Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

[Heart valve disesases : How sufficient is the knowledge of the German population?] / Herzklappenerkrankungen : Wie aufgeklärt ist die deutsche Bevölkerung?

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.

Temporal trends in transcatheter and surgical aortic valve replacement : An analysis of aortic valve replacements in Germany during 2012-2014.

This analysis of the data of the obligatory quality assurance programme AQUA shows the perioperative risk as well as the procedural outcome evaluated by the observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872 patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-), or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in 2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953). Between 2012 and 2014, the number of TAVI implanted in patients with a logistic EuroScore I (logESI) of ≤10 % (2012: 21 %; 2014: 26 %) as well as with a logESI <20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5 %) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %). The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73 (TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients (2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital mortality, as well as the O/E ratio for patients undergoing TAVI declined constantly during the last 3 years.

Effect of soaking, fermentation with lactobacillus and enzyme treatment on nitrogen-corrected apparent metabolizable energy values of wheat in cockerels and quails.

An experiment was carried out to determine nitrogen-corrected apparent metabolizable energy (AMEn) values of processed wheat products with two levels of enzyme (0 and 0.5 g/kg) and five processing methods [control (C), water-soaking for 12 h (SO12h), 24 h (SO24h) and 48 h (SO48h) and fermentation with lactobacillus (FL)] in two species of poultry (cockerel and Japanese quail). In this study, each processing method group had six replications with two cockerels or four quails per replication. The results showed that the calculated AMEn values of processed wheat by different methods were as follows: C-12.61 and 12.60; SO12h-12.75 and 12.73; SO24h-12.80 and 12.79; SO48h-12.97 and 12.96; and FL-13.36 and 13.33 MJ/kg for cockerels and quails, respectively, indicating that fermentation improved AMEn values compared with the others. The mean AMEn of processed wheat with enzyme (13.12 MJ/kg) was significantly higher than that of processed wheat without enzyme (12.64 MJ/kg). However, there were no significant differences in the AMEn of processed wheat between cockerels and quails. The interaction between species and levels of enzyme in AMEn values was not significant. There was no significant difference (p > 0.05) in three-way interactions among species, levels of enzyme and wheat processing methods for AMEn values. In conclusion, the results of the experiment suggest that the FL was more effective processing method of wheat to obtain high level of AMEn values than the others, and the combination of enzyme and processing methods can increase the AMEn values compared with processing methods alone.

The effect of phytase and fructooligosaccharide supplementation on growth performance, bone quality, and phosphorus utilization in broiler chickens.

An experiment was conducted to investigate the effects of phytase and 2 levels of fructooligosaccharide (FOS) supplementation on growth performance, bone mineralization, and P utilization of broiler chickens. A total of 210 day-old male broiler chickens (Ross) were randomly placed into 7 dietary treatments consisting of 6 replicates with 5 birds per pen. The experiment was designed as an augmented 2 × 3 factorial arrangement with 0 or 500 U/kg of phytase and 0, 0.5% or 1% of FOS added to a reduced Ca (0.8%) and available P (0.25%) negative control diet (NC). A positive control diet (PC) that contained 1% Ca and 0.45% available P was also included. During the entire experimental period, phytase supplementation significantly improved (P < 0.05) the feed conversion ratio (FCR), BW gain (BWG), and feed intake. Birds fed the PC diet showed significantly higher bone mineral density (BMD) and bone mineral content (BMC) in both femur and tibia bones (P < 0.0001) than those fed the NC diet. Phytase supplementation increased femur BMD (P < 0.05), whereas FOS decreased femur BMD and BMC (P < 0.05). Phosphorus utilization was significantly higher for the NC diet (P < 0.0001). Phytase alone and in combination with 0.5% FOS increased P utilization significantly when compared with other treatments (P < 0.05). Fructooligosaccharides, especially at the level of 0.5%, increased P retention. In conclusion, phytase supplementation in low Ca and P diets improved growth performance, bone quality, and P utilization. However, supplementing NC diets with phytase and FOS did not result in bone mineralization values comparable with that of the PC diet. The application of dietary FOS alone had a negative effect on broiler bone quality.

Do newly built homes affect rhinitis in children? The ISAAC phase III study in Korea.

BACKGROUND: As Korea has experienced rapid economic development, the lifestyles of Koreans have become more Westernized, in terms of urbanization and dietary habits. Also, the prevalences of allergic diseases, such as rhinitis, asthma, and dermatitis, have increased rapidly. This study aimed to identify the factors influencing the symptoms of rhinitis conditions, including rhinitis, allergic rhinitis, overlapped rhinitis, and overlapped allergic rhinitis, among Korean children aged 6-7 years. METHODS: The study subjects were drawn from participants in the International Study of Asthma and Allergies in Childhood (ISAAC) study in 2010 and were aged 6-7 years. We analysed data for a total of 3804 children. RESULTS: The prevalences of symptoms suggestive of rhinitis and allergic rhinitis in the previous 12 months were 43.4% and 22.1%, respectively. For overlapped rhinitis and overlapped allergic rhinitis, only 2.5% and 1.9% of the children had overlapping symptoms, having rhinitis with asthma and eczema simultaneously. Gender, a parental history of allergic disease, mould or dampness at home, and the risk factors for 'sick building syndrome' (SBS) were risk factors influencing rhinitis diseases. In particular, a history of moving to a newly built home in the child's infancy was strongly associated with symptoms of all the rhinitis diseases examined. CONCLUSIONS: This study identified patterns of the prevalence of rhinitis conditions among Korean children that were similar to those reported in Western countries. We confirmed that a history of moving to a newly built home during infancy was associated with a considerable risk of rhinitis conditions.

Effects of 25-hydroxycholecalciferol on performance, gut health, and bone quality of broilers fed with reduced calcium and phosphorus diet during Eimeria challenge.

This study evaluated the effects of 25-hydroxycholecalciferol (25-OHD) on performance, gut health, and bone quality of broilers fed with reduced calcium (Ca) and phosphorus (P) diet during Eimeria spp. challenge. A total of 576 fourteen-day-old Cobb 500 male chicks were randomly distributed in a 2 × 2 × 2 factorial arrangement, with 6 replicates of 12 birds each. The main factors were 25-OHD level (0 or 3,000 IU/kg of feed), mineral level (0.84% of Ca/0.42% of P, the levels recommended for the grower phase (NOR) or 0.64% of Ca/0.22% of P (RED), and mid-high mixed Eimeria challenge or nonchallenge. 25-OHD improved phosphorus retention (P = 0.019), bone ash weight (P = 0.04), cortical bone trabecular connectivity (P = 0.043) during coccidiosis. For birds fed with reduced mineral levels, 25-OHD supplementation increased bone ash weight (P = 0.04). However, 25-OHD did not improve bone ash weight when birds were challenged and fed with reduced mineral levels. The dietary 3,000 IU of 25-OHD supplementation did not improve performance or gut morphology but support bone health during coccidiosis. Future investigations are needed for better understand 25-OHD role on bone microarchitecture and oxidative metabolism during coccidiosis.

Research Note: Effect of dietary xylo-oligosaccharide on growth performance, intestinal histomorphology, and specific cecal bacteria in broiler chickens.

This study was conducted to evaluate the prebiotic effect of xylo-oligosaccharide (XOS) supplemented in a corn-soybean meal (SBM) based conventional diet on growth performance, intestinal histomorphology, and quantification of specific bacteria in the ceca of broilers. A total of 240 d of hatch Cobb 500 male broiler chicks were randomly assigned to 4 dietary treatments (corn-SBM-based control diet) containing 0, 0.05, 0.1, and 0.2% XOS. The broilers were raised for 21 d in 6 replicate cages, each containing 10 birds. Growth performance parameters were obtained weekly. Additionally, small intestinal tissues were collected to evaluate histomorphometry and whole ceca were collected to quantify bacterial populations on D21. The results showed that inclusion of XOS has similar body weight (BW), body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) as the control group during the 21-day study. The results further indicate a tendency for the jejunum villus to crypt ratio (VH:CD) to increase in birds given 0.05 and 0.2% XOS (P = 0.08). Cecal bacteria quantification showed a linear increase in Bifidobacterium with increasing XOS levels (P < 0.0001) and a decrease Clostridium perfringens levels compared to birds fed the control diet (P < 0.0001). However, there were no differences in the total counts of Lactobacillus and E. coli. Together these results showed that while there were no differences in growth parameters up to 21 d, the histomorphology findings and the increase in Bifidobacterium, along with the reduction in C. perfringens observed in the XOS groups, suggest a beneficial impact of XOS inclusion on gut health. Further research with longer feeding periods and higher XOS levels should be conducted to explore potential positive effects on both growth and gut health parameters.

