Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events

IntroductionLong-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE.MethodsWe studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization).ResultsThe average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013).ConclusionsHigher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials

Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone

Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6 h to DE at a PM2.5 concentration of 250-300 mu g/m(3), followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation

A review of the applicability of existing tree and forest characteristics prediction models to forest inventory in Vietnam and Nepal

Forest inventories provide vital and up-to-date information for use in basic decision making on the ma¬nagement and conservation of forest resources. Data collected in forest inventories are stored and pro¬cessed in databases which can be updated by conducting additional measurements or by applying pre¬dictive models for imputing missing values of tree and forest stand-level variables. The inventory results can thereafter be calculated based on sample units, i.e. sample plots or forest stands within them, after which the forest inventory variables can be aggregated using different stratification units. For strategic decision-making, however, the future development of forest resources needs to be predicted. For this purpose, growth and yield simulators comprising tree and stand-level growth models are utilised to ob¬tain prediction results for alternative scenarios based on inventory information, i.e. sample-based field data. In large-scale forest inventories, only easily assessable characteristics are measured for all tallied trees, whereas height characteristics and other variables, which are difficult to measure accurately, are collected from a sub-sample only. In order to generalise the variables measured from sample trees to also cover tally trees, generalization techniques need to be applied. The ongoing national-level forest as¬sessments conducted in Nepal and Vietnam require efficient calculation procedures for reporting inven¬tory results and quantifying the availability and location of forest resources. The aim of this review was to assess the availability of the existing models for the prediction of tree and forest characteristics and their applicability to large-scale forest inventory in Nepal and Vietnam. Through comparisons made bet¬ween country- and species-specific models and prediction systems and through an assessment based on modelling literature, recommendations are also given for further developing the model-based prediction systems used in the ongoing national forest inventories of Nepal and Vietnam. The existing model sets can be used to estimate conventional stand volume characteristics for the inventoried areas. However, according to the new reporting requirements set for the current National Forest Inventory (NFI) of Viet¬nam and the Forest Resource Assessment (FRA) of Nepal, it is recommended that their model bases, which are currently under upgrading, be updated and improved in the future

Additional file 11 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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Additional file 18 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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Additional file 3 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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Additional file 15 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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Additional file 23 of Integration of metabolomics, genomics, and immune phenotypes reveals the causal roles of metabolites in disease

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