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Effectiveness and cost-effectiveness of a sustainable obesity prevention programme for preschool children delivered at scale 'HENRY' (Health, Exercise, Nutrition for the Really Young): protocol for the HENRY III cluster randomised controlled trial.
Bryant, M, Burton, W, Collinson, M, Martin, A, Copsey, B, Groves-Williams, D, Foster, A, Willis, TA, Garnett, P, O'Cathain, A
BMJ open. 2024;(3):e081861
Abstract
INTRODUCTION One-fifth of children start school already overweight or living with obesity, with rates disproportionately impacting those living in the most deprived areas. Social, environmental and biological factors contribute to excess weight gain and programmes delivered in early years settings aim to support families to navigate these in order to prevent obesity. One of these programmes (Health, Exercise and Nutrition for the Really Young, HENRY) has been delivered in UK community venues (hereon named 'centres') in high deprivation areas since 2008 and aims to help families to provide a healthy start for their preschool children. We aim to establish the effectiveness and cost-effectiveness of HENRY, including its potential role from a wider systems perspective. METHODS AND ANALYSIS This is a multicentre, open-labelled, two-group, prospective, cluster randomised controlled trial, with cost-effectiveness analysis, systems-based process evaluation and internal pilot. Primary analysis will compare body mass index (BMI) z-score at 12 months in children (n=984) whose parents have attended HENRY to those who have not attended. Secondary outcomes include parent and staff BMI and waist circumference, parenting efficacy, feeding, eating habits, quality of life, resource use and medium term (3 years) BMI z-scores (child and siblings). 82 centres in ~14 local authority areas will be randomised (1:1) to receive HENRY or continue with standard practice. Intention-to-treat analysis will compare outcomes using mixed effects linear regression. Economic evaluation will estimate a within-trial calculation of cost-per unit change in BMI z-score and longer-term trajectories to determine lifelong cost savings (long-term outcomes). A systems process evaluation will explore whether (and how) implementation of HENRY impacts (and is impacted by) the early years obesity system. An established parent advisory group will support delivery and dissemination. ETHICS AND DISSEMINATION Ethical approval has been granted by the University of York, Health Sciences' Research Governance Committee (HSRGC/2022/537/E). Dissemination includes policy reports, community resources, social media and academic outputs. TRIAL REGISTRATION NUMBER ISRCTN16529380.
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A gene regulatory network in Arabidopsis roots reveals features and regulators of the plant response to elevated CO2.
Cassan, O, Pimparé, LL, Dubos, C, Gojon, A, Bach, L, Lèbre, S, Martin, A
The New phytologist. 2023;(3):992-1004
Abstract
The elevation of CO2 in the atmosphere increases plant biomass but decreases their mineral content. The genetic and molecular bases of these effects remain mostly unknown, in particular in the root system, which is responsible for plant nutrient uptake. To gain knowledge about the effect of elevated CO2 on plant growth and physiology, and to identify its regulatory in the roots, we analyzed genome expression in Arabidopsis roots through a combinatorial design with contrasted levels of CO2 , nitrate, and iron. We demonstrated that elevated CO2 has a modest effect on root genome expression under nutrient sufficiency, but by contrast leads to massive expression changes under nitrate or iron deficiencies. We demonstrated that elevated CO2 negatively targets nitrate and iron starvation modules at the transcriptional level, associated with a reduction in high-affinity nitrate uptake. Finally, we inferred a gene regulatory network governing the root response to elevated CO2 . This network allowed us to identify candidate transcription factors including MYB15, WOX11, and EDF3 which we experimentally validated for their role in the stimulation of growth by elevated CO2 . Our approach identified key features and regulators of the plant response to elevated CO2 , with the objective of developing crops resilient to climate change.
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TMPRSS2 is a functional receptor for human coronavirus HKU1.
