Mesoglycan for the secondary prevention of superficial vein thrombosis: a randomized, controlled, double-blind study (METRO Study)-rationale and protocol.

No data is available about pharmacological secondary prevention of superficial vein thrombosis (SVT) despite 10-15% of patients develop venous thromboembolic complications at 3-6 months after an adequate treatment of the acute phase. To verify efficacy and safety of mesoglycan in secondary prevention of SVT recurrence and venous thromboembolic complications. Phase III multicenter, double-blind, randomized, superiority trial comparing mesoglycan 50 mg bid vs placebo in consecutive patients with a SVT extended at least 5 cm, after the initial 45-day treatment course with fondaparinux 2.5 mg once-daily. Primary efficacy outcome: SVT recurrence/extension, symptomatic venous thromboembolism (VTE), asymptomatic proximal deep-vein thrombosis, death. Primary safety outcome: major bleeding. We hypothesized a 12-month 15% incidence of the primary efficacy outcome in placebo group and a 50% risk reduction in mesoglycan group. A bilateral log-rank test with a sample of 650 patients (randomization 1:1) reach a 90% power, with an α-error of 0.025, of detecting a 7.0% difference (HR = 0.51) after 12 months of treatment, considering a 10% patients drop-out. At deadline (December 31, 2022) 570 patients have been randomized (10% drop rate). Mean age was 63.9 years, 58.8% were women. SVT involved great saphenous vein in 69.3%, small saphenous vein in 13.1%, and collaterals in 17.6% of patients. SVT was the first event in 61.7%, a recurrence in 38.3%, provoked in 50.2% and unprovoked in 49.8%. Patients not experiencing a primary outcome, or not retiring their consent will be followed up to December 31, 2024 when the final data analysis will be performedClinicalTrials.gov: NCT03428711.

Distillers dried grains with soluble and enzyme inclusion in the diet effects broilers performance, intestinal health, and microbiota composition.

This study tested the effect of distillers dried grains with soluble (DDGS) inclusion in a broiler diet, with or without supplementation of exogenous enzymes, on the microbiota composition, intestinal health, diet digestibility and performance. A total of 288 one-day-old chickens was assigned to 6 treatments (8 replicate of 6 birds each) according to a completely randomized design with a 3 × 2 factorial scheme with 3 DDGS levels (0, 7 and 14%) and 2 inclusions of exogenous enzymes (with or without a multicarbohydrase complex + phytase [MCPC]). The results exhibited that DDGS inclusion up to 14% did not impair broilers performance up to 28 d, however, DDGS-fed animals exhibited significant improvement with the MCPC supplementation. No effects of the enzymes in the ileal digestibility were found at 21 d. DDGS inclusion in the diet affected dry matter and gross energy digestibility. Broilers fed diets with MCPC were found to have less intestinal histological alteration thus better gut health. No effect of DDGS, enzyme or interaction of those were observed for intestinal permeability and in the serum inflammatory biomarker (calprotectin) at 7 and 28 d. The increase of DDGS percentage in the diet reduced the diversity of the ileal microbiota but increased the cecal microbiota diversity. The inclusion of DDGS showed positive effects on microbiota composition due to a reduction of Proteobacteria phylum in the ileum at 28d and a reduction in the presence of Enterococcaceae family in the ileum at 14 and 28d. The inclusion of MCPC complex might promote beneficial changes in the ileal and cecal microbiota due reduce of Proteobacteria, Bacillaceae and Enterobacteriaceae. The supplementation of xylanase, ß-glucanase, arabinofuranosidase and phytase to a DDGS diet improves performance and intestinal health allowing the use of these subproduct in the poultry nutrition.

Novel model for chronic intestinal inflammation in chickens: (2) Immunologic mechanism behind the inflammatory response.

