Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study.

Background: The contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota. Methods: We conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry. Results: IVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS. Conclusion: Our findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship. Declaration: This study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material.

Chronic diarrhoea due to trichohepatoenteric syndrome (THES) in an infant.

An infant was admitted with suspected postinfectious malabsorption with watery diarrhoea, fever and failure to thrive. She had dehydration, acute kidney injury and metabolic acidosis, which were corrected with intravenous fluids and managed with empiric antibiotics and prophylactic antifungals. She also developed Escherichia coli sepsis, meningitis and Candida skin infections during hospitalisation, which were treated according to the culture reports. Intrauterine growth restriction, woolly hair and a broad nasal bridge with chronic refractory diarrhoea prompted genetic testing to rule out syndromic diarrhoea. Whole-exome sequencing revealed a pathogenic compound heterozygous mutation causing trichohepatoenteric syndrome. She succumbed to severe infections at 80 days of life. The condition is rare, and no established guidelines or specific treatments exist; the focus is to promote optimal growth through parenteral nutrition, elemental formula and infection control. Early suspicion and molecular genetic testing can help reduce the time to diagnosis, treatment and genetic counselling.

Long term outcomes in children with trichohepatoenteric syndrome.

Trichohepatoenteric syndrome (THES) is a rare autosomal recessive disorder caused by mutations in either TTC37 or SKIV2L, usually leading to congenital diarrhea as part of a multisystem disease. Here, we report on the natural history of the disease for the largest UK cohort of patients with THES from 1996 to 2020. We systematically reviewed the clinical records and pathological specimens of patients diagnosed with THES managed in a single tertiary pediatric gastroenterology unit. Between 1996 and 2020, 13 patients (7 female and 6 male) were diagnosed with THES either by mutation analysis or by clinical phenotype. Two patients died from complications of infection. All patients received parenteral nutrition (PN) of which six patients were weaned off PN. All patients had gastrointestinal tract inflammation on endoscopy. Almost half of the cohort were diagnosed with monogenic inflammatory bowel disease (IBD) by the age of 11 years, confirmed by endoscopic and histological findings. Protracted diarrhea causing intestinal failure improves with time in all patients with THES, but monogenic IBD develops in later childhood that is refractory to conventional IBD treatments. Respiratory issues contribute to significant morbidity and mortality, and good respiratory care is crucial to prevent comorbidity.

Severe Immune-Related Enteritis after In Utero Exposure to Pembrolizumab.

Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.

Analysis on the current situation of twin breastfeeding and its influencing factors.

Studies have found that exclusive breastfeeding can not only promote the growth and development of infants, but also increase the emotional communication between mothers and infants, and reduce the incidence of maternal breast diseases. To analysis the current situation and influencing factors of breastfeeding twins. A total of 420 twin mothers delivered in our hospital from January 2019 to December 2022 were selected to investigate the situation of breastfeeding within 6 months after delivery. An electronic questionnaire was conducted, and clinical information were collected. Univariate analysis and multivariate logistic regression analysis were applied to analyze the factors influencing exclusive breastfeeding. The rate of exclusive breastfeeding was 21.90%; in the exclusive breastfeeding group, the age <35 years old, bachelor degree or above, rural areas, no nipple depression or flat, no breast distension, no postpartum depression, adequate breast milk, participation in health education during pregnancy, husband support for breastfeeding, no infant feeding difficulties, infant diarrhea, lactose intolerance and return to milk were 96.74%, 53.26%, 65.22%, 80.43%, 76.09%, 80.43%, 73.91%, 63.04%, 69.57%, 71.74%, 65.22%, 70.65%, and 66.30%, respectively. It was significantly higher than that in the non-exclusive breastfeeding group (P < .05). The score of Edinburgh Postpartum Depression Scale (EPDS) was (8.08 ± 1.03) in the exclusive breastfeeding group, which was significantly lower than that in the non-exclusive breastfeeding group (P < .001), while the score of Perceived Social Support Scale (PSSS) was (67.32 ± 9.92), which was significantly higher than that in the non-exclusive breastfeeding one(P < .001). Logistic regression analysis showed that age, education level, nipple depression or flat, breast tenderness, postpartum depression, breast milk volume, health education training during pregnancy, husband support for breastfeeding, PSSS score, infant diarrhea, lactose intolerance, and delectation were the influencing factors of exclusive breastfeeding (P < .001). Our findings suggest that various factors were associated with a low rate of exclusive breastfeeding in twin births, such as age, educational level, and social support. Corresponding measures should be formulated for intervention to promote exclusive breastfeeding.

