Indigenous chicken production system in different agro-ecology of Indian Himalayan Region: implication on food and economic security.

The indigenous chicken production system (ICPS) has several use values and ecosystem services. In the last few years, ICPS has been recognized for its possible contribution to household food security, income generation, wildlife protection, and bettering the women's lives. This study aimed to collect, for the first time, comprehensive information about ICPS in three different agro-ecologies (tropical, sub-tropical, and sub-temperate) of the Indian Himalayan Region (IHR) and its role in food and economic security of traditional communities. In this study region, ICPS is semi-extensive, providing homegrown feed and temporary night shelter. In sub-temperate agro-ecology, females owned non-significant (p = 0.170) more indigenous chicken flocks than males. Households in sub-temperate agro-ecologies had significantly (p ≤ 0.001) larger flock sizes and tropical livestock units (chicken-TLU). However, the livestock diversity index (LDI) was significantly higher (p ≤ 0.001) in tropical and subtropical agro-ecology. The households in the sub-temperate region highly (p ≤ 0.001) valued indigenous chicken because of its survivability and adaptability. In absolute numbers significant (p ≤ 0.001) higher numbers of adult birds died in past 1 year in sub-temperate agro-ecology. The mortality rate of adult birds in sub-temperate agro-ecology was 9%, and it was 14 and 15% in tropical and sub-tropical agro-ecologies, respectively. In sub-temperate agro-ecology, larger flock size translated into significantly higher (p ≤ 0.001) egg production and subsequently a significant (p ≤ 0.001) higher egg consumption per household per month. In sub-temperate agro-ecology, households' dietary diversity score was significantly (p ≤ 0.001) higher. Similarly, the average annual income from ICPS was significantly higher (p ≤ 0.001) in sub-temperate agro-ecology and accounted for 18% of household income. ICPS' marketing chain was relatively short in the sub-temperate region. In all agro-ecologies, indigenous chicken and egg demand was significantly higher (p ≤ 0.001) in the winter. ICPS litter is used as farmyard manure, enhancing ecological resilience. In all agro-ecologies, the three most frequently cited obstacles to extending the indigenous chicken production system are illnesses, predators, and a lack of chicks availability. ICPS contributes to food and nutritional security, economic stability, and ecological resilience in this hilly and fragile ecosystem. Even though the system is self-sustaining, management and health interventions can increase production and productivity.

Participatory assessment of management and biosecurity practices of smallholder pig farms in North East India.

The present study was aimed at describing the pig production system, farm management, pig movement, and existing biosecurity level of smallholders' pig production system in North East India. A cross-sectional survey of 1,000 pig producers in four districts (two urban and two rural) in core pig-producing regions of India, where ASF occurrence had been reported, was conducted. The mean pig population was significantly (p < 0.05) higher in urban districts. In urban districts, most of the pig houses were isolated but located on the roadside, while in rural districts, commune pig houses along the roadside were more common. The majority of the respondent purchased (91%) or sold (60%) the pigs during the past 12 months. Swill feeding was common in the entire study area. The majority of the respondent (80%) in rural districts were unaware of ASF. Significant pig trade of live pigs and pork products was observed in the urban district. In the case of on-farm biosecurity measures, only 6.9% of respondents had fencing for the pig farm, 99.3% did not have provision for a footbath, and only 17.2% of the respondents restricted visitors' access to the pig farm. The study revealed that the pig production system is dominated by smallholding units with a frequent introduction or exit of pigs along with poor on-farm biosecurity measures. With the current level of farm management and biosecurity practices, smallholder pig farmers are at an increased risk of ASF and other contagious diseases.

Toxicological evaluation of brominated vegetable oil in Sprague Dawley rats.

Brominated vegetable oil (BVO) has been approved by the US Food and Drug Administration on an interim basis as a food additive. Past studies have raised concerns about potential toxicities from consuming BVO. To investigate further these toxicities, we conducted a 90-day dietary exposure study in Sprague Dawley rats and analyzed tissue distribution of the main metabolites. Six-week-old male and female rats were fed diets containing 0 (control), 0.002%, 0.02%, 0.1%, or 0.5% BVO by weight. Statistically significant increases were observed in the serum bromide in the high-dose group of both sexes and in the incidence of thyroid follicular cell hypertrophy in the two highest dose groups of males and the high-dose group of females. An increase in serum TSH was observed in the high-dose group for both sexes, as well as a decrease in serum T4 in the high-dose males. A clear dose-response was observed in di- and tetra-bromostearic acid levels in the heart, liver, and inguinal fat. These data expand upon previous observations in rats and pigs that oral exposure to BVO is associated with increased tissue levels of inorganic and organic bromine, and that the thyroid is a potential target organ of toxicity.