Intestinal inflammation in poultry is a complex response that involves immune and intestinal cells which is still not fully understood. Thus, to better understand the mechanisms that drive the chronic intestinal inflammation in fowl we conducted an experiment applying a previously established nutritional model of low-grade chronic intestinal inflammation to evaluate cytokine and chemokine profiles in the chicken intestine. For this, we placed 90 one-day chickens into two treatments: (1) a control group (CNT) fed a corn-soybean diet, and (2) a group fed a diet high in non-starch polysaccharides (NSP). At days 14, 22, 28 and 36 of age, 6 birds from each treatment were euthanized, jejunal and ileal samples were collected for histological examination and cytokine measurements. The cytokines interferon-alpha (IFN-α), IFN-γ, interleukin-16 (IL-16), IL-10, IL-21, IL-6, macrophage-colony stimulating factor (M-CSF), chemokine C-C motif ligand 20 (CCL20), CCL4, CCL5 and vascular endothelial growth factor (VEGF) were quantified in the intestinal tissue. Histologically, both jejunum and ileum of broilers fed NSP diet showed marked infiltration of mononuclear immune cells into the villi. Further, these birds exhibited a significant (P < 0.05) increase in CCL20 concentration in the jejunum at 14d, but a dramatic reduction of M-CSF at 14 and 21d. Later at 28d and 36d, birds fed the NSP diet exhibited increased IL-16 concentration in the jejunum. Since M-CSF is a monocyte stimulatory cytokine and CCL20 a chemokine of T-cells, the reduced M-CSF and increased production of CCL20 may indicate the involvement of the adaptive immune response, specifically driven by T-cells, occurring around the third week of age in the NSP model. Lastly, as a result of the mononuclear cell infiltration and activation of T-cells, IL-16, a pro-inflammatory T-cell cytokine, increased. Therefore, the current work indicates the importance of adaptive immune cells, especially T-cells, in the chronic intestinal inflammation in broiler chicken.

Evaluation of sodium butyrate and nutrient concentration for broiler chickens.

The relation between nutrition and intestinal health is a subject with an increasing interest in research, as nutritionists need knowledge about how formulation affects different parameters in the gastrointestinal tract (GIT). That is why 4 trials were conducted to evaluate the effect of nutrient concentration and a feed additive (sodium butyrate protected with sodium salts of palm fatty acid distillates (PSB, Gustor N'RGY produced by Norel S.A., Spain, dosed at 1 kg/t), on performance, diet digestibility, intestinal morphology, volatile fatty acid concentration (VFA) in the GIT and intestinal microbiota of broiler chickens, when fed diets with different energy and amino acids concentration. Control diets, C, with the recommended metabolizable energy (ME) and ideal amino acid (AA) composition; Reduction 1, R1, C - 60 kcal ME and - 2.3% AA and Reduction 2, R2, C - 120 kcal ME and - 4.6% AA) based on different feed ingredients (Corn Soy [CS] and Wheat Barley Soy (WBS) were formulated. All trials lasted 42 d. In trials 2 and 4, the nutrient dilution decreased performance of the animals. In all trials, PSB improved animal performance (growth or FCR), despite the different situations. In trials 1 and 4, animals receiving R1 diets and PSB showed similar performance to those receiving C diets without PSB. PSB improved Gross Energy metabolizability (69.94 vs. 72.55; P: 0.02). Nutrient concentration affected histology results in T2 (ileum) and T3 (jejunum); PSB showed effects in T2 (jejunum, ileum) and in T3 (jejunum). In T1, PSB affected VFA in duodenum, jejunum, and ileum, changing the profile depending on diet nutrient concentration. PSB altered microbiology in caecum of animals in T2. It can be concluded that the dilution of ME and AA concentration of the diet impairs animal performance, influences intestinal microbiota and affects intestinal histology. PSB improves animal performance, increases gross energy metabolizability, steers intestinal microbiota and alters VFA concentrations in the intestine. The addition of PSB may help the animal to counteract the negative effects of diluted diets.

A protected complex of biofactors and antioxidants improved growth performance and modulated the immunometabolic phenotype of broiler chickens undergoing early life stress.

