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Subclinical leaflet thrombosis (SLT) is a potentially serious complication of aortic valve replacement with a bioprosthetic valve in which blood clots form on the replacement valve. SLT is associated with increased risk of transient ischemic attacks and strokes and can progress to clinical leaflet thrombosis. SLT following aortic valve replacement also may be related to subsequent structural valve deterioration, which can impair the durability of the valve replacement. Because of the difficulty in clinical imaging of SLT, models are needed to determine the mechanisms of SLT and could eventually predict which patients will develop SLT. To this end, we develop methods to simulate leaflet thrombosis that combine fluid-structure interaction and a simplified thrombosis model that allows for deposition along the moving leaflets. Additionally, this model can be adapted to model deposition or absorption along other moving boundaries. We present convergence results and quantify the model's ability to realize changes in valve opening and pressures. These new approaches are an important advancement in our tools for modeling thrombosis because they incorporate both adhesion to the surface of the moving leaflets and feedback to the fluid-structure interaction.

This study aimed to investigate seasonal heat acclimatization in active adolescents following summer. Fifteen (5 females) active adolescents (14.6 ± 1.0 y) completed a 45-min heat response test (HRT) walking at 60% $\dot {\rm V}$ V ˙ O2peak in 40°C and 30% relative humidity before and after summer (i.e. November 2022 and March 2023). During the HRT, gastro-intestinal temperature (Tgi), skin temperature (Tsk), heart rate, local sweat rate (LSR) and whole-body sweat loss (WBSL) were recorded. Carbon monoxide rebreathing and dual-energy X-ray absorptiometry scans determined resting hematological measures and body composition. Participants completed physical activity (PA) diaries and wore an accelerometer for two one-week periods (pre- and post-summer). Daytime wet-bulb globe temperature (WBGT) was calculated for each summer day. Data are presented as posterior mean and 90% credible intervals. Participants reported 7 ± 4 h·wk−1 of outdoor PA, and daytime WBGT was 21.2 ± 4.6°C. Following summer, resting Tgi and heart rate were reduced by 0.2°C [−0.3, −0.1; probability of direction = 99%] and 7 beats·min−1 [−10, −3; 100%], respectively. During the HRT, there was an earlier onset of sweating (−0.2°C [−0.3, −0.0; 98%]), an attenuated rise of Tgi (0.2°C [−0.5, 0.0; 92%]) and mean Tsk changed by −0.2°C [−0.5, 0.1; 86%]. There was minimal evidence for heat adaptations in LSR or WBSL, hematological parameters or perceptual measures. This is the first study to demonstrate seasonal heat adaptations in active adolescents. Reductions in resting Tgi and exercising Tsk and a lower Tgi at the onset of sweating were associated with a smaller rise in Tgi during the HRT following summer. [ABSTRACT FROM AUTHOR]

