Efficacy of a multicomponent binding agent against combined exposure to zearalenone and ochratoxin A in weaned pigs.

Introduction: The study aimed to evaluate the efficacy of a novel multicomponent substance against combined exposure to the mycotoxins zearalenone (ZEN) and ochratoxin A (OTA) in weaned piglets. Methods: In total, 60 piglets at the age of 28 days were equally allocated to four experimental groups (A-D), consisting of eight female and seven male piglets each (15 animals per group, for a total trial duration of 42 days). Animals from group A received typical weaner feed without mycotoxins or the test product [multicomponent mycotoxin detoxifying agent (MMDA)]. Group B animals received the same weaner feed contaminated with 0.992 mg ZEN/kg feed and 0.531 mg OTA/kg feed without the addition of the MMDA. Animals in group C received the same contaminated feed as group B with the addition of 1.5 g MMDA/kg feed, whereas group D received the same feed as group B with the inclusion of 3 g MMDA/kg feed. Clinical signs and performance parameters [body weight (BW), average daily weight gain (ADWG), and feed conversion ratio (FCR)] were evaluated, while mycotoxin residues were also assessed in the liver and kidney tissues. Results: Findings showed improved FCR in the group that received the greatest dose of the test product (3 g MMDA/kg feed) compared to the group that received the lower dose (1.5 g MMDA/kg feed). A few hematological and biochemical parameters were slightly altered, predominantly within normal limits. The residue analysis demonstrated a reduction of OTA in liver samples, a-ZEL in the liver and total tested samples, and a total of ZEN and metabolite contents in all samples of the group that received the greatest MMDA dose in comparison to the group that received the toxins without the addition of the test product. Discussion: Therefore, a positive effect of the MMDA at the greatest dosage regime on reducing bioavailability and tissue deposition of ZEN and OTA, with a particularly positive effect on FCR in weaned pigs, is suggested under concurrent ZEN and OTA exposure in vivo.

Effects of supplemented multicomponent mycotoxin detoxifying agent in laying hens fed aflatoxin B1 and T2-toxin contaminated feeds.

The present study was conducted to determine the ability of multicomponent mycotoxin detoxifying agent (MMDA) in feed to prevent the gastrointestinal absorption of aflatoxin B1 (AFB1) and T2-toxin supplemented via spiked maize. For comparisons, hens were fed with uncontaminated basal diet without or with addition of MMDA at 2 g/kg feed. The trial consisted of 105 laying hens (Lohmann Brown) without obvious signs of disease allocated to 7 treatment groups in 35 pens. Responses were demonstrated on laying performance and health status throughout the 42 d experimental period. The results of laying performance indicated significantly decreased egg mass with increasing mycotoxin (AFB1 and T2-toxin) levels up to the maximum tolerated dosage, however simultaneous presence of MMDA laying performance was slightly modified linearly to increasing application. Dose-dependent pathological changes in liver and kidneys and their relative weights, changes in blood parameters and reduced eggshell weights were observed in the hens fed AFB1 and T2-toxin. The pathological changes in the hens fed with diets containing AFB1 and T2-toxin without MMDA were significantly higher as compared with the control group, but eggshell stability was not affected. The contents of AFB1, T2-toxin and their metabolites in liver and kidney tissues were significantly decreased in the hens supplemented with MMDA at 2 and 3 g/kg in feed. MMDA supplementation significantly reduced the deposition of AFB1, T2-toxin and their metabolites in liver and kidneys at the maximum tolerated dosage (2 and 3 g/kg) indicating specific binding to AFB1 and T2-toxin in the digestive tract as compared to the corresponding diets without MMDA. Exposure of AFB1 and T2-toxin indicated significantly decreased egg mass with increasing mycotoxin levels up to the maximum tolerated dosage because of the significantly reduced egg production. Therefore, in this study, MMDA could reduce negative effects of feeding AFB1 and T-2 to laying hens.

Evaluation of Effectiveness of a Novel Multicomponent Mycotoxins Detoxification Agent in the Presence of AFB1 and T-2 Toxin on Broiler Chicks.

This experimental study was conducted to determine the ability of a novel mycotoxins detoxification agent (MR) at a concentration of 0.2% to reduce the toxicity of aflatoxin B1 (AFB1) or T-2 toxin, alone or in combination, and to examine its effect on performance, pathohistological changes (PH) and the residue of these toxins in the tissues of broiler chicks. A total of 96 broiler chicks were divided into eight equal groups: group C, which served as control (without any additives); group MR, which received the novel detoxification agent (supplemented with 0.2%); group E-I (0.1 mg AFB1/kg of diet); group E-II (0.1 mg AFB1/kg of diet + MR 0.2%); group E-III (0.5 mg T-2 toxin/kg of diet); group E-IV (0.5 mg T-2 toxin/kg of diet + 0.2% MR); group E-V (combination of 0.1 mg AFB1/kg, 0.5 mg T-2 toxin/kg of diet); and group E-VI (combination of 0.1 mg AFB1/kg, 0.5 mg T-2 toxin + 0.2% MR). Results indicate that feeds containing AFB1 and T-2 toxin, alone or in combination, adversely affected the health and performance of poultry. However, the addition of MR to diets containing AFB1 and T-2 toxin singly and in combination exerted a positive effect on body weight, feed intake, weight gain, feed efficiency and microscopic lesions in visceral organs. Residual concentration of AFB1 in liver samples was significantly (p < 0.05) decreased when chicks were fed diets supplemented with 0.2% of MR.

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. METHODS: The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). RESULTS: The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). CONCLUSIONS: The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.

