Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. AIMS: To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. METHODS: Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. RESULT: Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). CONCLUSION: DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF.

Gene networks specific for innate immunity define post-traumatic stress disorder.

The molecular factors involved in the development of Post-Traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.

Development of an electronic medical record based intervention to improve medical care of osteoporosis.

UNLABELLED: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. An EMR-based intervention (osteoporosis order set) was developed with physician and patient input. There was a trend toward greater calcium supplementation from July 2008 to April 2009 (s = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. INTRODUCTION: Osteoporosis is infrequently addressed during hospitalization for osteoporotic fractures. The study population consisted of patients over 50 years of age. METHODS: Northwestern Memorial Hospital is a tertiary care academic hospital in Chicago. This study was conducted from September 1, 2007 through June 30, 2009. RESULTS: Physicians reported that barriers to care comprised nonacute nature of osteoporosis, belief that osteoporosis should be addressed by the PCP, low awareness of recurrent fractures, and radiographs with terms such as "compression deformity", "wedge deformity", or "vertebral height loss" which in their opinion were not clearly indicative of vertebral fractures. An EMR-based intervention was developed with physician and patient input. Over the evaluation period, 295 fracture cases in individuals over the age of 50 years in the medicine floors were analyzed. Mean age was 72 ± 11 years; 74% were female. Sites of fracture included hip n = 78 (27%), vertebral n = 87 (30%), lower extremity n = 61 (21%), upper extremity n = 43 (15%) and pelvis n = 26 (9%). There was no increase in documentation of osteoporosis in the medical record from pre- to post-EMR implementation (p = 0.89). There was a trend toward greater calcium supplementation from July 2008 to April 2009 (p = 0.058); however, use of antiresorptives (13%) or discharge instructions for BMD testing and osteoporosis treatment (10%) remained low. CONCLUSION: An electronic medical record intervention without electronic reminders created with physician input achieves an increase in calcium supplementation but fails to increase diagnosis or treatment for osteoporosis at the time of hospitalization for a fragility fracture.

The effects of micronutrient supplementation on vasomotor symptoms in postmenopausal women.

OBJECTIVE: Estrogen is the most effective treatment for vasomotor symptoms. Given its potential risks, herbal preparations and nutritional supplements have been developed as alternative remedies. The main aim of this double-blind, randomized, placebo-controlled trial was to assess any impact of a nutritional supplement containing 12 vitamins and nine minerals on the frequency and severity of hot flushes in postmenopausal women over a 3-month period. SUBJECTS AND METHODS: Ninety-one postmenopausal women were randomized to either the placebo (n = 45) or the treatment arm (n = 46). Seventy out of the 91 women completed the study (36 from the treatment group and 34 from the placebo group). At baseline and the 14-week post-intervention assessments, study participants completed questionnaires on the frequency and severity of hot flushes and night sweats, the Profile of Mood State questionnaire, the World Health Organization Quality of Life Questionnaire, the National Adult Reading Test and the Rey Auditory-Verbal Learning Test. Between assessments, the women also completed hot flush diaries. RESULTS: There was a significant decrease (p < 0.01) in the number (±standard error of the mean) of hot flushes experienced per week for treatment (pre 31.3 ± 4.7; post 23.1 ± 4.8) and placebo groups (pre 28.1 ± 4.7; post 17.3 ± 4.0). A significant decrease (p < 0.001) in the number of night sweats experienced per week was also observed in the treatment (pre 6.1 ± 1.0; post 4.2 ± 0.7) and placebo groups (pre 5.9 ± 0.7; post 3.7 ± 0.7). CONCLUSIONS: This study demonstrates a significant placebo effect on hot flushes and night sweats, as consistent with other studies. The micronutrient supplement containing 21 vitamins and minerals was not superior over placebo in effects on hot flushes and night sweat experiences.

Effect of dietary protein and lysine fluctuations in the absence and presence of ractopamine on performance and carcass quality of late-finishing pigs.