Sophisticated mathematical and computational tools have become widespread and important in veterinary pharmacology. Although the theoretical basis and practical applications of these have been widely explored in the literature, statistical inference in the context of these models has received less attention. Optimization methods, often with frequentist statistical inference, have been predominant. In contrast, Bayesian statistics have not been widely applied, but offer both practical utility and arguably greater interpretability. Veterinary pharmacology applications are generally well supported by relevant prior information, from either existing substantive knowledge, or an understanding of study and model design. This facilitates practical implementation of Bayesian analyses that can take advantage of this knowledge. This essay will explore the specification of Bayesian models relevant to veterinary pharmacology, including demonstration of prior selection, and illustrate the capability of these models to generate practically useful statistics, including uncertainty statements, that are difficult or impossible to obtain otherwise. Case studies using simulated data will describe applications in clinical trials, pharmacodynamics, and pharmacokinetics, all including multilevel modeling. This content may serve as a suitable starting point for researchers in veterinary pharmacology and related disciplines considering Bayesian estimation for their applied work. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the influence of biological sex, independent of differences in aerobic fitness and body fatness, on the change in gastrointestinal temperature (ΔTgi) and whole body sweat rate (WBSR) of children exercising under uncompensable heat stress. Seventeen boys (means ± SD; 13.7 ± 1.3 yr) and 18 girls (13.7 ± 1.4 yr) walked for 45 min at a fixed rate of metabolic heat production per kg body mass (8 W·kg−1) in 40°C and 30% relative humidity. Sex and peak oxygen consumption (V̇ o 2peak) were entered into a Bayesian hierarchical general additive model (HGAM) for Tgi. Sex, V̇ o 2peak, and the evaporative requirement for heat balance (Ereq) were entered into a Bayesian hierarchical linear regression for WBSR. For 26 (12 M and 14 F) of the 35 children with measured body composition, body fat percentage was entered in a separate HGAM and hierarchical linear regression for Tgi and WBSR, respectively. Conditional on sex-specific mean V̇ o 2peak, ΔTgi was 1.00°C [90% credible intervals (Crl): 0.84, 1.16] for boys and 1.17°C [1.01, 1.33] for girls, with a difference of 0.17°C [−0.39, 0.06]. When sex differences in V̇ o 2peak were accounted for, the difference in ΔTgi between boys and girls was 0.01°C [−0.25, 0.22]. The difference in WBSR between boys and girls was 0.03 L·h−1 [−0.02, 0.07], when isolated from differences in Ereq. The difference in ΔTgi between boys and girls was −0.10°C [−0.38, 0.17] when sex differences in body fat (%) were accounted for. Biological sex did not independently influence the ΔTgi and WBSR of children exercising under uncompensable heat stress. NEW & NOTEWORTHY: Limited studies have investigated the thermoregulatory responses of boys and girls exercising under uncompensable heat stress. Boys and girls often differ in physiological characteristics other than biological sex, such as aerobic fitness and body fat percentage, which may confound interpretations. We investigated the influence of biological sex on exercise thermoregulation in children, independent of differences in aerobic fitness and body fatness. [ABSTRACT FROM AUTHOR]

OBJECTIVES To determine, following oral administration of famciclovir, pharmacokinetic (PK) parameters for 2 of its metabolites (penciclovir and BRL42359) in plasma and tears of healthy cats so that famciclovir dosage recommendations for the treatment of herpetic disease can be optimized. ANIMALS 7 male domestic shorthair cats. PROCEDURES In a crossover study, each of 3 doses of famciclovir (30, 40, or 90 mg/kg) was administered every 8 or 12 hours for 3 days. Six cats were randomly assigned to each dosage regimen. Plasma and tear samples were obtained at predetermined times after famciclovir administration. Pharmacokinetic parameters were determined for BRL42359 and penciclovir by compartmental and noncompartmental methods. Pharmacokinetic-pharmacodynamic (PK-PD) indices were determined for penciclovir and compared among all dosage regimens. RESULTS Compared with penciclovir concentrations, BRL42359 concentrations were 5- to 11-fold greater in plasma and 4- to 7-fold greater in tears. Pharmacokinetic parameters and PK-PD indices for the 90 mg/kg regimens were superior to those for the 30 and 40 mg/kg regimens, regardless of dosing frequency. Penciclovir concentrations in tears ranged from 18% to 25% of those in plasma. Administration of 30 or 40 mg/kg every 8 hours achieved penciclovir concentrations likely to be therapeutic in plasma but not in tears. Penciclovir concentrations likely to be therapeutic in tears were achieved only with the two 90 mg/kg regimens. CONCLUSIONS AND CLINICAL RELEVANCE In cats, famciclovir absorption is variable and its metabolism saturable. Conversion of BRL42359 to penciclovir is rate limiting. The recommended dosage of famciclovir is 90 mg/kg every 12 hours for cats infected with feline herpesvirus.

