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The experiment aimed to investigate the effects of plant essential oils on the growth performance and serum indicators of Holstein calves. Sixty Holstein calves with the similar age and weight were selected and randomly divided into two groups: A control group (fed a concentrated feed) and a test group (fed a concentrated feed supplemented with 200 g/t of plant essential oils), with three replicates per group and ten calves per replicate. A preliminary trial was conducted for 7 days, followed by a formal experimental period of 30 days. The results showed that compared to the control group, the final weight and average daily weight gain of the calves in the test group increased (P>0.05), and the body oblique length and chest circumference were significantly improved (P<0.05). Compared to the control group, the serum urea nitrogen (BUN) content of calves in the test group was significantly reduced (P<0.05), while the levels of immunoglobulin A (IgA) and immunoglobulin M (IgM) were significantly increased (P<0.05). The total antioxidant capacity (T-AOC) was significantly enhanced (P<0.05), and the content of malondialdehyde (MDA) was significantly decreased (P<0.05). Compared to the control group, the incidence of diarrhea in the test group calves was reduced by 20%, and the mortality rate was reduced by 7%. The study indicates that under the conditions of this experiment, the addition of plant essential oils to the concentrated feed can improve the average daily weight gain and body size indicators of calves, enhance the immune system function, increase the antioxidant capacity, and reduce the incidence of diarrhea and mortality of calves. [ABSTRACT FROM AUTHOR]

The inducible T-cell costimulator (ICOS) deficiency was first described in 2003. Autosomal re-cessive inherited ICOS deficiency is classified as combined immunodeficiency (CID) and has a wide clinical spectrum including hypogammaglobulinemia, recurrent infections, enteropathies, autoimmunity, lymphoproliferation, and malignancy. WAS/WASL Interacting Protein Family Member 1 (WIPF1) mutation causes WIP deficiency, characterized by thrombocytopenia, immu-nodeficiency, and eczema. Here, we aimed to present a patient with coexisting ICOS and WIP de-ficiency. [ABSTRACT FROM AUTHOR]

Objective • This study aims to investigate and analyze the correlation between EGFR-TKI first-line therapy and EGFR mutation status in patients with advanced lung cancer. Methods • We selected 60 patients with advanced lung cancer and EGFR mutations (diagnosed as stage IIIb or IV) from our hospital between January 2019 and November 2022. Each patient underwent an EGFR mutation test and was categorized into two groups based on their mutation status: 28 patients with exon 21 mutations and 32 with exon 19 deletions. After three months of therapy, we assessed treatment efficacy and adverse reactions. Results • Our data revealed that in the EGFR exon 21 mutation group, the objective response rate (ORR) and disease control rate (DCR) were 57.14% and 60.71%, respectively. In the EGFR exon 19 deletion group, the ORR and DCR were 68.75% and 84.38%, respectively. There were significant differences in DCR and ORR between the two EGFR mutation states, with statistical significance (P < .05). The progression-free survival (PFS) in the EGFR exon 21 mutant group was 8.4 months after third-generation EGFR-TKI treatment, while the EGFR exon 19 deletion group had a PFS of 12.7 months after the same treatment, with a statistically significant difference (P < .05). Cox regression analysis showed that female patients with no smoking history and an adenocarcinoma pathological type had significantly better PFS after treatment compared to male patients with a smoking history and squamous cell carcinoma type, with statistical significance (P < .05). Age and clinical stage did not significantly impact PFS after thirdgeneration EGFR-TKI treatment (P > .05). Adverse reaction incidences, such as nausea, fatigue, diarrhea, vomiting, and rash, did not significantly differ in either the EGFR exon 21 mutation group or the EGFR exon 19 deletion group (P > .05). Conclusion • The status of EGFR mutations serves as a predictive factor for PFS, DCR, and ORR in lung cancer patients undergoing EGFR-TKI first-line therapy. This status can be a valuable predictive indicator of lung cancer treatment efficacy, with potential applications in clinical practice. [ABSTRACT FROM AUTHOR]

Classical potassium binders are used in the treatment of hyperkalemia and are widely associated with gastrointestinal side effects, with crystal colonic injury being rare but potentially fatal. In this report, we describe the case of an 82-year-old male with hyperkalemia and calcium polystyrene sulfonate crystal–associated colonic necrosis. Traditionally, this diagnosis has relied on the examination of crystal morphology and polarization through microscopy. Our study enhances crystal identification by incorporating an analysis of the physical characteristics of the crystals using infrared spectroscopy. This is the first description, to our knowledge, of the calcium polystyrene sulfonate infrared spectrum. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited. We present the case of a patient with hereditary MTC and large bilobar liver metastases who demonstrated tumor response and resolution of their paraneoplastic diarrhea following TARE with Y90 microspheres. [ABSTRACT FROM AUTHOR]

Introduction: Transabdominal Yancey-Soave and transanal endorectal pull-trough (TEPT) procedures are the most common surgical approach for Hirschsprung disease (HSCR). One crucial aspect to evaluate after pull-through is the quality of life (QoL) of HSCR patients. It leads to further management and predicts patients’ prognosis. This study aimed to provide quantitative dan qualitative data about QoL of HSCR patients. Methods: A mixed-method sequential explanatory design was conducted to determine the QoL of children with HSCR after Yancey-Soave and TEPT surgery at our hospital from 2013 to 2018. Results: There were 15 samples included in this study: Yancey-Soave (n=5) and TEPT (n=10). The median QoL score of patients who underwent TEPT (2.85, IQR=2.75-2.93) was higher than patients who underwent the Yancey-Soave procedure (2.63, IQR=2.61-2.81). The parents informed that the children have a better overall QoL following surgery. Both parents inform that their children sometimes experience soiling. The major complaint of a patient after Yancey-Soave surgery is frequent bloating meanwhile the major complaint of a patient after TEPT is diarrhea. Conclusion: Our study shows that patients who underwent TEPT surgery may develop an enhanced QoL than the Yancey-Soave pull-through. Our study provides a comprehensive quantitative and qualitative analysis of the patient’s QoL after definitive surgery from a specific population. [ABSTRACT FROM AUTHOR]

Summary: This open‐label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3–23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option. [ABSTRACT FROM AUTHOR]

