In recent years, Swine Acute Diarrhea Syndrome Coronavirus (SADS-CoV) has attracted our attention as a new outbreak of porcine coronavirus. Reports on SADS-CoV indicate that this virus is widely involved in innate immunity, but its mechanism of involvement in antagonizing interferon signaling is still unclear. In this article, we found that the nucleocapsid protein (N) of SADS-CoV can inhibit the JAK-STAT signaling pathway mediated by IFN. Specifically, we found that N protein can degrade STAT1 through the ubiquitin proteasome pathway, and further discovered that N protein can promote K48 ubiquitination modification of STAT1. In addition, through mass spectrometry, we identified that the recruitment of E3 ligase TRIM28 by N protein promotes the degradation of STAT1. In addition, SADS-CoV infection of cells downregulates the protein expression level of STAT1, while overexpression of STAT1 inhibits the replication of SADS-CoV. The above results indicate that SADS-CoV N protein antagonizes the JAK-STAT signaling pathway by recruiting E3 ligase TRIM28 to mediate STAT1 degradation. These findings reveal a new mechanism by which SADS-CoV N protein antagonizes host innate immunity and provide us with novel strategies for antagonizing SADS-CoV.

Child malnutrition remains a global crisis, exacerbated in border regions by Myanmar's post-2021 conflict. This study utilized Structural Equation Modeling (SEM) to examine the pathways linking household food insecurity (HFI) to undernutrition among migrant children along the Thailand-Myanmar border. A cross-sectional survey was conducted among 384 mothers in Tak and Mae Hong Son provinces with children aged 6-59 months. Data were collected via multistage sampling, face-to-face interviews, and anthropometric assessments. HFI was measured using the HFIAS scale. Undernutrition affected 37.0% of children, with specific prevalence for stunting (18.0%), wasting (19.8%), and underweight (18.5%). HFI was prevalent in 63.8% of households and served as a central structural mediator; notably, nearly 40% of stunted children resided in severely food-insecure households. SEM results indicated that higher socio-economic status (SES) consistently improved HAZ (β = 0.230, p < .001) and WAZ (β = 0.294, p < .001). Improved water availability, safe sanitation, and higher SES were strong predictors of better HFI status across all models (β ranging from 0.127 to 0.318, p < .023). Conversely, a higher number of children under five in the household negatively impacted food security (β ranging from -0.155 to -0.159, p < .003). This improved HFI status directly enhanced dietary diversity (β = 0.183, p = .001) and HAZ (β = 0.113, p = .033). Regarding acute outcomes, fever (β = -0.147, p = .008) and diarrhea (β = -0.131, p = .049) significantly reduced WHZ, while respiratory infections (β = -0.144, p = .014) negatively influenced WAZ. Addressing undernutrition in this migrant population requires integrated multi-sectoral interventions. Strategies must prioritize economic stability and HFI mitigation to address chronic growth failure, alongside WASH infrastructure and rapid illness response to mitigate acute and composite nutritional deficits through a synergistic, cross-sectoral approach.

Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used in the treatment of obesity and diabetes mellitus because of their efficacy in weight reduction, glycemic control, and overall metabolic benefits. Gastrointestinal adverse events are among the most frequently reported side effects associated with these agents and are typically transient, occurring predominantly during dose escalation. However, severe gastrointestinal intolerance requiring hospitalization has rarely been reported. We present the case of a 51-year-old woman with obesity, hypertension, hyperlipidemia, and anxiety who developed severe nausea, vomiting, and diarrhea one day after restarting semaglutide 2.4 mg following a five-week treatment interruption during Ramadan. The patient had previously tolerated semaglutide therapy for approximately one year, with successful weight loss. Laboratory evaluation revealed significant electrolyte abnormalities, while contrast-enhanced abdominal and pelvic CT showed no acute pathology. The patient was managed with supportive treatment, including intravenous hydration, electrolyte replacement, antiemetics, and dietary modifications. She was discharged after four days of hospitalization, and cautious semaglutide reinitiation with dose escalation was planned after two weeks. This case highlights an important educational opportunity during Ramadan counseling, as patients receiving GLP-1 receptor agonists should generally be advised not to discontinue therapy solely because of daytime fasting unless clinically indicated. If treatment interruption occurs for a prolonged period, cautious reinitiation beginning at a lower dose with gradual dose escalation should be considered to minimize gastrointestinal adverse events. Careful dose re-titration after extended lapses in therapy may help reduce this risk. Further studies are needed to establish evidence-based recommendations for semaglutide reinitiation after prolonged treatment interruptions.

This narrative review summarizes the latest clinical evidence on xanomeline-trospium in schizophrenia, a first-in-class centrally acting dual-target muscarinic receptor modulator. Xanomeline-trospium combines the muscarinic receptor agonist xanomeline, with with functional preference for M1/M4 subtypes, and the peripherally acting muscarinic antagonist trospium chloride in a 4.2:1 ratio. Xanomeline mediates central therapeutic effects, whereas trospium mitigates xanomeline-induced peripheral adverse effects, including nausea, vomiting, and diarrhea. Five EMERGENT trials were reviewed, comprising three short-term efficacy studies and two long-term extension studies evaluating efficacy and safety. In five-week short-term trials, xanomeline-trospium significantly reduced total Positive and Negative Syndrome Scale (PANSS) total scores, with reductions in positive symptoms approximately 1.5-2 times greater and negative symptoms 1.5-3.5 times greater than those observed with placebo. In the EMERGENT-4 and EMERGENT-5 long-term extension trials, sustained therapeutic effects were observed along with potential improvements in quality of life in patients with mild-to-moderate schizophrenia over 52 weeks. Nevertheless, tolerability remains a major challenge, with high overall discontinuation rates (EMERGENT-4: 78.2% discontinuation; EMERGENT-5: 51% withdrawal). Notably, voluntary withdrawal accounted for a substantial proportion of discontinuations, exceeding adverse event-related withdrawals in certain subgroups. The most common adverse events included gastrointestinal symptoms (nausea, constipation, vomiting) and syncope. Compared with traditional dopamine D2 antagonists, xanomeline-trospium was associated with lower risks of weight gain, hyperprolactinemia, and extrapyramidal symptoms. Key limitations of this review include reliance on placebo-controlled trials without head-to-head comparisons, exclusion of treatment-resistant schizophrenia populations, and limited generalizability to outpatient settings due to the focus on acute inpatient cohorts. Future research should focus on identifying risk factors for early discontinuation and developing both pharmacological and non-pharmacological strategies to improve long-term adherence. Overall, as a novel non-dopaminergic antipsychotic strategy, xanomeline-trospium offers an important therapeutic option for patients who are intolerant to the metabolic or motor adverse effects of traditional antipsychotics, although challenges related to long-term adherence remain to be addressed.

A commonly used mouse model of ulcerative colitis is the Dextran Sodium Sulphate (DSS) colitis model, including symptoms of weight loss, softening of stool up to diarrhea, and abdominal pain. To address 3R-refinement, we aimed to reduce severity in this model through pain therapy with metamizole. In addition to the potential analgesic effect, we investigated whether metamizole had a modulatory effect on inflammatory processes. In the study, ten-week-old female C57BL/6J mice were used. For pharmacological analysis, mice were treated with 200 mg/kg/d metamizole over 2 days to calculate baseline plasma concentration of metamizole metabolites using LC-MS/MS. After 14 days, DSS was administered via drinking water for 5 days, followed by metamizole for 2 days to determine plasma concentration. To assess disease severity and pain therapy, mice received DSS via drinking water for 5 days, controls received water only. Mice were then treated with metamizole via the drinking water for an additional 5 days, while corresponding sub-cohorts were left untreated (water+water, water+metamizole, DSS+water, DSS+metamizole). For severity assessment, changes in bodyweight, posture, stool consistency, voluntary wheel running (VWR) and Mouse Grimace Scale (MGS) were analyzed. Furthermore, colon samples were used for histology and gene expression analyses. LC-MS/MS analysis revealed significantly higher plasma concentrations of 4-methylaminoantipyrine and increased concentrations of 4-aminoantipyrine following DSS and subsequent metamizole treatment when compared to baseline. Assessing disease severity in control mice (water+water or water+metamizole-treated) demonstrated no clinical signs or changes in VWR. DSS+water and DSS+metamizole treated mice showed similar loss of body weight and clinical signs. VWR performances were decreased in DSS+water-treated mice as well as in DSS+metamizole-treated mice. There were no statistically significant differences between untreated and metamizole-treated animals with DSS-colitis. Interestingly, none of the groups showed elevated MGS scores, nor did the gene expression analyses detect relevant differences. This study showed that administering metamizole via drinking water led to detectable levels of metamizole metabolites in the plasma of treated mice. However, metamizole did not reduce disease severity or pain in this mouse model. Therefore, other refinement strategies should be explored in future studies.

Demographic and Health Survey (DHS) data are important for determining risk factors associated with childhood diarrhea and acute respiratory infections (ARI) in sub-Saharan Africa (SSA); however, missing data from DHS can bias analyses, and no systematic review has assessed this practice. To address this, peer-reviewed DHS/MICS studies from SSA with childhood diarrhea or ARI as health outcomes were systematically retrieved from OpenAlex, PubMed, AJOL, and Dimensions. Screening and data extraction were conducted independently by two reviewers using a checklist developed from the Joanna Briggs Institute approach for assessing risk of bias. Empirical missingness was analyzed using data from the Nigeria DHS 2018 (N = 33,924 under-five children). From a total of 2,148 articles, 103 fulfilled our inclusion criteria (41 on diarrhea, 62 on ARI). Only three diarrhea articles (7.3%) and no ARI articles (0.0%) reported missing data. Complete-case analysis (CCA) was used in 80.5% of diarrhea articles and 100% of ARI articles. Multiple imputation (MI) was used in two diarrhea studies (4.9%) and no ARI articles. The empirical missingness rate for outcomes in both diseases was 9.8% across the full analytical sample. Clean cooking fuel was associated with reduced risk of ARI (CCA OR = 0.82, MI OR = 0.81, bias = -0.9%) and diarrhea (CCA OR = 0.66, MI OR = 0.64, bias = -3.5%). Inadequate missing data handling exists in both fields, but the challenge is more pronounced for ARI, where no effective alternative has been adopted to address the issue. Therefore, journals must enforce missing data reporting, and researchers should prioritize MI.

Objective: Metagenomic sequencing was employed to analyze the pathogen detection profile in pediatric severe acute non-A-E hepatitis. Methods: Based on the platform of the China Childhood Severe Acute Hepatitis Collaborative Group, a case series study was conducted. This study enrolled 36 children with severe acute non-A-E hepatitis, who were admitted to 17 hospitals between April and July 2022. Clinical data, including etiological test results and liver function tests, were collected, and peripheral blood and nasopharyngeal swab specimens were obtained. Metagenomic next-generation sequencing (mNGS) was performed to detect potential infectious pathogens. Results: Among 36 children, there were 24 males and 12 females, with an onset age of 3.5 (1.1, 9.0) years. Common clinical symptoms were fever in 22 cases (61%), jaundice in 13 cases (36%), vomiting in 12 cases (33%), abdominal pain in 10 cases (28%), rash in 10 cases (28%), and diarrhea in 3 cases (8%). Serum alanine aminotransferase and aspartate aminotransferase levels were 950 (826, 1 404) and 811 (498, 1 295) U/L, respectively. Using PCR, plasma Epstein-Barr virus (EBV)-DNA was tested in 31 cases (86%) and plasma cytomegalovirus (CMV)-DNA in 25 cases (69%), and all results were below 5×10[5] copies/L. Plasma mNGS was performed on all 36 patients, detecting 11 viruses. These included EBV in 14 cases, CMV in 12 cases, human adenovirus in 2 cases, herpes simplex virus type 1 in 2 cases, adeno-associated virus type 2 (AAV2) in 1 case, and 6 other viruses. No patient tested positive for both human adenovirus and AAV2 simultaneously. Plasma mNGS results showed a viral read count of 4 (2, 10) per 1×10[8] reads. Nasopharyngeal swab mNGS was performed on 8 cases (22%), detecting 7 viruses. These included human herpesvirus 7 in 4 cases, EBV in 3 cases, and CMV in 3 cases, as well as 4 other viruses. Human adenovirus and AAV2 were not detected. Among the 4 children with human herpesvirus 7, 2 cases were also positive for human herpesvirus 6B, but neither virus was detected in their plasma mNGS. Conclusions: The detection rates of human adenovirus and AAV2 are both low among children with severe acute non-A-E hepatitis, and there are no cases of co-infection with both viruses.

Enteric duplication cysts (EDCs) are rare congenital abnormalities of the digestive tract. They may occur with different clinical presentations-including acute intestinal obstruction, perforation or bleeding. The aim of this educational case report is to present the diagnostic and therapeutic process of a young male patient admitted for intestinal bleeding. The peculiarity of this case lies in the association between a rare pathology, EDC, and an equally unusual anatomical condition such as intestinal malrotation. A 27-year-old Italian Caucasian man was admitted with diarrhea and currant jelly stool. No gastrointestinal disorders or previous history of bleeding or chronic abdominal pain were reported. He denied habitual use of nonsteroidal anti-inflammatory drugs (NSAIDs), or other enterotoxic drugs. A small bowel CT scan showed a suspected acute enteritis. A more careful analysis revealed radiological signs of intestinal malrotation. An endoscopic video-capsule could not clearly identify the source of bleeding. The device-assisted enteroscopy revealed, at the mid-distal jejunal level, a double intestinal lumen with traces of digested blood material. The patient successfully underwent a surgical definitive treatment of the jejunal duplication cyst, and was soon discharged. The combination of multiple diagnostic tools, both radiological and endoscopic (entero-CT scan, small bowel video-capsule, and finally device-assisted enteroscopy), allowed for a multidisciplinary approach that led to the diagnosis of a rare small intestinal duplication cyst in a young male patient with congenital intestinal malrotation.