32 research outputs found

    Perflurorochemical (PFC) exposure in children: Associations with impaired response inhibition

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    Background: Perfluorinated chemicals (PFCs) have been used widely in consumer products since the 1950s and are currently found at detectable levels in the blood of humans and animals across the globe. In stark contrast to this widespread exposure to PFCs, there is relatively little research on potential adverse health effects of exposure to these chemicals.Objectives: We performed this cross-sectional study to determine if specific blood PFC levels are associated with impaired response inhibition in children. Methods: Blood levels of 11 PFCs were measured in children (N = 83) and 6 PFCs: perfluorooctane sulfonate (PFOS), perfluorohexane sulfate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonamide (PFOSA), and perfluorodecanoic acid (PFDA)_ were found at detectable levels in most children (87.5% or greater had detectable levels). These levels were analyzed in relation to the differential reinforcement of low rates of responding (DRL) task. This task rewards delays between responses (i.e., longer inter-response times; IRTs) and therefore constitutes a measure of response inhibition. Results:Higher levels of blood PFOS, PFNA, PFDA, PFHxS, and PFOSA were associated with significantly shorter IRTs during the DRL task. The magnitude of these associations was such that IRTs during the task decreased by 29_34% for every 1 SD increase in the corresponding blood PFC. Conclusions: This study suggests an association between PFC exposure and children’s impulsivity. Although intriguing, there is a need for further investigation and replication with a larger sample of children

    Plasma prekallikrein levels are positively associated with circulating lipid levels and the metabolic syndrome in children.

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    Plasma prekallikrein (PK) has been shown to be associated with cardiovascular disease (CVD) and its risk factors, but these associations have not been investigated in children. The present study examined PK activity in relation to well-established cardiovascular risk factors in a cohort of children aged 9–11 years (N = 97). We found a significant and positive association between PK and fasting levels of total cholesterol (p \u3c 0.01), non-high-density lipoprotein cholesterol (p \u3c 0.01), and triglycerides (p \u3c 0.001). In addition, there was a significant association between PK activity and the metabolic syndrome, a clustering of risk factors considered to have an impact on atherosclerosis and CVD mortality. Finally, we found that children with a family history of CVD had significantly elevated PK activity. These novel findings warrant further investigations into the relationship between circulating PK levels and CVD risk factors because PK may be involved in the progression of the disease state. Il est bien connu que la pre´kallicre´ine (PK) est associe´e a` la maladie cardiovasculaire (CVD) et a` ses facteurs de risque, mais ces associations n’ont pas e´te´ ve´rifie´es chez les enfants. Cette e´tude se propose de ve´rifier l’association entre l’activite´ de la PK et les facteurs de risque de CVD aupre`s d’une cohorte d’enfants aˆge´s de 9 a` 11 ans (N = 97). On observe une corre´lation positive significative entre la PK et les variables suivantes : la concentration totale de choleste´rol a` jeun (p \u3c 0,01), les concentrations des lipoprote´ines non a` haute densite´ (p \u3c 0,01) et la concentration des triglyce´rides (p \u3c 0,001). De plus, on observe une corre´lation significative entre l’activite´ de la PK et le syndrome me´tabolique constitue par un ensemble de facteurs ayant un effet sur l’athe´roscle´rose et la mortalite´ due a` la CVD. En dernier lieu, les enfants avec des ante´ce´dents familiaux de CVD pre´sentent une plus importante activite´ de la PK, et ce, de fac¸on significative. Ces premie`res observations sugge`rent d’autres e´tudes sur la relation entre la concentration sanguine de PK et les facteurs de risque de CVD, car la PK pourrait eˆtre implique´e dans la progression de la malad

    The SU RD Team: Serving Research at Syracuse University

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    Research development is growing in many ways – both as a profession and as a common substructure among institutions of higher education. NORDP itself has helped to support the establishment, fostering, and recognition of the many forms research development has taken, while growing in tandem as an organization. Leadership and representatives from large centralized RD units have contributed to and benefited from the model of peer education, support and mentorship NORDP provides, as have the individuals who serve as one-man or one-woman shops for smaller schools or colleges. At Syracuse University, NORDP has served as the impetus for the development of a new model of research development support, the combined centralized and distributed “SU RD team.” In the spring of 2018, Syracuse University (SU) added a research development unit to the University’s Office of Research, to coordinate activities across the institution. The growth of the office has been slow in size, but the number of activities supported have been significant, such as the fostering of a new, large intramural funding program, a staggering growth in limited submission competitions, and the doubling of grant- and research-related training opportunities on campus. This level of activity, as well as a successful campus-wide adoption of these initiatives, is directly attributable to the University’s unique employment of a team of research development professionals, comprised of members of the centralized Office of Research, and from the Dean’s offices of five of the eleven degree granting schools and colleges at SU. The proposed poster will provide a written and visual representation of this network of RD professionals within one institution, as a case study designed to share best practices of intra-university research development collaborations. Emphasis will be placed on regular shared activities between team members, which both support and stem from the close, working relationships developed in the team

    A Genome-Wide Metabolic QTL Analysis in Europeans Implicates Two Loci Shaped by Recent Positive Selection

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    We have performed a metabolite quantitative trait locus (mQTL) study of the 1H nuclear magnetic resonance spectroscopy (1H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by 1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10−11<p<2.8×10−23). Three of these—trimethylamine, 3-amino-isobutyrate, and an N-acetylated compound—were measured in urine. The other—dimethylamine—was measured in plasma. Trimethylamine and dimethylamine mapped to a single genetic region (hence we report a total of three implicated genomic regions). Two of the three hit regions lie within haplotype blocks (at 2p13.1 and 10q24.2) that carry the genetic signature of strong, recent, positive selection in European populations. Genes NAT8 and PYROXD2, both with relatively uncharacterized functional roles, are good candidates for mediating the corresponding mQTL associations. The study's longitudinal twin design allowed detailed variance-components analysis of the sources of population variation in metabolite levels. The mQTLs explained 40%–64% of biological population variation in the corresponding metabolites' concentrations. These effect sizes are stronger than those reported in a recent, targeted mQTL study of metabolites in serum using the targeted-metabolomics Biocrates platform. By re-analysing our plasma samples using the Biocrates platform, we replicated the mQTL findings of the previous study and discovered a previously uncharacterized yet substantial familial component of variation in metabolite levels in addition to the heritability contribution from the corresponding mQTL effects

    A Genome-Wide Metabolic QTL Analysis in Europeans Implicates Two Loci Shaped by Recent Positive Selection

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    We have performed a metabolite quantitative trait locus (mQTL) study of the 1H nuclear magnetic resonance spectroscopy (1H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by 1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10−11<p<2.8×10−23). Three of these—trimethylamine, 3-amino-isobutyrate, and an N-acetylated compound—were measured in urine. The other—dimethylamine—was measured in plasma. Trimethylamine and dimethylamine mapped to a single genetic region (hence we report a total of three implicated genomic regions). Two of the three hit regions lie within haplotype blocks (at 2p13.1 and 10q24.2) that carry the genetic signature of strong, recent, positive selection in European populations. Genes NAT8 and PYROXD2, both with relatively uncharacterized functional roles, are good candidates for mediating the corresponding mQTL associations. The study's longitudinal twin design allowed detailed variance-components analysis of the sources of population variation in metabolite levels. The mQTLs explained 40%–64% of biological population variation in the corresponding metabolites' concentrations. These effect sizes are stronger than those reported in a recent, targeted mQTL study of metabolites in serum using the targeted-metabolomics Biocrates platform. By re-analysing our plasma samples using the Biocrates platform, we replicated the mQTL findings of the previous study and discovered a previously uncharacterized yet substantial familial component of variation in metabolite levels in addition to the heritability contribution from the corresponding mQTL effects

    Mitochondrial physiology

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    As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

    Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

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    Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

    A pragmatic approach to the comparison of wrist-based cutpoints of physical activity intensity for the MotionWatch8 accelerometer in children.

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    BackgroundA variety of wearable monitors are available for objectively assessing physical activity but there is a lack of established values for the activity intensity of MotionWatch8 (MW8) and a similar lack of studies on comparability across devices. Our study aimed to establish activity intensity cutpoints for the MW8 accelerometer in children, which are necessary to determine whether they are meeting physical activity guidelines.MethodsChildren (n = 39, ages 9-13 years) were asked to wear two different accelerometers (MW8 and ActiGraph) simultaneously on the same dominant wrist as they performed different activities designed to mimic activities of variable intensity that a child might perform in a free-living environment. Linear regression and receiver operating characteristic (ROC) curves were performed to assess sensitivity and specificity of the identified MW8 intensity cutpoints compared to established ActiGraph cutpoints.ResultsMean values for each activity were positively correlated using the MW8 and ActiGraph monitors (r = 0.85, pConclusionsOur study demonstrated the ability of MW8 to discriminate different intensity activities and provided the first cutoff values for researchers using the MW8 to measure physical activity patterns among children
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