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"text": "\n187333\nSelexipag for the Treatment of Pulmonary Arterial Hypertension.\n\nSitbon, O\n\nChannick, R\n\nChin, KM\n\nFrey, A\n\nGaine, S\n\nGaliè, N\n\nGhofrani, HA\n\nHoeper, MM\n\nLang, IM\n\nPreiss, R\n\nRubin, LJ\n\nDi Scala, L\n\nTapson, V\n\nAdzerikho, I\n\nLiu, J\n\nMoiseeva, O\n\nZeng, X\n\nSimonneau, G\n\nMcLaughlin, VV\n\nGRIPHON Investigators\n\nBeiträge in Fachzeitschriften\nNone\n26699168.0\n10.1056/NEJMoa1503184\nNone\nIn a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension.\n In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned 1156 patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both. The primary end point was a composite of death from any cause or a complication related to pulmonary arterial hypertension up to the end of the treatment period (defined for each patient as 7 days after the date of the last intake of selexipag or placebo).\n A primary end-point event occurred in 397 patients--41.6% of those in the placebo group and 27.0% of those in the selexipag group (hazard ratio in the selexipag group as compared with the placebo group, 0.60; 99% confidence interval, 0.46 to 0.78; P<0.001). Disease progression and hospitalization accounted for 81.9% of the events. The effect of selexipag with respect to the primary end point was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving treatment at baseline (including those who were receiving a combination of two therapies). By the end of the study, 105 patients in the placebo group and 100 patients in the selexipag group had died from any cause. Overall, 7.1% of patients in the placebo group and 14.3% of patients in the selexipag group discontinued their assigned regimen prematurely because of adverse events. The most common adverse events in the selexipag group were consistent with the known side effects of prostacyclin, including headache, diarrhea, nausea, and jaw pain.\n Among patients with pulmonary arterial hypertension, the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo. There was no significant difference in mortality between the two study groups. (Funded by Actelion Pharmaceuticals; GRIPHON ClinicalTrials.gov number, NCT01106014.).\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n2392\nSonographic evaluation of focal nodular hyperplasias (FNH) of the liver with a transpulmonary galactose-based contrast agent (Levovist).\n\nUggowitzer, M\n\nKugler, C\n\nGröll, R\n\nMischinger, HJ\n\nStacher, R\n\nFickert, P\n\nWeiglein, A\n\nBeiträge in Fachzeitschriften\nISI:000076473100006\n10211062.0\n10.1259/bjr.71.850.10211062\nNone\nFocal nodular hyperplasias (FNH) are hypervascular, benign focal liver lesions. Differentiation of FNH from other focal liver lesions is of clinical importance. The purpose of this study was to examine the impact of a new, transpulmonary echo-enhancing agent SHU 508A (Levovist) and recent Doppler techniques in the sonographic evaluation of FNH. 43 patients with 61 focal nodular hyperplasias of the liver were examined with grey scale ultrasound and power Doppler ultrasound. Levovist, a galactose-air-microbubble suspension was administered intravenously in all patients, either by bolus injection (400 mg ml-1) or continuous pump-infusion (300 mg ml-1). Visualization of the feeding vessels and vascularity of the lesions were evaluated. The resistance indexes (RI) in the feeding vessel and the hepatic artery were assessed and compared with the diameters of the FNH. The mean diameter of FNH was 4.3 cm (+/- 1.0). Echo enhanced power Doppler ultrasound was superior to unenhanced power Doppler ultrasound in the detection of the feeding artery (85% vs. 98%) in FNH and depicted the internal vascular architecture more clearly, especially in lesions located in the left lobe of the liver. Lesions smaller than 3 cm did not show a characteristic vascular