Data from 1,010 lactating lactating, predominately component-fed Holstein cattle from 25 predominately tie-stall dairy farms in southwest Ontario were used to identify objective thresholds for ...defining hyperketonemia in lactating dairy cattle based on negative impacts on cow health, milk production, or both. Serum samples obtained during wk 1 and 2 postpartum and analyzed for β-hydroxybutyrate (BHBA) concentrations that were used in analysis. Data were time-ordered so that the serum samples were obtained at least 1 d before the disease or milk recording events. Serum BHBA cutpoints were constructed at 200μmol/L intervals between 600 and 2,000μmol/L. Critical cutpoints for the health analysis were determined based on the threshold having the greatest sum of sensitivity and specificity for predicting the disease occurrence. For the production outcomes, models for first test day milk yield, milk fat, and milk protein percentage were constructed including covariates of parity, precalving body condition score, season of calving, test day linear score, and the random effect of herd. Each cutpoint was tested in these models to determine the threshold with the greatest impact and least risk of a type 1 error. Serum BHBA concentrations at or above 1,200μmol/L in the first week following calving were associated with increased risks of subsequent displaced abomasum odds ratio (OR)=2.60 and metritis (OR=3.35), whereas the critical threshold of BHBA in wk 2 postpartum on the risk of abomasal displacement was ≥1,800μmol/L (OR=6.22). The best threshold for predicting subsequent risk of clinical ketosis from serum obtained during wk 1 and wk 2 postpartum was 1,400μmol/L of BHBA (OR=4.25 and 5.98, respectively). There was no association between clinical mastitis and elevated serum BHBA in wk 1 or 2 postpartum, and there was no association between wk 2 BHBA and risk of metritis. Greater serum BHBA measured during the first and second week postcalving were associated with less milk yield, greater milk fat percentage, and less milk protein percentage on the first Dairy Herd Improvement test day of lactation. Impacts on first Dairy Herd Improvement test milk yield began at BHBA ≥1,200μmol/L for wk 1 samples and ≥1,400μmol/L for wk 2 samples. The greatest impact on yield occurred at 1,400μmol/L (−1.88kg/d) and 2,000μmol/L (−3.3kg/d) for sera from the first and second week postcalving, respectively. Hyperketonemia can be defined at 1,400μmol/L of BHBA and in the first 2 wk postpartum increases disease risk and results in substantial loss of milk yield in early lactation.
The objective of this observational study was to investigate the risk factors for metritis, purulent vaginal discharge, and cytological endometritis. The hypothesis was that purulent vaginal ...discharge and cytological endometritis would have different risk factors because they represent distinct manifestations of uterine disease. Data generated from 1,363 Holstein cows (3 herds) enrolled in a randomized clinical trial were used. Calving history, periparturient disease incidence, and body condition score at calving and at 63 d in milk (DIM) were recorded. Serum nonesterified fatty acid concentration was measured once during the week before expected calving. Serum nonesterified fatty acid, β-hydroxybutyric acid, and haptoglobin (Hapto) concentrations were measured at 4±3, 11±3, and 18±3 DIM. Serum progesterone concentration was measured at 21±3, 35±3, 49±3, and 63±3 DIM. Metritis was diagnosed by farm managers within the first 20 DIM using a standardized definition. Cows were examined at 35±3 DIM by a veterinarian for purulent vaginal discharge (mucopurulent or worse vaginal discharge; Metricheck device) and cytological endometritis (≥6% polymorphonuclear cells on endometrial cytology; cytobrush device). Statistical analyses were performed using multivariable logistic regression models for each disease, accounting for the random effect of herd. Risk factors for metritis included increased nonesterified fatty acid prepartum (≥0.6mmol/L), dystocia, retained placenta, and increased Hapto in the first week postpartum (≥0.8g/L). Risk factors for purulent vaginal discharge included twinning, dystocia, metritis, and increased Hapto (≥0.8g/L) in the first week postpartum. Risk factors for cytological endometritis included low body condition score at parturition (≤2.75), hyperketonemia (≥1,100μmol/L), and increased Hapto (≥0.8g/L) in the first week postpartum. These results support the hypothesis that some of the risk factors for purulent vaginal discharge and cytological endometritis are different, which supports that they are distinct manifestations of uterine disease.
