13 research outputs found

    Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium

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    Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10−6), methionine (p-value = 9.2 × 10−5), tyrosine (p-value = 2.1 × 10−4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10−4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10−4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10−4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality

    Metabolism, the thing as a living organism

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    Examining the effects of enhanced provider-patient communication on postoperative pain: protocol of a randomized controlled trial performed in daily clinical care.

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    Introduction: Placebo effects (true biopsychological effects not attributable to the active ingredients of medical technical interventions) can be attributed to several mechanisms, such as expectancy manipulation and empathy manipulation elicited by a provider’s communication. So far, effects have primarily been shown in laboratory settings. The aim of this study is to determine the separate and combined effects of expectancy manipulation and empathy manipulation during preoperative and postoperative tonsillectomy analgesia care on clinical adult patients’ outcomes. Methods and analysis: Using a two-by-two randomised controlled trial, 128 adult tonsillectomy patients will be randomly assigned to one out of four conditions differing in the level of expectancy manipulation (standard vs enhanced) and empathy manipulation (standard vs enhanced). Day care ward nurses are trained to deliver the intervention, while patients are treated via the standard analgesia protocol and hospital routines. The primary outcome, perceived pain, is measured via hospital routine by a Numeric Rating Scale, and additional prehospitalisation, perihospitalisation and posthospitalisation questionnaires are completed (until day 3, ie, 2 days after the operation). The manipulation is checked using audio recordings of nurse–patient interactions. Ethics and dissemination: Although communication is manipulated, the manipulations do not cross norms or values of acceptable behaviour. Standard medical care is provided. The ethical committee of the UMC Utrecht and the local OLVG hospital committee approved the study. Results will be published via (inter)national peer-reviewed journals and a lay publication

    Current Treatment of Vestibular, Ocular Motor Disorders and Nystagmus

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    Vertigo and dizziness are among the most common complaints with a lifetime prevalence of about 30%. The various forms of vestibular disorders can be treated with pharmacological therapy, physical therapy, psychotherapeutic measures or, rarely, surgery. In this review, the current pharmacological treatment options for peripheral and central vestibular, cerebellar and ocular motor disorders will be described. They are as follows for peripheral vestibular disorders. In vestibular neuritis recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease a recent study showed long-term high-dose treatment with betahistine has a significant effect on the frequency of the attacks. The use of aminopyridines introduced a new therapeutic principle in the treatment of downbeat and upbeat nystagmus and episodic ataxia type 2 (EA 2). These potassium channel blockers presumably increase the activity and excitability of cerebellar Purkinje cells, thereby augmenting the inhibitory influence of these cells on vestibular and cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus, and gabapentin and memantine, pendular nystagmus. However, many other eye movement disorders such as ocular flutter opsoclonus, central positioning, or see-saw nystagmus are still difficult to treat. Although progress has been made in the treatment of vestibular neuritis, downbeat and upbeat nystagmus, as well as EA 2, state-of-the-art trials must still be performed on many vestibular and ocular motor disorders, namely Menière's disease, bilateral vestibular failure, vestibular paroxysmia, vestibular migraine, and many forms of central eye movement disorders

    Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood

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    Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes. © 2018 The Author(s).Peer reviewe
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