Skeletal muscle and adipose tissue reserves and mobilisation in transition Holstein cows: Part 1 Biological variation and affecting factors.

Nutrient deficit during the periparturient period leads to mobilisation of body energy and protein reserves. Research regarding fat reserves and mobilisation is extensive, while, on the contrary, investigation of muscle mobilisation during the periparturient period is limited. The aim of this cohort study was to simultaneously investigate the biological variation of skeletal muscle and subcutaneous fat reserves together with their mobilisation in transition Holstein cows of different herds, using ultrasonography, and to assess potential affecting factors. For this purpose, ultrasound measurements of longissimus dorsi muscle thickness (LDT) and backfat thickness (BFT) from 238 multiparous cows of six dairy farms were obtained at six time points across the transition period (from 21 days pre- to 28 days postpartum). Concentrations of serum creatinine and non-esterified fatty acids were determined in order to confirm the loss of muscle mass and adipose tissue, respectively. Cases of clinical postparturient diseases and subclinical ketosis (scKET) during the first 28 days postcalving were recorded. Cows mobilised on average 32.8% and 37.3% of LDT and BFT reserves, respectively. Large between-cow variation was observed for both the onset and the degree of mobilisation. Time point, initial body condition score and parity were the most important predictors of LDT variation. Cows diagnosed with metritis (MET) had lower LDT postpartum and mobilised more muscle depth compared to cows not diagnosed with MET. Initial BCS, time point, initial BW (estimated by heart girth measurement) and parity were the most important predictors of BFT variation. Cows diagnosed with MET mobilised more backfat between -7d and 7d compared to cows not diagnosed with MET. Cows with scKET mobilised more backfat between 7- and 21 days postpartum compared to healthy ones. Variation of subcutaneous fat and skeletal muscle reserves during the transition period was large and affected by herd and several cow-level factors

Skeletal muscle and adipose tissue reserves and mobilisation in transition Holstein cows: Part 2 association with postpartum health, reproductive performance and milk production.

The aim of this study was, for the first time, to simultaneously assess the association of skeletal muscle and subcutaneous fat reserves and their mobilisation, measured by ultrasonography, with the incidence of specific postparturient health, reproduction, and milk production traits. For this purpose, ultrasound measurements of longissimus dorsi thickness (LDT) and backfat thickness (BFT) from 238 multiparous cows from 6 dairy farms were obtained at 6 time points during the transition period (from 21 days pre- to 28 days postpartum). In each case, LDT and BFT measurements at each time point and LDT and BFT mobilisation variables at each study period were assessed simultaneously. Cases of specific clinical postparturient diseases and subclinical ketosis were recorded. An additional disease trait was used, defined as the presence or absence of at least one clinical condition after calving (CD_1-28). The associated disease odds with LDT/BFT variables were assessed with binary logistic regression models. The associated hazard for 1st artificial insemination (AI) and for pregnancy by 150 days-in-milk (PREG_150DIM) was assessed with Cox proportional hazard models. Moreover, binary logistic models were used to assess the associated odds for pregnancy to 1stAI (PREG_1stAI). Finally, association with 30d, 100d and 305d milk yield was assessed with linear regression models. Increased muscle depth during transition was negatively associated with odds for metritis and CD_1-28, while associations with odds for subclinical ketosis were inconclusive. Moreover, increased LDT reserves were associated with greater hazard for 1st AI by 150 days-in-milk, but results were inconclusive regarding odds for PREG_1stAI. Increased LDT mobilisation was associated with increased odds for metritis. Increased BFT reserves were positively associated with odds for metritis, CD_1-28 and subclinical ketosis and with decreased hazard for PREG_150DIM. Increased BFT mobilisation was associated with increased odds for subclinical ketosis and with decreased odds for PREG_1stAI and decreased hazard for PREG_150DIM. Cows with moderate BFT reserves performed better. Finally, increased BFT mobilisation during -21d to -7d from parturition was associated with less milk by 30d and 100d. On the contrary, increased BFT mobilisation during -7d to 7d was associated with more milk by 305d. Metabolism of muscle and fat tissue during transition period was differently associated with different postparturient health, reproduction and milk production traits. In general, greater muscle mass and moderate fat reserves with limited muscle and fat mobilisation were associated with better performance

Variation in protein metabolism biomarkers during the transition period and associations with health, colostrum quality, reproduction, and milk production traits in Holstein cows

