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Case: We report the case of a healthy 17-year-old female softball player with a subacute full-thickness intramuscular tear of the pectoralis major (PM) muscle. A successful muscle repair was obtained using a modified Kessler technique., Conclusions: Despite initially being a rare injury pattern, the incidence of PM muscle rupture is likely to increase as interest in sports and weight training increases, and although this injury pattern is more common in men, it is becoming more common in women as well. Furthermore, this case presentation provides support for operative treatment of intramuscular ruptures of the PM muscle., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C38)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To evaluate the effectiveness and safety of an evidence-based urine culture stewardship program in reducing hospital catheter-associated urinary tract infections (CAUTIs) and the rate of CAUTIs across a 3-hospital system., Patients and Methods: This is a prospective, 2-year quality improvement program conducted from October 1, 2018, to September 30, 2020. An evidence-based urine culture stewardship program was designed, which consisted of the following: criteria for allowing or restricting urine cultures from catheterized patients, a best practice advisory integrated into the ordering system of an electronic medical record, and a systematic provider education and feedback program to ensure compliance. The system-wide rates of CAUTIs (total CAUTIs/catheter days×1000), changes in intercepts, trends, mortality, length of stay, rates of device utilization, and rates of hospital-onset sepsis were compared for 3 years before and 2 years after the launch of the program., Results: Catheter-associated urinary tract infections progressively decreased after the initiation of the program (B=-0.21, P =.001). When the trends before and after the initiation of the program were compared, there were no statistically significant increases in the ratio of actual to predicted hospital length of stay, intensive care unit length of stay, system-wide mortality, and intensive care unit mortality. Although the rates of hospital-acquired sepsis remained consistent after the implementation of the stewardship program through the first quarter of 2020, the rates showed an increase in the second and third quarters of 2020. However, hospital-onset sepsis events associated with the diagnosis of a urinary tract infection did not increase after the intervention., Conclusion: Urine culture stewardship is a safe and effective way to reduce CAUTIs among patients in a large multihospital health care system. Patient safety indicators appeared unchanged after the implementation of the program, and ongoing follow-up will improve confidence in the long-term sustainability of this strategy., (© 2022 The Authors.)

Resuming elective surgery amid shortages of rapid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests and personal protective equipment, while protecting patient and staff safety, posed a challenge at the study institution. Many hospital systems implemented testing of all presurgical patients, using results from tests performed 3 or more days prior to surgery. Among asymptomatic persons, the percent positive rates of coronavirus disease 2019 (COVID-19) tests in the region did not appear to justify this practice. Instead of universal preoperative COVID-19 testing, the authors elected to mitigate risk by implementing a preoperative program including 14 days of recommended patient self-quarantine and social distancing. For those unable to complete this program and for those undergoing high-risk, aerosol-generating procedures, targeted rapid polymerase chain reaction testing within 2 days of surgery was performed. Data from the initial 4 months suggests that this approach was noninferior to universal preoperative testing with regard to postoperative COVID-19 detection and patient exposure-related COVID-19 cases among hospital staff., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Immune-checkpoint blockade has revolutionized cancer treatment. However, most patients do not respond to single-agent therapy. Combining checkpoint inhibitors with other immune-stimulating agents increases both efficacy and toxicity due to systemic T-cell activation. Protease-activatable antibody prodrugs, known as Probody therapeutics (Pb-Tx), localize antibody activity by attenuating capacity to bind antigen until protease activation in the tumor microenvironment. Herein, we show that systemic administration of anti-programmed cell death ligand 1 (anti-PD-L1) and anti-programmed cell death protein 1 (anti-PD-1) Pb-Tx to tumor-bearing mice elicited antitumor activity similar to that of traditional PD-1/PD-L1-targeted antibodies. Pb-Tx exhibited reduced systemic activity and an improved nonclinical safety profile, with markedly reduced target occupancy on peripheral T cells and reduced incidence of early-onset autoimmune diabetes in nonobese diabetic mice. Our results confirm that localized PD-1/PD-L1 inhibition by Pb-Tx can elicit robust antitumor immunity and minimize systemic immune-mediated toxicity. These data provide further preclinical rationale to support the ongoing development of the anti-PD-L1 Pb-Tx CX-072, which is currently in clinical trials., (©2021 The Authors; Published by the American Association for Cancer Research.)

Tau prions feature in the brains of patients suffering from Alzheimer's disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound ( 1 ) was identified as a hit with an EC 50 value of 390 nM and 0.04 K p,uu . Analogs were synthesized using a hypothesis-based approach to improve potency and in vivo brain penetration resulting in compound 25 (EC 50 = 15 nM; K p,uu = 0.63). We investigated the mechanism of action of this series and found that a small set of active compounds were also CDK8 inhibitors., Competing Interests: The authors declare the following competing financial interest(s): The Institute for Neurodegenerative Diseases has a research collaboration with Daiichi Sankyo (Tokyo, Japan). Stanley B. Prusiner is a member of the Scientific Advisory Board of ViewPoint Therapeutics and a member of the Board of Directors of Trizell, Ltd., neither of which have contributed financial or any other support to these studies., (Copyright © 2020 American Chemical Society.)

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10 9 , Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.

Aims and Objectives: To examine how shift work affects intensive care nurses' lives outside work., Background: Shift work is unavoidable for many nurses. When attempting to minimise negative effects of shift work, it is important to identify areas which affect nurses working shifts., Design: A cross-sectional study., Methods: A questionnaire survey among Danish intensive care nurses concerning experiences with shift work and family life, spare time activities, sleep and health., Results: A total of 114 nurses (88%) participated. Shift work was found to influence the opportunities for spare time activities, and about 25% of both evening- and night-shift groups found that working shifts sometimes led to social isolation. A total of 58% of nurses working evening shifts sometimes to very often experienced having trouble falling asleep when working shifts. Night-shift workers had a higher percentage of physical and mental symptoms when working shifts compared with evening-shift workers, with mood swings and headaches being the most common. The median score for thriving on working shifts was 8 (IQR 5-9) for evening-shift workers and 8 (IQR 7-9) for night-shift workers (scale 0-10 with 10 being the highest level of thriving)., Conclusion: Shift workers reported that working shifts had a negative impact on life outside work. Opportunities for participating in spare time activities and difficulties falling asleep after shifts were the main issues for evening-shift workers, whereas physical symptoms such as headaches and mood swings were more dominant among night-shift workers. Despite the negative effects, the participants generally thrived on working shifts., Relevance to Clinical Practice: By identifying modifiable areas which negatively influence life outside work when working shifts, it will be possible subsequently to plan interventions aimed at decreasing the negative effects. Interventions may include nurses having increased influence on their work schedules and education in sleep hygiene and dietary habits., (© 2017 John Wiley & Sons Ltd.)

There exists a phenomenon in aging research whereby early life stress can have positive impacts on longevity. The mechanisms underlying these observations suggest a robust, long-lasting induction of cellular defense mechanisms. These include the various unfolded protein responses of the endoplasmic reticulum (ER), cytosol, and mitochondria. Indeed, ectopic induction of these pathways, in the absence of stress, is sufficient to increase lifespan in organisms as diverse as yeast, worms, and flies. Here, we provide an overview of the protein quality control mechanisms that operate in the cytosol, mitochondria, and ER and discuss how they affect cellular health and viability during stress and aging., (Copyright © 2018 Elsevier Inc. All rights reserved.)

