A microbial muramidase improves growth performance and reduces inflammatory cell infiltration in the intestine of broilers chickens under Eimeria and Clostridium perfringens challenge.

The objective of the present studies was to evaluate muramidase (MUR) supplementation in broilers under Eimeria and/or Clostridium perfringens challenge. For this, 2 experiments were conducted. Experiment 1. A total of 256 one-day old male Cobb 500 chicks were placed in battery cages in a completely randomized design, with 5 treatment groups, 7 replicate cages per treatment and 8 birds per cage. The treatments were: nonchallenged control (NC), challenged control (CC), CC + MUR at 25,000 or 35,000 LSU(F)/kg, and CC + Enramycin at 10 ppm (positive control-PC). Challenge consisted of 15× the recommended dose of coccidiosis vaccine at placement, and Clostridium perfringens (108 CFU/bird) inoculation at 10, 11, and 12 d. Macro and microscopic evaluation, immunohistochemistry, and gene expression were evaluated at 7, 14, 21, and 28 d of age. Experiment 2. A total of 1,120 one-day old male Cobb 500 chicks were placed in floor pens with fresh litter in a completely randomized design, with 4 treatment groups, 8 replicate pens per treatment, and 35 birds per pen. The treatments were: Control, supplementation of MUR at 25,000 or 45,000 LSU(F)/kg, and a positive control (basal diet plus Enramycin). At 10, 11, and 12 d of the experiment all the birds were inoculated by oral gavage with a fresh broth culture of a field isolate Clostridium perfringens (0.5 mL containing 106 CFU/bird). It was observed that in Experiment 1 MUR supplementation reduced the infiltration of macrophages and CD8+ lymphocytes in the liver and ileum of infected birds, downregulated IL-8 and upregulated IL-10 expression. In Experiment 2, MUR linearly improved the growth performance of the birds, increased breast meat yield, and improved absorption capacity. MUR supplementation elicited an anti-inflammatory response in birds undergoing a NE challenge model that may explain the improved growth performance of supplemented birds.

Effect of microbial muramidase supplementation in diets formulated with different fiber profiles for broiler chickens raised under various coccidiosis management programs.

The objective of the present study was to determine the effects of muramidase (MUR) supplemented to diets formulated with different fiber sources (inert or fermentable) on the growth performance and intestinal parameters of broiler chickens raised under different coccidiosis management programs. A total of 2,208 male Ross 308 broilers were housed in 96 floor pens and distributed into a 2 × 3 × 2 factorial arrangement in a completely randomized block design with 2 sources of fiber (inert or fermentable fiber), 3 coccidiosis management programs (none, vaccine, or Salinomycin), and with or without supplementation of MUR at 35,000 LSU(F)/kg of diet. Body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were calculated for each feeding phase (d 0-14, d 14-28, d 28-36) and from d 0 to 36. On d 17 and d 31, samples were taken to analyze several parameters. The experimental data were analyzed with 3-way ANOVA considering the main effect of fiber source, coccidiosis program, inclusion of MUR, and their interactions using JMP 16.2. 16S rDNA sequencing of the ileal and cecal content was carried out to analyze the diversity, composition, and predictive function of the microbiota. From d 0 to 36, BWG increased (P = 0.05) by 2.5% in birds supplemented with Salinomycin (P = 0.04), and by 2.2% with MUR supplementation (P = 0.02). Salinomycin and MUR improved FCR (P < 0.0001) when compared to nonsupplemented birds. The supplementation of MUR, regardless of the coccidiosis management program, reduced the intestinal viscosity (P = 0.03). On d 31, the highest blood concentration of carotenoids was observed in chickens fed diets supplemented with Salinomycin. MUR led to significant changes in the diversity, composition, and predictive function of the ileal microbiota, mainly on d 31. The results observed herein further explain the positive effects of MUR on the growth performance of broiler chickens.

A meta-analysis of the effect of Eimeria spp. and/or Clostridium perfringens infection on the microbiota of broiler chickens.

