Infrared milk analyzers: Milk urea nitrogen calibration.

Our first objective was to redesign a modified 14-sample milk calibration sample set to obtain a well-distributed range of milk urea nitrogen (MUN) concentrations while maintaining orthogonality with variation in fat, protein, and lactose concentration. Our second objective was to determine the within- and between-laboratory variation in the enzymatic spectrophotometric method on the modified milk calibration samples and degree of uncertainty in MUN reference values, and then use the modified milk calibration samples to evaluate and improve the performance of mid-infrared partial least squares (PLS) models for prediction of MUN concentration in milk. Changes in the modified milk calibration sample formulation and manufacturing procedure were made to achieve the desired range of MUN concentrations. A spectrophotometric enzymatic reference method was used to determine MUN reference values, and the modified milk calibration samples were used to calibrate 3 mid-infrared milk analyzers. The within- and between-laboratory variation in the reference values for MUN were 0.43 and 0.77%, respectively, and the average expanded analytical uncertainty for the mean MUN value of the 14-sample calibration set was (mean ± SD) 16.15 mg/100 g ± 0.09 of milk. After slope and intercept adjustment to achieve a mean difference of zero with the calibration samples, it could be seen that the standard deviation of the differences of predicted versus reference MUN values among 3 different instruments and their PLS models were quite different. The orthogonal sample set was used (1) to determine when a PLS model did not correctly model out the background variation in fat, true protein, or anhydrous lactose; (2) to calculate an intercorrection factor to eliminate that effect, and (3) to improve the model performance (i.e., 50% reduction in standard deviation of the difference between instrument predictions and reference chemistry values for MUN).

Performance evaluation of an enzymatic spectrophotometric method for milk urea nitrogen.

Our objective was to determine the within and between laboratory performance of an enzymatic spectrophotometric method for milk urea nitrogen (MUN) determination. This method first uses urease to hydrolyze urea into ammonia and carbon dioxide. Next, ammonia (as ammonium ions) reacts with 2-oxoglutarate, in the presence of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) and the enzyme glutamate dehydrogenase (GlDH), to form l-glutamic acid, water, and NADP+. The change in light absorption at 340 nm due to the conversion of NADPH to NADP+ is stoichiometrically a function of the MUN content of a milk sample. The relative within (RSDr) and between (RSDR) laboratory method performance values for the MUN enzymatic spectrophotometric method were 0.57% and 0.85%, respectively, when testing individual farm milks. The spectrophotometric MUN method demonstrated better within and between laboratory performance than the International Dairy Federation differential pH MUN method with a much lower RSDr (0.57 vs. 1.40%) and RSDR (0.85 vs. 4.64%). The spectrophotometric MUN method also had similar method performance statistics as other AOAC International official validated chemical methods for primary milk component determinations, with the average of all RSDr and RSDR values being <1%. An official collaborative study of the enzymatic spectrophotometric MUN method is needed to achieve International Dairy Federation, AOAC International, and International Organization for Standardization official method status.

Evaluation of a crosswalk between the European Quality of Life Five Dimension Five Level and the Menopause-Specific Quality of Life questionnaire.

OBJECTIVES: Postmenopausal (PM) women taking therapies using estrogens plus progestogens (EPTs) can experience side effects (breast pain, vaginal spotting/bleeding). Sensitivity of the European Quality of Life Five Dimension Five Level (EQ-5D-5L) in measuring quality of life of PM women experiencing side effects of EPTs is unknown. A crosswalk between the Menopause-Specific Quality of Life (MENQOL) questionnaire and the EQ-5D-5L was assessed. METHODS: The measures were administered to 352 PM women (side effects = 202; control = 75; untreated = 75) in a non-interventional study. MENQOL total scores, treated as continuous and categorical predictors, were mapped onto EQ-5D-5L utilities using regression. Ordinary least-squares regression using averaged scores over time, goodness of fit, and estimated coefficients was also assessed. RESULTS: Mean age was 53.7 years. The first model (MENQOL as a continuous variable) showed a moderate correlation (-0.589) and statistically significant relationship with the EQ-5D-5L (p < 0.001), with an equation of EQ-5D-5L = 0.992 - 0.042 × MENQOL. The EQ-5D-5L mean scores were comparable (side effects = 0.854; control = 0.927; untreated = 0.836) to MENQOL mean scores estimated in the first model (side effects = 0.865 [standard deviation 0.07]; control = 0.909; untreated = 0.833). Linearity assumptions were supported with MENQOL scores as a categorical predictor. Goodness of fit was moderate (R2 = 0.347; root mean squared error = 0.093). CONCLUSION: The crosswalk supports conversion of MENQOL scores to EQ-5D-5L-derived health utilities for group-level analyses in PM women.

Psychometric evaluation of electronic diaries assessing side-effects of hormone therapy.

OBJECTIVES: Postmenopausal women (PMW) can experience side-effects (breast pain/tenderness and vaginal spotting/bleeding) associated with estrogen plus progestin therapies (EPTs). To assess these outcomes, the Breast Pain and Tenderness Daily Diary (BPT-DD) and the Vaginal Bleeding and Spotting Daily Diary (VBS-DD) were developed for electronic completion (eDiaries). This study evaluated the psychometric properties of the eDiaries. METHODS: The eDiaries were completed daily for 28 days by 202 PMW experiencing breast pain/tenderness and/or vaginal spotting/bleeding while on EPTs. Confirmatory factor analysis (CFA) investigated the BPT-DD structure. Response distributions, test-retest reliability (intraclass correlation coefficient [ICC]), internal consistency (BPT-DD only), and construct validity (via known groups and convergent validity analyses) were assessed. RESULTS: Completion rates were high: over 90% of women missed <3 daily entries. CFA supported the BPT-DD unidimensional structure (Bentler's Comparative Fit Index >0.98). BPT-DD inter-item correlations (r = 0.77-0.89) and internal consistency (Cronbach's alpha = 0.95-0.97) were high and good test-retest reliability was demonstrated (ICC ≥ 0.70). The eDiaries correlated moderately (>0.40), in a logical pattern with other instruments, supporting convergent validity. Known-groups analyses indicated both measures demonstrated significant differences between patients of differing severity (p < 0.001). CONCLUSION: The study provides evidence of strong psychometric properties for the BPT-DD and VBS-DD to assess breast pain/tenderness and spotting/bleeding in PMW.

Effect of nivolumab on health-related quality of life in patients with treatment-naïve advanced melanoma: results from the phase III CheckMate 066 study.

BACKGROUND: Nivolumab has shown significant survival benefit and a favorable safety profile compared with dacarbazine chemotherapy among treatment-naïve patients with metastatic melanoma in the CheckMate 066 phase III study. Results from the health-related quality of life (HRQoL) analyses from CheckMate 066 are presented. PATIENTS AND METHODS: HRQoL was evaluated at baseline and every 6 weeks while on treatment using the European Organisation for Research and Treatment of Care (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and the EuroQoL Five Dimensions Questionnaire (EQ-5D). Via a multi-step statistical plan, data were analyzed descriptively, cross-sectionally, and longitudinally, adjusting for baseline covariates, in patients having baseline plus ≥1 post-baseline assessment. RESULTS: Baseline-adjusted completion rates for all HRQoL questionnaires across treatment arms were 65% and 70% for dacarbazine and nivolumab, respectively, and remained similar throughout treatment. The mean baseline HRQoL scores were similar for patients treated with nivolumab and dacarbazine. Baseline HRQoL levels with nivolumab were maintained over time. This exploratory analysis showed a between-arm difference in favor of nivolumab on the EQ-5D utility index and clinically meaningful EQ-5D improvements from baseline at several time points for patients receiving nivolumab. Patients treated with nivolumab did not show increased symptom burden as assessed by the EORTC QLQ-C30. No HRQoL change was noted with dacarbazine patients up to week 43, although the high attrition rate after week 13 did not allow any meaningful analyses. Patients receiving nivolumab deteriorated significantly later than those receiving dacarbazine on several EORTC QLQ-C30 scales and the EQ-5D utility index. CONCLUSIONS: In addition to prolonged survival, these exploratory HRQoL results show that nivolumab maintains baseline HRQoL levels to provide long-term quality of survival benefit, compared with dacarbazine in patients with advanced melanoma.

Lysine, methionine, phenylalanine, arginine, valine, isoleucine, leucine, and threonine maintenance requirements of broiler breeders.

Five hundred and sixty Cobb-Vantress broiler breeders were used to determine the maintenance requirement of dietary Arg, His, Ile, Leu, Lys, Met, Phe, Thr, and Val in 10 21-d assays using the comparative slaughter technique. Fifty sexually immature broiler breeder pullets per assay were given crystalline amino acid diets containing graded levels of Arg, His, Ile, Leu, Lys, Met, Phe, Thr, or Val, respectively, representing 0, 10, 20, 30, 40% of their suggested requirement level (NRC, 1994) with all other amino acids maintained at 40% of their suggested requirement level. Sixty hens were slaughtered prior to the beginning of the study to assess initial body composition at 3 weight groups. Linear regression lines (protein accretion vs. amino acid intake) were determined and the maintenance requirements were calculated based on zero protein accretion. The maintenance requirements expressed on a metabolic weight basis were determined to be 174, 94, 52, 81, 60, 126, 133, and 155 mg/kg(0.75)/d for Arg, Ile, Leu, Lys, Met, Phe, Thr, and Val, respectively. Additionally, the maintenance requirements, expressed on metabolic protein weight basis, were determined to be 651, 329, 172, 295, 223, 523, 478, and 546 mg/kgCP/d for Arg, Ile, Leu, Lys, Met, Phe, Thr, and Val, respectively. The requirement for His could not be established as the results obtained were outside of assay range.

Lysine partitioning in broiler breeders is not affected by energy or protein intake when fed at current industry levels.

A study was conducted to determine the effects of dietary energy and protein intake on the partitioning of lysine in broiler breeder hens. One hundred twenty-six broiler breeders were randomly assigned to 1 of 6 dietary treatments in a 2 (390, 450 kcal/d) × 3 (22, 24, 26 g of CP/d) fashion. Thirty-six hens were administered a daily oral dose of 15 mg of (15)N-Lys for a period of 2 wk or until first egg. After the 2-wk enrichment period, no isotopes were given for 2 d. After 2 d, a daily oral dose of 15 mg of (2)D4-Lys was administered until the 2nd, 3rd, and 4th egg (saved) after the initial (2)D4-Lys was given, at which point pectoralis muscle was sampled. Weeks 25, 29, and 45 were assessed. Isotopic enrichment of pectoralis muscle, egg yolk, and albumen was determined via gas chromatography-mass spectrometry. The (15)N-Lys was intended to represent endogenous lysine, whereas the (2)D4-Lys was intended to represent dietary lysine. Greater than 78% of all labeled lysine ((15)N and (2)D4-Lys) was found in breast muscle. Endogenous muscle was the main source of lysine for yolk formation at wk 25 and 45. Diet was the main source of lysine for albumen formation at wk 25 and 29. A consistent decrease in the (15)N-Lys in breast muscle from the 2nd to the 3rd egg was observed, while also seeing an increase in the (15)N-Lys in the egg from the 3rd to the 4th egg. No difference in the partitioning of lysine was determined by energy or protein intake at levels typical for the current poultry industry. Rather, age, and possibly rate of production, appear to be the main drivers of lysine partitioning in the broiler breeder hen.

The relationship between phosphorus retention and fibroblast growth factor 23 in broiler breeders.

Previous studies with broiler breeders indicate a P retention threshold when fed daily dietary levels of non-phytate P (NPP) exceeding 320 mg. Fibroblast growth factor 23 (FGF23) is a hormone secreted by osteocytes which modulates P retention and could be the biological agent which controls the P threshold in breeders. To evaluate the relationship between FGF23 and the P retention threshold, a 4-wk study with 32-wk-old breeders was conducted with 6 dietary treatments with daily NPP intake of 216 to 576 mg/d/h with increments of 80 mg/kg diet. The goals were 1) to elucidate how plasma FGF23 corresponds with the P retention threshold in broiler breeders and 2) to determine the amount of P for optimal egg production and bone health. Results showed that between daily 288 mg and 360 mg dietary NPP intake, P retention decreased from 33 to 26% but FGF23 levels increased from 130 pg/mL to 220 pg/mL with increasing NPP. The elevation of plasma FGF23 between the range of 288 mg to 360 mg dietary NPP/d intake suggests that FGF23 is related to the P retention threshold and may be the major hormone for regulating physiological P levels when intake of daily dietary P levels are increased above 288 mg NPP.

Amino acid requirements of broiler breeders at peak production for egg mass, body weight, and fertility.

Two trials were conducted to determine the amino acid and protein requirements of broiler breeders at peak production. In trial 1, 32-wk-old Cobb 500 broiler breeders with similar BW were selected to determine the digestible amino acid requirement for daily product output (g of egg mass + g of BW gain/b/d) and feed conversion (g of feed/g of product) for Met, Phe, Arg, Ile, Lys, and CP in a 42-d production study. In trial 2, 30-wk-old Cobb 500 broiler breeders were selected to determine the digestible requirement for Met, Lys, Ile, Arg, Cys, Val, Trp, and Thr in a 70-d production study. Breeders were given a corn-soy basal diet plus crystalline amino acids with 8 graded levels of amino acids (10 birds per level), representing 40 to 130% of the highest suggested requirements reported in the literature. All other amino acids were maintained at 100% of their suggested requirement level. All breeders were inseminated weekly and fertility was determined. A third trial consisted of 41-wk-old colostomized hens randomly assigned to 1 of 2 diets differing only in the amount of Ile. Urine was collected after a 6-wk feeding period. The average digestible requirements per breeder per day for both product and feed/product ratio from trials 1 and 2 for Met, Cys, TSAA, Phe, Phe + Tyr, Trp, Arg, Ile, Lys, Val, Thr, and CP were 424, 477, 901, 689, 997, 252, 1,026, 830, 916, 799, 613 mg/d, and 20.0 g/d, respectively. The ideal profile for digestible Met, Cys, TSAA, Phe, Phe + Tyr, Trp, Arg, Ile, Lys, Val, and Thr was 46, 52, 98, 76, 108, 28, 112.0, 91, 100.0, 87, and 67%, respectively. A significant decrease in fertility was noted with increasing levels of Ile and Lys. Urine pH was significantly more alkaline in hens fed the higher level of Ile. It is suggested that adequate dietary Lys and Ile should be provided for maximum hatching egg production but an excess may affect fertility.

Comparison of hematologic and serologic profiles of broiler birds with normal and severe degrees of white striping in breast fillets.

White striping is the white striation occasionally observed parallel to the direction of muscle fibers in broiler breast fillets and thighs at the processing plant. Broiler breast fillets can be categorized as normal (NORM), moderate (MOD), or severe (SEV) based on the degree of white striping. Histologically, SEV fillets are characterized by the highest degree of degeneration of muscle fibers along with fibrosis and lipidosis when compared with NORM. The present study was undertaken to compare the hematologic and serologic profiles of broilers with NORM and SEV degrees of white striping to get more information on the systemic changes associated with the condition. Day-old male broiler chicks of a commercial strain were grown on the same diet in 6 replicate pens (n = 32 birds/pen). Blood samples (5 mL) were collected from the wing vein of each bird on the day before processing for analyzing hematologic and serologic profiles. At 63 d, the birds were weighed and processed in a commercial inline processing system. Weight of the butterfly fillets, liver, and abdominal fat pad were recorded. Left-side fillets were scored to obtain the degree of white striping for each bird. Representative samples for NORM (n = 24) and SEV (n = 17) categories were selected to compare the hematologic and serologic profiles. The SEV birds had greater (P < 0.05) live, fillet, and liver weights, as well as fillet yield, compared with the NORM birds, but the abdominal fat yield was less (P < 0.05) in SEV birds. The NORM and SEV birds did not show any differences in various hematological parameters, including the differential leukocyte count. Conversely, SEV birds had elevated (P < 0.05) serum levels of creatine kinase, alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase. These results suggest that there is no systemic infectious or inflammatory condition associated with a SEV degree of white striping. The elevated serum enzyme levels confirm the muscle damage associated with the degenerative myopathy in SEV birds.

The effects of pullet body weight, dietary nonpyhtate phosphorus intake, and breeder feeding regimen on production performance, chick quality, and bone remodeling in broiler breeders.

A 3 × 2 × 2 factorial experiment, consisting of 52 hens per treatment, was conducted to determine the effects of pullet BW, dietary nonphytate phosphorus (NPP), and feeding regimen on performance, progeny quality, and bone remodeling. Cobb 500 broiler breeder pullets were reared to 3 different growth curves: 20% under, Cobb standard, and 20% over. Body weights were recorded weekly and feed adjustments made accordingly. At 21 wk, 624 hens were fed one of 2 breeder diets differing only in the amount of dietary NPP: 0.15 or 0.40%. A normal feeding regimen was appropriate for the particular growth curve; an alternative regimen considered the 3 growth curves together as a flock. At 24, 26, and 29 wk, blood was collected from 5 hens per treatment every 4 h over a 24-h period. Plasma samples were analyzed for total alkaline phosphatase, tartrate-resistant acid phosphatase, parathyroid hormone-related peptide, Ca, and inorganic P. Eggs per hen housed were diminished in hens fed the low dietary NPP and by low pullet target weight. Hens fed low dietary NPP also had lower egg weights but better eggshell quality. Mortality was significantly higher in hens fed low dietary NPP. Breeder tibia relative strength and ash were also significantly lower in hens fed low dietary NPP, regardless of the quantitative amount. Progeny tibia ash was not affected by any treatment. Total alkaline phosphatase responded to pullet BW, however by wk 29, total alkaline phosphatase also became sensitive to dietary NPP. The NPP by pullet BW interaction for tartrate-resistant acid phosphatase levels became significant by 29 wk, and pullet BW was significant at wk 24. The NPP by pullet growth curve interaction was also critical for plasma inorganic P levels throughout the sampling period. In summary, both 0.15% dietary NPP and reared pullets 20% under standard BW negatively affect egg production but do not impair progeny productivity. Body composition appears to be a main contributor in bone remodeling mechanisms, especially during the transition into egg production.

Effects of high fat diets or prednisolone treatment on femoral head separation in chickens.

1. The effects of high fat diets and prednisolone treatment were studied to understand the etiology of femoral head separation (FHS) in fast growing broiler chickens. Dietary effects on production parameters such as growth, feed conversion ratio (FCR) and blood chemistry were also measured. 2. Three groups of chickens, consisting of 30 birds each, in two replicate pens, were fed isonitrogenous diets containing 40 (control), 60, or 80 g poultry fat supplements per kg feed. The birds were fed a starter diet containing the fat supplements for the first three weeks, then switched to a grower diet containing the same supplements for the rest of the experimental period. Two groups of birds were also raised with the control diets, but were administered either cholesterol or prednisolone intramuscularly at 30 and 32 days of age to evaluate their effects on FHS incidences. 3. The chickens were euthanised and necropsied at 37 d of age. The presence of femoral head weakness was determined by applying mild pressure on the pelvic joint to cause the growth plate to become detached from its articular cartilage in affected cases. 4. High fat diets did not change FHS incidences, but increased 28 d body weights (BW) and FCR. At 37 d of age the BW differences were not significant but the FCR (gain: feed ratio) remained higher in high fat fed groups. Prednisolone treatment, by contrast, resulted in decreased BW, decreased feed efficiency, increased FHS index, and elevated blood lipid levels. 5. The results suggest that high dietary fats do not affect FHS incidence in broilers. Prednisolone treatment causes hyperlipidaemia and increases FHS index, and may therefore provide a suitable experimental model of FHS pathogenesis in growing chickens.

Undenatured type II collagen mitigates inflammation and cartilage degeneration in healthy Labrador Retrievers during an exercise regimen.

The aim of this experiment was to evaluate the effect of undenatured type II collagen supplementation on inflammation and cartilage degeneration after exercise in healthy dogs. Forty healthy Labrador Retrievers (20 male/20 female; range 5-12 yr; average 8 yr) were sorted into two groups: undenatured type II collagen group receiving 40 mg UC-II (10 mg collagen type II/min. 3% undenatured type II collagen; Lonza Consumer Health, Inc.) and placebo group receiving 40 mg maltodextrin daily by capsule. After 2-wk loading, all dogs began an 11-wk endurance exercise regimen consisting of two weekly runs, starting at 5 km and increasing incrementally to 8 km, with one final 16 km run. Blood samples were collected at baseline, pre and post first 5 km run, and pre- and post-16 km run. Activity per kilometer was greater in male undenatured type II collagen vs. male placebo over all runs (P = 0.004), and average moving speed was greater in all undenatured type II collagen dogs compared with placebo over all runs (P < 0.001). Hematology analysis indicated that during the first insult, undenatured type II collagen dogs had a greater lymphocyte count (P < 0.001) and lymphocyte percentage (P = 0.001) vs. placebo dogs. Undenatured type II collagen dogs had a lesser neutrophil percentage (P = 0.042) and neutrophil to lymphocyte ratios (P = 0.001) compared to placebo dogs. For the final insult, undenatured type II collagen dogs had greater lymphocyte percentage (P = 0.013) and lesser mean corpuscular hemoglobin concentration (P = 0.043) compared with placebo dogs. Both groups had significant changes between timepoints for several hematological parameters. Biomarker IL-6 was lesser in undenatured type II collagen dogs compared with placebo at post 5 km (P = 0.037). Cartilage oligomeric matrix protein (COMP) was lesser in undenatured type II collagen dogs at post 16 km (P = 0.023), and only the placebo dogs had a significant increase in COMP from pre to post 16 km (P = 0.021). In summary, Labrador Retrievers supplemented with undenatured type II collagen had decreased inflammation and cartilage degeneration compared with nonsupplemented dogs during exercise.

The effect of feeding adequate or deficient vitamin B6 or folic acid to breeders on methionine metabolism in 18-day-old chick embryos.

Three isotopic tracers ([2,3,3-2H3]-L-serine, [2H11]-L-betaine, and [1-13C]-L-methionine) were administered by amnion injection into 18-day-old chick embryos to investigate the kinetics of methionine metabolism. The embryos utilized were from eggs collected from 34-week-old Cobb 500 broiler breeders that were fed either a control diet containing folic acid (1.25 mg/kg diet) and pyridoxine HCl (5 mg/kg diet) or diets devoid of supplemental pyridoxine or folic acid. Intermediate metabolites of methionine metabolism and polyamines were analyzed in 18-day-old chick embryos. There were no differences in hepatic [2H2] methionine or [2H3] cysteine enrichments or in physiological concentrations of sulfur amino acids for chick embryos from breeders fed the control diet and embryos from breeders fed diets containing no pyridoxine or folic acid. Supplementation of B6 or folic acid did not affect the production of methionine and cysteine in chick embryos. However, breeders fed the control diet with both folic acid and pyridoxine supplementation produced embryos with a two-fold reduction of hepatic homocysteine and increased spermine compared with embryos from breeders fed diets containing no supplemental pyridoxine or folic acid (P < 0.05). Hepatic S-adenosylmethionine for embryos from breeders fed no supplemental B6 was half the concentration compared with embryos from breeders fed the control diet. Embryos from breeders fed the control diet were utilized to determine the proportion of homocysteine going through remethylation and transsulfuration and also to determine the pathway of remethylation. Sixty-five percent of the methyl groups used for homocysteine remethylation from control embryos was via the MFMT pathway. Alternatively, 61% of homocysteine from control embryos was remethylated via the MFMT and the BHMT reactions and 39% of homocysteine was catabolized to cysteine via the transsulfuration pathway. These data show that in embryos, intermediate metabolites of methionine and polyamines increase in concentration when pyridoxine levels are provided in deficient concentrations to the breeder hen. In addition, this research demonstrates that folic acid deficient embryos conserve methionine, rather than catabolize it to cysteine.

