Effects of OmniGen AF feed supplementation on glucocorticoids, blood leukocyte messenger RNA abundance, and energy metabolism in overstocked Holstein dairy cows.

The physiological consequences of overstocking require more investigation, and no research has explored whether dietary supplements could mitigate the anticipated negative physiological effects. OmniGen AF (OG, Phibro Animal Health Corporation, Teaneck, NJ, USA) is a nutritional supplement that has been shown to support the immune system of cattle following internal and environmental stressors. This study aimed to determine if a 45-day period of OG feed supplementation would influence whole blood leukocyte messenger RNA abundance, energy metabolism and glucocorticoid concentration, during a two-week period of overstocking. Two stocking density treatments (control: one headlock and lying stall per cow; overstocked: 0.5 headlocks and 0.5 lying stalls per cow) and two diet treatments (control: no added supplement; and OG: 56 g/cow per day) were investigated. Four pens of 15 cows were fed their assigned diet (two pens per diet; control stocking density) for 45 days after which each stocking density treatment was applied for a 14-day period using a cross-over design; this study design was replicated twice. During each 14-day period, blood was collected on day four to measure whole blood leukocyte messenger RNA abundance (cluster of differentiation 80, interleukin 8 receptor-beta, interleukin 10 receptor-beta and L-selectin) and fecal samples were collected every two days to measure fecal cortisol metabolite concentration (11,17-dioxoandrostanes). At the end of each 14-day period, eight cows from each pen were selected for an intravenous glucose tolerance test; glucose, insulin and non-esterified fatty acids were measured. There were no effects of diet or stocking density on leukocyte messenger RNA abundance. Fecal cortisol metabolite concentrations were highest for overstocked cows on the control diet on day four of the stocking density treatment; however, by day 10, overstocked cows fed OG had the highest fecal cortisol metabolite concentrations. Overstocked cows, regardless of diet, had an attenuated insulin response during the glucose tolerance test, represented by a lower area under the curve estimate. Cows fed OG but not overstocked, had a lower non-esterified fatty acid nadir during the glucose challenge, compared to all the other treatments. In conclusion, overstocking prompts a physiological stress response and alters energy metabolism by decreasing the insulin response to an intravenous glucose challenge. Feeding OG during overstocking delayed the increase in fecal cortisol metabolites by several days; however, it is unclear if this altered glucocorticoid response benefited the cow, as OG had no effect on insulin responses or immune parameters.

Effects of yeast culture supplementation on lactation performance and rumen fermentation profile and microbial abundance in mid-lactation Holstein dairy cows.

The continuous trend for a narrowing margin between feed cost and milk prices across dairy farms in the United States highlights the need to improve and maintain feed efficiency. Yeast culture products are alternative supplements that have been evaluated in terms of milk performance and feed efficiency; however, less is known about their potential effects on altering rumen microbial populations and consequently rumen fermentation. Therefore, the objective of this study was to evaluate the effect of yeast culture supplementation on lactation performance, rumen fermentation profile, and abundance of major species of ruminal bacteria in lactating dairy cows. Forty mid-lactation Holstein dairy cows (121 ± 43 days in milk; mean ± standard deviation; 32 multiparous and 8 primiparous) were used in a randomized complete block design with a 7-d adaptation period followed by a 60-d treatment period. Cows were blocked by parity, days in milk, and previous lactation milk yield and assigned to a basal total mixed ration (TMR; 1.6 Mcal/kg of dry matter, 14.6% crude protein, 21.5% starch, and 38.4% neutral detergent fiber) plus 114 g/d of ground corn (CON; n = 20) or basal TMR plus 100 g/d of ground corn and 14 g/d of yeast culture (YC; n = 20; Culture Classic HD, Cellerate Yeast Solutions, Phibro Animal Health Corp.). Treatments were top-dressed over the TMR once a day. Cows were individually fed 1 × /d throughout the trial. Blood and rumen fluid samples were collected in a subset of cows (n = 10/treatment) at 0, 30, and 60 d of the treatment period. Rumen fluid sampled via esophageal tubing was analyzed for ammonia-N, volatile fatty acids (VFA), and ruminal bacteria populations via quantitative PCR amplification of 16S ribosomal DNA genes. Milk yield was not affected by treatment effects. Energy balance was lower in YC cows than CON, which was partially explain by the trend for lower dry matter intake as % body weight in YC cows than CON. Cows fed YC had greater overall ruminal pH and greater total VFA (mM) at 60 d of treatment period. There was a contrasting greater molar proportion of isovalerate and lower acetate proportion in YC-fed cows compared with CON cows. Although the ruminal abundance of specific fiber-digesting bacteria, including Eubacterium ruminantium and Ruminococcus flavefaciens, was increased in YC cows, others such as Fibrobacter succinogenes were decreased. The abundance of amylolytic bacteria such as Ruminobacter amylophilus and Succinimonas amylolytica were decreased in YC cows than CON. Our results indicate that the yeast culture supplementation seems to promote some specific fiber-digesting bacteria while decreasing amylolytic bacteria, which might have partially promoted more neutral rumen pH, greater total VFA, and isovalerate.

Effects of peripartal yeast culture supplementation on lactation performance, blood biomarkers, rumen fermentation, and rumen bacteria species in dairy cows.

Feeding yeast culture fermentation products has been associated with improved feed intake and milk yield in transition dairy cows. These improvements in performance have been further described in terms of rumen characteristics, metabolic profile, and immune response. The objective of this study was to evaluate the effects of a commercial yeast culture product (YC; Culture Classic HD, Phibro Animal Health) on performance, blood biomarkers, rumen fermentation, and rumen bacterial population in dairy cows from -30 to 50 d in milk (DIM). Forty Holstein dairy cows were enrolled in a randomized complete block design from -30 to 50 DIM and blocked according to expected calving day, parity, previous milk yield, and genetic merit. At -30 DIM, cows were assigned to either a basal diet plus 114 g/d of ground corn (control; n = 20) or a basal diet plus 100 g/d of ground corn and 14 g/d of YC (n = 20), fed as a top-dress. Cows received the same close-up diet from 30 d prepartum until calving [1.39 Mcal/kg of dry matter (DM) and 12.3% crude protein (CP)] and lactation diet from calving to 50 DIM (1.60 Mcal/kg of DM and 15.6% CP). Blood samples and rumen fluid were collected at various time points from -30 to 50 d relative to calving. Cows fed YC compared with control showed a trend for increased energy-corrected milk (+3.2 kg/d). Lower somatic cell counts were observed in YC cows than in control. We detected a treatment × time interaction in nonesterified fatty acids (NEFA) that could be attributed to a trend for greater NEFA in YC cows than control at 7 DIM, followed by lower NEFA in YC cows than control at 14 and 30 DIM. In the rumen, YC contributed to mild changes in rumen fermentation, mainly increasing postpartal valerate while decreasing prepartal isovalerate. This was accompanied by alterations in rumen microbiota, including a greater abundance of cellulolytic (Fibrobacter succinogenes) and lactate-utilizing bacteria (Megasphaera elsdenii). These results describe the potential benefits of supplementing yeast culture during the late pregnancy through early lactation, at least in terms of rumen environment and performance.

Response to adrenocorticotropic hormone or corticotrophin-releasing hormone and vasopressin in lactating cows fed an immunomodulatory supplement under thermoneutral or acute heat stress conditions.

Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.

An immunomodulatory feed additive enhances in vitro viral vaccine recall antigen responses in dairy heifers.

Enhancing immunological responses to vaccination is an important goal in many herd health management systems. OmniGen-AF®(OG) is an immunomodulatory feed additive that has been shown to enhance innate immune function in ruminants and its effects on adaptive immunity require additional study. The objective of this study was to evaluate post-vaccine antibody titers and circulating cellular memory development in heifers fed OG and administered a commercially available modified-live bovine respiratory disease (BRD) vaccine. Twenty-four Holstein heifers were assigned to one of two diets for 170 days: Control TMR (CON; n = 11), or TMR plus OG (TRT; 9 g/100 kg BW/day; n = 13). Samples for hematology, serology, and cellular assays were collected on D-110, 0, 21, 42, and 60 of the trial. Heifers were administered two priming doses of a modified-live BRD vaccine, with a third dose given on D0. There were no significant differences in total WBC and absolute number or the percentage of circulating lymphocytes, monocytes, neutrophils, RBC, or platelets on D-110 through D21. On D42 and D60, CON had significantly higher numbers of lymphocytes. On D0, mean serum neutralizing (SN) titer to BHV-1 was significantly higher for CON compared to TRT. SN titers were not significantly different between CON and TRT at any other time point for BHV-1, BVDV type 1, or BVDV type 2. TRT mounted a significantly stronger recall proliferative response to 0.5 multiplicity of infection (MOI) of BHV-1, BVDV type 1 and BVDV type 2 on D42 and D60; 0.25 MOI of BVDV type 1 on D21 and D42; and 0.25 MOI BVDV type 2 on D42 compared to CON. IL-4 production induced by 0.5 and 1.0 MOI BHV-1 (D42 and D60); 0.25 MOI of BVDV type 1 (D21); and 0.25 and 0.5 MOI of BVDV type 2 (D60) were significantly higher for TRT than CON. IL-17 production induced by 0.25 MOI of BVDV type 1 was significantly higher on D60 for TRT compared to CON. IFN-gamma and IL-10 were not significantly different between treatments. These data indicate feeding OG has a beneficial effect on responses to vaccine antigens in Holstein dairy heifers.

Effects of an immunomodulatory feed additive on intramammary infection prevalence and somatic cell counts in a dairy herd experiencing major health issues.

A trial was conducted to determine if feeding OmniGen-AF® (OG) to 22 late lactation cows 60 days prior to and during the early dry period, a time of increased susceptibility to mastitis, could reduce disease incidence in a dairy herd experiencing major health issues. Treated cows (n = 11) consumed a ration containing OG [9 g/100 kg of body weight/day] beginning 60 days before dry-off, during the dry period, and through 30 days in milk (DIM). Control cows received the same ration during the dry period through 30 DIM only. Body weights, body condition scores (BCS), intramammary infection (IMI) prevalence, new IMI rates, somatic cell counts (SCC), milk yield, and adverse health events were measured. No differences were found between treatments for body weight or BCS. Adverse health event data at calving showed no differences between treatments except for percentage of cows with hyperketonemia, which was lower among treated cows (63.6% vs 100%). Prevalence of IMI from calving through 30 DIM for treated cows (6.1%) was lower than controls (11.05%); likewise, new IMI rate during this time for treated cows (0.61%) was lower than controls (5.81%). The SCC from calving through 30 DIM for treated cows (215,000/ml) was lower than controls (493,000/ml). Average production/day at the first DHIA test (~33 DIM) showed that treated cows produced more milk (39.9 kg) than controls (35.34 kg). In conclusion, feeding OG 60 days prior to dry-off reduced hyperketonemia and mastitis, lowered SCC, and numerically increased milk yield in a dairy herd experiencing major health issues.

Effect of varying prepartum dietary cation-anion difference and calcium concentration on postpartum mineral and metabolite status and milk production of multiparous cows.

