The Loozit(®) Study is a randomised controlled trial investigating extended support in a 24 month community-based weight management program for overweight to moderately obese, but otherwise healthy, 13 to 16 year olds.

Low levels of physical activity are a major public health concern, and interventions to promote physical activity have had limited success. Whether or not personalised feedback about physical activity following objective measurement motivates behaviour change has yet to be rigorously examined.

Correlates of physical activity (PA) are hypothesized to be context and behaviour specific, but there is limited evidence of this in young children. The aim of the current study is to investigate associations between personal, social and environmental factors and objectively measured light and moderate-to-vigorous PA (LPA and MVPA, respectively) in four-year-old children.

Type 2 diabetes (T2D) is associated with increased risk of morbidity and premature mortality. Among those at high risk, incidence can be halved through healthy changes in behaviour. Information about genetic and phenotypic risk of T2D is now widely available. Whether such information motivates behaviour change is unknown. We aim to assess the effects of communicating genetic and phenotypic risk of T2D on risk-reducing health behaviours, anxiety, and other cognitive and emotional theory-based antecedents of behaviour change.

To examine the effect on cardiovascular (CVD) risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes.

The genetic bases for most human sleep disorders and for variation in human sleep quantity and quality are largely unknown. Using the zebrafish, a diurnal vertebrate, to investigate the genetic regulation of sleep, we found that epidermal growth factor receptor (EGFR) signaling is necessary and sufficient for normal sleep levels and is required for the normal homeostatic response to sleep deprivation. We observed that EGFR signaling promotes sleep via mitogen-activated protein kinase/extracellular signal-regulated kinase and RFamide neuropeptide signaling and that it regulates RFamide neuropeptide expression and neuronal activity. Consistent with these findings, analysis of a large cohort of human genetic data from participants of European ancestry revealed that common variants in genes within the EGFR signaling pathway are associated with variation in human sleep quantity and quality. These results indicate that EGFR signaling and its downstream pathways play a central and ancient role in regulating sleep and provide new therapeutic targets for sleep disorders.

Negative affect is shown consistently to promote unhealthy food choices and dietary intake in laboratory studies. However, this relationship in naturalistic settings is less clear and previous research is limited by dietary assessment methodology and neglects to account for several important moderating variables. This observational study aimed to examine the association of negative affect and other psychological factors associated with eating behaviour simultaneously with discretionary energy intake and total energy intake, and whether these were moderated by emotional eating predisposition or age, sex and weight status.

Few trial data are available concerning the impact of personalised cancer risk information on behaviour. This study assessed the short-term effects of providing personalised cancer risk information on cancer risk beliefs and self-reported behaviour. We randomised 1018 participants, recruited through the online platform Prolific, to either a control group receiving cancer-specific lifestyle advice or one of three intervention groups receiving their computed 10-year risk of developing one of the five most common preventable cancers either as a bar chart, a pictograph or a qualitative scale alongside the same lifestyle advice. The primary outcome was change from baseline in computed risk relative to an individual with a recommended lifestyle (RRI)1 at three months. Secondary outcomes included: health-related behaviours, risk perception, anxiety, worry, intention to change behaviour, and a newly defined concept, risk conviction. After three months there were no between-group differences in change in RRI (p = 0.71). At immediate follow-up, accuracy of absolute risk perception (p < 0.001), absolute and comparative risk conviction (p < 0.001) and intention to increase fruit and vegetables (p = 0.026) and decrease processed meat (p = 0.033) were higher in all intervention groups relative to the control group. The increases in accuracy and conviction were only seen in individuals with high numeracy and low baseline conviction, respectively. These findings suggest that personalised cancer risk information alongside lifestyle advice can increase short-term risk accuracy and conviction without increasing worry or anxiety but has little impact on health-related behaviour. Trial registration: ISRCTN17450583. Registered 30 January 2018.

Emerging health care strategies addressing medication adherence include the use of direct-to-patient incentives or elements adapted from computer games. However, there is currently no published evidence synthesis on the use of gamification or financial incentives in mobile apps to improve medication adherence.

Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health conditions.

This systematic review examined change in eating disorder risk during weight management interventions. Four databases and clinical trials registries were searched in March and May 2022, respectively, to identify behavioral weight management intervention trials in adults with overweight/obesity measuring eating disorder symptoms at pre- and post-intervention or follow-up. Random effects meta-analyses were conducted examining within group change in risk. Of 12,023 screened, 49 were eligible (n = 6337, mean age range 22.1 to 59.9 years, mean (SD) 81(20.4)% female). Interventions ranged from 4 weeks to 18 months, with follow-up of 10 weeks to 36 months post-intervention. There was a within group reduction in global eating disorder scores (20 intervention arms; Hedges' g = -0.27; 95% CI -0.36, -0.17; I2 67.1%) and binge eating (49 intervention arms; -0.66; 95% CI -0.76, -0.56; I2 82.7%) post-intervention, both maintained at follow-up. Of 14 studies reporting prevalence or episodes of binge eating, all reported a reduction. Four studies reported eating disorder symptoms, not present at baseline, in a subset of participants (0%-6.5%). Overall, behavioral weight management interventions do not increase eating disorder symptoms for most adults; indeed, a modest reduction is seen post-intervention and follow-up. A small subset of participants may experience disordered eating; therefore, monitoring for the emergence of symptoms is important.

Single-cell RNA sequencing (scRNA-seq) offers a high-resolution molecular view into complex tissues, but suffers from high levels of technical noise which frustrates efforts to compare the gene expression programs of different cell types. "Spike-in" RNA standards help control for technical variation in scRNA-seq, but using them with recently developed, ultra-scalable scRNA-seq methods based on combinatorial indexing is not feasible. Here, we describe a simple and cost-effective method for normalizing transcript counts and subtracting technical variability that improves differential expression analysis in scRNA-seq. The method affixes a ladder of synthetic single-stranded DNA oligos to each cell that appears in its RNA-seq library. With improved normalization we explore chemical perturbations with broad or highly specific effects on gene regulation, including RNA pol II elongation, histone deacetylation, and activation of the glucocorticoid receptor. Our methods reveal that inhibiting histone deacetylation prevents cells from executing their canonical program of changes following glucocorticoid stimulation.

There is a growing interest in the effects of ultra-processed/energy-dense nutrient-poor foods on health outcomes, and few interventions to reduce their consumption have been tested. We tested a simple intervention to help people reduce the indulgences they consume (energy-dense nutrient-poor (EDNP) foods). Herein, we report the qualitative findings to understand how participants reduced their consumption by exploring intervention fidelity and the factors affecting consumption. We conducted a qualitative descriptive study of 23 adults who had taken part in a feasibility randomised controlled trial that asked participants to say no to seven indulgences/week and record what they said no to. Data were collected using face-to-face semi-structured interviews and analysed thematically. A total of 23 adults with an average BMI of 30.8 kg/m2 took part. Participants liked the term indulgence, as they could apply it to their normal dietary intake and make small changes. They found self-monitoring what they said no to helpful and reported that emotional eating and habits affected consumption. They had difficulty overcoming these. As most people are consuming too many foods that are EDNP, this simple intervention of "Say No" seven times/week has the potential to be developed as a public health campaign.

It is important to identify whether behavioural weight management interventions work well across different groups in the population so health inequalities in obesity are not widened. Previous systematic reviews of inequalities in the attendance and effectiveness of behavioural weight management interventions have been limited because few trials report relevant analyses and heterogeneity in the categorisation of inequality characteristics prevents meta-analysis. An individual participant data meta-analysis (IPD-MA) allows us to reanalyse all trials with available data in a uniform way. We aim to conduct an IPD meta-analysis of UK randomised controlled trials to examine whether there are inequalities in the attendance and effectiveness of behavioural weight interventions.

Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.

Sedentary time increases and total physical activity decreases with age. The magnitude and correlates of changes in sedentary time, light-intensity physical activity (LPA), moderate-to-vigorous intensity physical activity (MVPA), and overall physical activity remain unclear. We quantified these changes and identified their individual and sociodemographic correlates.

Alcohol drinking, in some individuals, culminates in pathologically aggressive and violent behaviors. Alcohol can escalate the urge to fight, despite causing disruptions in fighting performance. When orally administered under several dosing conditions the current study examined in a mouse model if repeated alcohol escalates the motivation to fight, the execution of fighting performance, or both. Specifically, seven daily administrations of alcohol (0, 1.8, or 2.2 g/kg) determined if changes in the motivation to initiate aggressive acts occur with, or without, shifts in the severity of fighting behavior. Responding under the control of a fixed interval (FI) schedule for aggression reinforcements across the initial daily sessions indicated the development of tolerance to alcohol's sedative effect. By day 7, alcohol augmented FI response rates for aggression rewards. While alcohol escalated the motivation to fight, fighting performance remained suppressed across the entire 7 days. Augmented FI responding for aggression rewards in response to a low dose of alcohol (1.0 g/kg) proved to be persistent, as we observed sensitized rates of responding for more than a month after alcohol pretreatment. In addition, this sensitization of motivated aggression did not occur with a general enhancement of motor activity. Antagonism of NMDA or AMPA receptors with ketamine, dizocilpine, or NBQX during later challenges with alcohol were largely serenic without having any notable impact on the expression of alcohol-escalated rates of FI responding. The current dissociation of appetitive and performance measures indicates that discrete neural mechanisms controlling aggressive arousal can be distinctly sensitized by alcohol.

Mammalian organogenesis is a remarkable process. Within a short timeframe, the cells of the three germ layers transform into an embryo that includes most of the major internal and external organs. Here we investigate the transcriptional dynamics of mouse organogenesis at single-cell resolution. Using single-cell combinatorial indexing, we profiled the transcriptomes of around 2 million cells derived from 61 embryos staged between 9.5 and 13.5 days of gestation, in a single experiment. The resulting 'mouse organogenesis cell atlas' (MOCA) provides a global view of developmental processes during this critical window. We use Monocle 3 to identify hundreds of cell types and 56 trajectories, many of which are detected only because of the depth of cellular coverage, and collectively define thousands of corresponding marker genes. We explore the dynamics of gene expression within cell types and trajectories over time, including focused analyses of the apical ectodermal ridge, limb mesenchyme and skeletal muscle.

There is limited evidence on the prospective association of time spent in activity intensity (sedentary (SED), moderate (MPA) or vigorous (VPA) physical activity) and dietary intake with adiposity indicators in young people. This study aimed to assess associations between (1) baseline objectively measured activity intensity, dietary energy density (DED) and 4-year change in adiposity and (2) 4-year change in activity intensity/DED and adiposity at follow-up. We conducted cohort analyses including 367 participants (10 years at baseline, 14 years at follow-up) with valid data for objectively measured activity (Actigraph), DED (4-d food diary), anthropometry (waist circumference (WC), %body fat (%BF), fat mass index (FMI), weight status) and covariates. Linear and logistic regression models were fit, including adjustment for DED and moderate-to-vigorous physical activity. Results showed that baseline DED was associated with change in WC (β for 1kJ/g difference: 0·71; 95% CI 0·26, 1·17), particularly in boys (1·26; 95% CI 0·41, 2·16 v. girls: 0·26; 95% CI -0·34, 0·87), but not with %BF, FMI or weight status. In contrast, baseline SED, MPA or VPA were not associated with any of the outcomes. Change in DED was negatively associated with FMI (β for 1kJ/g increase: -0·86; 95% CI -1·59, -0·12) and %BF (-0·86; 95% CI -1·25, -0·11) but not WC (-0·27; 95% CI -1·02, 0·48). Change in SED, MPA and VPA did not predict adiposity at follow-up. In conclusion, activity intensity was not prospectively associated with adiposity, whereas the directions of associations with DED were inconsistent. To inform public health efforts, future studies should continue to analyse longitudinal data to further understand the independent role of different energy-balance behaviours in changes in adiposity in early adolescence.

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis.