Association between somatic cell count early in the first lactation and the lifetime milk yield of cows in Irish dairy herds

Change in lifetime milk yield is an important component of the cost of diseases in dairy cows. Knowledge of the likelihood and scale of potential savings through disease prevention measures is important to evaluate how much expenditure on control measures is rational. The aim of this study was to assess the association between somatic cell count (SCC) at 5 to 30 d in milk during parity 1 (SCC1), and lifetime milk yield for cows in Irish dairy herds. The data set studied included records from 53,652 cows in 5,922 Irish herds. This was split into 2 samples of 2,500 and 3,422 herds at random. Linear models with lifetime milk yield and first-lactation milk yield as the outcomes and random effects to account for variation between herds were fitted to the data for the first sample of herds; data for the second sample were used for cross-validation. The models were developed in a Bayesian framework to include all uncertainty in posterior predictions and parameters were estimated from 10,000 Markov chain Monte Carlo simulations. The final model was a good fit to the data and appeared generalizable to other Irish herds. A unit increase in the natural logarithm of SCC1 was associated with a median decrease in lifetime milk yield of 864kg, and a median decrease in first-lactation milk yield of 105kg. To clarify the meaning of the results in context, microsimulation was used to model the trajectory of individual cows, and evaluate the expected outcomes for particular changes in the herd-level prevalence of cows with SCC1 ≥400,000cells/mL. Differences in mean lifetime milk yield associated with these changes were multiplied by an estimated gross margin for each cow to give the potential difference in milk revenue. Results were presented as probabilities of savings; for example, a 75% probability of savings of at least€97 or€115/heifer calved into the herd existed if the prevalence of cows with SCC1 ≥400,000cells/mL was reduced from ≥20 to <10 or <5%, respectively, and at least€71/heifer calved into the herd if the prevalence of cows with SCC1 ≥400,000cells/mL was reduced from ≥10 to <5%. The results indicate large differences in lifetime milk yield, depending on SCC early in the first lactation and the findings can be used to assess where specific interventions to control heifer mastitis prepartum are likely to be cost effective. Key words: dairy heifer, somatic cell count, lifetime milk yiel

Association of season and herd size with somatic cell count for cows in Irish,English, and Welsh dairy herds

The aims of this study were to describe associations of time of year, and herd size with cow somatic cell count (SCC) for Irish, English, and Welsh dairy herds. Random samples of 497 and 493 Irish herds, and two samples of 200 English and Welsh (UK) herds were selected. Random effects models for the natural logarithm of individual cow test day SCC were developed using data from herds in one sub-dataset from each country. Data from the second sub-datasets were used for cross validation. Baseline model results showed that geometric mean cow SCC (GSCC) in Irish herds was highest from February to August, and ranged from 111,000 cells/mL in May to 61,000 cells/mL in October. For cows in UK herds, GSCC ranged from 84,000 cells/mL in February and June, to 66,000 cells/mL in October. The results highlight the importance of monitoring cow SCC during spring and summer despite low bulk milk SCC at this time for Irish herds. GSCC was lowest in Irish herds of up to 130 cows (63,000 cells/mL), and increased for larger herds, reaching 68,000 cells/mL in herds of up to 300 cows. GSCC in UK herds was lowest for herds of 130–180 cows (60,000 cells/mL) and increased to 63,000 cells/mL in herds of 30 cows, and 68,000 cells/mL in herds of 300 cows. Importantly, these results suggest expansion may be associated with increased cow SCC, highlighting the importance of appropriate management, to benefit from potential economies of scale, in terms of udder health

Bayesian evaluation of budgets for endemic disease control: an example using management changes to reduce milksomatic cell count early in the first lactation of Irish dairy cows

The aim of this research was to determine budgets for specific management interventions to control heifer mastitis in Irish dairy herds as an example of evidence synthesis and 1-step Bayesian micro-simulation in a veterinary context. Budgets were determined for different decision makers based on their willingness to pay. Reducing the prevalence of heifers with a high milk somatic cell count (SCC) early in the first lactation could be achieved through herd level management interventions for pre- and peri-partum heifers, however the cost effectiveness of these interventions is unknown. A synthesis of multiple sources of evidence, accounting for variability and uncertainty in the available data is invaluable to inform decision makers around likely economic outcomes of investing in disease control measures. One analytical approach to this is Bayesian micro-simulation, where the trajectory of different individuals undergoing specific interventions is simulated. The classic micro-simulation framework was extended to encompass synthesis of evidence from 2 separate statistical models and previous research, with the outcome for an individual cow or herd assessed in terms of changes in lifetime milk yield, disposal risk, and likely financial returns conditional on the interventions being simultaneously applied. The 3 interventions tested were storage of bedding inside, decreasing transition yard stocking density, and spreading of bedding evenly in the calving area. Budgets for the interventions were determined based on the minimum expected return on investment, and the probability of the desired outcome. Budgets for interventions to control heifer mastitis were highly dependent on the decision maker's willingness to pay, and hence minimum expected return on investment. Understanding the requirements of decision makers and their rational spending limits would be useful for the development of specific interventions for particular farms to control heifer mastitis, and other endemic diseases. Keywords Bayesian; Micro-simulation; Dairy heifer; Mastitis control; Cost-effectiveness; Decision makin

