Search Results (2,798)

Background: There is a paucity of data on mesenteric lymph node cavitation syndrome (MLNCS), a rare condition associated with coeliac disease (CD), characterized by central necrosis within enlarged mesenteric lymph nodes. The largest case series of MLNCS was completed in 1984, (n = 6) and a poor prognosis was identified. Methods: A case series of all patients was conducted with MLNCS treated at the UK NHS England National Centre for Refractory Coeliac Disease between 2000 and 2023. A further literature review was conducted using PubMed and Google Scholar for patients with MLNCS and coeliac disease until 2023. Results: In total, there were 51 patients (6 from our case series and 45 from the literature review); 57% were female, and the mean age was 52.8 years (SD: 14.01 years). The most common presenting symptoms were weight loss (80%) and diarrhea (65%), and patients often had hyposplenism (80%). Persistent villous atrophy was present in 88% of the patients. Ten patients also had Refractory Coeliac Disease. Most of the patients (90%) were on a GFD, but the effect of this is unclear. Treatment with steroids and immunosuppressants resulted in a 40% survival rate. The overall mortality was 43%, associated with cachexia, sepsis, infectious complications, and lymphoma. Conclusions: MLNCS has a poor prognosis, and its diagnosis should prompt further intervention and careful follow-up. Patients commonly present with weight loss and hyposplenism should prompt further investigation. Current treatment options are inadequate and novel therapies are required. Full article

Two species of trichomonads, Tetratrichomonas buttreyi and Pentatrichomonas hominis, are common intestinal parasites that can impact animal health and productivity. Severe infection by these parasites can lead to diarrhea and wasting in affected animals. Notably, P. hominis is known to cause diarrhea and has the potential to be transmitted between animals and humans. Donkeys hold significant economic importance in China’s agricultural sector. However, whether donkeys are infected with T. buttreyi and P. hominis remains unknown globally. To address this gap in knowledge, 815 fecal samples were collected from donkeys in three representative regions in Shanxi Province, North China. Then, the presence and genetic characteristics of T. buttreyi and P. hominis were examined using species-specific PCR primers amplifying the small subunit ribosomal RNA genes. The overall prevalence was detected to be 25.4% (207/815) for T. buttreyi and 0.7% (6/815) for P. hominis in donkeys in Shanxi Province. All obtained P. hominis sequences were identified as genotype CC1. Genetic analysis revealed that all P. hominis isolates from donkeys were clustered into the same branch with isolates detected in humans, suggesting possible zoonotic transmission. This study is the first to report the occurrence and prevalence of T. buttreyi and P. hominis in donkeys globally. These findings expand the host range of trichomonads and improve our understanding of their genetic diversity and zoonotic potential, providing essential baseline data for the prevention and control of these parasites in donkeys in the region. Full article

This study investigated the effects of incorporating fermented feed into the post-weaning piglet diet, with a focus on its impact on the growth, health, serum markers, immune function, diarrhea rate, and microbial community of post-weaning piglets. Forty-two post-weaning piglets (Duroc × [Landrace × Yorkshire], castrated male), with good health and similar weight (11.40 ± 1.36 kg) at 40 days of age, were randomly assigned to two groups. Throughout the trial, one group received a standard diet (control group) while the other one was given a diet supplemented with fermented feed (experimental group), respectively. The findings revealed that compared to the control group, the post-weaning piglets fed with fermented feed showed increased daily weight gain. The fermented feed also led to an increase in the height of villi in the duodenum or jejunum of post-weaning piglets (p < 0.05), accompanied by an improved ratio of villus height to crypt depth in the experimental group (p < 0.05). Furthermore, the fermented feed enhanced the richness and diversity of the intestinal microbial community in post-weaning piglets (p < 0.05), particularly increasing the relative abundance of Lactobacillaceae and Bifidobacteriaceae. These findings demonstrate that incorporating the fermented feed into the diet can reduce the diarrhea rate, improve growth performance, enhance immune function, and promote intestinal development in post-weaning piglets. Full article

Diarrhea serves as a vital health indicator for assessing wildlife populations post-reintroduction. Upon release into the wild, wild animals undergo adaptation to diverse habitats and dietary patterns. While such changes prompt adaptive responses in the fecal microbiota, they also render these animals susceptible to gastrointestinal diseases, particularly diarrhea. This study investigates variations in fecal microorganisms and hormone levels between diarrhea-afflicted and healthy Przewalski’s horses. The results demonstrate a significant reduction in the alpha diversity of the fecal bacterial community among diarrheal Przewalski’s horses, accompanied by notable alterations in taxonomic composition. Firmicutes, Proteobacteria, and Bacteroidetes emerge as dominant phyla across all fecal samples, irrespective of health status. However, discernible differences in fecal bacterial abundance are observed between healthy and diarrhea-stricken individuals at the genus level, specifically, a diminished relative abundance of Pseudobutyrivibrio is observed. The majority of the bacteria that facilitate the synthesis of short-chain fatty acids, Christensenellaceae_R_7_group (Christensenellaceae), NK4A214_group (Ruminococcus), Lachnospiraceae_XPB1014_group (Lachnospiraceae), [Eubacterium]_coprostanoligenes_group (Eubacterium), Rikenellaceae_RC9_gut_group, Lachnospiraceae_AC2044_group (Lachnospiraceae), and Prevotellaceae_UcG_001 (Prevotella) are noted in diarrhea-affected Przewalski’s horses, while Erysipelotrichaceae, Phoenicibacter, Candidatus_Saccharimonas (Salmonella), and Mogibacterium are present in significantly increased amounts. Moreover, levels of immunoglobulin IgA and cortisol are significantly elevated in the diarrhea group compared with the non-diarrhea group. Overall, this study underscores substantial shifts in fecal bacterial diversity, abundance, and hormone levels in Przewalski’s horses during episodes of diarrhea. Full article

Diarrheal disease continues to be a major cause of global morbidity and mortality among children under 5 years of age. To address the current issues associated with oral attenuated rotavirus vaccines, the study of parenteral rotavirus vaccines has promising prospects. In our previous study, we reported that rotavirus nonstructural protein 4 (NSP4) did not increase the IgG antibody titer of co-immune antigen but did have a protective effect against diarrhea via the intramuscular injection method. Here, we explored whether NSP4 can exert adjuvant effects on mucosal immune pathways. In this study, we immunized mice via muscle and nasal routes, gavaged them with the rotavirus Wa strain or the rotavirus SA11 strain, and then tested the protective effects of immune sera against both viruses. The results revealed that the serum-specific VP8* IgG antibody titers of the mice immunized via the nasal route were much lower than those of the mice immunized by intramuscular injection, and the specific IgA antibodies were almost undetectable in the bronchoalveolar lavage fluid (BALF). NSP4 did not increase the titer of specific VP8* antibodies in either immune pathway. Therefore, in the two vaccines (PP-NSP4-VP8* and PP-VP8*+NSP4) used in this study, NSP4 was unable to perform its potential adjuvant role through the mucosal immune pathway. Instead, NSP4 was used as a co-immunized antigen to stimulate the mice to produce specific binding antibodies that play a protective role against diarrhea. Full article

For nearly twenty years, gnotobiotic (Gn) pigs have been used as a model of human norovirus (HuNoV) infection and disease. Unique in their ability to develop diarrhea and shed virus post oral challenge, Gn pigs have since been used to evaluate the infectivity of several genogroup II HuNoV strains. Nearly all major pandemic GII.4 variants have been tested in Gn pigs, with varying rates of infectivity. Some induce an asymptomatic state despite being shed in large quantities in stool, and others induce high incidence of both diarrhea and virus shedding. Non-GII.4 strains, including GII.12 and GII.6, have also been evaluated in Gn pigs. Again, rates of diarrhea and virus shedding tend to vary between studies. Several factors may influence these findings, including age, dosage, biological host factors, or bacterial presence. The impact of these factors is nuanced and requires further evaluation to elucidate the exact mechanisms behind increases or decreases in infection rates. Regardless, the value of Gn pig models in HuNoV research cannot be understated, and the model will surely continue to contribute to the field in years to come. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field. Full article

The pathogens responsible for porcine viral diarrhea are diverse, causing significant economic losses to the pig industry. PEDV and TGEV are well-known pathogens causing diarrheal diseases in pigs, leading to significant economic losses in the breeding industry. In contrast, the newly identified diarrhea virus, PKV, has not garnered as much attention. However, co-infection of PKV with PEDV results in more severe symptoms in piglets, such as acute gastroenteritis, and promotes increased replication of PEDV. Rapid and accurate diagnosis of viral diarrhea is essential for farms to identify pathogens early and mitigate economic losses. This study describes the development of a triplex real-time fluorescent quantitative RT-qPCR technique that can simultaneously detect three RNA viruses associated with porcine viral diarrhea: PEDV, TGEV, and PKV. To establish the triplex RT-qPCR method for the simultaneous detection and identification of the above three diarrhea viruses, conserved regions of the M gene of TGEV, the N gene of PEDV, and the 3D gene of PKV were selected to design specific primers and probes. After optimizing the reaction conditions, the method’s specificity, sensitivity, and reproducibility were evaluated. The triplex RT-qPCR method did not show a significant difference in PCR efficiency compared to the single RT-qPCR method. The method is specific to TGEV, PKV, and PEDV, exhibits no cross-reactivity with other pathogens, and demonstrates satisfactory sensitivity and reproducibility; the limit of detection (LOD) of PEDV, TGEV, and PKV is 11.42 copies/μL. Furthermore, the performance of the triplex RT-qPCR assay was compared with the Chinese standard single-assay method for detecting TGEV, PKV, and PEDV, showing complete consistency between the two methods (100% compliant). Subsequently, 1502 clinical diarrhea samples were collected from the Guangxi Zhuang Autonomous Region to investigate the local prevalence of TGEV, PKV, and PEDV and the positive rates were 16.38% (246/1502), 1.46% (22/1502), and 45.14% (678/1502), respectively. Co-infection of PEDV and PKV were most common, with a rate of 12.12% (182/1502). This study presents a valuable method for the rapid and simultaneous identification of PEDV, TGEV, and PKV in clinical animal farming practices, and provides a reassessment of the epidemiology of these diarrhea-causing viral pathogens in the Guangxi Zhuang Autonomous Region. Full article

Shiga toxin-producing E. coli (STEC) are considered important zoonotic pathogens of great economic significance, associated with diarrhea, hemolytic uremic syndrome (HUS), hemorrhagic colitis (HC), and death in humans. This study aimed to investigate the distribution of various STEC virulence gene markers and antimicrobial susceptibility (AST) profiles associated within E. coli isolates from the recto-anal mucosal swabs (RAMSs) of slaughtered cattle and buffaloes in Islamabad, Pakistan. The RAMSs (n = 200) were analyzed using multiplex PCR for the presence of stx1, stx2, eae, and ehxA genes. Samples that were positive for one or more of the virulence genes were inoculated with Sorbitol MacConkey agar (SMAC) for isolation of STEC. The isolates were further analyzed for the presence of virulence genes using multiplex PCR. Of the 200 RAMS, 118 (59%) were positive for one or more virulence genes. E. coli isolates (n = 18) with one or more virulence genes were recovered from the 118 positive samples. The DNA of the isolates positive for one or more virulent genes was extracted and subjected to whole genome sequencing using Illumina. Analysis of the WGS data indicated that the E. coli isolates could be differentiated into 11 serotypes. Most E. coli isolates (13/18; 72.2%) carried five genes (stx1, stx2, Iha, iss, and IpfA) in various combinations. In addition to these five genes, other virulence genes identified in these isolates were espI, ireA, espP, exhA, epeA, mcmA, mch, ast, celB, eilA, katP, and capU. The AST was performed using the Kirby–Bauer disk diffusion test. The study indicated that all the isolates were resistant to rifampicin and a significant proportion of the isolates were MDR. A wide range of antimicrobial resistance genes (ARGs) were detected among the isolates, reflecting the complex nature of resistance mechanisms. The study results indicate that cattle and buffaloes slaughtered in Islamabad might be the carriers of antimicrobial resistant STEC of zoonotic significance, thus representing a source of human infection. Full article