The aims of this study were to assess a) the variation of protein metabolism biomarkers and of factors affecting them during the transition period, b) the association of each biomarker with skeletal muscle reserves and their changes, and c) the association of these biomarkers with postpartum health, colostrum quality, reproduction, and milk production. For this purpose, 238 multiparous Holstein cows from 6 herds were used in a prospective cohort study. Plasma concentrations of 3-methylhistidine (3-MH) and 1-methylhistidine (1-MH) and serum concentrations of total protein (TP), albumin (ALB), urea nitrogen (BUN) and creatinine (SCR) were determined for each cow at -21d; -7d; 7d; 21d and 28d relative to calving. Clinical diseases were recorded during the first 28 d post-calving, and presence of subclinical ketosis (scKET) was investigated at 7d and 21d. Colostrum quality was estimated by Brix refractometry. Reproduction data by 150 d-in-milk (DIM) and milk production records were also available. Linear mixed models including the fixed effects of time point, herd, parity, body condition score (-21d), duration of dry period and post-parturient diseases were fitted to assess the variation in each biomarker's concentration. The association between the biomarkers' concentration during the pre-partum period with the odds for each post-parturient disease and for a combined trait (CD_1-28), defined as the presence of at least one clinical condition during the first 28 d after calving, were assessed with separate binary logistic models for time points -21d and -7d. The relationship of each biomarker's concentration with longissimus dorsi thickness (LDT) and the changes in LDT (ΔLDT) was assessed with pairwise correlations. Separate general linear models were used to assess the association of each biomarker with colostrum Brix values and milk production traits. Finally, the associated hazard for 1st artificial insemination (AI) and for pregnancy by 150 DIM (PREG_150DIM) was assessed with Cox proportional hazard models, while odds for pregnancy to the 1st AI (PREG_1stAI) were assessed with binary logistic models. 3-methylhistidine was affected mainly by herd, time points and their interaction. Higher 3-MH was associated with increased odds for metritis and CD_1-28, increased hazard for PREG_150 DIM and with increased milk production. 1-methylhistidine was affected mainly by herd, scKET and occurrence of displaced abomasum. Higher 1-MH was associated with better colostrum quality, increased odds for scKET, increased hazard for 1st AI by 150 DIM and with decreased milk production. Both 3-MH and 1-MH were weakly to moderately negatively correlated with LDT and moderately to strongly negatively correlated to ΔLDT at the corresponding time-periods. Additionally, higher TP was associated with increased odds for metritis and CD_1-28 and increased milk production, while higher ALB was associated with increased odds for scKET and increased milk production. Moreover, higher BUN was associated with decreased odds for scKET, increased odds for PREG_1stAI and increased milk production. Higher SCR was associated with decreased odds for retained fetal membranes, metritis, and CD_1-28. Peri-parturient protein metabolism is significantly associated with postpartum health, colostrum quality, reproduction, and milk production; mechanisms involved require further investigation

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Supplementary Materials - Variation in protein metabolism biomarkers during transition period and associations with health, colostrum quality, reproduction, and milk production traits in Holstein cows

Supplementary Materials - Variation in protein metabolism biomarkers during transition period and associations with health, colostrum quality, reproduction, and milk production traits in Holstein cowsTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Associations among post-partum rumen fill and motility, subclinical ketosis and fertility in Holstein dairy cows

This prospective observational study aimed to investigate the association of rumen fill and motility in post-partum Holstein cows with their future reproductive performance and subclinical ketosis (SCK). The study population consisted of two independent data sets: the first (DS1) included 237 cows from 6 herds and the second one (DS2) 709 cows from 9 herds. Rumen Fill Score (RFS) was transformed into a 3 level-trait, representing very low, low and adequate dry matter intake, respectively. A binary Rumen Contraction Score (RCS) was defined as: 0: &lt;2 contractions/2 min, impaired rumen motility and 1: ≥2 contractions/2 min, normal rumen motility. A combined binary trait based on RFS and RCS (RFCS) was also established, representing unsatisfactory and satisfactory rumen function. Three SCK traits were defined, based on 3 different thresholds, SCK_I: BHB≥1,000 mmol/L, SCK_II: BHB≥1,100 mmol/L and SCK_III: BHB≥1,200 mmol/L. Scores were assessed and blood samples collected on day 7 (DS1) or day 8 (DS2), postpartum. Kaplan-Meier survival analysis, multivariable Cox proportional hazards models and Generalized Linear Mixed Models were performed to evaluate the association of rumen and SCK traits with reproduction. Herd, parity, calving season and several postparturient diseases were also included as potential explanatory variables. Mean days from calving to pregnancy after the 1st artificial insemination (AI) and from calving to pregnancy (all AIs) were shorter for levels of rumen traits representing adequate DMI and normal rumen motility; in most cases these differences were statistically significant in both datasets. Cows with adequate DMI and normal rumen motility (only in DS2) had greater hazard (hazard ratio [HR] = 1.84 and 1.61, for RFS and RFCS, respectively) and odds (odds ratio [OR] = 2.49 and 1.98, for RFS and RFCS, respectively) for pregnancy at 1st AI. Assessment of the association of examined rumen traits with hazard and odds for pregnancy at all AIs yielded statistically significant results in both datasets. For RFS, RCS and RFCS, HRs ranged from 1.57 to 3.31 and ORs from 1.95 to 4.83. No statistically significant associations with hazard and odds for pregnancy at 1st or all AIs were detected, for any of the 3 SCK traits, in either dataset. Overall, the combined RFCS trait constantly identified more than twice the number of cows with future reproductive problems than a positive SCK blood test.</p

Physicians&apos; guideline adherence is associated with long-term heart failure mortality in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry

Background: Physicians&apos; adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry. Methods and results: Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87–0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94–0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9–1.02; CV: SHR 0.98, 95% CI 0.96–1.01; and HF: SHR 0.99, 95% CI 0.96–1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively). Conclusion: These results suggest that physicians&apos; adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians&apos; adherence to guidelines. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiolog