Personalised nutrition and health

This article is one of a series commissioned by The BMJ. Open access fees for the series were funded by SwissRe, which had no input into the commissioning or peer review of the articles.S

Bioinformatic interrogation of expression array data to identify nutritionally regulated genes potentially modulated by DNA methylation

DNA methylation occurs at CpG dinucleotide sites within the genome and is recognised as one of the mechanisms involved in regulation of gene expression. CpG sites are relatively underrepresented in the mammalian genome, but occur densely in regions called CpG islands (CGIs). CGIs located in the promoters of genes inhibit transcription when methylated by impeding transcription factor binding. Due to the malleable nature of DNA methylation, environmental factors are able to influence promoter CGI methylation patterns and thus influence gene expression. Recent studies have provided evidence that nutrition (and other environmental exposures) can cause altered CGI methylation but, with a few exceptions, the genes influenced by these exposures remain largely unknown. Here we describe a novel bioinformatics approach for the analysis of gene expression microarray data designed to identify regulatory sites within promoters of differentially expressed genes that may be influenced by changes in DNA methylation

The effect of polar lipids on tear film dynamics

In this paper we present a mathematical model describing the effect of polar lipids on the evolution of a precorneal tear film, with the aim of explaining the interesting experimentally observed phenomenon that the tear film continues to move upwards even after the upper eyelid has become stationary. The polar lipid is an insoluble surface species that locally alters the surface tension of the tear film. In the lubrication limit, the model reduces to two coupled nonlinear partial differential equations for the film thickness and the concentration of lipid. We solve the system numerically and observe that the presence of the lipid causes an increase in flow of liquid up the eye. We further exploit the size of the parameters in the problem to explain the initial evolution of the system

Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish.

KDM2A is a histone demethylase associated with transcriptional silencing, however very little is known about its in vivo role in development and disease. Here we demonstrate that loss of the orthologue kdm2aa in zebrafish causes widespread transcriptional disruption and leads to spontaneous melanomas at a high frequency. Fish homozygous for two independent premature stop codon alleles show reduced growth and survival, a strong male sex bias, and homozygous females exhibit a progressive oogenesis defect. kdm2aa mutant fish also develop melanomas from early adulthood onwards which are independent from mutations in braf and other common oncogenes and tumour suppressors as revealed by deep whole exome sequencing. In addition to effects on translation and DNA replication gene expression, high-replicate RNA-seq in morphologically normal individuals demonstrates a stable regulatory response of epigenetic modifiers and the specific de-repression of a group of zinc finger genes residing in constitutive heterochromatin. Together our data reveal a complex role for Kdm2aa in regulating normal mRNA levels and carcinogenesis. These findings establish kdm2aa mutants as the first single gene knockout model of melanoma biology

Life expectancy gains from dietary modifications: a comparative modeling study in 7 countries

\ua9 2024 The Author(s). Background: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains but did not consider height, weight, or physical activity. Objectives: We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes in China, France, Germany, Iran, Norway, the United Kingdom, and the United States. Methods: Our modeling study used data from meta-analyses presenting dose-response relationships between intake of 15 food groups and mortality. Background mortality data were from the Global Burden of Disease Study. We used national food intake data and adjusted for height, weight, and physical activity level. Results: For 40-y-olds, estimated life expectancy gains ranged from 6.2 y (with uncertainty interval [UI]: 5.7, 7.5 y) for Chinese females to 9.7 y (UI: 8.1, 11.3 y) for United States males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 y (UI: 4.0, 6.5 y) for Chinese females to 8.7 y (UI: 7.1, 10.3 y) for United States males following changes to optimized vegan dietary changes. Conclusions: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States

Potential influence of selection criteria on the demographic composition of students in an Australian medical school

<p>Abstract</p> <p>Background</p> <p>Prior to 1999 students entering our MBBS course were selected on academic performance alone. We have now evaluated the impact on the demographics of subsequent cohorts of our standard entry students (those entering directly from high school) of the addition to the selection process of an aptitude test (UMAT), a highly structured interview and a rural incentive program.</p> <p>Methods</p> <p>Students entering from 1985 to 1998, selected on academic performance alone (N = 1402), were compared to those from 1999 to 2011, selected on the basis of a combination of academic performance, interview score, and UMAT score together with the progressive introduction of a rural special entry pathway (N = 1437).</p> <p>Results</p> <p>Males decreased from 57% to 45% of the cohort, students of NE or SE Asian origin decreased from 30% to 13%, students born in Oceania increased from 52% to 69%, students of rural origin from 5% to 21% and those from independent high schools from 56% to 66%. The proportion of students from high schools with relative socio-educational disadvantage remained unchanged at approximately 10%. The changes reflect in part increasing numbers of female and independent high school applicants and the increasing rural quota. However, they were also associated with higher interview scores in females vs males and lower interview scores in those of NE and SE Asian origin compared to those born in Oceania or the UK. Total UMAT scores were unrelated to gender or region of origin.</p> <p>Conclusions</p> <p>The revised selection processes had no impact on student representation from schools with relative socio-educational disadvantage. However, the introduction of special entry quotas for students of rural origin and a structured interview, but not an aptitude test, were associated with a change in gender balance and ethnicity of students in an Australian undergraduate MBBS course.</p

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake

Introduction Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. Objectives To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. Methods We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). Results The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. Conclusion It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies

Capturing health and eating status through a nutritional perception screening questionnaire (NPSQ9) in a randomised internet-based personalised nutrition intervention : the Food4Me study

BACKGROUND: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. METHODS: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. RESULTS: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = -0.181, p < 0.001) and waist circumference (Β = -0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. CONCLUSIONS: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice. TRIAL REGISTRATION: NCT01530139 .Peer reviewedFinal Published versio