We evaluated the supplementation of a protected complex of biofactors and antioxidants [P(BF+AOx)] on growth performance, antioxidant activity, expression of immune-related genes, and immunometabolic phenotype of broilers submitted to early life stressors. The treatments were a nutritionally complete basal diet supplemented or not with P(BF+AOx) (Jefo Nutrition Inc., Saint-Hyacinthe, QC, Canada) from 1 to 14 d of age. 720 one-day old male Ross 308 chickens were placed into pens of 30 birds (12 replicates/treatment). Birds were double-vaccinated against infectious bronchitis (IB; MILDVAC-Ma5T) at the hatchery and submitted, on d 3, to an acute reduction on environmental temperature (from 32° C to 20°C) for 48 h. Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were calculated weekly. On d 7 and 15, samples were collected for expression of immune-related genes and kinome array analysis, and serum to evaluate the antioxidant status. Data were analyzed by ANOVA using SAS (SAS 9.4). From d 1 to 21 and d 1 to 28, the dietary supplementation of P(BF+AOx) significantly increased BWG (P < 0.05) by 3.6 and 3.8%, respectively, and improved FCR (P < 0.05) by 1.2 and 1.8%, respectively. From d 1 to 35, dietary supplementation enhanced BWG (P = 0.03) by 4%. Serum glutathione reductase activity on d 15 was higher in birds fed diets supplemented with P(BF+AOx) compared to the control diet-fed birds (P = 0.04). Dietary supplementation reduced the expression of IL-1ß (P = 0.03) in the lungs on d 7. On d 15, dietary supplementation increased the expression of IL-6 (P = 0.02) and IL-10 (P = 0.03) in the liver. It was observed that, via decreased phosphorylation, catalase was activated in the jejunum and liver, and the phosphorylation of immunoregulatory or proinflammatory proteins was decreased. Other important cellular signaling pathways were also changed in the liver and jejunum due to the supplementation. The supplementation of P(BF+AOx) improves growth performance by promoting a general anti-inflammatory and antioxidant response in chickens undergoing early life stress.

The impact of deoxynivalenol, fumonisins, and their combination on performance, nutrient, and energy digestibility in broiler chickens.

This study evaluated the effects of the mycotoxins deoxynivalenol (DON), fumonisins (FUM), and their combination on growth performance, nutrient, and energy digestibility in broilers. A total of 960 Cobb-Cobb male broilers were obtained on the day of hatch and placed 10 birds per cage with 8 cages per treatment. The experiment consisted of 12 treatments: control; DON 1.5 mg/kg; DON 5.0 mg/kg; FUM 20.0 mg/kg; DON 1.5 mg/kg + FUM 20.0 mg/kg; and DON 5.0 mg/kg + FUM 20 mg/kg. The remaining dietary treatments were the correlative nitrogen-free diets (NFD) for determining the endogenous nutrients loss. All birds were fed with a corn-soybean meal diet from days 1 to 15, until birds from latter 6 treatments were switched to their correlative NFD diet from days 15 to 21. Feed and BW were weighed by cage on days 8, 15, and 21. On day 21, ileal digesta was collected for digestibility determination. Both DON 1.5 mg/kg + FUM 20 mg/kg and DON 5.0 mg/kg + FUM 20 mg/kg treatments showed reduced feed intake (P ≤ 0.05) from days 8 to 15 and days 15 to 21. However, no significant effects were noted for BW gain or mortality-adjusted feed conversion ratio after adding single or combined mycotoxin on days 8 and 15. At day 21, cumulative BW gain was less (P ≤ 0.05) in birds fed with the mycotoxin combination diets than the control. No significant changes were shown for ileal endogenous amino acids losses. Control treatment had significantly higher (P ≤ 0.05) apparent ileal energy digestibility than the DON 5.0 mg/kg + FUM 20.0 mg/kg treatment (3,126 vs. 2,895 kcal/kg), representing a 5%-unit loss in apparent DM digestibility. No significant difference was found for standardized crude protein and amino acid digestibility. In conclusion, the combination of DON and FUM (DON 1.5 mg/kg + FUM 20 mg/kg or DON 5.0 mg/kg + FUM 20 mg/kg) reduced DM and ileal energy digestibility, which negatively affected BW gain in broilers.

Can dietary zinc diminish the impact of necrotic enteritis on growth performance of broiler chickens by modulating the intestinal immune-system and microbiota?