MW Polyomavirus in diarrheal Italian infants.

BACKGROUND: MXPyV, like MWPyV, was identified in stool samples from children suffering diarrhea in Mexico. In this study, we used a home-made real time PCR to investigate the presence of this novel viruses in stool specimen collected from under-five-year-old children with gastroenteritis. METHODS: A total of 192 fecal specimens previously screened for RV, ADV, NoV, HPeV and SaV, were tested for MWPyV with Taqman real time PCR. RESULTS: The most detected virus was NoV GII (33.8%), followed by RV (21.3%), SaV (10.9%), HPeV (8%), NoV GI (6.7%) and Adv (1%). Real time PCR detected MWPyV in 1/192 (0.5%) patients. CONCLUSIONS: We detected MWPyV in 0.5% of fecal specimens collected from pediatric patients suffering gastroenteritis which is smaller than the previously reported in literature (4.4% in Australia and 12% Mexico).

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: "VS002A" trial protocol.

BACKGROUND: Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is to compare the efficacy of amino acid-based ORS "VS002A" compared to standard glucose-based WHO-ORS in infants and young children suffering from acute non-cholera watery diarrhea. METHODS: It is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6-36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. DISCUSSION: Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT04677296 . Registered on December 21, 2020.

Traditional Chinese Medicine Moxibustion in the Treatment of Infantile Diarrhea.

The main contribution of this research paper is to summarize the results of Meta-analysis of moxibustion in the treatment of infantile diarrhea which is one the common disease and requires considerable attention from the research community and funding organizations. In order to verify that the proposed scheme has merits, a comprehensive searching methodology was adopted by considering various databases such as China Biomedical Literature Database (CBM), China National Knowledge Network Infrastructure (CNKI), Wanfang Database, Pub Med Database, Google Academic, and Cochrane Library. It is important to note that a powerful computer has been utilized to carry out this searching. Finally, only those literature contents are selected which meet the inclusion criteria. Likewise, exclusion criteria was used to exclude irrelevant contents of the literature. RevMan 5.3 was used to analyze the collected data and after reading the titles and abstracts, 29 well-designed studies were selected. Through searching the full text, reading literature, and quality evaluation, 17 papers were finally included. Response rates were reported in all 17 studies, and subgroup analysis was performed based on whether or not other therapies were combined. 7 studies compared the effectiveness of simple moxibustion and conventional therapy in the treatment of infantile diarrhea, and the results showed statistically significant differences [OR = 4.01, 95% CI (2.03, 7.84), P < 0.0001]; 10 studies compared the effectiveness of moxibustion combined with other therapies and conventional therapies in the treatment of diarrhea in children, and the results showed that the difference had general meaning [OR = 4.45, 95% CI (2.83, 7.10), P < 0.00001]. The funnel plot (in Figure) showed that the distribution of included studies was asymmetrical on both sides of the baseline, which could be considered as publication bias. Traditional Chinese medicine moxibustion could effectively relieve the symptoms of infantile diarrhea, and the effect was significant.

The mammalian SKIV2L RNA exosome is essential for early B cell development.

The SKIV2L RNA exosome is an evolutionarily conserved RNA degradation complex in the eukaryotes. Mutations in the SKIV2L gene are associated with a severe inherited disorder, trichohepatoenteric syndrome (THES), with multisystem involvement but unknown disease mechanism. Here, we reported a THES patient with SKIV2L mutations showing severe primary B cell immunodeficiency, hypogammaglobulinemia, and kappa-restricted plasma cell dyscrasia but normal T cell and NK cell function. To corroborate these findings, we made B cell-specific Skiv2l knockout mice (Skiv2lfl/flCd79a-Cre), which lacked both conventional B-2 and innate-like B-1 B cells in the periphery and secondary lymphoid organs. This was linked to a requirement of SKIV2L RNA exosome activity in the bone marrow during early B cell development at the pro-B cell to large pre-B cell transition. Mechanistically, Skiv2l-deficient pro-B cells exhibited cell cycle arrest and DNA damage. Furthermore, loss of Skiv2l led to substantial out-of-frame V(D)J rearrangement of immunoglobulin heavy chain and severely reduced surface expression of µH, both of which are crucial for pre-BCR signaling and proliferative burst during early B cell development. Together, our data demonstrated a crucial role for SKIV2L RNA exosome in early B cell development in both human and mice by ensuring proper V(D)J recombination and Igh expression, which serves as the molecular basis for immunodeficiency associated with THES.

[A Case of Congenital Tufting Enteropathy with EpCAM Gene Complex Heterozygous Mutation (c.491+1G>A; c.352_353ins CACC)].

The patient, a one-month-old male infant, was admitted for "recurrent diarrhea for 20 + days and vomiting for 4 days". On the 8th day after birth, the patient began to develop recurrent refractory diarrhea, accompanied by abdominal distension, vomiting, dehydration, acidosis, and malnutrition. There were many cases of malignant tumors of the digestive system in the patient's family. Genetic testing identified compound heterozygous mutations (c.491+1G>A; c.352_353ins CACC) in epithelial cell adhesion molecule (EpCAM) gene and the patient was hence diagnosed with congenital tufting enteropathy. The patient was given partial parenteral nutrition support. The patient's diarrheal symptom was improved, but it was difficult to increase the amount of formula because any increase in the amount of formula for the patient would inevitably result in abdominal distention and vomiting. The patient experienced repeated fever in the later period of hospitalization and was eventually discharged from the hospital with the family's signed consent. He still had diarrhea and vomiting after leaving the hospital. Four weeks after discharge, the patient lost about 1 kg of weight and eventually died.

EpCAM Is Essential to Maintaining the Immune Homeostasis of Intestines via Keeping the Expression of pIgR in the Intestinal Epithelium of Mice.

EpCAM deficiency causes congenital tufting enteropathy (CTE) which is considered as one kinds of very early onset inflammatory bowel disease (IBD). However, functions of EpCAM on regulating the immunity of intestines are still unclear. To study the mechanism of EpCAM on maintaining the intestinal immune homeostasis, the intestines of WT and EpCAM-/- mice at E18.5, P0 and P3 stages were collected for morphological, histological and gene expression tests. Serious inflammation was detected in the small intestines of P3 EpCAM-/- mice. Compared to WT mice, genes related to inflammatory factors and immunity cells, including TNFα, IL-1ß, IL-6, IL-8rb, MIP2, MCP1, Ly6d and Ly6g, were all significantly upregulated and the expression of intestinal abundance matrix metalloproteinases (MMPs) was also significantly increased in the intestines of EpCAM-/- mice at E18.5, P0 and P3 stages. Signals of p38, ERK1/2 and JNK were hyper-activated in the intestines of EpCAM-/- mice. The expression of pIgR was significantly decreased and the expression and activation of transcriptional factors which promote the expression of pIgR were also reduced in the intestines of EpCAM-/- mice compared to WT controls. In conclusion, EpCAM could maintain the immune homeostasis of intestines via keeping the expression of pIgR in the intestinal epithelium.

UNC45A deficiency causes microvillus inclusion disease-like phenotype by impairing myosin VB-dependent apical trafficking.

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45AKO Caco-2 cells. In keeping with impaired myosin VB function, UNC45AKO Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45AKO 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease.

The risk of water, sanitation and hygiene on diarrhea-related infant mortality in eastern Ethiopia: a population-based nested case-control.

