, and the environment (i.e., the 4 pillars underlying sustainable healthy diets). Results suggest that, without professional supervision, traditional plant-based diets (vegan, vegetarian, and pescatarian diets) can increase the risk of nutritional deficiencies among infants, children/adolescents, women, pregnant/lactating women, and the elderly. In contrast, flexitarian diets and territorial diversified diets (TDDs; e.g., Mediterranean and New Nordic diets) that include large quantities of plant-sourced foods, low amounts of red meat, and moderate amounts of poultry, fish, eggs, and dairy can meet the energy and nutrition needs of different populations without the need for dietary education or supplementation. Compared with vegan, vegetarian, and pescatarian diets, more diverse flexitarian diets and TDDs are associated with reduced volumes of food waste and may be more acceptable and easier to maintain for people who previously followed Western diets. Although flexitarian diets and TDDs have a greater impact on the environment than vegan, vegetarian, and pescatarian diets, the negative effects are considerably reduced compared with Western diets, especially if diets include locally sourced seasonal foods. Further studies are required to define more precisely optimal sustainable healthy diets for different populations and to ensure that diets are affordable and accessible to people in all countries

Alimentation des premiers mois de vie et prévention de l'allergie

National audienceAllergy consists in the different manifestations resulting from immune reactions triggered by food or respiratory allergens. Both its frequency and severity are increasing. The easiest intervention process for allergy prevention is the reduction of the allergenic load which, for a major allergen such as peanuts, has to begin in utero. The primary prevention strategy relies first on the detection of at risk newborns, i.e. with allergic first degree relatives. In this targeted population, as well as for the general population, exclusive breastfeeding is recommended until the age of 6 months. The elimination from the mother's diet of major food allergens potentially transmitted via breast milk may be indicated on an individual basis, except for peanut, which is systematically retrieved. In the absence of breastfeeding, prevention consists in feeding at-risk newborns until the age of 6 months with a hypoallergenic formula, provided that its efficiency has been demonstrated by well-designed clinical trials. Soy based formulae are not recommended for allergy prevention. Complementary feeding should not be started before the age of 6 months. Introduction of egg and fish into the diet can be made after 6 months but the introduction of potent food allergens (kiwi, celery, crustaceans, seafood, nuts, especially tree nuts and peanuts) should be delayed after 1 year. This preventive policy seems partially efficacious on early manifestations of allergy but does not restrain the allergic march, especially in its respiratory manifestations. Probiotics, prebiotics as well as n-3 fatty polyunsaturated acids have not yet demonstrated any definitive protective effect.L’allergie correspond à l’ensemble des tableaux cliniques résultant d’un mécanisme physiopathologique d’ordre immunologique, développé vis-à-vis d’allergènes alimentaires ou respiratoires. Sa fréquence et sa sévérité augmentent. La modalité de prévention de l’allergie la plus réalisable est la réduction de la charge allergénique qui, pour l’arachide, doit débuter dès la vie intra-utérine. La prévention primaire de l’allergie alimentaire repose d’abord sur la détection des enfants à risque ayant des antécédents familiaux au 1er degré d’allergie. Pour cette population ciblée comme pour la population générale, l’allaitement maternel exclusif est recommandé jusqu’à l’âge de 6 mois. L’éviction du régime de la mère des trophallergènes majeurs potentiellement transmis par le lait de mère est discutée au cas par cas, sauf pour l’arachide, systématiquement exclue.A défaut d’allaitement maternel ou en cas de biberons de complément, la prévention consiste, chez les enfants à risque, à donner une formule hypoallergénique jusqu’à 6 mois, en choisissant une de celles dont l’efficacité a été démontrée par des études contrôlées. Les formules à base de soja n’ont pas leur place en prévention. La diversification alimentairene doit pas débuter avant l’âge de 6mois. L’introduction de l’oeuf et du poisson peut débuter après 6 mois, mais celle des aliments à fort pouvoir allergénique (kiwi, céleri, arachide, fruits à coque, crustacés) doit être retardée après 1 an. Ces précautions ne modifient pas sensiblement la marche allergique ultérieure, en particulier dans ses expressions respiratoires. L’intérêt des probiotiques, prébiotiques et des acides gras polyinsaturés de la série n-3 reste à confirmer

Nutrition and intestinal rehabilitation of children with short bowel syndrome: a position paper of the ESPGHAN Committee on Nutrition. Part 1: from intestinal resection to home discharge

: Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-centre experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached > 90% agreement. The first the part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN

Nutrition and intestinal rehabilitation of children with short bowel syndrome: a position paper of the ESPGHAN Committee on Nutrition. Part 2: long term follow-up on home parenteral nutrition

: Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition (PN) which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-centre experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached > 90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications and on possible surgical and medical management to increase intestinal absorption

Acceptability, usability, and credibility of a mindfulness-based digital therapeutic for pediatric concussion: A mixed-method study

Background The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms. Objective This open-label mixed-methods pilot study assessed the acceptability and credibility of a mindfulness-based intervention delivered through a digital therapeutic (DTx; therapeutic smartphone app) for pediatric concussion. Methods Participants aged 12 to 18 years were recruited from an emergency department within 48 hours of a concussion (acute cohort) or from a tertiary care clinic at least 1-month post-concussion (persisting symptoms cohort). Participants completed a novel 4-week mindfulness-based intervention, for 10 to 15 minutes/day, at a minimum of 4 days/week. At 2 weeks, participants completed a credibility and expectancy questionnaire. At 4 weeks, participants completed questionnaires assessing satisfaction, usability and working alliance, as well as a semi-structured phone interview. Results Ten participants completed the study outcomes (7 acute; 3 persisting symptoms). The intervention was perceived as credible (median/max possible = 6.50/9.00 [6.83,8.75]) and DTx was usable (median/max possible = 70.00/100.00 [55.00,82.50]). Participants rated their satisfaction with the DTx (median/max possible = 27.00/32.00 [24.50,29.50]) and the working alliance with the digital mindfulness guides (median/max possible = 3.92/5.00 [3.38–4.33]) as high. Four themes were identified from the qualitative data: (a) positive attributes; (b) negative attributes; (c) ideas for modifications; and (d) technical issues. Conclusion Results show modifications to the DTx, instructions and mindfulness intervention, and potential ways to increase adherence by leveraging positive attributes. A randomized control trial will assess the effectiveness of the DTx MBI to decrease the risk of persisting symptoms and reduce the symptom burden following pediatric concussion

Endothelial function and mechanical properties of the common carotid artery in children on parenteral nutrition

Intravenous administration of nutrition mixtures induces endothelial damage and arterial wall remodeling in animal models. To study endothelial function and common carotid artery mechanical properties in children receiving parenteral nutrition, we used noninvasive ultrasonic measurements in 18 children on parenteral nutrition and 18 controls. No difference appeared in the geometry of the common carotid artery (intima media thickness, systolic and diastolic diameters) between the patients on parenteral nutrition and the controls. The incremental elastic modulus was significantly higher in the patients on parenteral nutrition (1.8 +/- 0.4 versus 1.4 +/- 0.5 4 mm Hg x 10(3), p < 0.05) reflecting alteration of the elastic properties of the arterial wall independent of the vessel geometry. The flow-mediated dilatation of the brachial artery was significantly lower in the patients on parenteral nutrition (6 +/- 3 versus 8 +/- 3%, p < 0.05), whereas the dilatation after glyceryl trinitrate administration was similar (22 +/- 9 versus 25 +/- 9%). Children on parenteral nutrition exhibit endothelial dysfunction and altered stiffness of the common carotid artery. The noninvasive methods used in this study may prove useful for objectively determining the effects of various preventive methods

Microvillous inclusion disease (microvillous atrophy)

<p>Abstract</p> <p>Microvillous inclusion disease (MVID) or microvillous atrophy is a congenital disorder of the intestinal epithelial cells that presents with persistent life-threatening watery diarrhea and is characterized by morphological enterocyte abnormalities. MVID manifests either in the first days of life (early-onset form) or in the first two months (late-onset form) of life. MVID is a very rare disorder of unknown origin, probably transmitted as an autosomal recessive trait. To date, no prevalence data are available. Ultrastructural analyses reveal: 1) a partial to total atrophy of microvilli on mature enterocytes with apical accumulation of numerous secretory granules in immature enterocytes; 2) the highly characteristic inclusion bodies containing rudimentary or fully differentiated microvilli in mature enterocytes. Light microscopy shows accumulation of PAS-positive granules at the apical pole of immature enterocytes, together with atrophic band indicating microvillus atrophy and, in parallel, an intracellular PAS or CD10 positive line (marking the microvillous inclusion bodies seen on electron microscopy). Intestinal failure secondary to diarrhea is definitive. To date, no curative therapy exists and children with MVID are totally dependent on parenteral nutrition. Long-term outcome is generally poor, due to metabolic decompensation, repeated states of dehydration, infectious and liver complications related to the parenteral nutrition. As MVID is a very rare disorder, which is extremely difficult to diagnose and manage, children with MVID should be transferred to specialized pediatric gastro-intestinal centers, if possible, a center equipped to perform small bowel transplantation. Early small bowel transplantation resulting in intestinal autonomy gives new hope for disease management and outcome.</p