The objective of this study was to compare the effects of inorganic and proteinate Zn in chickens challenged with coccidia and Clostridium perfringens. A 3 × 2 factorial design was used, with 3 dietary formulations (0 or 90 mg/kg supplemental Zn from ZnSO4 or Zn proteinate, with or without challenge). On day 14, challenged birds were orally gavaged with approx. 5,000 Eimeria maxima sporulated oocysts, and on day 19 to 21 with C. perfringens (108 CFU/D). Productive performance was assessed at day 21 and 28. At 21 D, necrotic enteritis (NE) lesion severity, intestinal permeability, gene expression, and ileal and cecal microbiota were evaluated. An interaction of Zn source by challenge was observed for lesion score and mortality, wherein Zn supplementation decreased the degree of NE lesions (P = 0.02) and mortality due to NE (P = 0.008). In the jejunum, an interaction of Zn source by challenge was observed for the expression of IL-8 (P = 0.001) and INF-γ (P = 0.03), wherein the NE challenge upregulated their expression, but not in the Zn proteinate supplemented birds. Zn proteinate supplementation downregulated iNOS vs. ZnSO4 supplemented birds (P = 0.0003), and supplemental Zn downregulated TLR-2 (P = 0.05) and ZnT5 (P = 0.04), regardless of the source. In the ileal microbiota, Zn proteinate supplementation decreased the frequency of Lactobacillus (P = 0.01), and the challenge increased Enterobacteriaceae (P = 0.01). Dietary Zn decreased NE lesion severity and mortality due to NE; Zn proteinate led to lower expression of IL-8 and INF-γ in challenged birds which may be an indicative of a lessened inflammatory response.

Effect of different challenge models to induce necrotic enteritis on the growth performance and intestinal microbiota of broiler chickens.

The objective of this study was to evaluate performance, diversity, composition, and predicted function of the intestinal microbiota of broilers raised under 3 different methods to induce necrotic enteritis (NE). The chicks in Experiments 1 and 2 were vaccinated against coccidiosis on day 1. Experiment 1: non-challenged and challenged birds were raised in floor pens with new litter and 58 birds/pen. The challenge consisted of Eimeria maxima inoculation on day 14 and Clostridium perfringens via water on days 18 to 19. Cecal microbiota was evaluated on days 18, 21, and 28. Experiment 2: non-challenged and challenged birds were raised in floor pens with recycled litter and 50 birds/pen. The challenge consisted of C. perfringens via feed from days 18 to 20. Ileal and cecal microbiota were evaluated on day 21. In Experiment 3, non-challenged and challenged birds were raised in battery cages with 8 birds/cage. Challenged birds were inoculated with E. maxima on day 14 and with C. perfringens on days 19 to 21. In the 3 experiments, ileal or cecal microbiota or both were analyzed through 16S rRNA sequencing. The performance of the birds was impaired in the 3 studies, regardless of the method used to induce NE. In Experiment 1, the microbiota did not significantly change across ages. In Experiment 2, α-diversity indices were lower in challenged vs. non-challenged birds in both ileal and cecal microbiota. The cecal microbiota composition and function was more affected than the ileal microbiota. In Experiment 3, Chao index (α-diversity) increased in challenged vs. non-challenged birds, and the composition of the ileal and cecal microbiota was not significantly affected. In conclusion, the overall feed conversion ratio was more affected in Experiment 3 (5.2, 11.1, and 30% for Experiments 1, 2, and 3, respectively), which also showed the highest degree of NE lesions. However, the largest variations of diversity and composition of the microbiota were observed in Experiment 2, when birds were raised in floor pens with reused litter, vaccinated against coccidiosis, and challenged with C. perfringens on days 19 to 21.

Zinc source modulates intestinal inflammation and intestinal integrity of broiler chickens challenged with coccidia and Clostridium perfringens.

