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The relationship between ambient air pollution and heart rate variability differs for individuals with heart and pulmonary disease.

Associations between concentrations of ambient fine particles [particulate matter < 2.5 microm aerodynamic diameter (PM2.5)] and heart rate variability (HRV) have differed by study population. We examined the effects of ambient pollution on HRV for 18 individuals with chronic obstructive pulmonary disease (COPD) and 12 individuals with recent myocardial infarction (MI) living in Atlanta, Georgia. HRV, baseline pulmonary function, and medication data were collected for each participant on 7 days in fall 1999 and/or spring 2000. Hourly ambient pollution concentrations were obtained from monitoring sites in Atlanta. The association between ambient pollution and HRV was examined using linear mixed-effect models. Ambient pollution had opposing effects on HRV in our COPD and MI participants, resulting in no significant effect of ambient pollution on HRV in the entire population for 1-, 4-, or 24-hr moving averages. For individuals with COPD, interquartile range (IQR) increases in 4-hr ambient PM2.5 (11.65 microg/m3)) and nitrogen dioxide (11.97 ppb) were associated with 8.3% [95% confidence interval (CI), 1.7-15.3%] and 7.7% (95% CI, 0.1-15.9%) increase in the SD of normal R-R intervals (SDNN), respectively. For individuals with MI, IQR increases in 4-hr PM2.5 (8.54 microg/m3) and NO2 (9.25 ppb) were associated with a nonsignificant 2.9% (95% CI, -7.8 to 2.3) and significant 12.1 (95% CI, -19.5 to -4.0) decrease in SDNN. Beta-blocker and bronchodilator intake and baseline forced expiratory volume in 1 sec modified the PM-SDNN association significantly, with effects consistent with those by disease group. Results indicate heterogeneity in the autonomic response to air pollution due to differences in baseline health, with significant associations for ambient NO2 suggesting an important role for traffic-related pollution.

Adrenergic beta-Antagonists↗

Depression and comorbid illness in elderly primary care patients: impact on multiple domains of health status and well-being.

PURPOSE: Our objective was to examine the relative association of depression severity and chronicity, other comorbid psychiatric conditions, and coexisting medical illnesses with multiple domains of health status among primary care patients with clinical depression. METHODS: We collected cross-sectional data as part of a treatment effectiveness trial that was conducted in 8 diverse health care organizations. Patients aged 60 years and older (N = 1,801) who met diagnostic criteria for major depression or dysthymia participated in a baseline survey. A survey instrument included questions on sociodemographic characteristics, depression severity and chronicity, neuroticism, and the presence of 11 common chronic medical illnesses, as well as questions screening for panic disorder and posttraumatic stress disorder. Measures of 4 general health indicators (physical and mental component scales of the SF-12, Sheehan Disability Index, and global quality of life) were included. We conducted separate mixed-effect regression linear models predicting each of the 4 general health indicators. RESULTS: Depression severity was significantly associated with all 4 indicators of general health after controlling for sociodemographic differences, other psychological dysfunction, and the presence of 11 chronic medical conditions. Although study participants had an average of 3.8 chronic medical illnesses, depression severity made larger independent contributions to 3 of the 4 general health indicators (mental functional status, disability, and quality of life) than the medical comorbidities. CONCLUSIONS: Recognition and treatment of depression has the potential to improve functioning and quality of life in spite of the presence of other medical comorbidities.

Aged↗

Short-term effects of different toothpaste formulations on total salivary calcium: A randomized crossover study.