An expanded hexanucleotide repeat in C9orf72 causes amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor Spt4 selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Knockdown of SUPT4H1, the human Spt4 ortholog, similarly decreased production of sense and antisense RNA foci, as well as DPR proteins, in patient cells. Therapeutic targeting of a single factor to eliminate c9FTD/ALS pathological features offers advantages over approaches that require targeting sense and antisense repeats separately., (Copyright © 2016, American Association for the Advancement of Science.)

Purpose: To examine the effect of designed dynamic light on staff's quality of sleep with regard to sleep efficiency, level of melatonin in saliva, and subjective perceptions of quality of sleep., Methods: An intervention group working in designed dynamic light was compared with a control group working in ordinary institutional light at two comparable intensive care units (ICUs). The study included examining (1) melatonin profiles obtained from saliva samples, (2) quality of sleep in terms of sleep efficiency, number of awakenings and subjective assessment of sleep through the use of sleep monitors and sleep diaries, and (3) subjective perceptions of well-being, health, and sleep quality using a questionnaire. Light conditions were measured at both locations., Results: A total of 113 nurses (88 %) participated. There were no significant differences between the two groups regarding personal characteristics, and no significant differences in total sleep efficiency or melatonin level were found. The intervention group felt more rested (OR 2.03, p = 0.003) and assessed their condition on awakening as better than the control group (OR 2.35, p = 0.001). Intervention-ICU nurses received far more light both during day and evening shifts compared to the control-ICU., Conclusions: The study found no significant differences in monitored sleep efficiency and melatonin level. Nurses from the intervention-ICU subjectively assessed their sleep as more effective than participants from the control-ICU.

Faecal transplantation as a therapeutic tool is increasingly reported in the scientific literature. Faecal transplantation is currently becoming a treatment for nosocomial, refractory infections with C. difficile. Furthermore, faecal transplantation has been suggested as a treatment for ulcerative colitis as well as for the metabolic syndrome. In the accumulated literature faecal transplantations appear to be safe, effective and superior to current treatments. Faecal transplantation remains a sparsely investigated treatment, however, especially for other diagnoses than C. difficile infection.

This study investigated the effect of water restriction on wool and blood cortisol concentrations and water consumption patterns in heat-stressed sheep. Nine Corriedale female sheep (average BW=43±6.5 kg) were individually fed diets based on maintenance requirement in metabolic crates. They were assigned to three treatments according to a Latin square design (3×3) for three periods with a 21-day duration for each period (nine sheep per treatment). Treatments included free access to water (FAW), 2 h water restriction (2hWR) and 3 h water restriction (3hWR) after feeding. Average temperature-humidity index in the experimental room was 27.9 throughout the experiment that defines heat stress conditions. Wool samples were taken at the end of each period on day 21. No differences were found in cortisol concentration in each fragment (dried, washed and residual extract) of wool (P<0.05). Total wool cortisol concentration was higher in the 3hWR group than the other treatments (P<0.05). Blood cortisol was not different among the treatments (P>0.05) and resulted in higher variable data compared with wool cortisol. Blood neutrophils and neutrophil/lymphocyte ratio suppressed in FAW and 3hWR groups compared with the 2hWR group (P<0.05). The duration of water consumption recorded after feeding in the 3hWR group was higher than in the 2hWR group when recorded in the afternoon (P<0.01). Water consumption rate was higher in the 3hWR group than in the 2hWR group (P<0.01). However, total water consumed was lower in the 3hWR group compared with other treatments (P>0.05). It can be concluded that wool cortisol provides more precise and accurate data than blood cortisol during heat stress conditions. Water restriction for 3 h after feeding can act as a stressor and is critical for sheep during heat stress as the consumption of water decreases with restriction.

Target-mediated toxicity constitutes a major limitation for the development of therapeutic antibodies. To redirect the activity of antibodies recognizing widely distributed targets to the site of disease, we have applied a prodrug strategy to create an epidermal growth factor receptor (EGFR)-directed Probody therapeutic-an antibody that remains masked against antigen binding until activated locally by proteases commonly active in the tumor microenvironment. In vitro, the masked Probody showed diminished antigen binding and cell-based activities, but when activated by appropriate proteases, it regained full activity compared to the parental anti-EGFR antibody cetuximab. In vivo, the Probody was largely inert in the systemic circulation of mice, but was activated within tumor tissue and showed antitumor efficacy that was similar to that of cetuximab. The Probody demonstrated markedly improved safety and increased half-life in nonhuman primates, enabling it to be dosed safely at much higher levels than cetuximab. In addition, we found that both Probody-responsive xenograft tumors and primary tumor samples from patients were capable of activating the Probody ex vivo. Probodies may therefore improve the safety profile of therapeutic antibodies without compromising efficacy of the parental antibody and may enable the wider use of empowered antibody formats such as antibody-drug conjugates and bispecifics.

The study of kinship systems has direct relevance for the field of human genetics and the study of microevolution in human populations. Some types of postmarital residence rules--rules requiring a married couple to live with or near relatives of the husband or wife--will have consequences for the distribution of mitochondrial DNA and Y chromosome lineages. Rules that proscribe or encourage marriage with close kin will also have consequences for allele frequency. A preference for marrying at a distance, both socially and geographically, creates alliances that can have survival value for individuals and groups in an environment of periodic or unpredictable scarcity. This article considers the nature of early contact between the indigenous foraging populations of the Philippines and Austronesian speaking settlers who began arriving ~4,500-4,000 BP. It argues that when the first Austronesians arrived they brought with them a kinship system based on symmetrical exchange between descent-based groups. It considers why such a system was gradually changed into the bilateral kinship systems that characterize the various peoples of the Philippines today, "negrito" and non-negrito alike., (Copyright © 2013 Wayne State University Press, Detroit, Michigan 48201-1309.)

A replicated 3×3 Latin square study was conducted to evaluate the effects of replacing a portion of ground corn in the diet with dietary glycerol on rumen environment, blood metabolites, and nutrient digestibility. Six rumen-cannulated Holstein cows, averaging 56±18 DIM and 38.0±8.2 kg of milk/d, were used in the study. Experimental periods included 3 wk for treatment adjustment period followed by 1 wk for data collection. Diets were corn silage based and balanced to be isocaloric and isonitrogenous. Treatments were 0 g of glycerol/d (control, CON), 200 g of glycerol/d (G2), and 400 g of glycerol/d (G4). Dry matter intake (DMI) decreased as the amount of glycerol fed increased. Milk yield was higher for CON and G2 cows in comparison with G4 cows. Milk fat percentage and yield were reduced when glycerol was fed compared with CON cows but increased the milk protein percentage at the highest concentration of dietary glycerol. These changes resulted in decreased energy-corrected milk yield and efficiency (milk/DMI) in diets supplemented with G4 compared with CON. No differences were observed in ruminal pH and ammonia concentrations. Molar proportions of acetate, valerate, and acetate:propionate ratio decreased, whereas propionate increased as the amount glycerol fed increased. Molar proportions of butyrate were greatest when glycerol was included in the diet compared with CON. Nutrient intake and digestion were not different among treatments. Results of this trial suggest that feeding increasing amounts of glycerol may decrease DMI and alters ruminal fermentation, resulting in reduced yield of milk, fat, and energy-corrected milk., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