This study aimed to assess the effects of substituting zinc oxide with terminalia chebula extract (TCE) on growth performance, antioxidant capacity, immune function, and intestinal health in weaned pigs. Initially, 72 weaned Duroc × Landrace × Large White piglets, 28 days old with an initial weight of 7.43 ± 0.14 kg, equally divided by gender, were randomly assigned into three groups, with six replicates and four piglets per replicate. They were fed a basal diet (CON group), a diet containing 2 g/kg zinc oxide (ZnO group), or 2 g/kg TCE (TCE group) for a duration of 28 days. Subsequently, to further confirm the most appropriate levels of TCE in piglets, 96 piglets of the same breeds and age, with an initial weight of 7.42 ± 0.12 kg, also equally divided by gender, were randomly assigned into four groups, each with six replicates and four piglets per replicate, and fed a basal diet (CON group), or diets supplemented with 1 g/kg TCE (LTCE group), 2 g/kg TCE (MTCE group), or 4 g/kg TCE (HTCE group) for a duration of 28 days. The results demonstrated that both TCE and ZnO reduced diarrhea rates (p = 0.001) and enhanced average daily gain (ADG) (p = 0.014) compared to the control group. TCE at 1 g/kg and 4 g/kg reduced the feed to gain ratio (p = 0.050). Dietary supplementing with TCE and ZnO increased serum total antioxidant capacity (T-AOC) (p = 0.020). Various doses of TCE also increased jejunal IgA (p = 0.000) levels and IL-10 expression (p = 0.004), and decreased the levels of TNF-α in both serum (p = 0.043) and jejunal mucosa (p = 0.000). Notably, TCE reduced the crypt depth (CD) of the duodenal (p = 0.007) and increased the villus height (VH) of the ileal (p = 0.045), and with increased dosage, there was a rise in the villus height to crypt depth ratio (VH:CD) in the duodenum (p = 0.000) and jejunum (p = 0.001). Higher abundances of Lactobacillaceae (p = 0.000) and lower levels of Streptococcaceae (p = 0.000) and Peptostreptococcaceae (p = 0.035) in cecal contents were fed the ZnO and TCE pigs compared with CON pigs. Therefore, TCE was firstly presented as being able to replace zinc oxide, improve intestinal morphology, and enhance antioxidant and immune functions, thus safeguarding intestinal mucosal health and promoting piglet growth. Full article

Immune checkpoint inhibitors (ICIs) activate T cells, causing immune-related adverse events (irAEs). Skin manifestations are common among irAEs, but ICI-associated bullous pemphigoid (BP) is rare. Inhibiting programmed death (PD)-1 signaling, in addition to causing epitope spreading, may disrupt B and T cell balance, causing excessive autoantibody production against the skin’s basement membrane, leading to BP. A 70-year-old woman developed late-onset multi-organ irAEs, including diarrhea, thyroid dysfunction, and BP, while receiving pembrolizumab, a PD-1 inhibitor. This highlights the long-term risk of irAEs, which can occur 2–3 years after starting ICIs. In cases of multi-organ irAE, C-reactive protein levels and neutrophil/lymphocyte ratio are often low. These characteristics were observed in our case. Few papers address multiple organ involvement, highlighting the need to consider irAEs in a multi-organ context. While it is known that drug-induced skin reactions worsen as blood eosinophil counts increase, in our case, the eosinophil count remained normal, suggesting that ICI-associated BP might have been controlled without discontinuing the ICI and through tapering of low-dose oral prednisone treatment. Additionally, in this case, significant CD4-positive T cell infiltration was observed in the immunostaining examination of the blisters, indicating that severe CD4-positive T cell infiltration induced by the ICI might have led to multi-organ involvement, including severe diarrhea. Few reports focus on blood eosinophil counts in BP cases or discuss CD4 and CD8 immunostaining in BP cases. Therefore, future research should explore the relationship between blood eosinophil counts, immunostaining results, and the prognosis of irAEs, including BP, in treatment courses. Full article