A biobank analysis of prognostic biomarkers of the systemic inflammatory response in patients presenting with malignancy of undefined primary origin.

BACKGROUND: Survival prediction in patients presenting with malignancy of undefined primary origin (MUO) is challenging, with a lack of validated prognostic tools. Biomarkers of the systemic inflammatory response independently predict survival in other cancer types, but their role in MUO is unclear. The aim of this study was to assess biomarkers of the systemic inflammatory response in patients presenting with MUO. PATIENTS AND METHODS: A biobank of 1049 patients presenting with MUO referred to a regional oncology service in Scotland was analysed. Key inflammatory biomarkers (white cell count, neutrophil count and C-reactive protein combined with albumin [to give the modified Glasgow Prognostic Score {mGPS}]) were examined. The relationship between these and survival was examined using Kaplan-Meier and Cox regression methods. RESULTS: Data were available for 1049 patients. Median survival was 4.3 months (interquartile range: 1.7-16.0 months). On multivariate analysis mGPS was independently associated with survival and stratified survival from 13.6 months (mGPS: 0) to 2.3 months (mGPS: 2) (p < 0.001). The mGPS was predictive of survival on multivariate analysis in patients found to have a non-cancer diagnosis (p = 0.034), an identified primary cancer (0.002), cancer of unknown primary (CUP) (p = 0.011), those for whom biopsy was not done (MUO) (p = 0.036), those found to have an identified primary cancer (0.002) and even those found to have a non-cancer diagnosis (p = 0.034) after further detailed investigations. In patients with CUP mGPS predicted survival regardless of the recognised clinicopathological prognostic subgroup (p < 0.001). CONCLUSIONS: The results of the present study demonstrate that biomarkers of the systemic inflammatory response are reliable prognostic factors in patients presenting with MUO. These simple, objective, routine clinical tests may inform clinical management.

A two-year toxicology study of bisphenol A (BPA) in Sprague-Dawley rats: CLARITY-BPA core study results.

We report the data from the guideline-compliant two-year toxicology study conducted as part of the Consortium Linking Academic and Regulatory Insights on Bisphenol A Toxicity (CLARITY-BPA). BPA (0, 2.5, 25, 250, 2,500, and 25,000 µg/kg body weight (bw)/day) was administered daily by gavage in 0.3% carboxymethylcellulose vehicle to NCTR Sprague-Dawley rats from gestation day 6 through the start of parturition and then directly to pups from the day after birth until postnatal day 21 (stop-dose arm) or continuously until termination at one or two years. The stop-dose arm was included to assess the potential for any BPA effects that were due to developmental exposure. No BPA-related effects were evident in the in-life and non-histopathology data. Neoplastic and nonneoplastic lesions diagnosed in both females and males were common age-associated lesions that were variable across control and BPA-treated groups. The lack of consistent responses within the continuous- and stop-dose arms within and across tissues brought into question the plausible relationship of most of these lesions to BPA treatment. There was a possible relationship between the increased incidences of lesions in the female reproductive tract and the male pituitary and exposure to the 25,000 µg BPA/kg bw/day dose level.

Model to evaluate the impact of hospital-based interventions targeting false-positive blood cultures on economic and clinical outcomes.

BACKGROUND: Blood culture contamination (BCC) increases length of stay (LOS) and leads to unnecessary antimicrobial therapy and/or hospital-acquired conditions (HACs). AIM: To quantify the magnitude of additional LOS, costs to hospitals and society, and harm to patients attributable to BCC. METHODS: A retrospective matched survival analysis was performed involving hospitalized patients with septicaemia-compatible symptoms. BCC costs, HACs and potential savings were calculated based on the primary LOS data, a modified Delphi process and published sources. The cost analysis compared standard care with interventions for reducing BCC, and estimated annual economic and clinical consequences for a typical hospital and for the USA as a whole. FINDINGS: Patients with BCC experienced a mean increase in LOS of 2.35 days (P=0.0076). Avoiding BCC would decrease costs by $6463 [$4818 from inpatient care (53% of which was from reduced LOS) and 26% from reduced antibiotic use]. Annually, in a typical 250- to 400-bed hospital, employing phlebotomists would save $1.3 million and prevent 24 HACs (including two cases of Clostridium difficile infection); based on clinical efficacy evidence, use of the studied initial specimen diversion device (ISDD) would save $1.9 million and prevent 34 HACs (including three cases of C. difficile infection). In the USA, the respective strategies would prevent 69,300 and 102,900 HACs (including 6000 and 8900 cases of C. difficile infection) and save $5 and $7.5 billion. CONCLUSION: Costs and clinical burdens associated with false-positive cultures are substantial and can be reduced by available interventions, including phlebotomists and use of ISDD.

Plasma essential amino acid concentrations in response to casein infusion or ration change in dairy cows: A multilevel, mixed-effects meta-analysis.

The objectives of the current meta-analysis were to review the relationships between plasma individual essential AA concentrations and their respective AA digestible flows (AADI) in 2 independent sets of studies. The first set of studies included 36 casein infusion studies (CN; 83 treatment means) and was regarded as the best comparison standard available, because differences in AADI achieved by casein infusion (up to 40% of total metabolizable protein supply) did not rely on any model assumptions and were directly estimated from casein infusions. The second set of studies included 42 feeding trials (FT; 94 treatment means) in which AADI were predicted using the 2001 National Research Council model. The 2 sets of studies were not balanced for dry matter intake and the supplies of metabolizable protein and net energy for lactation; therefore, a subset of 17 CN studies (35 treatment means) and 19 FT trials (49 treatment means) balanced for these variables was assembled to allow the comparison of linear terms from CN and FT studies. In the subset of data set, the linear terms of individual AA did not differ between CN and FT studies except for Met and Thr, with a slope lower by 23 and 62%, respectively, in CN versus FT studies. The agreement in linear slopes between CN and FT studies indicates, indirectly, that AADI were predicted accurately by the National Research Council model. In the large data set, the relationships between plasma concentrations of Ile, Leu, Val, and their sum (branched-chain AA; BCAA) and their respective AADI shared common characteristics that distinguished them from the other AA. For the plasma concentration of BCAA, the linear terms were significant in CN and FT studies, but the quadratic terms were significant only in FT studies. This decline in the response of plasma concentration of BCAA to increased BCAA digestible flow in FT studies was associated with diets rich in energy, diets with a high concentrate level, or diets based on corn silage. These dietary conditions can stimulate insulin secretion and decrease plasma concentration of BCAA. For the non-BCAA, a quadratic term was significant for plasma His, Lys, Met, and Thr in each set of studies, indicating an increased removal of these AA by the liver as AADI increased.

Interactions between levels of heat-treated soybean meal and prilled fat on growth, rumen fermentation, and blood metabolites of Holstein calves.

This study evaluated the interaction of RUP and fat levels on growth, rumen fermentation, and blood metabolites of Holstein calves. Forty 3-d-old calves (20 females and 20 males) with a starting BW of 40.6 ± 2.8 kg were used in a completely randomized design with a 2 × 2 factorial arrangement of treatments. Within sex treatments were: (1) high RUP and low fat (HRUP-LF); (2) low RUP and high fat (LRUP-HF); (3) high RUP and low fat (HRUP-LF); and high RUP and high fat (HRUP-HF). Low-RUP starter contained 21.5%, whereas high RUP starter contained 34.3% RUP as % of CP, whereas low fat starter contained 2.9% and high starter contained 5.8% crude fat based on DM. Isonitrogenous levels in the starter grain were maintained by replacing solvent soybean meal with heat treated soybean meal while fat levels were increased by the addition of prilled fatty acids. Calves were housed individually and had ad libitum access to water and calf starter throughout the study. All calves were weaned on d 60 of age but remained in the study until d 70 for final measurements. Overall, there was no interaction between RUP and fat levels for measured variables. Starter intake tended ( = 0.09) to be greater for calves fed low fat starter during the postweaning period, although over the whole experiment and during the preweaning period, differences in starter intake were not different. Although there were no differences for most VFA concentrations, the molar proportion of butyrate tended ( < 0.08) to be greater in the rumen of calves fed low-fat starter compared to those fed high-fat starter. Serum total protein was lower ( < 0.05) and serum cholesterol was greater ( < 0.01) for calves fed high-fat starter by d 65 of life. The concentration of alanine aminotransferase was also lower ( < 0.05) for calves fed high-fat starter compared to those fed low-fat starter on d 65, and these levels tended to increase with the addition of RUP ( < 0.07). In conclusion, no effects were attributable to feeding a high-RUP starter. However, feeding a calf starter with over 3% fat appeared to decrease starter intake as growth progressed.

Effects of rumen-protected methionine, lysine, and histidine on lactation performance of dairy cows.

The objective of this study was to evaluate the effects of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Met, Lys, and His, individually or combined, on the performance of lactating dairy cows. The experiment was a 9-wk randomized complete block design with 72 Holstein cows. Following a 2-wk covariate period, cows were blocked by days in milk, milk yield, and parity, and randomly assigned to 1 of the following 6 treatments: (1) MP-adequate diet [MPA; +243g/d MP balance, according to the National Research Council (2001) requirements]; (2) MP-deficient diet (MPD; -54g/d MP balance); (3) MPD supplemented with RPMet (MPDM); (4) MPD supplemented with RPLys (MPDL); (5) MPD supplemented with RPHis (MPDH); and (6) MPD supplemented with RPMet, RPLys, and RPHis (MPDMLH). Dry matter intake (DMI), yields of milk and milk components (fat, protein, lactose) and energy-corrected milk (ECM), feed and ECM feed efficiencies, and milk and plasma urea N were decreased by MPD, compared with MPA. Supplementation of the MPD diet with RPLys increased milk protein content and plasma glucose concentration and tended to increase milk urea N. Addition of RPHis tended to increase DMI, increased milk protein concentration, and numerically increased yields of milk fat, protein, and ECM. In addition to the trends for increased DMI and milk fat content, and higher milk protein concentration, supplementation of the 3 RP AA also increased yields of milk fat, protein, and ECM and ECM feed efficiency. Relative to MPA, milk N efficiency tended to be increased by MPD. Concentrations of plasma essential AA (except Met and Thr) were decreased by MPD compared with MPA. Supplementation of RPMet, RPLys, and RPHis increased plasma Met (except for MPDM), Lys, and His concentrations, respectively. Cows fed MPD had lower blood hemoglobin concentration and numerically higher plasma ghrelin than cows fed MPA. Concentration of total saturated fatty acids in milk fat were or tended to be higher for MPD compared with MPA and MPDMLH, respectively. Concentration of total polyunsaturated and yield of milk odd- and branched-chain fatty acids were or tended to be decreased by MPD compared with MPA. Overall, the results of this study confirm our previous data and suggest that His stimulates DMI and the combination of the 3 RP AA (Met, Lys, and His) has the potential to improve milk and milk component yields in dairy cows fed MP-deficient diets.

Relationships between circulating plasma concentrations and duodenal flows of essential amino acids in lactating dairy cows.

The objective of this study was to better define essential AA (EAA) requirements in lactating dairy cows through examination of the relationship between plasma essential AA concentration (p[EAA]) and predicted duodenal flow of essential AA (EAAduo). Our hypothesis was that at a given level of milk protein output, p[EAA] would remain steady in response to increasing EAAduo until the EAA requirement was met, at which point p[EAA] would increase rapidly in response to greater duodenal flow of EAA until p[EAA] reached a plateau as other body processes degraded excess EAA to avoid toxicity. Thus, the requirement of each EAA would be fulfilled when p[EAA] increased rapidly. To investigate this hypothesis, we compiled a literature database that included 102 studies with 420 treatment means that reported p[EAA], dietary nutrient content, body weight, and milk production. A second database was produced to validate relationships developed in the first database and included 32 studies with 98 treatment means. All relationships were evaluated as regression equations with study as a random factor. Breed, days in milk, body weight, and milk protein production had no effect on the plasma concentration of any EAA. Other than metabolizable protein supply, nutritional content of the rations did not affect p[EAA]. Only p[Arg] was affected by parity, with primiparous cows having higher concentrations of Arg than older cows. No break points in the relationship between p[EAA] versus EAAduo were detected as either steep increases or plateaus. Plasma Arg, Ile, Lys, Thr, and Val concentrations were best associated with their respective EAAduo as quadratic equations, whereas His, Leu, Met, and Phe were associated only linearly. Adding a quadratic term improved the adjusted R(2) or decreased the root mean square error marginally (<2.0%). Thus, we conclude that the main effect of EAAduo on p[EAA] is linear. Abomasal or duodenal infusions of Met, Lys, His, Lys+Met, and casein revealed that Met or Lys infused alone increased the plasma concentration of the infused EAA and lowered the concentration of other EAA, particularly His. Infusion of Lys+Met or His alone was associated with increases in concentrations of these EAA without affecting others. We conclude that over a wide range of protein intakes in lactating cows, plasma levels of EAA increase linearly with duodenal flow. No evidence was found that EAA requirements are reflected in blood plasma concentrations.

Effects of slow-release urea and rumen-protected methionine and histidine on performance of dairy cows.

This experiment was conducted with the objective to investigate the effects of slow-release urea and rumen-protected (RP) Met and His supplementation of a metabolizable protein (MP)-deficient diet (according to NRC, 2001) on lactation performance of dairy cows. Sixty lactating Holstein cows were used in a 10-wk randomized complete block-design trial. Cows were fed a covariate diet for 2 wk and then assigned to one of the following treatments for an 8-wk experimental period: (1) MP-adequate diet [AMP; 107% of MP requirements, based on the National Research Council (NRC, 2001)]; (2) MP-deficient diet (DMP; 95% of MP requirements); (3) DMP supplemented with slow-release urea (DMPU); (4) DMPU supplemented with RPMet (DMPUM); and (5) DMPUM supplemented with RPHis (DMPUMH). Total-tract apparent digestibility of dry matter, organic matter, neutral detergent fiber, and crude protein, and urinary N and urea-N excretions were decreased by DMP, compared with AMP. Addition of slow-release urea to the DMP diet increased urinary urea-N excretion. Dry matter intake (DMI) and milk yield (on average 44.0±0.9kg/d) were not affected by treatments, except DMPUMH increased DMI and numerically increased milk yield, compared with DMPUM. Milk true protein concentration and yield were increased and milk fat concentration tended to be decreased by DMPUMH, compared with DMPUM. Cows gained less body weight on the DMP diet, compared with AMP. Plasma concentrations of His and Lys were not affected by treatments, whereas supplementation of RPMet increased plasma Met concentration. Plasma concentration of 3-methylhistidine was or tended to be higher for DMP compared with AMP and DMPU, respectively. Addition of RPHis to the DMPUM diet tended to increase plasma glucose and creatinine. In conclusion, feeding a 5% MP-deficient diet (according to NRC, 2001) did not decrease DMI and yields of milk and milk components, despite a reduction in nutrient digestibility. Supplementation of RPHis increased DMI and milk protein concentration and yield. These results are in line with our previous data and suggest that His may have a positive effect on voluntary feed intake and milk production and composition in high-yielding dairy cows fed MP-deficient diets.

Rumen-protected lysine, methionine, and histidine increase milk protein yield in dairy cows fed a metabolizable protein-deficient diet.

The objective of this experiment was to evaluate the effect of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Lys, Met, and specifically His on dairy cow performance. The experiment was conducted for 12 wk with 48 Holstein cows. Following a 2-wk covariate period, cows were blocked by DIM and milk yield and randomly assigned to 1 of 4 diets, based on corn silage and alfalfa haylage: control, MP-adequate diet (ADMP; MP balance: +9 g/d); MP-deficient diet (DMP; MP balance: -317 g/d); DMP supplemented with RPLys (AminoShure-L, Balchem Corp., New Hampton, NY) and RPMet (Mepron; Evonik Industries AG, Hanau, Germany; DMPLM); and DMPLM supplemented with an experimental RPHis preparation (DMPLMH). The analyzed crude protein content of the ADMP and DMP diets was 15.7 and 13.5 to 13.6%, respectively. The apparent total-tract digestibility of all measured nutrients, plasma urea-N, and urinary N excretion were decreased by the DMP diets compared with ADMP. Milk N secretion as a proportion of N intake was greater for the DMP diets compared with ADMP. Compared with ADMP, dry matter intake (DMI) tended to be lower for DMP, but was similar for DMPLM and DMPLMH (24.5, 23.0, 23.7, and 24.3 kg/d, respectively). Milk yield was decreased by DMP (35.2 kg/d), but was similar to ADMP (38.8 kg/d) for DMPLM and DMPLMH (36.9 and 38.5kg/d, respectively), paralleling the trend in DMI. The National Research Council 2001model underpredicted milk yield of the DMP cows by an average (±SE) of 10.3 ± 0.75 kg/d. Milk fat and true protein content did not differ among treatments, but milk protein yield was increased by DMPLM and DMPLMH compared with DMP and was not different from ADMP. Plasma essential amino acids (AA), Lys, and His were lower for DMP compared with ADMP. Supplementation of the DMP diets with RP AA increased plasma Lys, Met, and His. In conclusion, MP deficiency, approximately 15% below the National Research Council requirements from 2001, decreased DMI and milk yield in dairy cows. Supplementation of the MP-deficient diet with RPLys and RPMet diminished the difference in DMI and milk yield compared with ADMP and additional supplementation with RPHis eliminated it. As total-tract fiber digestibility was decreased with the DMP diets, but DMI tended to increase with RP AA supplementation, we propose that, similar to monogastric species, AA play a role in DMI regulation in dairy cows. Our data implicate His as a limiting AA in high-producing dairy cows fed corn silage- and alfalfa haylage-based diets, deficient in MP. The MP-deficient diets clearly increased milk N efficiency and decreased dramatically urinary N losses.

Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses.

Clinical studies indicate that cigarette smoking increases the risk for developing acute pancreatitis. The nicotine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a major cigarette smoke toxin. We hypothesized that NNK could sensitize to pancreatitis and examined its effects in isolated rat pancreatic acini and in vivo. In acini, 100 nM NNK caused three- and fivefold activation of trypsinogen and chymotrypsinogen, respectively, above control. Furthermore, NNK pretreatment in acini enhanced zymogen activation in a cerulein pancreatitis model. The long-term effects of NNK were examined in vivo after intraperitoneal injection of NNK (100 mg/kg body wt) three times weekly for 2 wk. NNK alone caused zymogen activation (6-fold for trypsinogen and 2-fold for chymotrypsinogen vs. control), vacuolization, pyknotic nuclei, and edema. This NNK pretreatment followed by treatment with cerulein (40 µg/kg) for 1 h to induce early pancreatitis responses enhanced trypsinogen and chymotrypsinogen activation, as well as other parameters of pancreatitis, compared with cerulein alone. Potential targets of NNK include nicotinic acetylcholine receptors and ß-adrenergic receptors; mRNA for both receptor types was detected in acinar cell preparations. Studies with pharmacological inhibitors of these receptors indicate that NNK can mediate acinar cell responses through an nonneuronal α(7)-nicotinic acetylcholine receptor (α(7)-nAChR). These studies suggest that prolonged exposure to this tobacco toxin can cause pancreatitis and sensitize to disease. Therapies targeting NNK-mediated pathways may prove useful in treatment of smoking-related pancreatitis.

Lactation performance and digestibility of forages and diets in dairy cows fed a hemicellulose extract.

Inclusion of hemicellulose extract (HE) in cattle diets have shown potential for improving fiber digestibility and production efficiency. The objective of this research was to evaluate production and digestibility effects of a HE on midlactation cows. Twelve multiparous Holstein cows (142 ± 44 d in milk, 685 ± 19 kg of body weight) including 4 with ruminal fistula were used in a 2 × 2 Latin square design with 21-d periods. Cows were fed a control (CON) diet containing 55% forage [dry matter (DM) basis, 2/3 corn silage and 1/3 alfalfa hay] or a similar diet where 1.0% of the diet DM was replaced with HE (TRT). Dry matter intake averaged 27.1 and 26.9 kg/d, for CON and TRT respectively, and was not affected by addition of extract. The percentage of milk protein (3.40 vs. 3.29%) was greater, whereas the percentage of milk fat (3.91 vs. 3.80%) tended to be greater, for cows fed the CON compared with the TRT diet. Because of numerically greater milk production (38.8 vs. 39.2 kg/d) for cows fed the TRT diet, no differences were observed in component yields other than lactose (1.86 vs. 1.94 kg/d), which tended to be greater for cows fed the TRT ration. Treatment improved neutral detergent fiber (NDF) digestibility (38.6 vs. 48.1%) for the TRT diet compared with the CON diet but did not affect apparent total-tract DM (67.8 vs. 68.5%), crude protein (67.2 vs. 67.9%), acid detergent fiber (ADF; 37.1 vs. 43.3%), or starch (92.8 vs. 92.2%) digestibility. For in situ determinations, Dacron bags containing corn silage, alfalfa hay, and either the CON or TRT ration were incubated in triplicate in the rumens of the cannulated cows at 0, 3, 6, 9, 12, 24, and 48 h on d 18 of each period. Each total mixed ration was incubated only in cows assigned to the corresponding diet. For corn silage, the rate of disappearance of NDF (1.70 vs. 4.27%) and ADF (1.79 vs. 4.66%) increased for cows fed the TRT diet. For alfalfa hay, the disappearance of fraction A of DM, NDF, and ADF decreased and fraction B of DM and NDF increased with treatment. The rate of disappearance for DM (8.03 vs. 11.04%), NDF (6.30 vs. 10.28%), and ADF (5.52 vs. 9.19%) increased for the alfalfa hay in rumens of treated cows. For the total mixed ration, the disappearance of the A fraction of NDF and ADF increased for cows fed the TRT diet. Supplementing diets of lactating dairy cows with an HE has beneficial effects on fiber degradation characteristics and provides opportunities for improving animal performance.

Effects of acrylamide exposure on serum hormones, gene expression, cell proliferation, and histopathology in male reproductive tissues of Fischer 344 rats.

Acrylamide (AA) is a reactive monomer used in many technological applications, but it is the incidental formation during cooking of common starchy foods that leads to pervasive human exposure, typically in the range of 1 µg/kg body weight (bw)/day (d). AA is carcinogenic in multiple organs from both sexes of several rodent models and a consistent body of evidence points to a genotoxic mechanism based on metabolism to a DNA-reactive epoxide, glycidamide (GA). In F344 rats, tumorigenesis occurs in several hormonally regulated tissues (thyroid, mammary gland, and peri-testicular mesothelium), which has prompted speculation about endocrine dysregulation as a possible mechanism. The present study evaluated the effects of a 14 d exposure to AA administered through the drinking water on reproductive tissues and the hypothalamic-pituitary-testes (HPG) axis in male F344 rats. The doses selected encompass a range from approximately 2.5 mg/kg bw/d, which is carcinogenic after lifetime exposure, to 50 mg/kg bw/d, a maximally tolerable dose that causes hind limb paralysis. AA caused significant changes in serum hormones, histopathology, testicular gene expression, and cell proliferation, especially at the highest dose. Despite strong evidence for activation of the HPG axis subsequent to decreases in testosterone levels, and histopathological changes associated with significant effects on Leydig and germ cells, with concomitant mRNA expression changes, the precise mechanism(s) for AA-induced testicular toxicity remains unclear; however, the absence of evidence for increased proliferation of the peri-testicular mesothelium (Ki-67 immunoreactivity) does not support hormonal dysregulation as a contributing factor to the predisposition of this tissue to the carcinogenic effects of AA.

