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In Montreal, Quebec, 31% of the population is born outside Canada. Yet, only 9% of patient consultations for symptoms associated with functional gastrointestinal disorders (FGIDs) are from immigrants at the Paediatric Gastroenterology Clinic at Sainte-Justine's University Hospital Centre. This discrepancy inspired a multidisciplinary exploratory study (anthropological and paediatric) to examine the sociological, interpretative and pragmatic aspects of immigrant and non-immigrant patients and family life with FGIDs. This paper examines the discrepancy between immigrant and non-immigrant paediatric patients with FGIDs and presents the different pathways to care utilised by families. Semistructured interviews were carried out between November 2008 and June 2009, with children and their parents. In total, 38 families were recruited: with 27 families (including a child experiencing abdominal pain, his/her siblings, mother and/or father as well as any other significant individual living in the family home) from the community and 11 from the paediatric gastroenterology clinic. A comparative analysis between the immigrant and non-immigrant groups focused on perceptions, meanings and actions taken to relieve/alleviate symptoms. Immigrant and nonimmigrant families alternate and combine different therapeutic environments: home, alternative healing therapies and medical paths to care. Our analysis suggests that culture (as a set of values, beliefs and ways of being), as well as social interactions within family life and the clinic, shape pathways to care. The analysis highlights the centrality of receptiveness -- and more widely the social dimensions -- of all medical encounters. Treatment disparities between immigrant and non-immigrant families in pathways to care help us to understand these patients' social world and the intricate relationships between values and social milieux, between culture, practices of symptom management and rationales guiding diverse therapeutic actions. [ABSTRACT FROM AUTHOR]

Esophageal atresia/tracheoesophageal fistula (EA/TEF) is the most common congenital anomaly of the upper gastrointestinal tract affecting 1 in 3,000 which could stem from a developmental anomaly of the foregut. The cause is not fully understood. We generated three iPSC cell lines using peripheral blood mononuclear cells (PBMCs) from EA/TEF type C patients. Pluripotency and trilineage differentiation capacity of these three iPSC cell lines were confirmed by gene and protein expression profiles and the differentiation ability into the three germ layers. The generated disease-specific cell lines could serve as a tool to investigate the mechanisms of EA/TEF and acquired associated diseases. [ABSTRACT FROM AUTHOR]

Background & Aims: In adults, irritable bowel syndrome (IBS) and functional dyspepsia (FD) are chronic conditions that often start during childhood. We investigated mucosal serotonin (5-HT) signaling in children with the idea that data from subjects with a shorter history may improve our understanding of underlying pathophysiological mechanisms. Methods: Ninety-eight children undergoing gastroscopy or colonoscopy were studied prospectively. Biopsy specimens were evaluated for inflammation, enterochromaffin cell numbers, 5-HT content, and messenger RNA (mRNA) levels for the synthetic enzyme, tryptophan hydroxylase 1, and the serotonin transporter (SERT) were assessed by quantitative real-time reverse-transcription polymerase chain reaction. Results: Data from 12 children with IBS and 17 with FD were compared with age-matched controls (12 with rectal biopsies and 12 with gastric biopsies) and with subjects with organic disorders. In patients with FD, a small number of immune cells were observed in the gastric mucosa in half of the patients, but no abnormalities with respect to the 5-HT pathway were identified. In patients with IBS, no differences were detected between patients and controls regarding intraepithelial lymphocytes and CD3+ cells in the lamina propria although all patients showed at least a slight inflammatory infiltrate. In the IBS samples, higher 5-HT content (P < .01) and lower SERT mRNA (P < .05) were detected as compared with controls. Severe inflammation in the colonic mucosa had a high impact on 5-HT signaling with a significant decrease in enterochromaffin cells (P < .01) and 5-HT content (P < .01) and a high SERT mRNA expression (P < .01). Conclusions: These results confirm the role of 5-HT signaling in IBS in children and argue against such a role in FD. [Copyright &y& Elsevier]

The hypothesis that BMPs (bone morphogenetic proteins), which act early in gut morphogenesis, also regulate specification and differentiation in the developing enteric nervous system (ENS) was tested. Expression of BMP-2 and BMP-4, BMPR-IA (BMP receptor subunit), BMPR-IB, and BMPR-II, and the BMP antagonists, noggin, gremlin, chordin, and follistatin was found when neurons first appear in the primordial bowel at embryonic day 12 (E12). Agonists, receptors, and antagonists were detected in separated populations of neural crest- and noncrest-derived cells. When applied to immunopurified E12 ENS precursors, BMP-2 and BMP-4 induced nuclear translocation of phosphorylated Smad-1 (Sma and Mad-related protein). The number of neurons developing from these cells was increased by low concentrations and decreased by high concentrations of BMP-2 or BMP-4. BMPs induced the precocious appearance of TrkC-expressing neurons and their dependence on neurotrophin-3 for survival. BMP-4 interacted with glial cell line-derived neurotrophic factor (GDNF) to enhance neuronal development but limited GDNF-driven expansion of the precursor pool. BMPs also promoted development of smooth muscle from mesenchymal ceils immunopurified at E12. To determine the physiological significance of these observations, the BMP antagonist noggin was overexpressed in the developing ENS of transgenic mice under the control of the neuron-specific enolase promoter. Neuronal numbers in both enteric plexuses and smooth muscle were increased throughout the postnatal small intestine. These increases were already apparent by E18. In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal noggin-overexpressing animals, again an effect detectable at E18. BMP-2 and/or BMP-4 thus limit the size of the ENS but promote the development of specific subsets of enteric neurons, including those that express TrkC. [ABSTRACT FROM AUTHOR]

The International Network on Esophageal Atresia (INoEA) stands as a beacon of collaboration in addressing the complexities of this congenital condition on a global scale. The eleven board members, from various countries (USA, Canada, France, Australia, Italy, Sweden, Germany, and The Netherlands) and backgrounds (pediatric gastroenterology, pediatric surgery, pediatric pulmonology, nursing, and parents) met in a face-to-face symposium in Lille in November 2023, to identify challenges and solutions for improving global collaboration of the network. [ABSTRACT FROM AUTHOR]

Simple Summary: The brain senses and regulates all internal bodily processes, including the levels of the sugar molecule glucose in the blood stream (systemic regulation) or in specific organs, such as the gut. The contribution of the vagus nerve to this mechanism, the longest nerve connecting the brain with the rest of the body, has not been well understood. Moreover, it has remained unknown how the activity of the vagus nerve contributes to the inflammatory response as may be seen during infections when the immune system is activated. Here, we mechanically and electrically manipulated the vagus nerve activity, decreasing or increasing it selectively, and measuring the degree of change in the glucose levels and of the inflammatory response systemically and in the gut, an important site of neonatal injury. We reported a surprising dual (hormetic) anti- or pro-inflammatory effect of reduced vagal activity combined with increased levels of glucose dependent on the levels of the infectious agent inducing the inflammatory response. We further discussed the implications for future research and clinical practice. BACKGROUND. Glucosensing elements are widely distributed throughout the body and relay information about circulating glucose levels to the brain via the vagus nerve. However, while anatomical wiring has been established, little is known about the physiological role of the vagus nerve in glucosensing. The contribution of the vagus nerve to inflammation in the fetus is poorly understood. Increased glucose levels and inflammation act synergistically when causing organ injury, but their interplay remains incompletely understood. We hypothesized that vagotomy (Vx) will trigger a rise in systemic glucose levels and this will be enhanced during systemic and organ-specific inflammation. Efferent vagus nerve stimulation (VNS) should reverse this phenotype. METHODS. Near-term fetal sheep (n = 57) were surgically prepared using vascular catheters and ECG electrodes as the control and treatment groups (lipopolysaccharide (LPS), Vx + LPS, Vx + LPS + selective efferent VNS). The experiment was started 72 h postoperatively to allow for post-surgical recovery. Inflammation was induced with LPS bolus intravenously (LPS group, 400 ng/fetus/day for 2 days; n = 23). For the Vx + LPS group (n = 11), a bilateral cervical vagotomy was performed during surgery; of these n = 5 received double the LPS dose, LPS800. The Vx + LPS + efferent VNS group (n = 8) received cervical VNS probes bilaterally distal from Vx in eight animals. Efferent VNS was administered for 20 min on days 1 and 2 +/10 min around the LPS bolus. Fetal arterial blood samples were drawn on each postoperative day of recovery (-72 h, -48 h, and -24 h) as well as at the baseline and seven selected time points (3–54 h) to profile inflammation (ELISA IL-6, pg/mL), insulin (ELISA), blood gas, and metabolism (glucose). At 54 h post-LPS, a necropsy was performed, and the terminal ileum macrophages' CD11c (M1 phenotype) immunofluorescence was quantified to detect inflammation. The results are reported for p < 0.05 and for Spearman R2 > 0.1. The results are presented as the median (IQR). RESULTS. Across the treatment groups, blood gas and cardiovascular changes indicated mild septicemia. At 3 h in the LPS group, IL-6 peaked. That peak was decreased in the Vx + LPS400 group and doubled in the Vx + LPS800 group. The efferent VNS sped up the reduction in the inflammatory response profile over 54 h. The M1 macrophage activity was increased in the LPS and Vx + LPS800 groups only. The glucose and insulin concentrations in the Vx + LPS group were, respectively, 1.3-fold (throughout the experiment) and 2.3-fold higher vs. control (at 3 h). The efferent VNS normalized the glucose concentrations. CONCLUSIONS. The complete withdrawal of vagal innervation resulted in a 72-h delayed onset of a sustained increase in glucose for at least 54 h and intermittent hyperinsulinemia. Under the conditions of moderate fetal inflammation, this was related to higher levels of gut inflammation. The efferent VNS reduced the systemic inflammatory response as well as restored both the concentrations of glucose and the degree of terminal ileum inflammation, but not the insulin concentrations. Supporting our hypothesis, these findings revealed a novel regulatory, hormetic, role of the vagus nerve in the immunometabolic response to endotoxin in near-term fetuses. [ABSTRACT FROM AUTHOR]

Purpose: Anorexia Nervosa (AN) is a serious and potentially lethal mental disorder characterised by a deliberate quest to reduce one's weight. It can have multiple physical and psychological consequences. The clinical presentation of AN can include gastrointestinal symptoms, however, the pathophysiology of these symptoms in the context of AN remains uncertain. It is hypothesised that patients with AN may have an increase in intestinal permeability, which could lead to an increase in faecal calprotectin (fCP), a marker of intestinal inflammation. No relation between AN and elevation of fCP has been previously described in literature. Methods: Eight patients hospitalised for AN have a dosage of fCP. Results: Calprotectine was found to be elevated in 50% of cases, with or without any underlying comorbid gastrointestinal disease. Only the duration of illness tended to be associated with the increase in fCP suggesting a greater alteration as a function related to the time of denutrition. Conclusion: Although these findings provide insights in the potential pathophysiology of gastrointestinal symptoms in AN, further studies that evaluate the factors associated with elevated fCP in patients with AN are needed. Key points: What is already known on this subject? To our knowledge, our study is the first to describe faecal calprotectin (fCP) levels in patients who are malnourished due to anorexia nervosa (AN) and describe the patients' clinical characteristics in order to better explain the gastrointestinal tract implication in AN symptoms. What this study adds? This study's finding of a possible elevation of fCP in patients with AN raises interesting questions on the pathophysiology of AN, and the possibility of an underlying inflammatory process in these patients. Although this is a preliminary study, as the sample size is small, it is therefore important for clinicians to acknowledge that fCP can be elevated in patients with AN without any other disease. The literature remains scarce regarding the relationship between the gastrointestinal tract and AN, although it is a predominant aspect of the symptomatology of the disease. This offers opportunities and strengthen the need for further research on the effects of restriction, renutrition and weight gain on the gastrointestinal tract in patients with AN, and the possible role and use of fCP in this disease. [ABSTRACT FROM AUTHOR]