Sedentary Behavior and Cardiovascular Disease Risk: Mediating Mechanisms.

Sedentary behavior has a strong association with cardiovascular disease (CVD) risk, which may be independent of physical activity. To date, the mechanism(s) that mediate this relationship are poorly understood. We hypothesize that sedentary behavior modifies key hemodynamic, inflammatory, and metabolic processes resulting in impaired arterial health. Subsequently, these vascular impairments directly and indirectly contribute to the development of CVD

REVEL Is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants

This is the final version. Available on open access from Hindawi via the DOI in this recordData Availability: The list of variants used in this study are included in Supplementary Table 1.In silico predictive tools can help determine the pathogenicity of variants. The 2015 American College of Medical Genetics and Genomics (ACMG) guidelines recommended that scores from these tools can be used as supporting evidence of pathogenicity. A subsequent publication by the ClinGen Sequence Variant Interpretation Working Group suggested that high scores from some tools were sufficiently predictive to be used as moderate or strong evidence of pathogenicity. REVEL is a widely used metapredictor that uses the scores of 13 individual in silico tools to calculate the pathogenicity of missense variants. Its ability to predict missense pathogenicity has been assessed extensively; however, no study has previously tested whether its performance is affected by whether the missense variant acts via a loss-of-function (LoF) or gain-of-function (GoF) mechanism. We used a highly curated dataset of 66 confirmed LoF and 65 confirmed GoF variants to evaluate whether this affected the performance of REVEL. 98% of LoF and 100% of GoF variants met the author-recommended REVEL threshold of 0.5 for pathogenicity, while 89% of LoF and 88% of GoF variants exceeded the 0.75 threshold. However, while 55% of LoF variants met the threshold recommended for a REVEL score to count as strong evidence of pathogenicity from the ACMG guidelines (0.932), only 35% of GoF variants met this threshold (). GoF variants are therefore less likely to receive the highest REVEL scores which would enable the REVEL score to be used as strong evidence of pathogenicity. This has implications for classification with the ACMG guidelines as GoF variants are less likely to meet the criteria for pathogenicity. P = 0.0352 ). GoF variants are therefore less likely to receive the highest REVEL scores which would enable the REVEL score to be used as strong evidence of pathogenicity. This has implications for classification with the ACMG guidelines as GoF variants are less likely to meet the criteria for pathogenicity.Wellcome TrustResearch EnglandNational Institute for Health and Care Research (NIHR

Nutrient additions three decades on: potential interactions of nutrients and climate in the recovery of a high latitude serpentine system

Nutrient addition experiments initiated in 1980 on the Keen of Hamar, Shetland Isles, have produced a unique dataset of long-term vegetation response to amendments of major plant growth nutrients (N, P, NP, NPK and NPKCa). Previous studies have reported the notable impact of phosphorus on the ‘serpentine debris’ community, and the negligible effect of nitrogen. However, a survey in 2010 provided our first indication that the experimentally-induced phosphorus effect was weakening and this was consolidated by further surveys of vegetation cover and community composition. This community shift might have been different had the local climate acted synergistically with phosphorus additions: in the last few years of the study the Shetland Isles experienced particularly low spring rainfall – the dry spell may have been a well-timed environmental filter driving community recovery rather than a permanent change of state to heathland on an organic soil. The longevity of our investigation is a unique opportunity to explore vegetation response to the key drivers of global environmental change, namely climate change, eutrophication as a result of agricultural intensification, and the potential for invasion of species as new resource-rich niches become available

Relationship Between Sedentary Behavior and Physical Activity at Work and Cognition and Mood

Background: Sedentary behavior is negatively associated with cognition and mood. Adults often engage in high levels of sedentary behavior at work through sitting, which may impact productivity. Consequently, replacing sitting with standing and physical activity (PA) is recommended. However, the associations between sitting, standing, and PA at work and cognition and mood are unknown; this study, therefore, aimed to explore these relationships. Methods: A total of 75 healthy full-time workers (33 male, mean [SD]; 33.6 [10.4] y, 38 [7] work hr/wk) wore sedentary behavior (activPAL) and PA (SenseWear Pro) monitors for 7 days and recorded their work hours. The day after this monitoring period, participants completed cognitive tests (executive function, attention, and working memory) and mood questionnaires (affect, alert, content, and calm). Multiple linear regression analyses examined the associations between cognition and mood and the time spent sitting, standing, and in each PA intensity during work hours, weekday leisure time, and weekends. Results: Workplace sitting, standing, or PA were not significantly associated with cognition or mood (P > .05). No significant associations were observed between these variables during weekday leisure time or weekends (P > .05). Conclusions: In a cohort of healthy workers, workplace sitting, standing, and PA are not associated with cognition or mood. Further research in this population is needed, examining the influence of workplace behaviors on cognition and mood, because this will contribute to evidence-based workplace guidelines to increase productivity

Are acute sitting-induced changes in inflammation and cerebrovascular function related to impaired mood and cognition?