OBJECTIVES: Dental calculus formation can be inhibited by toothpastes containing pyrophosphate, which chelates calcium ions and prevents hydroxyapatite crystal formation. Although pyrophosphate may also influence salivary calcium availability, the short-term effects of commercially available toothpaste formulations on salivary calcium concentrations remain insufficiently characterized. This study investigated and compared the short-term effects of three fluoride toothpastes on salivary calcium concentration. METHODS: A randomized, three-treatment, three-period crossover trial was conducted in 48 healthy volunteers. The participants used three commercially available sodium fluoride toothpastes in randomized order: a formulation containing methyl vinyl ether/maleic acid copolymer, PVM/MA copolymer (Sensodyne), a formulation containing pyrophosphate and zinc (Dentalux), and a formulation containing sodium bicarbonate (Parodontax). Treatment periods were separated by a 2-day washout. Unstimulated saliva was collected at baseline (T0), immediately after brushing (T1), 30 min (T2), and 60 min (T3). Salivary calcium concentrations were quantified using a colorimetric assay. Data were analysed using linear mixed-effects models with toothpaste formulation, measurement time, treatment sequence, and the toothpaste-by-time interaction as fixed effects and participant as a random effect. RESULTS: Significant effects were observed for toothpaste formulation (F(2,103.35)=42.31, P&#x2009;<&#x2009;0.001), measurement time (F(3,141)=39.78, P&#x2009;<&#x2009;0.001), and the toothpaste-by-time interaction (F(6,141)=23.91, P&#x2009;<&#x2009;0.001), whereas treatment sequence had no significant effect (P&#x2009;=&#x2009;0.927). Compared with Dentalux&#xae; and Sensodyne&#xae;, Parodontax&#xae; resulted in significantly lower salivary calcium concentrations (both Bonferroni-adjusted P&#x2009;<&#x2009;0.001), immediately after brushing (T1). The differences decreased after 30 min and were no longer significant after 60 min. No significant differences were observed between Dentalux&#xae; and Sensodyne&#xae; at any time point. CONCLUSIONS: Commercially available fluoride toothpastes produced different short-term effects on the salivary calcium concentration, with the greatest differences occurring immediately after brushing. Because the products differed in terms of multiple formulation ingredients, the findings reflect product-level effects rather than ingredient-specific effects. Further multicentre studies are warranted to confirm these findings and evaluate their clinical relevance.

Humans↗

Comparison of specific gravity and creatinine for normalizing urinary reproductive hormone concentrations.

BACKGROUND: Specific gravity (SG) may perform as well as creatinine (CR) correction for adjusting urinary hormone concentrations, as well as offer some advantages. We compared the two methods and applied them to US and Bangladeshi specimens to evaluate their use in different populations. METHODS: Pearson correlations between serum concentrations and SG, CR, and uncorrected urinary concentrations were compared using paired daily urine and serum specimens from one menstrual cycle from 30 US women. Corrected urinary estrone conjugate and pregnanediol glucuronide concentrations were compared with serum estradiol and progesterone. Urine specimens across one menstrual cycle from 13 Bangladeshi women were used to evaluate the applicability of both methods to a nonindustrialized population. Linear mixed-effects models were used to compare CR and SG values in the Bangladeshi vs US specimens. RESULTS: There was no significant difference between SG-corrected vs serum and CR-corrected vs serum correlations for either assay. Usable CR results were obtained for all US specimens, but 37% of the Bangladeshi specimens were below the CR assay limit of detection. The Bangladeshi sample had significantly lower CR and higher inter- and intrasubject CR variability than the US sample. CONCLUSIONS: SG is a potentially useful alternative to CR correction for normalizing urinary steroid hormone concentrations, particularly in settings where CR values are highly variable or unusually low.

Adult↗

Influences of blood sample processing on low-molecular-weight proteome identified by surface-enhanced laser desorption/ionization mass spectrometry.

