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Key points Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstratein vitrothat maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodiumdl-beta-hydroxybutyrate, beta-HB; lithium acetoacetate, AcAc) to stimulatein vitromitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (similar to 30-35% of pyruvate), RG (similar to 10-30%), and human vastus lateralis (similar to 2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 mu m beta-HB, 801 mu mAcAc; RG: 782 mu m beta-HB, 267 mu mAcAc) were greater than KB content representative of the muscle microenvironment (similar to 100 mu m). This would predict low rates (similar to 1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s(-1) mg(-1)) and RG (3-6 pmol s(-1) mg(-1)) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 mu m) reduced the ability of physiological beta-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

International audience; Fiber tractography (FT) using diffusion magnetic resonance imaging (dMRI) is widely used for investigating microstructural properties of white matter (WM) fiber-bundles and for mapping structural connections of the human brain. While studying the architectural configuration of the brain's circuitry with FT is not without controversy, recent progress in acquisition, processing, modeling, analysis, and visualization of dMRI data pushes forward the reliability in reconstructing WM pathways. Despite being aware of the well-known pitfalls in analyzing dMRI data and several other limitations of FT discussed in recent literature, we present the superoanterior fasciculus (SAF), a novel bilateral fiber tract in the frontal region of the human brain that-to the best of our knowledge-has not been documented. The SAF has a similar shape to the anterior part of the cingulum bundle, but it is located more frontally. To minimize the possibility that these FT findings are based on acquisition or processing artifacts, different dMRI data sets and processing pipelines have been used to describe the SAF. Furthermore, we evaluated the configuration of the SAF with complementary methods, such as polarized light imaging (PLI) and human brain dissections. The FT results of the SAF demonstrate a long pathway, consistent across individuals, while the human dissections indicate fiber pathways connecting the postero-dorsal with the antero-dorsal cortices of the frontal lobe.

The final meeting of the EXPOsOMICS project "Final Policy Workshop and Stakeholder Consultation" took place 28-29 March 2017 to present the main results of the project and discuss their implications both for future research and for regulatory and policy activities. This paper summarizes presentations and discussions at the meeting related with the main results and advances in exposome research achieved through the EXPOsOMICS project; on other parallel research initiatives on the study of the exposome in Europe and in the United States and their complementarity to EXPOsOMICS; lessons learned from these early studies on the exposome and how they may shape the future of research on environmental exposure assessment; and finally the broader implications of exposome research for risk assessment and policy development on environmental exposures. The main results of EXPOsOMICS in relation to studies of the external exposome and internal exposome in relation to both air pollution and water contaminants were presented as well as new technologies for environmental health research (adductomics) and advances in statistical methods. Although exposome research strengthens the scientific basis for policy development, there is a need in terms of showing added value for public health to: improve communication of research results to non-scientific audiences; target research to the broader landscape of societal challenges; and draw applicable conclusions. Priorities for future work include the development and standardization of methodologies and technologies for assessing the external and internal exposome, improved data sharing and integration, and the demonstration of the added value of exposome science over conventional approaches in answering priority policy questions. This work has been supported by the Exposomics EC FP7 grant (Grant agreement no: 308610) to PV. MCT is supported by the Departament de Salut, Generalitat de Catalunya. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya

The standard for assessing dietary sodium intake is to measure 24‐hour urine sodium. On average, 93% of daily sodium intake is excreted over 24‐hours. Expense and difficulties in obtaining complete 24‐hour collections have led to the measurement of sodium concentration in spot and single‐void urine samples, using predictive equations to estimate 24‐hour urine sodium. Although multiple predictive equations have been developed, in addition to having an average bias, all the equations overestimate 24‐hour sodium at lower levels of 24‐hour sodium and underestimate 24‐hour urine sodium at higher levels of 24‐hour sodium. One of the least biased estimating equations is the INTERSALT equation, which incorporates a spot urine creatinine concentration. The authors hypothesized that differential fractional excretion of sodium (FeNa)(derived from a morning void collection) relative to creatinine would impact on the accuracy of the INTERSALT equation in estimating 24‐hour urine sodium. In a prospective study of 139 adults aged 65 years and over, three sequential morning void and 24‐hour urine samples were examined. There was a significant correlation between increasing FENa and the difference between estimated and measured 24‐hours urine sodium (r = 0.358, P < .01). In the lowest quartile of FENa, the INTERSALT equation overestimated 24‐hour urine sodium, but underestimated 24‐hour urine sodium with greater magnitude in each of the subsequent quartiles of FENa. Differential excretion of sodium relative to creatinine, potentially impacted by renal blood flow and hydration, among other factors, affected the accuracy of the INTERSALT equation. Additional research may refine the INTERSALT and other predictive equations to increase their accuracy.

Abstract Throughout its history the strategy and tactics of contextual behavioral science (CBS) research have had distinctive features as compared to traditional behavioral science approaches. Continued progress in CBS research can be facilitated by greater clarity about how its strategy and tactics can be brought to bear on current challenges. The present white paper is the result of a 2 1/2-year long process designed to foster consensus among representative producers and consumers of CBS research about the best strategic pathway forward. The Task Force agreed that CBS research should be multilevel, process-based, multidimensional, prosocial, and pragmatic, and provided 33 recommendations to the CBS community arranged across these characteristics. In effect, this report provides a detailed research agenda designed to maximize the impact of CBS as a field. Scientists and practitioners are encouraged to mount this ambitious agenda.