Supplementation of direct-fed microbials as an alternative to antibiotic on growth performance, immune response, cecal microbial population, and ileal morphology of broiler chickens.

An experiment was conducted to investigate the supplementation of direct-fed microbials (DFM) as an alternative to antibiotics on growth performance, immune response, cecal microbial population, and ileal morphology of broiler chickens. A total of 800 one-day-old male broiler chicks (Ross × Ross) were randomly allotted to 4 dietary treatments with 4 replicate pens per treatment (50 birds/replicate pen). The 4 dietary treatments fed for 35 d were a corn-soybean meal basal diet (control); control plus 0.1% virginiamycin, as an antibiotic growth promoter (AGP); control plus 0.1% direct-fed microbials that contained Lactobacillus reuteri (DFM 1); and control plus 0.1% direct-fed microbials that contained a mixture of L. reuteri, Bacillus subtilis, and Saccharomyces cerevisiae (DFM 2). Results showed that dietary AGP and DFM supplementation significantly increased (P < 0.05) the BW gain of broilers during 0 to 21 d. The feed intake was reduced, whereas the feed conversion was improved significantly when birds were fed DFM 2 at 0 to 7 d of age. The white blood cell and monocyte levels were significantly higher in the DFM 2 group compared with the control. In addition, feeding DFM significantly (P < 0.05) increased the plasma immunoglobulin levels where a higher level was observed in DFM 2 compared with those of the other treatments. Neither DFM nor AGP treatments affected the cecal Lactobacillus and Salmonella content; however, cecal Escherichia coli content significantly decreased in broiler chickens fed DFM and AGP. The ileal villus height, and width and total thickness of muscularis externa were significantly increased when birds were fed DFM compared with AGP and control. These results indicate that the dietary supplementation of DFM increases the growth performance of birds at an early age, stimulates the immune response, decreases the number of E. coli, and improves the ileal morphology of broiler chickens. Thus, DFM that contained a mixture of several beneficial microorganisms could be a viable alternative to antibiotics in the broiler diets.

[Transcatheter aortic valve implantation (TAVI)]. / Transkatheteraortenklappenersatz (TAVI).

Aortic valve stenosis (AS) is the most common acquired valve disease in the industrialized countries. Most patients--especially young and low-risk patients--can be safely and effectively operated with aortic valve replacement. Due to increasing life expectancy, however, the number of elderly patients with AS and various concomitant diseases will increase in the coming decades. For those elderly high-risk patients, transfemoral or transapical aortic valve implantation (TAVI) has evolved as a valuable alternative to conventional surgery. The TAVI approach has been shown to be superior to standard medical treatment in these high-risk patients. All patients considered for TAVI should be discussed in a consensus conference consisting of cardiac surgeons and cardiologists (heart team). Furthermore, for successful treatment with transcatheter techniques, sophisticated pre-interventional imaging is required to screen patients. Available data on TAVI from randomized trials and large-scale registries demonstrate that this method is very promising.

Impact of exogenous hydrogen peroxide on osteogenic differentiation of broiler chicken compact bones derived mesenchymal stem cells.

The effects of hydrogen peroxide (H2O2) on the osteogenic differentiation of primary chicken mesenchymal stem cells (MSCs) were investigated. MSCs were subjected to an osteogenic program and exposed to various concentrations of H2O2 for 14 days. Results showed that high concentrations of H2O2 (200 and 400 nM) significantly increased pro-apoptotic marker CASP8 expression and impaired osteogenic differentiation, as indicated by decreased mRNA expression levels of osteogenesis-related genes and reduced in vitro mineralization. In contrast, long-term H2O2 exposure promoted basal expression of adipogenic markers at the expense of osteogenesis in MSCs during osteogenic differentiation, and increased intracellular reactive oxygen species (ROS) production, as well as altered antioxidant enzyme gene expression. These findings suggest that long-term H2O2-induced ROS production impairs osteogenic differentiation in chicken MSCs under an osteogenic program.