This manuscript seeks to describe diagnostic considerations in individuals with diabetes mellitus presenting to the ED with abdominal pain. It highlights the importance of early investigation with computerised tomography to differentiate aetiologies that compel early surgical intervention from those which may be treated conservatively. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. This study aimed to evaluate the effects of direct-fed microbials (DFM) on health and growth responses of preweaning Bos indicus × Bos taurus (Gyr × Holstein) crossbred calves. Ninety newborn heifer calves (initial BW of 35 ± 4.0 kg) were used. At birth, calves were ranked by initial BW and parity of the dam and assigned to: (1) whole milk without DFM supplementation (CON; n = 30), (2) whole milk with the addition of 1.0 g/calf per day of a Bacillus -based DFM (BAC; n = 30), or (3) whole milk with the addition of 1.0 g/calf per day of BAC and 1.2 g/calf per day of Enterococcus faecium 669 (MIX; n = 30). Milk was fed individually during the study (77 d), and the BAC and MIX treatments were offered daily throughout the 77-d preweaning period. All calves were offered a starter supplement and corn silage starting on d 1 and 60 of age, respectively. Milk and starter supplement intake were evaluated daily, and BW was recorded on d 0 and at weaning (d 77). Diarrhea and pneumonia were assessed daily, and fecal samples were collected on d 0, 7, 14, 21, and at weaning (d 77) for assessment of the presence of bacterial and protozoal pathogens via qPCR. All data were analyzed using SAS (v. 9.4) with calf as the experimental unit and using single-df orthogonal contrasts (BAC + MIX vs. CON; BAC vs. MIX). Daily feeding of DFM, regardless of type, improved weaning BW. Odds ratio for occurrence of pneumonia was lower for DFM-supplemented calves, but its occurrence did not differ between BAC and MIX calves. No Salmonella spp. or Escherichia coli F41 were detected in any of the calves. The proportion of calves positive for E. coli F17 was greater for DFM calves on d 7 (92% and 96% vs. 81% for BAC, MIX, and CON, respectively), on d 21 (13% and 26% vs. 7% for BAC, MIX, and CON, respectively), and at weaning (48% and 35% vs. 22% for BAC, MIX, and CON, respectively). For Clostridium difficile , more DFM calves were positive on d 7 (65% and 30% vs. 35% for BAC, MIX, and CON, respectively) and 14 (20% and 28% vs. 7% for BAC, MIX, and CON, respectively), but proportion of positive calves was also greater for BAC versus MIX on d 7. More CON calves were positive for Clostridium perfringens on d 14 (14% vs. 3% and 8% for CON, BAC, and MIX, respectively) compared with DFM-fed calves. Incidence of calves positive for C. perfringens was greater in BAC than MIX on d 7 (50% vs. 18%), and greater for MIX than BAC at weaning (9% vs. 0%). For protozoa occurrence, a lower proportion of DFM calves were positive for Cryptosporidium spp. on d 7 (58% and 48% vs. 76% for BAC, MIX, and CON, respectively), but opposite results were observed on d 21 for Cryptosporidium spp. (3% and 11% vs. 0% for BAC, MIX, and CON, respectively) and Eimeria spp. on d 14 (7% and 8% vs. 0% for BAC, MIX, and CON, respectively) and 21 (50% and 59% vs. 38% for BAC, MIX, and CON, respectively). In summary, DFM feeding alleviated the occurrence of pneumonia and improved growth rates, while also modulating the prevalence of bacteria and protozoa in preweaning Gyr × Holstein calves. [ABSTRACT FROM AUTHOR]

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

Background: Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Methods: Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Results: Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2–11.2 years), and median time post‐transplant was 1.9 years (IQR 0.8–3.8 years). Median diarrheal duration was 16 days (IQR 6.0–41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty‐one (53%) patients developed acute kidney injury. Thirty‐five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: −17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Conclusion: Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare polyethylene glycol 4000 versus lactulose in chronic constipation during pregnancy. Methods: Women at 28–32 weeks' gestation attending antenatal clinic for routine care were screened using the Rome IV chronic constipation criterion. Eligible women were approached and consented. Participants were randomized to oral polyethylene glycol (10 g/day) or lactulose (10 g/day) for 4 weeks. A bowel movement diary was kept and outcomes using the Patient Assessment of Constipation Symptoms questionnaire (PAC‐SYM), Patient Assessment of Constipation Quality of Life questionnaire (PAC‐QoL) and Bristol Stool Form Scale (BSFS), which were evaluated at the start and end of the four‐week period. Relative risks (RR) were determined for the coprimary outcomes of complete spontaneous bowel movement (CSBM) and PAC‐SYM mean score improvement (decrease in score of >1 from the baseline). Results: A total of 4323 women underwent screening, of which 780 fulfilled the Rome IV criterion, and 360 consented to participate (180 randomized to PEG and lactulose, respectively). Data from 247 women who completed the study were analyzed. CSBM was achieved in 107/124 (86.3%) versus 102/123 (82.9%) (RR 1.04, 95% CI: 0.93–1.16, P = 0.464) for PEG and lactulose trial arms, respectively. PAC‐SYM mean score improvement was 62/118 (52.5%) in the PEG arm versus 44/118 (37.3%) in the lactulose arm (RR 1.40, 95% CI: 1.05–1.88). Of secondary outcomes, a significant difference was found in favor of PEG, with respect to PAC‐SYM abdominal symptoms subscale, normal stool versus loose stool consistency and side effects of vomiting and diarrhea. After controlling for parity, baseline PAC‐SYM, PAC‐QoL scores, characteristics different at baseline, only diarrhea and loose stools remained significant. Conclusion: Both PEG 4000 and lactulose are effective laxatives in pregnancy with similar performance after adjusted analysis. Diarrhea and loose stools are less frequently reported with PEG. Synopsis: Polyethylene glycol 4000 and lactulose are similarly effective as laxatives for constipation in pregnancy; diarrhea and loose stools are less frequent encountered with polyethylene glycol. [ABSTRACT FROM AUTHOR]

Infections from Clostridioides difficile (often called C. diff) have long presented challenges for both patients and clinicians. Traditionally, C. diff has been considered a nosocomial infection, but in recent years, a noticeable spike in community-acquired cases has occurred. C. diff infection (CDI) testing is often complicated, as various testing options with differing sensitivity and specificity for active infection are available. Also, recent guideline changes have altered the recommended treatment of infection. This article discusses recent changes to both the diagnosis and management of CDI and how they can be applied to everyday NP practice. [ABSTRACT FROM AUTHOR]

Background and Objectives: Helicobacters are gastric and enterohepatic and live in the gut. The role of enterohepatic Helicobacters as intestinal pathogens is uncertain, while stomach Helicobacters are well-known. The prevalence of Helicobacter species in cat feces helps us understand their impact on cat health and human disease transmission. This study used PCR to identify Helicobacter spp. in feces samples from healthy and diarrhoeic cats, independent of the reason. The study also compared intestinal and stomach Helicobacter species. Materials and Methods: PCR analysis was performed on fecal samples from 40 cats, with 20 cats having diarrhea and 20 cats showing no symptoms. The PCR analysis aimed to detect Helicobacter's presence using a method that identifies the bacteria through the 16S rRNA gene. Results: The diarrhoeic group had a greater prevalence of infection (17:9 ratio), with an overall 65% infection rate detected. Cats that were older than 2 years showed a higher incidence of disease. H. canis had the highest occurrence rate (69.2%), followed by H. bilis, H. bizzozeronii, and H. salomonis. Significantly, H. pylori, H. felis, and H. heilmannii were not reported. Conclusion: H. canis was the predominant species found in both healthy and diarrheic cats, indicating the need for more investigation. The detection of the gastric species H. salomonis and H. bizzozeronii further complicates the classification. This highlights the complex nature of Helicobacter infections in cats, emphasizing the need for further investigation to guide the development of preventative measures and treatment techniques for both veterinary and public health purposes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early weaning is prone to damage intestinal barrier function, resulting in diarrhea, whereas rutin, as a natural flavonoid with multiple biological functions, shows potential in piglets. Therefore, the effects of dietary rutin on growth, antidiarrheal, barrier function, antioxidant status and cecal microbiota of weaned piglets were investigated with the control group (CON) (basal diet) and Rutin (basal diet+500 mg kg−1 rutin) groups fed for 14 days. RESULTS: The results showed that dietary 500 mg kg−1 rutin significantly decreased diarrhea index, serum diamine oxidase activity and total aerobic bacterial population in mesenteric lymph nodes, whereas it significantly increased the gain‐to‐feed ratio (G:F) and serum growth hormone content, jejunal villus height and villus height to crypt depth ratio, and also enhanced jejunal claudin‐1 and zonula occludens‐1 mRNA and protein expression. Meanwhile, dietary rutin significantly decreased inflammation‐associated mRNA expression, malondialdehyde (MDA) content, swollen mitochondrial number and mitochondrial area in the jejunum, whereas it increased the total superoxide dismutase (T‐SOD) and glutathione peroxidase activities and activated the Nrf2 signaling pathway. Moreover, dietary rutin significantly increased Firmicutes abundance and decreased Campylobacterota abundance, which were closely associated with the decreased diarrhea index and MDA content or increased Claudin‐1 expression and T‐SOD activity. CONCLUSION: Dietary 500 mg kg−1 rutin increased G:F by improving intestinal morphology, and alleviated diarrhea by enhancing intestinal barrier, which might be associated with the enhanced antioxidant capacity via activating the Nrf2/Keap1 signaling pathway and the improved cecal microbial composition in weaned piglets. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The Canadian Association of Radiologists (CAR) Gastrointestinal Expert Panel consists of radiologists, a gastroenterologist, a general surgeon, a family physician, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 20 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 58 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 85 recommendation statements specific to the adult population across the 20 scenarios. This guideline presents the methods of development and the referral recommendations for dysphagia/dyspepsia, acute nonlocalized abdominal pain, chronic abdominal pain, inflammatory bowel disease, acute gastrointestinal bleeding, chronic gastrointestinal bleeding/anemia, abnormal liver biopsy, pancreatitis, anorectal diseases, diarrhea, fecal incontinence, and foreign body ingestion. [ABSTRACT FROM AUTHOR]

Objective: Pyrotinib, a new irreversible dual pan-human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase inhibitor blocking EGFR and HER2, has achieved a promising efficacy for advanced HER2-positive (HER2+) breast cancer. This study intended to further investigate the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2+ breast cancer treatment. Methods: Thirty-eight HER2+ breast cancer patients who received neoadjuvant pyrotinib and trastuzumab plus chemotherapy (docetaxel and carboplatin) were retrospectively reviewed. Clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), pathological complete response (pCR), and adverse events data was retrieved. Results: According to the RECIST, the complete response rate was 0.0%, 10.5%, and 15.8% after second-cycle, fourth-cycle, and sixth-cycle therapy, respectively; whereas the objective response rate was 76.3%, 92.1%, and 100.0%, accordingly. The total pCR (tpCR) rate was 52.6%, the pCR rate of the breast was also 52.6%, and the pCR rate of lymph nodes was 86.8%. The tpCR rate was lower in patients with HER2 immunohistochemistry (IHC)++ and amplification by fluorescent in situ hybridization (FISH) than in those with HER2 IHC+++ (14.3% vs. 61.3%, p = 0.024), which was also lower in patients with Ki-67 expression ≥30% than in those with Ki-67 expression <30% (40.0% vs. 76.9%, p = 0.031). The common adverse events included diarrhea (84.2%), anemia (73.7%), nausea and vomiting (63.2%), fatigue (50.0%), hypomagnesemia (44.7%), leukopenia (42.1%), thrombocytopenia (39.5%), elevated transaminase (36.8%), and pruritus (31.6%). Conclusions: Pyrotinib and trastuzumab plus chemotherapy serve as an acceptable neoadjuvant regimen exhibiting good efficacy and tolerance in HER2+ breast cancer patients, while further large-scale validation is warranted. [ABSTRACT FROM AUTHOR]

Problem: There is a higher incidence of irritable bowel syndrome with miscarriages, and recurrent miscarriages of otherwise normal embryos have been linked to subnormal expression of the immune checkpoint inhibitor CD200L. We sought to determine if alterations in the expression of the CD200 immune checkpoint inhibitor occur in colonic tissue in IBS‐D patients. Method of Study: Quantitative immunohistochemical staining of biopsies from proximal and distal colon or rectum for the inhibitory CD200L and CD200S molecules was done. CD56 cells were also enumerated as they play a role in recurrent miscarriages and may express CD200S. Results: CD200L was decreased and CD200S was unchanged in epithelium but not stroma of 3 IBS‐D cases. One case had an increase in both CD200L and CD200S. CD56 cells were also stained for CD200S. Degranulation was assessed by the percentage of extracellular CD200S that was increased as epithelial CD200L decreased. Conclusions: This pilot study was promising and warrants a larger sample to determine if a correlation between uterine implantation site CD200L and CD200S expression in normal and failing implantation sites is needed. Colonic epithelial CD200L may then provide useful information about the pathogenesis of the spontaneous miscarriage in individual cases. [ABSTRACT FROM AUTHOR]

Canine parvovirus 2 (CPV-2) is an important causative agent of segmental enteritis in young dogs and has globally distributed variants and subtypes. Viral mutations can alter the pathogenesis and clinical signs, making identifying the samples circulating in a given region relevant. This study described the epidemiological and clinical findings and the molecular characterization of CPV-2 samples circulating in the canine population of Uruguaiana, Rio Grande do Sul (RS), Brazil. We analyzed 27 cases with a complete clinical history and at least one confirmatory etiologic diagnosis. In addition to clinical and epidemiological data, whole blood samples or tissues were tested by PCR for viral DNA detection. Amplified products were sequenced and analyzed, and phylogeny was generated with reference sequences. The disease was diagnosed especially in the summer months, and the most common clinical findings were diarrhea, anorexia, listlessness, and vomiting. Infection was predominant in young (< 6 months) unvaccinated or partially immunized dogs, with mortality exceeding 93%. It was possible to identify 15 CPV-2 samples, four of which were CPV-2a and 11 were new CPV-2a. It can be concluded that canine parvovirus is a disease with high mortality rates, with young unvaccinated dogs being more susceptible, with a predominance of the new CPV-2a variant in the western region of Rio Grande do Sul. [ABSTRACT FROM AUTHOR]

Enterocytes and liver cells fulfill important metabolic and barrier functions and are responsible for crucial vectorial secretive and absorptive processes. To date, genetic diseases affecting metabolic enzymes or transmembrane transporters in the intestine and the liver are better comprehended than mutations affecting intracellular trafficking. In this review, we explore the emerging knowledge on intracellular trafficking defects and their clinical manifestations in both the intestine and the liver. We provide a detailed overview including more investigated diseases such as the canonical, variant and associated forms of microvillus inclusion disease, as well as recently described pathologies, highlighting the complexity and disease relevance of several trafficking pathways. We give examples of how intracellular trafficking hubs, such as the apical recycling endosome system, the trans‐Golgi network, lysosomes, or the Golgi‐to‐endoplasmic reticulum transport are involved in the pathomechanism and lead to disease. Ultimately, understanding these processes could spark novel therapeutic approaches, which would greatly improve the quality of life of the affected patients. [ABSTRACT FROM AUTHOR]

Myristoylation, the N-terminal addition of the fatty acid myristate to proteins, regulates membrane-bound signal transduction pathways important in cancer cell biology. This modification is catalyzed by two N-myristoyltransferases, NMT1 and NMT2. Zelenirstat is a first-in-class potent oral small molecule inhibitor of both NMT1 and NMT2 proteins. Patients with advanced solid tumors and relapsed/refractory (R/R) B-cell lymphomas were enrolled in an open label, phase I dose escalation trial of oral daily zelenirstat, administered in 28-day cycles until progression or unacceptable toxicity. The endpoints were to evaluate dose-limiting toxicities (DLT) to establish a maximum tolerated dose (MTD), pharmacokinetic parameters, and anticancer activity. Twenty-nine patients were enrolled (25 advanced solid tumor; 4 R/R B-cell lymphoma) and 24 were DLT-evaluable. Dosing ranged from 20 mg once daily (OD) to 210 mg OD without DLT, but gastrointestinal DLTS were seen in the 280 mg cohort. MTD and recommended phase 2 dose were 210 mg OD. Common adverse events were predominantly Gr ≤ 2 nausea, vomiting, diarrhea, and fatigue. Plasma concentrations peaked at 2 h with terminal half-lives averaging 10 h. Steady state was achieved by day 15, and higher doses achieved trough concentrations predicted to be therapeutic. Stable disease as best response was seen in eight (28%) patients. Progression-free survival and overall survival were significantly better in patients receiving 210 mg OD compared to those receiving lower doses. Zelenirstat is well-tolerated, achieves plasma exposures expected for efficacy, and shows early signs of anticancer activity. Further clinical development of zelenirstat is warranted. [ABSTRACT FROM AUTHOR]

Purpose: This phase I trial is to determine the recommended dose of the TAS-102, irinotecan plus bevacizumab regimen and assess its safety and efficacy in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin treatment. Methods: A 3 + 3 designed dose escalation was performed. Patients were administered TAS-102 (30–35 mg/m2 twice daily on days 1–5) and irinotecan (150–165 mg/m2 on day 1) combined with a fixed dose of bevacizumab (5 mg/kg on day 1) every two weeks. The primary endpoint was the determination of the recommended phase II dose. Results: Eighteen patients were enrolled: 6 at the Level 1 (TAS-102 30 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), six at the Level 2 (TAS-102 35 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), and six at the Level 3 (TAS-102 30 mg/m2 twice daily, irinotecan 165 mg/m2 plus bevacizumab 5 mg/kg). Five dose-limiting toxicities occurred: one observed at Level 1 (thrombocytopenia), two at Level 2 (neutropenia and diarrhea), and two at Level 3 (fatigue and neutropenia). The RP2D was established as TAS-102 30 mg/m2 twice daily and irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg. The most frequent grade 3/4 treatment-related adverse events were neutropenia (33.3%), diarrhea (16.7%), and thrombocytopenia (11.1%). No treatment-related death occurred. Two patients (11.1%) experienced partial responses and 14 (77.8%) had stable disease. Conclusion: The regimen of TAS-102, irinotecan, and bevacizumab is tolerable with antitumor activity for metastatic colorectal cancer patients refractory to first-line fluoropyrimidines and oxaliplatin treatment. [ABSTRACT FROM AUTHOR]

This phase 1b study aimed to evaluate the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics, and preliminary efficacy of HR070803, a novel nanoliposomal formulation of irinotecan, in combination with 5-fluorouracil and leucovorin in patients with pretreated advanced solid tumors. This study consisted of dose-escalation and expansion stages. Dose escalation was performed with a traditional 3 + 3 design; patients received intravenous infusion of HR070803 from 60 to 80 mg/m2, followed by leucovorin (200 mg/m2) and 5-fluorouracil (2000 mg/m2) every 2 weeks. In the expansion stage, patients received treatments at selected tolerable dose. Fifteen patients received treatments at 60 mg/m2 (n = 12) and 80 mg/m2 (n = 3). DLTs occurred in 2 patients at 80 mg/m2 (grade 2 neutropenia that resulted in a dose delay of ≥ 7 days, n = 1; grade 3 febrile neutropenia, n = 1). The MTD was determined to be 60 mg/m2. The most frequent HR070803related adverse events included anorexia, leukopenia, neutropenia, nausea, fatigue, and diarrhea. SN-38, the active metabolite of irinotecan, exhibited lower maximum plasma concentrations and a prolonged terminal half-life when irinotecan was administered via nanoliposome compared to conventional injection. Overall, 4 patients achieved a partial response (confirmed, n = 2), and 9 had stable disease. The MTD of HR070803 was 60 mg/m2 when infused with 5-fluorouracil and leucovorin. Nanoliposomal encapsulation modified the pharmacokinetics of irinotecan and SN-38. HR070803 with 5-fluorouracil and leucovorin demonstrated a manageable safety profile and promising antitumor efficacy in advanced solid tumors. Trial registration: Clinicaltrials.gov, NCT05086848. Retrospectively registered on Oct. 12, 2021. [ABSTRACT FROM AUTHOR]

Significant economic losses due to diarrhoea morbidity in newborn young animals lead to a decrease in the profitability of the sector in the structure of agricultural production. Therefore, the purpose of this study was to create and investigate the therapeutic effect of application of complex phytomineral preparation using local components: opoka of Taskala deposit and decoction of camelthorn (Alhagi maurorum) for treatment of diarrhoea in calves. The therapeutic effect of the preparation was studied in the conditions of dairy farm in Kyzylorda region on 5-7-day-old calves. The effect of the preparation was studied in a comparative aspect with an analogous preparation of imported production and the results obtained from healthy animals. Clinical, haematological, and biochemical methods of investigation were employed. The findings obtained suggest a high therapeutic effect of the created preparation. Its application allowed reducing the duration of the treatment period by 5-7 days compared to the imported preparation and restoring the positive dynamics of average daily gain as early as on the 5th day after the start of treatment. Haematological studies indicate stimulation of the immune system in animals that was manifested by a 14% increase in the count of lymphocytes and a 37% increase in the proteins of the γ-globulin fraction compared to healthy animals. These indices suggest an increase in the activity of the humoral part of the immune system in animals after treatment with the preparation. Another positive therapeutic effect of the preparation was observed in the protective effect on the liver of diseased animals. Despite the present effect of both preparations, the decrease in the activity of markers characterising hepatocyte destruction was higher with the Kazakh preparation. Thus, the created preparation is characterised by a higher therapeutic effect in comparison with the imported preparation and allow recommending it for treatment and prevention of diarrhoea in young animals. [ABSTRACT FROM AUTHOR]

Background: Clostridioides difficile (C. difficile) is an anaerobic bacterium associated with considerable wide-spectrum colonic infections. Various risk factors are recognized to increase the incidence of C. difficile infection (CDI) in certain age groups. COVID-19 pandemic and its association with CDI remains an area of research. Objectives: Our aim is to investigate the risk factors and outcomes of CDI among hospitalized patients with diarrhea with special consideration for COVID-19 patients. Results: The study included 1515 hospitalized patients with infectious diarrhea from 2017 to 2021, 195 (13%) of them had positive CDI tests and 1320 (87%) were CDI-negative. The risk for CDI was higher in the young adults aged between 18 and 35years (OR: 2.47, 95%CI: 1.37- 4.47, p=0.0028) and older patients aged ≥ 56 years (OR: 1.95, 95% CI: 1.87-3.21, p=0.0084). Older patients’ risk factors included stroke, administration of antibiotics, history of previous hospital admission within one month, and cancer. While young adults receiving two antibiotics were at greater risk of having CDI. 132 COVID-19 patients with diarrhea were identified and 7 (5%) of them were CDI positive. Conclusions: Investigating the risk factors of CDI in different age groups, including COVID-19 patients, is a crucial step to developing a risk-based prophylactic strategy to reduce the cost and burden on the healthcare system. [ABSTRACT FROM AUTHOR]

(1) Shigella spp. (Shigella) is known for causing dysentery with blood in stool, but most children infected with Shigella have non-dysentery Shigella-associated diarrhea (NDSD). The World Health Organization recommends the use of antibiotics when diarrhea is bloody, leaving most NDSD cases untreated. The absence of dysentery may not indicate a low risk of death and severe morbidity. Rapid diagnosis and treatment of shigellosis in vulnerable, young children may be lifesaving. INSIGHT aims to determine the potential benefit of identifying NDSD cases (n = 296) and their outcomes compared to cases of Shigella dysentery [DS (n = 148)] and non-Shigella watery diarrhea [WD (n = 148)]. (2) Children seeking care at hospitals in Bangladesh will be enrolled and followed for 1 year (NDSD and DS) or 90 days (WD). We will determine the impact of NDSD on morbidity, mortality, gut health, nutritional status, and cognitive development compared to DS and WD in children and whether the simple "Rapid LAMP-based Diagnostic Test (RLDT)" can accelerate the detection and treatment of shigellosis in the clinical settings of rural Bangladesh. (3) INSIGHT will determine the impact of NDSD in children and determine if the treatment guidelines of shigellosis need to be revisited to improve clinical outcomes and the development of these children. [ABSTRACT FROM AUTHOR]

Carbapenems are the antibiotics of choice for treating multidrug-resistant bacterial infections. Metallo-β-lactamases (MBLs) are carbapenemases capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, this research assessed the distribution of two MBL genes and three β-lactamases and their associated phenotypic resistance in diarrheal and urinary-tract infections (UTIs) to guide future policies. Samples were collected through a cross-sectional study, and β-lactamase genes were detected via PCR. A total of 228 diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively. A total of 142 UTI pathogens were identified from 150 urine samples. Klebsiella spp. (39%) and Escherichia coli (24%) were the major pathogens isolated. Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively. Twenty-four diarrheal isolates carried blaNDM-1 or blaVIM genes. The overall MBL gene prevalence was 10.5%. Thirty-six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes. MBL genes were strongly associated with phenotypic carbapenem and other β-lactam antibiotic resistance. blaOXA imparted significantly higher phenotypic resistance to β-lactam antibiotics. Active surveillance and stewardship programs are urgently needed to reduce carbapenem resistance in Bangladesh. [ABSTRACT FROM AUTHOR]

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Background: This study aimed to identify the specific areas of knowledge gaps regarding lactose intolerance among neonatologists in Chinese outpatient settings as well as to assess the availability of lactose intolerance testing in hospitals. Methods: A total of 278 neonatologists in outpatient settings from 144 hospitals were surveyed. To explore the awareness level, diagnosis, and treatment of neonatal lactose intolerance among neonatologists in outpatient settings, a multicenter cross-sectional survey was designed. Descriptive analysis based on frequency and percent distribution was performed for all variables. Results: Most respondents were senior doctors (256, 92.09%) from general hospitals and maternity/maternal and child health hospitals, had over 10 years of experience, and were dominantly associate chief physicians and chief physicians (211, 75.90%). A significant proportion of the participants (236, 84.89%) believed that neonatal lactose intolerance tends to be overlooked during clinical practice. When the most common symptoms of neonatal lactose intolerance were surveyed, diarrhea was selected by 142 (51.08%) respondents, followed by bloating and milk regurgitation or emesis (71, 25.54%). Other symptoms included unexplained crying (36, 12.85%), stool with milk flap or foam (15, 5.40%), and increased venting (14, 5.04%). Furthermore, the survey results indicated that the most common method for diagnosing neonatal lactose intolerance in the respondents' hospitals was qualitative test for urinary galactose (78, 28.06%). Of the respondents, 137 (49.28%) stated that their hospital could not test for lactose intolerance. For treating lactose intolerance, the neonatologists primarily opted for exogenous lactase rather than lactose-free formula milk. Conclusions: This study sheds light on Chinese neonatologists' awareness of neonatal lactose intolerance, revealing some knowledge gaps. The expeditious popularization and conduct of lactose intolerance-related examinations in hospitals will have a positive stimulative effect on the management of lactose intolerance in newborns. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. Methods: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. Results: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02–1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09–1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02–1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. Conclusion: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis. [ABSTRACT FROM AUTHOR]

This study aimed to assess an ultra-diluted (UD) complex, as a replacement for an antimicrobial growth promoter in diets, on growth performance, intestinal health, and inflammatory response of nursery piglets. The experiment lasted 37 days and involved 126 animals weaned at 21 ± 1.3 d, with an initial body weight of 5.62 ± 1.16 kg. Piglets were assigned to six dietary treatments in a randomized block design with seven replicates and three piglets per pen as experimental unit. The treatments were: positive control (PC)– basal diet + 120 mg/kg of chlorohydroxyquinoline; negative control (NC)– basal diet without additives; and NC containing 4.5; 6.0; 7.5 or 9.0 kg of UD additive/ton diet. Performance data were calculated, and daily diarrhea was observed. Blood samples were collected for hematological analysis. At the end of the experiment, one animal per pen was slaughtered for organ weighing, pH, and the collection of intestinal samples for histopathology. Feces and cecal contents were collected for microbiological and antibiogram analyses. There was no difference in the performance between the treatments. Throughout the study, UD levels were equal to those of PC for diarrhea occurrence. Higher levels of UD complex led to higher total leukocyte counts. The 4.5 treatment showed a reduction in total and thermotolerant Enterobacteriaceae populations in piglet feces and an increase in lactic acid bacteria compared to PC. All treatments resulted in fewer duodenal histopathological alterations than those in the NC group. The use of UD additives, especially at 4.5 kg/ton, is a good alternative to chlorohydroxyquinoline in piglet diets. [ABSTRACT FROM AUTHOR]

Diarrhea is among the leading cause of death especially among children aged under 5 years. Zinc has been included in the management and treatment of diarrhea. Nanoparticle is gaining importance in medicine. The aim of this study is to evaluate the antidiarrheal activity of biosynthesized zinc oxide nanoparticle in castor oil-induced diarrheal rats. Zinc oxide nanoparticle (ZnONP) was biosynthesized using Cassia occidentalis leaf. The biosynthesized ZnONP was characterized using ultra-violet (UV)-spectroscopy and Fourier transform infrared spectroscopy (FTIR). Twenty five albino rats were randomly grouped into five groups. All rats, except the control, were induced with diarrhea. Group1 received normal saline, group 2 received 3 mg/kg b.wt. loperamide while groups 3, 4 and 5 received 10, 20, and 50 mg/kg b.wt. biosynthesized ZnONP. UV spectroscopy showed an absorption peak at 320 nm. The SEM micrographs reveal the nanoparticles as flake like which are well agglomerated.. The SEM micrographs reveal the nanoparticles as flake like which are well agglomerated. The biosynthesized zinc oxide nanoparticle significantly delayed the onset of diarrhea, decreased the number of wet feces, increased the percentage gastrointestinal tract (GIT) inhibition and decreased the volume of intestinal fluid. Biosynthesized zincoxide nanoparticle from Cassia occidentalis leaf can be used in the treatment of diarrhea. [ABSTRACT FROM AUTHOR]