Porcine epidemic diarrhea virus (PEDV) has caused significant economic losses to the pig farming industry in various countries for a long time. Currently, there are no highly effective preventive or control measures available. Research into the pathogenic mechanism of PEDV has shown that it primarily causes infection by binding the S protein to the CD13 (APN) receptor on the membrane of porcine intestinal epithelial cells. The S1 region contains three neutralization epitopes and multiple receptor-binding domains, which are closely related to viral antigenicity and ad-sorption invasion. Nanobodies are a type of single-domain antibody that have been discovered in recent years. They can be expressed on a large scale through prokaryotic expression systems, which makes them cost-effective, stable, and less immunogenic. This study used a phage display library of nanobodies against the PEDV S1 protein. After three rounds of selection and enrichment, the DNA sequence of the highly specific nanobody S1Nb1 was successfully obtained. To obtain soluble nanobody S1Nb1, its DNA sequence was inserted into the vector Pcold and a solubility-enhancing SUMO tag was added. The resulting recombinant vector, Pcold-SUMO-S1Nb1, was then transformed into E. coli BL21(DE3) to determine the optimal expression conditions for the nanobody. Following purification using Ni-column affinity chromatography, Western blot analysis confirmed the successful purification of S1Nb1 carrying the solubility-enhancing tag. ELISA results demonstrated a strong affinity between the S1Nb1 nanobody and PEDV S1 protein. Full article

Grain processing produces many by-products, including wheat bran, wheat germ and rice bran, which are rich in carbohydrates, proteins and trace elements. In this study, these grain-derived by-products were used as raw materials to conduct solid-state fermentation using mixed strains of Aspergillus kawachii and Rhizopus oryzae, and the potential immunomodulatory and anti-allergic properties of fermented product were evaluated. Solid-state fermentation of a grain by-product mixture, consisting of rice bran, wheat bran, and wheat germ in a 2:1:1 weight ratio, using both A. kawachii L1 and R. oryzae L1 at 26 °C for 5 days, significantly increased the total phenolic, flavonoid, and amino acid contents. The anti-allergic activity of aqueous extract of the fermented product was evaluated in murine models of food allergy and delayed-type hypersensitivity. Oral administration of the fermented product extract (100–200 mg/kg) notably alleviated allergic symptoms such as diarrhea and histopathological changes in the intestines. Moreover, the extract effectively reduced allergen-specific serum antibodies, suppressed splenic cytokine secretion, and mitigated tissue edema and inflammation induced by allergens. Importantly, the extract induced the production of IL-10 and TGF-β, which are well-known cytokines primarily secreted by regulatory T cells. These results underscore the promising immunomodulatory effects of A. kawachii and R. oryzae fermented grain product, suggesting their potential as functional foods or additives for managing allergic disorders, with implications for future therapeutic and dietary applications. Full article

Porcine sapelovirus (PSV) is a new pathogen that negatively impacts the pig industry in China. Affected pigs experience severe diarrhea and even death. Vaccination is used to control disease outbreaks, and sensitive diagnostic methods that can distinguish infected animals from vaccinated animals (DIVA) are essential for monitoring the effectiveness of disease control programs. Tests based on the detection of the nonstructural protein (NSP) 3AB are reliable indicators of viral replication in infected and vaccinated animals. In this study, the recombinant PSV 3AB protein was expressed by a prokaryotic expression system, and an indirect ELISA method was established. Serum samples from healthy animals, immunized animals, and infected animals were evaluated. The ELISA method identified 3AB with high sensitivity (99.78%) and specificity (100.0%), and no cross-reaction was observed with serum antibodies against porcine reproductive and respiratory syndrome virus (PRRSV), infection with classical swine fever virus (CSFV), pseudorabies virus (PRV), bovine viral diarrhea virus (BVDV), porcine epidemic diarrhea virus (PEDV), or foot-and-mouth disease virus (FMDV). The ELISA method described here can effectively distinguish infected and vaccinated animals and is an important inexpensive tool for monitoring serum and controlling PSV. Full article

Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m²), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. Full article