Hyperimmune egg yolk antibodies developed against Clostridium perfringens antigens protect against necrotic enteritis.

Necrotic enteritis (NE) is a widespread infectious disease caused by Clostridium perfringens that inflicts major economic losses on the global poultry industry. Due to regulations on antibiotic use in poultry production, there is an urgent need for alternative strategies to mitigate the negative effects of NE. This paper presents a passive immunization technology that utilizes hyperimmune egg yolk immunoglobulin Y (IgY) specific to the major immunodominant antigens of C. perfringens. Egg yolk IgYs were generated by immunizing hens with 4 different recombinant C. perfringens antigens, and their protective effects against NE were evaluated in commercial broilers. Six different spray-dried egg powders were produced using recombinant C. perfringens antigens: α-toxin, NE B-like toxin (NetB; EB), elongation factor-Tu (ET), pyruvate:ferredoxin oxidoreductase, a mixture of 4 antigens (EM-1), and a nonimmunized control (EC). The challenged groups were either provided with different egg powders at a 1% level or no egg powders (EN). The NE challenge model based on Eimeria maxima and C. perfringens dual infection was used. In Experiments 1 and 2, the EB and ET groups exhibited increased body weight gain (BWG; P < 0.01), decreased NE lesion scores (P < 0.001), and reduced serum NetB levels (P < 0.01) compared to the EN and EC groups. IgY against NetB significantly reduced Leghorn male hepatocellular cytotoxicity in an in vitro test (P < 0.01). In Experiment 3, the protective effect of the IgYs mixture (EM-2) against C. perfringens antigens (NetB and EFTu) and Eimeria antigens (elongation factor-1-alpha: EF1α and Eimeria profilin: 3-1E) was tested. The EM-2 group showed similar body weight, BWG, and feed intake from d 7 to 22 compared to the NC group (P < 0.05). On d 20, the EM-2 group showed comparable intestinal permeability, NE lesion scores, and jejunal NetB and collagen adhesion protein levels to the NC group (P < 0.05). In conclusion, dietary mixture containing antibodies to NetB and EFTu provides protection against experimental NE in chickens through passive immunization.

Evaluation of a dacitic (rhyolitic) tuff breccia use on performance, inflammatory, and antioxidant responses in broilers mildly challenged with Eimeria spp.

The objective of the study was to investigate the effects of a dacitic tuff breccia (DTB) on Eimeria-infected broilers. A total of 600 one-day-old Cobb 500 male chickens were randomly assigned to 5 treatments with 10 replicates of 12 birds. Treatments were: an unchallenged control (UC), a challenged (CC) control (0% DTB), and 3 challenged groups with 0.125, 0.25, or 0.5% DTB. At d 14, birds in the CC and DTB groups were orally gavaged with mixed Eimeria spp., while the UC received water. Growth performance was evaluated during prechallenge, challenge, and postchallenge periods (0-14 d; 14-20 d; and 20-26 d, respectively). Gastrointestinal permeability was measured at 5 days postinfection (dpi). Intestinal histology and nutrient digestibility of dry matter (DM), crude protein (CP), and ileal digestible energy (IDE) were measured at 6 dpi. Liver activity of glutathione peroxidase (GSH-Px) was determined at 6 dpi, and concentrations of reduced (GSH) and oxidized glutathione (GSSG) were analyzed at 6 and 12 dpi. Data were analyzed using a linear mixed model analysis and Tukey's test (P ≤ 0.05). From 0 to 14 d, similar average daily gain (ADG) and average daily feed intake (ADFI, P > 0.05) were observed. Gain:feed ratio (GF) was higher in 0.125, 0.25, and 0.5% of DTB than the CC and UC (P < 0.001). From 14 to 20 d, the UC had the highest ADG, ADFI, and GF (P < 0.001). At 5 dpi, intestinal permeability was higher in the challenged groups than the UC. Additionally, the UC showed the highest apparent ileal digestibility of CP, whereas 0.125% DTB had higher CP digestibility than the CC and 0.5% DTB (P < 0.001). At 6 dpi, 0.125% DTB increased GSH-Px activity compared to the CC, 0.5% DTB, and UC (P < 0.001). At 12 dpi, 0.125% DTB showed increased GSH concentration compared to the CC, 0.25% DTB, and 0.5% DTB (P < 0.01). The mild coccidia infection negatively impacted growth performance, apparent ileal nutrient digestibility, intestinal histology, and gastrointestinal integrity in broilers. The use of 0.125% DTB exhibited potential in improving antioxidant responses, apparent ileal digestibility of CP, and growth performance.

Outcomes After Early Postoperative Myocardial Infarction Due to Graft Failure in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality. METHODS: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality. RESULTS: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02). CONCLUSION: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

Body composition, gastrointestinal, and reproductive differences between broiler breeders fed using everyday or skip-a-day rearing programs.

Broiler breeder feed restriction practices have intensified as broiler feed efficiency has been improved. Skip-a-day (SAD) rearing regimen has controlled breeder growth, although this practice has become questionable for the modern breeder. We compared everyday (ED) and SAD programs and evaluated their impact on pullet growth performance, body composition, gastrointestinal tract development, and reproduction. At d 0, Ross 708 (Aviagen) pullet chicks (n = 1,778) were randomly assigned to 7 floor pens. Three pens were fed using the ED and 4 pens with SAD program through wk 21 using a chain-feeder system. ED and SAD grower diets were formulated to be isonutritious, with the only difference that ED diets had more crude fiber. Pullets (n = 44 per pen) were moved to 16 hen pens by treatment at wk 21 with 3 YP males (Aviagen) in each pen. All birds were fed common laying diets. In addition to BW data, sampled pullets and hens were scanned using dual energy X-ray absorptiometry (DEXA) to obtain body bone density and composition. Hen performance and hatchery metrics were recorded through wk 60. ED birds were heavier with similar nutrient intake from wk 10 to 45 (P ≤ 0.013). Pullet uniformity was unaffected by feeding method (P ≥ 0.443). SAD pullets had less body fat at wk 19 (P = 0.034) compared to ED pullets, likely as a metabolic consequence of intermittent feeding. SAD birds had lower bone density at wk 7, 15, and 19 (P ≤ 0.026). At 4 wk of age, SAD pullets had less intestinal villi goblet cells compared to ED pullets (P ≤ 0.050), possibly explained by the effect that feed removal has on cell migration rates. Overall egg-specific gravity (P = 0.057) and hatch of fertile % (P = 0.088) tended to be higher in eggs from ED hens. Altogether, ED feeding increased young pullet intestinal goblet cells and increased both bone density and body fat at wk 19. ED program improved pullet feed conversion (2.6% less feed) and increased eggshell quality and hatch of fertile.

Genomic Grade Index predicts postoperative clinical outcome of GIST.

BACKGROUND: Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib. METHODS: We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib. RESULTS: We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index 'high-risk' tumours were more proliferative and genetically unstable than 'low-risk' tumours, and more sensitive to imatinib. CONCLUSION: GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.

Bacillus-derived poly-γ-glutamic acid reciprocally regulates the differentiation of T helper 17 and regulatory T cells and attenuates experimental autoimmune encephalomyelitis.

Forkhead box protein 3 (FoxP3(+)) regulatory T (T(reg)) cells and interleukin (IL)-17-producing T helper 17 (Th17) cells have opposing effects on autoimmunity, as the former are crucial for maintaining self-tolerance while the latter play a key role in precipitating inflammatory autoimmune diseases. Here we report that Bacillus-derived poly-γ-glutamic acid (γ-PGA) signals naive CD4(+) T cells to promote the selective differentiation of T(reg) cells and to suppress the differentiation of Th17 cells. The γ-PGA inducibility of FoxP3 expression was due partially to transforming growth factor (TGF)-ß induction through a Toll-like receptor (TLR)-4/myeloid differentiating factor 88 (MyD88)-dependent pathway. However, this pathway was dispensable for γ-PGA suppression of Th17 differentiation. γ-PGA inhibited IL-6-driven induction of Th17-specific factors including signal transducer and activator of transcription-3 (STAT-3) and retinoic acid-related orphan receptor γt (RORγt) while up-regulating the STAT-3 inhibitor suppressor of cytokine signalling 3 (SOCS3). Importantly, in vivo administration of γ-PGA attenuated the symptoms of experimental autoimmune encephalomyelitis and at the same time reduced Th17 cell infiltrates in the central nervous system. Thus, we have identified the microbe-associated molecular pattern, γ-PGA, as a novel regulator of autoimmune responses, capable of promoting the differentiation of anti-inflammatory T(reg) cells and suppressing the differentiation of proinflammatory Th17 cells. These findings draw attention to the potential of γ-PGA for treating Th17 cell-mediated autoimmune diseases.

