Rationalisation of the UK Nutrient Databank for Incorporation in a Web-Based Dietary Recall for Implementation in the UK National Diet and Nutrition Survey Rolling Programme.

The UK National Diet and Nutrition Survey rolling programme (NDNS RP) commenced in 2008 and moved in 2019 from a traditional paper food diary to a web-based 24 h recall, Intake24. This paper describes the approach to update and downsize the underlying UK Nutrient Databank (NDB) for efficient data management and integration into Intake24. Consumption data from the first 10 years (2008/2009 to 2017/2018) of NDNS RP informed decisions on whether foods from the extensive UK NDB were to be retained, excluded, revised or added to for creation of a rationalised NDB. Overall, 5933 food codes in the extensive NDB were reduced to 2481 food codes in the rationalised NDB. Impact on assessment of nutrient intakes was evaluated by re-coding NDNS 2017 data using the rationalised NDB. Small differences were observed between estimated intakes (Cohen's d ≤ 0.1) for all nutrients and there was a good level of agreement (Cohen's κ ≥ 0.6) between the extensive and rationalised NDBs. The evaluation provides confidence in dietary intake estimates for ongoing nutritional surveillance in the UK and strengthens the evidence of a good agreement between concise food databases and large food databases incorporated into web-based 24 h recalls for estimating nutrient intakes at the population level.

Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma.

In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/ß and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to controls. IL-1α/ß induced fibroblast pro-inflammatory responses (CXCL8/IL-8, IL-6, TSLP, GM-CSF) and suppressed ECM-production (collagen, fibronectin, periostin) and the cell's ability to repair and remodel fibrillar collagen I via LOX, LOXL1 and LOXL2 activity, as confirmed by inhibition with ß-aminopropionitrile. These data support a role for epithelial-derived-IL-1 in the dysregulated repair of the asthmatic-EMTU and provides new insights into the contribution of airway fibroblasts in inflammation and airway remodeling in asthma.

Defective Fibrillar Collagen Organization by Fibroblasts Contributes to Airway Remodeling in Asthma.

Rationale: Histologic stains have been used as the gold standard to visualize extracellular matrix (ECM) changes associated with airway remodeling in asthma, yet they provide no information on the biochemical and structural characteristics of the ECM, which are vital to understanding alterations in tissue function.Objectives: To demonstrate the use of nonlinear optical microscopy (NLOM) and texture analysis algorithms to image fibrillar collagen (second harmonic generation) and elastin (two-photon excited autofluorescence), to obtain biochemical and structural information on the remodeled ECM environment in asthma.Methods: Nontransplantable donor lungs from donors with asthma (n = 13) and control (n = 12) donors were used for the assessment of airway collagen and elastin fibers by NLOM, and extraction of lung fibroblasts for in vitro experiments.Measurements and Main Results: Fibrillar collagen is not only increased but also highly disorganized and fragmented within large and small asthmatic airways compared with control subjects, using NLOM imaging. Furthermore, such structural alterations are present in pediatric and adult donors with asthma, irrespective of fatal disease. In vitro studies demonstrated that asthmatic airway fibroblasts are deficient in their packaging of fibrillar collagen-I and express less decorin, important for collagen fibril packaging. Packaging of collagen fibrils was found to be more disorganized in asthmatic airways compared with control subjects, using transmission electron microscopy.Conclusions: NLOM imaging enabled the structural assessment of the ECM, and the data suggest that airway remodeling in asthma involves the progressive accumulation of disorganized fibrillar collagen by airway fibroblasts. This study highlights the future potential clinical application of NLOM to assess airway remodeling in vivo.

A Disaggregation Methodology to Estimate Intake of Added Sugars and Free Sugars: An Illustration from the UK National Diet and Nutrition Survey.

Various and inconsistent definitions for free and added sugars are used in the consideration and assessment of dietary intakes across public health, presenting challenges for nutritional surveillance, research, and policy. Furthermore, analytical methods to identify those sugars which are not naturally incorporated into the cellular structure of foods are lacking, thus free and added sugars are difficult to estimate in an efficient and accurate way. We aimed to establish a feasible and accurate method that can be applied flexibly to different definitions. Based on recipe disaggregation, our method involved five steps and showed good repeatability and validity. The resulting Free Sugars Database provided data for seven components of sugars; (1) table sugar; (2) other sugars; (3) honey; (4) fruit juice; (5) fruit puree; (6) dried fruit; and (7) stewed fruit, for ~9000 foods. Our approach facilitates a standardized and efficient assessment of added and free sugars, offering benefit and potential for nutrition research and surveillance, and for the food industry, for example to support sugar reduction and reformulation agendas.

Extended and standard duration weight-loss programme referrals for adults in primary care (WRAP): a randomised controlled trial.

BACKGROUND: Evidence exist that primary care referral to an open-group behavioural programme is an effective strategy for management of obesity, but little evidence on optimal intervention duration is available. We aimed to establish whether 52-week referral to an open-group weight-management programme would achieve greater weight loss and improvements in a range of health outcomes and be more cost-effective than the current practice of 12-week referrals. METHODS: In this non-blinded, parallel-group, randomised controlled trial, we recruited participants who were aged 18 years or older and had body-mass index (BMI) of 28 kg/m2 or higher from 23 primary care practices in England. Participants were randomly assigned (2:5:5) to brief advice and self-help materials, a weight-management programme (Weight Watchers) for 12 weeks, or the same weight-management programme for 52 weeks. We followed-up participants over 2 years. The primary outcome was weight at 1 year of follow-up, analysed with mixed-effects models according to intention-to-treat principles and adjusted for centre and baseline weight. In a hierarchical closed-testing procedure, we compared combined behavioural programme arms with brief intervention, then compared the 12-week programme and 52-week programme. We did a within-trial cost-effectiveness analysis using person-level data and modelled outcomes over a 25-year time horizon using microsimulation. This study is registered with Current Controlled Trials, number ISRCTN82857232. FINDINGS: Between Oct 18, 2012, and Feb 10, 2014, we enrolled 1269 participants. 1267 eligible participants were randomly assigned to the brief intervention (n=211), the 12-week programme (n=528), and the 52-week programme (n=528). Two participants in the 12-week programme had been found to be ineligible shortly after randomisation and were excluded from the analysis. 823 (65%) of 1267 participants completed an assessment at 1 year and 856 (68%) participants at 2 years. All eligible participants were included in the analyses. At 1 year, mean weight changes in the groups were -3·26 kg (brief intervention), -4·75 kg (12-week programme), and -6·76 kg (52-week programme). Participants in the behavioural programme lost more weight than those in the brief intervention (adjusted difference -2·71 kg, 95% CI -3·86 to -1·55; p<0·0001). The 52-week programme was more effective than the 12-week programme (-2·14 kg, -3·05 to -1·22; p<0·0001). Differences between groups were still significant at 2 years. No adverse events related to the intervention were reported. Over 2 years, the incremental cost-effectiveness ratio (ICER; compared with brief intervention) was £159 per kg lost for the 52-week programme and £91 per kg for the 12-week programme. Modelled over 25 years after baseline, the ICER for the 12-week programme was dominant compared with the brief intervention. The ICER for the 52-week programme was cost-effective compared with the brief intervention (£2394 per quality-adjusted life-year [QALY]) and the 12-week programme (£3804 per QALY). INTERPRETATION: For adults with overweight or obesity, referral to this open-group behavioural weight-loss programme for at least 12 weeks is more effective than brief advice and self-help materials. A 52-week programme produces greater weight loss and other clinical benefits than a 12-week programme and, although it costs more, modelling suggests that the 52-week programme is cost-effective in the longer term. FUNDING: National Prevention Research Initiative, Weight Watchers International (as part of an UK Medical Research Council Industrial Collaboration Award).

DINO (Diet In Nutrients Out) - an integrated dietary assessment system.

OBJECTIVE: The current paper describes Diet In Nutrients Out (DINO), an integrated dietary assessment system incorporating dietary data entry and nutritional analysis within one platform for use in dietary assessment in small-scale intervention studies to national surveys. DESIGN: DINO contains >6000 food items, mostly aggregated composites of branded foods, across thirty-one main food groups divided into 151 subsidiary groups for detailed reporting requirements, with fifty-three core nutrient fields. SETTING: MRC Human Nutrition Research (HNR), Cambridge, UK and MRC Keneba, Gambia. SUBJECTS: DINO is used across dietary assessment projects at HNR and MRC Keneba. RESULTS: DINO contains macro- and micronutrients as well as additional variables of current research and policy interest, such as caffeine, whole grains, vitamin K and added sugars. Disaggregated data are available for fruit, vegetables, meat, fish and cheese in composite foods, enabling greater accuracy when reporting food consumption or assessing adherence to dietary recommendations. Portion sizes are categorised in metric and imperial weights, with standardised portion sizes for each age group. Regular reviews are undertaken for portion sizes and food composition to ensure contemporary relevance. A training programme and a checking schedule are adhered to for quality assurance purposes, covering users and data. Eating context questions are integrated to record where and with whom the respondent is eating, allowing examination between these factors and the foods consumed. CONCLUSIONS: An up-to-date quality-assured system for dietary assessment is crucial for nutritional surveillance and research, but needs to have the flexibility to be tailored to address specific research questions.

