Summary of uteroplacental arteriovenous and umbilical venoarterial amino acid concentration differences adjusted for transfer of water across the placenta.

<p>Medians of significant concentration differences after adjustment for multiple testing by controlling the false discovery rate (FDR) according to the method of Benjamini and Hochberg are shown.</p

Summary of uteroplacental arteriovenous and umbilical venoarterial amino acid concentration differences adjusted for transfer of water across the placenta.

<p>Medians of significant concentration differences after adjustment for multiple testing by controlling the false discovery rate (FDR) according to the method of Benjamini and Hochberg are shown.</p

Amino acid concentrations on the maternal and fetal sides of the placenta.

<p>Amino acid concentrations on the maternal and fetal sides of the placenta.</p

Retinoic Acid Signalling Is Activated in the Postischemic Heart and May Influence Remodelling

<div><h3>Background</h3><p>All-trans retinoic acid (atRA), an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors (RARs) acting on retinoic acid response elements (RARE).We hypothesized that the retinoic acid (RA) signalling pathway is activated in myocardial ischemia and postischemic remodelling.</p> <h3>Methods and Findings</h3><p>Myocardial infarction was induced through ligating the left coronary artery in mice. <em>In vivo</em> cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM) and cardiofibroblasts (CF) were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity <em>in vivo</em> (p<0.001), which was ascribed to the heart through <em>ex vivo</em> imaging (p = 0.002) with the largest signal 1 week postinfarct. This was accompanied by increased cardiac gene and protein expression of the RAR target genes retinol binding protein 1 (p = 0.01 for RNA, p = 0,006 for protein) and aldehyde dehydrogenase 1A2 (p = 0.04 for RNA, p = 0,014 for protein), while gene expression of cytochrome P450 26B1 was downregulated (p = 0.007). Concomitantly, retinol accumulated in the infarcted zone (p = 0.02). CM and CF isolated from infarcted hearts had higher luminescence than those from sham operated hearts (p = 0.02 and p = 0.008). AtRA inhibited CF proliferation <em>in vitro</em> (p = 0.02).</p> <h3>Conclusion</h3><p>The RA signalling pathway is activated in postischemic hearts and may play a role in regulation of damage and repair during remodelling.</p> </div

Crude and adjusted uteroplacental arteriovenous and umbilical venoarterial concentration differences with p-values.

<p>Crude and adjusted uteroplacental arteriovenous and umbilical venoarterial concentration differences with p-values.</p

Expression of retinoic acid target genes in the infarct zone and effects on cardiofibroblast proliferation.

<p><b>A)</b> Gene expression of retinoic acid target genes in cardiofibroblast (CF) and cardiomyocytes (CM) isolated from left ventricles of infarcted RAR-luciferase reporter hearts 1 week after infarction. RNA was extracted from cells from the infarcted zone and amplified with real time PCR using primers specific for retinol binding protein 1 (RBP1), cytochrome P450 26B1 (CYP26B1), aldehyde dehydrogenase 1A2 (ALDH1A2), and retinoic acid receptors alpha, beta and gamma (RAR α,β,γ). The figure shows test gene expression relative to expression of rpl32, which was similar in both cell types. Data are mean±SD of n = 5 experiments in each group. <b>B)</b> Cardiofibroblasts were isolated from C57BL6 hearts and cultured in medium supplemented with 1 µM all-trans retinoic acid (atRA) and 10 µM EdU, as indicator of cell division. After 96 hours, EdU incorporation was evaluated by flow cytometry. Data are presented as mean±SD of n = 4 in each group.</p

<i>In vitro</i> imaging of retinoic acid signaling after myocardial infarction.

<p>Cardiomyocytes and cardiofibroblasts were isolated from left ventricular tissue from RARE-luciferase reporter hearts one week after myocardial infarction or sham operation (SHAM). Cells were isolated from the infarct (INF) and periinfarct zone (PERIINF). After plating for three hours, non-viable cells were removed and luciferin was added for imaging. The upper panel shows a representative image of one experiment (<b>A</b>). The lower panel shows mean±SD of n = 5 experiments in each group (<b>B</b>). Note that the Y-axis labelling is different.</p

Additional file 1: of Validation of two short questionnaires assessing physical activity in colorectal cancer patients

Physical activity, all participants in total and stratified by sex. Physical activity levels based on Norwegian Food Based Dietary Guideline (i.e. moderate intensity physical activity and vigorous intensity physical activity) are presented in minutes per week as both self-reported by NORDIET-FFQ and objectively measured by SenseWear Armband (SWA). (DOCX 18 kb

Expression of retinoic acid target genes and endogenous metabolites after infarction.

<p>Wild type C57Bl6 mice were subjected to <i>in vivo</i> ligation of the left coronary artery or sham surgery, and hearts were sampled serially for RNA extraction and amplification of retinoic acid target genes with real time PCR, or proteins were extracted for western blotting. Hearts were also sampled from mice without any surgery (preoperative). Gene expression of retinol binding protein 1 (RBP1) (<b>A</b>), aldehyde dehydrogenase 1A2 (ALDH1A2) (<b>B</b>), and cytochrome p45026B1 (CYP26B1) are shown (<b>C</b>). (n = 6–8 in each group at each time point). <b>D)</b> Representative western blot analysis of retinoic acid transporting and metabolizing proteins one week after induction of infarction or sham operation. Ponceau solution was used as protein loading (control). Histograms show the relative density of RBP1 at 16 kDa and ALDH1A2 at 53–57 kDa in infarcted and sham operated hearts. <b>E)</b> Endogenous retinoic acid metabolite concentrations were evaluated by triple-stage liquid chromatography/tandem mass spectrometry one week after induction of myocardial infarction. The infarcted zone of the left ventricle (INF), the periinfarcted zone (PERIINF) and left ventricles from sham operated hearts (SHAM) were investigated (n = 6). Data are shown as mean±SD.</p

Additional file 2: of Validation of two short questionnaires assessing physical activity in colorectal cancer patients

Bland-Altman plots depicting the mean differences (NORDIET-FFQ minus SenseWear Armband (SWA)) for physical activity in minutes per week; A. total-moderate intensity physical activity in minutes/week, B. total-vigorous intensity physical activity, minutes/week. The solid line represents the mean, and the dashed lines represent the 1.96 SDs of the observations. Females denoted as ♀ and males denoted as ♂. (TIF 1133 kb