Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na+/K+ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.

Heat stress can compromise intestinal integrity and induce leaky gut in a variety of species. Therefore, the objectives of this study were to determine if heat stress (HS) directly or indirectly (via reduced feed intake) increases intestinal permeability in growing pigs. We hypothesized that an increased heat-load causes physiological alterations to the intestinal epithelium, resulting in compromised barrier integrity and altered intestinal function that contributes to the overall severity of HS-related illness. Crossbred gilts (n=48, 43±4 kg BW) were housed in constant climate controlled rooms in individual pens and exposed to 1) thermal neutral (TN) conditions (20°C, 35-50% humidity) with ad libitum intake, 2) HS conditions (35°C, 20-35% humidity) with ad libitum feed intake, or 3) pair-fed in TN conditions (PFTN) to eliminate confounding effects of dissimilar feed intake. Pigs were sacrificed at 1, 3, or 7 d of environmental exposure and jejunum samples were mounted into modified Ussing chambers for assessment of transepithelial electrical resistance (TER) and intestinal fluorescein isothiocyanate (FITC)-labeled lipopolysaccharide (LPS) permeability (expressed as apparent permeability coefficient, APP). Further, gene and protein markers of intestinal integrity and stress were assessed. Irrespective of d of HS exposure, plasma endotoxin levels increased 45% (P<0.05) in HS compared with TN pigs, while jejunum TER decreased 30% (P<0.05) and LPS APP increased 2-fold (P<0.01). Furthermore, d 7 HS pigs tended (P=0.06) to have increased LPS APP (41%) compared with PFTN controls. Lysozyme and alkaline phosphatase activity decreased (46 and 59%, respectively; P<0.05) over time in HS pigs, while the immune cell marker, myeloperoxidase activity, was increased (P<0.05) in the jejunum at d 3 and 7. These results indicate that both HS and reduced feed intake decrease intestinal integrity and increase endotoxin permeability. We hypothesize that these events may lead to increased inflammation, which might contribute to reduced pig performance during warm summer months.

Twenty corn coproducts from various wet- and dry-grind ethanol plants were fed to finishing pigs to determine DE and ME and to generate equations predicting DE and ME based on chemical analysis. A basal diet comprised corn (97.05%), limestone, dicalcium phosphate, salt, vitamins, and trace minerals. Twenty test diets were formulated by mixing the basal diet with 30% of a coproduct, except for dried corn solubles and corn oil, which were included at 20 and 10%, respectively. There were 8 groups of 24 finishing gilts (n = 192; BW = 112.7 ± 7.9 kg). Within each group, gilts were randomly assigned to 1 of 5 test diets or the basal diet for a total of 4 replications per diet per group. Two groups of gilts were used for each set of coproducts, resulting in 8 replications per coproduct and 32 replications of the basal diet. The experiment was conducted as a completely randomized design. Gilts were placed in metabolism crates and offered 3 kg daily of their assigned test diet for 13 d, with total collection of feces and urine during the last 4 d. Ingredients were analyzed for DM, GE, CP, ether extract, crude fiber, NDF, ADF, total dietary fiber (TDF), ash, AA, and minerals, and in vitro OM digestibility was calculated for each ingredient. The GE was determined in the diets, feces, and urine to calculate DE and ME for each ingredient. The DE and ME of the basal diet were used as covariates among groups of pigs. The DE of the coproducts ranged from 2,517 kcal/kg of DM (corn gluten feed) to 8,988 kcal/kg of DM (corn oil), and ME ranged from 2,334 kcal/kg of DM (corn gluten feed) to 8,755 kcal/kg of DM (corn oil). By excluding corn oil and corn starch from the stepwise regression analysis, a series of DE and ME prediction equations were generated. The best fit equations were as follows: DE, kcal/kg of DM = -7,471 + (1.94 × GE) - (50.91 × ether extract) + (15.20 × total starch) + (18.04 × OM digestibility), with R(2) = 0.90, SE = 227, and P < 0.01; ME, kcal/kg of DM = (0.90 × GE) - (29.95 × TDF), with R(2) = 0.72, SE = 323, and P < 0.01. Additional equations for DE and ME included NDF in the instance that TDF data were not available. These results indicate that DE and ME varied substantially among corn coproducts and that various nutritional components can be used to accurately predict DE and ME in corn coproducts for finishing pigs.

To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and MethodsWithin the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. ResultsEngraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC (P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC (P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC (P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC (P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC (P = .58 and P = .08, respectively). ConclusionThis prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

The apparent DE and ME values of crude glycerol for growing pigs were determined in 5 experiments using crude glycerol (86.95% glycerol) from a biodiesel production facility, which used soybean oil as the initial feedstock. Dietary treatments were 0, 5, or 10% glycerol addition to basal diets in Exp. 1; 0, 5, 10, or 20% glycerol addition to basal diets in Exp. 2; and 0 and 10% crude glycerol addition to the basal diets in Exp. 3, 4, and 5. Each diet was fed twice daily to pigs in individual metabolism crates. After a 10-d adjustment period, a 5-d balance trial was conducted. During the collection period, feces and urine were collected separately after each meal and stored at 0 degrees C until analyses. The GE of each dietary treatment and samples of urine and feces from each pig were determined by isoperibol bomb calorimetry. Digestible energy of the diet was calculated by subtracting fecal energy from the GE in the feed, whereas ME was calculated by subtracting the urinary energy from DE. The DE and ME values of crude glycerol were estimated as the slope of the linear relationship between either DE or ME intake from the experimental diet and feed intake. Among all experiments, the crude glycerol (86.95% glycerol) examined in this study was shown to have a DE of 3,344 +/- 8 kcal/kg and an ME of 3,207 +/- 10 kcal/kg, thereby providing a highly available energy source for growing pigs.