Preventing declines in cerebral blood flow is important for maintaining optimal brain health with aging. We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cerebral blood velocity over 8 h in older adults. In a randomized crossover trial, overweight/obese older adults ( n = 12, 70 ± 7 yr; 30.4 ± 4.3 kg/m2), completed three acute conditions (6-day washout); SIT: prolonged sitting (8 h, control); EX+SIT: sitting (1 h), moderate-intensity walking (30 min), followed by uninterrupted sitting (6.5 h); and EX + BR: sitting (1 h), moderate-intensity walking (30 min), followed by sitting (6.5 h) interrupted with 3 min of light-intensity walking every 30 min. Bilateral middle cerebral artery velocities (MCAv) were determined using transcranial Doppler at 13 time points across the day. The temporal pattern and average MCAv over 8 h was determined. The pattern of MCAv over 8 h was a negative linear trend in SIT ( P < 0.001), but a positive quadratic trend in EX + SIT ( P < 0.001) and EX + BR ( P < 0.01). Afternoon time points in SIT were lower than baseline within condition ( P ≤ 0.001 for all). A morning dip in MCAv was observed in EX + SIT and EX + BR ( P < 0.05 relative to baseline), but afternoon time points were not significantly lower than baseline. The average MCAv over 8 h was higher in EX + SIT than SIT ( P = 0.007) or EX + BR ( P = 0.024). Uninterrupted sitting should be avoided, and moderate-intensity exercise should be encouraged for the daily maintenance of cerebral blood flow in older adults. The clinical implications of maintaining adequate cerebral blood flow include the delivery of vital oxygen and nutrients to the brain. NEW & NOTEWORTHY This is the first study to measure the combined effects of an exercise bout with breaks in sitting on cerebral blood velocity in older adults. Using frequent recordings over an 8-h period, we have performed a novel analysis of the pattern of cerebral blood velocity, adjusting for concurrent measures of mean arterial pressure and other potential confounders in a linear mixed effects regression.

Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (−0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 × 10−88). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78–2.78, p = 1.26 × 10−12). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19–1.64, p = 2.63 × 10−5) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.

Several systematic reviews have reported mixed associations between access to parks and physical activity, and suggest that this is due to inconsistencies in the study methods or differences across countries. An international study using consistent methods is needed to investigate the association between access to parks and physical activity.\ud \ud The International Physical Activity and Environment Network (IPEN) Adult Study is a multi-country cross-sectional study using a common design and consistent methods. Accelerometer, survey and Geographic Information Systems (GIS) data for 6181 participants from 12 cities in 8 countries (Belgium, Brazil, Czech Republic, Denmark, Mexico, New Zealand, UK, USA) were used to estimate the strength and shape of associations of 11 measures of park access (1 perceived and 10 GIS-based measures) with accelerometer-based moderate-to-vigorous physical activity (MVPA) and four types of self-reported leisure-time physical activity. Associations were estimated using generalized additive mixed models.\ud \ud More parks within 1 km from participants' homes were associated with greater leisure-time physical activity and accelerometer-measured MVPA. Respondents who lived in the neighborhoods with the most parks did on average 24 min more MVPA per week than those living in the neighborhoods with the lowest number of parks. Perceived proximity to a park was positively associated with multiple leisure-time physical activity outcomes. Associations were homogeneous across all cities studied.\ud \ud Living in neighborhoods with many parks could contribute with up to 1/6 of the recommended weekly Having multiple parks nearby was the strongest positive correlate of PA. To increase comparability and validity of park access measures, we recommend that researchers, planners and policy makers use the number of parks within 1 km travel distance of homes as an objective indicator for park access in relation to physical activity.

Close and intimate relationships are important promoters of health. Oxytocin and its association with social cognition have been investigated in a large number of studies, especially highlighting the neuropeptide’s involvement in attachment behavior and intimate relationships. However, mixed findings on exogenous oxytocin application have led to the focus on moderators and mediators, suggesting that the effects are depended on specific factors – namely context and salience. The objective of the current study was to assess the effect of intranasal oxytocin on social appraisal of own and others’ close intimate relationship characteristics. Different characteristics of relationships, including trust or closeness, between romantic couples (unknown and own) were assessed using the Couple Appraisal Task. In a randomized controlled double-blind cross-over within subject design, N = 71 healthy men and women were investigated after receiving first intranasal oxytocin and 2 weeks later placebo, or vice versa. We found an oxytocin-induced increase in the positive appraisal of one’s own overall relationship characteristics but not in the evaluation of the relationship of others. The present study – one of the first of its kind administrating oxytocin in a repeated measures cross-over design – adds further evidence to the mediating role of oxytocin in social cognition, specifically with regard to romantic relationship characteristics.

© 2020 SAGE Publications. This study compares the individual-level and sample-level predictive utility of a measure of the cultural logics of dignity, honor, and face. University students in 29 samples from 24 nations used a simple measure to rate their perceptions of the interpersonal cultural logic characterizing their local culture. The nomological net of these measures was then explored. Key dependent measures included three different facets of independent versus interdependent self-construal, relevant attitudes and values, reported handling of actual interpersonal conflicts, and responses to normative settings. Multilevel analyses revealed both individual- and sample-level effects but the dignity measure showed more individual-level effects, whereas sample-level effects were relatively more important with the face measure. The implications of this contrast are discussed.