BACKGROUND: Profiling approaches in proteomics, such as surface-enhanced laser desorption/ionization (SELDI) mass spectrometry, are used in disease marker discovery. The aim of this study was to investigate the potential influence of selected preanalytical factors on the results obtained. METHODS: Plasma samples anticoagulated with EDTA, citrate, or heparin, and serum samples from healthy volunteers were profiled by SELDI on CM10, immobilized metal affinity capture (IMAC) array with copper, and H50 chip surfaces. Using linear mixed-effects models, we examined the influence of elapsed time between venipuncture and sample separation (immediate to 24 h) and the type of serum tube used (Greiner Vacuette activator, gel serum separator, or plain tubes). We analyzed purified platelets, as well as platelet-poor and platelet-rich plasma samples treated with calcium and/or thrombin to determine the platelet contribution, directly or via the clotting process, to the profiles generated. We then used cluster analysis to identify samples with similar peak profiles. RESULTS: Different plasma types and sera could be distinguished on the basis of cluster analyses of their spectral profiles. Elapsed time between venipuncture and separation of plasma and serum from blood samples altered the profiles obtained, particularly for serum samples and particularly on IMAC chips. The type of serum collection tube also affected the profiles because of differences in clotting time. In vitro manipulation of platelets revealed that specific peaks in IMAC profiles of serum appeared to be derived directly from platelets. Several other peaks, including some of those exhibiting time-dependent changes, arose during the clotting process. CONCLUSION: Preanalytical variables, such as sample handling, can markedly influence results.

Adult↗

Maternal dietary intake in twin pregnancies: does it diminish towards term?

We tested the hypothesis that energy intake among women with twin pregnancies decreases in late gestation, as the uterus enlarges and they become increasingly uncomfortable. We asked women to recall dietary intake for the previous 24 hours, every 2 weeks from around 29 weeks of gestation, using a photographic atlas and other strategies to estimate portion size. Eighty women provided data at around 29, 31, 33 and 35 weeks of gestation. We calculated total energy intake, and energy intake from carbohydrate, fat and protein. Data were log transformed to reduce skewness. Using mixed effects linear regression models, we found minimal evidence that total energy intake changed over this time period, either before or after adjustment for potential confounding factors (95% confidence interval for relative change per week: -1.4%, 0.6%). There was weak evidence of a small decline in carbohydrate intake over time, both before and after controlling for energy intake. We cannot exclude change in energy intake or diet composition before 29 weeks or after 35 weeks of twin gestation.

Diet↗

Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive rats.

In the present study, the cardiovascular toxicity of PM(2.5) was determined in spontaneously hypertensive (SH) rats using the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences of adjacent normal-to-normal intervals (RMSSD) as outcome measurements. Four SH rats implanted with radiotelemetry transmitters were repeatedly exposed to concentrated PM(2.5) in nose-only exposure chambers. Gravimetric analysis revealed the mean post-concentrating mass concentration of particles during the 5 h of exposure was 202 mug/m(3). Using each animal as its own control and linear mixed-effects model, to adjust for circadian nature and individual differences, we found that SDNN decreased by 15% initially then gradually decreased to 60% of the initial value at the end of exposure. Our results indicate that concentrated PM(2.5) may decrease SDNN on SH rats during PM exposure. The study also showed that SDNN is more sensitive to PM induced effects than RMSSD.

Air Pollutants↗

[Determinants of postpartum weight retention according to skin color among women in Rio de Janeiro, Brazil].

OBJECTIVE: To investigate factors associated with postpartum weight retention according to skin color in the city of Rio de Janeiro, Brazil, as part of the effort to help control overweight and obesity. METHODS: We carried out a cohort study with data collection at four points after delivery: 15 days, 2 months, 6 months, and 9 months. The 450 participants (15 to 45 years of age) were recruited from a maternity center and a city health center in Rio de Janeiro. Postpartum weight retention was defined as the dependent variable. The following covariates were investigated: maternal age, marital status, ability to read a letter, smoking, monthly family income, number of children, age at first delivery, a score for physical activity at work, and a score for physical activity during leisure time. The data were analyzed using multivariate linear mixed-effects models for longitudinal data. RESULTS: The factors that remained associated with postpartum weight retention for white women were time after delivery (beta = -0.0061, P = 0.0002), marital status (married/single beta = -0.9279, P = 0.0457), and age at first delivery (beta = -0.1553, P = 0.0364). The factors for brown women were time after delivery (beta = -0.0062, P < 0.0001), marital status (married/single beta = -0.6000, P = 0.0145), and work physical activity score (beta = -0.1068, P = 0.0003). The factors for black women were smoking (beta = -1.4635, P = 0.0535) and score for physical activity during leisure time (beta = -0.2422, P = 0.0145). CONCLUSIONS: The factors associated with postpartum weight retention were different for the three skin-color categories. Nevertheless, the data do not indicate the need for different interventions for the three skin-color groups. That is particularly true because the physical activity scores were among the variables associated with weight retention, and any initiative to control obesity should take physical activity into consideration. On the other hand, given the socioeconomic differences among the three skin-color categories, new studies should be developed to investigate in more detail the pattern of postpartum weight retention according to skin color.

Adolescent↗

Sucrose concentration in blood: a new method for assessment of gastric permeability in horses with gastric ulceration.

A urine sucrose test has recently been reported to be a reliable method of detecting gastric ulcers in horses; however, technical difficulties associated with urine collection have limited the practical value of the test. The objective of this pilot study was to determine whether gastric sucrose permeability, as evaluated by serum sucrose concentration, could be used to detect gastric mucosal injury in horses. Twelve adult horses with naturally acquired gastric ulceration were studied. After a 20-hour nonfeeding period, each horse was dosed with 250 g of sucrose via nasogastric intubation. Blood samples were collected at 0, 15, 30, 45, 60, and 90 minutes, and horses underwent gastroscopy 4 hours later. The severity of gastric ulceration in each horse was defined by means of a 4-point ulcer-scoring system, and the relationship with serum sucrose concentration was analyzed by means of a linear mixed-effects model. Serum sucrose concentration was measured by liquid chromatography operating in tandem with electrospray mass spectrometry. After nasogastric administration of table sugar, horses with moderate to severe gastric ulceration had significant increase in serum sucrose concentration at 30, 45, 60, and 90 minutes, relative to earlier times (P < .05). Peak sucrose concentration was observed at 45 minutes, and was correlated with ulcer severity (Spearman's rank correlation coefficient = 0.898, P < .05). These data indicate that determination of sucrose concentration in equine serum may be a useful test for identifying horses with endoscopically visible gastric ulceration and has potential use as a noninvasive method for screening and monitoring horses engaged in racing training and other performance-related disciplines.

Animals↗

Validation of oligonucleotide microarray data using microfluidic low-density arrays: a new statistical method to normalize real-time RT-PCR data.

Profiling studies using microarrays to measure messenger RNA (mRNA) expression frequently identify long lists of differentially expressed genes. Differential expression is often validated using real-time reverse transcription PCR (RT-PCR) assays. In conventional real-time RT-PCR assays, expression is normalized to a control, or housekeeping gene. However, no single housekeeping gene can be used for all studies. We used TaqMan Low-Density Arrays, a medium-throughput method for real-time RT-PCR using microfluidics to simultaneously assay the expression of 96 genes in nine samples of chronic lymphocytic leukemia (CLL). We developed a novel statistical method, based on linear mixed-effects models, to analyze the data. This method automatically identifies the genes whose expression does not vary significantly over the samples, allowing them to be used to normalize the remaining genes. We compared the normalized real-time RT-PCR values with results obtained from Affymetrix Hu133A GeneChip oligonucleotide microarrays. We found that real-time RT-PCR using TaqMan Low-Density Arrays yielded reproducible measurements over seven orders of magnitude. Our model identified numerous genes that were expressed at nearly constant levels, including the housekeeping genes PGK1, GAPD, GUSB, TFRC, and 18S rRNA. After normalizing to the geometric mean of the unvarying genes, the correlation between real-time RT-PCR and microarrays was high for genes that were moderately expressed and varied across samples.

Algorithms↗

A Web-Based, Pedometer-Mediated Intervention Increases Amount and Intensity of Physical Activity in COPD: A Randomized Controlled Trial.

INTRODUCTION: Ground-based walking training is an aerobic exercise used in supervised pulmonary rehabilitation (PR). Physical activity (PA) interventions typically promote step counts, but it is unclear whether community-based walking intensity can be targeted as aerobic exercise. This randomized controlled trial evaluated a web-based, pedometer-mediated PA intervention designed to increase walking amount and intensity. MATERIAL AND METHODS: Participants with COPD who had never enrolled in PR were randomized 1:1 to control or intervention. The intervention included individualized step-count goals, iterative feedback, educational content, and an online community forum. The Fitbit Inspire Heart Rate objectively monitored daily step counts. Participants were instructed to achieve step-count goals with as many steps of moderate-intensity as possible guided by a modified Borg rating of 4-5 for dyspnea. The primary outcome was change in PA measured as average daily step count at 12&#xa0;weeks. Aerobic intensity was assessed by the Rapid Assessment of PA Questionnaire which uses self-reported moderate or vigorous PA to categorize responders as underactive or active. Linear mixed-effects models (PROC MIXED, SAS v9.4), adjusting for group, time, group*time, FEV1%predicted, enrollment season, and study modality (eg, in-person, virtual, hybrid), assessed between-group change. RESULTS: Participants (57 intervention, 52 control) were 97% male, mean age 73&#xb1;7 years, and baseline FEV1 73&#xb1;23% predicted. Baseline daily steps were 4,222&#xb1;1,929 (intervention) and 4,851&#xb1;2,637 (control). Intervention participants increased average daily steps by 1,410 steps/day more than controls (p=0.005). The intervention group showed greater transitions from underactive to active intensity (between-group: p=0.025), with 20 (41%) moving to active status (within-group: p=0.001). CONCLUSION: Technology-mediated community-based walking increased PA amount and intensity. These findings support further evaluation of this intervention as a potential option for ground-based walking training with objective measurement of exercise intensity.

Humans↗

High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.

OBJECTIVES: To describe plasma concentrations of indinavir alone or combined with ritonavir, and of nelfinavir and its active metabolite M8, and to measure their variabilities in HIV-infected patients treated with a stable antiretroviral regimen and experiencing a sustained virological response for at least 12 months. PATIENTS AND METHODS: In this prospective trial, blood samples were drawn during a 6-hour time interval between two doses at enrolment to assess protease inhibitor (PI) pharmacokinetic parameters, and 4 months later to assess plasma trough and peak concentrations. Safety and adherence assessments and laboratory data were collected during an 8-month period. PI pharmacokinetic characteristics were analysed using a non-compartmental approach. Inter- and intrapatient variabilities were estimated using a linear mixed-effect model. The impact of different covariates on plasma trough concentrations was investigated. Eighty-eight patients were analysed: 42 treated with indinavir and 46 with nelfinavir. RESULTS: The interquartile range (IQR) of the plasma trough concentration corrected for the sampling time (Ccalc) was 116-374 microg/L for indinavir alone and 163-508 microg/L for indinavir/ritonavir. Ritonavir significantly increased indinavir elimination half-life and plasma exposure. For nelfinavir, the IQR of Ccalc was 896-2059 microg/L for three-times-daily administration and 998-2124 microg/L for twice-daily administration. Variabilities were high for both PIs. Intrapatient variability for indinavir alone (and indinavir + ritonavir) was 76% (107%) and interpatient variability was 58% (10%) in adherent patients. Intrapatient variability for nelfinavir three times daily (and twice daily) was 41% (74%) and interpatient variability was 62% (50%). Intrapatient variability was lowered in patients with a high adherence level. CONCLUSION: Although performed in a homogeneous population, this study documented a high interpatient but also intrapatient variability of indinavir and nelfinavir pharmacokinetics, which should be taken into account when interpreting therapeutic drug monitoring. Once patients have reached a sustained virological response, plasma PI monitoring may have a limited impact.

Adult↗

Patients' preferences for healthcare system reforms in Hungary: a conjoint analysis.

