Changes in diet and physical activity following a community-wide pilot intervention to tackle childhood obesity in a deprived inner-London ward.

BACKGROUND: Local authorities in England have an important role in shaping healthy local environments contributing to childhood obesity. This study examined changes in diet and physical activity in primary school children following a three-year, complex, community-based intervention in Golborne ward, the second most deprived ward in London. METHODS: The Go-Golborne intervention aimed to shape the local environment across multiple settings with the engagement of a large number of local government and community stakeholders in a joint approach. Activities focused on six co-created themes to make changes to local environments and reduce sugary snacks and beverage consumption, increase fruit and vegetable intake, promote healthy snacks, increase active play and travel, and reduce screen time. We analysed changes in self-reported diet and physical activity, collected annually between 2016 and 2019, from 1,650 children aged 6-11 years through six local schools, who all received the intervention. We used multilevel, linear and logistic random-slope regression models adjusted for time on study, baseline age, gender, ethnicity, deprivation quintile, school, and baseline weight status. RESULTS: After three years of follow-up, there were reductions in sugar-sweetened beverage consumption (adjusted beta -0·43 occasions/day, 95% CI -0·55 to -0·32), fruit and vegetable consumption (adjusted beta -0.22 portions, 95% CI -0.44 to 0.001) and car travel to and from school (adjusted OR 0·19, 95% CI 0·06 to 0·66), while screen time increased (high versus moderate/low: OR 2·30, 95% CI 1·36 to 3·90). For other behavioural outcomes, there was no statistically significant evidence of changes. CONCLUSION: Local authorities have substantial powers to make positive changes to the obesogenic environment but programmes remain under-evaluated. Results from the ambitious Go-Golborne intervention demonstrated mixed results in health behaviours following programme implementation. These results underline the importance of a coordinated and comprehensive policy response to support changes in wider environmental and social conditions as well as appropriate and holistic evaluations of initiatives to inform local actions on obesogenic environments.

Olaparib: A Clinically Applied PARP Inhibitor Protects from Experimental Crohn's Disease and Maintains Barrier Integrity by Improving Bioenergetics through Rescuing Glycolysis in Colonic Epithelial Cells.

Crohn's disease (CD) is an inflammatory disorder of the intestines characterized by epithelial barrier dysfunction and mucosal damage. The activity of poly(ADP-ribose) polymerase-1 (PARP-1) is deeply involved in the pathomechanism of inflammation since it leads to energy depletion and mitochondrial failure in cells. Focusing on the epithelial barrier integrity and bioenergetics of epithelial cells, we investigated whether the clinically applied PARP inhibitor olaparib might improve experimental CD. We used the oral PARP inhibitor olaparib in the 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced mouse colitis model. Inflammatory scoring, cytokine levels, colon histology, hematological analysis, and intestinal permeability were studied. Caco-2 monolayer culture was utilized as an epithelial barrier model, on which we used qPCR and light microscopy imaging, and measured impedance-based barrier integrity, FITC-dextran permeability, apoptosis, mitochondrial oxygen consumption rate, and extracellular acidification rate. Olaparib reduced the inflammation score, the concentration of IL-1ß and IL-6, enhanced the level of IL-10, and decreased the intestinal permeability in TNBS-colitis. Blood cell ratios, such as lymphocyte to monocyte ratio, platelet to lymphocyte ratio, and neutrophil to lymphocyte ratio were improved. In H2O2-treated Caco-2 monolayer, olaparib decreased morphological changes, barrier permeability, and preserved barrier integrity. In oxidative stress, olaparib enhanced glycolysis (extracellular acidification rate), and it improved mitochondrial function (mitochondrial coupling efficiency, maximal respiration, and spare respiratory capacity) in epithelial cells. Olaparib, a PARP inhibitor used in human cancer therapy, improved experimental CD and protected intestinal barrier integrity by preventing its energetic collapse; therefore, it could be repurposed for the therapy of Crohn's disease.

Impact of the NHS Health Check on inequalities in cardiovascular disease risk: a difference-in-differences matching analysis.

BACKGROUND: We assessed impacts of a large, nationwide cardiovascular disease (CVD) risk assessment and management programme on sociodemographic group inequalities in (1) early identification of hypertension, type 2 diabetes (T2D) and chronic kidney disease (CKD); and (2) management of global CVD risk among high-risk individuals. METHODS: We obtained retrospective electronic medical records from the Clinical Practice Research Datalink for a randomly selected sample of 138 788 patients aged 40-74 years without known CVD or diabetes, who were registered with 462 practices between 2009 and 2013. We estimated programme impact using a difference-in-differences matching analysis that compared changes in outcome over time between attendees and non-attendees. RESULTS: National Health Service Health Check attendance was 21.4% (29 672/138 788). A significantly greater number of hypertension and T2D incident cases were identified in men than women (eg, an additional 4.02%, 95% CI 3.65% to 4.39%, and 2.08%, 1.81% to 2.35% cases of hypertension in men and women, respectively). A significantly greater number of T2D incident cases were identified among attendees living in the most deprived areas, but no differences were found for hypertension and CKD across socioeconomic groups. No major differences in CVD risk management were observed between sociodemographic subgroups (eg, programme impact on 10-year CVD risk score was -1.13%, -1.48% to -0.78% in male and -1.53%, -2.36% to -0.71% in female attendees). CONCLUSION: During 2009-2013, the programme had low attendance and small overall impacts on early identification of disease and risk management. The age, sex and socioeconomic subgroups appeared to have derived similar level of benefits, leaving existing inequalities unchanged. These findings highlight the importance of population-wide interventions to address inequalities in CVD outcomes.