Review: Physiological growth trend of current meat broilers and dietary protein and energy management approaches for sustainable broiler production.

The food production system needs to be sustainable including poultry sector to feed the increasing global population. An accepted economical and environmental approach of broiler production is to produce larger broilers faster while using less feed. Broiler production is aimed at producing consumable meat and meat products. The global broiler meat market has evolved over the years with increasing selection pressure shifted toward attaining yield characteristics for increased cut-up parts such as breast and thighs. There is a shift toward a big bird market in the U.S. with approximately 70% of the broiler meat produced from large birds (>2.72 kg). Genetic selection of broilers for quantitative traits such as growth rate and lean muscle mass without increasing the fat mass has altered broiler physiological homeostasis to adapt toward the larger rates of muscle protein turnover. Physiological stresses created due to selection pressures in broilers have produced several muscle myopathies including an emerging one called woody breast myopathy. The sustainable broiler production practice may require humane consideration of raising broilers in less stressful grow-out regimes that will have minimal impact on broiler metabolic health. Another sustainability approach of broiler production toward feed efficiency lies on understanding dietary formulation approach of amino acids and energy that promote optimal nutrient utilization and minimal nutrient output to environment while also fulfilling the growth demands and body composition changes associated with increased protein gain in current meat broilers brought by the genetic progress.

The role of feeding regimens in regulating metabolism of sexually mature broiler breeders.

A trial was conducted to determine the effects of different rearing feed regimens on plasma hormone and metabolite levels and hepatic lipid metabolism and gene expression on sexually mature broiler breeders. Cobb 500 birds were divided into 2 groups at 4 wk and fed either an everyday (ED) or skip-a-day (SKP) regimen. At 24 wk of age, all birds were switched over to an ED regimen. At 26.4 wk, breeder hens were randomly selected and killed at intervals after feeding. Livers were sampled from 4 hens at 4-h intervals for 24 h for a total of 28 samples per treatment. Blood was sampled from 4 hens per sampling time; sampling times were 0, 30, and 60 min and 2 and 4 h after feeding and then every 4 h up to 24 h for a total of 36 samples per treatment. Main feeding regimen, time, and interaction effects were analyzed. Significant interaction effects were found between time and feeding regimen for acetyl-coenzyme A carboxylase and malic enzyme mRNA expression. The peak for acetyl-coenzyme A carboxylase expression was higher in ED-reared birds, whereas the peak for malic enzyme expression was higher in SKP-reared birds. Overall, plasma levels of insulin-like growth factor-II were higher in SKP-reared birds. Overall, plasma corticosterone levels were also higher in SKP-reared birds and significant interaction effects between time and feeding regimen were seen. The expression of apolipoprotein A1 was significantly higher in ED-reared birds: significant interaction effects were also noted. Other researchers also found some of the differences observed in the present study in 16-wk-old pullets. In summary, different feeding regimens alter metabolic responses, some of which carry over into sexual maturity.

Matrix metalloproteinase-1 promotes breast cancer angiogenesis and osteolysis in a novel in vivo model.

Matrix metalloproteinase-1 (MMP-1) is critical for mediating breast cancer metastasis to bone. We investigated the role of MMP-1 in breast cancer invasion of soft tissues and bone using human MDA MB-231 breast cancer cells stably transfected with shRNAs against MMP-1 and a novel murine model of bone invasion. MMP-1 produced by breast cancer cells with control shRNA facilitated invasion of tumors into soft tissue in vivo, which correlated with enhanced blood vessel formation at the invasive edge, compared to tumors with silenced MMP-1 expression. Tumors expressing MMP-1 were also associated with osteolysis in vivo, whereas tumors with inhibited MMP-1 levels were not. Additionally, tumor-secreted MMP-1 activated bone-resorbing osteoclasts in vitro. Together, these data suggest a mechanism for MMP-1 in the activation of osteoclasts in vivo. We conclude that breast cancer-derived MMP-1 mediates invasion through soft tissues and bone via mechanisms involving matrix degradation, angiogenesis, and osteoclast activation.

The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.