Two experiments with finishing pigs were conducted to evaluate the effects of fluctuating dietary CP levels and ractopamine on performance and carcass traits. In Exp. 1, a total of 408 finishing pigs (mixed sex) were assigned to 1 of 4 protein regimens. Average initial and final BW were 89 and 123 kg, respectively. Pigs on treatments 1 to 4 were fed 16, 11, 16, and 13% CP from wk 0 to 2, respectively. From wk 2 to 5, the pigs on regimens 1 to 4 were then fed 15, 18.33, 18, and 20% CP, respectively, with regimens 3 and 4 also containing supplemental ractopamine (9.9 mg/kg) from wk 2 to 5. Overall (wk 0 to 5), BW gain, G:F, loin depth, percentage of lean, and dressing percentage were improved (P < 0.05) in pigs on regimens 3 and 4 compared with those on regimens 1 and 2. No statistically significant overall (wk 0 to 5) protein sequence regimen differences occurred between the standard regimens (1 and 3) and the low-high CP regimens (2 and 4). Experiment 2 involved 172 finishing pigs (mixed sex) in 2 protein regimens. Average initial and final BW were 91 and 136 kg, respectively. The diets consisted of 1) a control (16% CP from d 0 to 14, 18% CP + 4.95 mg of ractopamine/kg from d 14 to 24, and 18% CP + 9.9 mg of ractopamine/kg from d 24 to 35; 2) a low-high CP regimen (12.5% CP from d 0 to 14, 20.33% CP + 4.95 mg of ractopamine/kg from d 14 to 24, and 20.33% CP + 9.9 mg of ractopamine/kg from d 24 to 35. From d 0 to 14, pigs fed the low CP diet (12.5% CP) had reduced (P < 0.05) BW gain and G:F compared with those fed the control diet (16% CP). In contrast, from d 14 to 35, pigs on the low-high regimen had improved (P < 0.08) BW gain and G:F compared with pigs on the control regimen. Despite the wide dietary CP fluctuations for pigs in Exp. 2, performance and carcass traits were similar for both regimens over the 35-d test period. These data indicate that pigs fed deficient levels of CP and Lys for 14 d, followed by increased levels of CP and Lys during a subsequent 21-d period can recover and achieve growth performance and carcass merit equal to that achieved with a conventional protein feeding regimen.

Cyst(e)ine imbalance and its effect on methionine precursor utilization in chicks.

Five 9- or 12-d chick growth bioassays were done in batteries using 2 Met-deficient diets: a purified AA-based diet containing (by analysis, as-fed) 20.3% CP, 0.12% Met, and 0.05% cyst(e)ine; and an AA-fortified corn-peanut meal diet containing (by analysis, as-fed) 19.0% CP, 0.22% Met, and 0.23% cyst(e) ine. Feed-grade DL-Met (dl-M; 99%) was compared with feed-grade DL-OH-Met, Ca (OH-M; 84%). When the purified diet was modified to contain 0.12% Met and 0.20% or greater cyst(e)ine, slope-ratio assays involving graded dosing of DL-M (0, 404, 808, and 1,212 mg of DL-M/kg) or isosulfurous levels of OH-M resulted in linear (P < 0.01) BW gain and G:F responses. Multiple linear regression analysis (BW gain vs. supplemental sulfur intake, R(2) = 0.98) resulted in a mean bioefficacy estimate of 78.1% for OH-M vs. DL-M (equivalent to 65.6% on a supplemental compound basis). In assay 3, the purified diet was modified to be equally deficient in Met and cyst(e)ine [i.e., 0.12% Met, 0.12% cyst(e)ine]. When this diet was supplemented with either 404 mg of DL-M/kg or 476 mg of OH-M/kg, BW gain and G:F responded (P < 0.01) markedly to either compound, and differences between DL-M and OH-M were not significant (P > 0.10). Assays 4 and 5 used the corn-peanut meal basal diet containing 0.22% total Met and 0.23% total cyst(e)ine. In both assays, addition of either 465 mg of DL-M/kg or 554 mg of OH-M/kg resulted in increased (P < 0.01) BW gain and G:F, regardless of dietary cyst(e)ine concentration. In the absence of excess cyst(e)ine, BW gain responses to DL-M and OH-M were similar, but when 0.10% excess cyst(e)ine was provided as L-cystine or feather meal, DL-M responses tended to exceed those of OH-M. Moreover, this small excess of dietary cyst(e)ine, regardless of source, depressed (P < 0.01) feed intake and BW gain when added to the basal diet. Overall, these results suggest that excess dietary cyst(e)ine, when included in Met-deficient diets, has the potential to be both anorexigenic and pernicious to OH-M utilization.

