Vascular health in children and adolescents: effects of obesity and diabetes

The foundations for cardiovascular disease in adults are laid in childhood and accelerated by the presence of comorbid conditions, such as obesity, diabetes, hypertension, and dyslipidemia. Early detection of vascular dysfunction is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Typically, cardiovascular screening is recommended for young adults, especially in people with a family history of cardiovascular conditions. Children and adolescents were once considered to be at low risk, but with the growing health concerns related to sedentary lifestyle, poor diet and obesity, cardiovascular screening may be needed earlier so that interventions to improve cardiovascular health can be initiated. This review describes comorbid conditions that increase cardiovascular risk in youth, namely obesity and diabetes, and describes noninvasive methods to objectively detect vascular disease and quantify vascular function and structure through measurements of endothelial function, arterial compliance, and intima-media thickness. Additionally, current strategies directed toward prevention of vascular disease in these populations, including exercise, dietary interventions and pharmacological therapy are described

Sex Differences in Vascular Compliance in Normal-Weight but Not Obese Boys and Girls: The Effect of Body Composition

Objectives. To determine the effect of sex and obesity on vascular function in children and explore potential mechanisms that account for differences in vascular function. Methods. Participants were 61 (30 boys) normal-weight (BMI 25–75% ile for age and sex) and 62 (30 boys) obese (BMI ≥ 95% ile) children of ages 8–18 years. Measurements of large and small artery elastic index (LAEI and SAEI, resp.) and reactive hyperemia index (RHI) were obtained at rest, along with anthropometric and biochemical information. Results. In normal-weight children, LAEI was 16% higher in males than females (P = 0.04) with a similar trend for SAEI (13% higher in males, P = 0.067). In obese children, no sex-related differences in vascular measures were observed. In multivariable models, sex differences in arterial compliance were explained by higher lean mass in normal-weight boys. Fat mass predicted LAEI and SAEI in both normal-weight and obese females, but fat mass predicted arterial compliance in boys when fat mass exceeded 24 kg (37% of the sample). Conclusions. Normal-weight males have higher arterial compliance than normal-weight females due to increased lean mass, but sex-related differences were not observed among obese children due to a lack of sex-related differences in lean or fat mass

The Effect of Short and Long Recovery Periods on the Contribution of Oxidative Processes to Energy Expenditure During Multiple Bouts of Supramaximal Exercise

The Effect of Short and Long Recovery Periods on the Contribution of Oxidative Processes to Energy Expenditure During Multiple Bouts of Supramaximal Exercise Olson, E. (undergraduate), Christensen, K., Jajtner, A., Copeland, J., Unthank, M., and Mitchell, J. Exercise Physiology Lab, Texas Christian University, Ft. Worth, TX. The contribution of oxidative energy production to multiple sprint exercises is of interest due to implications for the training needs of people engaging in anaerobic activities. PURPOSE: The purpose of this study was to examine the effect of short and long active recovery durations on oxidative and anaerobic contributions to energy output during maximal intensity cycle ergometry. METHODS: Six male subjects, including well-trained endurance athletes and well-trained strength athletes, completed the study. After a VO2max test on the bicycle ergometer, each subject completed two conditions: a short recovery condition (SRC) and a long recovery condition (LRC). The SRC consisted of 10, 10-sec. supramaximal sprints with 30-sec. recovery periods. The LRC consisted of 10, 10-sec supramaximal sprints with 3-min. recovery periods. The load applied to the ergometer was 1.2 g/kg and the RPM during the sprints varied based on the maximal output. During recovery, no load was applied and subjects maintained a cadence of 80 RPM. Oxygen uptake was measured during the entirety of both conditions and peak power and total work were calculated from two, 5-sec RPM averages generated during the sprints. Blood samples were taken pre-exercise, after sprints 4, 7, and 10, and 3 minutes post-exercise. RESULTS: Peak power and total work were significantly greater (p \u3c 0.05) in the LRC (1091.3 + 88.7 W and 1363.6 + 34.6 kg-m) compared to the SRC (915.3 + 109.2 W and 1161.6 + 33.9 kg-m). In addition, peak power decayed by 21.7% over the 10 sprints in the SRC compared to no decay in the LRC. Oxygen uptake averaged 28.3 + 0.9 ml/kg/min for the entirety of the LRC; whereas, in the SRC there was a large increase in oxygen uptake during the second sprint that remained elevated and averaged 47 + 1.5 ml/kg/min for the remaining 8 sprints. There was no difference in blood lactate concentrations between conditions. CONCLUSION: The heightened aerobic response and the lower work and power outputs seen in the SRC are suggestive of a decrement in both anaerobic glycolysis and phosphocreatine (PCr) activity as successive sprints were completed. After repeated bouts of explosive exercise with short rest periods, oxidative processes play a more important role in energy production, most likely due to fatigue occurring in the anaerobic energy producing systems. These findings point to the need for enhancing the aerobic capacity of athletes engaging in consecutive high intensity bouts of exercise when rest intervals are short

Normal sex differences in prenatal growth and abnormal prenatal growth retardation associated with 46,XY disorders of sex development are absent in newborns with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

<p>Abstract</p> <p>Background</p> <p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences.</p> <p>Methods</p> <p>In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses.</p> <p>Results</p> <p>Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (<it>P </it>> 0.05). The expected sex difference in favor of heavier males was not seen (<it>P </it>> 0.05). Of the 105 subjects, 44 (27%; 34 females, 10 males) had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (<it>P </it>= 0.0082). The expected sex difference in favor of longer males was also not seen (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants.</p

Eukaryotic DNA Polymerases: Proposal for a Revised Nomenclature

Pol polymeraseIn 1975, a Greek letter nomenclature system was introduced to designate DNA polymerases from mammalian cells (1). Ten years ago, progress in the biochemical analysis of eukaryotic DNA polymerases and in the isolation of their genes, particularly in the yeast Saccharomyces cerevisiae, necessitated a revision of the Greek letter nomenclature system and an expansion to include all eukaryotic organisms (2). Until a few years ago, this system sufficed to designate the six known DNA polymerases α, β, γ, δ, ε, and ζ

Cognitive health among older adults in the United States and in England

<p>Abstract</p> <p>Background</p> <p>Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries.</p> <p>Methods</p> <p>Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87% for the HRS vs. 67% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale).</p> <p>Results</p> <p>US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment × country interaction).</p> <p>Conclusion</p> <p>Despite methodological differences in the administration of the surveys in the two countries, US adults aged ≥ 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.</p

Seeing the Lexus for the Olive Trees? Public Opinion, Economic Interdependence, and Interstate Conflict

Many scholars argue that economic interdependence and more extensive economic ties between countries decreases the risk of violent conflict between them. However, despite considerable research on the “capitalist peace” at the macro or dyadic level, there has been less attention to its possible individual-level microfoundations or underpinnings. We argue that public perceptions about economic ties with other states and the costs of conflict should influence the expected constraints on the use of force for leaders. Actual high interdependence and potential economic costs may not suffice to create political constraints on the use of force if people are unaware of the degree of interdependence or fail to understand the benefits of trade and the likely economic costs of disruptive conflict. We examine the linkages between individual perceptions about economic interdependence and their views on conflict and peace through a survey experiment, where we ask respondents in Japan about approval for belligerent actions in a territorial dispute with China and varying information about economic ties. Our findings indicate that greater knowledge and information about economic interdependence affects attitudes about territorial disputes and increases support for peaceful solutions with China

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Summary Background Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.Peer reviewe

Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis