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1.
Hypoxia-Inducible Factor Signaling in Inflammatory Lung Injury and Repair.
Evans, CE
Cells. 2022;(2)
Abstract
Inflammatory lung injury is characterized by lung endothelial cell (LEC) death, alveolar epithelial cell (AEC) death, LEC-LEC junction weakening, and leukocyte infiltration, which together disrupt nutrient and oxygen transport. Subsequently, lung vascular repair is characterized by LEC and AEC regeneration and LEC-LEC junction re-annealing, which restores nutrient and oxygen delivery to the injured tissue. Pulmonary hypoxia is a characteristic feature of several inflammatory lung conditions, including acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19). The vascular response to hypoxia is controlled primarily by the hypoxia-inducible transcription factors (HIFs) 1 and 2. These transcription factors control the expression of a wide variety of target genes, which in turn mediate key pathophysiological processes including cell survival, differentiation, migration, and proliferation. HIF signaling in pulmonary cell types such as LECs and AECs, as well as infiltrating leukocytes, tightly regulates inflammatory lung injury and repair, in a manner that is dependent upon HIF isoform, cell type, and injury stimulus. The aim of this review is to describe the HIF-dependent regulation of inflammatory lung injury and vascular repair. The review will also discuss potential areas for future study and highlight putative targets for inflammatory lung conditions such as ALI/ARDS and severe COVID-19. In the development of HIF-targeted therapies to reduce inflammatory lung injury and/or enhance pulmonary vascular repair, it will be vital to consider HIF isoform- and cell-specificity, off-target side-effects, and the timing and delivery strategy of the therapeutic intervention.
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Understanding the science of portion control and the art of downsizing.
Hetherington, MM, Blundell-Birtill, P, Caton, SJ, Cecil, JE, Evans, CE, Rolls, BJ, Tang, T
The Proceedings of the Nutrition Society. 2018;(3):347-355
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Offering large portions of high-energy-dense (HED) foods increases overall intake in children and adults. This is known as the portion size effect (PSE). It is robust, reliable and enduring. Over time, the PSE may facilitate overeating and ultimately positive energy balance. Therefore, it is important to understand what drives the PSE and what might be done to counter the effects of an environment promoting large portions, especially in children. Explanations for the PSE are many and diverse, ranging from consumer error in estimating portion size to simple heuristics such as cleaning the plate or eating in accordance with consumption norms. However, individual characteristics and hedonic processes influence the PSE, suggesting a more complex explanation than error or heuristics. Here PSE studies are reviewed to identify interventions that can be used to downsize portions of HED foods, with a focus on children who are still learning about social norms for portion size. Although the scientific evidence for the PSE is robust, there is still a need for creative downsizing solutions to facilitate portion control as children and adolescents establish their eating habits.
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Glycemic index, glycemic load, and blood pressure: a systematic review and meta-analysis of randomized controlled trials.
Evans, CE, Greenwood, DC, Threapleton, DE, Gale, CP, Cleghorn, CL, Burley, VJ
The American journal of clinical nutrition. 2017;(5):1176-1190
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Background: High blood pressure is a strong risk factor for cardiovascular disease.Objective: The aim of this study was to determine the associations of dietary glycemic index (GI) and glycemic load (GL) with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in healthy individuals.Design: A systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out. Databases were searched for eligible RCTs in 2 phases. MEDLINE, Embase, CAB Abstracts, BIOSIS, ISI Web of Science, and the Cochrane Library were searched from January 1990 to December 2009. An updated search was undertaken with the use of MEDLINE and Embase from January 2010 to September 2016. Trials were included if they reported author-defined high- and low-GI or -GL diets and blood pressure, were of ≥6 wk duration, and comprised healthy participants without chronic conditions. Data were extracted and analyzed with the use of Stata statistical software. Pooled estimates and 95% CIs were calculated with the use of weighted mean differences and random-effects models.Results: Data were extracted from 14 trials comprising 1097 participants. Thirteen trials provided information on differences in GI between control and intervention arms. A median reduction in GI of 10 units reduced the overall pooled estimates for SBP and DBP by 1.1 mm Hg (95% CI: -0.3, 2.5 mm Hg; P = 0.11) and 1.3 mm Hg (95% CI: 0.2 mm Hg, 2.3; P = 0.02), respectively. Nine trials reported information on differences in GL between arms. A median reduction in GL of 28 units reduced the overall pooled estimates for SBP and DBP by 2.0 mm Hg (95% CI: 0.2, 3.8 mm Hg; P = 0.03) and 1.4 mm Hg (95% CI: 0.1, 2.6 mm Hg; P = 0.03), respectively.Conclusions: This review of healthy individuals indicated that a lower glycemic diet may lead to important reductions in blood pressure. However, many of the trials included in the analysis reported important sources of bias. This trial was registered at PROSPERO as CRD42016049026.
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Evaluation of the impact of school gardening interventions on children's knowledge of and attitudes towards fruit and vegetables. A cluster randomised controlled trial.