DL-Methionine is as efficacious as L-methionine, but modest L-cystine excesses are anorexigenic in sulfur amino acid-deficient purified and practical-type diets fed to chicks.

Three bioassays were conducted to elucidate the effects of dietary cystine on the efficacy of L-Met and DL-Met fed to chicks. In assay 1, a purified diet markedly deficient in Met (0.12%) and cyst(e)ine (0.05%) was used to compare the relative effectiveness of L-Met and DL-Met in the presence of graded levels of dietary cystine. Addition of 0.05% Met improved (P < 0.01) weight gain when added to diets with 0 or 0.07% added L-cystine, but weight gain decreased linearly (P < 0.01) with greater cystine supplementation up to 0.35%, regardless of Met supplementation. There were no differences in growth performance due to supplementation of L-Met vs. DL-Met. In assay 2, a corn-soybean meal-peanut meal diet (0.25% Met and 0.25% cyst(e)ine) was supplemented with 0, 0.025, 0.05, or 0.075% L-Met plus 0 or 0.2% added L-cystine. Supplemental Met improved (P < 0.01) growth performance, but weight gain and feed intake were depressed (P < 0.01) by cystine supplementation. Whereas 0.2% added L-cystine depressed feed intake 6.9%, weight gain was reduced only 3.6%. Thus, cystine supplementation actually improved (P < 0.01) gain:feed. In assay 3, the corn-soybean meal-peanut meal diet was supplemented with 0 or 0.03% L-Met or DL-Met in the absence or presence of 0.2% added L-cystine. Again, Met supplementation improved (P < 0.01) growth performance, whereas supplemental cystine reduced (P < 0.05) weight gain and feed intake, but increased (P < 0.01) gain:feed. From these bioassays, it may be concluded that there is no evidence to suggest differences in effectiveness between L-Met and DL-Met in purified or practical-type low-protein diets of varying sulfur amino acid (SAA) content fed to chicks from 8 to 20 d of age. However, supplemental cystine has a negative impact on voluntary feed intake when supplemented in diets markedly deficient in SAA. This effect is evident with minimal SAA intake and when greater than 50% of SAA intake is provided by cyst(e)ine, rather than Met.

Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine.

Relative bioavailability and toxicity of N-acetyl-l-Cys (NAC) were evaluated in 9-d chick growth assays. The bioavailability of NAC relative to Cys was determined by feeding young chicks a highly purified crystalline AA diet singly deficient in Cys. Bio-availability estimates were obtained using standard slope-ratio methodology. N-Acetyl-l-cysteine was shown to be as effective as Cys in supporting chick growth, and was assigned a relative bioavailability value of 100%. To assess toxicity, a nutritionally adequate corn-soybean meal diet was supplemented with graded concentrations of NAC (isomolar to 10, 20, 30, or 40 g/kg of Cys, as-fed). When NAC supplied 10 or 20 g/kg of Cys, chick growth performance was unaffected, but NAC supplying 30 or 40 g/kg of Cys reduced (P < 0.05) BW gain by 13 and 34%, respectively, relative to the unsupplemented control diet. Only plasma-free NAC was substantially increased (P < 0.05) because of excess dietary NAC; plasma-free Cys was unaltered. We concluded that dietary NAC is efficacious in supplying Cys in support of chick growth, and only large excesses of NAC are growth depressing. Hence, the human clinical benefits of oral NAC likely result from its ability to deliver Cys safely and effectively to the portal circulation.

An Escherichia coli phytase expressed in yeast effectively replaces inorganic phosphorus for finishing pigs and laying hens.

Two experiments determined the efficacy of an Escherichia coli phytase (ECP) added to P-deficient, corn-soybean meal diets fed to finishing pigs and second-cycle laying hens. Sixty finishing pigs (49 +/- 0.9 kg) were formed into blocks within sex based on weight and ancestry and allotted to a P-deficient diet unsupplemented or supplemented with 0.10% inorganic P (iP) from KH2PO4 or ECP at 250, 500, 1,000, or 10,000 phytase units (FTU)/kg. Individually fed pigs were allowed ad libitum access to the experimental diets until a BW of 120 +/- 3 kg was achieved, at which time the pigs were euthanized and the left fibula and fourth metatarsal were excised for determination of bone ash. Pigs were fed a 2-phase diet program for early- and late-finishing pigs; available P in the basal diets was set 0.10% below the requirement. Dietary supplementation of iP or ECP increased weight gain (P < 0.10) and G:F (P < 0.01); performance was not different (P > 0.13) among the phytase-supplemented groups. Fibula ash was greatest (P < 0.01) for pigs fed diets containing 10,000 FTU of ECP/kg. Two hundred forty second-cycle hens were allotted to a P-deficient diet or a P-deficient diet supplemented with 0.10% iP or ECP at 150, 300, or 10,000 FTU/kg for a 12-wk experiment. The basal diet was a corn-soybean meal diet with no added iP (17% CP, 3.8% Ca, 0.10% available P). Hens fed the P-deficient diet were removed from the experiment after 4 wk due to poor egg production. Supplementation of iP or ECP resulted in increased (P < 0.01) feed intake, egg weight, and egg production during the first 4 wk. During the entire 12-wk period, there were no differences (P > 0.28) between the iP- and ECP-supplemented groups in feed intake, egg weight, or egg production. These experiments reveal that ECP was as efficacious as supplemental iP and that supplementation of an excess dose of ECP was efficacious and without negative effects in finishing pigs and laying hens.

Excess dietary lysine increases growth of chicks fed niacin-deficient diets, but dietary quinolinic acid has no niacin-sparing activity.

Catabolism of Trp and Lys produces alpha-ketoadipic acid as an intermediary metabolite. An alternate pathway of Trp turnover leads to NAD synthesis. We hypothesized that excess Lys might improve the conversion of Trp to niacin by causing a buildup of alpha-ketoadipic acid, thereby endproduct inhibiting the main Trp catabolic pathway and resulting in more niacin synthesis from Trp. Six bioassays were carried out in which 12 to 20 chicks were fed each experimental diet from d 8 to d 20 or 21 posthatching. The basal diet (4 mg/kg of bioavailable niacin) used for all assays was a semipurified corn gluten meal diet fortified with crystalline amino acids to 22.5% CP and 0.96% true digestible Lys. Assay 1 through 3 established the requirements for digestible Trp (0.16%) and bioavailable niacin (19.5 mg/kg) and showed that 0.96% digestible Lys was adequate for chick growth in the presence of adequate Trp and niacin. The fourth assay was done to determine the effect of 1% Lys (1.25% food-grade L-Lys x HCl) on niacin utilization. Excess Lys improved (P < 0.01) weight gain of niacin-deficient chicks. The fifth assay showed that 1% excess food-grade Lys improved weight gain in niacin-deficient (4 mg/kg) chicks but depressed weight gain in niacin-adequate (24 mg/kg) chicks (niacin x Lys interaction, P < 0.01). In assay 6, chicks fed 6 mg/kg of niacin gained faster (P < 0.01) than control chicks, but neither quinolinic acid (100 mg/kg) nor picolinic acid (4,200 mg/kg) elicited a response. These results suggest that excess Lys leads to an accumulation of alpha-ketoadipic acid, which causes endproduct inhibition of the main Trp catabolic pathway to CO(2), therefore increasing flux of 2-amino-3-carboxymuconate semialdehyde to NAD.

Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep.

A flock of Rambouillet sheep was examined because of increased lamb mortality caused by ineffective hemostasis at parturition. Neonatal-affected lambs presented with inadequate hemostasis at the umbilicus, pale mucus membranes, and markedly prolonged activated clotting time. Affected lambs had consistently prolonged 1-stage prothrombin times and activated partial thromboplastin times that supported a defect in the common pathway or defects in both the intrinsic and extrinsic pathway of the coagulation cascade. Decreased activity of vitamin K-dependent procoagulant factors II, VII, IX, and X in male and female lambs suggested either a defect of the hepatic enzyme gamma-glutamyl carboxylase, or vitamin K(1) 2,3 epoxide reductase. Affected lamb hepatic gamma-glutamyl carboxylase activity was markedly decreased compared with that of age- and sex-matched control lambs, while vitamin K(1) 2,3 epoxide reductase and glucose-6-phosphatase activities were similar between an affected and normal lamb. Subcutaneous vitamin K(1) supplementation did not increase vitamin K-dependent procoagulant factor activities in 3 lambs administered vitamin K(1) daily. These data confirm defective gamma-glutamyl carboxylase activity as the cause of impaired coagulation of sheep in this flock. This flock represents the only viable animal model of hereditarily defective gamma-glutamyl carboxylase activity.

