Heat stress (HS) reduces production and efficiency in almost every metric of the dairy operation, and it thus compromises profitability and sustainability. If the magnitude of HS progresses, it can ...become lethal. Death can occur acutely or days following the heat load, even if environmental conditions have become nonstressful. Consequently, lethal heat stress (LHS) is often difficult to identify and almost always misdiagnosed. The precise mechanisms of death when dairy cows succumb to LHS has not been fully elucidated or documented, but the pathophysiology of LHS appears to be conserved among several species. The unique digestive physiology of ruminants adds additional layers of complexity that contribute to failure of multiple systems involved with LHS. Consequently, the ostensible etiology and pathogenesis of LHS described herein is extended from the physiological adaptations cows use to survive HS and pertinent pathology extrapolated from other species. The multifactorial causes of death likely involve dysfunction and imbalance of several interdependent systems as follows: (1) electrolyte dyshomeostasis, (2) unstable blood pH, (3) gastrointestinal tract hyperpermeability, (4) sepsis, (5) severe immune activation-induced inflammation, (6) disseminated intravascular hypercoagulation, (7) systemic endothelial permeability, (8) multiple organ failure, and (9) circulatory failure. Having a better understanding of the mechanisms of LHS will improve diagnosis, enable a more accurate prognosis, and provide insight into strategies aimed at preventing dairy cow mortality and morbidity.
The objective was to evaluate relationships between putative periparturient management and dietary factors at the pen and herd levels with metabolic- and inflammation-related analytes, health ...disorders, milk yield, and reproductive performance. Multiparous and primiparous cows from 72 farms in the northeastern United States were enrolled in a prospective cohort study. Farms were visited 3 times during the prepartum and postpartum periods: during the far-off dry, close-up dry, and fresh periods. Pen measurements were taken at each visit for the pens where cows sampled were housed, and particle size was determined for the total mixed ration for the pen. A survey was used to acquire data on herd-level management variables. Blood samples were collected from the same 11 to 24 cows per farm during the close-up and fresh period visits. Whole blood was analyzed for postpartum β-hydroxybutyrate (BHB) concentrations, and plasma was analyzed for prepartum and postpartum nonesterified fatty acids (NEFA) and postpartum haptoglobin (Hp) concentrations. Health event, milk yield, and reproductive records were acquired through the records management software program used on the farm. For the pen-level analysis, primiparous and multiparous cows were analyzed separately. For the pen- and herd-level analysis, a simple linear regression was conducted on all possible explanatory variables. Variables were included in the full multivariable general linear model if P < 0.20, and a manual backward stepwise elimination process ensued until all variables had P < 0.10. Our results indicate that pen- and herd-level management factors are associated with blood biomarkers, health, milk yield, and reproductive performance. For the prepartum period, our results support increasing the proportion of particles on the 19-mm sieve of the Penn State Particle Separator, optimizing bunk space, and not overfeeding metabolizable energy (ME), to decrease the prevalence of elevated postpartum NEFA, BHB, and Hp concentrations, decrease disorder incidence, maximize milk yield, and improve pregnancy risk to first service. For the fresh period, our results generally support optimizing bunk space, avoiding commingling, increasing feeding frequency, avoiding high physically effective undigested neutral detergent fiber (NDF) after 240 h of in vitro fermentation and high total fermentable carbohydrate diets while optimizing the inclusion of forage NDF, and ensuring adequate diet ME and metabolizable protein to reduce the prevalence of elevated postpartum NEFA, BHB, and Hp concentrations, minimize disorder incidence, maximize milk yield, and improve pregnancy risk to first service. At the herd level, our results generally support not vaccinating in the calving pen, minimizing the number of prepartum and postpartum pen moves, and avoiding long stays in the calving pen after parturition to reduce the prevalence of elevated biomarker concentrations, decrease disorder incidence, increase milk yield, and improve reproductive performance.