architecture with echo enhanced Doppler ultrasound. The resistance index of the feeding artery (mean: 0.51 +/- 0.08) is significantly (p < 0.0001) lower than that of the hepatic artery (mean 0.65 +/- 0.06) with a mean difference of -0.14 +/- 0.01 in the same patient. The RI of the feeding artery significantly decreased as the size of the FNH increased, whereas RI differences between the hepatic artery and the feeding artery increased with lesion size. Intravenous (i.v.) bolus injection of the contrast agent will depict the hypervascular nature of FNH more clearly than i.v. infusion, although the latter will significantly prolong the diagnostic window. In conclusion, i.v. infusion of Levovist improves the visualization of the feeding artery and the radiating vascular architecture in FNH located in the left lobe of the liver due to improved signal-to-noise ratio and results in more effective suppression of motion artefacts. Although echo enhanced Doppler ultrasound improves the detection of the low resistance arterial feeding vessel in small FNH, it will not, however, reveal a specific vascular pattern in these lesions.\n\nFickert, Peter\n\nMischinger, Hans-Joerg\n\n\n"
},
{
"text": "\n5055\nThe effect of caffeine on peripheral vascular resistance in isolated perfused guinea pig hind limbs.\n\nBrodmann, M\n\nLischnig, U\n\nLueger, A\n\nPilger, E\n\nStark, G\n\nBeiträge in Fachzeitschriften\nISI:000185607200008\n14508236.0\n10.1097%2F00005344-200310000-00008\nNone\nBACKGROUND: The role of caffeine in cardiovascular disease is controversial. Most of its pharmacologic actions are attributed to its role as an adenosine antagonist. Adenosine is one of the most important endogenous vasodilatative substances and is released under ischemic conditions, for example, in the skeletal muscle of patients with peripheral arterial occlusive disease. We aimed to investigate the influence of caffeine on peripheral vascular resistance and on the beneficial vasodilatory effect of adenosine in isolated perfused guinea pig hind limbs. MATERIALS AND METHODS: (1) Caffeine was administered at 0.5, 5, and 50 micromol/L under normoxic conditions. (2) The vasculature of the perfused guinea pig hind limb was precontracted with noradrenaline (3 micromol/L), followed by adenosine (10 micromol/L) under normoxic conditions. When vascular resistance (VR) had reached a steady state, caffeine was administered additionally at dosages of 0.5, 5, and 50 micromol/L. (3) This protocol was repeated using iloprost 0.1 micromol/L instead of adenosine as vasodilatory substance. (4) Under hypoxia, caffeine was again administered at the above dosages. (5) Under hypoxia, experiments with adenosine A2-receptor antagonists (alloxazine 10 micromol/L and ZM 241385 100 nmol/L) were done. RESULTS: Under normoxic conditions, 0.5 and 5 micromol/L caffeine had nearly no effect on vascular resistance compared with baseline conditions. A slight, but statistically not significant decrease in VR was achieved with 50 micromol/L caffeine. In the presence of noradrenaline, the vasodilatory effect of adenosine was reduced by 7.6 +/- 1.6% after the addition of 0.5 micromol/L caffeine, and by 37.3 +/- 3.8% at a dosage of 5 micromol/L caffeine. A dosage of 50 micromol/L caffeine completely abolished the vasodilatative effect of adenosine. In the presence of iloprost, only a slight but statistically insignificant inhibitory influence (0.9%) of caffeine at a dosage of 50 micromol/L could be seen. Hypoxia significantly reduced VR. Caffeine at 0.5 micromol/L diminished this effect by about 53.2 +/- 4.6% and abolished it at 5 and 50 micromol/L. The hypoxia-induced adenosine-mediated vasodilatation seems to be an adenosine A2A-receptor-mediated effect. CONCLUSIONS: The observed effect of hypoxia-induced vasodilatation in peripheral arteries may be the result of the vasodilatory effect of elevated endogenous adenosine during hypoxia. For patients with peripheral arterial disease, drinking of caffeine-containing beverages may reduce the beneficial vasodilatory effect of elevated endogenous adenosine levels.\n\nBrodmann, Marianne\n\nLueger, Andreas\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n128009\nThe molecular genetic architecture of self-employment.\n\nvan der Loos, MJ\n\nRietveld, CA\n\nEklund, N\n\nKoellinger, PD\n\nRivadeneira, F\n\nAbecasis, GR\n\nAnkra-Badu, GA\n\nBaumeister, SE\n\nBenjamin, DJ\n\nBiffar, R\n\nBlankenberg, S\n\nBoomsma, DI\n\nCesarini, D\n\nCucca, F\n\nde Geus, EJ\n\nDedoussis, G\n\nDeloukas, P\n\nDimitriou, M\n\nEiriksdottir, G\n\nEriksson, J\n\nGieger, C\n\nGudnason, V\n\nHöhne, B\n\nHolle, R\n\nHottenga, JJ\n\nIsaacs, A\n\nJärvelin, MR\n\nJohannesson, M\n\nKaakinen, M\n\nKähönen, M\n\nKanoni, S\n\nLaaksonen, MA\n\nLahti, J\n\nLauner, LJ\n\nLehtimäki, T\n\nLoitfelder, M\n\nMagnusson, PK\n\nNaitza, S\n\nOostra, BA\n\nPerola, M\n\nPetrovic, K\n\nQuaye, L\n\nRaitakari, O\n\nRipatti, S\n\nScheet, P\n\nSchlessinger, D\n\nSchmidt, CO\n\nSchmidt, H\n\nSchmidt, R\n\nSenft, A\n\nSmith, AV\n\nSpector, TD\n\nSurakka, I\n\nSvento, R\n\nTerracciano, A\n\nTikkanen, E\n\nvan Duijn, CM\n\nViikari, J\n\nVölzke, H\n\nWichmann, HE\n\nWild, PS\n\nWillems, SM\n\nWillemsen, G\n\nvan Rooij, FJ\n\nGroenen, PJ\n\nUitterlinden, AG\n\nHofman, A\n\nThurik, AR\n\nBeiträge in Fachzeitschriften\nISI:000319108100052\n23593239.0\n10.1371/journal.pone.0060542\nPMC3617140\nEconomic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σ(g)(2)/σ(P)(2) = 25%, h(2) = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50, 27 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10(-5) were tested in a replication sample (n = 3, 71), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.\n\nKoini, Marisa\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n129027\nPARP1 impact on DNA repair of platinum adducts: preclinical and clinical read-outs.\n\nOlaussen, KA\n\nAdam, J\n\nVanhecke, E\n\nVielh, P\n\nPirker, R\n\nFriboulet, L\n\nPopper, H\n\nRobin, A\n\nCommo, F\n\nThomale, J\n\nKayitalire, L\n\nFilipits, M\n\nLe Chevalier, T\n\nAndré, F\n\nBrambilla, E\n\nSoria, JC\n\nBeiträge in Fachzeitschriften\nISI:000318262500016\n23410825.0\n10.1016/j.lungcan.2013.01.014\nNone\nEvaluation of DNA repair proteins might provide meaningful information in relation to prognosis and chemotherapy efficacy in Non-Small Cell Lung Cancer (NSCLC) patients. The role of Poly(ADP-Ribose) Polymerase (PARP) in DNA repair of platinum adducts has not been firmly established. We used a DNA repair functional test based on antibody recognition of cisplatin intrastrand platinum adducts on DNA. We evaluated the effect of PARP inhibition on DNA repair functionality in a panel of cisplatin cell lines treated by the clinical-grade pharmacological inhibitor CEP8983 (a 4-methoxy-carbazole derivate) and the commercially available inhibitor PJ34 (phenanthridinone). We determined PARP1 protein expression in whole tumor sections from the International Adjuvant Lung cancer Trial (IALT)-bio study and tested a 3-marker PARP1/MSH2/ERCC1 algorithm combining PARP1 tumor status with previously published data. Chemosensitivity of cisplatin in NSCLC cell lines was correlated with the accumulation of cisplatin DNA adducts (P=0.0004). Further, the pharmacological inhibition of PARP induced a 1.7 to 2.3-fold increase in platinum adduct accumulation (24h) in A549 cell line suggesting a slow-down of platinum DNA-adduct repair capacity. In parallel, PARP1 inhibition increased the sensitivity to cisplatin treatment. In patient samples, PARP1 expression levels did not influence patient survival or the effect of platinum-based post-operative chemotherapy in the global IALT-bio population (interaction P=0.79). Among cases with high expression of all three markers (triple positive), untreated