Purpose: Sedentary behaviour is negatively associated with mood and cognition, yet how acute sitting contributes to these overall associations is unknown. Since sitting heightens inflammation and impairs cerebrovascular function, this study investigated the hypothesis that these sitting-induced changes are related to impaired mood and cognition. Methods: Twenty-five healthy desk workers (18 male, 28.3 ± 7.5 years, BMI: 24.2 ± 3.3 kg∙m-2) were recruited. During laboratory visit one, participants were familiarised with cognitive performance tests measuring executive function, attention and working memory. During laboratory visit two, participants completed 6 h of continuous, uninterrupted sitting. At baseline and after 6 h, serum markers of inflammation, middle cerebral artery blood flow velocity (MCAv), cerebrovascular carbon dioxide reactivity (CVR), dynamic cerebral autoregulation (CA), cognitive performance and mood (positive and negative affect, alert, contented and calm) were assessed. Data were analysed using paired-samples t tests and correlation analyses. Results: Following sitting, C-reactive protein (∆-1.0 µg/ml) and tissue plasminogen activator (∆-360.4 pg/ml) decreased (p  0.05). The observed changes in inflammation and cerebrovascular function were not related to changes in mood (p > 0.05). Conclusion: Alterations in inflammation or cerebrovascular function following six hours of prolonged, uninterrupted sitting are not related to the observed reductions in mood, indicating other mechanisms underlie the relationship between acute sitting and mood disturbances

Effect of different walking break strategies on superficial femoral artery endothelial function.

Breaking up prolonged sitting with physical activity (PA) breaks prevents conduit artery dysfunction. However, the optimal break strategy to achieve this, in terms of the frequency or duration of PA, is not known. This study assessed the effect of breaking up sitting with different PA break strategies on lower limb peripheral artery endothelial function. Fifteen participants (10 male, 35.8 ± 10.2 years, BMI: 25.5 ± 3.2 kg m-2 ) completed, on separate days, three 4-h conditions in a randomized order: (1) uninterrupted sitting (SIT), (2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or (3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, superficial femoral artery function (flow-mediated dilation; FMD), blood flow, and shear rate (SR) were assessed using Doppler ultrasound. For each condition, the change in outcome variables was calculated and data were statistically analyzed using a linear mixed model. There was no significant main effect for the change in FMD (P = 0.564). A significant main effect was observed for the change in blood flow (P = 0.022), with post hoc analysis revealing a greater reduction during SIT (-42.7 ± 14.2 mL·min) compared to 8WALK (0.45 ± 17.7 mL·min; P = 0.012). There were no significant main effects for mean, antegrade, or retrograde SR (P > 0.05). Superficial femoral artery blood flow, but not FMD, was reduced following uninterrupted sitting. This decline in blood flow was prevented with longer duration, less frequent walking breaks rather than shorter, more frequent breaks suggesting the dose (duration and frequency) of PA may influence the prevention of sitting-induced decreases in blood flow

Cerebral and peripheral vascular differences between pre- and post-menopausal women

Objective: Menopause is associated with lower peripheral vascular function however cerebrovascular responses to this time-period are unclear. We aimed to describe peripheral vascular and cerebrovascular differences between pre- and post-menopausal women. Methods: Fifty pre- and post-menopausal women (N=100) underwent assessments of cerebral blood flow, cerebrovascular reactivity and autoregulation, carotid artery reactivity, brachial and femoral artery flow-mediated dilation and carotid, brachial and femoral artery intima-media thickness. Comparisons were made between pre- and post-menopausal women followed by a secondary-analysis (N=20) between late-pre-menopausal women and those within five years of menopause using a general linear model. Results: Cerebral blood flow (-11 [-17, -4 cm/s]; p=0.03) and carotid reactivity (-2.3 [-4.3, - 0.3%] p=0.03) were lower post-menopause compared to pre-menopause while cerebrovascular reactivity and autoregulation did not differ (p>0.05). Post-menopausal women had a larger carotid (0.16 [0.13, 0.20 mm] p<0.001), brachial (0.07 [0.03, 0.11mm] p=0.004) and femoral artery intima-media-thickness (0.09 [0.05, 0.14 mm] p=0.04), alongside lower brachial (-2.3 [-3.9, -0.7%] p=0.004) and femoral artery flow-mediated dilation (-3.0 [-4.3, - 1.8 %] p<0.001). In the secondary-analysis, early-post-menopausal women had a lower femoral artery flow-mediated dilation (-1.9 [-3.9, -0.0 %] p=0.05) and larger carotid intimamedia-thickness (0.07 [0.00, 0.14 mm] p=0.03) compared to late-pre-menopausal women. Conclusions: Cerebral blood flow, carotid artery reactivity, peripheral vascular function and structure are negatively affected by age. Preliminary data indicates that femoral artery function and carotid artery structure may be potentially impaired in early-post-menopause compared with late-pre-menopause. These findings suggest that conduit arteries susceptible to atherosclerosis may be important targets for lifestyle intervention in early menopause

Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

In Scotland, a national HPV immunisation programme began in 2008 for 12-13 year olds, with a catch-up campaign from 2008-2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.  We analysed colposcopy data from a cohort of women born between 1988-1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012.  By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1) (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008), CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< 0.0001) for women who received 3 doses of vaccine compared with unvaccinated women.  To our knowledge, this is one of the first studies to show a reduction of low and high grade cervical intraepithelial neoplasia associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake

Using an e-Health Intervention to Reduce Prolonged Sitting in UK Office Workers: A Randomised Acceptability and Feasibility Study

Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees’ health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials: Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted

Impact of green tea on the deleterious cardiometabolic effects of 7-days unhealthy lifestyle in young healthy males.

PURPOSE: The aim of this study was to examine if catechin-rich green tea abrogates the negative effects of 7-days of physical inactivity and excessive calorie-intake on insulin homeostasis and peripheral vascular function. METHODS: Using a randomized, double-blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7-days unhealthy lifestyle (UL), including physical inactivity (-50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL-tea; 3 doses/day) or placebo (UL-placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3-h after a 1,202 kcal meal) and upper and lower limb vascular function (flow-mediated dilation (FMD%)) and carotid artery reactivity (CAR%). RESULTS: UL-placebo increased postprandial glucose and insulin, while UL-tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p  0.05) for brachial FMD%. CONCLUSION: Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin-rich green tea