The objectives were as follows: (1) establish cow-level thresholds for prepartum nonesterified fatty acids (NEFA) and postpartum NEFA, β-hydroxybutyrate (BHB), and haptoglobin (Hp) concentrations ...associated with negative health events; (2) evaluate cow-level associations between biomarkers and 305-d mature equivalent milk at the fourth test day (ME305) and reproductive performance; and (3) identify herd-alarm levels (proportion of cows sampled above the critical threshold) for biomarkers that are associated with herd-level changes in disorder incidence (displaced abomasum and clinical ketosis), reproductive performance, and ME305. In a prospective cohort study, 1,473 cows from 72 farms were enrolled from the northeastern United States. Blood samples were collected from the same 11 to 24 cows per herd during the late-prepartum and early-postpartum periods. Whole blood was analyzed for postpartum BHB concentrations; plasma was analyzed for prepartum and postpartum NEFA and postpartum Hp concentrations. Critical thresholds for the biomarkers associated with health events for all cows were established using a receiver operating characteristic curve analysis. Poisson, linear mixed effects, and Cox proportional hazards models investigated the association of the biomarkers with health and performance. The prepartum NEFA and Hp threshold associated with culling was ≥0.17 mmol/L and 0.45 g/L, respectively. The postpartum NEFA and BHB thresholds associated with diagnosis of metritis, displaced abomasum, or clinical ketosis were ≥0.46 mmol/L and ≥0.9 mmol/L, respectively. Multiparous cows with prepartum NEFA concentration ≥0.17 mmol/L produced 479 kg less ME305. Multiparous and primiparous cows with postpartum NEFA concentration ≥0.46 mmol/L produced 280 kg less and 446 kg more ME305, respectively. Cows with BHB concentration ≥0.9 and ≥1.1 mmol/L produced 552 kg more ME305 and had a 20% decreased risk of pregnancy within 150 d in milk, respectively; however, multiparous cows with BHB concentration ≥1.5 mmol/L produced 376 kg less ME305. Cows with Hp concentration ≥0.45 g/L produced 492 kg less ME305 and had 28% decreased risk of pregnancy within 150 DIM. Cows with Hp concentration ≥0.45 g/L had 19% decreased pregnancy risk to first service (PRFS). Herds above the herd-alarm levels for prepartum NEFA had a 6.0-percentage unit increase in disorder incidence and a 6.0-percentage unit decrease in 21-d pregnancy rate (PR) for multiparous cows, a 3.9-percentage unit increase in PR and a 5.8-percentage unit increase in the probability of pregnancy for primiparous cows. Herds above the herd-alarm levels for postpartum NEFA had a 5.8- and 4.2-percentage unit increase in disorder incidence for multiparous and primiparous cows, respectively, a 789 kg decrease in ME305 for multiparous cows, and a 6.8- and 6.3-percentage unit decrease and increase in PR and PRFS for multiparous cows, respectively. Herds above the herd-alarm levels for BHB had an 8.5-percentage unit increase in disorder incidence, a 332 and 229 kg increase in ME305 for primiparous and multiparous cows, respectively, and a 3.2-, 5.2-, and 7.0-percentage unit decrease in PR, probability of pregnancy, and PRFS, respectively. Herds above the herd-alarm levels for postpartum Hp had a 5.3-percentage unit increase in disorder incidence. At the cow level and herd level, elevated biomarker concentrations were associated with an increased disorder risk and varied performance responses.
Our objective was to describe management and herd characteristics of the transition period on freestall dairy herds in the northeastern United States using an on-farm survey and prospective cohort ...design. Enrolled herds (n = 72) had a median of 900 milking cows (range: 345–2,900) and a rolling herd average of 12,674 kg (standard deviation ± 1,220 kg), and 87.2% (n = 82/94) of fresh pens were milked at least 3×/d. The prevalence of herds with ≥15% of sampled cows with elevated concentrations of nonesterified fatty acids prepartum (≥0.27 mmol/L, 2–14 d before parturition) and postpartum primiparous: ≥0.60 mmol/L, multiparous: ≥0.70 mmol/L, 3–14 d in milk (DIM), β-hydroxybutyrate postpartum (≥1.2 mmol/L, 3–14 DIM), and haptoglobin postpartum (≥1 g/L, 0–12 DIM) was 51%, 51%, 51%, and 57%, respectively. In most herds, cows were moved to a calving pen when showing signs of labor (73.6%; n = 53/72) instead of 0 to 3 d before expected calving (26.4%, n = 19/72). Cows remained in the calving or maternity pen for a median (range) time of 2 (0–24) h after parturition before moving to the next pen. Primiparous cows remained in the first pen moved to after parturition for a longer period than multiparous cows median (range) days: 12 (1.5–25) vs. 6 (1.5–22). Approximately 20% of herds had routine vaccinations administered in the maternity or calving pen, first pen after parturition, or both. Almost all herds (n = 69/72) performed fresh cow health checks; however, only 53% (n = 38/72) locked up all fresh cows daily. More herds housed primiparous and multiparous cows in separate pens during the far-off dry (65.3%; n = 47/72) and high-lactation (81.9%; n = 59/72) periods compared with the close-up dry (31.9%; n = 23/72) and fresh periods (27.8%; n = 20/72). At least half of the pens observed during the far-off dry, close-up dry, and fresh periods had a stocking density <100%. Approximately one-third of pens observed during the far-off dry period had feed pushed up ≤4×/d compared with approximately 15 to 20% of pens observed during the close-up dry, fresh, and high-lactation periods. More than half of the total mixed ration samples acquired from the far-off and close-up dry period visits had greater than the recommended proportion of particles in the 19-mm screen of the Penn State Particle Separator. The results of this observational study illustrated the range of management practices used in freestall herds in this region and lay the groundwork for future hypothesis-driven studies using this sampled population.
The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa peptide produced by alveolar epithelial cells in the lung. To discern the role of SP-C in lung function, SP-C-deficient ...(-/-) mice were produced. The SP-C (-/-) mice were viable at birth and grew normally to adulthood without apparent pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (-/-) mice, nor was mature SP-C protein detected by Western blot of alveolar lavage from SP-C (-/-) mice. The levels of the other surfactant proteins (A, B, D) in alveolar lavage were comparable to those in wild-type mice. Surfactant pool sizes, surfactant synthesis, and lung morphology were similar in SP-C (-/-) and SP-C (+/+) mice. Lamellar bodies were present in SP-C (-/-) type II cells, and tubular myelin was present in the alveolar lumen. Lung mechanics studies demonstrated abnormalities in lung hysteresivity (a term used to reflect the mechanical coupling between energy dissipative forces and tissue-elastic properties) at low, positive-end, expiratory pressures. The stability of captive bubbles with surfactant from the SP-C (-/-) mice was decreased significantly, indicating that SP-C plays a role in the stabilization of surfactant at low lung volumes, a condition that may accompany respiratory distress syndrome in infants and adults.
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•The early postpartum cow is characterized as being in an increased inflammatory state.•Integrating multiple biomarkers into an index may be useful for assessing transition cow ...success.•The LHI was associated with health, milk, and reproduction.•Our LHI may be useful for evaluating transition cow success.
The objective was to evaluate a liver health index (LHI) by evaluating its association with negative health events, milk yield, and risk of pregnancy within 150 d in milk (DIM). In a retrospective cohort study, an LHI was calculated based on plasma albumin, cholesterol, and bilirubin concentrations for 265 primiparous and 611 multiparous cows 3 to 12 DIM enrolled across 72 farms in the northeastern United States. Mixed effects linear regression models were used to evaluate if (1) metritis (MET), (2) displaced abomasum (DA), (3) clinical ketosis (CK), (4) one or more of the 3 disorders (MET, DA, or CK), (5) 2 or more of the 3 disorders (MET, DA, or CK), or (6) culling within 30 DIM was associated with LHI. Mixed effects linear regression models were used to evaluate if LHI was associated with 305-d mature equivalent milk at the fourth test day (ME305; mean ± standard deviation: 114 ± 13 DIM) and a Cox proportional hazards model was used to evaluate if LHI was associated with pregnancy within 150 DIM. Cows that were diagnosed with MET, DA, CK, one or more of the disorders, 2 or more of the disorders, or were culled within 30 DIM had a lower LHI than cows that were not diagnosed with a disorder or culled. A 1-unit increase in LHI was associated with a 154 ± 38 kg increase in ME305 and a 8% increased risk of pregnancy within 150 DIM hazard ratio (95% confidence interval): 1.08 (1.03 to 1.14) for multiparous cows; however, we did not identify a relationship between LHI and ME305 or pregnancy within 150 DIM for primiparous cows. These results suggest that the LHI is associated with health, milk yield, and pregnancy within 150 DIM for multiparous cows and health for primiparous cows; therefore, the LHI can be used as a tool to evaluate transition cow success.
Empirical evidence suggests that prolonged underfeeding of protein to late-pregnant dry cows can have modest negative carry-over effects on milk volume and/or protein yield during early lactation, ...and may also cause increased incidence of metabolic diseases associated with fatty liver. However, assessment of requirements is hampered by lack of information on relationships between dietary intake of crude protein (N x 6.25) and metabolizable protein supply during late pregnancy, and by incomplete understanding of the quantitative metabolism of amino acids in maternal and conceptus tissues. Inability of the postparturient cow to consume sufficient protein to meet mammary and extra-mammary amino acid requirements, including a significant demand for hepatic gluconeogenesis, necessitates a substantial, albeit transient, mobilization of tissue protein during the first 2 weeks of lactation. Ultimately, much of this mobilized protein appears to be derived from peripheral tissues, especially skeletal muscle and, to a lesser extent, skin, through suppression of tissue protein synthesis, and possibly increased proteolysis. In the shorter term, soon after calving, it is likely that amino acids required for hepatic glucose synthesis are diverted from high rates of synthesis of splanchnic tissue and export proteins, including serum albumin. The prevailing endocrine milieu of the periparturient cow, including major reductions in plasma levels of insulin and insulin-like growth factor-I, together with insulin resistance in peripheral tissues, must permissively facilitate, if not actively promote, net mobilization of amino acids from these tissues.
Surfactant protein C (SP-C) is expressed in alveolar Type II epithelial cells of the lung. In order to determine the mechanism(s)
that regulate gene transcription, we have analyzed the activation of ...the murine SP-C promoter in mouse lung epithelial cells
(MLE cells) and in HeLa cells after co-transfection with a vector expressing rat thyroid transcription factor-1 (TTF-1). TTF-1
transactivated SP-C-chloramphenicol acetyltransferase constructs containing â13 kilobase pairs to â320 base pairs (bp) of
the 5â² flanking region of the SP-C gene. Essential cis-acting elements were functionally localized to between â320 and â180
bp from the start of transcription by transfection analysis. Five DNase-protected regions, indicating multiple protein-DNA
interactions within the â320 bp TTF-1-responsive region of the SP-C gene, were identified by DNase footprint analysis. A 40-bp
segment of SP-C DNA from â197 to â158 linked to a heterologous promoter-chloramphenicol acetyltransferase construct activated
expression after co-transfection with CMV-TTF-1 in HeLa and MLE cells. The â197 to â158 segment contained two consensus TTF-1
sites, which were specifically identified as TTF-1 binding sites by gel retardation and antibody supershift with MLE cell
nuclear extracts and purified TTF-1 homeodomain protein. Site-specific mutagenesis of either of the TTF-1 binding sites completely
blocked activation by TTF-1, indicating both sites are required for TTF stimulation of SP-C transcription.
We used transgenic mice to identify cis-active regions of the human pulmonary surfactant protein C (SP-C) gene that impart tissue- and cell-specific expression in vivo in the lung. Approximately 3.7 ...kb of genomic SP-C DNA upstream of the transcription start site was sufficient to direct chloramphenicol acetyltransferase (CAT) reporter gene expression specifically in bronchiolar and alveolar epithelial cells of the lung. To further define cis-active regulatory elements that mediate cell-specific expression, we tested deletions of the parental 3.7-kb human SP-C sequence in transgenic mice. Tissue CAT assays of mice generated with truncations or overlapping internal deletions of the 3.7-kb construct functionally map alveolar cell-specific regulatory elements to within -215 bp of the SP-C promoter. Analysis of SP-C promoter deletions demonstrate that sequences between -3.7 kb and -1.9 kb contain enhancer sequences that stimulate SP-C transgene expression. In situ hybridization studies demonstrate that deletion of the -1,910- to -215-bp region abolishes the ectopic bronchiolar expression seen with the original 3.7-kb SP-C promoter construct. Comparison of sequences from -215 to +1 bp identified consensus binding sites for the homeodomain transcription factor thyroid transcription factor-1 (TTF-1). Cotransfection assays of the human 3.7-kb SP-C or -1,910- to -215-bp SP-C deletion construct with a TTF-1 expression plasmid demonstrates that TTF-1 transactivates the human SP-C gene. These results suggest that the TTF-1 cis-active sites are important in directing cell-specific expression of the SP-C gene in vivo.
Uncertainties in the understanding of Johne's disease make the pursuit of disease control confusing for producers and veterinarians. Genetic control recommendations have limited adoption or success ...because they fail to account for the unique circumstances of individual farms. A systematic and pragmatic approach for developing farm control plans is presented. It targets the development of plans that are adapted to individual farm circumstances and are thus more likely to be implemented and effective.
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