patients had prolonged survival with a median DFS of 7.8 years, (HR=0.34, 95%CI [0.19-0.61], adjusted P=0.0003) compared to triple negative patients (1.4 years). Remarkably, triple positive patients suffered from a detrimental effect (4.9-year reduction of median DFS) by post-operative cisplatin-based chemotherapy (HR=1.79, 95%CI [1.01-3.17], adjusted P=0.04, chemotherapy vs. control). Combinatorial sub-group analysis of the 3 markers further suggested that PARP1 tumor positivity might constitute a molecular context with high theranostic interest of ERCC1 and MSH2 in NSCLC. In conclusion, our data confirm that platinum DNA adduct accumulation is linked to chemosensitivity, which increase by pharmacological PARP inhibitors points to a role of PARP-dependent DNA repair in the process. We further suggest DNA repair biomarkers should be analyzed in a larger context of multiple DNA repair pathway regulation.\n\nPopper, Helmuth\n\n\n"
},
{
"text": "\n135080\nColorectal cancer stage at diagnosis in migrants versus non-migrants (KoMigra): study protocol of a cross-sectional study in Germany.\n\nDahlhaus, A\n\nGuethlin, C\n\nSchall, A\n\nTaubenroth, M\n\nvan Ewijk, R\n\nZeeb, H\n\nAlbay, Z\n\nSchulz-Rothe, S\n\nBeyer, M\n\nGerlach, FM\n\nBlettner, M\n\nSiebenhofer, A\n\nBeiträge in Fachzeitschriften\nISI:000332527000002\n24559172.0\n10.1186/1471-2407-14-123\nPMC3939398\nIn Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences.\n Data on tumour and migration status will be collected for 1, 00 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants.\n An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants.\n German Clinical Trials Register DRKS00005056.\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n151848\nExtracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.\n\nReininghaus, EZ\n\nLackner, N\n\nBirner, A\n\nBengesser, S\n\nFellendorf, FT\n\nPlatzer, M\n\nRieger, A\n\nQueissner, R\n\nKainzbauer, N\n\nReininghaus, B\n\nMcIntyre, RS\n\nMangge, H\n\nZelzer, S\n\nFuchs, D\n\nDejonge, S\n\nMüller, N\n\nBeiträge in Fachzeitschriften\nISI:000373124400007\n27016286.0\n10.1111/bdi.12380\nNone\nMatrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported.\n The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters.\n MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2) = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2) = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2) = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms.\n A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population.\n © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nFellendorf, Frederike\n\nMangge, Harald\n\nPlatzer, Martina\n\nQueissner, Robert\n\nReininghaus, Eva\n\nRieger, Alexandra\n\nZelzer, Sieglinde\n\n\n"
},
{
"text": "\n4701\nDeterminants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).\n\nRoy, DK\n\nO'Neill, TW\n\nFinn, JD\n\nLunt, M\n\nSilman, AJ\n\nFelsenberg, D\n\nArmbrecht, G\n\nBanzer, D\n\nBenevolenskaya, LI\n\nBhalla, A\n\nBruges Armas, J\n\nCannata, JB\n\nCooper, C\n\nDequeker, J\n\nDiaz, MN\n\nEastell, R\n\nYershova, OB\n\nFelsch, B\n\nGowin, W\n\nHavelka, S\n\nHoszowski, K\n\nIsmail, AA\n\nJajic, I\n\nJanott, I\n\nJohnell, O\n\nKanis, JA\n\nKragl, G\n\nLopez Vaz, A\n\nLorenc, R\n\nLyritis, G\n\nMasaryk, P\n\nMatthis, C\n\nMiazgowski, T\n\nGennari, C\n\nPols, HA\n\nPoor, G\n\nRaspe, HH\n\nReid, DM\n\nReisinger, W\n\nScheidt-Nave, C\n\nStepan, JJ\n\nTodd, CJ\n\nWeber, K\n\nWoolf, AD\n\nReeve, J\n\nEuropean Prospective Osteoporosis Study (EPOS)\n\nBeiträge in Fachzeitschriften\nISI:000181251200004\n12577181.0\n10.1007/s00198-002-1317-8\nNone\nThe aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n68381\nTumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: a comparative study featuring dynamic 18F-MISO and 124I-IAZG PET in the same study cohort.