Two dietary sources of zinc (ZnSO4 or organic Zn) were tested in chickens challenged with coccidiosis (Co) or coccidiosis plus Clostridium perfringens (CoCPF). On day 14, the chickens were orally gavaged with ∼5,000 Eimeria maxima sporulated oocysts. On day 19, 20, and 21 chickens challenged with C. perfringens were given a broth culture containing 108 cfu of this bacterium. Productive performance parameters were determined at d 14, 21, and 28. On day 21, necrotic enteritis (NE) lesions were scored, and intestinal permeability was evaluated. Jejunum and cecal tonsils were collected for morphology and gene expression analysis. On day 21, organic Zn improved BW gain by 18.6% (P = 0.07), and FCR by 12% (P = 0.09) in CoCPF challenged chickens vs. birds fed ZnSO4. From 1 to 28, organic Zn increased BW gain (P = 0.02), and improved FCR (P = 0.03) vs. birds fed ZnSO4. At 21 d, NE lesions were only observed in CoCPF birds (P < 0.001), and mortality due to NE was only observed when CoCPF birds were fed ZnSO4 (P = 0.001). Organic Zn fed birds had increased villus height in the jejunum (P = 0.005) and decreased intestinal permeability (P = 0.01) vs. ZnSO4. In the jejunum, organic Zn fed birds showed a downregulation of expression of IL-8 (P = 0.02), and upregulation of IL-10 (P = 0.05) in CoCPF birds vs. ZnSO4- CoCPF birds. As main effect, birds supplemented with organic Zn had higher mRNA expression of TLR-2 (P = 0.02) and IgA (P = 0.01). In the cecal tonsils, organic Zn fed birds showed upregulation of iNOS (P = 0.008) in CoCPF birds vs. ZnSO4-CoCPF birds. Organic Zn supplementation reduced intestinal permeability and attenuated intestinal inflammation of broilers co-challenged with coccidia and C. perfringens.

Zinc source influences the gene expression of zinc transporters in jejunum and cecal tonsils during broiler challenge with Eimeria maxima and Clostridium perfringens.

The objective of this experiment was to study the effects of dietary zinc (Zn) source on gene expression of Zn transporters (metallothionein [MT], ZIP 3, 5, 8, 9, 10, 11, 13, and 14, and ZnT 1, 4, 5, 6, 7, 9, and 10) in the jejunum and cecal tonsils of broilers challenged with coccidia or coccidia plus Clostridium perfringens. A 2 × 2 factorial design was used with 2 Zn sources (90 mg Zn/kg from either ZnSO4 or an organic Zn, Bioplex® Zn) and challenged with approximately 5,000 oocysts of Eimeria maxima at 14 d of age with or without C. perfringens (108 CFU/bird) at 18, 19, and 20 d of age (8 pens per treatment and 8 birds per pen) after which 1 bird/pen was sampled at 21 d of age. In the jejunum, co-infection resulted in higher ZnT 5 and 6 gene expression, while organic Zn fed birds had lower ZIP 5 and 11, and higher ZnT1. Additionally, an interaction of challenge by Zn source was noted wherein ZnT10 was unaffected by the C. perfringens in the organic Zn treatment but was 2.7-fold lower in the co-infected ZnSO4 fed birds. S100A9 gene expression, a biomarker of inflammatory response in necrotic enteritis, increased 2 and 2.8-fold in the cecal tonsils and jejunum with the co-infection, respectively. Supplementation with organic Zn lowered S100A9 by 1.9 and 4.4-fold in the cecal tonsils and jejunum, respectively, when birds were supplemented with ZnSO4. Notably, MT, ZIP 3, 8, 9, 10, 13, or 14, and ZnT 4, 7, and 9 were unaffected by Zn source and/or method of challenge. An interaction of challenge by Zn source was also noted for serum Zn concentration, which was reduced when birds were challenged with C. perfringens and fed ZnSO4 but no difference between challenge method when birds were fed organic Zn. Based on the expression of ZnT and ZIP genes, more Zn trafficking due to treatment occured in the jejunum than cecal tonsils, but further studies are needed to ascertain how Zn source regulates intracellular free Zn concentrations and whole-body Zn status during an enteric challenge.

Comparison between McMaster and Mini-FLOTAC methods for the enumeration of Eimeria maxima oocysts in poultry excreta.

Monitoring Eimeria shedding has become more important due to the recent restrictions to the use of antibiotics within the poultry industry. Therefore, there is a need for the implementation of more precise and accurate quantitative diagnostic techniques. The objective of this study was to compare the precision and accuracy between the Mini-FLOTAC and the McMaster techniques for quantitative diagnosis of Eimeria maxima oocyst in poultry. Twelve pools of excreta samples of broiler chickens experimentally infected with E. maxima were analyzed for the comparison between Mini-FLOTAC and McMaster technique using, the detection limits (dl) of 23 and 25, respectively. Additionally, six excreta samples were used to compare the precision of different dl (5, 10, 23, and 46) using the Mini-FLOTAC technique. For precision comparisons, five technical replicates of each sample (five replicate slides on one excreta slurry) were read for calculating the mean oocyst per gram of excreta (OPG) count, standard deviation (SD), coefficient of variation (CV), and precision of both aforementioned comparisons. To compare accuracy between the methods (McMaster, and Mini-FLOTAC dl 5 and 23), excreta from uninfected chickens was spiked with 100, 500, 1,000, 5,000, or 10,000 OPG; additional samples remained unspiked (negative control). For each spiking level, three samples were read in triplicate, totaling nine reads per spiking level per technique. Data were transformed using log10 to obtain normality and homogeneity of variances. A significant correlation (R = 0.74; p = 0.006) was observed between the mean OPG of the McMaster dl 25 and the Mini-FLOTAC dl 23. Mean OPG, CV, SD, and precision were not statistically different between the McMaster dl 25 and Mini-FLOTAC dl 23. Despite the absence of statistical difference (p > 0.05), Mini-FLOTAC dl 5 showed a numerically lower SD and CV than Mini-FLOTAC dl 23. The Pearson correlation coefficient revealed significant and positive correlation among the four dl (p ≤ 0.05). In the accuracy study, it was observed that the Mini-FLOTAC dl 5 and 23 were more accurate than the McMaster for 100 OPG, and the Mini-FLOTAC dl 23 had the highest accuracy for 500 OPG. The McMaster and Mini-FLOTAC dl 23 techniques were more accurate than the Mini-FLOTAC dl 5 for 5,000 OPG, and both dl of the Mini-FLOTAC were less accurate for 10,000 OPG counts than the McMaster technique. However, the overall accuracy of the Mini-FLOTAC dl 23 was higher than the McMaster and Mini-FLOTAC dl 5 techniques.

Threonine, arginine, and glutamine: Influences on intestinal physiology, immunology, and microbiology in broilers.

Even though the intestine represents a small proportion of body weight in broiler chickens, its requirements for energy and nutrients are high. A healthy broiler intestine has a well-coordinated immune system that must accommodate commensal microbiota while inhibiting the colonization and proliferation of harmful pathogens. Modern commercial intensive practices impose a high sanitary pressure that may exacerbate the progression of intestinal diseases such as coccidiosis and necrotic enteritis. The incidence of these diseases may increase worldwide due to mounting pressure to limit the use of subtherapeutic antibiotics as growth promoters or ionophores for coccidial suppression/prevention in the diets of broilers. For this reason, altering dietary concentrations of some amino acids, particularly trophic amino acids, may be beneficial to modulate the intestinal physiology, immunology, and microbiology of broilers. Trophic amino acids, such as threonine, arginine, and glutamine, play a very important role on the intestinal mucosa and may support increased epithelial turnover rates to improve intestinal recovery following an insult. Furthermore, these amino acids may help to minimize over-activation of the innate immune system, which is the most expensive in terms of nutrients and energy, as well as modulate the intestinal microbiota. The objective of this review is to provide insight into the potential role of trophic amino acids in these processes and report some updated studies of their use in diets for broiler chickens.

Sodium butyrate improved performance while modulating the cecal microbiota and regulating the expression of intestinal immune-related genes of broiler chickens.

