Quantitative assignment of reaction directionality in a multicompartmental human metabolic reconstruction.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Reaction directionality is a key constraint in the modeling of genome-scale metabolic networks. We thermodynamically constrained reaction directionality in a multicompartmental genome-scale model of human metabolism, Recon 1, by calculating, in vivo, standard transformed reaction Gibbs energy as a function of compartment-specific pH, electrical potential, and ionic strength. We show that compartmental pH is an important determinant of thermodynamically determined reaction directionality. The effects of pH on transport reaction thermodynamics are only seen to their full extent when metabolites are represented as pseudoisomer groups of multiple protonated species. We accurately predict the irreversibility of 387 reactions, with detailed propagation of uncertainty in input data, and manually curate the literature to resolve conflicting directionality assignments. In at least half of all cases, a prediction of a reversible reaction directionality is due to the paucity of compartment-specific quantitative metabolomic data, with remaining cases due to uncertainty in estimation of standard reaction Gibbs energy. This study points to the pressing need for 1), quantitative metabolomic data, and 2), experimental measurement of thermochemical properties for human metabolites.Icelandic Research Fund/00406022 eu-repo/grantAgreement/EC/FP7/23281

Diagnostic accuracy of 64-slice computed tomography compared with coronary angiography

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenObjective: The aim of this study was to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) of 64-slice multidetector computed tomography (MDCT) compared with quantitative coronary angiography (QCA) for detection of coronary artery disease (CAD). Material and methods: Sixty-nine patients participating in a study of coronary in-stent restenosis were investigated. After a 64-slice MDCT scan patients were evaluated by QCA. The coronary arteries were divided into 15 segments and stenosis was graded for each segment by both methods. The diagnostic accuracy of 64-slice MDCT was evaluated using the QCA as the gold standard. Results: Among the 69 patients included in the study 13 (19%) were female and 56 male. The mean age was 63 (SD 10) years. The following risk factors were present: high blood pressure 67%, elevated blood cholesterol 54%, diabetes 12% and family history of CAD 71%. Current smokers were 22% and previous smokers were 48%. Altogether 663 segments were examined. Of those 221 (33%) segments were excluded; 103 because of stents, 48 because of heavy calcification, 41 because of motion artifacts and 29 because the segments were less than 1.5 mm in diameter. The mean time between MDCT and QCA was 6.3 (SD 12.1) days. The sensitivity of 64-slice MDCT for diagnosing significant stenosis (>/= 50% according to QCA) was 20%, the specificity was 94%, PPV was 16%, NPV was 95% and the accuracy was 89%. Conclusion: High NPV and specificity indicates that MDCT is useful for accurately excluding significant CAD but the low sensitivity and low PPV indicate that the method is not accurate in diagnosing coronary artery stenosis of 50% or more according to QCA. Key words: coronary artery disease, multidetector computed tomography, cardiac catheterisation. Correspondence: Karl Andersen, [email protected]: Markmið rannsóknarinnar var að meta greiningarhæfni (næmi, sértæki, jákvætt forspárgildi, neikvætt forspárgildi og nákvæmni) 64 sneiða tölvusneiðmyndatækni (TS-tækni) á kransæðasjúkdómi með hjartaþræðingu sem viðmið. Efniviður og aðferðir: Rannsóknarhópurinn samanstóð af 69 sjúklingum sem tóku þátt í rannsókn á endurþrengslum í stoðnetum kransæða. Framkvæmd var TS af kransæðum til að meta æðaþrengsli. Nokkrum dögum síðar voru þátttakendur hjartaþræddir. Kransæðatrénu var skipt upp í 15 hluta. Æðaþrengsli voru metin í öllum hlutum æðatrésins með báðum aðferðunum. Greiningarhæfni 64 sneiða TS-tækni var metin og kransæðaþræðing höfð sem viðmið. Niðurstöður: Í rannsókninni voru 13 (19%) konur og 56 karlar. Meðalaldur þátttakenda var 63 (SD 10) ár, háþrýsting höfðu 67%, háar blóðfitur 54%, sykursýki 12% og ættarsaga um kransæðasjúkdóm var til staðar í 71% tilvika. Reykingamenn voru 22% og fyrrum reykingamenn 48%. Samtals 663 æðahlutar voru rannsakaðir. Af þeim voru 221 (33,4%) útilokaðir; 103 vegna stoðneta, 48 vegna truflana af völdum kalks, 41 vegna hreyfitruflana og 29 þar sem æðin var minni en 1,5 mm í þvermál. Meðaltími milli TS og hjartaþræðingar voru 6,3 (SD 12,1) dagar. Næmi 64 sneiða TS til greiningar marktækra þrengsla (?50% þrengsli samkvæmt hjartaþræðingu) var 20%, sértæki 94%, jákvætt forspárgildi 16%, neikvætt forspárgildi 95% og nákvæmni 89%. Ályktun: Hátt neikvætt forspárgildi og hátt sértæki gefur til kynna að TS-rannsókn sé gagnleg til að útiloka kransæðasjúkdóm. Lágt næmi og lágt jákvætt forspárgildi benda til að aðferðin sé ekki góð til að meta hvort kransæðaþrengsli séu 50% eða meiri við hjartaþræðingu