Long Bone Mineral Loss, Bone Microstructural Changes and Oxidative Stress After Eimeria Challenge in Broilers.

The objective of this study was to evaluate the impact of coccidiosis on bone quality and antioxidant status in the liver and bone marrow of broiler chickens. A total of 360 13-day old male broilers (Cobb 500) were randomly assigned to different groups (negative control, low, medium-low, medium-high, and highest dose groups) and orally gavaged with different concentrations of Eimeria oocysts solution. Broiler tibia and tibia bone marrow were collected at 6 days post-infection (6 dpi) for bone 3-D structural analyses and the gene expression related to osteogenesis, oxidative stress, and adipogenesis using micro-computed tomography (micro-CT) and real-time qPCR analysis, respectively. Metaphyseal bone mineral density and content were reduced in response to the increase of Eimeria challenge dose, and poor trabecular bone traits were observed in the high inoculation group. However, there were no significant structural changes in metaphyseal cortical bone. Medium-high Eimeria challenge dose significantly increased level of peroxisome proliferator-activated receptor gamma (PPARG, p < 0.05) and decreased levels of bone gamma-carboxyglutamate protein coding gene (BGLAP, p < 0.05) and fatty acid synthase coding gene (FASN, p < 0.05) in bone marrow. An increased mRNA level of superoxide dismutase type 1 (SOD1, p < 0.05) and heme oxygenase 1 (HMOX1, p < 0.05), and increased enzyme activity of superoxide dismutase (SOD, p < 0.05) were found in bone marrow of Eimeria challenged groups compared with that of non-infected control. Similarly, enzyme activity of SOD and the mRNA level of SOD1, HMOX1 and aflatoxin aldehyde reductase (AKE7A2) were increased in the liver of infected broilers (p < 0.05), whereas glutathione (GSH) content was lower in the medium-high challenge group (p < 0.05) compared with non-challenged control. Moreover, the mRNA expression of catalase (CAT) and nuclear factor kappa B1 (NFKB1) showed dose-depend response in the liver, where expression of CAT and NFKB1 was upregulated in the low challenge group but decreased with the higher Eimeria challenge dosage (p < 0.05). In conclusion, high challenge dose of Eimeria infection negatively affected the long bone development. The structural changes of tibia and decreased mineral content were mainly located at the trabecular bone of metaphyseal area. The change of redox and impaired antioxidant status following the Eimeria infection were observed in the liver and bone marrow of broilers.

Influence of Brassica spp. rapeseed and canola meal, and supplementation of bioactive compound (AITC) on growth performance, intestinal-permeability, oocyst shedding, lesion score, histomorphology, and gene expression of broilers challenged with E. maxima.

This study was performed to investigate the effect of feeding Brassica spp. including full-fat rapeseed, canola meal, and allyl isothiocyanate (AITC) to broiler chicken challenged with E. maxima. A total of 576 one-day old male broiler chicks were completely randomized to 8 treatments with 6 replicated cages and 12 birds per cage. The treatment diets consisted of nonchallenge control (NC, corn-SBM based diet), challenge control (CC), 10% rapeseed (10RS), 30% rapeseed (30RS), 20% canola (20CLM), 40% canola (40CLM), 500 ppm AITC (500AITC), and 1,000 ppm AITC (1000AITC). At d 14, all birds were challenged, except NC group, with a subclinical dose of E. maxima. Intestinal permeability was conducted on 5 d post-infection (dpi) and for oocyst shedding 5 to 6 dpi feces were pooled and collected. On 6 dpi, growth performance, lesion score, histomorphology, and gene expression were measured. The growth performance result showed that 10RS and 30RS groups had lower BW, BWG, FI, and higher FCR (P < 0.0001). During the challenge and overall periods, NC group had highest BW, BWG, and FI, and lowest FCR. The inclusion of canola meal showed lower performance during prechallenge period but was able to catch up BWG during challenge period. The AITC levels showed similar growth performance to CC group. Intestinal permeability for 20CLM, 40CLM, 500AITC and 1000AITC was similar to NC group, whereas CC, 10RS, and 30RS had higher permeability compared to NC (P < 0.0001). Oocyst shedding was significantly lower for 40CLM and NC, whereas all other treatments had higher oocyst shedding (P < 0.0001). All the challenged treatment groups had higher lesion score and microscore than NC (P < 0.0001). Histomorphology data showed that jejunum villus height (VH) for 1000AITC was similar to NC group, whereas CC group had the lowest VH (P = 0.01). The 30RS group had lower VH: crypt depth (CD) ratio in the jejunum and ileum. The gene expression at 6 dpi for claudin1, occludin, IL2, IL6, GLUT5, EAAT, BoAT, and LAT1 was significantly changed among the treatments. The results suggest that 30RS retards growth performance and deteriorate gut health during coccidiosis and should not be fed to chicken during the starter phase. Canola meal showed decline in growth prechallenge but maintained growth and intestinal health during the challenge period at 40% inclusion. AITC at 1,000 ppm showed similar growth as control group, but with improved gut health during the challenge period. Canola meal could be a good alternative to SBM especially during coccidiosis, whereas AITC needs to be tested vigorously in animal feeding regime.