Coccidiosis in chickens is caused by Eimeria spp. The infection provides a growth advantage to Clostridium perfringens (CP), frequently leading to necrotic enteritis. One approach to alleviate the negative impacts of the diseases is to improve the bacterial composition in chickens, and many experiments investigating chicken enteric health in recent years include the characterization of the bacterial microbiota. This meta-analysis synthesized the data of studies investigating the intestinal microbiota after infection with coccidia and/or CP to provide a basis for future research. Inclusion criteria were that experiments contained a group infected with one or both pathogens and an uninfected control group, the use of 16SrRNA Illumina sequencing and the availability of raw data. A total of 17 studies could be included. Meta-analyses of 3 different data sets were performed: 1 on data of 9 experiments on chickens infected with coccidia only; the second on data of 4 studies on chickens infected with CP only; the third on raw data of 8 experiments with chickens infected with coccidia and CP. The meta-analysis of relative abundance and alpha diversity of the data sets was performed in R using the SIAMCAT and metafor packages. The number of families of interest identified by the analyses of experiments with infection with coccidia only, CP only and the combined infection were 23, 2, and 29, respectively. There was an overlap of 13 families identified by analyses of experiments with infection with coccidia only and of experiments with the combined infections. Machine learning was not able to find a model to predict changes of the microbiota in either 1 of the 3 analyses. Meta-analyses of functional profiles showed a more uniform reaction to the infections with the relative abundance of many pathways significantly altered. Alpha diversity was not affected by infection with either pathogen or the combination. In conclusion, the heterogeneity of these microbiota studies makes recognizing common trends difficult, although it seems that coccidia infection affects the microbiota more than an infection with CP. Future studies should focus on the bacterial functions that are changed due to these infections using metagenome techniques.

Microbiome modulation by a precision biotic in broilers chickens: a commercial study validation.

Precision biotics (PBs) are chemically synthesized complex glycans that modulate specific microbiome metabolic functions. The objective of the present study was to evaluate the effect of the supplementation of PB on the growth performance, and cecal microbiome modulation of broiler chickens raised under commercial conditions. A total of 190,000-day-old Ross 308 straight-run broilers were randomly assigned to 2 dietary treatments. There were 5 houses per treatment with 19,000 birds per house. In each house, there were 6 rows of battery cages with 3 tiers. The 2 dietary treatments included a control diet (a commercial broiler diet) and a PB supplemented diet at 0.9 kg/MT. On a weekly basis, 380 birds were randomly selected for body weight (BW) determination. At 42 d of age, the BW and feed intake (FI) of each house were recorded, the feed conversion ratio (cFCR) was calculated and corrected with the final BW, and the European production index (EPI) was calculated. Additionally, 8 birds per house (40 birds/experimental group) were randomly selected to collect cecal content for microbiome analysis. The supplementation of PB significantly improved (P < 0.05) the BW of the birds at 7, 14, and 21 d and numerically improved the BW of the birds by 64 and 70 g at 28 and 35 d of age, respectively. At 42 d, the PB numerically improved BW by 52 g, and significantly improved (P < 0.05) the cFCR by 2.2 points and the EPI by 13 points. The functional profile analysis showed a clear and significant difference in the cecal microbiome metabolism between control vs. PB supplemented birds. A higher abundance of pathways was modulated by PB which were associated with amino acid fermentation and putrefaction, particularly from lysine, arginine, proline, histidine, and tryptophane which led to a significant increase (P = 0.0025) in the Microbiome Protein Metabolism Index (MPMI) compared to nonsupplemented birds. In conclusion, the supplementation of PB efficiently modulated pathways related to protein fermentation and putrefaction, resulting in higher MPMI and improved growth performance of broilers.

Microbiome modulation, microbiome protein metabolism index, and growth performance of broilers supplemented with a precision biotic.