Green tea extract only affects markers of oxidative status postprandially: lasting antioxidant effect of flavonoid-free diet

Epidemiological studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease and cancer. The objective of the present study was to investigate the effect of green tea extract (GTE) used as a food antioxidant on markers of oxidative status after dietary depletion of flavonoids and catechins. The study was designed as a 2×3 weeks blinded human cross-over intervention study (eight smokers, eight non-smokers) with GTE corresponding to a daily intake of 18·6 mg catechins/d. The GTE was incorporated into meat patties and consumed with a strictly controlled diet otherwise low in flavonoids. GTE intervention increased plasma antioxidant capacity from 1·35 to 1·56 (P<0·02) in postprandially collected plasma, most prominently in smokers. The intervention did not significantly affect markers in fasting blood samples, including plasma or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the erythrocyte superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase. Neither were fasting plasma triacylglycerol, cholesterol, α-tocopherol, retinol, β-carotene, or ascorbic acid affected by intervention. Urinary 8-oxo-deoxyguanosine excretion was also unaffected. Catechins from the extract were excreted into urine with a half-life of less than 2 h in accordance with the short-term effects on plasma antioxidant capacity. Since no long-term effects of GTE were observed, the study essentially served as a fruit and vegetables depletion study. The overall effect of the 10-week period without dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood proteins, and plasma lipids, concomitantly with marked changes in antioxidative defenc

Fruit and vegetable intake in a sample of 11-year-old children in 9 European countries: The pro children cross-sectional survey

Background/Aims: An adequate fruit and vegetable intake provides essential nutrients and nutritive compounds and is considered an important part of a healthy lifestyle. No simple instrument has been available for the assessment of fruit and vegetable intake as well as its determinants in school-aged children applicable in different European countries. Within the Pro Children Project, such an instrument has been developed. This paper describes the cross-sectional survey in 11-year-olds in 9 countries. Methods: The cross-sectional survey used nationally, and in 2 countries regionally, representative samples of schools and classes. The questionnaires, including a precoded 24-hour recall component and a food frequency part, were completed in the classroom. Data were treated using common syntax files for portion sizes and for merging of vegetable types into four subgroups. Results: The results show that the fruit and vegetable intake in amounts and choice were highly diverse in the 9 participating countries. Vegetable intake was in general lower than fruit intake, boys consumed less fruit and vegetables than girls did. The highest total intake according to the 24-hour recall was found in Austria and Portugal, the lowest in Spain and Iceland. Conclusion: The fruit and vegetable intake in 11-year-old children was in all countries far from reaching population goals and food-based dietary guidelines on national and international levels. Copyrigh

Changes in immunocompetent cells after interstitial laser thermotherapy of breast cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes. METHODS: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens. RESULTS: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone. CONCLUSIONS: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer

Relative validity of a semiquantitative food frequency questionnaire designed for schoolchildren in western Greece

<p>Abstract</p> <p>Background</p> <p>The use of food frequency questionnaires (FFQs) has become increasingly important in epidemiologic studies. During the past few decades, a wide variety of nutritional studies have used the semiquantitative FFQ as a tool for assessing and evaluating dietary intake. One of the main concerns in a dietary analysis is the validity of the collected dietary data.</p> <p>Methods</p> <p>This paper discusses several methodological and statistical issues related to the validation of a semiquantitative FFQ. This questionnaire was used to assess the nutritional habits of schoolchildren in western Greece. For validation purposes, we selected 200 schoolchildren and contacted their respective parents. We evaluated the relative validity of 400 FFQs (200 children's FFQs and 200 parents' FFQs).</p> <p>Results</p> <p>The correlations between the children's and the parents' questionnaire responses showed that the questionnaire we designed was appropriate for fulfilling the purposes of our study and in ranking subjects according to food group intake.</p> <p>Conclusion</p> <p>Our study shows that the semiquantitative FFQ provides a reasonably reliable measure of dietary intake and corroborates the relative validity of our questionnaire.</p

Patterns in sedentary and exercise behaviors and associations with overweight in 9–14-year-old boys and girls - a cross-sectional study.