A study was conducted to evaluate the effects of a direct-fed microbial (M) and dietary glycerol (G) on milk yield, efficiency of yield, and nutrient digestibility during hot weather. Sixty Holstein cows averaging 120 d in milk (DIM) and 36.2 kg/d of milk were used in a 12-wk 2×2 factorial design trial from June through September 2008. Cows were fed a common diet during the 2-wk standardization period and were blocked by milk yield, DIM, parity, and dry matter intake. Diets were based on corn and ryegrass silages and balanced to be isocaloric and isonitrogenous. Treatments included a negative control (M- or G-), 4 × 10(9) cfu/head of a combination of Lactobacillus acidophilus NP51 and Propionibacterium freudenreichii NP24 (M+), control plus 400 g/h per day of 99% pure food-grade glycerol (G+), and 4×10(9) cfu/h per day of a combination of Lactobacillus acidophilus NP51 and Propionibacterium freudenreichii NP24 plus 400 g/h per day of 99% pure food-grade glycerol (MG++). No interactions were observed between direct-fed microbials and dietary glycerol in the study except on apparent nutrient digestibility. No differences were observed in dry matter intake, which averaged 22.7, 23.1, 23.4, and 22.9 for M-, G-, M+, and G+, respectively. Milk yield was increased for M+ compared with M- at 34.1 and 31.7 kg/d, but G+ had no effect on yield. No treatment effect was noted for milk fat percentage or milk protein percentage among diets. Milk protein yield was higher for M+ compared with M- at 0.93 versus 0.87 kg/d. Energy-corrected milk was improved for the M+ versus M- groups at 33.5 and 31.6 kg/d, respectively. No differences in respiratory rate, skin temperature, body temperature, or concentrations of serum glucose or urea N were observed among treatments. Improvement in apparent digestibility was observed with M+ and G+ compared with M-/G- in this experiment. The addition of a direct-fed microbial alone improved milk and protein yield, energy-corrected milk, and apparent digestibility of crude protein, neutral detergent fiber, and acid detergent fiber, and the inclusion of glycerol (G+) had a positive effect on apparent dry matter and acid detergent fiber digestibility compared with M-/G-. The addition of a direct-fed microbial and dietary glycerol may improve yield and digestibility for cows subject to heat stress., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Members of the CD28 family play important roles in regulating T-cell functions and share a common gene structure profile. We have identified VSTM3 as a protein whose gene structure matches that of the other CD28 family members. This protein (also known as TIGIT and WUCAM) has been previously shown to affect immune responses and is expressed on NK cells, activated and memory T cells, and Tregs. The nectin-family proteins CD155 and CD112 serve as counter-structures for VSTM3, and CD155 and CD112 also bind to the activating receptor CD226 on T cells and NK cells. Hence, this group of interacting proteins forms a network of molecules similar to the well-characterized CD28-CTLA-4-CD80-CD86 network. In the same way that soluble CTLA-4 can be used to block T-cell responses, we show that soluble Vstm3 attenuates T-cell responses in vitro and in vivo. Moreover, animals deficient in Vstm3 are more sensitive to autoimmune challenges indicating that this new member of the CD28 family is an important regulator of T-cell responses., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Holstein rumen-cannulated cows [n=7; initial body weight (BW) 640.56±71.43 kg] were fed a corn silage basal diet with 1 of 3 concentrates (C=control; P10=10% pigeon peas; P20=20% pigeon peas). Cows were randomly assigned to treatments in a replicated 3×3 Latin square and individually fed using Calan gates. Each experimental period was 21 d with 7 d for adaption and 14 d for sample collection. Ruminal fluid samples were taken the last day of each experimental period and analyzed for pH, ammonia, long-chain fatty acids, and volatile fatty acids (VFA). Consecutive a.m. and p.m. milk samples were taken during the last 2 wk of the 21-d period and analyzed for fat, protein, long-chain fatty acids, and somatic cell count. Dry matter intake (kg/d) was reduced during the second period and was greater for P10 diets. Milk protein was greater for cows fed P20 compared with P10. Energy-corrected milk was greater for cows fed the control diet compared with P10. Treatment had no effect on milk yield. Ruminal fluid pH decreased over sampling times; however, pH remained at or above 5.5. Diets did not affect ruminal fluid pH; however, pH was different for sampling periods. Ruminal ammonia decreased until 8h postfeeding at which time it peaked consistent with changes in ammonia concentrations that usually peak 3 to 5h postfeeding on diets high in plant proteins. Dietary treatments altered ruminal fluid VFA with reduced concentrations of acetate and greater concentrations of propionate for control diet, resulting in reduced acetate:propionate ratio. Isobutyrate exhibited an hour by treatment interaction, in which isobutyrate decreased until 8h postfeeding and then tended to be greater for P10 than for other treatments. Animals fed the P10 diet had greater concentrations of ruminal isovalerate. Ruminal cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid (CLA) isomers were not affected by dietary treatments. The P10 diet had greatest ruminal synthesis of cis-9,trans-11, but control cows had greatest ruminal synthesis of trans-10,cis-12. Milk CLA isomers were similar among treatments. Trends were observed for greater cis-9,trans-11 and trans-10,cis-12 for the P10 diet. Pigeon peas may be used as a protein supplement in dairy diets without affecting milk production, dry matter intake, or ruminal environment when they replace corn and soybean meal., (Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Forty-four lactating Holstein cows (173±30 DIM, 42.5±6.8 kg of milk, 4.03±0.69% fat, 674±78 kg of body weight) were used in an 8-wk, completely randomized trial with a 2 × 2 factorial arrangement of treatments to determine the effect of forage source and supplemental cellulase enzyme on performance. Treatments included 2 forage combinations (corn silage plus 12.2% dry matter, DM, from either alfalfa hay or Tifton 85 bermudagrass haylage) with or without a commercial cellulase enzyme applied to the total mixed ration at the rate of 4 g/head per day (Promote N.E.T.-L, Cargill Animal Nutrition, Minneapolis, MN). Experimental diets were formulated to provide similar concentrations of protein (16.5% of DM), energy (1.63 Mcal of net energy for lactation/kg of DM), and neutral detergent fiber (41.7% of DM) and were fed once daily as a total mixed ration behind Calan doors for ad libitum intake. The cellulase enzyme provided 1,200 cellulase units of activity/g of product and was applied to the total mixed ration and allowed to mix for 5min before feeding. Before beginning the trial, all cows were trained to use Calan (American Calan, Northwood, NH) doors and then fed the alfalfa hay-based diet for 2 wk. Data collected during wk 2 were used as a covariate in the statistical analysis. At the beginning of the 6-wk experimental period, cows were assigned randomly to 1 of the 4 experimental diets. No interactions were observed between forage and enzyme for any measures. Daily DM intake; milk yield; concentrations of milk fat, true protein, lactose, and solids not fat; energy-corrected milk yield; and dairy efficiency were not different among alfalfa or Tifton 85 bermudagrass rations with or without cellulase enzyme supplementation. The results of this trial indicate that Tifton 85 bermudagrass haylage can replace alfalfa hay in diets fed to high-producing, lactating dairy cows without depressing DM intake or milk yield when rations are balanced for NDF. Although supplemental cellulase enzymes have been shown to improve ration digestibility and animal performance in previous trials, no advantages were observed in the current trial., (Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Forty-eight mid-lactation Holstein cows were used in a 6-wk completely randomized block design trial with a 4 x 3 factorial arrangement of treatments to determine the effects of feeding different proportions of corn silage and ryegrass silage with supplemental ground corn (GC), steam-flaked corn (SFC), and hominy feed (HF) on the performance of lactating dairy cows. Forage provided 49% of the dietary dry matter in the experimental diets, which were formulated to meet National Research Council requirements. Ryegrass silage provided 100, 75, 50, or 25% of the total forage dry matter, with corn silage supplying the remainder. There were no interactions between the proportion of forage provided by ryegrass silage and energy supplement. Dry matter intake and milk protein percentage decreased linearly with increasing proportions of ryegrass silage, but milk protein yield was similar among forage treatments. There were no differences among forage treatments in milk yield, milk fat percentage and yield, and energy-corrected milk yield. Dry matter intake was higher and there was a tendency for increased milk fat percentage for GC compared with SFC or HF. No other differences were observed in milk yield or composition among energy supplements. Plasma urea nitrogen and glucose concentrations were similar among treatments. Under the conditions of this trial, our results indicate that feeding a combination of corn silage and ryegrass silage is more desirable than feeding ryegrass silage alone, whereas supplementation with GC, SFC, or HF supports similar levels of milk production.