Effect of reciprocating dietary lysine fluctuations on chick growth and carcass yield.

Three experiments (Exp) were conducted to study the effect of reciprocating (i.e., back-and-forth) fluctuations in dietary Lys concentration on growth performance of male broiler chicks. The Lys, CP, and ME concentrations were fluctuated in Exp 1 by varying corn and soybean meal concentrations. Corn-peanut meal diets in Exp 2 and 3 contained a constant calorie-protein ratio, but Lys concentrations were fluctuated by varying supplemental L-Lys x HCl. During 7-d feeding periods from d 8 to 43 posthatch, chicks fed the fluctuating regimen were provided diets with nutrient concentrations arranged in the following order (relative to control diets at any given point): excess-deficient-excess-deficient-adequate. In each Exp, differences in feed intake and gain:feed were observed during the first 7 d. Weight gain was never affected by dietary regimen. Overall, chicks fed the fluctuating regimen showed similar weight gain and feed intakes relative to chicks fed the control regimen. Additionally, efficiency of feed, Lys, CP, and ME utilization over the 35-d growth period of Exp 2 and 3 were not affected by dietary regimen. An increase in carcass yield (dressed, carcass weight as a percentage of live weight) of birds fed the fluctuating regimen was observed, but there were no differences in abdominal fat yield (as a percentage of dressed, carcass weight). These data support the conclusion that reciprocating 7-d periods of nutrient excess and deficiency do not affect overall growth performance of growing chicks.

Truncated gamma-glutamyl carboxylase in rambouillet sheep.

A flock of Rambouillet sheep was examined because of increased lamb mortality due to ineffective hemostasis at parturition. Decreased activities of coagulation factors II, VII, IX, and X, and severely reduced hepatic gamma-glutamyl carboxylase activity with adequate vitamin K 2,3 epoxide reductase activity was determined.(1,)(21) Parenteral vitamin K(1) supplementation did not improve vitamin K-dependent coagulation factor activities in 3 affected lambs. Affected lamb gamma-glutamyl carboxylase deoxyribonucleic acid was sequenced, and 4 single nucleotide polymorphisms (SNPs 2-5) of the gamma-glutamyl carboxylase gene were identified. Single nucleotide polymorphism-4 results in an arginine to stop codon (UGA) substitution, which prematurely terminates the peptide at residue 686 (R686Stop). This genotype (GATT/GATT) has a strong association with the coagulopathy observed in clinically affected lambs, P < 0.001. The frequency of SNP-3 in exon 11 (R486H) within the MARC 1.1 database is high in the US sheep population overall. Gamma-glutamyl carboxylase activity in hepatic microsomes from a SNP-3 homozygous lamb lacking the SNP-4 mutation (GACC/GACC) was similar to control sheep homozygous for arginine at 486 and also lacking SNP-4 (TGCC/TGCC), indicating that the R486H does not measurably impact gamma-glutamyl carboxylase activity. The remaining two SNPs (2 and 5) are located within non-coding intron sequences. These 4 SNPs allowed for determining the genotype associated with the observed fatal coagulopathy. Screening for the premature truncation (SNP-4) based on the presence of a Bbv I restriction site in clinically normal lambs but not in the homozygous affected lambs allows for detection of the heterozygous state (GATT/GACC), because carrier animals are clinically normal.

Effect of a novel phytase on growth performance, bone ash, and mineral digestibility in nursery and grower-finisher pigs.

To compare the effectiveness of 2 phytase enzymes (Phyzyme and Natuphos), growth performance, fibula ash, and Ca and P digestibilities were evaluated in 4 studies. The first 3 studies used 832 pigs (i.e., 288 in the nursery phase, initial BW 8.1 kg; 288 in the grower phase, initial BW 24.2 kg; and 256 in the finisher phase, initial BW 57.8 kg) and were carried out over periods of 28, 42, and 60 d, respectively. Dietary treatments in each study consisted of a positive control [available P (aP) at requirement level]; negative control (Ca remained as in the positive control, and aP at 66, 56, and 40% of the requirement for the nursery, grower, and finisher studies, respectively); negative control plus graded levels of Phyzyme [250, 500, 750, or 1,000; measured as phytase units (FTU)/kg] or Natuphos (250 and 500 FTU/kg for the nursery and grower studies, or 500 and 1,000 FTU/kg for the finisher study) plus a very high dose of Phyzyme (tolerance level, at 10,000 FTU/kg) in the nursery and grower experiments. Across the 3 studies, there was no effect of any dietary treatment on ADFI, but the negative control reduced ADG (10%), G:F (7%), and bone ash (8%) compared with the positive control. In the nursery study, phytase addition increased G:F and bone ash linearly (P < 0.01). In the grower study, phytase increased ADG, G:F, and bone ash linearly (P < 0.01). In the finisher study, phytase addition increased ADG and bone ash linearly (P < 0.01) and increased G:F quadratically (P < 0.05); G:F was, on average, 5% greater (P < 0.05) with Phyzyme than with Natuphos. The fourth study was conducted to investigate the P-releasing efficacy of the 2 phytases. The apparent fecal digestibility of P, measured with chromic oxide as an external marker in 35 pigs (55.9 kg of BW), showed that aP increased (P < 0.001) by 0.17 and 0.06 g (+/- 0.023) per 100 FTU consumed for Phyzyme and Natuphos, respectively. Also, Phyzyme at 10,000 FTU/kg was not detrimental to animal health or growth performance. At doses intended for commercial conditions, Phyzyme proved to be effective in releasing phytate bound P from diets, with an efficacy superior to a commercially available enzyme.

Effect of microbial phytase and citric acid on phosphorus bioavailability, apparent metabolizable energy, and amino acid digestibility in distillers dried grains with solubles in chicks.

Three experiments were conducted to evaluate the effectiveness of OptiPhos phytase and citric acid for releasing the P that is not bioavailable in distillers dried grains with solubles (DDGS). The effect of OptiPhos phytate on AME(n) and amino acid digestibility was also determined. New Hampshire x Columbian chicks were fed experimental diets from 8 to 21 d of age. For Experiment 1, a basal P-deficient diet contained 40% DDGS plus supplemental amino acids, and DDGS was the only source of P. The basal diet was then supplemented with 1,000 or 10,000 phytase units (FTU)/kg of OptiPhos phytase or with 0.2% of P from KH2PO4. In Experiment 2, a slope-ratio chick growth and tibia ash assay used a P-deficient soybean meal basal diet, and it was found that the bioavailability of P in DDGS was 67%. For Experiment 3, a P-deficient basal diet with 30% DDGS plus supplemental amino acids was supplemented with 0.05 or 0.1% P from KH2PO4, with 3% citric acid, or with 1,000 or 10,000 FTU/kg of OptiPhos phytase. In Experiment 1, both 1,000 and 10,000 FTU/kg of phytase increased tibia ash but had no effect on AME(n). Both 10,000 phytase units (FTU)/kg of phytase and supplemental P increased digestibility of amino acids. In Experiment 3, supplemental phytase and citric acid increased tibia ash (mg/tibia), and it was estimated that phytase and citric acid could release from 0.04 to 0.07% P from DDGS. In terms of bioavailability coefficients, the bioavailability of the P in DDGS was increased from 62 to 72%. These results indicate that phytase and citric acid increase the bioavailability of P in DDGS, but phytase at 1,000 FTU/kg had no consistent effect on AME(n) and amino acid digestibility.

Citric acid improves phytate phosphorus utilization in crossbred and commercial broiler chicks.

Previous research in our laboratory has shown that citric acid (CA) improves phytate P utilization in New Hampshire x Columbian (NHC) crossbred chicks fed a P-deficient corn-soybean meal diet. The current study was conducted to determine if CA is also effective in commercial broiler chicks (Ross x Ross). In 3 experiments, 4 replicate groups of 5 male NHC chicks and male commercial chicks were fed corn-soybean meal diets varying in CA and nonphytate P (NPP) from 8 to 22 d of age. In experiment 1, a 2 x 2 x 2 factorial treatment arrangement was used to evaluate the effect of 2 levels of CA (0 and 3%) and NPP (0.13 and 0.28%) in NHC chicks and commercial chicks. The commercial chicks, but not the NHC chicks, fed the 0.13% NPP diet had to be removed from the experiment after 3 to 5 d due to very poor growth and severe leg problems. Chick weight gain and tibia ash were significantly increased (P < 0.05) by CA in both types of chicks. In experiment 2, the same 2 x 2 x 2 factorial treatment arrangement was again used except that the NPP levels were 0.18 and 0.28%. Tibia ash was increased significantly (P < 0.05) with the addition of CA in both breeds of chicks; response was greater at 0.18% NPP than at 0.28% NPP. In experiment 3, graded levels of CA (0, 1, 2, 3, and 4%) were evaluated in commercial chicks fed diets containing 0.18% NPP. Tibia ash increased linearly (P < 0.05) as CA increased from 0 to 4%. The average increase in bone ash resulting from 3% CA supplementation in experiments 2 and 3 was 41%. These results indicate that CA markedly improved phytate P utilization in NHC and Ross x Ross commercial broiler chicks.

