Cohort profile: LifeLines DEEP, a prospective, general population cohort study in the northern Netherlands:Study design and baseline characteristics

Purpose There is a critical need for population-based prospective cohort studies because they follow individuals before the onset of disease, allowing for studies that can identify biomarkers and disease-modifying effects, and thereby contributing to systems epidemiology. Participants This paper describes the design and baseline characteristics of an intensively examined subpopulation of the LifeLines cohort in the Netherlands. In this unique subcohort, LifeLines DEEP, we included 1539 participants aged 18 years and older. Findings to date We collected additional blood (n=1387), exhaled air (n=1425) and faecal samples (n=1248), and elicited responses to gastrointestinal health questionnaires (n=1176) for analysis of the genome, epigenome, transcriptome, microbiome, metabolome and other biological levels. Here, we provide an overview of the different data layers in LifeLines DEEP and present baseline characteristics of the study population including food intake and quality of life. We also describe how the LifeLines DEEP cohort allows for the detailed investigation of genetic, genomic and metabolic variation for a wide range of phenotypic outcomes. Finally, we examine the determinants of gastrointestinal health, an area of particular interest to us that can be addressed by LifeLines DEEP. Future plans We have established a cohort of which multiple data levels allow for the integrative analysis of populations for translation of this information into biomarkers for disease, and which will offer new insights into disease mechanisms and prevention

Resonance raman optical activity shows unusual structural sensitivity for systems in resonance with multiple excited states: vitamin B12 case

In this work, cobalamins with different upper axial substituents and a cobalamin derivative with a ring modification were studied using chiroptical spectroscopies, in particular resonance Raman optical activity (RROA), to shed light on the influence of structural modifications on RROA spectra in these strongly chiral systems in resonance with multiple excited states at 532 nm excitation. We have demonstrated that for these unique systems RROA possesses augmented structural specificity, surpassing resonance Raman spectroscopy and enabling at the same time measurement of cobalamins at fairy low concentrations of ∼10–5 mol dm–3. The enhanced structural specificity of RROA is a result of bisignate spectra due to resonance via more than one electronic state. The observation of increased structural capability of RROA for cobalamins opens a new perspective for studying chiral properties of other biological systems incorporating d-metal ions

Antiatherosclerotic Effects of 1-Methylnicotinamide in Apolipoprotein E/Low-Density Lipoprotein Receptor-Deficient Mice: A Comparison with Nicotinic Acid

ABSTRACT 1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/ low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/ LDLR 2/2 mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F 1a and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B 2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR 2/2 mice, an effect associated with an improvement in prostacyclin-and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA

Factors that influence the volatile organic compound content in human breath

Background. Thousands of endogenous and exogenous volatile organic compounds (VOCs) are excreted in each breath. Inflammatory and deviant metabolic processes affect the level of endogeneous VOCs, which can serve as specific biomarkers for clinical diagnosis and disease monitoring. Important issues that still need to be tackled are related to potential confounding factors like gender and age and endogenous and exogenous factors, like f.i. smoking. Methods. The aim of this study was to systematically access the effect of endogenous and exogenous factors on VOC composition of exhaled breath. In the current study breath samples from 1417 adult participants from the LifeLines cohort, a general population cohort in the Netherlands, were collected and the total content of VOCs was measured using gas chromatography-time-of-flight-mass spectrometry. Breath samples were collected in Groningen and transferred to carbon tubes immediately. These samples were then shipped to Maastricht and measured in batches. VOCs profiles were correlated to 14 relevant characteristics of all participants including age, BMI, smoking and blood cell counts and metabolic parameters as well as to 16 classes of medications. Results. VOCs profiles were shown to be significantly influenced by smoking behavior and to a lesser extent by age, BMI and gender. These factors need to be controlled for in breath analysis studies. We found no evidence whatsoever in this 1417 subjects' cohort that white blood cell counts, cholesterol or triglycerides levels have an influence on the VOC profile. Thus they may not have to be controlled for in exhaled breath studies. Conclusion. The large cohort of volunteers used here represents a unique opportunity to gauge the factors influencing VOCs profiles in a general population i.e. the most clinically relevant population. Classical clinical parameters and smoking habits clearly influence breath content and should therefore be accounted for in future clinical studies involving breath analysis