Defining ruminal and total-tract starch degradation for adult dairy cattle using in vivo data.

Literature was searched for studies performed in adult dairy cattle that simultaneously measured starch degradability in the rumen (RSDeg) and starch digestion in the total tract to compute postruminal starch digestion (PRSDig). Forty-one studies with 161 dietary treatments were used to form the data set. Of these diets, the major starch source was corn for 83 diets, small grain for 58 diets, and sorghum for 8 diets. Corn RSDeg was more variable than other sources. As measured in vivo across all starch sources, the percent RSDeg was influenced only by the amount of starch consumed, with the amount of degradation being approximately 75% at low starch intakes and decreasing to about 60% when 4 kg or more of starch were consumed. Small grain starch had greater RSDeg than corn or sorghum starch, which were approximately equal. The PRSDig of corn and small grain starches were approximately equal, but sorghum was about 15% less. Across all diets, models derived from the Cornell Net Carbohydrate Protein System predicted percentage of total-tract digestibility of starch very accurately, but overpredicted RSDeg and, as a result, underpredicted percent PRSDig. Calculation of RSDeg using a French model predicted the mean RSDeg with greater accuracy but less precisely. The relative differences in RSDeg percent among starch sources was correctly predicted by these models. A model using a revised rate of digestion as a way of combining effects of starch type and processing was developed, which predicted corn starch RSDeg and PRSDig with greater accuracy than nutrition models but only slightly better than using the mean observed degradation or the French calculation. Inaccuracies in prediction of RSDeg may be due mainly to processing effects and particle sizes, but these were not well reported in literature studies and were difficult to estimate. More accurate assessment of RSDeg and PRSDig will require better and more consistent reporting of grain processing. Based on this study, the French calculation is the most accurate of the models examined, although adjustments will be required to improve accuracy.

Ability of commercially available dairy ration programs to predict duodenal flows of protein and essential amino acids in dairy cows.

The objective of this analysis was to compare the rumen submodel predictions of 4 commonly used dairy ration programs to observed values of duodenal flows of crude protein (CP), protein fractions, and essential AA (EAA). The literature was searched and 40 studies, including 154 diets, were used to compare observed values with those predicted by AminoCow (AC), Agricultural Modeling and Training Systems (AMTS), Cornell-Penn-Miner (CPM), and National Research Council 2001 (NRC) models. The models were evaluated based on their ability to predict the mean, their root mean square prediction error (RMSPE), error bias, and adequacy of regression equations for each protein fraction. The models predicted the mean duodenal CP flow within 5%, with more than 90% of the variation due to random disturbance. The models also predicted within 5% the mean microbial CP flow except CPM, which overestimated it by 27%. Only NRC, however, predicted mean rumen-undegraded protein (RUP) flows within 5%, whereas AC and AMTS underpredicted it by 8 to 9% and CPM by 24%. Regarding duodenal flows of individual AA, across all diets, CPM predicted substantially greater (>10%) mean flows of Arg, His, Ile, Met, and Lys; AMTS predicted greater flow for Arg and Met, whereas AC and NRC estimations were, on average, within 10% of observed values. Overpredictions by the CPM model were mainly related to mean bias, whereas the NRC model had the highest proportion of bias in random disturbance for flows of EAA. Models tended to predict mean flows of EAA more accurately on corn silage and alfalfa diets than on grass-based diets, more accurately on corn grain-based diets than on non-corn-based diets, and finally more accurately in the mid range of diet types. The 4 models were accurate at predicting mean dry matter intake. The AC, AMTS, and NRC models were all sufficiently accurate to be used for balancing EAA in dairy rations under field conditions.

A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change.

The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) was revised in October 2009. This revision was anticipated, based upon in vitro tests, to reduce UFH potency by approximately 10%. To study the potential in vivo consequences of the monograph change, we evaluated activated partial thromboplastin time (aPTT) and activated clotting time (ACT) responses in animals. Female mini-pigs and monkeys (n=8/species) were administered intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg "old" (pre-USP revision) UFH, respectively, in a Williams 4×4 crossover design. Blood samples for aPTT and ACT were collected at 15 min after dosing. The same study design was then repeated using "new" (post-USP revision) UFH. Mean "new" UFH aPTT and ACT values were generally lower than those for "old" UFH although individual animal responses varied considerably. The aPTT and ACT response was generally dose-proportional for both "old" and "new" UFH. These studies indicate that the USP monograph alteration for UFH may result in a modest reduction in the anticoagulant response across a population, but the variability in animal responses underscores the importance of individualization of clinical UFH dosing and the importance of anticoagulant test monitoring.

The biochemical aftermath of anti-amyloid immunotherapy.

BACKGROUND: Active and passive immunotherapy in both amyloid-beta precursor protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have resulted in remarkable reductions in amyloid plaque accumulation, although the degree of amyloid regression has been highly variable. Nine individuals with a clinical diagnosis of AD dementia were actively immunized with the Aß peptide 1-42 (AN-1792) and subjected to detailed postmortem biochemical analyses. These patients were compared to 6 non-immunized AD cases and 5 non-demented control (NDC) cases. RESULTS: All patients were assessed for the presence of AD pathology including amyloid plaques, neurofibrillary tangles and vascular amyloidosis. This effort revealed that two immunotherapy recipients had dementia as a consequence of diseases other than AD. Direct neuropathological examination consistently demonstrated small to extensive areas in which amyloid plaques apparently were disrupted. Characterization of Aß species remnants by ELISA suggested that total Aß levels may have been reduced, although because the amounts of Aß peptides among treated individuals were extremely variable, those data must be regarded as tentative. Chromatographic analysis and Western blots revealed abundant dimeric Aß peptides. SELDI-TOF mass spectrometry demonstrated a substantive number of Aß-related peptides, some of them with elongated C-terminal sequences. Pro-inflammatory TNF-α levels were significantly increased in the gray matter of immunized AD cases compared to the NDC and non-immunized AD groups. CONCLUSIONS: Immunotherapy responses were characterized by extreme variability. Considering the broad range of biological variation that characterizes aging and complicates the recognition of reliable AD biomarkers, such disparities will make the interpretation of outcomes derived from epidemiologic and therapeutic investigations challenging. Although in some cases the apparent removal of amyloid plaques by AN-1792 was impressive, proportionate alterations in the clinical progression of AD were not evident. The fact that plaque elimination did not alter the trajectory of decline into dementia suggests the likelihood that these deposits alone are not the underlying cause of dementia.

Effect of rumen-protected methionine on feed intake, milk production, true milk protein concentration, and true milk protein yield, and the factors that influence these effects: a meta-analysis.

A meta-analysis of published studies was used to investigate the effect of rumen-protected methionine (RPM) added to the diets of lactating dairy cattle on dry matter intake, milk production, true milk protein (TMP) production, and milk fat yield. Differences in responses between 2 commonly used RPM products, Mepron (Evonik Industries, Hanau, Germany) and Smartamine (Adisseo, Antony, France), were investigated as well as dietary and animal factors that could influence responses. Diets were coded with respect to the amino acid (AA) deficiency of the control diet as predicted by the AminoCow model (version 3.5.2, http://www.makemilknotmanure.com/aminocow.php; 0=no AA deficiency, 1=Met deficiency, 2=Met and Lys deficiency, 3=Met and Lys plus at least 1 other AA deficiency) to test the effect of AA deficiencies on RPM response. Thirty-five studies were identified, 17 studies evaluating Mepron, 18 studies evaluating Smartamine, and 1 study evaluating both. This permitted 75 dietary comparisons between control and RPM-added diets. Diets were entered into the AminoCow and the 2001 National Research Council models to compare predictions of Met, Lys, and metabolizable protein (MP) flow. Mean Met and Lys in diets where RPM was fed were estimated to be 2.35 and 6.33% of MP, respectively. Predictions of flows between models were similar. Overall, RPM addition to diets increased production of TMP, both as percentage (0.07%) and yield (27 g/d). Dry matter intake and milk fat percentage were slightly decreased, whereas milk production was slightly increased. Differences between products were detected for all production variables, with Mepron-fed cows producing less TMP percentage but greater milk production, resulting in twice as much TMP yield. Milk protein response to RPM was not related to predicted AA deficiency, calculated Met deficiency, or Met as a percentage of MP. Other dietary factors, including Lys flow (g/d), Lys as percentage of MP, neutral detergent fiber percentage, crude protein percentage, or energy balance, had no detectable effects on TMP response. When cows with a predicted positive AA balance were fed RPM, milk production increased, but when AA balance was negative, milk production decreased. Amount of RPM added to the diet was not correlated to TMP response. This study does not support the necessity of a high Lys level as a prerequisite to obtaining a TMP response to feeding RPM or the MP requirement suggested by the National Research Council model (2001). However, more dose-response studies over a wide range of milk production and dietary regimens will be required to more clearly establish AA requirements and to predict responses to RPM supplementation.