Statement of Problem: Ultraviolet light absorber (UVA) and hindered amine light stabilizer (HALS) retard sun-induced pigment degradation in silicone elastomeric maxillofacial prostheses. HALS inhibits polymer degradation and UVA dissipates UV radiation. Their effects on oral cells are unknown., Purpose: The purpose of this study was to evaluate the effects of UVA and HALS on membrane integrity, viability, and proliferation of human gingival fibroblasts and epithelial cells., Material and Methods: Tinuvin 123 (HALS) and Tinuvin 213 (UVA) were assessed for cytotoxicity, individually and in a 1:1 ratio (used in elastomers; HALS/UVA). The cells were exposed to HALS, UVA, or HALS/UVA (or control media containing only the diluent), and colorimetric assays measured membrane damage, viability, and proliferation. The data (% cytotoxicity or % control) were analyzed using 3-way cross-classified fixed effects ANOVA (alpha=.05)., Results: HALS did not negatively affect either cell type. UVA or HALS/UVA (>or= approximately 0.004%) decreased viability by >or=90% in both cell lines; lower concentrations decreased activity in epithelial cells while increasing it in fibroblasts. UVA or HALS/UVA damaged membranes of both cell lines, but epithelial cells were more resistant. UVA or HALS/UVA inhibited proliferation of both cell types similarly. There was a slight synergistic effect of HALS and UVA on membrane damage in both cell lines, but generally not on other parameters., Conclusions: Although it is unknown if HALS or UVA leaches from silicone elastomers in vivo, these data suggest that relative resistance of epithelial cells to UVA-induced membrane damage, and UVA's stimulation of fibroblast viability at some concentrations, might provide some protective effect.

Twenty-four lactating Holstein cows were used in a 6-wk randomized block design trial with a 2 x 2 factorial arrangement of treatments to determine the effects of feeding ground corn (GC) or steam-flaked corn (SFC) in diets based on either annual ryegrass silage (RS) or a 50:50 blend of annual ryegrass and corn silages (BLEND). Experimental diets contained 49.6% forage and were fed as a total mixed ration once daily for 4 wk after a 2-wk preliminary period. No interactions were observed among treatments. Cows fed BLEND consumed more dry matter (DM), organic matter (OM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) than those fed RS, but total-tract digestibility of OM, NDF, and ADF was greater for RS than for BLEND. No differences in nutrient intake were observed among treatments during wk 4 when nutrient digestibility was measured, but digestibility of DM and OM was greater for SFC than for GC. Cows fed BLEND tended to produce more energy-corrected milk than those fed RS, resulting in improved efficiency (kg of milk per kg of DM intake). When diets were supplemented with SFC, cows consumed less DM and produced more milk that tended to have lower milk fat percentage. Yield of milk protein and efficiency was greatest with SFC compared with GC. Blood glucose and milk urea nitrogen concentrations were similar among treatments, but blood urea nitrogen was greater for cows fed GC compared with those fed SFC. Results of this trial indicate that feeding a blend of annual ryegrass and corn silage is more desirable than feeding diets based on RS as the sole forage. Supplementing diets with SFC improved performance and efficiency compared with GC across forage sources.

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.

Eight primiparous lactating Holstein cows (47 +/- 10 d in milk) fitted with ruminal cannulae were used to determine the effect of dietary cation-anion difference (DCAD) and dietary crude protein (CP) concentration on milk yield and composition, acid-base chemistry, and measures of N metabolism in lactating dairy cows. Treatments were arranged as a 2 x 2 factorial in a randomized complete block design to provide 15 or 17% CP and DCAD of 25 or 50 mEq (Na + K - Cl)/100 g of feed dry matter [15 or 39 mEq (Na + K) - (Cl + S)/100 g of feed dry matter]. High DCAD improved dry matter intake, milk yield, and concentrations of milk fat and protein. An interaction of DCAD and CP was observed for uric acid excretion, an indicator of microbial protein yield. Uric acid excretion was higher for high DCAD than for low DCAD in low CP diets and was similar for low and high DCAD with high CP. Serum bicarbonate concentration, urinary bicarbonate excretion, blood pH, and serum Na were elevated for high DCAD compared with low DCAD. Fractional excretion of Na, K, Cl, and Ca increased for high DCAD. Blood urea N and urinary urea N were greater for high than for low CP diets. No differences due to DCAD were observed for these parameters. Results of this study suggest that, in early lactation cows, blood acid-base chemistry is altered by differences in DCAD that range between the high and low ends of the desired DCAD range. Modifications of acid-base chemistry and the corresponding changes in protein metabolism may allow for more efficient feeding of protein and better nutritional management of the lactating dairy cow.

Twenty-four lactating Holstein cows were used in an 8-wk completely randomized design trial to examine the effects of feeding whole cottonseed (WCS) with elevated concentrations of free fatty acids (FFA) in the oil on intake and performance. Treatments included WCS with normal concentrations of FFA (6.8%, control) and 2 sources of WCS with elevated FFA [HFFA1 (24.1%) or HFFA2 (22.3%)]. The 2 sources of WCS with elevated FFA differed in that HFFA2 were discolored from being initially stored with excess moisture, which led to heating and deterioration during storage, whereas HFFA1 were normal in appearance and the increase in FFA occurred without heating and visible damage to the WCS. Nutrient concentrations were similar among WCS treatments, which provided 14% of the total dietary dry matter. Dry matter intake tended to be higher for cows fed HFFA2 compared with control and HFFA1. Yield of milk and components was similar among treatments, but milk fat percentage was lower for HFFA1 and HFFA2 compared with control. In a concurrent 3 x 3 Latin square trial with 6 ruminally cannulated Holstein cows, molar proportions of isobutyrate were higher for HFFA2 than control and HFFA1, but no differences were observed in acetate or propionate. Results of these trials indicate that feeding WCS with high concentrations of FFA decreases milk fat percentage but does not alter dry matter intake, milk yield, or concentrations of other components. The minor changes in ruminal fermentation that were observed do not account for the decrease in milk fat percentage.

Thirty-two lactating Holstein cows (225 +/- 63 d in milk) were used in a 6-wk trial to determine the effect of dietary cation-anion difference (DCAD) and dietary crude protein (CP) concentration on milk and component yield, acid-base status, and serum AA concentrations during hot weather. Treatments were arranged as a 2 x 2 factorial within a randomized complete block design to provide 15 or 17% CP and a DCAD of 25 or 50 mEq (Na + K - Cl)/100 g of dry matter (DM). A DCAD x CP interaction was detected for milk yield; milk yield was less for high DCAD than for low DCAD for the high-CP diets. No differences were noted at low dietary CP. Milk fat percentage was greater for high DCAD than for low DCAD, and high-CP diets supported greater milk fat percentage than low-CP diets. No differences were observed among treatments for dry matter intake or milk protein percentage. Serum total AA and essential AA concentrations and ratio of essential AA:total AA were greater for high DCAD. These results suggest that increasing DCAD improves AA availability for protein synthesis by taking the place of AA that would otherwise be used for maintenance of acid-base balance. A better understanding of the mechanisms behind this AA-sparing effect will improve management of protein nutrition in the lactating dairy cow.

Forty-two lactating Holstein cows 188 +/- 59 d in milk were used in an 8-wk randomized complete block trial with a 2 x 3 factorial arrangement of treatments. The objective was to determine the effects of high dietary cation-anion difference (DCAD) and K:Na ratio on milk yield and composition and blood acid-base chemistry. Treatments included DCAD concentrations of 45 or 60 mEq (Na + K -Cl)/100 g of feed dry matter and K:Na ratios of 2:1, 3:1, or 4:1. Mean DCAD values were later determined to be 41 and 58. Dry matter intake was similar across treatments. Yield of milk and energy corrected milk were lower for the 3:1 K:Na ratio compared with 2:1 and 4:1 ratios. Blood urea N was lower for the highest DCAD, suggesting that DCAD possibly reduced protein degradation or altered protein metabolism and retention. Mean temperature-humidity index was 75.6 for the duration of the trial, exceeding the critical value of 72 for all weeks during the treatment period. Cows maintained relatively normal body temperature with mean a.m. and p.m. body temperature of 38.5 and 38.7 degrees C, respectively. These body temperatures suggest that cows were not subject to extreme heat stress due to good environmental control. Results of this trial indicate that the greatest effect on milk yield occurs when either Na or K is primarily used to increase DCAD, with the lowest yield of energy-corrected milk at a 3:1 K:Na ratio (27.1 kg/d) compared with ratios of 2:1 (29.3 kg/d) and 4:1 (28.7 kg/d). Results also suggest that greater DCAD improves ruminal N metabolism or N utilization may be more efficient with a high DCAD.

Thirty lactating Holstein cows were used in an 8-wk randomized design trial to test the viability of select additives included in the gelatinized corn starch coating applied to whole cottonseed (WCS) on nutrient intake and digestibility and milk yield and composition. Treatments included WCS coated with 2.5% gelatinized corn starch (control); control plus 0.5% urea; or control plus 2.0% yeast culture. The treated WCS represented 12.6% of the dietary dry matter. Cellulose intake was lower for the control coating compared with either the urea or yeast coating because of slightly lower cellulose concentrations in the control treatment. Intake of all other nutrients was similar for all treatments. Whole-tract nutrient apparent digestibility was not altered by treatment. Dry matter intake and milk yield were similar among treatments. Percentage solids-not-fat was lower for the yeast treatment compared with control, but no other differences were observed in milk composition among treatments. Efficiency of milk production (energy-corrected milk yield per unit of dry matter intake) was higher for the urea and yeast treatments compared with control because of slightly higher yield of milk fat and energy-corrected milk. No differences were observed in body weight change during the trial between treatments. Results of this trial indicate that including urea or yeast culture in the gelatinized starch coating does not change whole tract digestibility, but does improve milk production efficiency.

Cattle drinking water is a source of on-farm Escherichia coli O157:H7 transmission. The antimicrobial activities of disinfectants to control E. coli O157:H7 in on-farm drinking water are frequently neutralized by the presence of rumen content and manure that generally contaminate the drinking water. Different chemical treatments, including lactic acid, acidic calcium sulfate, chlorine, chlorine dioxide, hydrogen peroxide, caprylic acid, ozone, butyric acid, sodium benzoate, and competing E. coli, were tested individually or in combination for inactivation of E. coli O157:H7 in the presence of rumen content. Chlorine (5 ppm), ozone (22 to 24 ppm at 5 degrees C), and competing E. coli treatment of water had minimal effects (<1 log CFU/ml reduction) on killing E. coli O157:H7 in the presence of rumen content at water-to-rumen content ratios of 50:1 (vol/wt) and lower. Four chemical-treatment combinations, including (i) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.05% caprylic acid (treatment A); (ii) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.1% sodium benzoate (treatment B); (iii) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 0.5% butyric acid (treatment C); and (iv) 0.1% lactic acid, 0.9% acidic calcium sulfate, and 100 ppm chlorine dioxide (treatment D); were highly effective (>3 log CFU/ml reduction) at 21 degrees C in killing E. coli O157:H7, O26:H11, and O111:NM in water heavily contaminated with rumen content (10:1 water/rumen content ratio [vol/wt]) or feces (20:1 water/feces ratio [vol/wt]). Among them, treatments A, B, and C killed >5 log CFU E. coli O157:H7, O26:H11, and O111:NM/ml within 30 min in water containing rumen content or feces, whereas treatment D inactivated approximately 3 to 4 log CFU/ml under the same conditions. Cattle given water containing treatment A or C or untreated water (control) ad libitum for two 7-day periods drank 15.2, 13.8, and 30.3 liters/day, respectively, and cattle given water containing 0.1% lactic acid plus 0.9% acidic calcium sulfate (pH 2.1) drank 18.6 liters/day. The amounts of water consumed for all water treatments were significantly different from that for the control, but there were no significant differences among the water treatments. Such treatments may best be applied periodically to drinking water troughs and then flushed, rather than being added continuously, to avoid reduced water consumption by cattle.

Nine multiparous and 12 primiparous cows were fed diets containing an anionic salt supplement and moderate Ca (0.99%) or high Ca (1.50%) concentrations for 21 d prepartum to determine the effects of dietary Ca concentration on serum and urine electrolytes and on postpartum intake and milk yield. Blood samples were collected during 21 to 1 d prepartum, 0 to 2 d postpartum, and 3 to 21 d postpartum. Dietary cation-anion difference (DCAD) for prepartum diets was approximately -6 mEq/100 g of dry matter (Na + K - Cl - S). Immediately postpartum, cows were fed diets with positive DCAD with greater than 1.00% Ca concentration. Mean serum Ca concentrations 21 to 1 d prepartum, 0 to 2 d postpartum, and 3 to 21 d postpartum were 9.62, 8.41, and 9.38 mg/dL. There were no treatment effects on serum Ca concentration. Mean serum Ca concentration was higher for primiparous than multiparous cows (9.34 vs. 8.93 mg/dL) for the trial and at calving (8.77 vs. 8.13 mg/dL). Mean serum HCO(3)(-) and urinary pH, respectively, were 20.32 mEq/L and 5.67 prepartum, 25.82 mEq/L and 7.62 at calving, and 26.08 mEq/L and 8.25 postpartum. No differences due to treatment were observed for serum and urinary concentrations of HCO(3)(-), pH, Mg, Na, K, and Cl. Milk yield was similar for 0.99 and 1.50% Ca treatments (22.8 and 20.7 kg/d). Diets containing 0.99 or 1.5% Ca maintained serum Ca at adequate levels around parturition and resulted in similar dry matter intake and postpartum milk yield.