Eighty-two multiparous Holstein cows were enrolled 28 d before expected calving and assigned to 1 of 4 dietary treatments in a randomized block design experiment with a 2 × 2 factorial arrangement of treatments to determine the effect of feeding a neutral or acidogenic diet varying in Ca concentration on prepartum and postpartum intake, blood mineral and metabolite concentrations, and postpartum milk production. Prepartum diets were formulated to provide a dietary cation-anion difference (DCAD) of -21 (negative, NEG) or -2 (neutral, NEU) mEq/100 g of dry matter with either 1.3% or 1.8% Ca. After calving, cows remained on trial through 63 d in milk (DIM) and were fed a common lactation diet. Urine pH was lower for NEG compared with NEU and tended to be lower for 1.8% Ca compared with 1.3% Ca. Fractional excretion of Ca and Mg in urine was greater for NEG than for NEU. Prepartum plasma bicarbonate was lower and P was higher for NEG compared with NEU. Prepartum plasma P and blood urea nitrogen to creatinine ratio was higher for 1.3% compared with 1.8% Ca. Postpartum, concentrations of plasma total protein, albumin, blood urea nitrogen, Mg, and ionized Mg (iMg) were higher and Na was lower for NEU compared with NEG. An interaction of DCAD and Ca was observed for plasma creatinine, which was highest for cows fed NEU and 1.3% Ca compared with all other treatments. Interactions of DCAD and DIM were observed for plasma bicarbonate and iMg. Bicarbonate was higher at 3 DIM and lower at 14 DIM for NEU compared with NEG. Concentrations of iMg were higher at 1, 2, and 14 DIM for NEU compared with NEG. Interactions of Ca and DIM were observed for plasma Ca, Cl, and anion gap. Compared with cows fed 1.5% Ca, those fed 1.3% Ca had lower Ca and anion gap and higher Cl at 1 DIM and lower Cl and higher anion gap at 14 DIM. No differences were observed in body weight or body condition score due to DCAD or Ca. Prepartum dry matter intake (DMI) was lower for NEG compared with NEU and lower for 1.8% compared with 1.3% Ca. Postpartum DMI was not different among treatments. An interaction was observed for DCAD and DIM due to higher milk yield after 45 DIM for NEG compared with NEU. No differences were observed in milk component percentage or yield among treatments. There was an interaction of DIM and Ca for milk urea concentrations, which were higher at 5 wk and lower at 6 wk for 1.3% Ca compared with 1.8% Ca. These results suggest that feeding NEG prepartum alters plasma and urine mineral concentrations compared with feeding NEU and supports increased milk yield after 45 DIM. Feeding 1.8% Ca prepartum only improved plasma Ca at 1 DIM. Feeding either NEG or 1.8% Ca reduced DMI prepartum compared with NEU or 1.3% Ca.

Short communication: Blood mineral and gas concentrations of calves born to cows fed prepartum diets differing in dietary cation-anion difference and calcium concentration.

Eighty-two multiparous Holstein cows were fed diets differing in dietary cation-anion difference (DCAD) and Ca concentrations in a randomized block design experiment beginning 4 wk before anticipated calving to determine the effects on colostrum yield and quality and acid-base balance and mineral status of newborn calves. Treatments were arranged as a 2 × 2 factorial to provide 2 DCAD [-22 mEq/100 g of dry matter (NEG) or -3 mEq/100 g of dry matter (NEU)] and 2 supplemental Ca concentrations (1.3 or 1.8% of dry matter). After calving, cows were milked within 2 to 8 h and colostrum yield was recorded. Calves were fed 200 g of IgG of a commercial colostrum replacer within 4 h of birth. No differences were observed in birth weight or dystocia score among treatments, which averaged 42.7 kg and 1.12, respectively. Colostrum yield was not different among treatments and averaged 8.75 kg. Colostrum quality, as measured using a Brix refractometer, was not affected by DCAD but was higher for 1.3% compared with 1.8% Ca: 21.58% and 19.87%, respectively. Colostrum IgG concentrations were higher for NEG compared with NEU and for 1.3% compared with 1.8% Ca. No differences were observed in concentrations of serum IgG, Ca, P, K, Cl, anion gap, or whole-blood pH, partial pressure of O2, or SO2 of calves among treatments. Serum Mg and lactate concentrations were higher and CO2 tended to be lower for calves born to cows fed 1.3% compared with 1.8% Ca. Interactions of DCAD and Ca were observed for serum Na and Cl, which were higher for NEU-1.3% Ca and NEG-1.8% Ca compared with NEU-1.8% Ca and NEG-1.3% Ca. Whole-blood partial pressure of CO2, and HCO3 exhibited an interaction of DCAD and Ca and tended to be lower for NEU-1.3% Ca and NEG-1.8% Ca compared with NEU-1.8% Ca and NEG-1.3% Ca. Results of this trial indicate that feeding prepartum diets with 1.8% compared with 1.3% supplemental Ca reduced colostrum quality and serum concentrations of Mg and lactate in calves immediately after birth. Feeding NEG supported higher colostrum IgG concentrations. Blood mineral concentrations and blood gas balance tended to differ, but the effects were not consistent across DCAD and Ca.

An evaluation of an immunomodulatory feed ingredient in heat-stressed lactating Holstein cows: Effects on hormonal, physiological, and production responses.

Holstein cows (n = 30) were balanced by days in milk, milk production, and parity (91 ± 5.9 d in milk, 36.2 ± 2.5 kg/d, and 3.1 ± 1.4, respectively) and fed OmniGen-AF (OG; Phibro Animal Health, Teaneck, NJ), an immune stimulant, at 0 g/cow per d for control (CON) or 56 g/cow per d for OG for 52 d on a commercial dairy. At 52 d of the study cows were randomly selected (n = 12) from both groups (6 OG and 6 CON) and housed in environmentally controlled rooms at the Agricultural Research Complex for 21 d at the University of Arizona. Cows were subjected to 7 d of thermoneutral (TN) conditions, 10 d of heat stress (HS), and 4 d of recovery (REC) under TN conditions. Feed intake, milk production, and milk composition were measured daily. Rectal temperatures (RT) and respiration rates (RR) were recorded 3 times per day (600, 1400, and 1800 h). Blood samples were taken on d 7 (TN), 8 (HS), 10 (HS), 17 (HS), and 18 (TN) during the Agricultural Research Complex segment. Cows in HS had higher RR and RT and water intake and lower dry matter intake and milk yield than these measures in TN. There was a treatment × environment interaction with cows fed OG having lower RR and RT and higher dry matter intake during peak thermal loads than CON. However, milk yield did not differ between groups. Cows fed OG had lower milk fat percent than CON (3.7 vs 4.3%) during HS. The SCC content of milk did not differ between treatment groups but rose in both groups during the REC phase following HS. Plasma insulin and plasma glucose levels were not different between groups. However, plasma insulin in both groups was lower during acute HS, then rose across the HS period, and was highest during the REC phase. Plasma cortisol levels were highest in all cows on the first day of HS (d 8) but were lower in cows fed OG compared with CON. However, plasma ACTH concentrations were elevated in OG-fed animals at all times samples were collected. Plasma ACTH was also elevated in cows fed both OG and CON during HS. Feeding OG reduced plasma cortisol during acute but not chronic HS and increased basal plasma ACTH, suggesting that OG treatment may alter the hypothalamic pituitary adrenal axis.

Effect of nutritional immunomodulation and heat stress during the dry period on subsequent performance of cows.

Heat stress in dairy cows during the dry period impairs milk yield in the next lactation. Feeding OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ) to lactating cows during heat stress may increase dry matter intake (DMI) and lowers respiration rate (RR) and rectal temperature (RT), but the effects in dry cows are not known. We hypothesized that OG supplementation before, during, and after the dry period (approximately 160 d total) would overcome the effects of heat stress and improve cow performance in the next lactation. Cows were randomly assigned to OG or control (placebo) treatments for the last 60 d in milk (DIM), based on mature-equivalent milk yield in the previous lactation. Cows were dried off 45 d before expected calving and randomly assigned to heat stress (HT) or cooling (CL) treatments. Thus, cows received dietary supplementation during late lactation before they were exposed to either CL or HT. After dry-off, treatment groups included heat stress with placebo (HT, only shade, 56 g/d of placebo, n = 17), HT with OG supplementation (HTOG, 56 g/d of OG, n = 19), cooling with placebo (CL, shade, fans, and soakers, 56 g/d of placebo, n = 16), and CL with OG supplementation (CLOG, 56 g/d of OG, n = 11). After parturition, all cows were kept under the same CL system and management, and all cows continued to receive OG or control treatment until 60 DIM. Cooling cows during the dry period reduced afternoon RT (CL vs. HT; 38.9 ± 0.05 vs. 39.3 ± 0.05°C) and RR (CL vs. HT; 45 ± 1.6 vs. 77 ± 1.6 breaths/min). Respiration rate was also decreased by OG supplementation under HT conditions (HTOG vs. HT; 69.7 ± 1.6 vs. 77.2 ± 1.6 breaths/min). An interaction was observed between OG supplementation and HT; HTOG cows tended to have lower morning RT compared with HT cows. During the dry period, OG reduced DMI relative to control cows. Birth weight was greater in calves from CL cows (CL vs. HT; 40.6 ± 1.09 vs. 38.7 ± 1.09 kg). No differences were detected among treatments in hematocrit, total protein, and body condition score. Cows offered CLOG, CL, and HTOG treatments had greater body weight during the dry period (794.9 ± 17.9, 746.8 ± 16.7, and 762.9 ± 14.9 kg, respectively) than HT cows (720 ± 16.2 kg). Gestation length was approximately 4 d longer for CL cows compared with HT cows. Cows offered CLOG, CL, and HTOG treatments produced more milk (41.3 ± 1.6, 40.7 ± 1.6, and 40.5 ± 1.6 kg/d, respectively) than HT treatment (35.9 ± 1.6 kg/d). Body weight after parturition and DMI were evaluated up to 60 DIM and averaged 661.5 ± 15.8 and 19.4 ± 0.7 kg/d, respectively, with no differences observed among treatments. These results confirm that exposure of dry cows to heat stress negatively affects milk yield in the subsequent lactation. Active cooling of dry cows and OG supplementation can reduce the negative effects of heat stress in the dry period on subsequent performance.

A commercial immune modulating feed additive restores L-selectin and CCL5 expression following dexamethasone treatment of murine immune cells in a MyD88-dependent manner.

Bovine mastitis costs the dairy industry billions of dollars every year and presents a health challenge in dairy facilities. Immunosuppressive effects of the periparturient period increase the incidence of mastitis. During this time, cattle experience an elevation in circulating cortisol, which reduces polymorphonuclear cell function and ability to clear infection. OmniGen-AF (OMN; Phibro Animal Health, Teaneck, NJ) is an immunomodulatory feed additive that alters gene expression and is used to reduce rates of mastitis. We hypothesized that OMN restores gene expression during periods of immune stress through inhibiting the suppressive effects of glucocorticoid receptor signaling on Toll-like receptor signaling. To test our hypothesis, wild-type (WT) or MyD88 knockout mice were supplemented with OMN and challenged with lipopolysaccharide following dexamethasone (Dex) treatment. Polymorphonuclear cell and macrophage RNA was isolated from intraperitoneal lavages and analyzed for gene expression profiles. Treatment of mice with Dex suppressed expression of l-selectin and CCL5 as compared with phosphate-buffered saline treatment of WT mice. Expression of l-selectin and CCL5 was significantly reduced with Dex treatment in control-fed but not OMN-supplemented WT mice. The protective effect of OMN supplementation on l-selectin expression during Dex treatment was abolished in MyD88 knockout mice. These results suggest that OMN supplementation restores responses of certain genes suppressed by Dex in immune cells in a MyD88-dependent manner. Future research will determine the specific Toll-like receptors, transcription factors, and biochemical properties of OMN that restore gene expression in immunosuppressed cells.

Effects of prepartum dietary cation-anion difference on aspects of peripartum mineral and energy metabolism and performance of multiparous Holstein cows.

The objectives of this study were to determine the effect of decreasing dietary cation-anion difference [DCAD; (Na+ + K+) - (Cl- + S2-)] of the prepartum diet on aspects of mineral metabolism, energy metabolism, and performance of peripartum dairy cows. Multiparous Holstein cows (n = 89) were enrolled between 38 and 31 d before expected parturition and randomized to treatments in a completely randomized design (restricted to balance for previous 305-d mature equivalent milk production, parity, and body condition score) at 24 d before expected parturition. Treatments consisted of a low-K ration without anion supplementation [CON; n = 30, DCAD = +18.3 mEq/100 g of dry matter (DM)]; partial anion supplementation to a low-K ration (MED; n = 30, DCAD = +5.9 mEq/100 g of DM); and anion supplementation to a low-K ration to reach a targeted average urine pH between 5.5 and 6.0 (LOW; n = 29, DCAD = -7.4 mEq/100 g of DM). Cows were fed a common postpartum diet and data collected through 63 d in milk. Urine pH (CON = 8.22, MED = 7.89, and LOW = 5.96) was affected quadratically by decreasing prepartum DCAD. A linear relationship between urine pH and urine Ca:creatinine ratio was observed (r = -0.81). Plasma Ca concentrations in the postpartum period (d 0 to 14; CON = 2.16, MED = 2.19, and LOW = 2.27 mmol/L) were increased linearly with decreasing prepartum DCAD. A treatment by parity (second vs. third and greater) interaction for postpartum plasma Ca concentration suggested that older cows had the greatest response to the low DCAD diet and older cows fed LOW had decreased prevalence of hypocalcemia after calving. A quadratic effect of decreasing DCAD on prepartum DMI was observed (CON = 13.6, MED = 14.0, and LOW = 13.2 kg/d). Milk production in the first 3 wk postpartum was increased linearly with decreasing DCAD (CON = 40.8, MED = 42.4, and LOW = 43.9 kg/d) and DMI in this period also tended to linearly increase (CON = 20.2, MED = 20.9, and LOW = 21.3 kg/d). Overall, effects on intake and milk yield analyzed over wk 1 to 9 postpartum were not significant. This study demonstrates that feeding lower DCAD diets prepartum improves plasma Ca status in the immediate postpartum period and results in increased DMI and milk production in the 3 wk after parturition. Compared with no anion supplementation or lower levels of anion supplementation, greater improvements were observed with the lower DCAD feeding strategy, in which an average urine pH of 5.5 to 6.0 was targeted.

Effect of feeding a negative dietary cation-anion difference diet for an extended time prepartum on postpartum serum and urine metabolites and performance.

Forty-five multiparous Holstein cows and 15 springing Holstein heifers were used in a randomized block design trial to determine the effect of length of feeding a negative dietary anion-cation difference (DCAD) diet prepartum on serum and urine metabolites, dry matter (DM) intake, and milk yield and composition. After training to eat through Calan doors (American Calan Inc., Northwood, NH), cows within parity were assigned randomly to 1 of 3 treatments and fed a negative-DCAD diet for 3 (3 W), 4 (4 W), or 6 wk (6 W) before predicted calving. Actual days cows were fed negative-DCAD diets was 19.2 ± 4.1, 27.9 ± 3.1, and 41.5 ± 4.1d for 3 W, 4 W, and 6 W, respectively. Before the trial, all cows were fed a high-forage, low-energy diet. During the trial, cows were fed a diet formulated for late gestation (14.6% CP, 42.3% NDF, 20.5% starch, 7.1% ash, and 0.97% Ca) supplemented with Animate (Prince Agri Products Inc., Quincy, IL), with a resulting DCAD (Na + K - Cl - S) of -21.02 mEq/100g of DM. After calving, cows were fed a diet formulated for early lactation (18.0% CP, 36.4% NDF, 24.2% starch, 8.1% ash, and 0.94% Ca) for the following 6 wk with a DCAD of 20.55 mEq/100g of DM. Urine pH was not different among treatments before calving and averaged 6.36. No differences were observed in prepartum DM intake, which averaged 11.4, 11.5, and 11.7 kg/d for 3 W, 4 W, and 6 W, respectively. Prepartum serum total protein, albumin, and Ca concentrations, and anion gap were within normal limits but decreased linearly with increasing time cows were fed a negative-DCAD diet. No differences were observed in serum metabolite concentrations on the day of calving. Postpartum, serum total protein and globulin concentrations increased linearly with increasing length of time the negative-DCAD diet was fed. No differences were observed in postpartum DM intake, milk yield, or concentration of fat or protein among treatments: 19.1 kg/d, 40.6 kg/d, 4.30%, and 2.80%; 19.6 kg/d, 41.5 kg/d, 4.50%, and 2.90%; and 18.6 kg/d, 41.0 kg/d, 4.30%, and 2.73% for 3 W, 4 W, and 6 W, respectively. Results of this trial indicate that no differences existed in health or milk production or components in cows fed a negative-DCAD diet for up to 6 wk prepartum compared with those fed a negative-DCAD diet for 3 or 4 wk prepartum.

Can the two mechanisms of tumor cell killing by radiation be exploited for therapeutic gain?