Objective: To determine the influence of health-related fitness on cardiometabolic risk factors in college students. Participants: 75 traditional students (33 men and 42 women, 21.8±1.8 years old) at a university in southeastern U.S. Methods: Height, weight, waist circumference, body composition, blood pressure, lipids, glucose, insulin, c-reactive protein, and glucose tolerance were measured. Indices of insulin sensitivity were calculated. Aerobic and muscular fitness were measured. Regression and correlation analyses, and comparisons of cardiometabolic markers in low- vs high-fit participants were performed. Results: Men and women with low muscular fitness exhibited higher fasting insulin, and poorer insulin sensitivity index scores than those with high muscular fitness. In addition, women with high body fat percentage exhibited higher fasting and 2-hour insulin levels and lower insulin sensitivity index scores than those with low body fat percentages. Conclusions: College students possessing low levels of health-related physical fitness exhibited less favorable cardiometabolic risk profiles.

Abstract Background Cotton fiber development undergoes rapid and dynamic changes in a single cell type, from fiber initiation, elongation, primary and secondary wall biosynthesis, to fiber maturation. Previous studies showed that cotton genes encoding putative MYB transcription factors and phytohormone responsive factors were induced during early stages of ovule and fiber development. Many of these factors are targets of microRNAs (miRNAs) that mediate target gene regulation by mRNA degradation or translational repression. Results Here we sequenced and analyzed over 4 million small RNAs derived from fiber and non-fiber tissues in cotton. The 24-nucleotide small interfering RNAs (siRNAs) were more abundant and highly enriched in ovules and fiber-bearing ovules relative to leaves. A total of 31 miRNA families, including 27 conserved, 4 novel miRNA families and a candidate-novel miRNA, were identified in at least one of the cotton tissues examined. Among 32 miRNA precursors representing 19 unique miRNA families identified, 7 were previously reported, and 25 new miRNA precursors were found in this study. Sequencing, miRNA microarray, and small RNA blot analyses showed a trend of repression of miRNAs, including novel miRNAs, during ovule and fiber development, which correlated with upregulation of several target genes tested. Moreover, 223 targets of cotton miRNAs were predicted from the expressed sequence tags derived from cotton tissues, including ovules and fibers. The cotton miRNAs examined triggered cleavage in the predicted sites of the putative cotton targets in ovules and fibers. Conclusions Enrichment of siRNAs in ovules and fibers suggests active small RNA metabolism and chromatin modifications during fiber development, whereas general repression of miRNAs in fibers correlates with upregulation of a dozen validated miRNA targets encoding transcription and phytohormone response factors, including the genes found to be highly expressed in cotton fibers. Rapid and dynamic changes in siRNAs and miRNAs may contribute to ovule and fiber development in allotetraploid cotton.

Hypertension becomes more prevalent with increasing age. Telomere length (TL) has been proposed as a candidate biomarker and can be accessibly extracted from saliva. However, clarity is needed to evaluate the suitability of using TL as a predictor in such instances. This study investigated salivary TL in a cohort of older adults from the 2008 Health and Retirement Study (n = 3329; F: 58%, mean age: 69.4, SD: 10.3 years) to examine any associations with blood pressure (BP). A Bayesian robust regression model was fit using weakly informative priors to predict the effects of TL with age, sex, systolic BP (SBP), diastolic BP (DBP), and treatment status. There were small effects of treatment (β: −0.07, 95% CrI [−0.33, 0.19], pd: 71.91%) and sex (β: −0.10, 95% CrI [−0.27, 0.07], pd: >86.78%). Population effects showed a reduction of 0.01 log2 units in TL with each year of advancing age (95% CrI [−0.01, −0.00]). Conditional posterior predictions suggest that females, and treated individuals, experience greater change in TL with increasing age. Bayes R2 was ~2%. TL declines with increasing age, differs between sexes, and appears to be influenced by antihypertensive drugs. Overall, all effects were weak. The data do not currently support the suitability of salivary TL as a biomarker to predict or understand any age‐related changes in BP. [ABSTRACT FROM AUTHOR]

Radioactive iodine (131I) has previously been reported to prolong survival in dogs with thyroid carcinoma. This study aimed to describe tumour response and progression‐free interval (PFI) in dogs with thyroid carcinomas treated with 131I. Secondary aims were to describe overall survival time (OST) and prognostic factors. A bi‐institutional retrospective review of records identified 66 dogs with thyroid carcinoma treated with 131I from January 2010 to April 2020. Response was described using RECIST or a subjective response assessment where specific tumour measurements were not available. Forty‐eight dogs (72.7%) were treatment naïve and 18 dogs (27.3%) had received prior therapy at the time of 131I treatment. Objective responses were available for 34 dogs and subjective responses for 58 dogs. The overall response rate was 35.3% (four complete and eight partial responses). Improvement of clinical signs was seen in 76.2% of dogs (32/42). Kaplan–Meier‐estimated median PFI (95% confidence interval [CI]) was 301 (217–578) days and OST (95% CI) was 564 (421–865) days. Prior therapy was associated with a lower hazard for progression (hazard ratio [HR] 0.260 95% CI 0.123–0.548, p =.0004). Treatment of thyroid carcinoma using 131I can effectively alleviate clinical signs and reduce disease burden in a proportion of dogs. [ABSTRACT FROM AUTHOR]

Abstract Background Microarrays offer a powerful tool for diverse applications plant biology and crop improvement. Recently, two comprehensive assemblies of cotton ESTs were constructed based on three Gossypium species. Using these assemblies as templates, we describe the design and creation and of a publicly available oligonucleotide array for cotton, useful for all four of the cultivated species. Results Synthetic oligonucleotide probes were generated from exemplar sequences of a global assembly of 211,397 cotton ESTs derived from >50 different cDNA libraries representing many different tissue types and tissue treatments. A total of 22,787 oligonucleotide probes are included on the arrays, optimized to target the diversity of the transcriptome and previously studied cotton genes, transcription factors, and genes with homology to Arabidopsis. A small portion of the oligonucleotides target unidentified protein coding sequences, thereby providing an element of gene discovery. Because many oligonucleotides were based on ESTs from fiber-specific cDNA libraries, the microarray has direct application for analysis of the fiber transcriptome. To illustrate the utility of the microarray, we hybridized labeled bud and leaf cDNAs from G. hirsutum and demonstrate technical consistency of results. Conclusion The cotton oligonucleotide microarray provides a reproducible platform for transcription profiling in cotton, and is made publicly available through http://cottonevolution.info.

To determine the bioavailability and pharmacokinetic properties of the serotonin 5‐HT1A receptor agonist R‐8‐OH‐DPAT in goats, and 0.1 mg kg−1 R‐8‐OH‐DPAT hydrobromide was administered intramuscularly (i.m.) and intravenously (i.v.) to six goats in a two‐phase cross‐over design experiment. Venous blood samples were collected from the jugular vein 2, 5, 10, 15, 20, 30, 40 and 60 min following treatment and analysed by liquid chromatography tandem mass spectrometry. Bioavailability and pharmacokinetic parameters were determined by a one‐compartment analysis. Mean bioavailability of R‐8‐OH‐DPAT when injected i.m. was 66%. The mean volume of distribution in the central compartment was 1.47 L kg−1. The mean plasma body clearance was 0.056 L kg−1 min−1. All goats injected i.v. and two of six goats injected i.m. showed signs of serotonin toxicity. In conclusion, R‐8‐OH‐DPAT is well absorbed following i.m. injection and the observed pharmacokinetics suggest that administration via dart is feasible. Administration of R‐8‐OH‐DPAT hydrobromide, at a dosage of 0.1 mg kg−1, resulted in the observation of clinical signs of serotonin toxicity in the goats. It is suggested that dosages for the clinical use of the compound should be lower in order to achieve the desired clinical effect without causing serotonin toxicity. [ABSTRACT FROM AUTHOR]