The objectives of this observational study were to determine and compare diagnostic criteria for postpartum endometritis in dairy cows. Data generated from 1,044 Holstein cows (6 herds) enrolled in a ...randomized clinical trial were used. Cows were examined for endometritis at 35±3 d (exam 1) and 56±3 d (exam 2) after parturition, using endometrial cytology (cytobrush technique), vaginal discharge scoring (Metricheck device; Simcrotech, Hamilton, New Zealand), and cervical diameter measurement (transrectal palpation). Reproductive data were recorded until 200 d after parturition. Diagnostic criteria for cytological and clinical endometritis were determined based on detrimental effect on subsequent reproductive performance, using logistic regression and Cox proportional hazard models accounting for the effect of herd clustering. Comparison of diagnostic criteria was performed using endometrial cytology as reference test or by quantifying the agreement between diagnostic approaches. At exam 1, diagnostic criteria were ≥6% polymorphonuclear cells and mucopurulent or worse (purulent or foul) vaginal discharge for cytological and clinical endometritis, respectively. At exam 2, diagnostic criteria were ≥4% polymorphonuclear cells and mucopurulent or worse vaginal discharge for cytological and clinical endometritis, respectively. Cows were classified as having cytological endometritis only, clinical endometritis only, or both cytological and clinical endometritis. Prevalence at exam 1 was 13.5, 9.4, and 5.8% for cytological endometritis only, clinical endometritis only, and both cytological and clinical endometritis, respectively. The detrimental effects of cytological and clinical endometritis on reproductive performance were additive. Among cows with clinical endometritis, only 38 and 36% had cytological endometritis at exam 1 and exam 2, respectively. Combination of diagnostic criteria improved neither the accuracy for predicting cytological endometritis nor the agreement between cytological and clinical endometritis. Overall, these results suggested that cytological and clinical endometritis may represent different manifestations of reproductive tract disease. They also suggested that use of the terminology clinical endometritis may not be accurate and that purulent vaginal discharge may be more descriptive.
Mastitis is a common and costly production disease on dairy farms. In Canada, the incidence rate of clinical mastitis (IRCM) has been determined for conventionally managed dairy farms; however, no ...studies to date have assessed rates in organically managed systems. The objectives of this observational study were (1) to determine the producer-reported IRCM and predominant pathogen types on conventional and organic dairy farms in Southern Ontario, Canada, and (2) to evaluate the association of both mean overall IRCM and pathogen-specific IRCM with management system, housing type, and pasture access. Data from 59 dairy farms in Southern Ontario, Canada, distributed across conventional (n=41) and organic management (n=18) systems, were collected from April 2011 to May 2012. In addition to management system, farms were categorized by housing method (loose or tie-stall) and pasture access for lactating cows. Participating producers identified and collected samples from 936 cases of clinical mastitis. The most frequently isolated mastitis pathogens were coagulase-negative staphylococci, Bacillus spp., Streptococcus spp., Staphylococcus aureus, and Escherichia coli. The IRCM was higher on conventional farms than organic (23.7 vs. 13.2 cases per 100 cow-years) and was not associated with housing type (loose or tie-stall), pasture access, or herd-average milk yield. Bulk tank somatic cell count tended to be lower on conventional farms than organic (222,000 vs. 272,000cells/mL). Pathogen-specific IRCM attributed to Staph. aureus, Bacillus spp., and E. coli was greater on conventional than organic farms, but was not associated with housing or any other factors. In conclusion, organic management was associated with reduced overall and pathogen-specific IRCM.
This paper describes some of the major points of progress and challenges in health management of dairy cattle in the last 25 yr. A selection of the leading contributors in the field is acknowledged. ...Specific advances in the areas of transition cow management, epidemiology, udder health, applied immunology, housing design, calf health, and health-monitoring tools are described. The greatest advances in dairy health in the last 25 yr have been the shifts to disease prevention, rather than treatment, as well as from focus on individual animals to groups and herds. A fundamental advancement has been recognition of the multifactorial nature of almost all diseases of importance in dairy cattle. Epidemiology has been a critical new tool used to describe and quantify the interconnected risk factors that produce disease. Another major advance has been redefining disease more broadly, to include subclinical conditions (e.g., subclinical mastitis, ketosis, rumen acidosis, and endometritis). This expansion resulted both from improved technology to measure function at the organ level and, just as importantly, from the evolution of the health management paradigm in which any factor that limits animal or herd performance might be considered a component of disease. Links between cattle and people through consideration of environmental or ecosystem health are likely to further expand the concept of disease prevention in the future.
Notable successes are decreases in the incidence of milk fever, clinical respiratory disease in adults, contagious mastitis, and clinical parasitism. There has also been improved protection through vaccination against coliform mastitis and bovine virus diarrhea. Since 1980, average herd size and milk production per cow have increased dramatically. Despite these increased demands on cows’ metabolism and humans’ management skills, the incidence of most common and important diseases has remained stable. Great progress has been made in understanding the biology of energy metabolism and immune function in transition dairy cows, the time at which the majority of disease occurs. Coupled with an emerging understanding of how best to provide for dairy cows’ behavioral needs, transition cow management promises to be the foundation for progress in maintenance and enhancement of the health of dairy cows in the next 25 yr.
The objective was to examine the associations of peripartum concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and calcium with milk production in early lactation and ...pregnancy at the first artificial insemination (AI) across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were visited weekly for blood sample collection from 2,365 cows. For each week of sampling (from wk −1 through wk 3 relative to calving) and for each metabolite, serum concentrations were dichotomized at various thresholds to identify the thresholds with the best negative associations with milk production and pregnancy at first AI. These thresholds were used to categorize the serum concentrations into higher and lower risk categories. Repeated-measures ANOVA and multivariable logistic regression were conducted for milk production and pregnancy at the first AI data, respectively, considering cow as the experimental unit and herd as a random effect. In the week before calving, serum NEFA ≥0.5mEq/L, BHBA ≥600μmol/L, and calcium ≤2.1mmol/L were associated with 1.6 to 3.2 kg/d milk loss across the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of NEFA and BHBA in wk 1 and 2 after calving (≥0.7 and ≥1.0mEq/L for NEFA, and ≥1,400 and ≥1,200μmol/L for BHBA), and low levels of calcium (≤2.1mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low concentrations of calcium around parturition were associated with early lactation milk loss, and low calcium concentration around parturition was associated with impaired early lactation reproduction.
With the rise of e-cigarette use, teen nicotine exposure is becoming more widespread. Findings from clinical and preclinical studies show that the adolescent brain is particularly sensitive to ...nicotine. Animal studies have demonstrated that adolescent nicotine exposure increases reinforcement for cocaine and other drugs. However, the mechanisms that underlie these behaviors are poorly understood. Here, we report reactive microglia are critical regulators of nicotine-induced increases in adolescent cocaine self-administration. Nicotine has dichotomous, age-dependent effects on microglial morphology and immune transcript profiles. A multistep signaling mechanism involving D2 receptors and CX3CL1 mediates nicotine-induced increases in cocaine self-administration and microglial activation. Moreover, nicotine depletes presynaptic markers in a manner that is microglia-, D2- and CX3CL1-dependent. Taken together, we demonstrate that adolescent microglia are uniquely susceptible to perturbations by nicotine, necessary for nicotine-induced increases in cocaine-seeking, and that D2 receptors and CX3CL1 play a mechanistic role in these phenomena.
Evidence exists that early life experiences may influence development of characteristic feeding patterns in dairy cattle. The objective of this study was to determine the effect of milk feeding level ...on performance and development of feeding patterns in dairy calves. Twenty Holstein bull calves were assigned at birth to a milk replacer feeding level, fed via a teat: (1) ad libitum (ADL) or (2) restricted feeding at 5L/d (0.75kg of milk replacer) in 2 feedings/d (RES). All calves were offered concentrate ad libitum during the milk feeding stage. Calves were weaned gradually during wk 7 and then fed a pelleted diet ad libitum for 7 wk. Calves were weighed 2 times/wk. Feed and milk intakes were recorded daily. Feeding behavior was recorded from video for 5d in each of wk 3, 6, 8, 11, and 14. Calves fed ADL consumed 2.6 times more milk, had greater weight gain (1.2 vs. 0.6kg/d), and consumed less solid feed (45.2 vs. 98.0g/d) during the milk feeding period than did calves fed RES. As expected, providing milk ADL resulted in more frequent meals (in wk 6, 7.1 vs. 2.0) and more evenly distributed diurnal patterns of feeding activity compared with the RES milk level. When considering all sucking bouts (milk feeding and nonnutritive sucking), no difference was observed between treatments in daily bout frequency or sucking time/bout. Postweaning, calves fed RES had initially greater rate of intake (24.9 vs. 17.8g/min) and meal size (160.8 vs. 117.2g/meal). Diurnal feeding patterns also differed in the first week after weaning, with ADL calves feeding less continuously at the time of feed delivery. Meal characteristics and diurnal patterns of feeding activity were similar between calves by the end of the trial. However, milk feeding level had a longer-term effect on variability in feeding behavior, with calves fed RES having greater day-to-day variability in feeding time and meal size. Variability of meal characteristics also decreased over time across treatments. These results suggest that milk feeding level may have a short-term influence on postweaning feeding behavior. However, differences in early feeding patterns due to milk feeding level do not appear to affect longer-term development of feeding patterns.
Summary
Background
B cells play many roles in health and disease. However, little is known about the mechanisms that drive B cell responses in the airways, especially in humans. Chronic ...rhinosinusitis (CRS) is an inflammatory disease of the upper airways that affects 10% of Europeans and Americans. A subset of CRS patients develop nasal polyps (NPs), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ILC2s). We have reported that NP contain elevated levels of B cells and antibodies, making NP an ideal system for studying B cells in the airways.
Objective
We sought to determine the mechanisms that drive B cell activation and antibody production during chronic airway inflammation.
Methods
We analysed B cells from NP or tonsil, or after ILC2 coculture, by flow cytometry. Antibody production from tissue was measured using Luminex assays and the frequency of antibody‐secreting cells by ELISpot. Formation of B cell clusters was assessed using immunohistochemistry. Expression of genes associated with B cell activation and class switch recombination was measured by qRT‐PCR.
Results
NP contained significantly elevated frequencies of plasmablasts, especially those that expressed the extrafollicular marker Epstein–Barr virus‐induced protein 2 (EBI2), but significantly fewer germinal centre (GC) B cells compared with tonsil. Antibody production and the frequency of antibody‐secreting cells were significantly elevated in NP, and there was evidence for local class switch recombination in NP. Finally, ILC2s directly induced EBI2 expression on B cells in vitro.
Conclusions and Clinical Relevance
Our data suggest there is a unique B cell activation environment within NP that is distinct from classic GC‐mediated mechanisms. We show for the first time that ILC2s directly induce EBI2 expression on B cells, indicating that ILC2s may play an important role in B cell responses. B cell‐targeted therapies may provide new treatment options for CRSwNP.
The objective was to identify herd-level indicators expressed as a proportion of sampled animals with increased nonesterified fatty acids (NEFA) or β-hydroxybutyric acid (BHBA), or decreased calcium ...in wk −1 and wk +1 relative to calving that were associated with herd-level incidence of retained placenta, metritis and displaced abomasum, milk production, and probability of pregnancy at the first artificial insemination (AI). Fifty-five Holstein freestall dairy herds in the United States and Canada were visited weekly. Blood was collected from 2,365 cows around parturition, and serum concentrations of NEFA, BHBA, and calcium were determined. Different cow-level metabolite thresholds associated with detrimental health or productivity in previous studies were used to classify animals into high- and low-risk metabolite concentration groups. For wk −1 and wk +1 relative to calving, a herd-level threshold was determined as the proportion of sampled animals in the high-risk metabolite concentration groups with the strongest association with increased incidence of disease, milk loss, or decreased pregnancy at the first AI. The odds of displaced abomasum after calving were higher in herds that had ≥25% of the animals with BHBA ≥1,400μmol/L in wk +1 odds ratio (OR)=2.1; 95% confidence interval (CI)=1.0–4.2) or ≥35% of the animals with calcium ≤2.1mmol/L in wk +1 (OR=2.4; CI=1.3–4.3). Herd-level thresholds of ≥15% of the cows with BHBA ≥800μmol/L in wk −1 and ≥15% of the cows with calcium ≤2.1mmol/L in wk +1 were associated with milk loss (±SE) of 4.4±1.7 and 3.8±1.4kg/d per cow, respectively. When only multiparous cows were considered, herds with ≥30% of the multiparous cows with NEFA ≥0.5mEq/L in wk −1 were associated with a 3.0±1.5kg/d per cow milk loss. The odds of pregnancy at first AI were lower in herds that had ≥5% of the cows with calcium ≤2.1mmol/L in wk −1 (OR=0.7; CI=0.5–1.0), or ≥30% of the cows with NEFA ≥1.0mEq/L (OR=0.6; CI=0.4–0.9) or ≥25% of the cows with calcium ≤2.1mmol/L in wk +1 (OR=0.7; CI=0.5–0.9). When only multiparous cows were considered, the odds of pregnancy at first AI were lower in herds that had ≥50% of multiparous cows with NEFA ≥0.5mEq/L in wk −1 (OR=0.5; CI=0.2–0.9). In conclusion, several herd-level thresholds for the proportion of cows with increased NEFA or BHBA, or decreased calcium in the week before and after calving were associated with higher risk of displaced abomasum, milk loss at the first Dairy Herd Improvement Association test, and decreased pregnancy at first AI. The association found between precalving BHBA and milk production is promising due to the availability of several cow-side tests for measuring BHBA. Some of the herd-level associations differed from the previously described cow-level associations, suggesting the potential of interpreting periparturient metabolic challenges at the herd level, where changes in diet and management are generally implemented.
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