OBJECTIVES: To illustrate how conjoint analysis can be used to identify patient preferences for healthcare policies, and to measure preferences for healthcare reforms in Hungary. DATA SOURCE/STUDY SETTING: Data was collected via a mail-based survey and a direct survey administered in a rheumatology out-patient centre in Flór Ferenc County Hospital, Budapest, Hungary (n = 86). STUDY DESIGN: We designed and administered a conjoint analysis to the study population. Attributes and attribute levels were developed on the basis of key informant interviews and a literature review. Additional demographic, occupation and healthcare utilisation data were also collected using surveys. A mixed effects linear probability model was estimated holding respondent characteristics constant and correcting for clustering. DATA COLLECTION: Conjoint analysis questionnaires were administered by a physician to 50 consecutive rheumatology patients in a clinic and an additional 36 were mailed by post. PRINCIPAL FINDINGS: The response rate for the physician-administered survey was 98% (but 18% of these were excluded for inconsistent preferences) and 53% for the mail survey, leaving a final sample of 59. Regression results (R2 = 56.8%) indicated that patients preferred a health system that was not cost constrained (p = 0.003), was based on solidarity (p < 0.001) and where patients were empowered (p = 0.024). Further, they would choose a system with no choice of provider to avoid co-payments (p = 0.005). CONCLUSIONS: This study demonstrates that patients have clear preferences for healthcare system policy. In order to develop evidence-based healthcare policy and to empower patients in the healthcare system, methods such as conjoint analysis offer a simple yet theoretically grounded basis for policy making.

Adult↗

Effect of peroxisome proliferator-activated receptor gamma agonist treatment on subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes.

OBJECTIVE: To determine the effect of thiazolidinedione treatment on subclinical atherosclerosis progression in insulin-requiring patients with clinical characteristics suggesting type 2 diabetes. RESEARCH DESIGN AND METHODS: Eligible participants (n = 299) were randomized within strata of baseline common carotid artery (CCA) intima-media thickness (IMT) (<0.8 mm, >or=0.8 mm) to 400 mg troglitazone daily or placebo for 2 years. A general linear mixed-effects model was used to compare the rate of change in CCA-IMT between treatment groups. RESULTS: Overall, average rates of CCA-IMT change were not significantly different between troglitazone- and placebo-treated subjects (0.0030 +/- 0.021 vs. 0.0066 +/- 0.021 mm/year; P = 0.17). In the stratum of subjects with CCA-IMT >or=0.8 mm, troglitazone significantly reduced the progression of CCA-IMT relative to placebo (0.0013 +/- 0.022 vs. 0.0084 +/- 0.023 mm/year; P = 0.03). Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01). Whereas blood pressure significantly differed between treatment groups in the >or=0.8-mm stratum, there was no difference between treatment groups in the <0.8-mm stratum. CONCLUSIONS: Insulin sensitization and reduction in blood pressure may be contributory mechanisms by which troglitazone reduced subclinical atherosclerosis progression in this cohort of well-controlled insulin-dependent patients with clinical characteristics suggesting type 2 diabetes.

Adult↗

Genome-wide association study of estimated glomerular filtration rate using repeated measurements in the Taiwan Biobank.

BACKGROUND: Chronic kidney disease (CKD) is a major global public health issue, with genetic factors playing a significant role in kidney function. Although genome-wide association studies (GWAS) have identified numerous loci associated with estimated glomerular filtration rate (eGFR), most studies relied on a single time-point measurement, which limits the capacity to account for within-individual measurement variability. METHODS: We performed a repeated-measurement GWAS in the prospective Taiwan Biobank (Taiwanese ancestry; n = 25,004) using two repeated creatinine-based eGFR measurements. Repeated eGFR values were analyzed using a linear mixed-effects model with a subject-specific random intercept and time-varying covariates, providing a more precise estimate of eGFR level. Identified loci underwent functional annotation (expression quantitative trait locus, deleteriousness prediction, and epigenetic markers) and were compared with results from a single-measurement GWAS. RESULTS: Six loci associated with eGFR were identified, including four previously reported regions (1q22, 4q21.1, 11p14.1, and 17q21.2) and two additional loci (6p21.32 and 15q24.2). Functional annotation implicated several candidate genes-such as MUC1/EFNA1, SHROOM3, HLA-DQB1, MPPED2, NRG4, and PGAP3/FBXL20-in the regulation of kidney function. CONCLUSION: Incorporating repeated eGFR measurements into GWAS may improve phenotypic precision for identifying genetic associations with kidney function. This study identified eGFR-associated loci and biologically plausible candidate genes in a Taiwanese population, which require further replication and functional validation.

Chronic kidney disease↗

Estimation of energy balance at the individual and herd level using blood and milk traits in high-yielding dairy cows.

This study aimed to estimate individual and herd-level energy balance (EB) using blood and milk traits in 90 multiparous high-yielding Holstein cows, held on a research farm, from wk 1 to 10 postpartum (p.p.) and to investigate the precision of prediction with successively decreased data sets simulating smaller herd sizes and with pooled samples. Dry matter intake, milk yield, and BW were measured daily from parturition through wk 10 p.p. Milk composition was determined 4 times per week, and milk acetone was measured weekly. Blood samples for the determination of metabolites, hormones, electrolytes, and enzyme activities were taken weekly from wk 1 to 10 p.p. between 0730 and 0900. Body condition scores and ultrasonic measurements of backfat thickness and fat depth in the pelvic area were evaluated in wk 1, 4, and 8 p.p. Concentrations of glucose, cholesterol, urea, insulin, insulin-like growth factor-1, triiodothyronine, and thyroxine (T4) in blood plasma and of lactose and urea in milk were positively correlated with EB, whereas concentrations of nonesterified fatty acids (NEFA), creatinine, albumin, beta-hydroxybutyrate, and growth hormone and enzyme activities in blood, and concentrations of fat, protein, fat:lactose ratio, and acetone in milk were negatively correlated with EB. Leptin concentration was not correlated to EB over the first 10 wk p.p. To estimate EB linear mixed-effects, models were developed by backward selection procedures. The most informative traits for estimation of EB were the fat:lactose ratio in milk and NEFA and T4 concentrations in blood. The precision of estimation of EB in individual cows was low. Using blood in addition to milk traits did not result in higher precision of estimation of herd-level EB, and decreasing sample sizes considerably lowered the precision of EB prediction. Estimation of overall mean herd-level EB over the first 10 wk p.p. using pooled samples was precise even with small sample sizes, but does not consider the level of EB in particular weeks. In conclusion, estimation of herd-level EB at individual weeks using milk traits only has practical implication with herd sizes of > or = 100 cows if calving is highly seasonal and of or = 400 cows if calving is uniformly distributed. Using blood in addition to milk traits does not improve precision of estimation of herd-level EB, regardless of sample size.

3-Hydroxybutyric Acid↗

Milk cortisol concentration in automatic milking systems compared with auto-tandem milking parlors.

Milk cortisol concentration was determined under routine management conditions on 4 farms with an auto-tandem milking parlor and 8 farms with 1 of 2 automatic milking systems (AMS). One of the AMS was a partially forced (AMSp) system, and the other was a free cow traffic (AMSf) system. Milk samples were collected for all the cows on a given farm (20 to 54 cows) for at least 1 d. Behavioral observations were made during the milking process for a subset of 16 to 20 cows per farm. Milk cortisol concentration was evaluated by milking system, time of day, behavior during milking, daily milk yield, and somatic cell count using linear mixed-effects models. Milk cortisol did not differ between systems (AMSp: 1.15 +/- 0.07; AMSf: 1.02 +/- 0.12; auto-tandem parlor: 1.01 +/- 0.16 nmol/L). Cortisol concentrations were lower in evening than in morning milkings (1.01 +/- 0.12 vs. 1.24 +/- 0.13 nmol/L). The daily periodicity of cortisol concentration was characterized by an early morning peak and a late afternoon elevation in AMSp. A bimodal pattern was not evident in AMSf. Finally, milk cortisol decreased by a factor of 0.915 in milking parlors, by 0.998 in AMSp, and increased by a factor of 1.161 in AMSf for each unit of ln(somatic cell count/1,000). We conclude that milking cows in milking parlors or AMS does not result in relevant stress differences as measured by milk cortisol concentrations. The biological relevance of the difference regarding the daily periodicity of milk cortisol concentrations observed between the AMSp and AMSf needs further investigation.

Animals↗

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 &#xb1; 9 years, 41% were women, mean eGFR was 48.2 &#xb1; 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