Saunders, N, Fernandez, I, Planchais, C, Michel, V, Rajah, MM, Baquero Salazar, E, Postal, J, Porrot, F, Guivel-Benhassine, F, Blanc, C, et al
Nature. 2023;(7990):207-214
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Abstract
Four endemic seasonal human coronaviruses causing common colds circulate worldwide: HKU1, 229E, NL63 and OC43 (ref. 1). After binding to cellular receptors, coronavirus spike proteins are primed for fusion by transmembrane serine protease 2 (TMPRSS2) or endosomal cathepsins2-9. NL63 uses angiotensin-converting enzyme 2 as a receptor10, whereas 229E uses human aminopeptidase-N11. HKU1 and OC43 spikes bind cells through 9-O-acetylated sialic acid, but their protein receptors remain unknown12. Here we show that TMPRSS2 is a functional receptor for HKU1. TMPRSS2 triggers HKU1 spike-mediated cell-cell fusion and pseudovirus infection. Catalytically inactive TMPRSS2 mutants do not cleave HKU1 spike but allow pseudovirus infection. Furthermore, TMPRSS2 binds with high affinity to the HKU1 receptor binding domain (Kd 334 and 137 nM for HKU1A and HKU1B genotypes) but not to SARS-CoV-2. Conserved amino acids in the HKU1 receptor binding domain are essential for binding to TMPRSS2 and pseudovirus infection. Newly designed anti-TMPRSS2 nanobodies potently inhibit HKU1 spike attachment to TMPRSS2, fusion and pseudovirus infection. The nanobodies also reduce infection of primary human bronchial cells by an authentic HKU1 virus. Our findings illustrate the various evolution strategies of coronaviruses, which use TMPRSS2 to either directly bind to target cells or prime their spike for membrane fusion and entry.
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Dietary fat restriction affects brain reward regions in a randomized crossover trial.
Darcey, VL, Guo, J, Courville, AB, Gallagher, I, Avery, JA, Simmons, WK, Ingeholm, JE, Herscovitch, P, Martin, A, Hall, KD
JCI insight. 2023;(12)
Abstract
BACKGROUNDWeight-loss diets often target dietary fat or carbohydrates, macronutrients that are sensed via distinct gut-brain pathways and differentially affect peripheral hormones and metabolism. However, the effects of such diet changes on the human brain are unclear. METHODSWe investigated whether selective isocaloric reductions in dietary fat or carbohydrates altered dopamine D2/3 receptor binding potential (D2BP) and neural activity in brain-reward regions in response to visual food cues in 17 inpatient adults with obesity as compared with a eucaloric baseline diet using a randomized crossover design. RESULTSOn the fifth day of dietary fat restriction, but not carbohydrate restriction, both D2BP and neural activity to food cues were decreased in brain-reward regions. After the reduced-fat diet, ad libitum intake shifted toward foods high in both fat and carbohydrates. CONCLUSIONThese results suggest that dietary fat restriction increases tonic dopamine in brain-reward regions and affects food choice in ways that may hamper diet adherence. TRIAL REGISTRATIONClinicalTrials.gov NCT00846040 FUNDING. NIDDK 1ZIADK013037.
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Protocol to evaluate the effectiveness and cost-effectiveness of an environmental nutrition and physical activity intervention in nurseries (Nutrition and Physical Activity Self Assessment for Child Care - NAP SACC UK): a multicentre cluster randomised controlled trial.
Kipping, R, Pallan, M, Hannam, K, Willis, K, Dobell, A, Metcalfe, C, Jago, R, Johnson, L, Langford, R, Martin, CK, et al
Research square. 2023
Abstract
UNLABELLED Background One in seven UK children have obesity when starting school, with higher prevalence associated with deprivation. Most pre-school children do not meet UK recommendations for physical activity and nutrition. Formal childcare settings provide opportunities to deliver interventions to improve nutritional quality and physical activity to the majority of 3-4-year-olds. The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA with high acceptability in the UK. The study aims to evaluate the effectiveness and cost-effectiveness of the NAP SACC UK intervention to increase physical activity, reduce sedentary time and improve nutritional intake. Methods Multi-centre cluster RCT with process and economic evaluation. Participants are children aged 2 years or over, attending UK early years settings (nurseries) for ≥ 12 hours/week or ≥ 15 hours/week during term time and their parents, and staff at participating nurseries. The 12-month intervention involves nursery managers working with a Partner (public health practitioner) to self-assess policies and practices relating to physical activity and nutrition; nursery staff attending one physical activity and one nutrition training workshop and setting goals to be achieved within six months. The Partner provides support and reviews progress. Nursery staff receive a further workshop and new goals are set, with Partner support for a further six months. The comparator is usual practice. Up to 56 nurseries will be stratified by area and randomly allocated to intervention or comparator arm with minimisation of differences in level of deprivation. PRIMARY OUTCOMES accelerometer-assessed mean total activity time on nursery days and average total energy (kcal) intake per eating occasion of lunch and morning/afternoon snacks consumed within nurseries. SECONDARY OUTCOMES accelerometer-assessed mean daily minutes of moderate-to-vigorous physical activity and sedentary time per nursery day, total physical activity on nursery days compared to non-nursery days, average serving size of lunch and morning/afternoon snacks in nursery per day, average percentage of core and non-core food in lunch and morning/afternoon snacks, zBMI, proportion of children who are overweight/obese and child quality-of-life. A process evaluation will examine fidelity, acceptability, sustainability and context. An economic evaluation will compare costs and consequences from the perspective of the local government, nursery and parents. TRIAL REGISTRATION ISRCTN33134697.
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Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study.
Sarici, K, Yordi, S, Martin, A, Lunasco, L, Mugnaini, C, Chu, K, Moini, H, Vitti, R, Srivastava, SK, Ehlers, JP
Ophthalmology. Retina. 2023;(6):543-552
Abstract
OBJECTIVE The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. DESIGN This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). SUBJECTS Subjects with DME that underwent UWFA across all treatment groups (n = 44). METHODS A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. MAIN OUTCOME MEASURES Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. RESULTS Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. CONCLUSIONS Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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Protocol to evaluate the effectiveness and cost-effectiveness of an environmental nutrition and physical activity intervention in nurseries (Nutrition and Physical Activity Self Assessment for Child Care - NAP SACC UK): a multicentre cluster randomised controlled trial.
Kipping, R, Pallan, M, Hannam, K, Willis, K, Dobell, A, Metcalfe, C, Jago, R, Johnson, L, Langford, R, Martin, CK, et al
BMC public health. 2023;(1):1475
Abstract
BACKGROUND One in seven UK children have obesity when starting school, with higher prevalence associated with deprivation. Most pre-school children do not meet UK recommendations for physical activity and nutrition. Formal childcare settings provide opportunities to deliver interventions to improve nutritional quality and physical activity to the majority of 3-4-year-olds. The nutrition and physical activity self-assessment for childcare (NAP SACC) intervention has demonstrated effectiveness in the USA with high acceptability in the UK. The study aims to evaluate the effectiveness and cost-effectiveness of the NAP SACC UK intervention to increase physical activity, reduce sedentary time and improve nutritional intake. METHODS Multi-centre cluster RCT with process and economic evaluation. Participants are children aged 2 years or over, attending UK early years settings (nurseries) for ≥ 12 h/week or ≥ 15 h/week during term time and their parents, and staff at participating nurseries. The 12-month intervention involves nursery managers working with a Partner (public health practitioner) to self-assess policies and practices relating to physical activity and nutrition; nursery staff attending one physical activity and one nutrition training workshop and setting goals to be achieved within 6 months. The Partner provides support and reviews progress. Nursery staff receive a further workshop and new goals are set, with Partner support for a further 6 months. The comparator is usual practice. Up to 56 nurseries will be stratified by area and randomly allocated to intervention or comparator arm with minimisation of differences in level of deprivation. PRIMARY OUTCOMES accelerometer-assessed mean total activity time on nursery days and average total energy (kcal) intake per eating occasion of lunch and morning/afternoon snacks consumed within nurseries. SECONDARY OUTCOMES accelerometer-assessed mean daily minutes of moderate-to-vigorous physical activity and sedentary time per nursery day, total physical activity on nursery days compared to non-nursery days, average serving size of lunch and morning/afternoon snacks in nursery per day, average percentage of core and non-core food in lunch and morning/afternoon snacks, zBMI, proportion of children who are overweight/obese and child quality-of-life. A process evaluation will examine fidelity, acceptability, sustainability and context. An economic evaluation will compare costs and consequences from the perspective of the local government, nursery and parents. TRIAL REGISTRATION ISRCTN33134697, 31/10/2019.