Background: Globally, rotavirus (RV) A (RVA) is the most common cause of severe and sometimes fatal diarrhea in young children. It is also the major cause of acute gastroenteritis among children in Ethiopia. Currently, the WHO has prequalified four RVA vaccines for universal childhood immunization. Ethiopia introduced the monovalent Rotarix vaccine into its national immunization program in 2013. Since then, only a few studies on the burden and genotype distribution of RVA infection post-vaccine introduction have been conducted (mostly at sentinel surveillance sites). Therefore, this study aimed to assess RVA prevalence and genotype distribution among children under five years in Ethiopia (February 2021–December 2022). Methods: This multi-center hospital-based cross-sectional study involved 537 diarrheic children under-five years old. Rotavirus A detection was conducted using a one-step reverse-transcriptase polymerase chain reaction (RT-PCR). Genotyping was conducted by Sanger sequencing of the VP7 (complete) and VP4 (partial) genes. Descriptive analysis and Pearson's chi-squared test were carried out using SPSS version 29. Phylogenetic analysis with 1000 bootstrap replicates was performed using MEGA version 11 software. Statistical significance was set at p < 0.05 for all analyses. Results: The prevalence of RVA infection among diarrheic children was 17.5%. The most prevalent G-types identified were G3 (37%), the previously uncommon G12 (28%), and G1 (20%). The predominant P-types were P[8] (51%), P[6] (29%), and P[4] (14%). The three major G/P combinations observed were G3P[8] (32.8%), G12P[6] (28.4%), and G1P[8] (19.4%). Phylogenetic analysis revealed clustering of Ethiopian strains with the globally reported strains. Many strains exhibited amino acid differences in the VP4 (VP8* domain) and VP7 proteins compared to vaccine strains, potentially affecting virus neutralization. Conclusions: Despite the high RVA vaccination rate, the prevalence of RVA infection remains significant among diarrheic children in Ethiopia. There is an observable shift in circulating RVA genotypes from G1 to G3, alongside the emergence of unusual G/P genotype combinations such as G9P[4]. Many of these circulating RVA strains have shown amino acid substitutions that may allow for neutralization escape. Therefore, further studies are warranted to comprehend the emergence of these unusual RVA strains and the diverse factors influencing the vaccine's diminished effectiveness in developing countries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Shigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine. METHODS AND FINDINGS: We used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings. CONCLUSIONS: Our simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (

Immunoglobulin G4 (IgG4)-related disease is an immune-mediated, fibroinflammatory condition that causes multisystemic contrast enhancement and is predominantly observed in elderly male patients. The most prominent features of IgG4-related disease are systemic involvement affecting from two to six systems. In the central nervous system, these contrast enhancements are typically found in the meninges and orbit. This case study describes a 78-year-old female patient with persistent headaches and constant diarrhea who underwent treatment for IgG4-related disease. Despite two months of treatment with non-steroidal and opioid analgesics, the patient remained unresponsive and continued to experience diarrhea for 4 months. Brain magnetic resonance imaging revealed contrast enhancement in the leptomeningeal surfaces, and a biopsy of the gastrointestinal mucosa confirmed the diagnosis of IgG4-related disease, showing widespread plasma cell infiltration and IgG4 expression on plasma cells. The patient was initially treated with 1.0 g/day of pulse therapy for 5 days, followed by a maintenance dose of 1.0 mg/kg oral azathioprine. When azathioprine caused significant pancytopenia, rituximab therapy was initiated. The patient’s headaches resolved completely, and the diarrheal attacks were controlled. This case highlights the importance of considering IgG4-related disease as a potential cause of headache or multiorgan symptoms in elderly patients with new-onset headache unresponsive to conventional analgesics. IgG4-related disease can often be effectively treated with steroids and monoclonal antibodies.

Aim: to optimize outcomes of the treatment and prevention of gastrointestinal diseases in adults and children. Key points. The Methodological Guidelines contain sections on the terminology, classification, mechanisms of action, requirements for sale in the Russian Federation, requirements for proving the efficacy and safety of probiotics, prebiotics, synbiotics and metabiotics, as well as functional foods enriched with them. An overview of relevant data allowing to include these drugs and products in the treatment an d prevention of gastrointestinal diseases in adults and children is presented. Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and metabiotics depends on the specificity and quantity of their components, the dosage form, the regimen and duration of treatment. Products and functional foods with proven efficacy and safety are recommended for the treatment and prevention of gastrointestinal diseases in adults and children.

Abstract Background Despite the fact that diarrhea is more accurately described as a clinical symptom than a disease. Diarrhea is one of the most important issues in ovine medicine, particularly in lambs, and because of high morbidity and mortality rate, sluggish growth performance, and veterinary costs, it is believed to be a major source of economic loss. Salmonella and enterotoxigenic Escherichia coli are the most common and commercially significant agents responsible for diarrhea. Objective The objective of this study was to monitor the nucleotide sequence variations, gene expression, serum inflammatory and oxidative stress biomarkers in diarrheic lambs. Another aim was to identify different pathotypes and virulence genes of Salmonella and E. coli causing diarrhea. Methodology Blood samples were taken from 50 Barki who were diarrheal and 50 who appeared to be healthy, and then divided in 3 portions, with EDTA added to the first part for CBC, DNA and RNA extraction. The second sample received 5000 I.U. of heparin calcium, and a clean plain tube was used for the third component. The second and third sections were centrifuged to extract serum and plasma until the biochemical and immunological analysis was completed. Fecal samples were collected for bacteriological examination, and the bacteria were identified by PCR analysis. PCR-DNA sequencing was conducted for immune (SELL, JAK2, SLC11A1, IL10, FEZF1, NCF4, LITAF, SBD2, NFKB, TNF-α, IL1B, IL6, LGALS, and CATH1), antioxidant (SOD1, CAT, GPX1, GST, Nrf2, Keap1, HMOX1, and NQO1), and GIT health (CALB1, GT, and MUC2) genes in healthy and diarrheic lambs. Results Virulent genetic markers of pathogenic characteristics of E. coli (astA, Vt2e (Stx2e), CFA/I, groES and luxS) and Salmonella (invA, SopB, bcfC and avrA) were detected in all diarrheic lambs. PCR-DNA sequencing of immune, antioxidant and intestinal health genes found eleven single nucleotide polymorphisms (SNPs) linked to either diarrhea resistance or susceptibility in Barki lambs. Transcript levels of immune, antioxidant, and GIT health (CALB1, GT, and MUC2) genes varied between healthy and diarrheic lambs. Nucleotide sequence variation of the genes under inquiry between reference sequences in GenBank and those of the animals under investigation verified all identified SNPs. Significant (P = 0.001) erythrocytosis, neutrophilic leukocytosis, with lymphocytopenia were observed in diarrheic lambs. Significant (P = 0.001) increases in serum IL-1α, IL-1β, IL-6, TNF-α (90.5 ± 1.7, 101.8 ± 1.7, 72.3 ± 6.6, 71.26 ± 4.89 Pg/ml, respectively), serum Fb, Cp, Hp, SAA (230.7 ± 12.4 mg/dl, 6.5 ± 0.07 mg/dl, 2.5 ± 0.09 g/dl, 7.4 ± 0.4 mg/L, respectively), free radicals (MDA, NO), cortisol (6.91 ± 0.18 μg/dl) and growth hormone, with significant (P = 0.001) decreases in serum IL-10 (81.71 ± 1.05 Pg/ml), antioxidants (CAT, GPx), insulin, triiodothyronine (T3) and thyroxine (T4) in diarrheic lambs. Conclusions The study's findings provided credence to the theory that marker-assisted selection (MAS) could be used to predict and prevent diarrhea in Barki sheep by selecting lambs based on SNPs in genes linked to inflammation, antioxidants, and intestinal health. In order to establish an efficient management protocol and determine the most susceptible risk period for disease occurrence, gene expression profiles of the genes under investigation, pro-inflammatory cytokines and acute phase proteins may also be utilized as proxy biomarkers for lamb enteritis.

