Berberine alleviates ETEC-induced intestinal inflammation and oxidative stress damage by optimizing intestinal microbial composition in a weaned piglet model.

Introduction: Enterotoxigenic Escherichia coli (ETEC) is the main diarrhea-causing pathogen in children and young animals and has become a global health concern. Berberine is a type of "medicine and food homology" and has a long history of use in China, particularly in treating gastrointestinal disorders and bacterial diarrhea. Methods: In this study, we explored the effects of berberine on growth performance, intestinal inflammation, oxidative damage, and intestinal microbiota in a weaned piglet model of ETEC infection. Twenty-four piglets were randomly divided into four groups-a control group (fed a basal diet [BD] and infused with saline), a BD+ETEC group (fed a basal diet and infused with ETEC), a LB+ETEC group (fed a basal diet with 0.05% berberine and infused with ETEC infection), and a HB+ETEC group (fed a basal diet with 0.1% berberine and infused with ETEC). Results: Berberine significantly improved the final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) (P<0.05) of piglets, and effectively decreased the incidence of diarrhea among the animals (P<0.05). Additionally, berberine significantly downregulated the expression levels of the genes encoding TNF-α, IL-1ß, IL-6, IL-8, TLR4, MyD88, NF-κB, IKKα, and IKKß in the small intestine of piglets (P<0.05). ETEC infection significantly upregulated the expression of genes coding for Nrf2, CAT, SOD1, GPX1, GST, NQO1, HO-1, GCLC, and GCLM in the small intestine of the animals (P<0.05). Berberine significantly upregulated 12 functional COG categories and 7 KEGG signaling pathways. A correlation analysis showed that berberine significantly increased the relative abundance of beneficial bacteria (Gemmiger, Pediococcus, Levilactobacillus, Clostridium, Lactiplantibacillus, Weissella, Enterococcus, Blautia, and Butyricicoccus) and decreased that of pathogenic bacteria (Prevotella, Streptococcus, Parabacteroides, Flavonifractor, Alloprevotella) known to be closely related to intestinal inflammation and oxidative stress in piglets. In conclusion, ETEC infection disrupted the intestinal microbiota in weaned piglets, upregulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, and consequently leading to intestinal inflammation and oxidative stress-induced damage. Discussion: Our data indicated that berberine can optimize intestinal microbiota balance and modulate the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, thus helping to alleviate intestinal inflammation and oxidative damage caused by ETEC infection in weaned piglets.

Nutritional status and its associated factors among infants and young children aged 6-23 months in Addis Ababa, Central Ethiopia, 2021: a cross-sectional study.

The aim of this study is to assess nutritional status and associated factors among infants and young children aged 6-23 months in Yeka sub-city, Ethiopia, 2021. An institution-based cross-sectional study was conducted in selected health centres found in the Yeka sub-city from May 2021 to July 2021. In total, 396 systematically selected infants and young children aged 6-23 months attended the selected health centres were included in the study. Data were collected by using a structured questionnaire and anthropometric measurements. A multinomial logistic regression model was used. The overall magnitude of undernutrition and overnutrition among infants and young children were 24.7% and 5.5%, respectively. Dietary diversity score (DDS) ((adjusted odd ratio (AOR) = 5.65; 95% CI = 2.301, 10.87; P value = 0.003), minimum meal frequency (MMF) (AOR = 5.435; 95% CI = 2.097, 11.09; P value = 0.0052), and diarrhoea (AOR = 2.52; 95% CI = 1.007, 6.310; P value = 0.002) were statistically significantly associated factors for nutritional status among infants and young children. Malnutrition (undernutrition and overnutrition) is a public health problem among infants and young children in Yeka sub-city, Ethiopia. DDS, MMF, and diarrhoeal disease were associated with higher odds of undernutrition.

Viral diarrheas - newer advances in diagnosis and management.