Influence of rapeseed, canola meal and glucosinolate metabolite (AITC) as potential antimicrobials: effects on growth performance, and gut health in Salmonella Typhimurium challenged broiler chickens.

Poultry is the major sources of foodborne salmonellosis. Antibiotic resistance and a surge in zoonotic diseases warrant the use of natural alternatives. Glucosinolates (GLs) are naturally occurring antimicrobial compounds in rapeseed and canola. This study investigated the effect of feeding rapeseed, canola meal, and allyl isothiocyanate (AITC; Brassica secondary metabolites) on growth performance (GP), gut health, and the potential antimicrobial activity against nalidixic acid-resistant Salmonella Typhimurium (STNR) in chickens. A total of 640 one-day-old male Cobb 500 broilers were randomly allocated to 8 treatments with 8 replicated cages and 10 birds per cage. Dietary treatments were nonchallenge control (NC, corn-SBM based), challenge (Salmonella) control (CC), 10% rapeseed (10RS), 30% rapeseed (30RS), 20% canola meal (20CLM), 40% canola meal (40CLM), 500 ppm AITC (500AITC), and 1,500 ppm AITC (1500AITC). On d 1, all the birds except NC were orally challenged with STNR (7 log CFU/bird). The chickens were reared for 21 d, and their FI and BW were recorded weekly. Salmonella cecal colonization and fecal shedding were quantified, whereas organ translocation (OT) of STNR to the spleen, liver, and kidney was tested on 0, 3, 6, 13, and 20-d postchallenge (dpc). Data were subjected to one-way ANOVA, and the means were separated by Duncan's test, except mortality and OT data analyzed after transformation by square root of (n +1) (P < 0.05). Overall, feeding 30RS resulted in reduced BW (P = 0.003), BWG (P = 0.003), and FI (P = 0.001) compared to CC, 500AITC, and 1500AITC. Similarly, feeding 20CLM resulted in lower BW and BWG compared to CC (P < 0.05) and increased FCR compared to 1500AITC (P = 0.03). Feeding CC resulted in higher mortality compared to NC and 30RS (P = 0.03). Cecal colonization of STNR was reduced (P < 0.0001) for 30RS on 6 dpc and 500AITC on 6 and 13 dpc (P < 0.0001). Although no difference in gut permeability was observed 6 dpc (P > 0.05), OT of STNR population was the highest for CC in the spleen (P = 0.05). In the liver, 10RS showed reduced OT compared to 20CLM on 13 dpc (P = 0.03), whereas 30RS showed the lowest OT on 6 dpc in the kidney. Fecal shedding was lowest for 30RS on 6 dpc (P = 0.004). Histomorphology showed 30RS had the highest duodenum (P = 0.01) and jejunum (P = 0.02) villus height (VH) and VH to crypt depth (CD) ratio compared to the other treatments, whereas 1500AITC showed similar results to 30RS. Both 30RS and 1500AITC contained comparatively higher functional GL metabolites and were able to maintain gut health. Including higher levels of rapeseed or AITC in poultry feed can reduce Salmonella colonization in the feces and their translocation to other organs.