Patterns of sociodemographic and food practice characteristics in relation to fruit and vegetable consumption in children: results from the U.K. National Diet and Nutrition Survey Rolling Programme (2008-2010).

OBJECTIVE: Few studies have considered the combined effects of home-related determinants on children's diet. The present study investigated independent associations between sociodemographic and food practice (SFP) characteristics and fruit and vegetable consumption in U.K. children and the combined effects of SFP on consumption using pattern analysis. DESIGN: Diet was assessed using 4 d food diaries, SFP were collected using computer-assisted personal interview. Linear regressions were used to test associations; principal component analysis was used to identify patterns of SFP characteristics. Regression of fruit (g/d) and vegetables (g/d) v. component scores of each pattern were performed. SETTING: U.K. National Diet and Nutrition Survey Rolling Programme (2008­2010). SUBJECTS: Children aged 1.5­10 years (n 642). RESULTS: Significant associations were found between fruit and vegetable consumption and household socio-economic status. Pattern 1, which was positively correlated with household structure characteristics, was associated with increased fruit consumption (P < 0.001). Pattern 2, characterised by positive correlations for socio-economic status, fruit availability and organic food purchase, and negatively correlated with household size and the number of children per household, was associated with higher fruit and vegetable consumption (both P < 0.001). Pattern 3, characterised by high frequency of eating out and eating takeaway, was associated with a lower consumption of both fruit (P < 0.012) and vegetables (P < 0.023). CONCLUSIONS: Patterns of SFP determinants may be more informative than individual characteristics in relation to dietary outcomes. Results have public health implications on the healthfulness of meals eaten out of home and in takeaways, as well as the need to reduce diet inequality in larger households with lower socio-economic status.

Assessing caffeine intake in the United Kingdom diet.

Caffeine occurs naturally in the leaves and seeds of many plants and is artificially added to some beverages. Consumption of caffeine has been linked to both positive and adverse health outcomes. We incorporated estimates of caffeine content (mg/100g or ml) of foods and drinks, taken from the published literature, to provide a preliminary estimate of caffeine intake for the UK population, based on data collected in the National Diet and Nutrition Survey 2008-10. Among consumers mean total caffeine intakes of adult men 19+ y were significantly greater than intakes by boys 4-10y and 11-18y (p<0.05), with the same age-related differences seen for females. 4.1% of men 19+ y and 3.8% of women 19+ y had caffeine intakes in excess of 300mg/d. The addition of caffeine to UK food composition databases will allow more detailed study of the health effects of caffeine consumption.

DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women.

BACKGROUND: Animal models show that periconceptional supplementation with folic acid, vitamin B-12, choline, and betaine can induce differences in offspring phenotype mediated by epigenetic changes in DNA. In humans, altered DNA methylation patterns have been observed in offspring whose mothers were exposed to famine or who conceived in the Gambian rainy season. OBJECTIVE: The objective was to understand the seasonality of DNA methylation patterns in rural Gambian women. We studied natural variations in dietary intake of nutrients involved in methyl-donor pathways and their effect on the respective metabolic biomarkers. DESIGN: In 30 women of reproductive age (18-45 y), we monitored diets monthly for 1 y by using 48-h weighed records to measure intakes of choline, betaine, folate, methionine, riboflavin, and vitamins B-6 and B-12. Blood biomarkers of these nutrients, S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), homocysteine, cysteine, and dimethylglycine were also assessed monthly. RESULTS: Dietary intakes of riboflavin, folate, choline, and betaine varied significantly by season; the most dramatic variation was seen for betaine. All metabolic biomarkers showed significant seasonality, and vitamin B-6 and folate had the highest fluctuations. Correlations between dietary intakes and blood biomarkers were found for riboflavin, vitamin B-6, active vitamin B-12 (holotranscobalamin), and betaine. We observed a seasonal switch between the betaine and folate pathways and a probable limiting role of riboflavin in these processes and a higher SAM/SAH ratio during the rainy season. CONCLUSIONS: Naturally occurring seasonal variations in food-consumption patterns have a profound effect on methyl-donor biomarker status. The direction of these changes was consistent with previously reported differences in methylation of metastable epialleles. This trial was registered at www.clinicaltrials.gov as NCT01811641.

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle.

Airway smooth muscle (ASM) cellular and molecular biology is typically studied with single-cell cultures grown on flat 2D substrates. However, cells in vivo exist as part of complex 3D structures, and it is well established in other cell types that altering substrate geometry exerts potent effects on phenotype and function. These factors may be especially relevant to asthma, a disease characterized by structural remodeling of the airway wall, and highlights a need for more physiologically relevant models of ASM function. We utilized a tissue engineering platform known as microfabricated tissue gauges to develop a 3D culture model of ASM featuring arrays of ∼0.4 mm long, ∼350 cell "microtissues" capable of simultaneous contractile force measurement and cell-level microscopy. ASM-only microtissues generated baseline tension, exhibited strong cellular organization, and developed actin stress fibers, but lost structural integrity and dissociated from the cantilevers within 3 days. Addition of 3T3-fibroblasts dramatically improved survival times without affecting tension development or morphology. ASM-3T3 microtissues contracted similarly to ex vivo ASM, exhibiting reproducible responses to a range of contractile and relaxant agents. Compared with 2D cultures, microtissues demonstrated identical responses to acetylcholine and KCl, but not histamine, forskolin, or cytochalasin D, suggesting that contractility is regulated by substrate geometry. Microtissues represent a novel model for studying ASM, incorporating a physiological 3D structure, realistic mechanical environment, coculture of multiple cells types, and comparable contractile properties to existing models. This new model allows for rapid screening of biochemical and mechanical factors to provide insight into ASM dysfunction in asthma.

Assessing eating context and fruit and vegetable consumption in children: new methods using food diaries in the UK National Diet and Nutrition Survey Rolling Programme.

BACKGROUND: Eating context is the immediate environment of each eating occasion (EO). There is limited knowledge on the effects of the eating context on food consumption in children, due to the difficulty in measuring the multiple eating contexts children experience throughout the day. This study applied ecological momentary assessment using food diaries to explore the relationships between eating context and fruit and vegetable consumption in UK children. METHODS: Using 4 d unweighed food diaries, data were collected for 642 children aged 1.5-10y in two years of the UK National Diet and Nutrition Survey (2008-2010). Participants recorded all foods and drinks consumed at each EO, where and with whom the food was consumed, whether the TV was on and if eaten at a table. Mixed logistic regression and mixed multinomial logistic regression were used to calculate associations between eating contexts and fruit and vegetables (FV) consumed by quartiles. RESULTS: Of 16,840 EOs, 73% took place at home and 31% with parents only. Frequency of eating alone and with friends increased with age. Compared to eating at home, children aged 1.5-3y were more likely to consume fruit at care outside home (>10-50g OR:2.39; >50-100g OR:2.12); children aged 4-6y were more likely to consume fruit (>50-100g OR:3.53; >100g OR:1.88) and vegetables at school (>30-60g OR:3.56). Compared to eating with parents only, children aged 1.5-3y were more likely to consume fruit with friends (>10-50g OR:2.69; >50-100g OR:3.49), and with carer and other children/others (>10-50g OR:2.25); children aged 4-6y were more likely to consume fruit (>50-100g OR:1.96) and vegetables with friends (>30-60g OR:3.56). Children of all ages were more likely to eat vegetables when the TV was off than on and at a table than not at table. CONCLUSIONS: The use of food diaries to capture multiple eating contexts and detailed fruit and vegetable consumption data was demonstrated at a population level. Higher odds of FV consumption were seen from structured settings such as school and care outside home than at home, as well as when eating at a table and the TV off. This study highlights eating contexts where provision of fruit and vegetables could be improved, especially at home. Future research should take eating context into consideration when planning interventions to target children's food consumption and eating behaviour.

National Diet and Nutrition Survey: UK food consumption and nutrient intakes from the first year of the rolling programme and comparisons with previous surveys.

The National Diet and Nutrition Survey (NDNS) is a cross-sectional survey designed to gather data representative of the UK population on food consumption, nutrient intakes and nutritional status. The objectives of the present paper were to identify and describe food consumption and nutrient intakes in the UK from the first year of the NDNS rolling programme (2008-09) and compare these with the 2000-01 NDNS of adults aged 19-64 years and the 1997 NDNS of young people aged 4-18 years. Differences in median daily food consumption and nutrient intakes between the surveys were compared by sex and age group (4-10 years, 11-18 years and 19-64 years). There were no changes in energy, total fat or carbohydrate intakes between the surveys. Children aged 4-10 years had significantly lower consumption of soft drinks (not low calorie), crisps and savoury snacks and chocolate confectionery in 2008-09 than in 1997 (all P < 0·0001). The percentage contribution of non-milk extrinsic sugars to food energy was also significantly lower than in 1997 in children aged 4-10 years (P < 0·0001), contributing 13·7-14·6 % in 2008-09 compared with 16·8 % in 1997. These changes were not as marked in older children and there were no changes in these foods and nutrients in adults. There was still a substantial proportion (46 %) of girls aged 11-18 years and women aged 19-64 years (21 %) with mean daily Fe intakes below the lower reference nutrient intake. Since previous surveys there have been some positive changes in intakes especially in younger children. However, further attention is required in other groups, in particular adolescent girls.

Chronic oscillatory strain induces MLCK associated rapid recovery from acute stretch in airway smooth muscle cells.

A deep inspiration (DI) temporarily relaxes agonist-constricted airways in normal subjects, but in asthma airways are refractory and may rapidly renarrow, possibly due to changes in the structure and function of airway smooth muscle (ASM). Chronic largely uniaxial cyclic strain of ASM cells in culture causes several structural and functional changes in ASM similar to that in asthma, including increases in contractility, MLCK content, shortening velocity, and shortening capacity. However, changes in recovery from acute stretch similar to a DI have not been measured. We have therefore measured the response and recovery to large stretches of cells modified by chronic stretching and investigated the role of MLCK. Chronic, 10% uniaxial cyclic stretch, with or without a strain gradient, was administered for up to 11 days to cultured cells grown on Silastic membranes. Single cells were then removed from the membrane and subjected to 1 Hz oscillatory stretches up to 10% of the in situ cell length. These oscillations reduced stiffness by 66% in all groups (P < 0.05). Chronically strained cells recovered stiffness three times more rapidly than unstrained cells, while the strain gradient had no effect. The stiffness recovery in unstrained cells was completely inhibited by the MLCK inhibitor ML-7, but recovery in strained cells exhibiting increased MLCK was slightly inhibited. These data suggest that chronic strain leads to enhanced recovery from acute stretch, which may be attributable to the strain-induced increases in MLCK. This may also explain in part the more rapid renarrowing of activated airways following DI in asthma.

Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling.

The application of mechanical stresses to the airway smooth muscle (ASM) cell causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank NJ, Fabry B, Smith PG, and Maksym GN. Am J Physiol Cell Physiol 287: C440-C448, 2004). We investigated here the extent to which these behaviors are modulated by the state of cell activation (tone). Localized mechanical stress was applied to the ASM cell in culture via oscillating beads (4.5 mum) that were tightly bound to the actin cytoskeleton (CSK). Tone was reduced from baseline level using a panel of relaxant agonists (10(-3) M dibutyryl cAMP, 10(-4) M forskolin, or 10(-6) M formoterol). To assess functional changes, we measured cell stiffness (G') using optical magnetic twisting cytometry, and to assess structural changes of the CSK we measured actin accumulation in the neighborhood of the bead. Applied mechanical stress caused a twofold increase in G' at 120 min. After cessation of applied stress, G' diminished only 24 +/- 6% (mean +/- SE) at 1 h, leaving substantial residual effects that were largely irreversible. However, applied stress-induced stiffening could be prevented by ablation of tone. Ablation of tone also inhibited the amount of actin accumulation induced by applied mechanical stress (P < 0.05). Thus the greater the contractile tone, the greater was applied stress-induced CSK stiffening and remodeling. As regards pathobiology of asthma, this suggests a maladaptive positive feedback in which tone potentiates ASM remodeling and stiffening that further increases stress and possibly leads to worsening airway function.