Tryptophan metabolites and incident cardiovascular disease: The EPIC-Norfolk prospective population study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) remains the largest cause of death globally due to various risk factors. One novel potential contributor to CVD might be the metabolism of the essential amino acid tryptophan (Trp), which through many pathways can produce immunomodulatory metabolites such as kynurenine, indole-3-propionate and serotonin. We aim to identify the metabolites with the strongest association with cardiovascular disease, utilizing a substantial and diverse cohort of individuals. In our pursuit of this aim, our primary focus is to validate and reinforce the findings from previous cross-sectional studies. METHODS: We used the community-based EPIC-Norfolk cohort (46.3 % men, age 59.8 ± 9.0) with a median follow-up of 22.1 (17.6-23.3) years to study associations between the relative levels of Trp metabolites measured with untargeted metabolomics and incident development of CVD. Serum from n = 11,972 apparently healthy subjects was analysed, of which 6982 individuals had developed CVD at the end of follow-up. Cox proportional hazard models were used to study associations, adjusted for sex, age, conventional cardiovascular risk factors and CRP. All metabolites were Ln-normalised prior to analysis. RESULTS: Higher levels of Trp were inversely associated with mortality (HR 0.73; CI 0.64-0.83) and fatal CVD (HR 0.76; CI 0.59-0.99). Higher levels of kynurenine (HR 1.33; CI 1.19-1.49) and the [Kynurenine]/[Tryptophan]-ratio (HR 1.24; CI 1.14-1.35) were associated with a higher incident development of CVD. Serotonin was not associated with overall CVD, but we did find associations for myocardial infarction and stroke. Adjustment for CRP did not yield any discernible differences in effect size. CONCLUSIONS: Tryptophan levels were inversely correlated with CVD, while several of its major metabolites (especially kynurenine and serotonin) were positively correlated. These findings indicate that mechanistic studies are required to understand the role of Trp metabolism in CVD with the goal to identify new therapeutic targets.

How to improve sleep in a neonatal intensive care unit: A systematic review.

There is increasing evidence that sleep plays a major role in the development of neural pathways in the neonatal brain. Several studies have suggested evidence-based approaches to improve sleep for infants admitted to the neonatal intensive care unit (NICU); however, in many neonatal centers very few of these strategies seem to be implemented in routine care. OBJECTIVE: To systematically review the literature to determine interventions promoting neonatal sleep on the NICU, in order to develop key guidelines to improve neonatal sleep. METHODS: A systematic search was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for conducting and reporting systematic reviews. The search was performed in Pubmed, CINAHL and the Cochrane Library on 19 September 2016 and again on 28 January 2017. RESULTS: In total, fourteen studies were included (10 RCT's and three quasi-experimental study designs): four studies were of high quality, eight of moderate quality and two of low quality. Two studies investigating kangaroo care reported significant effect on infant sleep behavior, two studies comparing Yakson and Gentle Human Touch (GHT) found significant effect on behavioral states and one study reported an increase in sleep behavior using different sleep surfaces. One study showed a significant effect on sleep patterns using music as an intervention and one study showed no significant effect using music. Two studies showed no significant effect on infant sleep using cycled light and different types of LED-light and one study showed significant effect of cycled lightning. There were no effects of Neonatal Individualized Developmental Care Program (NIDCAP) or massage therapy. CONCLUSION: Although many different interventions have been reported to promote sleep in infants who require intensive care, there is great heterogeneity across studies: the methods of sleep assessment, the targeted sleep behaviors, and the study populations vary significantly across published reports. Based on the results there seems to be insufficient evidence to recommend any new intervention to promote neonatal sleep on the NICU. However because of the importance of sleep for the development of the neonatal brain we do suggest some key guidelines based on moderate evidence, expert opinion and parental values to improve sleep on the NICU and to direct future neonatal sleep studies.