The objectives of the present studies were to evaluate: 1) the in vivo impact of the supplementation with a precision biotic (PB) on the growth performance and microbiome modulation of broiler chickens; 2) the role of PB on the modulation of functional pathways of the microbiome collected from animals with low and high body weight gain, and 3) to develop a Microbiome Protein Metabolism Index (MPMI) derived from gut metagenomic data to link microbial protein metabolism with performance. The in vivo work consisted of 2 experiments with 2 treatments: Control vs. PB at 1.1 kg/MT of PB with 21 or 14 replicates of 40 birds per replicate, in experiments 1 and 2, respectively. Growth performance was evaluated in both experiments, and from experiment 1, cecal samples from one bird/replicate was collected on d 21 and 42 (n = 21/treatment) to evaluate the microbiome through whole genome sequencing. In the ex vivo assay, 6 cecal samples were collected from low body weight (BW) birds (at 10% below average), and 6 samples from high BW birds (at least 10% above average). The samples were incubated in the presence or absence of PB. After incubation, DNA was isolated to develop a functional genomic assay and the supernatant was separated to measure short-chain fatty acid (SCFA) production. The MPMI is the sum of beneficial genes in the pathways related to protein metabolism. In the in vivo grow out experiments, it was observed that the supplementation improved the BW gain by 3% in both studies, and the corrected feed conversion ratio (cFCR) by 3.7 and 3.4% in studies 1 and 2, respectively (P < 0.05). The functional microbiome analysis revealed that the PB shifted the microbiome pathways toward a beneficial increase in protein utilization, as shown by higher MPMI. In the ex vivo experiment, the PB increased the abundance of genes related to the beneficial metabolism of protein (quantitative MPMI), and the concentration of SCFA, regardless of the underline BW of the birds. Taken together, the microbiome metabolic shift observed in the in vivo study and higher MPMI, plus the observations from the ex vivo assay with higher SFCA production, may explain the improvement in growth performance obtained with the supplementation of PB.

Clinical Significance and Outcome in Patients with Asymptomatic Versus Symptomatic Subsegmental Pulmonary Embolism.

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37-9.74), DVT (HR: 0.53; 95% CI: 0.03-2.80), or major bleeding (HR: 0.85; 95% CI: 0.21-2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25-2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20-4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92-4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.

Effects of a microbial muramidase on the growth performance, intestinal permeability, nutrient digestibility, and welfare of broiler chickens.

The objective of these studies was to evaluate the inclusion of a microbial muramidase (MUR) in the diets of broiler chickens on the growth performance, intestinal permeability (IP), total blood carotenoid content, apparent ileal digestibility (AID), and foot pad dermatitis (FPD). In Experiment 1, a total of 1,000 one-day-old chicks were placed in floor-pens with reused litter, and randomly distributed into 4 treatments with 10 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 15,000; 25,000 or 35,000 LSU (F)/kg of MUR. Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were evaluated at d 21 and 43. Intestinal permeability was evaluated on d 35 by FITC-d, and FPD and AID on d 43. In Experiment 2, a total of 800 one-day-old chicks were placed in floor-pens with fresh litter, and randomly distributed into 4 treatments with 8 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 25,000 or 35,000 LSU (F)/kg of MUR, and a fourth group where the basal diet was supplemented with enramycin. The birds were induced to a mild intestinal challenge. Feed intake, BWG, and FCR were evaluated on d 21 and d 42, and total blood concentration of carotenoids was evaluated on d 28. In experiment 1, 35,000 LSU (F)/kg of MUR promoted the best FCR (P < 0.05). Muramidase supplementation linearly increased the AID of dry matter, ash, and fat (P < 0.01), and regardless of the dose, MUR decreased the IP (P < 0.05). In Experiment 2, the supplementation of 35,000 LSU (F)/kg of MUR improved BWG and FCR in the entire cycle (1-42 d) and increased the concentration of carotenoids in the blood on d 28 compared to the control group (P < 0.05). These studies show that MUR improves growth performance of broilers by improving intestinal permeability, digestibility of dry matter, ash and fat, absorption of carotenoids, and reducing FPD.

Safety and Efficacy of Rivaroxaban as Extended-Phase Anticoagulation in Patients with Cancer and Venous Thromboembolism: A Preliminary Data Analysis from the Mac Project.

Extended-phase anticoagulation with direct oral Xa inhibitors (OAXI) is suggested in patients with cancer-associated venous thromboembolism (CAT). We report on patients enrolled in the MAC (Monitoring AntiCoagulants) Project, given rivaroxaban as extended-phase anticoagulation after CAT. The primary efficacy outcome was the incidence of symptomatic recurrent VTE; the primary safety outcomes were incidence of major and non-major clinically relevant bleeding, adverse events, and all-cause mortality. The mean patients' follow-up was 19 months (SD 16); 64/604 (11%) had CAT. Recurrent VTE occurred in 9.3% and in 8.1% of patients with and without CAT (OR 1.2, 95% CI 0.5 to 2.9; p = 0.6). Major bleeding occurred in 4.7% and in 2.6%, respectively (OR = 1.8, 95% CI 0.5 to 6.6, p = 0.4), and non-major clinically-relevant bleeding in 4.7% and in 4.1% (OR = 1.2, 95% CI 0.3 to 3.9, p = 0.7). The relative figures for fatal haemorrhage and all-cause death were 1.6% versus 0%, and 1.6% versus 0.4%. Rivaroxaban appears to be effective and safe as extended-phase anticoagulation in patients with CAT. The mean treatment period was 3-times the standard 6-month course.

Evaluation of a Novel Precision Biotic on Enterohepatic Health Markers and Growth Performance of Broiler Chickens under Enteric Challenge.

This study evaluated the supplementation of a precision biotic (PB) on the enterohepatic health markers and growth performance of broiler chickens undergoing an enteric challenge. In the first study, three treatments were used: Unchallenged Control (UC); Challenged Control (CC; dietary challenge and 10× dose of coccidia vaccine); and a challenged group supplemented with PB (1.3 kg/ton). In the second study, three treatments were used: control diet, diet supplemented with Avilamycin (10 ppm), and a diet supplemented with PB (0.9 kg/ton). All the birds were exposed to natural challenge composed by dietary formulation and reused litter from a coccidiosis positive flock. In Trial 1, PB decreased ileal histological damage, increased villi length, and the expression of SLC5A8 in ileal tissue versus CC; it reduced ileal expression of IL-1ß compared to both UC and CC treatments. PB increased the expression of cell cycling gene markers CCNA2 and CDK2 in the ileum compared to CC. In Trial 2, PB improved the growth performance, intestinal lesion scores and intestinal morphology of broiler chickens. These results indicate that birds supplemented with PB are more resilient to enteric challenges, probably by its action in modulating microbiome metabolic pathways related to nitrogen metabolism and protein utilization.

Safety and Efficacy of Rivaroxaban for Extended-Phase Anticoagulation of Patients with Unprovoked or Recurrent Venous Thromboembolism: Real-Life Data from the MAC Project.

Venous thromboembolism (VTE) is a major cause of death in the world. After the acute-phase treatment, the optimal duration of anticoagulation is still debatable. The latest guidelines suggest maintaining long-term anticoagulation in patients with cancer-associated thrombosis (CAT) or with unprovoked VTE and a low bleeding risk. Methods: The MAC Project is an ongoing prospective-cohort, multi-center, observational study in Italy. The project aims to collect real-life clinical information in unselected patients given oral anticoagulants for VTE over a 5-year follow-up period. There were no exclusion criteria, except for life expectancy <6 months and refusal to sign the informed consent form or to attend the planned follow-up visit. All patients were followed-up prospectively with clinical controls scheduled at 3, 6, and 12 months after the index event, and then annually for up to 5 years. The primary efficacy and safety outcomes were symptomatic recurrent VTE and major bleeding. Results: We analyzed 450 consecutive patients treated with rivaroxaban and referred them to the MAC Project database for unprovoked or recurrent VTE. Of these, 267 (55%) were unprovoked VTE, and 377 (87%) were symptomatic. We followed up with the patients for a mean of 22 months (Q1 10.7; Q3 37.4 months). Recurrent VTE occurred in 12 patients on rivaroxaban treatment (IR 1.7 per 100 person-years). Males had more recurrence than women. During the follow-up period, we recorded 13 (2.9%) major bleeding, 12 (2.7%) clinically relevant non-major bleeding, 8 minor bleeding, and no fatal bleeding events. Overall, bleeding events occurred in 33 (7.3%) patients, most occurring within the first 2 years of treatment. In addition, we observed a statistically significant higher incidence of bleeding in patients with a baseline HAS-BLED score of 3 to 4 compared with those with a score of 0 to 2, with most events occurring during the first 3 months of treatment (RR 5.9). Discussion: Rivaroxaban appears to be safe and effective for the long-term treatment of patients with recurrent or unprovoked VTE. Our results match previously published data, and we are confident that the continuation of the follow-up for up to 5 years will confirm these outcomes.

Laboratory "In-vitro" Evaluation of the Parallel Stent Graft Association for the Iliac Sandwich Technique.

OBJECTIVES: The Iliac Sandwich is an off-label technique that uses parallel stent grafts to treat aortoiliac aneurysms. The purpose of this experimental study is to evaluate the conformability and juxtaposition of stent grafts combinations used in this technique through in-vitro mechanical evaluation, computed tomography (CT) analyses, and a controlled pulsatile flow system. METHODS: The combinations of two Viabahn® ("V-V") or Viabahn® and Excluder® iliac extension ("V-E") were analysed using CT imaging with measurement of the gutter area by two independent analysts before and after balloon angioplasty. In a second phase, the parallel stent combinations were also evaluated using CT imaging after being implanted in the aortic aneurysm model with a pulsatile flow system with controlled temperature, viscosity, and density. RESULTS: The "V-E" group had a better conformability when compared to the "V-V" group, ensuring smaller gutter areas (0.0064 cm2 ± 0.01 vs. 0.0228 cm2 ± 0.03, p < 0.001). Post dilatation with two non-compliant balloons resulted in enlargement of the gutter area (Area A, p 0.065; Area B, p 0.071). Conversely, post dilatation with a non-compliant balloon for the internal iliac component and a compliant balloon for the external iliac device reduced the gutter area (Area A, p 0.008; Area B, p 0.010). CONCLUSION: The combination of Viabahn® and Excluder® iliac extension device ("V-E") had a smaller gutter area compared to two Viabahn® parallel stents for the Iliac Sandwich Technique. Post dilatation using a non-compliant balloon for the internal iliac device and a compliant balloon for the external iliac provided superior conformability and juxtaposition.

Evaluation of a Precision Biotic on the Growth Performance, Welfare Indicators, Ammonia Output, and Litter Quality of Broiler Chickens.

A dietary glycan-based precision biotic (Glycan PB) was evaluated on the performance, welfare indicators, and litter characteristics of broiler chickens. In Trial 1, the main effects of Glycan PB dose (0, 250 and 500 g/metric ton (MT)) and xylanase supplementation (0 or 100 g/MT) were tested, as was their interaction. In Trial 2, pens located inside a commercial house were used to test the effect of Glycan PB supplementation (500 g/MT) versus a control diet. In Trial 1, Glycan PB supplementation at 250 and 500 g/MT improved feed conversion ratio (FCR) by 7 and 11 points when compared to diets without Glycan PB (p < 0.001). At 35 d, Glycan PB reduced the pH and ammonia concentration in diets with xylanase. In Trial 1, the supplementation with 500 g of Glycan PB/MT of feed reduced litter scores (p < 0.05). In both trials, 500 g of Glycan PB/MT of feed increased the proportions of birds without footpad lesions (Trial 1: 72.2% vs. 82.7%; p < 0.001; Trial 2: 14 to 27.3% (p = 0.05) or gait defects (Trial 1: 96.1% vs. 98.4%; p < 0.001) and decreased the proportion of birds with footpad lesions (Trial 2: 86% vs. 72.7%; p = 0.05).

Potential Replacements for Antibiotic Growth Promoters in Poultry: Interactions at the Gut Level and Their Impact on Host Immunity.

The chicken gastrointestinal tract (GIT) has a complex, biodiverse microbial community of ~ 9 million bacterial genes plus archaea and fungi that links the host diet to its health. This microbial population contributes to host physiology through metabolite signaling while also providing local and systemic nutrients to multiple organ systems. In a homeostatic state, the host-microbial interaction is symbiotic; however, physiological issues are associated with dysregulated microbiota. Manipulating the microbiota is a therapeutic option, and the concept of adding beneficial bacteria to the intestine has led to probiotic and prebiotic development. The gut microbiome is readily changeable by diet, antibiotics, pathogenic infections, and host- and environmental-dependent events. The intestine performs key roles of nutrient absorption, tolerance of beneficial microbiota, yet responding to undesirable microbes or microbial products and preventing translocation to sterile body compartments. During homeostasis, the immune system is actively preventing or modulating the response to known or innocuous antigens. Manipulating the microbiota through nutrition, modulating host immunity, preventing pathogen colonization, or improving intestinal barrier function has led to novel methods to prevent disease, but also resulted in improved body weight, feed conversion, and carcass yield in poultry. This review highlights the importance of adding different feed additives to the diets of poultry in order to manipulate and enhance health and productivity of flocks.

Protected Organic Acid and Essential Oils for Broilers Raised Under Field Conditions: Intestinal Health Biomarkers and Cecal Microbiota.

The objective of the present study was to evaluate the effect of protected organic acids (OA) and essential oils (EO) [P(OA + EO)] on the intestinal health of broiler chickens raised under field conditions. The study was conducted on four commercial farms. Each farm consisted of four barns, two barns under a control diet and two tested barns supplemented with P(OA + EO), totaling 16 barns [8 control and 8 under P(OA + EO)]. The control group was supplemented with antibiotic growth promoters [AGP; Bacitracin Methylene Disalicylate (50 g/ton) during starter, grower and finisher 1, and flavomycin (2 g/ton) during finisher 2]. The tested group was supplemented with 636, 636, 454, and 454 g/ton of P(OA + EO) during starter, grower, finisher 1 and 2, respectively. Eighty birds were necropsied (40/treatment; 20/farm; and 5/barn) to collect blood, jejunal tissue, and cecal contents. The data were submitted to analysis of variance (ANOVA) (P < 0.05) or Kruskal-Wallis' test and the frequency of antimicrobial resistant (AMR) genes was analyzed by Chi-Square test (P < 0.05). It was observed that the supplementation of P(OA + EO) reduced (P < 0.05) the histopathology scores, such as the infiltration of inflammatory cells in the epithelium and lamina propria and tended (P = 0.09) to reduce the serum concentration of calprotectin (CALP). The supplementation of P(OA + EO) reduced the serum concentration of IL-12 (P = 0.0001), IL-16 (P = 0.001), and Pentraxin-3 (P = 0.04). Additionally, P(OA + EO) maintained a cecal microbiota similar to birds receiving AGP. The substitution of AGP by P(OA + EO) reduced (P < 0.05) the frequency of four AMR genes, related to gentamicin (three genes), and aminoglycoside (one gene). Overall, the inclusion of P(OA + EO), and removal of AGP, in the diets of commercially raised broiler chickens beneficially changed the phenotype of the jejunum as shown by the lowered ISI scores which characterizes an improved intestinal health. Furthermore, P(OA + EO) significantly reduced the serum concentration of several inflammatory biomarkers, while maintaining the diversity and composition of the cecal microbiota similar to AGP fed chickens and reducing the prevalence of AMR genes.

Classic and Non-Classic Effects of the Duration of Supplementation of 25-Hydroxicholecalciferol in Broiler Chicken Diets.

The present study aimed to determine the effect of different times of supplementation of 25-hydroxycholecalciferol (25(OH)D3) in broiler chickens on the performance, carcass and cuts yield, bone resistance, plasma concentration of 25(OH)D3, and expression of the mTOR gene. The treatments were a control diet (CD) supplemented with 3000 IU vitamin D3/kg of feed from 1 to 46 d, or the CD + 2760 IU (69 mcg) of 25(OH)D3/kg of feed from 1 to 21 d, from 1 to 35 d, or from 1 to 46 d. The period of supplementation of 25(OH)D3 did not affect the growth performance of broilers, but the breast meat yield was linearly increased in response to increasing days of supplementation (p < 0.05). Birds supplemented with 25(OH)D3 at the time of the analysis showed an increase (p < 0.05) in the plasma concentration of 25(OH)D3 when compared to non-supplemented birds. The mTOR gene expression (p < 0.05), and breast protein deposition (p < 0.05) presented a quadratic response related to the supplementation period of 25(OH)D3. The fat content of the breast linearly decreased (p < 0.05) as the period of supplementation was extended. The results also showed a positive linear correlation between mTOR expression and 25(OH)D3 plasma levels (r = 0.593; p < 0.05).