\n\nRiedl, CC\n\nBrader, P\n\nZanzonico, P\n\nReid, V\n\nWoo, Y\n\nWen, B\n\nLing, CC\n\nHricak, H\n\nFong, Y\n\nHumm, JL\n\nBeiträge in Fachzeitschriften\nISI:000251456800007\n17786438.0\n10.1007/s00259-007-0522-2\nPMC2723938\nPURPOSE: The purpose of this paper is to compare the uptake of two clinically promising positron emission tomography (PET) hypoxia targeting agents, (124)I-iodoazomycin galactopyranoside ((124)I-IAZG) and (18)F-fluoromisonidazole ((18)F-FMISO), by dynamic microPET imaging, in the same rats bearing liver tumors and peritoneal metastasis. METHODS: Morris hepatoma (RH7777) fragments were surgically implanted into the livers of four nude rats. Tumors formed in the liver and disseminated into the peritoneal cavity. Each rat had a total of two to three liver tumors and peritoneal metastasis measuring 10-15 mm in size. Animals were injected with (18)F-FMISO, followed on the next day (upon complete (18)F decay) by (124)I-IAZG. The animals were imaged in list mode on the microPET system from the time of injection of each tracer for 3 h and then again at 6 h and 24 h for the long-lived (124)I-IAZG tracer (4.2-day half-life). Micro computed tomography (CT) scans of each rat were performed for co-registration with the microPET scans acquired with a liver contrast agent, allowing tumor identification. Regions of interest (ROIs) were drawn over the heart, liver, muscle, and the hottest areas of the tumors. Time-activity curves (TACs) were drawn for each tissue ROI. RESULTS: The (18)F-FMISO signal increased in tumors over the 3-h time course of observation. In contrast, after the initial injection, the (124)I-IAZG signal slowly and continuously declined in the tumors. Nevertheless, the tumor-to-normal-tissue ratios of (124)I-IAZG increased, but more slowly than those of (18)F-FMISO and as a result of the differentially faster clearance from the surrounding normal tissues. These pharmacokinetic patterns were seen in all 11 tumors of the four animals. CONCLUSIONS: (18)F-FMISO localizes in the same intra-tumor regions as (124)I-IAZG. The contrast ratios (tumor/background) reach similar values for the two hypoxia tracers, but at later times for (124)I-IAZG than for (18)F-FMISO and, therefore, with poorer count statistics. As a consequence, the (18)F-FMISO images are of superior diagnostic image quality to the (124)I-IAZG images in the Morris hepatoma McA-R-7777 tumor model.\n\n\n"
},
{
"text": "\n175075\nAdvancing Biomarker Development Through Convergent Engagement: Summary Report of the 2nd International Danube Symposium on Biomarker Development, Molecular Imaging and Applied Diagnostics; March 14-16, 2018; Vienna, Austria.\n\nLim, MS\n\nBeyer, T\n\nBabayan, A\n\nBergmann, M\n\nBrehme, M\n\nBuyx, A\n\nCzernin, J\n\nEgger, G\n\nElenitoba-Johnson, KSJ\n\nGückel, B\n\nJačan, A\n\nHaslacher, H\n\nHicks, RJ\n\nKenner, L\n\nLanganke, M\n\nMitterhauser, M\n\nPichler, BJ\n\nSalih, HR\n\nSchibli, R\n\nSchulz, S\n\nSimecek, J\n\nSimon, J\n\nSoares, MO\n\nStelzl, U\n\nWadsak, W\n\nZatloukal, K\n\nZeitlinger, M\n\nHacker, M\n\nBeiträge in Fachzeitschriften\nISI:000513265700011\n31049831.0\n10.1007/s11307-019-01361-2\nNone\nHere, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting "lumpology" for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking "What can we do with our expertise to help patients?"\n\nSchulz, Stefan\n\nZatloukal, Kurt\n\n\n"
},
{