Association between somatic cell count during the first lactation and the cumulative milk yield of cows in Irish dairy herds

Reduced potential milk yield is an important component of mastitis costs in dairy cows. The first aim of this study was to assess associations between somatic cell count (SCC) during the first lactation, and cumulative milk yield over the first lactation and subsequent lifetime of cows in Irish dairy herds. The second aim was to assess the association between SCC at 5 to 30 d in milk during parity 1 (SCC1), and SCC over the entire first lactation for cows in Irish dairy herds. The data set studied included records from 51,483 cows in 5,900 herds. Somatic cell count throughout the first lactation was summarized using the geometric mean and variance of SCC. Data were analyzed using linear models that included random effects to account for the lack of independence between observations, and herdlevel variation in coefficients. Models were developed in a Bayesian framework and parameters were estimated from 10,000 Markov chain Monte Carlo simulations. The final models were a good fit to the data. A 1-unit increase in mean natural logarithm SCC over the first lactation was associated with a median decrease in first lactation and lifetime milk yield of 135 and 1,663 kg, respectively. A 1-unit increase in the variance of natural logarithm SCC over the first lactation was associated with a median decrease in lifetime milk yield of 719 kg. To demonstrate the context of lifetime milk yield results, microsimulation was used to model the trajectory of individual cows and evaluate the expected outcomes for particular changes in herd-level geometric mean SCC over the first lactation. A 75% certainty of savings of at least €199/heifer in the herd was detected if herd-level geometric mean SCC over the first lactation was reduced from ≥120,000 to ≤72,000 cells/mL. The association between SCC1 and SCC over the remainder of the first lactation was highly herd dependent, indicating that control measures for heifer mastitis should be preferentially targeted on an individual-herd basis toward either the pre- and peripartum period, or the lactating period, to optimize the lifetime milk yield of dairy cows

Circulating Zonulin, a Marker of Intestinal Permeability, Is Increased in Association with Obesity-Associated Insulin Resistance

Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase

The SPINK gene family and celiac disease susceptibility

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n = 15) and diet-treated patients (n = 31) and controls (n = 16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population

Farnesoid X Receptor (FXR) Activation and FXR Genetic Variation in Inflammatory Bowel Disease

Contains fulltext : 96924.pdf (publisher's version ) (Open Access)BACKGROUND: We previously showed that activation of the bile salt nuclear receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We investigated whether FXR activation is repressed in the ileum and colon of inflammatory bowel disease (IBD) patients in remission. Additionally, we evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA expression of FXR and FXR target gene SHP was determined in ileal and colonic biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n = 12), all in clinical remission, and healthy controls (n = 17). Seven common tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls. RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's colitis but not in patients with UC compared to controls. mRNA expression of villus marker Villin was correlated with FXR and SHP in healthy controls, a correlation that was weaker in UC patients and absent in CD patients. None of the SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD. CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's colitis. This may be secondary to altered enterohepatic circulation of bile salts or transrepression by inflammatory signals but does not seem to be caused by the studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have benefit in CD patients

'Gut health': a new objective in medicine?

'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine

Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice

Bayesian evaluation of budgets for endemic disease control: An example using management changes to reduce milk somatic cell count early in the first lactation of Irish dairy cows

The aim of this research was to determine budgets for specific management interventions to control heifer mastitis in Irish dairy herds as an example of evidence synthesis and 1-step Bayesian micro-simulation in a veterinary context. Budgets were determined for different decision makers based on their willingness to pay. Reducing the prevalence of heifers with a high milk somatic cell count (SCC) early in the first lactation could be achieved through herd level management interventions for pre- and peri-partum heifers, however the cost effectiveness of these interventions is unknown. A synthesis of multiple sources of evidence, accounting for variability and uncertainty in the available data is invaluable to inform decision makers around likely economic outcomes of investing in disease control measures. One analytical approach to this is Bayesian micro-simulation, where the trajectory of different individuals undergoing specific interventions is simulated. The classic micro-simulation framework was extended to encompass synthesis of evidence from 2 separate statistical models and previous research, with the outcome for an individual cow or herd assessed in terms of changes in lifetime milk yield, disposal risk, and likely financial returns conditional on the interventions being simultaneously applied. The 3 interventions tested were storage of bedding inside, decreasing transition yard stocking density, and spreading of bedding evenly in the calving area. Budgets for the interventions were determined based on the minimum expected return on investment, and the probability of the desired outcome. Budgets for interventions to control heifer mastitis were highly dependent on the decision maker\u27s willingness to pay, and hence minimum expected return on investment. Understanding the requirements of decision makers and their rational spending limits would be useful for the development of specific interventions for particular farms to control heifer mastitis, and other endemic diseases