BACKGROUND: Before starting interventions addressing energy-balance related behaviors, knowledge is needed about the prevalence of sedentary behaviors and low physical exercise, their interrelationships, possible gender differences. Therefore this study aimed to describe gender differences in sedentary and physical exercise behaviors and their association with overweight status in children from nine European countries. Additionally, to identify clusters of children sharing the same pattern regarding sedentary and physical exercise behavior and compare these groups regarding overweight status. METHODS: Cross-sectional study among 11-year-old children in nine countries (n = 12538). Self-administered questionnaires assessed the time spent on TV viewing during dinner and during the day, PC use and on physical exercise. The parents reported children's weight and height. Descriptive statistics, cluster analyses, and logistic regression analyses were used for data analyses. RESULTS: Boys spent more time on sedentary behaviors but also more on physical exercise than girls. High TV viewing and low exercise behavior independently increased the risk of being overweight. Based on the behaviors, five clusters were identified. Among boys, clear associations with being overweight were found, with the most unhealthy behavior pattern having the highest risks of being overweight. Among girls, high TV viewers and high PC users had increased risk of being overweight. In girls sedentary behaviors seemed more important than physical exercise with regard to overweight status. CONCLUSION: Despite selective non-response on BMI and reliance on self-reports, the associations between clusters and overweight in boys were clear, and differences between boys and girls regarding the behaviors and risks for overweight are noteworthy. These differences need to be considered when developing tailored intervention strategies for prevention of overweight

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

Publisher's version (útgefin grein).Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.We are grateful to the participants and we thank the staff at the Research Recruitment Center. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. We are grateful to the Benefit Society for Children with Disabilities (Styrktarfélag Lamaðra og Fatlaðra; SLF) for their participation. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no. 115008 (NEWMEDS) and no. 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007–2013), from EU-FP7 grants no. 602450 (IMAGEMEND) and no. 502805 (Aggressotype), EU-FP7-People-2011-IAPP grant no. 286213 (PsychDPC), and The Research Council of Norway (#226971, 229129, 223273, 213694, 248778), the KG Jebsen Stiftelsen (SKGJ-MED-002 and SKGJ-MED-008), and The South-East Norway Health Authority (#2012–132).Peer Reviewe

Moiety vectors for DAS.

<p>Moiety vectors for DAS.</p

Instantaneous iCore moieties.

<p>Carbon and phosphate containing moieties in an extreme pathway of the <i>E. coli</i> core network that corresponds to glycolysis. Four conserved moieties are distinguished by shape in the figure. The pathway also conserves one oxygen atom moiety and two hydrogen atom moieties that were omitted to simplify the figure. Metabolite abbreviations are, Glc: D-glucose (VMH [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004999#pcbi.1004999.ref023" target="_blank">23</a>] ID: glc_D), PEP: phosphoenolpyruvate (VMH ID: pep), Pyr: pyruvate (VMH ID: pyr), F6P: D-fructose 6-phosphate (VMH ID: f6p), ATP: adenosine triphosphate (VMH ID: atp), ADP: adenosine diphosphate (VMH ID: adp), FDP: D-fructose 1,6-bisphosphate (VMH ID: fdp), DHAP: dihydroxyacetone phosphate (VMH ID: dhap), G3P: glyceraldehyde 3-phosphate (VHM ID: g3p), NAD: nicotinamide adenine dinucleotide (VMH ID: nad), P_<i>bluei</i>: orthophosphate (VMH ID: pi), NADH: reduced nicotinamide adenine dinucleotide (VMH ID: nadh), DPG: 1,3-bisphospho-D-glycerate (VMH ID: 13dpg), Lac: D-lactate (VMH ID: lac_D). The glucose moiety (circles) is transitive whereas the other three moieties are internal, including the phosphate moiety (squares) which was classified as integrative in the full iCore network.</p