The influence of fitness on exercise blood pressure and its association with cardiac structure in adolescence

Purpose: Exaggerated exercise blood pressure (BP) is associated with altered cardiac structure and increased cardiovascular risk. Fitness modifies these associations, but the effect in healthy adolescents is unknown. We performed an observational study to determine the influence of fitness on post-exercise BP, and on its relationship with cardiac structure in adolescents. Methods: 4835 adolescents from the Avon Longitudinal Study of Parents and Children, (15.4 (0.3) years, 49% male) completed a submaximal cycle test. Fitness was estimated as physical work capacity 170 adjusted for lean body mass and post-exercise BP measured immediately posttest. Cardiovascular structure and function, including left ventricular (LV) mass (n = 1589), left atrium (LA) size (n = 1466), cardiac output (CO, n = 1610), and total peripheral resistance (TPR, n = 1610) were measured at rest by echocardiography 2.4 (0.4) years later. Results: Post-exercise systolic BP increased stepwise by fitness tertile (131.2 mm Hg [130.4, 132.1]; 137.3 mm Hg [136.5, 138.0]; 142.3 mm Hg [141.5, 143.1]). Each 5 mm Hg of post-exercise systolic BP was associated with 2.46 g [1.91, 3.01] greater LV mass, 0.02 cm [0.02, 0.03] greater LA size, and 0.25 g/m2.7 [0.14, 0.36] greater LV mass index. Adjustment for fitness abolished associations (0.29 g [-0.16, 0.74]; 0.01 cm [-0.001, 0.014] and 0.08 g/m2.7 [-0.001, 0.002]). Similar associations between post-exercise systolic BP and each outcome were found between the lowest and highest fitness thirds. CO increased with fitness third (difference 0.06 L/min [-0.05, 0.17]; 0.23 L/min [0.12, 0.34]) while TPR decreased (difference -0.13 mm Hg·min/L [-0.84,0.59]; -1.08 mm Hg·min/L [-0.1.80, 0.35]). Conclusions: Post-exercise systolic BP increased with fitness, which modified its association with cardiac structure. Higher CO, but lower TPR suggests a physiologically adapted cardiovascular system with greater fitness, highlighting the importance of fitness in adolescence

Adiposity, depression and anxiety: interrelationship and possible mediators

OBJECTIVES: To explore the association between adiposity, major depressive disorder and generalized anxiety disorder, and to assess the role of inflammation, diet quality and physical activity in this association. METHODS: We used data from 2,977 individuals from the 1993 Pelotas Cohort (Brazil) who attended the 18- and 22-year follow-ups. We assessed general obesity using body mass index, fat mass index, and abdominal obesity using waist circumference. Major Depressive Disorder and generalized anxiety disorder were assessed using the mini-international neuropsychiatric interview. C-reactive protein and interleukin-6 (IL-6) levels were used as a measure of inflammation; diet quality was estimated using the revised diet quality index, and physical activity was assessed by the International physical activity questionnaire (IPAQ, min/day). The association between adiposity and major depressive disorder and generalized anxiety disorder was assessed using logistic regression, and the natural indirect effect via the mediators was estimated using G-computation. RESULTS: General obesity assessed by body mass index (OR: 2.3; 95% CI:1.13; 4.85), fat mass index (OR: 2.6; 95%CI: 1.37; 4.83), and abdominal obesity (OR: 2.5; 95%CI: 1.18; 5.39) were associated with higher odds of major depressive disorder, whereas major depressive disorder was only associated with obesity assessed by body mass index (OR=1.9; 95% CI: 1.09; 3.46). Obesity and generalized anxiety disorder were not associated. C-reactive protein, diet quality and physical activity did not mediate the effect of obesity on major depressive disorder, and C-reactive protein mediated about 25% of the effect of major depressive disorder on adiposity. CONCLUSIONS: Depression, but not generalized anxiety disorder, is associated with adiposity in both directions, with a stronger evidence for the direction obesity-depression. Inflammation explains part of the effect of major depressive disorder on obesity but not the other way around. Further research should explore other mechanisms that could be involved in the association between obesity and depression

Masked hypertension and submaximal exercise blood pressure among adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC)

Purpose: Masked hypertension is associated with increased cardiovascular risk but is undetectable by clinic blood pressure (BP). Elevated systolic BP responses to submaximal exercise reveal the presence of masked hypertension in adults, but it is unknown whether this is the case during adolescence. We aimed to determine if exercise BP was raised in adolescents with masked hypertension, and its association with cardiovascular risk markers.Methods: A total of 657 adolescents (aged 17.7 ± 0.3 years; 41.9% male) from the Avon longitudinal study of parents and children (ALSPAC) completed a step-exercise test with pre-, post-, and recovery-exercise BP, clinic BP and 24-hour ambulatory BP. Masked hypertension was defined as clinic BP Results: Fifty participants (7.8%) were classified with masked hypertension. Clinic, pre-, post-, and recovery-exercise systolic BP were associated with masked hypertension (AUC ≥ 0.69 for all, respectively), with the clinic systolic BP threshold of 115 mm Hg having high sensitivity and specificity and exercise BP thresholds of 126, 150, and 130 mm Hg, respectively, having high specificity and negative predictive value (individually or when combined) for ruling out the presence of masked hypertension. Additionally, this exercise systolic BP above the thresholds was associated with greater left-ventricular mass index and aortic PWV.Conclusions: Submaximal exercise systolic BP is associated with masked hypertension and adverse cardiovascular structure in adolescents. Exercise BP may be useful in addition to clinic BP for screening of high BP and cardiovascular risk in adolescents

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria.

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of $\textit{Synechocystis }$ sp. PCC 7002 and $\textit{Synechocystis }$ sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that $\textit{Synechocystis }$ sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.T.L. was supported by BBSRC Research Grant BB/J016985/1 to C.W.M. D.J.L-S. was supported by the Environmental Services Association Education Trust. L.L.B was supported by a BBSRC Doctoral Training Grant (BB/F017464/1)

Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review

Diseases diagnosed in adulthood may have antecedents throughout (including prenatal) life. Gaining a better understanding of how exposures at different stages in the lifecourse influence health outcomes is key to elucidating the potential benefits of disease prevention strategies. Mendelian randomisation (MR) is increasingly used to estimate causal effects of exposures across the lifecourse on later life outcomes. This systematic literature review explores MR methods used to perform lifecourse investigations and reviews previous work that has utilised MR to elucidate the effects of factors acting at different stages of the lifecourse. We conducted searches in PubMed, Embase, Medline and MedRXiv databases. Thirteen methodological studies were identified. Four studies focused on the impact of time-varying exposures in the interpretation of "standard" MR techniques, five presented methods for repeat measures of the same exposure, and four described methodological approaches to handling multigenerational exposures. A further 127 studies presented the results of an applied research question. Over half of these estimated effects in a single generation and were largely confined to the exploration of questions regarding body composition. The remaining mostly estimated maternal effects. There is a growing body of research focused on the development and application of MR methods to address lifecourse research questions. The underlying assumptions require careful consideration and the interpretation of results rely on select conditions. Whilst we do not advocate for a particular strategy, we encourage practitioners to make informed decisions on how to approach a research question in this field with a solid understanding of the limitations present and how these may be affected by the research question, modelling approach, instrument selection, and data availability

Social Inequalities in Height: Persisting Differences Today Depend upon Height of the Parents

BACKGROUND: Substantial increases in height have occurred concurrently with economic development in most populations during the last century. In high-income countries, environmental exposures that can limit genetic growth potential appear to have lessened, and variation in height by socioeconomic position may have diminished. The objective of this study is to investigate inequalities in height in a cohort of children born in the early 1990s in England, and to evaluate which factors might explain any identified inequalities. METHODS AND FINDINGS: 12,830 children from The Avon Longitudinal Study of Parents and Children (ALSPAC), a population based cohort from birth to about 11.5 years of age, were used in this analysis. Gender- and age-specific z-scores of height at different ages were used as outcome variables. Multilevel models were used to take into account the repeated measures of height and to analyze gender- and age-specific relative changes in height from birth to 11.5 years. Maternal education was the main exposure variable used to examine socioeconomic inequalities. The roles of parental and family characteristics in explaining any observed differences between maternal education and child height were investigated. Children whose mothers had the highest education compared to those with none or a basic level of education, were 0.39 cm longer at birth (95% CI: 0.30 to 0.48). These differences persisted and at 11.5 years the height difference was 1.4 cm (95% CI: 1.07 to 1.74). Several other factors were related to offspring height, but few changed the relationship with maternal education. The one exception was mid-parental height, which fully accounted for the maternal educational differences in offspring height. CONCLUSIONS: In a cohort of children born in the 1990s, mothers with higher education gave birth to taller boys and girls. Although height differences were small they persisted throughout childhood. Maternal and paternal height fully explained these differences.Bruna Galobardes, Valerie A. McCormack, Peter McCarron, Laura D. Howe, John Lynch, Debbie A. Lawlor and George Davey Smit

The Genome of C57BL/6J Eve , the Mother of the Laboratory Mouse Genome Reference Strain.

Isogenic laboratory mouse strains enhance reproducibility because individual animals are genetically identical. For the most widely used isogenic strain, C57BL/6, there exists a wealth of genetic, phenotypic, and genomic data, including a high-quality reference genome (GRCm38.p6). Now 20 years after the first release of the mouse reference genome, C57BL/6J mice are at least 26 inbreeding generations removed from GRCm38 and the strain is now maintained with periodic reintroduction of cryorecovered mice derived from a single breeder pair, aptly named Adam and Eve. To provide an update to the mouse reference genome that more accurately represents the genome of today\u27s C57BL/6J mice, we took advantage of long read, short read, and optical mapping technologies to generate a de novo assembly of the C57BL/6J Eve genome (B6Eve). Using these data, we have addressed recurring variants observed in previous mouse genomic studies. We have also identified structural variations, closed gaps in the mouse reference assembly, and revealed previously unannotated coding sequences. This B6Eve assembly explains discrepant observations that have been associated with GRCm38-based analyses, and will inform a reference genome that is more representative of the C57BL/6J mice that are in use today

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson