Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth

A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene expression levels, uterine weights, and histologic parameters were analyzed 1, 2, 4, 8, 24, 48, and 72 hr after exposure to the reference physiologic estrogen 17β-estradiol (E(2)). A multistep analysis method, involving unsupervised hierarchical clustering followed by supervised gene ontology–driven clustering, was used to define the transcriptional program associated with E(2)-induced uterine growth and to identify groups of genes that may drive specific histologic changes in the uterus. This revealed that uterine growth and maturation are preceded and accompanied by a complex, multistage molecular program. The program begins with the induction of genes involved in transcriptional regulation and signal transduction and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation, and epithelial cell differentiation. Furthermore, we have identified genes with common molecular functions that may drive fluid uptake, coordinated cell division, and remodeling of luminal epithelial cells. These data define the mechanism by which an estrogen induces organ growth and tissue maturation, and demonstrate that comparison of temporal changes in gene expression and conventional toxicology end points can facilitate the phenotypic anchoring of toxicogenomic data

Systematic Review of the Relationships Between Objectively Measured Physical Activity and Health Indicators in School-Aged Children and Youth

Moderate-to-vigorous physical activity (MVPA) is essential for disease prevention and health promotion. Emerging evidence suggests other intensities of physical activity (PA), including light-intensity activity (LPA), may also be important, but there has been no rigorous evaluation of the evidence. The purpose of this systematic review was to examine the relationships between objectively measured PA (total and all intensities) and health indicators in school-aged children and youth. Online databases were searched for peer-reviewed studies that met the a priori inclusion criteria: population (apparently healthy, aged 5–17 years), intervention/exposure/comparator (volumes, durations, frequencies, intensities, and patterns of objectively measured PA), and outcome (body composition, cardiometabolic biomarkers, physical fitness, behavioural conduct/pro-social behaviour, cognition/academic achievement, quality of life/well-being, harms, bone health, motor skill development, psychological distress, self-esteem). Heterogeneity among studies precluded meta-analyses; narrative synthesis was conducted. A total of 162 studies were included (204 171 participants from 31 countries). Overall, total PA was favourably associated with physical, psychological/social, and cognitive health indicators. Relationships were more consistent and robust for higher (e.g., MVPA) versus lower (e.g., LPA) intensity PA. All patterns of activity (sporadic, bouts, continuous) provided benefit. LPA was favourably associated with cardiometabolic biomarkers; data were scarce for other outcomes. These findings continue to support the importance of at least 60 min/day of MVPA for disease prevention and health promotion in children and youth, but also highlight the potential benefits of LPA and total PA. All intensities of PA should be considered in future work aimed at better elucidating the health benefits of PA in children and youth

Reaction Time and Mortality from the Major Causes of Death:The NHANES-III Study

Studies examining the relation of information processing speed, as measured by reaction time, with mortality are scarce. We explored these associations in a representative sample of the US population

Effect of weekly physical activity frequency on weight loss in healthy overweight and obese women attending a weight loss program: a randomized controlled trial

ABSTRACT Background: The effect of intensity and duration of physical activity (PA) on weight loss has been well described. However, the effect of the frequency of weekly PA on weight loss is still unknown. Objective: The purpose of this study was to evaluate the effect of the frequency of weekly PA sessions while maintaining the same total activity time on weight loss during a 24-wk weight loss program. Design: Overweight and obese women [n = 75; body mass index(BMI; in kg/m2): 27–37; age: 18–40 y] who had a normally sedentary lifestyle were randomly allocated to 1 of 2 intervention groups: a high-frequency physical activity (HF) or a low-frequency physical activity (LF) group. The HF group included 50 min/d PA, 6 d/wk (300 min/wk). The LF group included 100 min/d PA, 3 d/wk (300 min/wk). Both groups were advised to follow the same dietary weight loss program. Results: Both groups showed a significant decrease in anthropometric measurements and significant improvements in cardiometabolic disease risk characteristics over the 24 wk of the study. Compared with the HF group, the LF group had a greater decrease in weight (mean 6 SD; LF: 9.58 6 3.77 kg; HF: 7.78 6 2.68 kg; P = 0.028), BMI (LF: 3.62 6 1.56; HF: 2.97 6 1.02; P = 0.029) and waist circumference (LF: 9.36 6 4.02 cm; HF: 7.86 6 2.41 cm; P = 0.031). However, there were no significant differences in carbohydrate metabolism characteristics or lipid profile after the 24 wk of intervention. Conclusion: Weekly PA undertaken over fewer sessions of longer duration during the week could be more effective for weight loss than when undertaken as more frequent shorter sessions in overweight and obese women on a weight loss program. This may be helpful for those who are neither willing nor able to schedule time for PA almost every day to achieve weight loss. This trial was registered at www.irct.ir as IRCT201402157754N4

The CardioMetabolic Health Alliance Working Toward a New Care Model for the Metabolic Syndrome

AbstractThe Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future

Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors

Background: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. Methods: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. Results: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk−1, p = .024, 382.2 MET-min∙wk−1, p = .010, and 264.1 MET-min∙wk−1, p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, −1.6 kg, p = .040, and −.6 kg/m2, p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p= .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p=.007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, −.38 mmol∙L−1, p=.001; and −.3 mmol∙L−1, p=.023, respectively). Conclusions: We found that home-based PA resulted in significant albeit small to moderate improvements in selfreported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care

Clustering of Unhealthy Behaviors in the Aerobics Center Longitudinal Study

Background Clustering of unhealthy behaviors has been reported in previous studies; however the link with all-cause mortality and differences between those with and without chronic disease requires further investigation. Objectives To observe the clustering effects of unhealthy diet, fitness, smoking, and excessive alcohol consumption in adults with and without chronic disease and to assess all-cause mortality risk according to the clustering of unhealthy behaviors. Methods Participants were 13,621 adults (aged 20–84) from the Aerobics Center Longitudinal Study. Four health behaviors were observed (diet, fitness, smoking, and drinking). Baseline characteristics of the study population and bivariate relations between pairs of the health behaviors were evaluated separately for those with and without chronic disease using cross-tabulation and a chi-square test. The odds of partaking in unhealthy behaviors were also calculated. Latent class analysis (LCA) was used to assess clustering. Cox regression was used to assess the relationship between the behaviors and mortality. Results The four health behaviors were related to each other. LCA results suggested that two classes existed. Participants in class 1 had a higher probability of partaking in each of the four unhealthy behaviors than participants in class 2. No differences in health behavior clustering were found between participants with and without chronic disease. Mortality risk increased relative to the number of unhealthy behaviors participants engaged in. Conclusion Unhealthy behaviors cluster together irrespective of chronic disease status. Such findings suggest that multi-behavioral intervention strategies can be similar in those with and without chronic disease

Maximum residue levels:Fact or fiction?

Maximum residue levels (MRLs) are trading standards that represent the maximum residue that could be found if a crop protection product (CPP) is applied according to critical good agricultural practice (cGAP). Foodstuffs are monitored for MRL compliance and exceedence can have economic, social and political consequences. There is a trade-off when calculating MRLs, as low MRLs prevent misuse of CPPs and high MRLs prevent an 'unlucky' fanner exceeding the MRL by chance. Chance exceedence has not been previously investigated despite the high probability of exceedence due to small data sets and calculation method. In this study, MRL calculation methods were investigated and policy for using these methods to control chance exceedence was defined. The shape and parameters of the residue distribution, LOQ and number of trials all affected the accuracy and precision of the estimated MRL. The two European methods were least accurate and precise at small numbers of trials and high CVs, with up to four different MRLs possible. Eight to 16 trials gave the best estimate of the MRL, but exceedence by chance could occur in up to 45% of samples. Policy was defined for using existing methods, and involved calculation of the MRL by both methods and taking the highest

Influences on Land Valuation Formulation:Research Briefing

What were we trying to find out?Land prices in Scotland took at dramatic upward turn around 2019-21. This was partly due to the interest in natural capital markets, as the Scottish Government introduced ambitious plans for reaching Net Zero and significant financial incentives to pursue Nature Based Solutions to carbon sequestration.We were interested to find out whether the means in which land values are determined had changed due to this changing landscape.What did we do?We interviewed land agents and valuers operating across Scotland and asked about their approaches to valuing land, particularly land with the potential for Nature Based Solutions for carbon sequestration. These expert opinions were collected over two years (November 2022 - February 2023 and December 2023 - February 2024) and in total 38 interviews were conducted (21 in 2022-23, 17 in 2023-24).What did we learn?Land agents considered that the general approach to valuing land for agriculture and forestry remained consistent. Nevertheless, the price of land has changed dramatically over the last five years, reflecting changing investment demand and wider market conditions.A key driver of change has been an increase in demand for land for tree planting, meaning that plantability has become a highly significant factor in determining land values, particularly for hill land. Land values have also been influenced by various external market factors notably interest rates, inflation, timber prices and carbon credits which have impacted investment demand and therefore the value of sales in the market.The potential to monetise land through carbon credits has been another key strand within this picture, creating a new use case for valuation. While carbon was noted as a strong influence on the market, agents commonly took a cautious view on the reliability of carbon price forecasting. The influence of carbon is strongest for hill land and is particularly relevant to the valuation of Scottish Estates. Agents reported that the plantability and the extent of degraded peat have replaced sporting metrics when assessing the value of upland estates.What do we recommend and what happens next?We will continue to monitor developments across the land market and report on changing dynamics. Subsequent briefings are scheduled in 2024