PURPOSE OF REVIEW: Viruses are the most common etiological agents of diarrhea in children. Despite rotavirus vaccine introduction, rotavirus remains as the leading cause of death globally, followed by norovirus, which represents a diagnostic challenge. Here, we describe new advances in the diagnosis and management of viral diarrheas. RECENT FINDINGS: Although immunoassays are widely used for their fast turnaround time and low cost, molecular techniques have become the most reliable diagnostic method due to their high sensitivity and capacity to analyze multiple pathogens in gastrointestinal panels. Isothermal nucleic acid amplification assays (LAMP and RPA) are promising techniques since they do not require sophisticated equipment and can be used as point-of-care testing. CRISPR/Cas nucleic acid detection systems are new diagnostic methods with great potential. Several recent published articles describe the role of human intestinal enteroids to characterize norovirus infection, to test new drugs, and for vaccine development. The interaction between the human gut microbiota and gastrointestinal viral infections has been extensively reviewed and offers some innovative mechanisms for therapeutic and preventive measures. SUMMARY: Although important advances have been made, more research is needed to address remaining challenges and further improve diagnostic capabilities and better management strategies for this critical infectious disease.

Mobile phone call reminders to improve oral rehydration salt and zinc adherence for acute diarrhea in children: a single-center, randomized controlled trial.

BACKGROUND: Low-osmolarity oral rehydration salt (ORS) and zinc therapy effectively manage diarrhea in children under five years of age, offering both short- and long-term benefits. Despite this, caregivers' adherence to ORS and zinc is often unsatisfactory due to factors such as forgetfulness, resolution of symptoms, and underestimation of the disease's severity. This study assessed the effect of mobile call reminders on ORS and zinc tablet adherence among children with acute diarrhea in a secondary-level health facility in Kwara State, Nigeria. METHODS: Using an open-label, randomized controlled trial design, this study compared caregiver-child pairs with acute diarrhea aged 6-59 months who received standard instructions (SI) alone (control group) and an intervention group (IG) who received SI plus phone call reminders on days three and seven of zinc sulfate therapy. All participants used a pictorial diary to track loose/watery stools and ORS and zinc tablet treatments for ten days. The primary outcome measures were independent and combined adherence to ORS and zinc therapy. The secondary outcomes were independent and combined adherence scores, defined as the percentage of times the ORS was given post-diarrhea and the percentage of prescribed zinc tablets administered out of ten. RESULTS: A total of 364/400 mother-child pairs completed the study. The percentage of mothers with full adherence in the intervention group was 82.5% for ORS, 72.1% for zinc, and 58.5% for combined use, compared to 78.8%, 60.8%, and 43.6%, respectively, in the control group. The odds of full adherence to ORS and zinc were 1.6 and 1.7 times higher among intervention mothers [ORS: OR = 1.561, 95% CI = 0.939-2.598, P = 0.085; zinc: OR = 1.671, 95% CI = 1.076-2.593, P = 0.022], and 1.8 times higher for combined use according to WHO guidelines [OR = 1.818, 95% CI = 1.200-2.754, P = 0.005]. The mean adherence scores for the intervention group were higher than those for the control group by 4.1% (95% CI = 0.60-7.60) for ORS, 7.3% (95% CI = 3.74-10.86) for zinc, and 5.7% (95% CI = 3.23-8.17) for the combined treatment. CONCLUSION: Phone reminders can effectively improve consistency of home treatment administered by caregivers for children under five years old. TRIAL REGISTRATION: The study was registered retrospectively (17/3/2023) with the Pan African Clinical Trial Registry (PACTR202301560735856).

Detection and molecular characterization of major enteric pathogens in calves in central Ethiopia.

BACKGROUND: Calf diarrhea is a major cause of morbidity and mortality in the livestock sector worldwide and it can be caused by multiple infectious agents. In Ethiopia, cattle are the most economically important species within the livestock sector, but at the same time the young animals suffer from high rates of morbidity and mortality due to calf diarrhea. However, studies including both screening and molecular characterization of bovine enteric pathogens are lacking. Therefore, we aimed to both detect and molecularly characterize four of the major enteric pathogens in calf diarrhea, Enterotoxigenic Escherichia coli (E. coli K99 +), Cryptosporidium spp., rotavirus A (RVA), and bovine coronavirus (BCoV) in calves from central Ethiopia. Diarrheic and non-diarrheic calves were included in the study and fecal samples were analyzed with antigen-ELISA and quantitative real-time PCR (qPCR). Positive samples were further characterized by genotyping PCRs. RESULTS: All four pathogens were detected in both diarrheic and non-diarrheic calves using qPCR and further characterization showed the presence of three Cryptosporidium species, C. andersoni, C. bovis and C. ryanae. Furthermore, genotyping of RVA-positive samples found a common bovine genotype G10P[11], as well as a more unusual G-type, G24. To our knowledge this is the first detection of the G24 RVA genotype in Ethiopia as well as in Africa. Lastly, investigation of the spike gene revealed two distinct BCoV strains, one classical BCoV strain and one bovine-like CoV strain. CONCLUSIONS: Our results show that Cryptosporidium spp., E. coli K99 + , RVA and BCoV circulate in calves from central Ethiopia. Furthermore, our findings of the rare RVA G-type G24 and a bovine-like CoV demonstrates the importance of genetic characterization.

Genetic diversity of Cryptosporidium species from diarrhoeic ungulates in the United Arab Emirates.

Cryptosporidiosis has previously been reported in animals, humans, and water sources in the United Arab Emirates (UAE). However, most reports were only to the genus level, or generically identified as cryptosporidiosis. We aimed to investigate the genetic diversity of Cryptosporidium species occurring in diarrhetic ungulates which were brought to the Central Veterinary Research Laboratory (CVRL) in Dubai. Using a combination of microscopic and molecular methods, we identified five species of Cryptosporidium occurring among ungulates in the UAE, namely C. parvum, C. hominis, C. xiaoi, C. meleagridis, and C. equi. Cryptosporidium parvum was the most prevalent species in our samples. Furthermore, we identified subtypes of C. parvum and C. hominis, which are involved in both human and animal cryptosporidiosis. This is also the first reported occurrence of Cryptosporidium spp. in the Arabian Tahr, to our knowledge. Since the animals examined were all in contact with humans, the possibility of zoonotic spread is possible. Our study correlates with previous reports in the region, building upon the identification of Cryptosporidium sp. However, there is a need to further investigate the endemic populations of Cryptosporidium, including more hosts, sampling asymptomatic animals, and location data.

Determinants of diarrhoeal diseases among under-five children in Africa (2013-2023): a comprehensive systematic review highlighting geographic variances, socioeconomic influences, and environmental factors.

BACKGROUND: Diarrhea diseases continue to present a significant threat to the well-being of children under the age of five in Africa, thereby contributing substantially to both morbidity and mortality rates. The period spanning between January 2013 and December 2023 has witnessed persistent challenges in the fight against these diseases, thereby necessitating a thorough investigation into the factors that determine their occurrence. It is important to note that the burden of diarrhea diseases is not evenly distributed across the continent, with residence, socioeconomic, and environmental factors playing pivotal roles in shaping the prevalence and incidence rates. Consequently, this systematic review aimed to consolidate and analyze the existing body of literature on the determinants of diarrhea diseases among children under the age of five in Africa between January 2013 and December 2023. METHOD: The systematic review employed a rigorous methodological approach to examine the determinants of diarrhea diseases among children under the age of five in Africa between January 2013 and December 2023. A comprehensive search strategy was implemented, utilizing databases such as PubMed, Scopus, and Web of Science, and incorporating relevant keywords. The inclusion criteria focused on studies published within the specified timeframe, with a specific focus on the determinants of diarrhea disease among children under the age of five in Africa. The study selection process involved a two-stage screening, with independent reviewers evaluating titles, abstracts, and full texts to determine eligibility. The quality assessment, employing a standardized tool, ensured the inclusion of studies with robust methodologies. Data extraction encompassed key study details, including demographics, residence factors, socioeconomic influences, environmental variables, and intervention outcomes. RESULTS: The search yielded a total of 12,580 articles across 25 African countries; however, only 97 of these articles met the inclusion criteria and were ultimately included in the systematic review. The systematic review revealed geographic and seasonal disparities in the prevalence of diarrhoeal diseases across different countries in Africa. Factors such as age-related vulnerabilities, gender disparities, maternal occupation, disposal of young children's stools, and economic status were identified as significant determinants of the prevalence of diarrhea disease. CONCLUSION: This systematic review provides a comprehensive understanding of the determinants of diarrhea diseases among children under the age of five in Africa between January 2013 and December 2023. The nuanced analysis of residence variations, socioeconomic influences, environmental factors, and intervention outcomes underscores the complex nature of this issue. The findings highlight the necessity for region-specific and context-sensitive interventions to address the unique challenges faced by diverse communities. This review serves as a valuable resource for policymakers, healthcare professionals, and researchers, guiding the development of evidence-based strategies aimed at reducing the burden of diarrhea diseases and improving child health outcomes in Africa.

Exploring the Effects and Potential Mechanisms of Hesperidin for the Treatment of CPT-11-Induced Diarrhea: Network Pharmacology, Molecular Docking, and Experimental Validation.

Chemotherapy-induced diarrhea (CID) is a potentially serious side effect that often occurs during anticancer therapy and is caused by the toxic effects of chemotherapeutic drugs on the gastrointestinal tract, resulting in increased frequency of bowel movements and fluid contents. Among these agents, irinotecan (CPT-11) is most commonly associated with CID. Hesperidin (HPD), a flavonoid glycoside found predominantly in citrus fruits, has anti-oxidation properties and anti-inflammation properties that may benefit CID management. Nevertheless, its potential mechanism is still uncertain. In this study, we firstly evaluated the pharmacodynamics of HPD for the treatment of CID in a mouse model, then used network pharmacology and molecular docking methods to excavate the mechanism of HPD in relieving CID, and finally further proved the predicted mechanism through molecular biology experiments. The results demonstrate that HPD significantly alleviated diarrhea, weight loss, colonic pathological damage, oxidative stress, and inflammation in CID mice. In addition, 74 potential targets for HPD intervention in CID were verified by network pharmacology, with the top 10 key targets being AKT1, CASP3, ALB, EGFR, HSP90AA1, MMP9, ESR1, ANXA5, PPARG, and IGF1. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the PI3K-Akt pathway, FoxO pathway, MAPK pathway, TNF pathway, and Ras pathway were most relevant to the HPD potential treatment of CID genes. The molecular docking results showed that HPD had good binding to seven apoptosis-related targets, including AKT1, ANXA5, CASP3, HSP90AA1, IGF1, MMP9, and PPARG. Moreover, we verified apoptosis by TdT-mediated dUTP nick-end labeling (TUNEL) staining and immunohistochemistry, and the hypothesis about the proteins above was further verified by Western blotting in vivo experiments. Overall, this study elucidates the potential and underlying mechanisms of HPD in alleviating CID.

Transcriptomic Module Discovery of Diarrhea-Predominant Irritable Bowel Syndrome: A Causal Network Inference Approach.

Irritable bowel syndrome with diarrhea (IBS-D) is the most prevalent subtype of IBS, characterized by chronic gastrointestinal symptoms in the absence of identifiable pathological findings. This study aims to investigate the molecular mechanisms underlying IBS-D using transcriptomic data. By employing causal network inference methods, we identify key transcriptomic modules associated with IBS-D. Utilizing data from public databases and applying advanced computational techniques, we uncover potential biomarkers and therapeutic targets. Our analysis reveals significant molecular alterations that affect cellular functions, offering new insights into the complex pathophysiology of IBS-D. These findings enhance our understanding of the disease and may foster the development of more effective treatments.

Application of longitudinal multilevel zero inflated Poisson regression in modeling of infectious diseases among infants in Ethiopia.

BACKGROUND: In sub-Saharan African countries, preventable and manageable diseases such as diarrhea and acute respiratory infections still claim the lives of children. Hence, this study aims to estimate the rate of change in the log expected number of days a child suffers from Diarrhea (NOD) and flu/common cold (NOF) among children aged 6 to 11 months at the baseline of the study. METHODOLOGY: This study used secondary data which exhibit a longitudinal and multilevel structure. Based on the results of exploratory analysis, a multilevel zero-inflated Poisson regression model with a rate of change in the log expected NOD and NOF described by a quadratic trend was proposed to efficiently analyze both outcomes accounting for correlation between observations and individuals through random effects. Furthermore, residual plots were used to assess the goodness of fit of the model. RESULTS: Considering subject and cluster-specific random effects, the results revealed a quadratic trend in the rate of change of the log expected NOD. Initially, low dose iron Micronutrient Powder (MNP) users exhibited a higher rate of change compared to non-users, but this trend reversed over time. Similarly, the log expected NOF decreased for children who used MNP and exclusively breastfed for six months, in comparison to their counterparts. In addition, the odds of not having flu decreased with each two-week increment for MNP users, as compared to non-MNP users. Furthermore, an increase in NOD resulted in an increase in the log expected NOF. Region and exclusive breastfeeding also have a significant relationships with both NOD and NOF. CONCLUSION: The findings of this study underscore the importance of commencing analysis of data generated from a study with exploratory analysis. The study highlights the critical role of promoting EBF for the first six months and supporting children with additional food after six months to reduce the burden of infectious diseases.

Gut microbiota patterns associated with duration of diarrhea in children under five years of age in Ethiopia.

Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (<7 days' duration) is decreasing, but prolonged (7-13 days) and persistent (≥14 days of duration) diarrhea remains a massive challenge. Here, we use a case-control study to decipher if fecal gut microbiota compositional differences between Ethiopian children with acute (n=554) or prolonged/persistent (n=95) diarrhea and frequency-matched non-diarrheal controls (n=663) are linked to diarrheal etiology. We show that diarrhea cases are associated with lower bacterial diversity and enriched in Escherichia spp., Campylobacter spp., and Streptococcus spp. Further, diarrhea cases are depleted in gut commensals such as Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus, with depletion being most pronounced in prolonged/persistent cases, suggesting that prolonged duration of diarrhea is accompanied by depletion of gut commensals and that re-establishing these via e.g., microbiota-directed food supplements offer a potential treatment strategy.

Zinc adherence among caregivers of under five children with diarrhea in Gondar City, Northwest Ethiopia.

INTRODUCTION: Zinc with oral re-hydration salt supplementation provides much improved outcomes for managing childhood diarrhea. There is scarcity of evidence in the study area regarding zinc supplementation adherence and factors associated with. Thus, the aim of this study was to assess zinc supplementation adherence and associated factors among caregivers of under five children with diarrhea attending health centers in Gondar City. METHODS: An institutional based cross-sectional study was conducted with 405 caregivers of under-five children with diarrhea who received zinc supplementation in Gondar City health centers. Bivariable and multivariable logistic regression analysis were computed. RESULTS: 35% (95% CI: 29.91, 39.21) of caregivers of under five children adhered for zinc supplementation. Adherence was observed among caregivers with good knowledge about zinc supplementation (AOR = 3.01 95%CI = 1.73, 5.24), and who received counseling (AOR = 8.4, 95%CI = 4.66, 15.13), presence of side effects (AOR = 0.35, 95% CI 0.20, 0.65) was negatively associated with zinc supplementation adherence. CONCLUSION: In the study area, more than one third of children with diarrhea were adhered to zinc supplementation. Thus, improving the knowledge of caregivers and enhancing counseling services on benefits, dosage, duration and side effects of zinc supplementation are vital to improve adherence in the area.

The impact of cancer-related diarrhea on changes in cancer therapy.

PURPOSE: The impact of cancer-related diarrhea (CRD) on changes in cancer therapy remains poorly characterized despite its prevalence. METHODS: We performed a longitudinal observational study using IQVIA PharMetrics Plus claims data. Patients included adults with CRD identified by diagnosis codes or pharmacy claims and compared their outcomes to matched (1:1) patients without CRD. Treatment parameters (discontinuation, persistence, augmentation, dose titration, adherence) were evaluated and stratified for the first cancer therapy (chemotherapy vs. targeted therapy vs. both). A multivariate Cox proportional hazards model was used to estimate the difference in risk of each treatment parameter between cohorts, adjusting for cancer type, therapy, and comorbidities. RESULTS: We identified 104,135 matched pairs of patients with solid (n = 94,411) or hematologic cancers (n = 9,724) receiving chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both (n = 5,313). Patients with CRD discontinued therapy more frequently than those without CRD (chemotherapy [81.5% vs. 62.3%], targeted therapy [69.2% vs. 64.3%], both [96.0% vs. 85.5%], p < 0.0001). The overall proportion of discontinuation was higher (82.4% vs. 64.6%, p < 0.0001), including a higher risk of discontinuation (HR = 1.40, p < 0.001) for patients with CRD. The mean time to discontinuation (59.6 ± 54.1 vs. 68.3 ± 76.6 days), switch (72.0 ± 48.6 vs. 96.9 ± 84.0 days), persistence (95.1 ± 98.1 vs. 154.3 ± 142.7 days), and adherence (25.5% ± 37.2 vs. 47.9 ± 41%) were all lower (p < 0.0001) among patients with CRD. CONCLUSION: Patients who develop CRD undergo significant and clinically impactful index treatment discontinuation, treatment switching, and have lower adherence and persistence of anticancer therapy compared to patients without CRD. Strategies to control CRD to optimize cancer therapy are urgently needed.

Comparative analysis of machine learning algorithms for predicting diarrhea among under-five children in Ethiopia: Evidence from 2016 EDHS.

Background: Diarrhea is a major cause of mortality and morbidity in under-5 children globally, especially in developing countries like Ethiopia. Limited research has used machine learning to predict childhood diarrhea. This study aimed to compare the predictive performance of ML algorithms for diarrhea in under-5 children in Ethiopia. Methods: The study utilized a dataset of 9501 under-5 children from the Ethiopia Demographic and Health Survey 2016. Five ML algorithms were used to build and compare predictive models. The model performance was evaluated using various metrics in Python. Boruta feature selection was employed, and data balancing techniques such as under-sampling, over-sampling, adaptive synthetic sampling, and synthetic minority oversampling as well as hyper parameter tuning methods were explored. Association rule mining was conducted using the Apriori algorithm in R to determine relationships between independent and target variables. Results: 10.2% of children had diarrhea. The Random Forest model had the best performance with 93.2% accuracy, 98.4% sensitivity, 85.5% specificity, and 0.916 AUC. The top predictors were residence, wealth index, and child age, number of living children, deworming, wasting, mother's occupation, and education. Association rule mining identified the top 7 rules most associated with under-5 diarrhea in Ethiopia. Conclusion: The RF achieved the highest performance for predicting childhood diarrhea. Policymakers and healthcare providers can use these findings to develop targeted interventions to reduce diarrhea. Customizing strategies based on the identified association rules has the potential to improve child health and decrease the impact of diarrhea in Ethiopia.

Faecal microbiota and cytokine profiles of rural Cambodian infants linked to diet and diarrhoeal episodes.

The gut microbiota of infants in low- to middle-income countries is underrepresented in microbiome research. This study explored the faecal microbiota composition and faecal cytokine profiles in a cohort of infants in a rural province of Cambodia and investigated the impact of sample storage conditions and infant environment on microbiota composition. Faecal samples collected at three time points from 32 infants were analysed for microbiota composition using 16S rRNA amplicon sequencing and concentrations of faecal cytokines. Faecal bacterial isolates were subjected to whole genome sequencing and genomic analysis. We compared the effects of two sample collection methods due to the challenges of faecal sample collection in a rural location. Storage of faecal samples in a DNA preservation solution preserved Bacteroides abundance. Microbiota analysis of preserved samples showed that Bifidobacterium was the most abundant genus with Bifidobacterium longum the most abundant species, with higher abundance in breast-fed infants. Most infants had detectable pathogenic taxa, with Shigella and Klebsiella more abundant in infants with recent diarrhoeal illness. Neither antibiotics nor infant growth were associated with gut microbiota composition. Genomic analysis of isolates showed gene clusters encoding the ability to digest human milk oligosaccharides in B. longum and B. breve isolates. Antibiotic-resistant genes were present in both potentially pathogenic species and in Bifidobacterium. Faecal concentrations of Interlukin-1alpha and vascular endothelial growth factor were higher in breast-fed infants. This study provides insights into an underrepresented population of rural Cambodian infants, showing pathogen exposure and breastfeeding impact gut microbiota composition and faecal immune profiles.

Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Congenital Diarrhoeas and Enteropathies.

Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure.

The first time devastating food poisoning happened in Taiwan - Bongkrekic acid poisoning.

Bongkrekic acid (BKA), a rarely happened foodborne toxin by Burkholderia gladioli pathovar cocovenenans (Burkholderia cocovenenans) might leads to devastating life-threatening condition after eating meal contaminated BKA. Unbelievable event from March 19, 2024, to March 24, 2024, there was an outbreak of BAP in a luxury shopping area of eastern Taipei, Taiwan. Most of the victims are young to middle-aged people who made a tour over there and ate the cooked wet rice noodles. Of them, 13 males and 20 females, aged 40.9 ± 14.7 years old visited or were sent by ambulances to the emergency department presenting with watery diarrhea, and vomiting. Some progressed to severe hepatic and renal failure, altered mental status, disseminated intravascular coagulation, and fatalities within several hours within 2 days. The primary health workers especially emergency physicians need to keep in mind of BKA poisoning is quite different in presentations from other infectious colitis commonly seen before. Knowing the toxic-kinetic and toxic-dynamic mechanisms is important to farseeing the presentation of these BAP patients. Throughout this outbreak, we gathered abundant experiences in mitigating and managing these debilitated patients. Aggressively supportive care and early liver transplantation if there is no concurrent inflammatory process and the patient's condition is tolerable to surgical intervention saves lives. For food safety education, it is crucial to enhance our understanding of inhibiting BKA production and promote proper food preservation methods and a suitable environment to ensure food safety.

Incidence and risk factors of common infections among children in Wonago, southern Ethiopia: a prospective cohort study.

OBJECTIVE: There are limited data in Ethiopia on common childhood illnesses. We aimed to measure the incidence and risk factors of common childhood illnesses in rural parts of southern Ethiopia. DESIGN: A community-based cohort study. PARTICIPANTS AND STUDY SETTING: A total of 903 children of 5 years or younger were included between July 2017 and January 2018. We randomly selected households from three administrative units (kebeles) in Wonago district in Ethiopia. OUTCOMES: Data on incidence of illnesses were collected by interviewing the mothers of the children every second week, in 6 months. Incidence densities per child-week of observation were calculated, and predictors or recurrent illnesses were evaluated in multilevel Poisson regression models. RESULTS: Out of 903 children, 882 were included (97.6%). At least one illness was experienced among 87.3% of the children. Overall illness incidence rate was 19.7 episodes per 100 child-weeks, 95% CI 18.4 to 20.7. The incidence rate of fever symptoms was 5.5 episodes per 100 child-weeks; of acute respiratory infections (ARIs) 4.2 episodes per 100 child-weeks; of diarrhoea, 3.4 episodes per 100 child-weeks. In the multilevel analysis, household wealth status, child age, child nutritional status, source of drinking water, place for cooking and number of children below 5 years of age in the household were main risk factors for illnesses. CONCLUSIONS: Children below 5 years of age in Ethiopia often experience fever, ARIs and diarrhoea. The identified risk factors were related to poverty and highlighted the importance of preventive measures to reduce the incidence of these diseases.