Use of 1,470 nm laser for treatment of superficial venous insufficiency.

BACKGROUND: There are several ways to treat varicose veins of the lower limbs, among which use of 1470nm diode lasers stands out. This technique can be used to treat patients in outpatient settings, with early return to work, good esthetic results, and low rates of complications. However, variables such as the laser wavelength, the power administered in each area, the type of fiber, and the linear intravenous energy density (LEED) are still extensively discussed. OBJECTIVES: To analyze the results of superficial venous insufficiency treatment with a 1470nm diode laser. METHODS: Retrospective study conducted at a private clinic in a private hospital in Florianopolis, based on a database collected prospectively. The sample comprised 287 patients who underwent surgery to treat superficial venous insufficiency with 1470nm diode laser, from January 2016 to December 2018, totaling 358 great saphenous veins (GSVs) and 84 small saphenous veins (SSVs) treated. RESULTS: The total occlusion rates after 12 months of surgery were 94.4% in the GSVs, with an average LEED of 45.90 J/cm, and 96.4% in the SSVs, with an average LEED of 44.07 J/cm. CONCLUSIONS: During the follow-up period, the 1470nm diode laser proved to be a safe treatment, with great efficacy and low rates of complications (pain, edema, bruising, deep vein thrombosis, and endothermal heat-induced thrombosis - EHIT).

Novel Models for Chronic Intestinal Inflammation in Chickens: Intestinal Inflammation Pattern and Biomarkers.

For poultry producers, chronic low-grade intestinal inflammation has a negative impact on productivity by impairing nutrient absorption and allocation of nutrients for growth. Understanding the triggers of chronic intestinal inflammation and developing a non-invasive measurement is crucial to managing gut health in poultry. In this study, we developed two novel models of low-grade chronic intestinal inflammation in broiler chickens: a chemical model using dextran sodium sulfate (DSS) and a dietary model using a high non-starch polysaccharide diet (NSP). Further, we evaluated the potential of several proteins as biomarkers of gut inflammation. For these experiments, the chemical induction of inflammation consisted of two 5-day cycles of oral gavage of either 0.25mg DSS/ml or 0.35mg DSS/ml; whereas the NSP diet (30% rice bran) was fed throughout the experiment. At four times (14, 22, 28 and 36-d post-hatch), necropsies were performed to collect intestinal samples for histology, and feces and serum for biomarkers quantification. Neither DSS nor NSP treatments affected feed intake or livability. NSP-fed birds exhibited intestinal inflammation through 14-d, which stabilized by 36-d. On the other hand, the cyclic DSS-treatment produced inflammation throughout the entire experimental period. Histological examination of the intestine revealed that the inflammation induced by both models exhibited similar spatial and temporal patterns with the duodenum and jejunum affected early (at 14-d) whereas the ileum was compromised by 28-d. Calprotectin (CALP) was the only serum protein found to be increased due to inflammation. However, fecal CALP and Lipocalin-2 (LCN-2) concentrations were significantly greater in the induced inflammation groups at 28-d. This experiment demonstrated for the first time, two in vivo models of chronic gut inflammation in chickens, a DSS and a nutritional NSP protocols. Based on these models we observed that intestinal inflammation begins in the upper segments of small intestine and moved to the lower region over time. In the searching for a fecal biomarker for intestinal inflammation, LCN-2 showed promising results. More importantly, calprotectin has a great potential as a novel biomarker for poultry measured both in serum and feces.

Influence of Enzyme Supplementation in the Diets of Broiler Chickens Formulated with Different Corn Hybrids Dried at Various Temperatures.

We evaluated the influence of enzymatic supplementation on the growth performance and cecal microbiota of broilers. A total of 2160 1-day-old male chicks were used in a 3 × 2 × 2 factorial arrangement (three corn hybrids, two drying temperatures -80 and 110 °C, with or without the inclusion of an enzymatic blend (amylase, xylanase, and protease) (20 birds/pen, n = 9). For all performance and digestibility parameters, we observed, in general, isolated effects of the corn hybrids and drying temperature. Birds that received the enzymatic blend in the diet showed better weight gain from 1 to 21 days (d) and better digestibility coefficients of nutrients at 42 d. Birds fed diets with corn dried at 80 °C showed a better feed conversion ratio from 1 to 42 d. At 21 d of age, enzymatic supplementation had positive effects on jejunum morphology. Enzyme supplementation increased the abundance of the phylum Tenericutes, class Bacilli and Mollicutes, reduced Clostridia, and increased the abundances of the families Lactobacillaceae, Anaeroplasmataceae, and O_RF39;F. In conclusion, the addition of amylase, xylanase, and protease led to a better nutrient digestibility, performance, and intestinal morphology. In addition, enzyme supplementation changed the diversity, composition, and predicted function of the cecal microbiota at d 21.

Different enzymatic associations in diets of broiler chickens formulated with corn dried at various temperatures.

The effect of supplementation of different enzymatic associations in the feed of broiler chickens formulated with corn dried at 80°C or 110°C on growth performance and carcass yield was evaluated. In addition, the influence of the different enzymatic associations on the cecal microbiota was studied. One-day-old male broiler chicks (1,320) were distributed in a completely randomized design in a 2 × 5 factorial arrangement (6 replicates; 22 birds/replicate). The treatments were 2 corn drying temperatures (80°C and 110°C) and 5 diets. The diets consisted of a positive control (PC), a negative control (NC) with a reduction of 100 kcal/kg of apparent metabolizable energy, and 3 enzyme combinations added to the NC diet: amylase, amylase + xylanase, and amylase + xylanase + protease. The feed conversion ratio (FCR) from 1 to 7 d of chickens fed diets formulated with corn dried at 80°C was better (P = 0.045) than that of chickens fed diets dried at 110°C. Regardless of the enzymatic association, the supplementation improved body weight gain (P = 0.01) of the NC group to the same level as the PC group. The FCR of the NC was similar to that of the PC only when the 3 enzymes were included from 1 to 21 d (P = 0.001) and regardless of the enzymatic association for the period from 1 to 42 d (P = 0.007). Regarding cecal microbiota, the alpha diversity was similar among the groups (P > 0.05). The beta-diversity analysis showed that the microbiota of the birds receiving the combination of the 3 enzymes was similar to that of birds fed the PC diet (P = 0.18; R = 0.074), with a similar effect observed for the predicted metabolic functions (Linear discriminant analysis effect size). In conclusion, chickens fed diets formulated with corn dried at 80°C had better FCR during the prestarter phase. The enzymatic supplementation improved the FCR of the birds, which may partially be explained by the modulation of the cecal microbiota.

Management of isolated distal deep-vein thrombosis with direct oral anticoagulants in the RIETE registry.

Isolated distal deep-vein thrombosis (DVT, infra-popliteal DVT without pulmonary embolism) is a common presentation of venous thromboembolism (VTE), but was an exclusion criterion from the pivotal trials that validated the use of direct oral anticoagulants (DOACs) for VTE management. Using data from the international RIETE registry, we analyzed and compared trends in DOACs prescription between January 2011 and June 2019 in patients with distal vs. proximal DVT. We also assessed DOACs' prescriptions and compared the outcomes (VTE recurrence, bleeding and death) of distal DVT patients treated with DOACs vs. those on vitamin K antagonists (VKAs). 2308 patients with distal DVT and 11,364 patients with proximal DVT were included in the current analysis. DOACs were more frequently prescribed in patients with distal than proximal DVT (25% vs. 16%, p < 0.001). DOACs use increased sharply during the observation period (P < 0.001 for trend). In 2018, 56% of patients with distal DVT received DOACs. Distal DVT patients treated with rivaroxaban or edoxaban received the dose recommended for VTE management in most (> 85%) cases. Patients treated with apixaban were older, more likely to have underlying conditions than patients treated with rivaroxaban and, in most cases (> 75%), did not receive the recommended 1-week loading dose for acute VTE management. Outcomes between distal DVT patients treated with VKAs or DOACs appeared to be similar. In patients with distal DVT, DOACs have become the most common anticoagulant regimen. Specific trials are needed to determine the optimal DOACs dose regimen for treatment of distal DVT.