Dietary and circulating long-chain omega-3 polyunsaturated fatty acids and mortality risk after myocardial infarction:A long-term follow-up of the alpha omega cohort

BACKGROUND: Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. METHODS AND RESULTS: We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52– 0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86– 0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53–1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53– 0.94] for >2.52% versus ≤1.29%; 0.85 [0.77– 0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. CONCLUSIONS: In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03192410

Prevalence and distribution of (micro)albuminuria in toddlers

Background. Microalbuminuria is common in the general adult population, with a prevalence of similar to 7%, and is an independent indicator of renal and cardiovascular risks. Whether albuminuria is acquired during life (as a result of hypertension/diabetes) or is congenital and already present at birth is unknown. We studied the prevalence of microalbuminuria in toddlers and compared the distribution of albuminuria with that of the general adult population. In addition, we looked for possible associations between microalbuminuria and antenatal, postnatal and maternal factors.Methods. The urinary albumin concentration (U-AC) was measured in 1352 children and the urinary albumin:creatinine ratio (U-ACR) in 1288 children from the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe cohort (age range 20-40 months). Albuminuria distribution was compared with the albuminuria distribution in 40 854 participants of the general adult cohort of the Prevention of Renal and Vascular End stage Disease (PREVEND) study. Associations between albuminuria (expressed as U-AC and U-ACR) and antenatal, postnatal and maternal factors were tested with linear regression analysis.Results. The median U-AC in the GECKO study was 2.3 mg/L (5th-95th percentiles: 2.1-25.5) and in the PREVEND study it was 6.0 mg/L (2.3-28.6) (P distribution comparison 0.053). The prevalence of U-AC a parts per thousand yen 20 mg/L was 6.9% in the GECKO study and 7.8% in the PREVEND study (P = 0.195). The prevalence of U-ACR a parts per thousand yen 30 mg/g in the GECKO study was 23.4%. U-AC and U-ACR were lower in boys. U-AC was not associated with other determinants, but U-ACR was associated with age and gestational diabetes.Conclusions. The distribution of U-AC and the prevalence of U-AC &gt; 20 mg/L in toddlers and in the young general adult population are comparable. These findings suggest that microalbuminuria is a congenital condition that may predispose to a higher cardiovascular risk later in life.</p

Maternal alcohol consumption and offspring DNA methylation: Findings from six general population-based birth cohorts

Aim: Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero. Materials & methods: We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium. Results: We found no strong evidence of association at either individual CpGs or across larger regions of the genome. Conclusion: Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association

Identifying potential causal effects of age at menarche: A Mendelian randomization phenome-wide association study

Background: Age at menarche has been associated with various health outcomes. We aimed to identify potential causal effects of age at menarche on health-related traits in a hypothesis-free manner. Methods: We conducted a Mendelian randomization phenome-wide association study (MR-pheWAS) of age at menarche with 17,893 health-related traits in UK Biobank (n = 181,318) using PHESANT. The exposure of interest was the genetic risk score for age at menarche. We conducted a second MR-pheWAS after excluding SNPs associated with BMI from the genetic risk score, to examine whether results might be due to the genetic overlap between age at menarche and BMI. We followed up a subset of health-related traits to investigate MR assumptions and seek replication in independent study populations. Results: Of the 17,893 tests performed in our MR-pheWAS, we identified 619 associations with the genetic risk score for age at menarche at a 5% false discovery rate threshold, of which 295 were below a Bonferroni-corrected P value threshold. These included potential effects of younger age at menarche on lower lung function, higher heel bone-mineral density, greater burden of psychosocial/mental health problems, younger age at first birth, higher risk of childhood sexual abuse, poorer cardiometabolic health, and lower physical activity. After exclusion of variants associated with BMI, the genetic risk score for age at menarche was related to 37 traits at a 5% false discovery rate, of which 29 were below a Bonferroni-corrected P value threshold. We attempted to replicate findings for bone-mineral density, lung function, neuroticism, and childhood sexual abuse using 5 independent cohorts/consortia. While estimates for lung function, higher bone-mineral density, neuroticism, and childhood sexual abuse in replication cohorts were consistent with UK Biobank estimates, confidence intervals were wide and often included the null. Conclusions: The genetic risk score for age at menarche was related to a broad range of health-related traits. Follow-up analyses indicated imprecise evidence of an effect of younger age at menarche on greater bone-mineral density, lower lung function, higher neuroticism score, and greater risk of childhood sexual abuse in the smaller replication samples available; hence, these findings need further exploration when larger independent samples become available

DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring

Background: We examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood. Methods: First, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR)<0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis. Results: We found 35 differentially methylated CpGs (FDR<0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P<1×10-7). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P<0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity. Conclusions: Maternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system

Maternal Mediterranean diet in pregnancy and newborn DNA methylation:a meta-analysis in the PACE Consortium

Data de publicació electrònica: 02-03-2022Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation.We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother-child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0-18 and an adjusted rMED excluding alcohol (rMEDp, range 0-16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5-7.8 y).rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10-8). This cytosine-phosphate-guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood.In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.This work was supported by the Foundation for the National Institutes of Health [R01 HD034568, UH3 OD023286, R01 NR013945, R01 HL111108]; Joint Programming Initiative A healthy diet for a healthy life [529051023, MR/S036520/1, 529051022, MR/S036520/1, MR/S036520/1]; National Institute of Environmental Health Sciences [R00ES025817]; National institute of diabetes and digestive and kidney diseases [R01DK076648]; National Institutes of Health Office of the Director [UH3OD023248]; Horizon 2020 research and innovation [874739, 733206, 848158, 824989]; Medical Research Council [MR/S009310/1]

Engaging fringe stakeholders in business and society research: applying visual participatory research methods

Business and society (B&S) researchers, as well as practitioners, have been critiqued for ignoring those with less voice and power (e.g. women, non-literate or indigenous peoples) often referred to as ‘fringe stakeholders’. Existing methods used in B&S research often fail to address issues of meaningful participation, voice and power, especially in developing countries. In this article we stress the utility of visual participatory research (VPR) methods in B&S research to fill this gap. Through a case study on engaging Ghanaian cocoa farmers on gender inequality issues we explore how VPR methods may be used by researchers to achieve more inclusive, and thus more credible, stakeholder research that can improve decision-making within businesses. Furthermore, we argue that ingrained social and environmental problems tackled by B&S research and the unique context in which they occur may open up new opportunities to develop participatory visual methods for social change

OSIRIS – The scientific camera system onboard Rosetta

The Optical, Spectroscopic, and Infrared Remote Imaging System OSIRIS is the scientific camera system onboard the Rosetta spacecraft (Figure 1). The advanced high performance imaging system will be pivotal for the success of the Rosetta mission. OSIRIS will detect 67P/Churyumov-Gerasimenko from a distance of more than 106 km, characterise the comet shape and volume, its rotational state and find a suitable landing spot for Philae, the Rosetta lander. OSIRIS will observe the nucleus, its activity and surroundings down to a scale of ~2 cm px−1. The observations will begin well before the onset of cometary activity and will extend over months until the comet reaches perihelion. During the rendezvous episode of the Rosetta mission, OSIRIS will provide key information about the nature of cometary nuclei and reveal the physics of cometary activity that leads to the gas and dust coma. OSIRIS comprises a high resolution Narrow Angle Camera (NAC) unit and a Wide Angle Camera (WAC) unit accompanied by three electronics boxes. The NAC is designed to obtain high resolution images of the surface of comet 7P/Churyumov-Gerasimenko through 12 discrete filters over the wavelength range 250–1000 nm at an angular resolution of 18.6 μrad px−1. The WAC is optimised to provide images of the near-nucleus environment in 14 discrete filters at an angular resolution of 101 μrad px−1. The two units use identical shutter, filter wheel, front door, and detector systems. They are operated by a common Data Processing Unit. The OSIRIS instrument has a total mass of 35 kg and is provided by institutes from six European countrie

Sustainable development and well-being: a philosophical challenge

This paper aims at gaining a better understanding of the inherent paradoxes within sustainability discourses by investigating its basic assumptions. Drawing on a study of the metaphoric references operative in moral language, we reveal the predominance of the 'well-being = wealth' construct, which may explain the dominance of the 'business case' cognitive frame in sustainability discourses (Hahn et al. in Acad Manag Rev 4015:18–42, 2015a). We incorporate economic well-being variables within a philosophical model of becoming well (Küpers in Cult Organ 11(3):221–231, 2005), highlighting the way in which these variables consistently articulate a combination of 'objective' and 'subjective' concerns. We then compare this broad understanding of well-being with the metaphors operative in the sustainable development discourse and argue that the sustainability discourse has fallen prey to an overemphasis on the 'business case'. We proceed to draw on Georges Bataille to challenge the predominance of these value priorities and to explore which mindshifts are required to develop a more comprehensive understanding of what is needed to enable 'sustainable development'