Early lactation Holsteins cows (15 primiparous and 18 multiparous) were offered rations with dietary cation-anion difference, calculated as mEq (Na + K - Cl - S)/100 g of feed dry matter (DCAD:S), of 20, 35, or 50 mEq from d 0 (calving) to 42 d postpartum (August 20, 2000 to January 9, 2001) to determine the effects of increasing DCAD:S on dry matter intake (DMI), milk yield, and blood metabolites. For DCAD:S of 20, 35, and 50, DMI was 3.30, 3.38, 2.96 kg/100 kg of body weight (BW); milk yield was 25.5, 24.2, and 22.4 kg/d, respectively. No differences were observed for concentration or yield of milk fat or milk protein. Serum Ca, P, Mg, Na, K, Cl, cation-anion difference, insulin, and glucose did not differ with DCAD. Serum HCO3- was 26.07, 25.88, and 27.64 mEq/L for 20, 35, and 50 DCAD:S. Serum Ca, Mg, Na, and K concentrations were greater for primiparous cows (9.52 mg/dL, 2.35 mg/dL, 140.03 mEq/L, 4.66 mEq/L, respectively) than for multiparous cows (9.27 mg/dL, 2.12 mg/dL, 137.63 mEq/L, 4.46 mEq/ L, respectively). A DCAD:S between 23 and 33 mEq/100 g of dry matter (DM) appears to be adequate during cool weather for the milk yield that occurred in the present study based on DMI (kg/100 kg of BW), whereas DCAD:S of 50 mEq/100 g of DM may be excessive and could be too alkaline or unpalatable, resulting in decreased DMI (kg/100 kg of BW).

Two corn varieties predicted to differ in digestibility were harvested at 2 cutting heights (10.2 or 30.5 cm) to determine effects on the nutrient content of the resulting silage, nutrient intake, nutrient digestibility, and production of lactating cows fed such corn silage originally harvested at two-thirds milk line. Acid detergent fiber (ADF) concentration was higher and in vitro true dry matter (DM) digestibility (IVTDMD) was lower for the variety predicted to have average digestibility. An interaction was observed between variety and cutting height because of decreased ADF and increased IVTDMD for the average digestibility variety cut at 30.5 vs. 10.2 cm; no differences were observed for the higher digestibility variety at each cutting height. When silages were fed to 32 Holstein cows in a 5-wk randomized design trial, DM intake, milk yield, and milk composition were similar. There was an interaction between variety and cutting height for DM intake and total tract apparent digestibility of DM, crude protein, and neutral detergent fiber because of lower intake and digestibility for the diets containing either the high cut, average quality variety or low cut, higher quality variety. These results suggest that increasing the cutting height to 30.5 cm does not improve silage quality or improve milk yield of cows. Although the 2 varieties selected for this trial were predicted to differ in digestibility, these differences were not great enough to influence milk yield or composition of lactating cows.

Four lactating Jersey cows fitted with ruminal and duodenal cannulae were used in a 4 x 4 Latin square design trial to determine the effect of supplemental lysine in diets containing dry ground (GC) or steam-flaked (SFC, 360 g/L) corn on ruminal fermentation and amino acid (AA) flow to the duodenum. Supplemental L-lysine-HCL provided 10 g/d of additional Lys to the total mixed rations. There were no interactions between supplemental Lys and corn source. Supplemental Lys increased Lys intake, but did not alter nutrient intake and digestibility or N flow to the duodenum. Intake of dry matter (DM), organic matter (OM), and neutral detergent fiber (NDF) and ruminal digestibility of starch tended to be higher, whereas ruminal digestibility of DM, OM, acid detergent fiber, and NDF was lower for diets supplemented with SFC compared with GC. Whole-tract digestibility was similar for both corn supplements. Ruminal pH and molar proportions of volatile fatty acids were not affected by supplemental Lys or corn source; however, ruminal NH(3) concentrations were lowest when SFC was fed. Intake of N tended to be higher and the flow of total N and individual AA to the duodenum was higher for diets supplemented with SFC. There was a trend for increased flow of microbial N for diets supplemented with SFC. Supplemental L-lysine-HCL did not alter ruminal fermentation, flow of amino acid to the small intestine, or nutrient digestibility, but feeding SFC reduced ruminal fiber digestion and increased microbial protein synthesis and flow of amino acid to the duodenum.

Four ruminally and duodenally cannulated Jersey cows were used in a 4 x 5 incomplete Latin square study to determine the effects of including urea in the gelatinized corn starch coating applied to whole cottonseed (WCS) on ruminal fermentation, fiber digestion, and bacterial protein synthesis. Treatments included uncoated WCS (control) and four coated WCS treatments. The coatings provided two concentrations each of gelatinized corn starch (2.5 [2S] or 5% [5S]) and feed grade urea (0.25 [2U] or 0.5% [5U]). Treated WCS comprised 15% of the ration dry matter that was fed as a total mixed ration once daily. Ruminal pH and molar proportions of isobutyrate was higher and NH3-N concentrations lower for control compared with coated WCS. Molar proportions of propionate tended to be higher and valerate was lower with 2S compared with 5S. Molar proportions of acetate tended to be lower, whereas butyrate was higher for 5U than 2U. Nutrient intake was lower for WCS coated with 5S5U compared with 2S5U. Ruminal NDF digestibility of NDF tended to be higher with 5U compared with 2U, but no differences were observed in ruminal or total tract apparent digestibility of nutrients. No differences were observed in the flow of total N or bacterial N to the duodenum, but the flow of nonbacterial N tended to be higher for WCS coated with 5U. Coating WCS appears to slightly alter ruminal metabolism while providing similar amounts of N flowing to the duodenum without altering fiber digestion.

The southeastern United States is characterized as humid subtropical and is subject to extended periods of high ambient temperature and relative humidity. Because the primary nonevaporative means of cooling for the cow (radiation, conduction, convection) become less effective with rising ambient temperature, the cow becomes increasingly reliant upon evaporative cooling in the form of sweating and panting. High relative humidity compromises evaporative cooling, so that under hot, humid conditions common to the Southeast in summer the dairy cow cannot dissipate sufficient body heat to prevent a rise in body temperature. Increasing air temperature, temperature-humidity index and rising rectal temperature above critical thresholds are related to decreased dry matter intake (DMI) and milk yield and to reduced efficiency of milk yield. Modifications including shade, barns which enhance passive ventilation, and the addition of fans and sprinklers increase body heat loss, lowering body temperature and improving DMI. New technologies including tunnel ventilation are being investigated to determine if they offer cooling advantages. Genetic selection for heat tolerance may be possible, but continued selection for greater performance in the absence of consideration for heat tolerance will result in greater susceptibility to heat stress. The nutritional needs of the cow change during heat stress, and ration reformulation to account for decreased DMI, the need to increase nutrient density, changing nutrient requirements, avoiding nutrient excesses and maintenance of normal rumen function is necessary. Maintaining cow performance in hot, humid climatic conditions in the future will likely require improved cooling capability, continued advances in nutritional formulation, and the need for genetic advancement which includes selection for heat tolerance or the identification of genetic traits which enhance heat tolerance.

The localization of 14.3.3 proteins was studied in different subtypes of brain amyloid plaques. We examined paraffin-embedded brain sections of sporadic MV2 Creutzfeldt-Jakob disease (sCJD) with Kuru plaques, sporadic VV2 CJD with plaque-like PrP(sc) (the abnornal form of prion protein) deposits, variant CJD (vCJD) with florid plaques, Gerstmann-Straüssler-Scheinker (GSS) with multicentric plaques and of Alzheimer's disease (AD) with senile plaques. Adjacent immunostaining revealed PrP(sc) and 14.3.3 zeta deposits in the same amyloid plaques in all cases of sporadic CJD and vCJD, whereas 14.3.3 zeta was not seen in amyloid plaques of GSS with A117V, P102L and D202N mutations. The same immunostaining method using anti-betaA4 and anti-14.3.3 zeta antibodies revealed no colocalization in patients with AD. Our data suggest that 14.3.3 zeta protein could interact either with PrP or with other components of PrP(sc) deposits in CJD.

Lactating cows were exposed to moderate and hot, humid weather to determine the effect of increasing ambient temperature, relative humidity, or temperature-humidity index (THI) on intake, milk yield, and milk temperature. Minimum and maximum temperatures averaged 17.9 and 29.5 degrees C (cool period) and 22.5 and 34.4 degrees C (hot period), and minimum and maximum THI averaged 63.8 and 76.6 (cool period) and 72.1 and 83.6 (hot period). Environmental conditions had minor effects on intake and milk yield during the cool period. During the hot period, the THI 2 d earlier and mean air temperature 2 d earlier had the greatest impact on milk yield and DMI, respectively. Both breeds maintained milk temperature within normal ranges during the cool period, but Holstein and Jersey p.m. milk temperatures averaged 39.6 and 39.2 degrees C during the hot period. Current day mean air temperature during the hot period had the greatest impact on cow p.m. milk temperature, and minimum air temperature had the greatest influence on a.m. milk temperature. Dry matter intake and milk yield declined linearly with respective increases in air temperature or THI during the hot period and milk temperature increased linearly with increasing air temperature. Dry matter intake and milk yield both exhibited a curvilinear relationship with milk temperature. Environmental modifications should target the effects of high temperatures on cow body temperature and should modify the environment at critical times during the day when cows are stressed, including morning hours when ambient temperatures are typically cooler and cows are not assumed to be stressed.

Twenty Holstein cows were used in an 8-wk randomized block design study to determine the effects of replacing corn silage with ryegrass silage on nutrient intake, apparent digestion, milk yield, and milk composition. The 8-wk trial consisted of a 2-wk preliminary period followed by a 6-wk collection period. Experimental diets were formulated to provide 55.5% of the total dry matter (DM) as forage. Ryegrass silage was substituted for 0, 35, 65, and 100% of DM provided by corn silage. Dietary concentrations of neutral detergent fiber (NDF) and acid detergent fiber (ADF) increased as ryegrass silage replaced corn silage. Intake of DM and crude protein (CP) was similar for all treatments, but intake of NDF and ADF increased linearly as ryegrass silage replaced corn silage. Apparent digestibility of DM declined linearly, whereas digestibility of CP increased linearly as ryegrass silage replaced corn silage. Apparent digestibility of NDF and ADF was highest for the diets in which ryegrass or corn silages provided all of the forage, resulting in a quadratic response. Dry matter intake was not different among treatments. Yield of milk, fat, and protein increased as ryegrass silage replaced corn silage. No differences were observed for body weight change, body condition score, and serum urea nitrogen concentration, but serum glucose concentration increased with increasing dietary proportion of ryegrass silage. These results indicate that substituting ryegrass silage for a portion or all of the corn silage in diets fed to lactating dairy cows can improve yield of milk and components.

We have characterized platelet-derived growth factor (PDGF) C, a novel growth factor belonging to the PDGF family. PDGF-C is a multidomain protein with the N-terminal region homologous to the extracellular CUB domain of neuropilin-1, and the C-terminal region consists of a growth factor domain (GFD) with homology to vascular endothelial growth factor (25%) and PDGF A-chain (23%). A serum-sensitive cleavage site between the two domains allows release of the GFD from the CUB domain. Competition binding and immunoprecipitation studies on cells bearing both PDGF alpha and beta receptors reveal a high affinity binding of recombinant GFD (PDGF-CC) to PDGF receptor-alpha homodimers and PDGF receptor-alpha/beta heterodimers. PDGF-CC exhibits greater mitogenic potency than PDGF-AA and comparable or greater mitogenic activity than PDGF-AB and PDGF-BB on several mesenchymal cell types. Analysis of PDGF-CC in vivo in a diabetic mouse model of delayed wound healing showed that PDGF-CC significantly enhanced repair of a full-thickness skin excision. Together, these studies describe a third member of the PDGF family (PDGF-C) as a potent mitogen for cells of mesenchymal origin in in vitro and in vivo systems with a binding pattern similar to PDGF-AB.

Lactating cows were offered diets with increasing neutral detergent fiber concentrations to determine the effects on intake, milk yield and composition, blood hormones, and nutrient digestion during cool or hot weather conditions. Tifton 85 bermudagrass hay was substituted for corn silage so that the forage portion of diets were: 1) 40% corn silage (control), 2) 32.4% corn silage, 7.6% bermudagrass, 3) 24.8% corn silage, 15.2% bermudagrass, or 4) 17.2% corn silage, 22.8% bermudagrass (dry basis). Dietary neutral detergent fiber concentrations (% dry matter) were 30.2, 33.8, 37.7, and 42.0, respectively. Intake of dry matter declined with increasing dietary neutral detergent fiber during cool and hot periods, but intake adjusted for cool weather treatment differences did not change further during hot weather. Milk yield declined linearly with increasing neutral detergent fiber during cool weather and changed quadratically during hot weather. Milk temperature declined with increasing dietary neutral detergent fiber for the p.m. milking during the cool period and declined with increasing dietary neutral detergent fiber for the a.m. and p.m. milkings during the hot period. Digestibility of neutral detergent fiber improved and ruminal turnover of particulate digesta was increased with greater dietary neutral detergent fiber content. No dietary fiber level by hot weather interaction was observed, suggesting that total energy intake may have and a greater effect on milk yield than dietary fiber content during hot, humid weather.