Comparison of multiple mycotoxins in harvested maize samples in three years (2018-2020) in four continents.

This study has examined the pattern of mycotoxin contamination of maize destined for animal feed in different global regions over a period of 3 years (2018-2020) with up to 1000+ samples analysed in each year. Overall, >75% of samples in each of the survey years were contaminated with multiple mycotoxins regardless of the global region (Europe, Africa, Asia, South Americas countries). Using LC-MS/MS, it was possible to quantify the relative contamination present in the samples in each year from the different regions of eight different mycotoxins including aflatoxin B1 (AFB1), ochratoxin A (OTA) deoxynivalenol (DON), fumonisin B1 (FB1) and B2, zearalenone (ZEA), T-2 and HT-2 toxins. The trends in mycotoxin contamination showed that there was a consistent contamination with DON in the 3 sampling years in all four regions. Interestingly, AFB1 contamination was prevalent in all regions in 2018, but more predominant in Europe and in 2019. In contrast, in 2020 it was found to be the major contaminant in Africa only. However, FB1 contamination of maize which was prevalent in Europe in 2018, became more prevalent in Asia and LATAM countries in 2019 and even in African maize in 2020. Comparisons of contamination with different mycotoxins in each of the years globally showed significant differences for AFB1, FB1, DON and ZEA between the different years. These results are discussed in relation to the trends of contamination of maize with mixtures of mycotoxins and the implication for their control in this key commodity used as an important ingredient in animal feed.

Effect of a Mycotoxin Binder (MMDA) on the Growth Performance, Blood and Carcass Characteristics of Broilers Fed Ochratoxin A and T-2 Mycotoxin Contaminated Diets.

The present study was conducted to evaluate the efficacy of the feed additive, a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls, and silymarin, as detoxifiers of 0.5 mg/kg (0.5 ppm) ochratoxin A (OTA) and 1 mg/kg (1 ppm) T-2 toxin on broiler chickens. A total of 240 1-old broiler chickens (Ross 308) were randomly distributed into five different dietary treatments: (1) control (non-contaminated diet); (2) non contaminated diet + 3 g/kg of MMDA; (3) non-contaminated diet + 0.5 mg/kg OTA + 1 mg/kg T-2 toxin; (4) non-contaminated diet + 0.5 mg/kg OTA + 1 mg/kg T-2 toxin + 1 g/kg MMDA; and (5) non-contaminated diet + 0.5 mg/kg OTA + 1 g/kg T-2 toxin + 3 g/kg MMDA. The results showed that, in the starter period, from 1 to 10 days, the presence of OTA and T-2 mycotoxins reduced the consumption of feed and the growth of the broilers, and no effects of the detoxifying product were observed in the productivity of the chickens, at any of the doses tested, compared to the contaminated control (treatment 3). However, in the growing period, the same negative effect of mycotoxins was registered, but a recovery was observed in the consumption of feed and in the weight of the broilers that consumed 3 g/kg of the MMDA mycotoxin binder, reaching similar values to those of chickens fed uncontaminated control diets. The presence of mycotoxins in feed led to a reduction in the concentration of total proteins and albumin in blood compared to controls, and the presence of the detoxifying product partially reversed this effect. The breast yield of the chickens fed with mycotoxins was lower than that of the animals fed with the control feed and was not affected by the presence of the product tested, at 1 or 3 g/kg. The weight of the different organs (liver, gizzard, kidneys, or spleen), the intestinal pH, the histology of the small intestine, and oral lesions were not affected by the experimental treatments. In summary, the productive parameters and some blood and carcass characteristics of broiler chickens were impaired by the dietary presence of OTA and T-2 toxin. The tested product included at 1 or 3 g/kg feed in contaminated diets improved performance and seems to be effective in partly counteracting the deleterious effects of the tested mycotoxins.

Hypertriglyceridemia-induced acute pancreatitis: A prospective, multicenter, international cohort analysis of 716 acute pancreatitis cases.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (<1.7 mmol/l, 1.7-2.19 mmol/l, 2.2-5.59 mmol/l, 5.6-11.29 mmol/l, 11.3-22.59 mmol/l, ≥22.6 mmol/l). RESULTS: Hypertriglyceridemia (≥1.7 mmol/l) presented in 30.6% of the patients and was significantly and dose-dependently associated with younger age and male gender. In 7.7% of AP cases, hypertriglyceridemia was considered as a causative etiological factor (≥11.3 mmol/l); however, 43.6% of these cases were associated with other etiologies (alcohol and biliary). Hypertriglyceridemia was significantly and dose-dependently related to obesity and diabetes. The rates of local complications and organ failure and maximum CRP level were significantly and dose-dependently raised by hypertriglyceridemia. Triglyceride above 11.3 mmol/l was linked to a significantly higher incidence of moderately severe AP and longer hospital stay, whereas triglyceride over 22.6 mmol/l was significantly associated with severe AP as well. CONCLUSION: Hypertriglyceridemia dose-dependently aggravates the severity and related complications of AP. Diagnostic workup for hypertriglyceridemia requires better awareness regardless of the etiology of AP.

Multiple Hits in Acute Pancreatitis: Components of Metabolic Syndrome Synergize Each Other's Deteriorating Effects.

INTRODUCTION: The incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations. METHODS: From 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: 1257 patients (55.7 ± 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33-6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39-8.37)], renal failure [OR: 7.46 (CI: 1.61-34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10-2.07)], renal failure [OR: 6.4 (CI: 1.93-21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26-5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age ± SD: 56.9 ± 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors. CONCLUSION: OB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other's detrimental effect. It is important to search for and follow up on the components of MetS in AP.