Tolerance for excess basic zinc chloride and basic copper chloride in chicks.

(1) Four chick experiments were conducted to determine toxicity estimates for basic zinc chloride (BZC) and basic copper chloride (BCC), now being used as sources for these minerals. (2) In experiment 1, New Hampshire x Columbian crossbred chicks were fed 0, 500, 1000, 1500, 3000 and 5000 mg Zn/kg from BZC (Zn5Cl2(OH)8). Broken-line regression analysis showed that the minimal toxic break points for chick weight gain and gain:food were 1720 and 2115 mg Zn/kg, respectively. (3) Crossbred chicks were fed 0, 150, 250, 500, 750 and 1000 mg Cu/kg from BCC (Cu2(OH)3C) in experiment 2. Regression analysis indicated that the minimal toxic break points for chick weight gain and gain:food were 642 and 781 mg Cu/kg, respectively. (4) In experiment 3, commercial broiler chicks were fed 0, 1500, 2000 and 2500 mg supplemental Zn/kg from BZC or 0, 500, 650 and 800 mg supplemental Cu/kg from BCC. Broiler chicks fed those high inclusion rates of Zn did not show reduced weight gain in comparison to chicks fed no supplemental Zn. All high concentrations of supplemental Cu depressed chick weight gain in comparison to control chicks. (5) Experiment 4 involved two separate 4 x 2 factorial designs with supplemental Zn (0, 2500, 3500 and 4500 mg/kg) or Cu (0, 500, 750 and 1000 mg/kg) and two breeds of chicks (crossbred and commercial). Significant interactions for weight gain, food intake, gain:food and liver Cu suggested that the crossbred and commercial chicks responded differently to high concentrations of supplementary dietary Cu.

Vitamin E supplementation does not mitigate the acute morbidity effects of porcine reproductive and respiratory syndrome virus in nursery pigs.

The objective of this study was to determine whether feeding a vitamin E-rich diet would benefit nursery pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV). Sixty-four pigs were subjected to one of four treatment combinations (2 x 2 factorial) of dietary vitamin E (adequate or excess) and PRRSV (medium or inoculation with VR-2385 isolate P-129). Pigs were fed experimental diets during a 3-wk period before inoculation as well as during a 12-d period after inoculation. Growth performance was determined throughout the study, and lipid peroxidation in liver, glutathione peroxidase (GPX) activity in serum, circulating white blood cells, and serum interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) were determined in samples collected from pigs killed 4 or 12 d after inoculation. Infection by PRRSV (P < 0.001) induced a marked decrease in both ADFI and ADG, but neither the main effect of diet nor the diet x PRRSV interaction was significant. Neither diet nor PRRSV affected feed efficiency. At 12 d after inoculation, lipid peroxidation in liver and GPX activity in serum were lower in pigs fed excess vitamin E than in those fed adequate vitamin E (P < 0.01), suggesting that the diet high in vitamin E bolstered the antioxidant status of the pigs. However, PRRSV did not affect lipid peroxidation in liver or serum GPX activity, and the diet x PRRSV interaction was not significant. White blood cell counts were decreased and IFN-gamma, and IL-1beta were increased (P < 0.05) 4 and 12 d after inoculation in PRRSV-infected pigs, but neither diet nor the diet x PRRSV interaction was significant. Collectively, these results indicate that increasing antioxidant defenses by feeding high levels of vitamin E did not ameliorate the effects of PRRSV on decreased growth, leukopenia, and increased serum IL-1beta and IFN-gamma. Thus, feeding nursery pigs a diet high in vitamin E may not be useful for mitigating the acute morbidity effects of PRRSV infection.

