Correlates of physical activity and sedentary time in young adults: The Western Australian Pregnancy Cohort (Raine) Study

Background: The socioecological model proposes a wide array of factors that influence behaviours. There is a need to understand salient correlates of these activity behaviours in a specific population. However, few studies identified socio-demographic, behavioural, physical, and psychological correlates of objectively-assessed physical activity and sedentary time in young adults. Methods: This was a cross-sectional analysis of participants in the Raine Study (a pregnancy cohort started in 1989). Australian young adults (mean 22.1 years ± SD 0.6) wore Actigraph GT3X+ accelerometers on the hip 24 h/day for seven days to assess moderate-to-vigorous physical activity (MVPA) and sedentary time (n = 256 women, n = 219 men). Potential correlates were assessed via clinical assessment and questionnaire and included socio-demographic variables (ethnicity, relationship status, work/study status, education, mothers education), health behaviours (food intake, alcohol consumption, smoking status, sleep quality), and physical and psychological health aspects (anthropometrics, diagnosed disorders, mental health, cognitive performance). Backwards elimination (p < 0.2 for retention) with mixed model regressions were used and the gender-stratified analyses were adjusted for demographic variables, waking wear time and number of valid days. Results: Increased time spent in MVPA was associated with: being single (IRR 1.44 vs in a relationship living together, 95%CI: 1.17, 1.77, p =.001) in women; and better sleep quality in men (lower scores better IRR 0.97, 95%CI: 0.93, 1.00). Less time spent sedentary was associated with: lower mother's education (- 32.1 min/day, 95%CI -52.9, 11.3, p = 0.002 for having mother with no university degree vs at least a baccalaureate degree) and smoking (- 44.3 min/day, 95%CI: - 72.8, - 15.9, p =.0002) for women; lower education status (- 32.1 min/day, 95%CI: -59.5, - 4.8, p = 0.021 for having no university degree vs at least a baccalaureate degree) and lower depression scores in men (- 2.0, 95%CI: - 3.5, - 0.4, p = 0.014); more alcoholic drinks per week for women (- 1.9 min/day, 95%CI: -3.1, - 0.6, p = 0.003) and men (- 1.0, 95%CI: -1.8, - 0.3, p = 0.007). Conclusions: Less desirable correlates were associated with positive levels of activity in young Australian adult women and men. Interventions to increase MVPA and decrease sedentary activity in young adults need to specifically consider the life stage of young adults

Neuroendocrine and neurotrophic signaling in Huntington\u27s disease: Implications for pathogenic mechanisms and treatment strategies

Huntington\u27s disease (HD) is a fatal neurodegenerative disease caused by an extended polyglutamine tract in the huntingtin protein. Circadian, sleep and hypothalamic-pituitary-adrenal (HPA) axis disturbances are observed in HD as early as 15 years before clinical disease onset. Disturbances in these key processes result in increased cortisol and altered melatonin release which may negatively impact on brain-derived neurotrophic factor (BDNF) expression and contribute to documented neuropathological and clinical disease features. This review describes the normal interactions between neurotrophic factors, the HPA-axis and circadian rhythm, as indicated by levels of BDNF, cortisol and melatonin, and the alterations in these intricately balanced networks in HD. We also discuss the implications of these alterations on the neurobiology of HD and the potential to result in hypothalamic, circadian, and sleep pathologies. Measurable alterations in these pathways provide targets that, if treated early, may reduce degeneration of brain structures. We therefore focus here on the means by which multidisciplinary therapy could be utilised as a non-pharmaceutical approach to restore the balance of these pathways

Immune function during early adolescence positively predicts adult facial sexual dimorphism in both men and women

Evolutionary theories suggest that humans prefer sexual dimorphism in faces because masculinity in men and femininity in women may be an indicator of immune function during development. In particular, the immunocompetence handicap hypothesis proposes that sexual dimorphism indicates good immune function during development because the sex hormones, particularly testosterone in men, required for the development of sexually dimorphic facial features also taxes the immune system. Therefore, only healthy males can afford the high level of testosterone for the development of sexually dimorphic traits without compromising their survival. Researchers have suggested that a similar mechanism via the effects of oestrogen might also explain male preferences for female femininity. Despite the prominence of the immunocompetence handicap hypothesis, no studies have tested whether immune function during development predicts adult facial sexual dimorphism. Here, using data from a longitudinal public health dataset, the Western Australian Pregnancy Cohort (Raine) Study (Generation 2), we show that some aspects of immune function during early adolescence (14 years) positively predict sexually dimorphic 3D face shape in both men and women. Our results support a fundamental assumption that facial sexual dimorphism is an indicator of immune function during the development of facial sexual dimorphism.PostprintPeer reviewe