BACKGROUND: Diarrhea is still appeared to be as one of the leading global killers and disability-adjusted life-years lost, particularly in the infant and children. As per WHO, about 88% of diarrhea-related deaths are attributable to unsafe water, inadequate sanitation and insufficient hygiene, mainly in developing world. Thus, the main objective of this study was to find out the risk of such factors that contribute for diarrhea-related infant mortality in Eastern Ethiopia. METHODS: This study employed community based unmatched nested case-control study design in Eastern Ethiopia. The cases were infants who died from diarrheal disease while controls were those who survived their first year of life from September, 2016 to August, 2018. A total of 305 study subjects (61 cases and 244 controls) were included in the study. Infants dying from diarrhea were compared to four neighborhood controls in terms of several risk components of Water, Sanitation and Hygiene. Data were collected from mothers/care takers of infants using pre-tested structured questionnaires, and entered onto CSpro version 5.1 and transform to SPSS version 23 to analyzed potential risk factors. FINDINGS: Finding of this study revealed that the risk factors that found to be significantly associated with infant death from diarrhoea after adjustment for confounding variables included the age of mother with < 20 years old (P = 0.009, AOR: 0.01, 95% CI: 0.01, 0.47), unsafe drinking water storage (P = 0.013, AOR: 0.4, 95% CI: 0.18, 0.81), infants in households without point-of-use water treatment practices (P = 0.004, AOR: 0.21, 95% CI: 0.08, 0.61), households with unimproved sanitation (P = 0.050, AOR: 0.36, 95% CI: 0.13, 1.00), unsafe disposing of child feces (P = 0.014, AOR: 0.34, 95% CI: 0.15, 0.81), and improper management of solid waste (P = 0.003, AOR: 0.29, 95% CI: 0.13, 0.66). These exposure factors had lower risk for the contribution of infants dying from diarrhoea than those with their reference group in the study area. However, infants in households with improper management of liquid waste management showed strongly significant association which had three times more likely to occur diarrhea-related infant death (P = 0.010, AOR: 3.43, 95% CI: 1.34, 8.76). Similarly, infants whose mother/caretaker practiced hand washing with less critical time (one-two occasions) had three times greater risk to infant death from diarrhea than those who had practice more than three critical times of hand washing (P = 0.027, AOR: 3.04, 95% CI: 1.13, 8.17). CONCLUSION: This study suggests that infants in households with improper management of liquid waste and hand washing practices with fewer occasions (one-two critical time) are a greater risk of getting a diarrhea-related infant death. Therefore, efforts should be made to ensure intervention taking such risk factors into consideration, typically in the infantile period.

Tricho-Hepato-Eenteric Syndrome: Same Genotype but Different Phenotypes in Two Pakistani Children.

Tricho-hepato-enteric syndrome (THES) is characterised by infantile diarrhea with characteristic facies, trichorrhexis nodosa and hepatic involvement. The underlying genetic mutation is in tetratricopeptide repeat domain 37 (TTC37) gene. It is a very rare syndrome and only 44 cases have been reported so far in the medical literature. We recently diagnosed two children with THES on genetic analysis, who had same genotype but different phenotypes. Using these cases as a precedent, we reviewed what is known about this rare syndrome, as well as the novelties in our cases and treatment options. Key Words: Chronic diarrhea, Liver disease, Genetic mutation, TTC37.

Examining knowledge and traditional practices of mothers with children under five in Turkey on diarrhoea according to education levels.

BACKGROUND: Diarrhoea still ranks among the top causes of the deaths of children under five years old in the world. In solving this important health problem, it is necessary and imperative to know the health-related knowledge levels of mothers who take care of the child individually and the traditional practices they perform when their children are sick, in order to provide effective health education. AIM: This study aims to examine the knowledge levels and traditional practices of mothers with children younger than 5 years old regarding diarrhoea in relation to their education levels. METHODS: We conducted a cross-sectional web-based survey. The population of this cross-sectional study consisted of mothers with children under the age of 5 who lived in the metropolitan city Bursa in the South Marmara Region of Turkey. The survey was applied among the mothers of children under the age of 5 using the snowball sampling method via mobile platforms. The data were collected via Google Forms using a "Socio-Demographic Data Collection Form", an "Information Form on Measuring the Knowledge Level of Mothers on Diarrhoea" and a "Form on Main Traditional Practices Used When Children Have Diarrhoea in Turkey" prepared by the researchers after a review of the relevant literature. RESULTS: In the study, the mean total diarrhoea knowledge score of the participating mothers was found to be 22.01 ± 3.72 (high). Multiple linear regression analysis was used to determine the relationship between the total diarrhoea knowledge scores of the participants and other variables. The difference in the knowledge scores based on education levels was statistically significant (p < .001). The most prevalently preferred traditional practice in the case of children's diarrhoea was "feeding the child banana" (92.5%). CONCLUSION: Maternal education level is determined to be a significant variable that positively affects diarrhoea knowledge levels.KEY MESSAGESDiarrhoea continues to be among the top five preventable causes of death in the world and Turkey among children under the age of 5.The knowledge level of mothers about diarrhoea plays an important role in diarrhoea management. The level of knowledge about diarrhoea differs according to the education level of mothers.Traditional practices have an important place in the management of diarrhoea by mothers.

Cytoplasmic RNA quality control failure engages mTORC1-mediated autoinflammatory disease.

Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA-mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a SKIV2L-deficient patient. Epidermis-specific deletion of Skiv2l caused hyperproliferation of keratinocytes and disrupted epidermal stratification, leading to impaired skin barrier with no appreciable IFN activation. Moreover, Skiv2l-deficient T cells were chronically hyperactivated and these T cells attacked lesional skin as well as hair follicles. Mechanistically, SKIV2L loss activated the mTORC1 pathway in both keratinocytes and T cells. Both systemic and topical rapamycin treatment of Skiv2l-deficient mice ameliorated epidermal hyperplasia and skin inflammation. Together, we demonstrate that mTORC1, a classical nutrient sensor, also senses cytoplasmic RNA quality control failure and drives autoinflammatory disease. We also propose SKIV2L-associated trichohepatoenteric syndrome (THES) as a new mTORopathy for which sirolimus may be a promising therapy.

Sensing of RNA stress by mTORC1 drives autoinflammation.

Loss-of-function mutations in SKIV2L underlie trichohepatoenteric syndrome (THES2), a rare inborn error of immunity characterized by diarrhea, skin lesions, brittle hair, and immunodeficiency. SKIV2L is part of a multiprotein complex required for exosome-mediated RNA surveillance through RNA decay. In this issue of the JCI, Yang et al. delineate a mechanism underlying autoinflammatory skin disease in Skiv2l-deficient mice. Thus, a lack of SKIV2L activates mTORC1 signaling in keratinocytes and T cells, impeding skin barrier integrity and T cell homeostasis. Interestingly, treatment with the mTOR inhibitor rapamycin improves skin symptoms in Skiv2l-deficient mice, suggesting a possible therapeutic avenue for patients with THES2.

Tricho-hepato-enteric syndrome: Retrospective multicenter experience in Saudi Arabia.

Background: Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases. Methods: Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in TTC37 or SKIV2L, were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants. Results: The median age of THES patients was 3.7 years (0.9-23 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in SKIV2L, with biallelic variants in TTC37 accounting for the remaining cases. A total of seven variants were identified in TTC37 (n = 3) and SKIV2L (n = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in TTC37-related THES. Conclusion: Our data helps define the natural history of THES and provide clinical management guidelines.

Association between Attitude towards Wife Beating and Childhood Diarrhea: A Demographic and Health Survey-Based Study in 25 Sub-Saharan African Countries.

BACKGROUND: Childhood diarrhea remains a major public health problem in sub-Saharan Africa (SSA). Women empowerment reduces child mortality, and wife beating attitude is one of the indicators of women empowerment. There is a dearth of evidence about wife beating attitudes and childhood diarrhea in SSA. Therefore, the present study aimed to examine the association between attitude towards wife beating and diarrhea among under-five children. METHODS: We used Demographic and Health Surveys from 25 countries in SSA that were conducted between 2010 and 2020. Using Stata version 14 software, we carried out the analysis on 153,864 children under five. Bivariate and multivariate logistic regression analyses were applied, and the results were presented using adjusted odd ratios (aOR) at 95% confidence interval (CI). RESULTS: The pooled results show that 71.4% of married women disagreed with wife beating. About 20.5% of under-five children of married women had diarrhea. Childhood diarrhea varied from highest prevalence in Chad (27.9%) to the lowest prevalence in Sierra-Leone (8.5%). The study showed lower odds of diarrhea among children of married women who disagreed with wife beating (aOR = 0.66 95% CI; 0.54-0.80) compared to children of married women who agreed with wife beating. Moreover, the study results show that women's age (35-39 years-aOR = 0.48, 95% CI; 0.31-0.74, 40-44 years-aOR = 0.57, 95% CI; 0.35-0.93, 45-49 years-aOR = 0.35, 95% CI; 0.16-0.79) was negatively associated with childhood diarrhea, while husband's education (primary school-aOR = 1.36, 95% CI; 1.05-1.77), parity (ever born 3-4 children-aOR = 1.36, 95% CI; 1.09-1.70, and 5+ children-aOR = 1.56, 95% CI; 1.14-2.12), and religion (Muslim-aOR = 3.56, 95% CI; 1.44-8.83) were positively associated with diarrhea among under-five children. CONCLUSIONS: The study shows association between women attitude towards wife beating and childhood diarrhea. Therefore, empowering women, especially young women by increasing awareness about domestic violence, their rights, and empowering them through education and economic advancement need to be considered in order to reduce childhood diarrhea. Moreover, fertility control or birth spacing and working closely with religious leaders are important factors to consider in reducing childhood diarrhea.