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Background/Objectives: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. Methods: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. Results: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis. [ABSTRACT FROM AUTHOR]

(1) Objectives: Assessment of novel impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been proposed to enhance the accuracy of gastroesophageal reflux disease (GERD) diagnosis. We aimed to evaluate the clinical value of MNBI and the PSPW index in discerning different phenotypes of GERD in children. (2) Methods: We conducted a prospective, observational study that included 49 children aged 5–18 years, referred for MII-pH monitoring due to negative endoscopy and persisting gastroesophageal reflux symptoms despite acid-suppressant treatment. The PSPW index and MNBI were assessed along with conventional metrics. (3) Results: Using a receiver operating characteristic (ROC) curve analysis, MNBI (AUC 0.864) and the PSPW index (AUC 0.83) had very good performance in differentiating between non-erosive reflux disease (NERD) and functional phenotypes. The PSPW index (AUC 0.87) discriminated better between functional heartburn (FH) and reflux hypersensitivity (RH) compared to the MNBI (AUC 0.712). A PSPW cut-off value of 65% provided a sensitivity of 76.9% and a specificity of 90% in distinguishing FH and RH. The PSPW index (AUC 0.87) proved to have better performance than the MNBI (AUC 0.802) in differentiating between FH and non-FH patients. MNBI diagnosed FH with a sensitivity of 84% and a specificity of 80.6% at a cut-off value of 2563 Ω. (4) Conclusions: The PSPW index and MNBI are useful to distinguish between GERD phenotypes in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Food allergy (FA) affects approximately 8% of children and may be immunoglobulin E (IgE)-mediated or non-IgE-mediated. It is recognized clinically that children with both subtypes of FA may present with features of pediatric feeding disorder (PFD); however, there is currently a limited detail of presenting characteristics. Objective: The objective of this study was to synthesize the current evidence regarding the feeding characteristics of children with FA, with a focus on the feeding skills and psychosocial domains of PFD. Method: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Papers published between 2001 and 2022 describing feeding characteristics in the feeding skills and psychosocial domains in children with FA/history of FA were included. Papers that focused solely on characteristics from the medical or nutritional domains were excluded. Descriptive information regarding demographics, methodology, allergy profile and history, and the characteristics of PFD observed was extracted using a preconceived data extraction form. Results: Overall, 40 papers contained descriptions of feeding characteristics of children with non-IgE-mediated FA (n = 22) and IgE-mediated FA (n = 11), while four were nonspecific. In the psychosocial domain, food refusal/aversion, anxiety with eating, and poor intake were the most frequently reported, regardless of FA subtype. Less information was reported regarding feeding skills, although slowness in eating, immature diet, and delays in oral sensory-motor skills were described. Conclusions: Children with FA/history of FA may present with a range of characteristics that map across the feeding skill and psychosocial domains of PFD. Systematic research is needed to fully describe the feeding characteristics of children with FA. [ABSTRACT FROM AUTHOR]

The realization that soluble factors secreted by heterotypic cells play an importanta role in paracrine signaling, which facilitates intercellular communication, enabled the development of physiologically relevant co‐culture models for drug screening and the engineering of tissues, such as hepatic tissues. The most crucial issues confronting the use of conventional membrane inserts in segregated co‐culture models that are used to study paracrine signaling between heterotypic cells have been identified as long‐term viability and retention of cell‐specific functions, especially when isolated primary cells are used. Herein, we present an in vitro segregated co‐culture model consisting of a well plate incubated with rat primary hepatocytes and normal human dermal fibroblasts which were segregated using a membrane insert with silica nonwoven fabric (SNF) on it. SNF, which mimics a physiological environment much more effectively than a two‐dimensional (2D) one, promotes cell differentiation and resultant paracrine signaling in a manner that is not possible in a conventional 2D culture, owing to high mechanical strength generated by its inorganic materials and interconnected network structure. In segregated co‐cultures, SNF clearly enhanced the functions of hepatocytes and fibroblasts, thereby showing its potential as a measure of paracrine signaling. These results may advance the understanding of the role played by paracrine signaling in cell‐to‐cell communication and provide novel insights into the applications of drug metabolism, tissue repair, and regeneration. [ABSTRACT FROM AUTHOR]