Protocol of the PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusions

Introduction: Pleural effusion is a common clinical problem that can complicate many medical conditions. Breathlessness is the most common symptom of pleural effusion of any cause and the most common reason for pleural drainage. However, improvement in breathlessness following drainage of an effusion is variable; some patients experience either no benefit or a worsening of their breathlessness. The physiological mechanisms underlying breathlessness in patients with a pleural effusion are unclear and likely to be multifactorial with patient-related and effusion-related factors contributing. A comprehensive study of the physiological and symptom responses to drainage of pleural effusions may provide a clearer understanding of these mechanisms, and may identify predictors of benefit from drainage. The ability to identify those patients whose breathlessness will (or will not) improve after pleural fluid drainage can help avoid unnecessary pleural drainage procedures, their associated morbidities and costs. The PLeural Effusion And Symptom Evaluation (PLEASE) study is a prospective study to comprehensively evaluate factors contributing to pleural effusion-related breathlessness. Methods and analysis: The PLEASE study is a single-centre prospective study of 150 patients with symptomatic pleural effusions that require therapeutic drainage. The study aims to identify key factors that underlie breathlessness in patients with pleural effusions and develop predictors of improvement in breathlessness following effusion drainage. Participants will undergo evaluation pre-effusion and post-effusion drainage to assess their level of breathlessness at rest and during exercise, respiratory and other physiological responses as well as respiratory muscle mechanics. Pre-drainage and post-drainage parameters will be collected and compared to identify the key factors and mechanisms that correlate with improvement in breathlessness. Ethics and dissemination: Approved by the Sir Charles Gairdner Group Human Research Ethics Committee (HREC number 2014-079). Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000820404). Results will be published in peer-reviewed journals and presented at scientific meetings

Childhood sleep health and epigenetic age acceleration in late adolescence: Cross-sectional and longitudinal analyses

Aim: Investigate if childhood measures of sleep health are associated with epigenetic age acceleration in late adolescence. Methods: Parent-reported sleep trajectories from age 5 to 17, self-reported sleep problems at age 17, and six measures of epigenetic age acceleration at age 17 were studied in 1192 young Australians from the Raine Study Gen2. Results: There was no evidence for a relationship between the parent-reported sleep trajectories and epigenetic age acceleration (p ≥ 0.17). There was a positive cross-sectional relationship between self-reported sleep problem score and intrinsic epigenetic age acceleration at age 17 (b = 0.14, p = 0.04), which was attenuated after controlling for depressive symptom score at the same age (b = 0.08, p = 0.34). Follow-up analyses suggested this finding may represent greater overtiredness and intrinsic epigenetic age acceleration in adolescents with higher depressive symptoms. Conclusion: There was no evidence for a relationship between self- or parent-reported sleep health and epigenetic age acceleration in late adolescence after adjusting for depressive symptoms. Mental health should be considered as a potential confounding variable in future research on sleep and epigenetic age acceleration, particularly if subjective measures of sleep are used

Health behaviour profiles in young Australian adults in relation to physical and mental health: The Raine study

Issues Addressed: We aimed to identify latent health behaviour profiles of young adults and examine their associations with physical and mental health outcomes. We also characterised the profiles by socio-demographic characteristics. Methods: Data were collected between 2012 and 2014. Participants (N = 476) were young adults (M age [SD] = 22.1 [.57] years) from Generation 2 of the Raine Study longitudinal cohort. Health behaviours were measured via ActiGraph GT3X waist monitors (physical activity, sedentary behaviour) and questionnaires (diet quality, alcohol, smoking and sleep). Physical and mental health were measured using clinical health assessments, blood biomarkers, and questionnaires. Latent Profile Analysis using Mplus (8.2) was employed to identify profiles. Results: Four latent profiles were identified: ‘heavy drinkers with moderately unhealthy eating habits’ (high takeaway foods; n = 135), ‘unhealthy food abstainers’ (low takeaway foods; n = 138), ‘moderately sedentary alcohol abstainers’ (n = 139) and ‘physically active drinkers with unhealthy eating habits’ (high takeaway foods and sugary drinks; n = 64). ‘Physically active drinkers with unhealthy eating habits’ had the poorest (physical and mental) health outcomes, yet the lowest insulin resistance. ‘Unhealthy food abstainers’ had the most favourable health outcomes (adiposity, health perceptions, blood pressure). Sex differed among the profiles. Conclusions: The profiles identified among young adults are different to profiles with general adult populations. A novel finding was that ‘physically active drinkers with unhealthy eating habits’ had low insulin resistance. The findings also suggest that future interventions may need to be sex specific. So What: Our findings suggest that health behaviour interventions for young adults should be targeted to distinct profile characteristics

Ground-based walking training improves quality of life and exercise capacity in COPD

This study was designed to determine the effect of ground-based walking training on health-related quality of life and exercise capacity in people with chronic obstructive pulmonary disease (COPD). People with COPD were randomised to either a walking group that received supervised, ground-based walking training two to three times a week for 8–10 weeks, or a control group that received usual medical care and did not participate in exercise training. 130 out of 143 participants (mean±SD age 69±8 years, forced expiratory volume in 1 s 43±15% predicted) completed the study. Compared to the control group, the walking group demonstrated greater improvements in the St George’s Respiratory Questionnaire total score (mean difference -6 points (95% CI -10– -2), p<0.003), Chronic Respiratory Disease Questionnaire total score (mean difference 7 points (95% CI 2–11), p<0.01) and endurance shuttle walk test time (mean difference 208 s (95% CI 104–313), p<0.001). This study shows that ground-based walking training is an effective training modality that improves quality of life and endurance exercise capacity in people with COPD

Sex-specific variation in facial masculinity/femininity associated with autistic traits in the general population

Reports linking prenatal testosterone exposure to autistic traits and to a masculinized face structure have motivated research investigating whether autism is associated with facial masculinization. This association has been reported with greater consistency for females than for males, in studies comparing groups with high and low levels of autistic traits. In the present study, we conducted two experiments to examine facial masculinity/femininity in 151 neurotypical adults selected for either low, mid-range, or high levels of autistic traits. In the first experiment, their three-dimensional facial photographs were subjectively rated by 41 raters for masculinity/femininity and were objectively analysed. In the second experiment, we generated 6-face composite images, which were rated by another 36 raters. Across both experiments, findings were consistent for ratings of photographs and composite images. For females, a linear relationship was observed where femininity ratings decreased as a function of higher levels of autistic traits. For males, we found a U-shaped function where males with mid-range levels of traits were rated lowest on masculinity. Objective facial analyses revealed that higher levels of autistic traits were associated with less feminine facial structures in females and less masculine structures in males. These results suggest sex-specific relationships between autistic traits and facial masculinity/femininity

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Synthesis of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) derivatives functionalised with two, four or eight hydroxyl groups

Short synthetic routes to a range of BEDT-TTF derivatives functionalised with two, four or eight hydroxyl groups are reported, of interest because of their potential for introducing hydrogen bonding between donor and anion into their radical cation salts. The cycloaddition of 1,3-dithiole-2,4,5-trithione with alkenes to construct 5,6-dihydro-1,3-dithiolo[4,5-b]1,4-dithiin-2-thiones is a key step, with homo- or hetero-coupling procedures and O-deprotection completing the syntheses. The first synthesis of a single diastereomer of tetrakis(hydroxymethyl)BEDT-TTF, the cis, trans product, was achieved by careful choice of O-protecting groups to facilitate separation of homo- and hetero-coupled products. Cyclisation of the trithione with enantiopure 1R,2R,5R,6R-bis(O,O-isopropylidene)hex-3-ene-1,2,5,6-tetrol (from D-mannitol) gave two separable diastereomeric thiones, which can be transformed to enantiomeric BEDT-TTF derivatives with four or eight hydroxyl groups