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Development of the Canadian Eating Practices Screener to assess eating practices based on 2019 Canada's Food Guide recommendations.
Wallace, A, Martin, A, Bédard, A, Pitre, C, Lemieux, S, Simpson, JR, Kirkpatrick, SI, Hutchinson, JM, Williams, TE, Westaway, AM, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2023;(12):907-918
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Abstract
In 2019, Health Canada released a new iteration of Canada's Food Guide (2019-CFG), which, for the first time, highlighted recommendations regarding eating practices, i.e., guidance on where, when, why, and how to eat. The objective of this study was to develop a brief self-administered screener to assess eating practices recommended in the 2019-CFG among adults aged 18-65 years. Development of the screener items was informed by a review of existing tools and mapping of items onto 2019-CFG recommendations. Face and content validity were assessed with experts in public health nutrition and/or dietary assessment (n = 16) and individuals from Government of Canada (n = 14). Cognitive interviews were conducted with English-speaking (n = 16) and French-speaking (n = 16) adults living in Canada to assess face validity and understanding of the screener items. While some modifications were identified to improve relevance or clarity, overall, the screener items were found to be relevant, well-constructed, and clearly worded. This comprehensive process resulted in the Canadian Eating Practices Screener/Questionnaire court canadien sur les pratiques alimentaires, which includes 21 items that assess eating practices recommended in the 2019-CFG. This screener can facilitate monitoring and surveillance efforts of the 2019-CFG eating practices as well as research exploring how these practices are associated with various health outcomes.
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The decline of plant mineral nutrition under rising CO2: physiological and molecular aspects of a bad deal.
Gojon, A, Cassan, O, Bach, L, Lejay, L, Martin, A
Trends in plant science. 2023;(2):185-198
Abstract
The elevation of atmospheric CO2 concentration has a strong impact on the physiology of C3 plants, far beyond photosynthesis and C metabolism. In particular, it reduces the concentrations of most mineral nutrients in plant tissues, posing major threats on crop quality, nutrient cycles, and carbon sinks in terrestrial agro-ecosystems. The causes of the detrimental effect of high CO2 levels on plant mineral status are not understood. We provide an update on the main hypotheses and review the increasing evidence that, for nitrogen, this detrimental effect is associated with direct inhibition of key mechanisms of nitrogen uptake and assimilation. We also mention promising strategies for identifying genotypes that will maintain robust nutrient status in a future high-CO2 world.
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Management of Dyslipidemia in Patients with Non-Alcoholic Fatty Liver Disease.
Martin, A, Lang, S, Goeser, T, Demir, M, Steffen, HM, Kasper, P
Current atherosclerosis reports. 2022;(7):533-546
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PURPOSE OF REVIEW Patients with non-alcoholic fatty liver disease (NAFLD), often considered as the hepatic manifestation of the metabolic syndrome, represent a population at high cardiovascular risk and frequently suffer from atherogenic dyslipidemia. This article reviews the pathogenic interrelationship between NAFLD and dyslipidemia, elucidates underlying pathophysiological mechanisms and focuses on management approaches for dyslipidemic patients with NAFLD. RECENT FINDINGS Atherogenic dyslipidemia in patients with NAFLD results from hepatic and peripheral insulin resistance along with associated alterations of hepatic glucose and lipoprotein metabolism, gut dysbiosis, and genetic factors. Since atherogenic dyslipidemia and NAFLD share a bi-directional relationship and are both major driving forces of atherosclerotic cardiovascular disease (ASCVD) development, early detection and adequate treatment are warranted. Thus, integrative screening and management programs are urgently needed. A stepwise approach for dyslipidemic patients with NAFLD includes (i) characterization of dyslipidemia phenotype, (ii) individual risk stratification, (iii) definition of treatment targets, (iv) lifestyle modification, and (v) pharmacotherapy if indicated.