Endotoxin, also referred to as lipopolysaccharide (LPS), can stimulate localized or systemic inflammation via the activation of pattern recognition receptors. Additionally, endotoxin and inflammation can regulate intestinal epithelial function by altering integrity, nutrient transport, and utilization. The gastrointestinal tract is a large reservoir of both gram-positive and gram-negative bacteria, of which the gram-negative bacteria serve as a source of endotoxin. Luminal endotoxin can enter circulation via two routes: 1) nonspecific paracellular transport through epithelial cell tight junctions, and 2) transcellular transport through lipid raft membrane domains involving receptor-mediated endocytosis. Paracellular transport of endotoxin occurs through dissociation of tight junction protein complexes resulting in reduced intestinal barrier integrity, which can be a result of enteric disease, inflammation, or environmental and metabolic stress. Transcellular transport, via specialized membrane regions rich in glycolipids, sphingolipids, cholesterol, and saturated fatty acids, is a result of raft recruitment of endotoxin-related signaling proteins leading to endotoxin signaling and endocytosis. Both transport routes and sensitivity to endotoxin may be altered by diet and environmental and metabolic stresses. Intestinal-derived endotoxin and inflammation result in suppressed appetite, activation of the immune system, and partitioning of energy and nutrients away from growth toward supporting the immune system requirements. In livestock, this leads to the suppression of growth, particularly suppression of lean tissue accretion. In this paper, we summarize the evidence that intestinal transport of endotoxin and the subsequent inflammation leads to decrease in the production performance of agricultural animals and we present an overview of endotoxin detoxification mechanisms in livestock.

The effects of dietary crude glycerin on growth performance, carcass characteristics, meat quality indices, and tissue histology in growing pigs were determined in a 138-d feeding trial. Crude glycerin utilized in the trial contained 84.51% glycerin, 11.95% water, 2.91% sodium chloride, and 0.32% methanol. Eight days postweaning, 96 pigs (48 barrows and 48 gilts, average BW of 7.9 ± 0.4 kg) were allotted to 24 pens (4 pigs/ pen), with sex and BW balanced at the start of the experiment. Dietary treatments were 0, 5, and 10% crude glycerin inclusion in corn-soybean meal-based diets and were randomly assigned to pens. Diets were offered ad libitum in meal form and formulated to be equal in ME, sodium, chloride, and Lys, with other AA balanced on an ideal AA basis. Pigs and feeders were weighed every other week to determine ADG, ADFI, and G:F. At the end of the trial, all pigs were scanned using real-time ultrasound and subsequently slaughtered at a commercial abattoir. Blood samples were collected pretransport and at the time of slaughter for plasma metabolite analysis. In addition, kidney, liver, and eye tissues were collected for subsequent examination for lesions characteristic of methanol toxicity. After an overnight chilling of the carcass, loins were removed for meat quality, sensory evaluation, and fatty acid profile analysis. Pig growth, feed intake, and G:F were not affected by dietary treatment. Dietary treatment did not affect 10th-rib backfat, LM area, percent fat free lean, meat quality, or sensory evaluation. Loin ultimate pH was increased (P = 0.06) in pigs fed the 5 and 10% crude glycerin compared with pigs fed no crude glycerin (5.65 and 5.65 versus 5.57, respectively). Fatty acid profile of the LM was slightly changed by diet with the LM from pigs fed 10% crude glycerin having less linoleic acid (P< 0.01) and more eicosapentaenoic acid (P = 0.02) than pigs fed the 0 or 5% crude glycerin diets. Dietary treatment did not affect blood metabolites or frequency of lesions in the examined tissues. This experiment demonstrated that pigs can be fed up to 10% crude glycerin with no effect on pig performance, carcass composition, meat quality, or lesion scores. KeywordsFood Science and Human Nutrition, biofuel, crude glycerin, fatty acid, growing pig, histology, meat quality RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. ABSTRACT:The effects of dietary crude glycerin on growth performance, carcass characteristics, meat quality indices, and tissue histology in growing pigs were determined in a 138-d feeding trial. Crude glycerin utilized in the trial contained 84.51% glycerin, 11.95% water, 2.91% sodium chloride, and 0.32% methanol. Eight days postweaning, 96 pigs (48 barrows and 48 gilts, average BW of 7.9 ± 0.4 kg) were allotted to 24 pens (4 pigs/pen), with sex and BW balanced at the start of the experiment. Dietary treatments were 0, 5, and 10% crude glycerin inclusion...

Purpose Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults. Methods Patients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saint antoi ne.aphp.fr/score /) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded. Results The study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17-87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*10 9 /l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival. Conclusion Close multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.