Hutchinson, J, Christian, MS, Evans, CE, Nykjaer, C, Hancock, N, Cade, JE
Appetite. 2015;:405-14
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Involvement of children in gardening has the potential to increase liking of fruit and vegetables (FV) and consequently, intake, but research results are mixed. School gardening led by external specialists such as the Royal Horticultural Society (RHS) could have more impact than teacher-led gardening on children's knowledge of, and attitudes towards, FV. Data from a cluster randomised controlled trial were used to compare a RHS-led school gardening intervention with a teacher-led gardening intervention amongst 7-10 year olds in 21 London schools. A short questionnaire was developed and used to identify children's knowledge and attitudes towards FV consumption before the garden intervention and 18 months afterwards. Results from multilevel regression models, both unadjusted and adjusted for baseline responses and socio-demographic factors, were reported. Attitudes to FV intake were compared between groups. Change in FV knowledge was used to predict change in FV consumption assessed using 24-hour food diaries. In comparison with the RHS-led group (n = 373), teacher-led children (n = 404) were more likely to agree they ate lots of fruit (p < 0.009) and tried new fruits (p = 0.045), but RHS-led gardening was associated with a greater increase in the total number of vegetables recognised (p = 0.031). No other differences in improvements in attitudes, or associations between change in FV recognition and intake were found. In relation to improvements in children's recognition and attitudes towards eating FV, this trial produced limited evidence that gardening activity packages led by external specialists (RHS-led) provide additional benefits over those led by teachers trained by the RHS. Indeed, the latter were potentially more effective.
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School-Based Interventions to Reduce Obesity Risk in Children in High- and Middle-Income Countries.
Evans, CE, Albar, SA, Vargas-Garcia, EJ, Xu, F
Advances in food and nutrition research. 2015;:29-77
Abstract
School-based interventions are relatively new and were first introduced in the United States in the 1990s. Early programs were mainly education based with many of the findings now embedded in school policy in the form of a healthy eating curriculum. More recent school programs have taken education outside the classroom and attempted to engage parents as well as teachers. Environmental changes such as improving the quality of foods available at lunchtime and at other times during the school day are now common. Reviews of evaluations of school-based programs have demonstrated that they are effective and successfully improve dietary quality such as increasing fruit and vegetable intake and decreasing sweet and savory snacks and sweetened drinks; not just in school but over the whole day and particularly in younger school children. School-based interventions are also effective at reducing obesity if components to increase physical activity and reduce sedentary behaviors are also targeted but not if only dietary behaviors are tackled. Most of the high-quality evaluation studies using randomized controlled trials have been carried out in high-income countries as they are costly to run. However, middle-income countries have benefitted from the information available from these evaluation studies and many are now starting to fund and evaluate school-based programs themselves, resulting in unique problems such as concomitant under- and overnutrition being addressed. Action for the future demands more focus on populations most at risk of poor dietary quality and obesity in order to reduce inequalities in health and on adolescents who have not benefited as much as younger children from school-based interventions. This will involve innovative solutions within schools as well as targeting the food environment outside schools such as reducing the density of fast-food outlets and marketing of sweet and savory snacks and drinks.
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Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies.
Greenwood, DC, Threapleton, DE, Evans, CE, Cleghorn, CL, Nykjaer, C, Woodhead, C, Burley, VJ
The British journal of nutrition. 2014;(5):725-34
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The intake of sugar-sweetened soft drinks has been reported to be associated with an increased risk of type 2 diabetes, but it is unclear whether this is because of the sugar content or related lifestyle factors, whether similar associations hold for artificially sweetened soft drinks, and how these associations are related to BMI. We aimed to conduct a systematic literature review and dose-response meta-analysis of evidence from prospective cohorts to explore these issues. We searched multiple sources for prospective studies on sugar-sweetened and artificially sweetened soft drinks in relation to the risk of type 2 diabetes. Data were extracted from eleven publications on nine cohorts. Consumption values were converted to ml/d, permitting the exploration of linear and non-linear dose-response trends. Summary relative risks (RR) were estimated using a random-effects meta-analysis. The summary RR for sugar-sweetened and artificially sweetened soft drinks were 1·20/330 ml per d (95 % CI 1·12, 1·29, P< 0·001) and 1·13/330 ml per d (95 % CI 1·02, 1·25, P= 0·02), respectively. The association with sugar-sweetened soft drinks was slightly lower in studies adjusting for BMI, consistent with BMI being involved in the causal pathway. There was no evidence of effect modification, though both these comparisons lacked power. Overall between-study heterogeneity was high. The included studies were observational, so their results should be interpreted cautiously, but findings indicate a positive association between sugar-sweetened soft drink intake and type 2 diabetes risk, attenuated by adjustment for BMI. The trend was less consistent for artificially sweetened soft drinks. This may indicate an alternative explanation, such as lifestyle factors or reverse causality. Future research should focus on the temporal nature of the association and whether BMI modifies or mediates the association.