Summary: Motivation: Countries facing challenges of nutrition security confront a trade‐off when dealing with pandemics such as COVID‐19. Implementing lockdown measures, widely used worldwide, can help "flatten the curve" (of disease), but such measures may worsen nutrition security. Purpose: We aim to identify and justify nutrition‐sensitive lockdown measures to reduce trade‐offs with nutrition security. Methods and approach: We propose a conceptual framework which distinguishes eight lockdown measures and six pathways to nutrition security. To demonstrate the relevance of the pathways, we reviewed emerging literature on COVID‐19 and nutrition security. We analysed the content of 1188 newspaper articles on lockdown effects in five African countries: Benin, Ghana, Kenya, Uganda and Zambia. Findings Some lockdown measures, such as closing workplaces and restricting movement, potentially worsen nutrition far more than others. Banning events and public gatherings have far less impact on nutrition. This can be seen from the framework, the academic literature, and is supported by the analysis of newspaper reports in the five countries. Policy implications: It is better, when possible, to test and trace disease than to lock down. But when lockdowns are needed, the first recourse should be to measures that have few nutritional consequences, such as banning public events. When more drastic measures are necessary, nutritional harm should be mitigated by, for example, exempting farm labour from restrictions on movement, by replacing school meals with take‐home rations, and, above all, providing income support to the most affected and most vulnerable households. [ABSTRACT FROM AUTHOR]

Coeliac disease is a common immune-mediated inflammatory disorder caused by dietary gluten in genetically susceptible individuals. While the diagnosis of coeliac disease is based on serological and histological criteria, HLA-DQ genotyping can be useful, especially in excluding the diagnosis in patients who do not carry the relevant DQ heterodimers: DQA1*05 DQB1*02, DQB1*03:02 or DQA1*02 DQB1*02 (commonly referred to as DQ2.5, DQ8 and DQ2.2, respectively). External quality assessment results for HLA genotyping in coeliac disease have revealed concerning errors in HLA genotyping, reporting and clinical interpretation. In response, these guidelines have been developed as an evidence-based approach to guide laboratories undertaking HLA genotyping for coeliac disease and provide recommendations for reports to standardise and improve the communication of results., (© 2023 John Wiley & Sons Ltd.)

Constipation commonly occurs during childhood, and more than 95% of cases are classified as functional constipation. If not effectively treated, 20% of patients with childhood constipation can continue to exhibit symptoms into adulthood, which seriously affects their mental health and quality of life. The main feature of acupuncture or acupoint stimulation, a special branch of traditional Chinese medicine, is the selection of different acupoints for different diseases, and many worthy guidelines have been established for matching acupoints. The back-shu and front-mu point combination adheres to an important acupoint compatibility law that has been used since its proposal 2,500 years ago but has not yet been verified by the modern evidence-based experiments. This study focused on the back-shu and front-mu point combination using the Dachangshu (BL25) and Tianshu (ST25) points as examples to explore possible research methods for network acupoint-based stimulation based on existing evidence and to elucidate the mechanisms induced by BL25 and ST25 in the treatment of functional constipation in children (FCC). The study found that BL25 and ST25 have 20 common targets, namely, AQP8, DRD2, VIP, TAC1, IL6R, TNF, FOS, KIT, CHAT, HTR3A, GAS8, SOD3, TRPV1, MPO, CALCA, IL1B, P2RX7, NPY2R, IL10RA, and TPH1, and these targets may provide a strategy for the combined usage of BL25 and ST25. In addition, BL25 and ST25 can affect FCC treatment through inflammation-relatedTh17-cell differentiation, the NF-kappa B signaling pathway, and the Toll-like receptor signaling pathway. Adipocytokines or leptin may also comprise the mechanism through which BL25 and ST25 regulate FCC. In addition, BL25 and ST25 regulate FCC through 13 core targets, namely, NFKBIA, RELA, TNF, IKBKB, IRAK1, TLR4, MYD88, TNFRSF1A, IL1R1, TLR2, IL1B, TRAF6, and TNFRSF1B. In short, this study provides new ideas and methods for studying the mechanism of acupuncture points. [ABSTRACT FROM AUTHOR]

Background: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) results from haploinsufficiency of the mesenchymal transcription factor FOXF1 gene. To date, only one case of an ACDMPV‐causative CNV deletion inherited from a very‐low level somatic mosaic mother has been reported. Methods: Clinical, histopathological, and molecular studies, including whole genome sequencing, chromosomal microarray analysis, qPCR, and Sanger sequencing, followed by in vitro fertilization (IVF) with preimplantation genetic testing (PGT) were used to study a family with a deceased neonate with ACDMPV. Results: A pathogenic CNV deletion of the lung‐specific FOXF1 enhancer in the proband was found to be inherited from an unaffected mother, 36% mosaic for this deletion in her peripheral blood cells. The qPCR analyses of saliva, buccal cells, urine, nail, and hair samples revealed 19%, 18%, 15%, 19%, and 27% variant allele fraction, respectively, indicating a high recurrence risk. Grandparental studies revealed that the deletion arose on the mother's paternal chromosome 16. PGT studies revealed 44% embryos with the deletion, reflecting high‐level germline mosaicism. Conclusion: Our data further demonstrate the importance of parental testing in ACDMPV families and reproductive usefulness of IVF with PGT in families with high‐level parental gonosomal mosaicism. [ABSTRACT FROM AUTHOR]

Background: Many pediatric inflammatory bowel disease (IBD) patients are now using biosimilars of anti-tumor necrosis factor-α (TNF-α), with increasing trends in recent years. This study reviewed all available data regarding the use of biosimilars in children with IBD. Methods: PubMed, Google Scholar, Scopus, and CENTRAL databases were searched through keywords; inflammatory bowel diseases, Crohn's disease, ulcerative colitis, biosimilar and child were combined using "AND" and "OR." Original research articles involving pediatric patients receiving one of the biosimilar medications based on the anti-TNF-α biologic drugs approved for pediatric IBD treatment, independently from efficacy and drug response, were included. Results: Nine studies were included in the evidence synthesis. CT-P13 was the biosimilar used in all studies. Four studies assessed the induction effectiveness of CT-P13. Clinical response and remission rates of biosimilar treatment were 86–90% and 67–68%, respectively, and they were not significantly different to the originator group. Five prospective studies on patients elected to switch from originator IFX to CT-P13 yielded similar results. Adverse events related to CT-P13 were mostly mild. The most frequently reported were upper respiratory tract infections. The switch from the originator had no significant impact on immunogenicity. Conclusion: The current review showed reported CT-P13 effectiveness as measured by clinical response and/or remission rates after induction or during maintenance and suggest that there is no significant difference with that of the originator IFX. Further studies are warranted, including clinical, and pharmacovigilance studies. [ABSTRACT FROM AUTHOR]

Objective. To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. Methods. By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade. Results. There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease. Conclusions. The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ. [ABSTRACT FROM AUTHOR]

Celiac disease is one of the most common food-related chronic disorders in children. Unfortunately, this multifaceted disease is challenging to recognize and remains markedly underdiagnosed. Screening of either known at-risk groups or even the whole population could increase the suboptimal diagnostic yield substantially. Many recent guidelines recommend screening of at least selected risk groups, but more wide-scale screening remains controversial. The increasing prevalence of celiac disease and the development of autoantibody assays have also led to a gradual shift in the diagnostics towards less invasive serology-based criteria in a subgroup of symptomatic children. The main open questions concern whether these criteria are applicable to all countries and clinical settings, as well as to adult patients. On the other hand, widening screening and the mistaken practice of initiating a gluten-free diet before the appropriate exclusion of celiac disease increase the number of borderline seropositive cases, which may also challenge the classical histopathological diagnostics. Sophisticated diagnostic methods and a deeper understanding of the natural history of early developing celiac disease may prove useful in these circumstances. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) include colitis ulcerosa and Crohn's disease, besides the rare microscopic colitis. Both diseases show a long-lasting, relapsing-remitting, or even chronic active course with tremendous impact on quality of life. IBDs frequently cause disability, surgical interventions, and high costs; as in other autoimmune diseases, their prevalent occurrence at an early phase of life raises the burden on health care systems. Unfortunately, our understanding of the pathogenesis is still incomplete and treatment therefore largely focuses on suppressing the resulting excessive inflammation. One obstacle for deciphering the causative processes is the scarcity of models that parallel the development of the disease, since intestinal inflammation is mostly induced artificially; moreover, the intestinal epithelium, which strongly contributes to IBD pathogenesis, is difficult to assess. Recently, the development of intestinal epithelial organoids has overcome many of those problems. Here, we give an overview on the current understanding of the pathogenesis of IBDs with reference to the limitations of previous well-established experimental models. We highlight the advantages and detriments of recent organoid-based experimental setups within the IBD field and suggest possible future applications. [ABSTRACT FROM AUTHOR]

The safe disposal of human excreta is of paramount importance for the health and welfare of populations living in low income countries as well as the prevention of pollution to the surrounding environment. On-site sanitation (OSS) systems are the most numerous means of treating excreta in low income countries, these facilities aim at treating human waste at source and can provide a hygienic and affordable method of waste disposal. However, current OSS systems need improvement and require further research and development. Development of OSS facilities that treat excreta at, or close to, its source require knowledge of the waste stream entering the system. Data regarding the generation rate and the chemical and physical composition of fresh feces and urine was collected from the medical literature as well as the treatability sector. The data were summarized and statistical analysis was used to quantify the major factors that were a significant cause of variability. The impact of this data on biological processes, thermal processes, physical separators, and chemical processes was then assessed. Results showed that the median fecal wet mass production was 128 g/cap/day, with a median dry mass of 29 g/cap/day. Fecal output in healthy individuals was 1.20 defecations per 24 hr period and the main factor affecting fecal mass was the fiber intake of the population. Fecal wet mass values were increased by a factor of 2 in low income countries (high fiber intakes) in comparison to values found in high income countries (low fiber intakes). Feces had a median pH of 6.64 and were composed of 74.6% water. Bacterial biomass is the major component (25–54% of dry solids) of the organic fraction of the feces. Undigested carbohydrate, fiber, protein, and fat comprise the remainder and the amounts depend on diet and diarrhea prevalence in the population. The inorganic component of the feces is primarily undigested dietary elements that also depend on dietary supply. Median urine generation rates were 1.42 L/cap/day with a dry solids content of 59 g/cap/day. Variation in the volume and composition of urine is caused by differences in physical exertion, environmental conditions, as well as water, salt, and high protein intakes. Urine has a pH 6.2 and contains the largest fractions of nitrogen, phosphorus, and potassium released from the body. The urinary excretion of nitrogen was significant (10.98 g/cap/day) with urea the most predominant constituent making up over 50% of total organic solids. The dietary intake of food and fluid is the major cause of variation in both the fecal and urine composition and these variables should always be considered if the generation rate, physical, and chemical composition of feces and urine is to be accurately predicted. [ABSTRACT FROM PUBLISHER]

This study was aimed at determining (a) the extent of proliferation of peripheral blood mononuclear cells (PBMC) in response to stimulation by cytomegalovirus (CMV)-infected fibroblasts and (b) the levels of Th1 and Th2 cytokine production in kidney transplant recipients with and without active CMV infection. Thirty patients with, and 39 without active CMV infection, diagnosed by a CMV antigenemia assay (AA), were studied. PBMC of patients with active CMV infection showed significantly lower proliferation than those without ongoing CMV infection (P<0.0001). The levels of Th2-type cytokines (interleukin (IL-) 4 and IL-10) in AA-negative and AA-positive kidney transplant recipients were similar but the levels of the Th1-type cytokines interferon-γ, tumor necrosis factor-α (P<0.05) and IL-2 were significantly lower in AA-positive kidney transplant recipients (P<0.0005). [Copyright &y& Elsevier]

Celiac disease (CD) is a chronic gluten-responsive immune mediated enteropathy and is treated with a gluten-free diet (GFD). However, a strict diet for life is not easy due to the ubiquitous nature of gluten. This review aims at examining available evidence on the degree of adherence to a GFD, the methods to assess it, and the barriers to its implementation. The methods for monitoring the adherence to a GFD are comprised of a dietary questionnaire, celiac serology, or clinical symptoms; however, none of these methods generate either a direct or an accurate measure of dietary adherence. A promising advancement is the development of tests that measure gluten immunogenic peptides in stools and urine. Causes of adherence/non-adherence to a GFD are numerous and multifactorial. Inadvertent dietary non-adherence is more frequent than intentional non-adherence. Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD. Therefore, several studies in the last decade have indicated that many patients with CD who follow a GFD still have difficulty controlling their diet and, therefore, regularly consume enough gluten to trigger symptoms and damage the small intestine. [ABSTRACT FROM AUTHOR]

CMV disease is an important peristent factor for enhanced morbidity and mortality in immunocompromised patients. In high-risk patients the prevention of primary infection or reactivation of latent infection is endeavoured by means of various antiviral strategies. However, the prevention of CMV disease by immunomodulators appears to be a hopeful additional tool for the treatment of immunocompromised patients and ought to be further investigated. [ABSTRACT FROM AUTHOR]

A simple fluorometric assay requiring only a single sample of cells to determine the number of cells, from the DNA linked to the fluorochrome 4′,6-diamidino-2- phenylindol (DAPI), and the uptake of ciprofloxacin, a natural fluorescent quinolone is described. Mouse peritoneal macrophages were found to concentrate ciprofloxacin up to 12·7 (± 1·5)-fold. Combined fluorometry provides a precise, sensitive method for determining the intracellular concentration of fluoroquinolones, as well as that of naturally fluorescent or fluorochrome-linked drugs. [ABSTRACT FROM PUBLISHER]

Mice with targeted disruption of the cftr gene show pathophysiologic changes in the gallbladder, which correlate with hepatobiliary disease seen in cystic fibrosis patients. As gallbladder epithelium secretes mucin, and as this epithelium consists of a relatively homogenous cell type, study of CFTR function in these cells would be beneficial to delineate the complex cellular functions of this protein. The size and anatomic location of the murine gallbladder makes such studies difficult in vivo. Therefore, the need exists for in vitro models of gallbladder epithelium. We describe a method to isolate and culture murine gallbladder epithelium from wild-type and CF mice. Cells were grown in a monolayer on porous inserts over a feeder layer of fibroblasts. These nontransformed cells can be successively passaged and maintain a well-differentiated epithelial cell phenotype as shown by morphologic criteria, characterized by polarized columnar epithelial cells with prominent microvilli and intercellular junctions. Organotypic cultures showed columnar cells simulating in vivo morphology. This culture system should be valuable in delineating cellular processes relating to CFTR in gallbladder epithelium. [ABSTRACT FROM AUTHOR]

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups—a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease. [ABSTRACT FROM AUTHOR]

Author(s): Ludi Zhang [1]; Lijian Hui (corresponding author) [1] Bile, which facilitates the absorption of lipids in the small intestine, is highly toxic to cells of the liver, where it [...]