Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis

Objective To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality. Design Systematic review and harmonised meta-analysis. Data sources PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018. Eligibility criteria Prospective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals. Data extraction and analysis Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis. Main outcome measure All cause mortality. Results 39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56). Conclusion Higher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults. Systematic review registration PROSPERO CRD42018091808

Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

Is there an association between seeing incidents of alcohol or drug use in films and young Scottish adults' own alcohol or drug use? A cross sectional study

<p>Background: As the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images of certain behaviours in films are associated with uptake of those behaviours in young people. Associations have been reported between exposure to smoking images in films and smoking initiation, and between exposure to film alcohol images and initiation of alcohol consumption, in younger adolescents in the USA and Germany. To date no studies have reported on film images of recreational drug use and young people's own drug use.</p> <p>Methods: Cross sectional multivariable logistic regression analysis of data collected at age 19 (2002-4) from a cohort of young people (502 boys, 500 girls) previously surveyed at ages 11 (in 1994-5), 13 and 15 in schools in the West of Scotland. Outcome measures at age 19 were: exceeding the 'sensible drinking' guidelines ('heavy drinkers') and binge drinking (based on alcohol consumption reported in last week), and ever use of cannabis and of 'hard' drugs. The principle predictor variables were an estimate of exposure to images of alcohol, and of drug use, in films, controlling for factors related to the uptake of substance use in young people.</p> <p>Results: A third of these young adults (33%) were classed as 'heavy drinkers' and half (47%) as 'binge drinkers' on the basis of their previous week's consumption. Over half (56%) reported ever use of cannabis and 13% ever use of one or more of the 'hard' drugs listed. There were linear trends in the percentage of heavy drinkers (p = .018) and binge drinkers (p = 0.012) by film alcohol exposure quartiles, and for ever use of cannabis by film drug exposure (p = .000), and for ever use of 'hard' drugs (p = .033). The odds ratios for heavy drinking (1.56, 95% CI 1.06-2.29 comparing highest with lowest quartile of film alcohol exposure) and binge drinking (1.59, 95% CI 1.10-2.30) were attenuated by adjustment for gender, social class, family background (parental structure, parental care and parental control), attitudes to risk-taking and rule-breaking, and qualifications (OR heavy drinking 1.42, 95% CI 0.95-2.13 and binge drinking 1.49, 95% CI 1.01-2.19), and further so when adjusting for friends' drinking status (when the odds ratios were no longer significant). A similar pattern was seen for ever use of cannabis and 'hard' drugs (unadjusted OR 1.80, 95% CI 1.24-2.62 and 1.57, 95% CI 0.91-2.69 respectively, 'fully' adjusted OR 1.41 (0.90-2.22 and 1.28 (0.66-2.47) respectively).</p> <p>Conclusions: Despite some limitations, which are discussed, these cross-sectional results add to a body of work which suggests that it is important to design good longitudinal studies which can determine whether exposure to images of potentially health-damaging behaviours lead to uptake of these behaviours during adolescence and early adulthood, and to examine factors that might mediate this relationship.</p&gt

Validity and reliability of subjective methods to assess sedentary behaviour in adults: a systematic review and meta-analysis.

BACKGROUND: Subjective measures of sedentary behaviour (SB) (i.e. questionnaires and diaries/logs) are widely implemented, and can be useful for capturing type and context of SBs. However, little is known about comparative validity and reliability. The aim of this systematic review and meta-analysis was to: 1) identify subjective methods to assess overall, domain- and behaviour-specific SB, and 2) examine the validity and reliability of these methods. METHODS: The databases MEDLINE, EMBASE and SPORTDiscus were searched up to March 2020. Inclusion criteria were: 1) assessment of SB, 2) evaluation of subjective measurement tools, 3) being performed in healthy adults, 4) manuscript written in English, and 5) paper was peer-reviewed. Data of validity and/or reliability measurements was extracted from included studies and a meta-analysis using random effects was performed to assess the pooled correlation coefficients of the validity. RESULTS: The systematic search resulted in 2423 hits. After excluding duplicates and screening on title and abstract, 82 studies were included with 75 self-reported measurement tools. There was wide variability in the measurement properties and quality of the studies. The criterion validity varied between poor-to-excellent (correlation coefficient [R] range - 0.01- 0.90) with logs/diaries (R = 0.63 [95%CI 0.48-0.78]) showing higher criterion validity compared to questionnaires (R = 0.35 [95%CI 0.32-0.39]). Furthermore, correlation coefficients of single- and multiple-item questionnaires were comparable (1-item R = 0.34; 2-to-9-items R = 0.35; ≥10-items R = 0.37). The reliability of SB measures was moderate-to-good, with the quality of these studies being mostly fair-to-good. CONCLUSION: Logs and diaries are recommended to validly and reliably assess self-reported SB. However, due to time and resources constraints, 1-item questionnaires may be preferred to subjectively assess SB in large-scale observations when showing similar validity and reliability compared to longer questionnaires. REGISTRATION NUMBER: CRD42018105994

Multimodal Chemosensory Integration through the Maxillary Palp in Drosophila

Drosophila melanogaster has an olfactory organ called the maxillary palp. It is smaller and numerically simpler than the antenna, and its specific role in behavior has long been unclear. Because of its proximity to the mouthparts, I explored the possibility of a role in taste behavior. Maxillary palp was tuned to mediate odor-induced taste enhancement: a sucrose solution was more appealing when simultaneously presented with the odorant 4-methylphenol. The same result was observed with other odors that stimulate other types of olfactory receptor neuron in the maxillary palp. When an antennal olfactory receptor was genetically introduced in the maxillary palp, the fly interpreted a new odor as a sweet-enhancing smell. These results all point to taste enhancement as a function of the maxillary palp. It also opens the door for studying integration of multiple senses in a model organism

Adult Consequences of Late Adolescent Alcohol Consumption: A Systematic Review of Cohort Studies

In a systematic review of cohort studies of adolescent drinking and later outcomes, Jim McCambridge and colleagues show that although studies suggest links to worse adult physical and mental health and social consequences, existing evidence is of poor quality