Abstract Background Monoglycerides have emerged as a promising alternative to conventional practices due to their biological activities, including antimicrobial properties. However, few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance, immune response, and gut health using a disease challenge model. Therefore, this study aimed to investigate the effects of dietary monoglycerides of short- and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18. Results Pigs supplemented with high-dose zinc oxide (ZNO) had greater (P

Mingmin Guo,1,2 Yi Wu,2,3 Maijiao Peng,1,2 Nenqun Xiao,1,2 Zhijun Lei,1,2 Zhoujin Tan2,3 1School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Changsha, People’s Republic of China; 3School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Zhijun Lei, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email lzj-707@163.com Zhoujin Tan, School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China, Email tanzhjin@sohu.comBackground: Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP’s therapeutic effects, providing experimental evidence for its mechanism of action.Methods: A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with Folium sennae. After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured.Results: SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.05), and a significant negative correlation with Prevotellaceae UCG− 001, Rikenella (p< 0.05), Acinetobacter (p< 0.05), Parasutterella (p< 0.05), and Lacticaseibacillus (p< 0.05). TNF-α levels showed a significant negative correlation with Lacticaseibacillus (p< 0.05), Prevotellaceae UCG− 001 (p< 0.01), Parasutterella (p< 0.05), and Candidatus Saccharimonas (p< 0.05). IL-6 levels exhibited a significant negative correlation with Rikenella (p< 0.05), Acinetobacter (p< 0.05), Prevotellaceae UCG− 001 (p< 0.05), Lacticaseibacillus (p< 0.01), and Parasutterella (p< 0.05), and a significant positive correlation with Faecalibaculum (p< 0.05), Chryseobacterium (p< 0.01), and A2. Serum TMAO levels showed a significant positive correlation with Faecalibaculum (p< 0.05) and Chryseobacterium (p< 0.01), and hepatic TMAO levels exhibited a significant positive correlation with Chryseobacterium (p< 0.05).Conclusion: SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.Keywords: Diarrhea, Kidney-Yang Deficiency Syndrome, Sishen Pill, CutC, Cecal microbiota, TMAO, Inflammation

Objective To investigate the clinical effect and mechanism of compound azintamide combined with bifidobacteria triple viable capsules in the prevention and treatment of antibiotic-associated diarrhea (AAD) in the elderly. Methods A retrospective analysis was performed for 62 elderly patients with or comorbid with infectious diseases who were admitted to Department of Geriatrics, Taian 88 Hospital, from October 2019 to February 2021 and received intravenous drip of antibiotics, and according to the treatment method, they were divided into observation group with 32 patients (treated with compound azintamide combined with bifidobacteria triple viable capsules) and control group with 30 patients (treated with bifidobacteria triple viable capsules alone). The drugs were used in addition to antibiotics for 14 d. The two groups were compared in terms of the incidence rate of AAD, time to the onset of diarrhea, number of times of diarrhea per day, and duration of diarrhea during treatment, as well as related biochemical parameters before treatment and on day 14 of treatment, including hemoglobin (Hb), plasma albumin (Alb), total protein (TP), and the serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and complement C3 and C4. Results Compared with the control group, the observation group had a significantly lower incidence rate of AAD during treatment (χ2=5.77,P

ObjectiveTo analyze the effects of stachyose on the structural composition and metabolic pathways of gut microbiota in children with diarrhea using metagenomic sequencing technology. MethodsSix stool samples were collected from children with diarrhea admitted to a tertiary hospital from December 2021 to March 2022 using the direct selection method. The samples were inoculated into stachyose medium (STS group) and control medium (Ctrl group) using in vitro simulated fermentation technology. Fecal genomic DNA was extracted, and the effects of stachyose on the composition and diversity of gut microbiota were analyzed through metagenomic sequencing. At the COG and KEGG metabolic function levels, PCoA analysis was performed to determine the contribution of dominant gut microbiota to KEGG functional pathways, and the correlations between metabolites and gut microbiota and KEGG metabolic pathways were analyzed. ResultsAlpha diversity analysis showed that except for the Simpson index (0.29, 0.24, P < 0.05), the differences in the Ace index (143.17, 127.00), Chao index (143.17, 127.00), and Shannon index (1.69, 1.79) between the STS and Ctrl groups were not statistically significant. The relative abundances of Bifidobacterium longum (0.06%), Ruminococcus (0.05%), and Lactobacillus salivarius (0.04%) were higher in the STS group than in the Ctrl group. PCoA analysis at the COG and KEGG metabolic function levels revealed that the differences between the two groups were statistically significant (P < 0.05). The STS group upregulated characteristic metabolic pathways such as purine metabolism, starch and sucrose metabolism, and galactose metabolism while downregulating the characteristic metabolic pathways of the Ctrl group. Compared with the Ctrl group, the increased abundance of microbiota in the STS group showed high contributions to metabolic functions related to KEGG level 3. Spearman's correlation coefficient analysis found close associations between metabolic products of gut microbiota and related gut microbiota and KEGG metabolic pathways. ConclusionStachyose can regulate the structural composition of gut microbiota in children with diarrhea, increase gut microbiota diversity, promote related metabolic functions, and produce more beneficial substances for the human body.

Abstract Introduction Enteral nutrition (EN) is the recommended nutritional support in most critically ill populations. When given by feeding tube, EN may be administered either continuously or intermittently. It is unclear which approach is superior in reducing gastrointestinal complications—such as diarrhea—and meeting nutritional targets. The main objectives of this systematic review and meta-analysis are to (1) determine whether continuous or intermittent enteral nutrition is associated with higher incidence of adverse gastrointestinal outcomes, including diarrhea, and (2) determine which feeding modality is associated with reaching nutritional goals. Methods and analysis This systematic review protocol is reported in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. We will search MEDLINE, Embase, the Cochrane Library, and the World Health Organization (WHO) International Clinical Trials Registry (ICTRP) search portal for studies comparing continuous EN and intermittent EN in critically ill patients with no date or language restrictions. Studies will be screened, selected, and extracted independently and in duplicate. We will assess the risk-of-bias assessment using the Cochrane Collaboration’s Risk of Bias (RoB) 2 tool. The primary outcome will include the incidence of diarrhea; secondary outcomes include other adverse GI outcomes (nausea, vomiting, abdominal pain, and constipation), as well as reaching nutritional goals, and length of ICU and hospital stay and mortality. We will pool data using a random-effects model and assess the certainty of the evidence for each outcome using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Ethics and dissemination Ethics approval is not required for this study as no original data will be collected. We will disseminate results through peer-reviewed publication and conference presentations. Systematic review registration PROSPERO CRD42022330118.

Abstract Background This hospital-based cross-sectional study aims to investigate the epidemiologic and clinical characteristics of rotavirus group A (RVA) infection among children with acute gastroenteritis and to detect the most common G and P genotypes in Egypt. Methods A total of 92 stool samples were collected from children under five who were diagnosed with acute gastroenteritis. RVA in stool samples was identified using ELISA and nested RT-PCR. Common G and P genotypes were identified utilizing multiplex nested RT-PCR assays. Results RVA was detected at a rate of 24% (22 /92) using ELISA and 26.1% (24 /92) using VP6 nested RT-PCR. The ELISA test demonstrated diagnostic sensitivity, specificity, and accuracy of 91.7%, 100%, and 97.8%, respectively. G3 was the most prevalent G type (37.5%), followed by G1 (12.5%), whereas the most commonly detected P type were P[8] (41.7%) and P[6] (8.2%). RVA-positive samples were significantly associated with younger aged children (p = 0.026), and bottle-fed (p = 0.033) children. In addition, RVA-positive samples were more common during cooler seasons (p = 0.0001). Children with rotaviral gastroenteritis had significantly more frequent episodes of diarrhea (10.87 ± 3.63 times/day) and vomiting (8.79 ± 3.57 times/day) per day (p = 0.013 and p = 0.011, respectively). Moreover, they had a more severe Vesikari clinical score (p = 0.049). Conclusion RVA is a prevalent cause of acute gastroenteritis among Egyptian children in our locality. The discovery of various RVA genotypes in the local population, as well as the identification of common G and P untypeable strains, highlights the significance of implementing the rotavirus vaccine in Egyptian national immunization programs accompanied by continuous monitoring of strains.