A study was undertaken to compare Tifton 85 (T85) and Coastal (CBG) bermudagrasses for effects of cultivar and age at harvest on yields of DM and digestible DM, in vitro digestion, nutrient content, cell wall composition, in situ digestion kinetics, and feed intake and digestion by growing beef steers. In Exp. 1, T85 and CBG forages staged for growth in May or July of 1993 were harvested at 3, 4, 5, 6, 7, and 8 wk from subplots. Tifton 85 bermudagrass had 7.1% greater DM yield, 18.2% higher (P < .05) digestible DM yield, and 7.1% greater IVDMD than CBG, and, after 5 wk of forage growth, IVDMD of both T85 and CBG decreased with increased age at harvest (P < .05). In Exp. 2, T85 and CBG forages staged for growth in July 1997 were harvested at 2, 3, 4, 5, 6, and 7 wk from subplots. Even though T85 had higher concentrations of NDF and ADF than CBG, T85 had 34.1% higher DM yield, 47.9% higher digestible DM, 55.0% higher digestible NDF, 91.7% higher digestible ADF, greater IVDMD, in vitro NDF and ADF disappearances, and higher in situ DM and NDF digestion (P < .05). Coastal bermudagrass had higher concentrations of lignin and lower concentrations of total neutral sugars, arabinose, glucose, and xylose than T85 (P < .05). In vitro digestibilities of DM, NDF, and ADF were lower and concentrations of ADF and lignin were greater for 7- vs 6-wk harvests of both T85 and CBG (P < .05). In Exp. 3, T85 and CBG forages staged for growth in July 1997 were harvested as hay at 3, 5, and 7 wk from .8-ha pastures and fed to 36 individually penned growing beef steers (initial BW = 244 kg) to quantify ad libitum intake without supplementation. Tifton 85 bermudagrass had lower concentrations of lignin and ether-linked ferulic acid and greater concentrations of NDF, ADF, hemicellulose, and cellulose than CBG (P < .05). Steers fed T85 had higher (P < .05) digestion of DM, OM, NDF, ADF, hemicellulose, and cellulose than steers fed CBG. Digestion of NDF, ADF, hemicellulose, and cellulose decreased (P < .05) with increased age at harvest for both cultivars. In conclusion, T85 produced more DM and had more digestible nutrients in vitro, in situ, and in vivo than CBG, and 3 and 5 wk of growth would be recommended ages to harvest either cultivar.

Heat stress results from the animal's inability to dissipate sufficient heat to maintain homeothermy. Environmental factors, including ambient temperature, radiant energy, relative humidity, and metabolic heat associated with maintenance and productive processes, contribute to heat stress. The focus of this article is to identify environmental and metabolic factors that contribute to excessive heat load, describe how disruption of homeothermy alters physiologic systems of the cow, and discuss nutritional modifications that help to maintain homeostasis or prevent nutrient deficiencies that result from heat stress. Changes in diet are needed during hot weather to maintain nutrient intake, increase dietary nutrient density, or to reestablish homeostasis. Formulation for adequate nutrient intake is challenging because of the competition between nutrient density and other needs for the cow, including energy density and adequate dietary fiber. Lower DMI during hot weather reduces nutrients available for absorption, and absorbed nutrients are used less efficiently. An excess of degradable dietary protein is undesirable because of energy costs to metabolize and excrete excess N as urea. Optimizing ruminally undegraded protein improves milk yield in hot climates. Mineral losses via sweating (primarily K) and changes in blood acid-base chemistry resulting from hyperventilation reduce blood bicarbonate and blood buffering capacity and increase urinary excretion of electrolytes. Theoretical heat production favors feed ingredients with a lower heat increment, such as concentrates and fats, whereas forages have a greater heat increment. Improved dietary energy density and the lower heat increment associated with the inclusion of dietary fat must be coupled with limitations to fat feeding to avoid ruminal and metabolic disorders. Numerous nutritional modifications are used for hot weather feeding; however, many need further investigation to achieve specific recommendations.

Lactating dairy cows were offered diets containing increasing quantities of Tifton 85 bermudagrass hay or silage and increasing dietary neutral detergent fiber (NDF) to determine effects of method of bermudagrass storage and dietary fiber content on intake, milk yield, and nutrient digestion. Bermudagrass was added as hay or silage at the rate of 8.5, 15.9, or 23.3% of dietary dry matter and was substituted for an equal quantity of corn silage. The method of bermudagrass storage did not affect intake [20.8 vs. 20.3 (+/- 0.3) kg/d for bermudagrass hay and silage diets; respectively], but an increase in the amount of bermudagrass and NDF in the diet did reduce intake. Dietary NDF concentration was well above minimum recommendations of the National Research Council. Milk yield was not altered by method of bermudagrass storage but declined as dietary NDF increased. Digestion of NDF tended to be lower for bermudagrass silage than for bermudagrass hay. An increase in the amount of bermudagrass in the diet improved digestion of dietary dry matter, acid detergent fiber, and NDF; however, milk yield declined because total intake declined. Improved NDF digestion caused by added bermudagrass hay or silage was confirmed by in vitro analyses. High quality bermudagrass hybrids could potentially be used in diets of lactating dairy cows because of the good digestion characteristics and relatively small effects on intake despite the high dietary fiber content. Tifton 85 bermudagrass may serve as a forage alternative for lactating dairy cows.

Two data files, one from New Hampshire (n = 3308) and one from Georgia (n = 678), containing 4-wk or weekly means, respectively, of ad libitum dry matter intakes (DMI) and related variables were used to predict DMI and yields of 4% fat-corrected milk and milk protein in lactating Holstein cows. The DMI ranged from 5.9 to 30.4 kg/d, and milk yield ranged from 5.8 to 64.3 kg/d. Because of the lack of data from < 14 d in milk, prediction was not possible for the first 2 wk of lactation. Factors considered for inclusion in the DMI prediction model were parity number (1 or > or = 2), treatment with bovine somatotropin (bST), day of year, days in milk, minimum (nighttime) temperature-humidity index, body weight, 4% fat-corrected milk yield, milk protein yield, and corn silage and total silage percentages in forage dry matter. In separate models, the silage predictors were replaced with more specific descriptors of ration dry matter, including percentages of crude protein, fat (ether extract plus soaps of fatty acids), concentrate, acid detergent fiber or neutral detergent fiber, and forage acid detergent fiber or neutral detergent fiber. The square and sometimes natural logarithm of predictors were included in models, which then were subjected to a stepwise backward elimination option of a multiple regression procedure. Several useful equations were developed to predict ad libitum DMI; the best models accounted for about 80% of the variability in DMI, and standard deviations were < 9% of mean DMI. Depression in DMI related to heat stress was higher in pluriparous cows than in primiparous cows (22% vs. 6%). The negative coefficient for effects of bST treatment on DMI suggested that milk yield increased proportionally more in response to bST than did DMI. About 74 to 77% of DMI predictions were within 2 kg/d of observed DMI.

Lactating cows were used to determine the effects of increasing forage content from alfalfa (Medicago sativa L.) hay or Tifton 85 bermudagrass (Cynodon sp.) hay or Tifton 85 bermudagrass (Cynodon sp.) hay on dry matter intake (DMI), milk yield, and nutrient digestion. Forage proportions and neutral detergent fiber (NDF) content of diets were (dry basis) 1) 45% corn (Zea mays L.) silage (control), 33.5% NDF; 2) 15% bermudagrass hay and 30% corn silage, 39.5% NDF; 3) 30% bermudagrass hay and 15% corn silage, 46.6% NDF; 4) 15% alfalfa hay and 30% corn silage, 35.5% NDF; or 5) 30% alfalfa hay and 15% corn silage, 33.5% NDF. The DMI was greater with alfalfa diets than with bermudagrass diets, with low hay diets than with high hay diets, and with the control diet than with the hay diets. Digestibility of NDF in bermudagrass diets was greater than that in alfalfa diets, in high hay diets than in low hay diets, and in hay diets than in the control diet. In vitro NDF digestion was most rapid for bermudagrass hay, intermediate for corn silage, and slowest for alfalfa hay. Results suggest that NDF from bermudagrass was digested more completely and rapidly than was NDF from corn silage or alfalfa, which improved the rate of passage despite the high NDF content of diets containing bermudagrass. Milk yield followed trends for DMI. The control diet and diets containing alfalfa elicited the greatest DMI and milk yield, but DMI per 100 kg of body weight for Holsteins was equal for diets containing either bermudagrass or alfalfa. High quality bermudagrass can be used in rations for lactating dairy cows.