The radiation killing of tumor cells by ionizing radiation is best described by the linear-quadratic (LQ) model. Research into the underlying mechanisms of α- and ß-inactivation has suggested that different molecular targets (DNA in different forms) and different microdosimetric energy deposits (spurs versus electron track-ends) are involved. Clinical protocols with fractionated doses of about 2.0 Gy/day were defined empirically, and we now know that they produce cancer cures mainly by the α-inactivation mechanism. Radiobiology studies indicate that α and ß mechanisms exhibit widely different characteristics that should be addressed upfront as clinical fractionation schemes are altered. As radiation treatments attempt to exploit the advantages of larger dose fractions over shorter treatment times, the LQ model can be used to predict iso-effective tumor cell killing and possibly iso-effective normal tissue complications. Linking best estimates of radiobiology and tumor biology parameters with tumor control probability (TCP) and normal tissue complication probability (NTCP) models will enable us to improve and optimize cancer treatment protocols, delivering no more fractions than are strictly necessary for a high therapeutic ratio.

Effect of rocker shoe design features on forefoot plantar pressures in people with and without diabetes.

BACKGROUND: There is no consensus on the precise rocker shoe outsole design that will optimally reduce plantar pressure in people with diabetes. This study aimed to understand how peak plantar pressure is influenced by systematically varying three design features which characterise a curved rocker shoe: apex angle, apex position and rocker angle. METHODS: A total of 12 different rocker shoe designs, spanning a range of each of the three design features, were tested in 24 people with diabetes and 24 healthy participants. Each subject also wore a flexible control shoe. Peak plantar pressure, in four anatomical regions, was recorded for each of the 13 shoes during walking at a controlled speed. FINDINGS: There were a number of significant main effects for each of the three design features, however, the precise effect of each feature varied between the different regions. The results demonstrated maximum pressure reduction in the 2nd-4th metatarsal regions (39%) but that lower rocker angles (<20°) and anterior apex positions (>60% shoe length) should be avoided for this region. The effect of apex angle was most pronounced in the 1st metatarsophalangeal region with a clear decrease in pressure as the apex angle was increased to 100°. INTERPRETATION: We suggest that an outsole design with a 95° apex angle, apex position at 60% of shoe length and 20° rocker angle may achieve an optimal balance for offloading different regions of the forefoot. However, future studies incorporating additional design feature combinations, on high risk patients, are required to make definitive recommendations.

The use of a formal sensitivity analysis on epidemic models with immune protection from maternally acquired antibodies.

This paper considers the outcome of a formal sensitivity analysis on a series of epidemic model structures developed to study the population level effects of maternal antibodies. The analysis is used to compare the potential influence of maternally acquired immunity on various age and time domain observations of infection and serology, with and without seasonality. The results of the analysis indicate that time series observations are largely insensitive to variations in the average duration of this protection, and that age related empirical data are likely to be most appropriate for estimating these characteristics.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

Search for active neutrino disappearance using neutral-current interactions in the MINOS long-baseline experiment.

We report the first detailed comparisons of the rates and spectra of neutral-current neutrino interactions at two widely separated locations. A depletion in the rate at the far site would indicate mixing between nu(mu) and a sterile particle. No anomalous depletion in the reconstructed energy spectrum is observed. Assuming oscillations occur at a single mass-squared splitting, a fit to the neutral- and charged-current energy spectra limits the fraction of nu(mu) oscillating to a sterile neutrino to be below 0.68 at 90% confidence level. A less stringent limit due to a possible contribution to the measured neutral-current event rate at the far site from nu(e) appearance at the current experimental limit is also presented.

Testing Lorentz invariance and CPT conservation with NuMI neutrinos in the MINOS near detector.

A search for a sidereal modulation in the MINOS near detector neutrino data was performed. If present, this signature could be a consequence of Lorentz and CPT violation as predicted by the effective field theory called the standard-model extension. No evidence for a sidereal signal in the data set was found, implying that there is no significant change in neutrino propagation that depends on the direction of the neutrino beam in a sun-centered inertial frame. Upper limits on the magnitudes of the Lorentz and CPT violating terms in the standard-model extension lie between 10(-4) and 10(-2) of the maximum expected, assuming a suppression of these signatures by a factor of 10(-17).