This study evaluated the effect of sodium butyrate (SB) on performance, expression of immune-related genes in the cecal tonsils, and cecal microbiota of broiler chickens when dietary energy and amino acids concentrations were reduced. Day-old male Ross 708 broiler chicks were fed dietary treatments in a 3 × 2 factorial design (8 pens per treatment) with 3 dietary formulations (control diet; reduction of 2.3% of amino acids and 60 kcal/kg; and reduction of 4.6% of amino acids and 120 kcal/kg) with or without the inclusion of 0.1% of SB. Feed intake (FI), body weight gain (BW gain), and feed conversion ratio (FCR) were recorded until 28 d of age. From 14 to 28 d, there was an interaction of nutrient density by SB (P = 0.003) wherein BW gain of birds fed SB was impaired less by the energy/amino acids reduction than unsupplemented birds. A similar result was obtained from 1 to 28 d (P = 0.004). No interaction (P < 0.05) between nutrient density by SB was observed for FCR. Nutritional density of the diets and SB modified the structure, composition, and predicted function of the cecal microbiota. The nutritionally reduced diet altered the imputed function performed by the microbiota and the SB supplementation reduced these variations, keeping the microbial function similar to that observed in chickens fed a control diet. The frequency of bacterial species presenting the butyryl-CoA: acetate CoA-transferase gene increased in the microbiota of chickens fed a nutritionally reduced diet without SB supplementation, and was not changed by nutrient density of the diet when supplemented with SB (interaction; P = 0.01). SB modulated the expression of immune related genes in the cecal tonsils; wherein SB upregulated the expression of A20 in broilers fed control diets (P < 0.05) and increased IL-6 expression (P < 0.05). These results show that SB had positive effects on the productive performance of broilers fed nutritionally reduced diets, partially by modulating the cecal microbiota and exerting immune-modulatory effects.

Once versus twice daily enoxaparin for the initial treatment of acute venous thromboembolism.

Essentials In venous thromboembolism (VTE), it is uncertain if enoxaparin should be given twice or once daily. We compared the 15- and 30-day outcomes in VTE patients on enoxaparin twice vs. once daily. Patients on enoxaparin once daily had fewer major bleeds and deaths than those on twice daily. The rate of VTE recurrences was similar in both subgroups. SUMMARY: Background In patients with acute venous thromboembolism (VTE), it is uncertain whether enoxaparin should be administered twice or once daily. Methods We used the RIETE Registry data to compare the 15- and 30-day rates of VTE recurrence, major bleeding and death between patients receiving enoxaparin twice daily and those receiving it once daily. We used propensity score matching to adjust for confounding variables. Results The study included 4730 patients: 3786 (80%) received enoxaparin twice daily and 944 once daily. During the first 15 days, patients on enoxaparin once daily had a trend towards more VTE recurrences (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.55-5.88), fewer major bleeds (OR, 0.42; 95% CI, 0.17-1.08) and fewer deaths (OR, 0.32; 95% CI, 0.13-0.78) than those on enoxaparin twice daily. At day 30, patients on enoxaparin once daily had more VTE recurrences (OR, 2.5; 95% CI, 1.03-5.88), fewer major bleeds (OR, 0.40; 95% CI, 0.17-0.94) and fewer deaths (OR, 0.58; 95% CI, 0.33-1.00). On propensity analysis, patients on enoxaparin once daily had fewer major bleeds at 15 (hazard ratio [HR], 0.30; 95% CI, 0.10-0.88) and at 30 days (HR, 0.16; 95% CI, 0.04-0.68) and also fewer deaths at 15 (HR, 0.37; 95% CI, 0.14-0.99) and at 30 days (HR, 0.19; 95% CI, 0.07-0.54) than those on enoxaparin twice daily. Conclusions Our findings confirm that enoxaparin prescribed once daily results in fewer major bleeds than enoxaparin twice daily, as suggested in a meta-analysis of controlled clinical trials.

Replacing corn with sorghum in the diet alters intestinal microbiota without altering chicken performance.

Sorghum grain can be used to replace corn in broiler diets. However, the effects related to an abrupt change between these grains are not yet clear. The aim of this study was to evaluate the performance and intestinal health of broilers fed diets containing corn and/or sorghum during different periods of rearing. To accomplish this aim, 2100 male chicks were fed the following experimental diets: C100% (corn-based diet); S100% (sorghum-based diet); C:S50% (diet based on corn and sorghum 1:1); PC-S (corn-based diet in the pre-starter phase and sorghum-based diet in subsequent phases); and PS-C (sorghum-based diet in the pre-starter phase and corn-based diet in subsequent phases). The study was conducted with two simultaneous trials in a randomized block design as follows: a performance trial up to 40 days occurred in floor pens (n = 8), and the metabolism trial occurred in cages (n = 10). Performance, jejunal morphometry, number of goblet cells, apparent metabolizable energy (AME), apparent metabolizable energy corrected for nitrogen (AMEn) and the coefficient of apparent metabolizability of dry matter (CMDM) of the diets, and the intestinal microbiota of small intestine and caeca at 10 and 21 days of age (16S gene sequencing) were evaluated. The different experimental diets did not affect performance, jejunal epithelium, AME, AMEn or CMDM. However, the experimental diets altered the percentages of the genera Clostridium, Weissella, Bacillus and Alkaliphilus in the small intestine. In addition, the genera Lactobacillus and Desulfotomaculum in the caeca were altered. The age also affected the microbiota of the intestinal segments. In conclusion, feeding sorghum in place of corn as well as the grain change after the pre-starter phase does not alter broiler performance. However, sorghum alters the intestinal microbiota, resulting in a lower percentage of Clostridium and a higher percentage of Lactobacillus in the small intestine and caeca, respectively.

Single stage incubators and Hypercapnia during incubation affect the vascularization of the chorioallantoic membrane in broiler embryos.

Incubation management can have direct effects on neonate health and consequently affect post-hatching development. The effects of incubation in multiple and single stage incubators with different concentrations of CO2 were evaluated in terms of the vessel density in the chorioallantoic membrane, hatching, heart morphology, and body development of the neonate up to the tenth day. A total of 2,520 fertile eggs were used and distributed in a completely randomized design with 4 levels of CO2 in 4 single-stage incubators (4,000; 6,000; 8,000; and 10,000 ppm) and a control treatment based on multiple-stage incubation, totaling 5 treatments. The levels of CO2 were used during the first 10 d of the incubation period, and after this period, all eggs were submitted to the same level of CO2 (4,000 ppm). Eggs that were incubated in multiple-stage incubators presented a lower percentage of vessels in the chorioallantoic membrane, lower yolk absorption by the embryo, wall depth of the right ventricle, and greater humidity losses in the eggs when compared to eggs in the single-stage incubators. The eggs submitted to hypercapnia, between 5,000 and 6,000 ppm of CO2, had a higher percentage of vessels in the chorioallantoic membrane; the embryos originating from these eggs had higher weight, with higher relative weight of the liver. However, the same levels reduced the yolk absorption. Single-stage incubation with moderate levels of hypercapnia is an efficient tool to be adopted by the hatcheries when attempting to improve chick quality.

Intestinal alkaline phosphatase and sodium butyrate may be beneficial in attenuating LPS-induced intestinal inflammation.

In this study, we evaluated the effect of intestinal alkaline phosphatase (IAP) and sodium butyrate (NaBu) on lipopolysaccharide (LPS)-induced intestinal inflammation. Intestinal alkaline phosphatase and RelA/p65 (NF-κB) gene expressions in porcine jejunum explants were evaluated following exposure to sodium butyrate (NaBu) and essential oil from Brazilian red pepper (EO), alone or in combination with NaBu, as well as exogenous IAP with or without LPS challenge. Five piglets weighing approximately 20 kg each were sacrificed, and their jejunum were extracted. The tissues were segmented into 10 parts, which were exposed to 10 treatments. Gene expressions of IAP and RelA/p65 (NF-κB) in jejunal explants were evaluated via RT-PCR. We found that EO, NaBu, and exogenous IAP were able to up-regulate endogenous IAP and enhance RelA/p65 (NF-κB) gene expression. However, only NaBu and exogenous IAP down-regulated LPS-induced inflammatory response via RelA/p65 (NF-κB). In conclusion, we demonstrated that exogenous IAP and NaBu may be beneficial in attenuating LPS-induced intestinal inflammation.