The common ‘thermolabile' variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia

Mild hyperhomocysteinaemia is a major risk factor for vascular disease and neural tube defects (NTDs), conferring an approximately three-fold relative risk for each condition. It has several possible causes: heterozygosity for rare loss of function mutations in the genes for 5,10-methylene tetrahydrofolate reductase (MTHFR) or cystathionine-β-synthase (CBS); dietary insufficiency of vitamin co-factors B6, B12 or folates; or homozygosity for a common ‘thermolabile' mutation in the MTHFR gene which has also been associated with vascular disease and NTDs. We quantified the contribution of the thermolabile mutation to the hyperhomocysteinaemic phenotype in a working male population (625 individuals). Serum folate and vitamin B12 concentrations were also measured and their relationship with homocysteine status and MTHFR genotype assessed. The homozygous thermolabile genotype occurred in 48.4, 35.5, and 23.4% of the top 5,10, and 20% of individuals (respectively) ranked by plasma homocysteine levels, compared with a frequency of 11.5% in the study population as a whole, establishing that the mutation is a major determinant of homocysteine levels at the upper end of the range. Serum folate concentrations also varied with genotype, being lowest in thermolabile homozygotes. The MTHFR thermolabile genotype should be considered when population studies are designed to determine the effective homocysteine-lowering dose of dietary folate supplements, and when prophylactic doses of folate are recommended for individual

Smoking, atopy and certain furry pets are major determinants of respiratory symptoms in children: the International Study of Asthma and Allergies in Childhood Study (Ireland)

BACKGROUND: Environmental, cultural and health care differences may account for variation among countries in the prevalence of asthma and respiratory symptoms in teenagers. OBJECTIVE: To examine the prevalence of respiratory symptoms and the level of diagnosis, and to compare determinants of asthma and severe wheeze in two countries. METHODS: Self-completion questionnaires based on the International Study of Asthma and Allergies in Childhood (ISAAC) protocol were provided to school children in Ireland (Republic and Northern Ireland). In the Republic of Ireland, all children in classes largely aged 13-14 years from 30 post-primary schools were selected by random sampling stratified by school size, composition and Health Board in Spring 1995. In Northern Ireland, all children largely aged 13-14 years of age from 26 post-primary schools were selected by random sampling stratified by school type, composition and Education and Library Board in Spring 1996. RESULTS: Questionnaires were completed by 2,364 children from Northern Ireland and 2,671 from the Republic, about 90% of those eligible to participate. The prevalences of wheeze at various levels of severity, of diagnosed asthma and of treated wheeze were very similar in Northern Ireland and the Republic of Ireland. A significant proportion of those reporting more severe symptomatology (four or more attacks of wheeze in the past 12 months and/or one or more nights disturbed and/or moderate or greater disruption of daily activities and/or speech restriction due to wheeze) had been neither diagnosed nor treated for asthma (20-37%). To investigate the determinants of the more severe symptomatology of asthma or treated wheeze a series of stepwise multiple regression analyses was performed. A history of atopy, cigarette smoking, the possession of a furry pet other than a dog or cat and age were each independently associated with severe wheeze, whilst atopy, a furry pet (as above) and gender were each independently associated with asthma or treated wheeze. CONCLUSIONS: Cigarette smoking is closely associated with the reporting of significant respiratory symptoms together with atopy and exposure to furry pets. Some 20-37% of severe symptoms were neither diagnosed nor treated as asthma

Comparison of dietary intakes in four selected European populations.

The composition of diet and food intakes in four selected European populations were compared. Dietary data (from the World Health Organization Project on Monitoring Trends and Determinants in Cardiovascular Disease) were measured by record methods and were available for middle-aged men in Finland (n = 653), France (n = 1128), Northern Ireland (n = 356), and southern Germany (Augsburg region; n = 899). Nutritional variables - which are independent of the absolute energy intake, such as the percentage supply of energy from macronutrients and the ratio of polyunsaturated to saturated fatty acids - were on the whole similar. However, striking differences were found in food intake and in the percentage supply of fat from different foods. The results indicate that detailed knowledge of consumption figures is necessary to develop prudent and acceptable nutrition intervention programs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press