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Dietary fiber intake and risk of first stroke: a systematic review and meta-analysis.
Threapleton, DE, Greenwood, DC, Evans, CE, Cleghorn, CL, Nykjaer, C, Woodhead, C, Cade, JE, Gale, CP, Burley, VJ
Stroke. 2013;(5):1360-8
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BACKGROUND AND PURPOSE Fiber intake is associated with reduced stroke risk in prospective studies, but no meta-analysis has been published to date. METHODS Multiple electronic databases were searched for healthy participant studies reporting fiber intake and incidence of first hemorrhagic or ischemic stroke, published between January 1990 and May 2012. RESULTS Eight cohort studies from the United States, northern Europe, Australia, and Japan met inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke, with some evidence of heterogeneity between studies (I(2); relative risk per 7 g/day, 0.93; 95% confidence interval, 0.88-0.98; I(2)=59%). Soluble fiber intake, per 4 g/day, was not associated with stroke risk reduction with evidence of low heterogeneity between studies, relative risk 0.94 (95% confidence interval, 0.88-1.01; I(2)=21%). There were few studies reporting stroke risk in relation to insoluble fiber or fiber from cereals, fruit, or vegetables. CONCLUSIONS Greater dietary fiber intake is significantly associated with lower risk of first stroke. Overall, findings support dietary recommendations to increase intake of total dietary fiber. However, a paucity of data on fiber from different foods precludes conclusions regarding the association between fiber type and stroke. There is a need for future studies to focus on fiber type and to examine risk for ischemic and hemorrhagic strokes separately.
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Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis.
Threapleton, DE, Greenwood, DC, Evans, CE, Cleghorn, CL, Nykjaer, C, Woodhead, C, Cade, JE, Gale, CP, Burley, VJ
BMJ (Clinical research ed.). 2013;:f6879
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OBJECTIVE To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease. DESIGN Systematic review of available literature and dose-response meta-analysis of cohort studies using random effects models. DATA SOURCES The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching. ELIGIBILITY CRITERIA FOR STUDIES Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013. RESULTS 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I(2)=45% (0% to 74%)) and coronary heart disease (I(2)=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease. CONCLUSIONS Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.
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Glycemic index, glycemic load, carbohydrates, and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies.
Greenwood, DC, Threapleton, DE, Evans, CE, Cleghorn, CL, Nykjaer, C, Woodhead, C, Burley, VJ
Diabetes care. 2013;(12):4166-71
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OBJECTIVE Diets with high glycemic index (GI), with high glycemic load (GL), or high in all carbohydrates may predispose to higher blood glucose and insulin concentrations, glucose intolerance, and risk of type 2 diabetes. We aimed to conduct a systematic literature review and dose-response meta-analysis of evidence from prospective cohorts. RESEARCH DESIGN AND METHODS We searched the Cochrane Library, MEDLINE, MEDLINE in-process, Embase, CAB Abstracts, ISI Web of Science, and BIOSIS for prospective studies of GI, GL, and total carbohydrates in relation to risk of type 2 diabetes up to 17 July 2012. Data were extracted from 24 publications on 21 cohort studies. Studies using different exposure categories were combined on the same scale using linear and nonlinear dose-response trends. Summary relative risks (RRs) were estimated using random-effects meta-analysis. RESULTS The summary RR was 1.08 per 5 GI units (95% CI 1.02-1.15; P = 0.01), 1.03 per 20 GL units (95% CI 1.00-1.05; P = 0.02), and 0.97 per 50 g/day of carbohydrate (95% CI 0.90-1.06; P = 0.5). Dose-response trends were linear for GI and GL but more complex for total carbohydrate intake. Heterogeneity was high for all exposures (I(2) >50%), partly accounted for by different covariate adjustment and length of follow-up. CONCLUSIONS Included studies were observational and should be interpreted cautiously. However, our findings are consistent with protective effects of low dietary GI and GL, quantifying the range of intakes associated with lower risk. Future research could focus on the type of sugars and other carbohydrates associated with greatest risk.
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A history and review of school meal standards in the UK.
Evans, CE, Harper, CE
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2009;(2):89-99
Abstract
This review details the history of school meals in the UK, from their origin in the mid-19th Century, to the present day, and provides a summary of how each country has independently developed its own food and or nutrient-based standards for school meals. The standards in place in the UK are amongst some of the most detailed and comprehensive in the world. Regular monitoring to ensure that these standards are being met and that schools are improving healthy eating is essential to their success. Of no lesser importance are assessments to determine whether changes to school meals are having an impact on the diets of school children. It is early days in terms of evaluation because food-based standards have only recently been introduced and nutrient-based standards are in the process of being developed and implemented. Studies in England provide some evidence that the re-introduction of standards for school food is having a positive impact on both pupil's food choices and the nutritional profile of school lunches. At present, there does not appear to be a pattern between current obesity levels and the types of school meals provided, although it is anticipated that, in the long term, these comprehensive standards may contribute to a less obesogenic environment.