Abstract Gallibacterium anatis (G. anatis) is an opportunistic pathogen previously associated with deaths in poultry and is also a pathogen that rarely causes human diseases. G. anatis has only been reported twice as the causative agent of a human disease (both in France). Here, we report a 62-year-old male patient with hypertension and type 2 diabetes who suffered from acute watery diarrhea caused by this bacterium which was identified by MALDI-TOF MS and 16 S rRNA sequencing. Despite human diarrhea caused by G.anatis is rare, with the continuous emergence of multidrug-resistant isolates of G. anatis in recent years, this case report will inform clinicians that G. anatis especially drug-resistant G. anatis may be a possible infectious source of human diarrhea in immune-suppressed populations.

Abstract Introduction Metformin is the most prescribed medication for type 2 diabetes mellitus (T2DM); there is a well-established link with the elevated incidence of gastrointestinal (GI) adverse events (AE) limiting its administration or intensification. Objectives The objective of this systematic review and meta-analysis of observational studies was to evaluate the pooled incidence of GI AE related to metformin use in patients with T2DM. Materials and methods PUB MED/CINAHL/Web of Science/Scopus were searched from database inception until 29.07.2024 for observational studies in English describing the frequency of GI AE in patients with T2DM treated with metformin. Random-effects meta-analyses were used to derive effect sizes: event rates. Results From 7019 publications, we identified 211 potentially eligible full-text articles. Ultimately, 21 observational studies were included in the meta-analysis. The prevalence of GI AE was as follows: diarrhea 6.9% (95% CI: 0.038–0.123), bloating 6,2% (95% CI: 0.020–0.177), abdominal pain 5,3% (95% CI: 0.003–0.529), vomiting 2.4% (95%: CI 0.007–0.075), constipation 1.1% (95%: CI 0.001–0.100). The incidence of bloating (coefficient -4.46; p

Abstract Background Diarrheal disease is still the leading cause of morbidity and mortality in children, despite significant progress in diarrhea interventions. Zoonotic transmission is the main cause of the emergence and re-emergence of diseases. Domestic animals are often close to humans, particularly in resource-poor countries. Despite evidence of environmental contamination, there have been limited studies conducted to examine the association between domestic animal exposure and diarrheal disease in low- and middle-income countries (LMIC). Therefore, this systematic review and meta-analysis examines the association between domestic animal exposure and diarrheal disease in children under five years of age in LMIC. Methods The search strategy followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for the reporting of systematic reviews. All appropriate databases were searched to find relevant articles. Research studies were selected for review if they reported an outcome variable that measured diarrhea and exposure variables of any domestic animals. A data extraction form was used to extract information from each study. The quality of the individual articles was assessed using the Joanna Briggs Institute (JBI’s) critical appraisal tools. Publication bias was checked using a funnel plot, Egger’s regression test, and Begg’s test. The heterogeneity of studies was checked using the Galbraith plot and the I-squared test. A sensitivity analysis was conducted, and a meta-analysis was conducted using STATA 17. Results After reviewing 113 articles, 11 articles fulfilled the inclusion criteria hence considered for meta-analysis. The finding of these 11 studies revealed that study participants who had animal exposure had 1.95 higher odds of diarrhea as compared to participants who hadn’t animal exposure (OR: 1.95, 95%CI: 1.25, 2.66). Conclusions and recommendations This study reported that diarrheal disease was associated with study subjects who had domestic animal exposure. Therefore, more comprehensive research is needed on specific behaviors and interventions surrounding animal husbandry that may affect the transmission of pathogens between animals and humans; this would facilitate the design and implementation of measures to reduce animal exposure in the domestic environment.

Abstract 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.

Diarrheas are common risks faced by piglets during the weaning period. This study investigated the alleviating effects of artificial parasin I protein (API) on growth performance and intestinal health of weaned pigs upon enterotoxigenic Escherichia coli (ETEC) challenge. Sixty piglets were randomly divided into five groups and fed a basal diet (CON) or basal diet supplemented with API at 0, 750, and 1500 mg/kg or antibiotics for 5 weeks. On d 15 and 25, piglets were challenged with ETEC K88 except for the CON group. Before the ETEC challenge (d 1–14), dietary API supplementation improved growth performance, and 750 mg API increased (P

Objective: The aim of this study was to determine the prevalence and antibiotic susceptibility patterns of pathogenic Escherichia (E.) coli causing diarrhea and urinary tract infection (UTI) in patients admitted for treatment in selected health care facilities in Odisha, an eastern Indian State. Methods: A total of 189 rectal swabs from patients with diarrhea and 297 urine samples from patients with UTI were collected from selected health care facilities. E. coli isolates were phenotypically confirmed using MacConkey agar, MacConkey sorbitol agar and blood agar along with biochemical tests. These phenotypically confirmed E. coli isolates were investigated genotypically for known pathogenic E. coli via multiplex PCR. Finally, the pathogenic E. coli was subjected to antibiotic sensitivity test. Results: Culture of 189 rectal swabs and 297 urine samples revealed 46 (24.3%) diarrheagenic E. coli (DEC) and 36 (12.1%) uropathogenic E. coli (UPEC). PCR analysis of DEC identified 27 (14.3%) enterotoxigenic E. coli (ETEC), 8 (4.2%) enteropathogenic E. coli, 10 (5.3%) enteroaggregative E. coli and 1 (0.5%) Enterohemorrhagic E. coli (EHEC) in diarrhea patients and 5 (1.7%) ETEC, 7 (2.4%) enteroaggregative E. coli, 11 (3.7%) EHEC O157:H7 and 1 (0.3%) EHEC non-O157:H7 in UTI patients. DEC and UPEC exhibited multidrug resistance with a high rate of resistance to commonly prescribed antibiotics. A high frequency of ETEC causing diarrhea, atypical enteropathogenic E. coli harboring the eae gene was found among children with acute diarrhea, and ETEC (est+) and EHEC O157:H7 were detected in UTI patients along with high antibiotic resistance among DEC and UPEC were important findings. Conclusions: To the best of our knowledge, this is the first study to report the prevalence of DEC and UPEC in patients admitted to hospital in Odisha, India, revealing a high rate of antimicrobial resistance.

Abstract Background Foodborne diseases (FBDs) represent a significant risk to public health, with nearly one in ten people falling ill every year globally. The large incidence of foodborne diseases in African low- and middle-income countries (LMIC) shows the immediate need for action, but there is still far to a robust and efficient outbreak detection system. The detection of outbreak heavily relies on clinical diagnosis, which are often delayed or ignored due to resource limitations and inadequate surveillance systems. Methods In total, 68 samples of non-typhoidal Salmonella isolates from human, animal and environmental sources collected between November 2021 and January 2023 were analyzed using sequencing methods to infer phylogenetic relationships between the samples. A source attribution model using a machine-learning logit-boost that predicted the likely source of infection for 20 cases of human salmonellosis was also run and compared with the results of the cluster detection. Results Three clusters of samples with close relation (SNP difference