Phytase, citric acid, and 1alpha-hydroxycholecalciferol improve phytate phosphorus utilization in chicks fed a corn-soybean meal diet.

Previous research from our laboratory has shown that phytase, citric acid, and 1alpha-hydroxycholecalciferol [1alpha-(OH) D3] individually improve phytate P use in young chicks fed a P-deficient corn-soybean meal (C-SBM) diet. The current study was conducted to evaluate combinations of these additives on phytate P utilization. In 3 chick experiments, male crossbred chicks (New Hampshire x Columbian) were fed experimental diets from 8 to 21 d of age. The C-SBM basal diet used in all assays contained no supplemental P and was calculated to provide 23% CP, 0.13% nonphytate P (0.39% total P), 0.62% Ca, 25 mg of cholecalciferol/kg, and 3,260 kcal of TME/kg. In all 3 experiments, factorial arrangements (2 x 2 or 2 x 2 x 2) were used to evaluate 2 levels of phytase (0 and 300 units/kg), citric acid (0 and 3 or 4%), and 1alpha(OH) D3 (0 and 5, 10, or 15 microg/kg). Phytase, citric acid, and 1alpha-(OH) D3 each increased weight gain and tibia ash in all 3 experiments. There were some significant interactions among the compounds, but these were not consistent across experiments. Using standard curve methodology for tibia ash data, it was estimated that 0.03, 0.02, and 0.04% P were released by 3% citric acid, 300 units of phytase/kg, and 5 microg 1alpha-(OH) D3/kg, respectively, and that the combination of all 3 compounds resulted in the release of 0.13% P. Our results indicate that all 3 compounds increased phytate P use, and that their effects were generally additive, with some possible synergism between citric acid and 1alpha-(OH) D3.

Effect of copper, zinc, and manganese supplementation and source on reproduction, mineral status, and performance in grazing beef cattle over a two-year period.

Crossbred, multiparous beef cows (n = 178 in Year 1; n = 148 in Year 2) were used to evaluate the effects of Cu, Zn, and Mn supplementation and source on reproduction, mineral status, and performance in grazing cattle in eastern Colorado over a 2-yr period. Cows were stratified by expected calving date, age, BW, BCS, and liver mineral status and assigned to the following treatments: 1) control (no supplemental Cu, Zn, or Mn); 2) organic (ORG; 50% organic and 50% inorganic Cu, Zn, and Mn); and 3) inorganic (ING; 100% inorganic CuSO4, ZnSO4, and MnSO4). Free-choice mineral feeders were used to provide current NRC-recommended concentrations of Cu, Zn, and Mn from 82 d (Year 1) and 81 d (Year 2) before the average calving date of the herd through 110 d (Year 1) and 135 d (Year 2) after calving. At the end of Year 1, supplemented cows had greater liver Cu (P < 0.01), Zn (P < 0.05), and Mn (P < 0.01) concentrations compared with controls, whereas liver Cu concentration was greater (P < 0.01) in ORG vs. ING cows. At the end of Year 2, supplemented cows had greater (P < 0.01) liver Cu concentrations relative to controls, whereas control cows had greater (P < 0.02) liver Mn concentration than did supplemented cows. In Year 1, pregnancy rate to AI in control cows did not differ (P = 0.47) from supplemented cows, but there was a trend (P < 0.08) for pregnancy rate to be higher for ORG than ING cows. In Year 2, supplemented cows had a higher (P < 0.02) pregnancy rate to AI than controls. In both years, when cows were inseminated after an observed estrus, supplemented cows had a higher (P < 0.04) pregnancy rate than did controls. Also, for both years, overall 60-d pregnancy rate tended (P = 0.10) to be higher for supplemented cows than for controls. In Year 1, kilograms of calf weaned per cow exposed was greater (P < 0.02) in controls than in supplemented cows, and kilograms of calf weaned per cow exposed was greater (P < 0.01) in ING than ORG treatments. However, in Year 2, kilograms of calf weaned per cow exposed was greater (P < 0.02) in controls than in supplemented cows, and tended (P = 0.09) to be greater in ORG than ING treatments. Results indicate that supplementation and source of trace minerals affected mineral status and kilograms of calf weaned per cow exposed in grazing beef cows. Supplementation also improved pregnancy rate to AI compared with cows not supplemented with Cu, Zn, or Mn for more than 1 yr. Furthermore, mineral source may influence pregnancy rate to AI.