"text": "\n21922\nSildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial.\n\nGhofrani, HA\n\nReichenberger, F\n\nKohstall, MG\n\nMrosek, EH\n\nSeeger, T\n\nOlschewski, H\n\nSeeger, W\n\nGrimminger, F\n\nBeiträge in Fachzeitschriften\nISI:000223068600001\n15289213.0\n10.7326/0003-4819-141-3-200408030-00005\nNone\nBACKGROUND: Alveolar hypoxia causes pulmonary hypertension and enhanced right ventricular afterload, which may impair exercise tolerance. The phosphodiesterase-5 inhibitor sildenafil has been reported to cause pulmonary vasodilatation. OBJECTIVE: To investigate the effects of sildenafil on exercise capacity under conditions of hypoxic pulmonary hypertension. DESIGN: Randomized, double-blind, placebo-controlled crossover study. SETTING: University Hospital Giessen, Giessen, Germany, and the base camp on Mount Everest. PARTICIPANTS: 14 healthy mountaineers and trekkers. MEASUREMENTS: Systolic pulmonary artery pressure, cardiac output, and peripheral arterial oxygen saturation at rest and during assessment of maximum exercise capacity on cycle ergometry 1) while breathing a hypoxic gas mixture with 10% fraction of inspired oxygen at low altitude (Giessen) and 2) at high altitude (the Mount Everest base camp). INTERVENTION: Oral sildenafil, 50 mg, or placebo. RESULTS: At low altitude, acute hypoxia reduced arterial oxygen saturation to 72.0% (95% CI, 66.5% to 77.5%) at rest and 60.8% (CI, 56.0% to 64.5%) at maximum exercise capacity. Systolic pulmonary artery pressure increased from 30.5 mm Hg (CI, 26.0 to 35.0 mm Hg) at rest to 42.9 mm Hg (CI, 35.6 to 53.5 mm Hg) during exercise in participants taking placebo. Sildenafil, 50 mg, significantly increased arterial oxygen saturation during exercise (P = 0.005) and reduced systolic pulmonary artery pressure at rest (P < 0.001) and during exercise (P = 0.031). Of note, sildenafil increased maximum workload (172.5 W [CI, 147.5 to 200.0 W]) vs. 130.6 W [CI, 108.8 to 150.0 W]); P < 0.001) and maximum cardiac output (P < 0.001) compared with placebo. At high altitude, sildenafil had no effect on arterial oxygen saturation at rest and during exercise compared with placebo. However, sildenafil reduced systolic pulmonary artery pressure at rest (P = 0.003) and during exercise (P = 0.021) and increased maximum workload (P = 0.002) and cardiac output (P = 0.015). At high altitude, sildenafil exacerbated existing headache in 2 participants. LIMITATIONS: The study did not examine the effects of sildenafil on normoxic exercise tolerance. CONCLUSIONS: Sildenafil reduces hypoxic pulmonary hypertension at rest and during exercise while maintaining gas exchange and systemic blood pressure. To the authors' knowledge, sildenafil is the first drug shown to increase exercise capacity during severe hypoxia both at sea level and at high altitude.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n111319\nExpression of pancreatitis-associated protein after traumatic brain injury: a mechanism potentially contributing to neuroprotection in human brain.\n\nMärz-Weiss, P\n\nKunz, D\n\nBimmler, D\n\nBerkemeier, C\n\nÖzbek, S\n\nDimitriades-Schmutz, B\n\nHaybaeck, J\n\nOtten, U\n\nGraf, R\n\nBeiträge in Fachzeitschriften\nISI:000296090300003\n21643999.0\n10.1007/s10571-011-9715-0\nNone\nNeuronal cell death after severe traumatic brain injury (TBI) is caused by a complex interplay of pathological mechanisms including excitotoxicity, oxidative stress, mitochondrial dysfunction, extensive neuroinflammation, and ischemia-reperfusion injury. Pancreatitis-associated protein I (PAP I/reg2) was reported to be a survival factor for peripheral neurons, particularly sensory and motor neurons. In rat brains, by experimental TBI as well as by kainic acid induced brain seizure, PAP I and PAP III were found to be up-regulated in central neurons. In this study, we performed immunohistochemical staining in postmortem human brain from patients who died after severe TBI to demonstrate PAP expression on protein level in cerebellar Purkinje cells, pyramidal and granular neurons in cerebral cortex, and cortical neurons in the fore- and mid-brain. In primary cultures of rat brain cortical, hippocampal, and cerebellar neurons, we found neuroprotective effects for PAP I on H(2)O(2)-induced oxidative stress. Moreover, serum K(+)-deprivation induces apoptotic cell death in 55% of cerebellar granule neurons (CGN), whereas upon treatment with PAP I only 32% of CGN are apoptotic. Using Western blot analyses, we compared protein phosphorylation in neuronal signaling pathways activated by PAP I versus Interleukin-6 (IL-6). We found a rapid activation of Akt-kinase phosphorylation by PAP I with a peak at 15 min, whereas IL-6 induces Akt-phosphorylation lasting longer than 30 min. Phosphorylation of MAP-42/44 kinases is stimulated in a comparable fashion. Both, IL-6 and PAP I increase phosphorylation of NFêB for activation of gene transcription, whereas only IL-6 recruits STAT3 phosphorylation, indicating that STAT3 is not a target of PAP I transcription activation in brain neurons. Application of the Akt-inhibitor Wortmanin reveals only a partial inhibition of PAP I-dependent protection of CGN from H(2)O(2)-induced oxidative stress. Based on our findings, we suggest that PAP I is a long lasting neurotrophic signal for central neurons. The neuroprotective effects parallel those that have been described for effects of PAP I in ciliary neurotrophic factor (CNTF)-mediated survival of sensory and motor neurons. PAP I may act in autocrine and/or paracrine fashion and thus may contribute to endogenous protective mechanisms relevant under harmful conditions like oxidative stress, brain injury, or neurodegeneration.\n\nHaybäck, Johannes\n\n\n"
},
{
"text": "\n111505\nGenome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium.\n\nFornage, M\n\nDebette, S\n\nBis, JC\n\nSchmidt, H\n\nIkram, MA\n\nDufouil, C\n\nSigurdsson, S\n\nLumley, T\n\nDeStefano, AL\n\nFazekas, F\n\nVrooman, HA\n\nShibata, DK\n\nMaillard, P\n\nZijdenbos, A\n\nSmith, AV\n\nGudnason, H\n\nde Boer, R\n\nCushman, M\n\nMazoyer, B\n\nHeiss, G\n\nVernooij, MW\n\nEnzinger, C\n\nGlazer, NL\n\nBeiser, A\n\nKnopman, DS\n\nCavalieri, M\n\nNiessen, WJ\n\nHarris, TB\n\nPetrovic, K\n\nLopez, OL\n\nAu, R\n\nLambert, JC\n\nHofman, A\n\nGottesman, RF\n\nGarcia, M\n\nHeckbert, SR\n\nAtwood, LD\n\nCatellier, DJ\n\nUitterlinden, AG\n\nYang, Q\n\nSmith, NL\n\nAspelund, T\n\nRomero, JR\n\nRice, K\n\nTaylor, KD\n\nNalls, MA\n\nRotter, JI\n\nSharrett, R\n\nvan Duijn, CM\n\nAmouyel, P\n\nWolf, PA\n\nGudnason, V\n\nvan der Lugt, A\n\nBoerwinkle, E\n\nPsaty, BM\n\nSeshadri, S\n\nTzourio, C\n\nBreteler, MM\n\nMosley, TH\n\nSchmidt, R\n\nLongstreth, WT\n\nDeCarli, C\n\nLauner, LJ\n\nBeiträge in Fachzeitschriften\nISI:000292003100006\n21681796.0\n10.1002/ana.22403\nPMC3122147\nObjective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9, 61 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3, 24 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 x 10(-9); p(replication) = 1.3 x 10(-7); p(combined) = 4.0 x 10(-15)). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 x 10(-9)), rs11869977 (p = 5.7 x 10(-9)), rs936393 (p = 6.8 x 10(-9)), rs3744017 (p = 7.3 x 10(-9)), and rs1055129 (p = 4.1 x 10(-8)). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. ANN NEUROL 2011;69:928-939\n\nCavalieri, Margherita\n\nEnzinger, Christian\n\nFazekas, Franz\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n128595\nEffect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials.\n\nChaturvedi, N\n\nPorta, M\n\nKlein, R\n\nOrchard, T\n\nFuller, J\n\nParving, HH\n\nBilous, R\n\nSjølie, AK\n\nDIRECT Programme Study Group\n\nBeiträge in Fachzeitschriften\nISI:000260228200025\n18823656.0\n10.1016/S0140-6736(08)61412-9\nNone\nBackground Results of previous studies suggest that renin-angiotensin system blockers might reduce the burden of diabetic retinopathy. We therefore designed the DIabetic REtinopathy Candesartan Trials (DIRECT) Programme to assess whether candesartan could reduce the incidence and progression of retinopathy in type 1 diabetes. Methods Two randomised, double-blind, parallel-design, placebo-controlled trials were done in 309 centres worldwide. Participants with normotensive, normoalbuminuric type 1 diabetes without retinopathy were recruited to the DIRECT-Prevent I trial and those with existing retinopathy were recruited to DIRECT-Protect 1, and were assigned to candesartan 16 mg once a day or matching placebo. After I month, the dose was doubled to 32 mg. Investigators and participants were unaware of the treatment allocation status. The primary endpoints were incidence and progression of retinopathy and were defined as at least a two-step and at least a three-step increase on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, respectively. These trials are registered with ClinicalTrials.gov, numbers NCT00252733 for DIRECT-Prevent 1 and NCT00252720 for DIRECT-Protect 1. Findings 1421 participants (aged 18-50 years) were randomly assigned to candesartan (n=711) or to placebo (n=710) in DIRECT-Prevent 1, and 1905 (aged 18-55 years) to candesartan (n=951) or to placebo (n=954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%) participants in the candesartan group versus 217 (31%) in the placebo group. Progression of retinopathy occurred in 127 (13%) participants in the candesartan group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs placebo) was 0.82 (95% CI 0.67-1.00, p=0.0508) for incidence of retinopathy and 1.02 (0.80-1.31, p=0.85) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0.65 (0.48-0.87, p=0.0034), which was attenuated but still significant after adjustment for baseline characteristics (0.71, 0.53-0.95, p=0.046). Final ETDRS level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1.16, 95% CI 1.05-1.30, p=0.0048) and DIRECT-Protect 1 (1.12, 95% CI 1.01-1.25, p=0.0264). Adverse events did not differ between the treatment groups. Interpretation Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression.\n\nPilger, Ernst\n\n\n"
},
{
"text": "\n182741\nLess sedentary time is associated with a more favourable glucose-insulin axis in obese pregnant women-a secondary analysis of the DALI study.\n\nDieberger, AM\n\nDesoye, G\n\nStolz, E\n\nHill, DJ\n\nCorcoy, R\n\nSimmons, D\n\nHarreiter, J\n\nKautzky-Willer, A\n\nDunne, F\n\nDevlieger, R\n\nWender-Ozegowska, E\n\nZawiejska, A\n\nLapolla, A\n\nDalfra, MG\n\nBertolotto, A\n\nGaljaard, S\n\nAdelantado, JM\n\nJensen, DM\n\nAndersen, LL\n\nTanvig, M\n\nDamm, P\n\nMathiesen, ER\n\nSnoek, FJ\n\nJelsma, JGM\n\nvan Poppel, MNM\n\nBeiträge in Fachzeitschriften\nISI:000548090900002\n32661292.0\n10.1038/s41366-020-0639-y\nPMC7840500\nObese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women.\n In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m2, without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness.\n 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011).\n As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.\n\nDesoye, Gernot\n\nDieberger, Anna Maria\n\nStolz, Erwin\n\n\n"
},
{
"text": "\n107537\nHCV genotypes and age distribution in patients of Vienna and surrounding areas.\n\nHaushofer, AC\n\nKopty, C\n\nHauer, R\n\nBrunner, H\n\nHalbmayer, WM\n\nBeiträge in Fachzeitschriften\nISI:000166232800008\n11163582.0\n10.1016/S1386-6532(00)00154-2\nNone\nBackground: Chronic hepatitis C (CHC) can result in liver cirrhosis and hepatocellular carcinoma. Determination of the hepatitis C virus (HCV) genotype:subtype may be of prognostic value to estimate the risk of development of liver cirrhosis. Objective: The HCV genotype/subtype was determined in patients with CHC and possible associations with age, source of HCV transmission, duration of HCV infection. and development of liver cirrhosis were investigated. Study design: A total of 250 consecutive patients with CHC were studied. HCV genotypes/subtypes were determined with a commercially available assay based on the reverse-hybridization principle. Source of HCV transmission and duration of HCV infection were taken from the patient documentation and liver cirrhosis was diagnosed by clinical, biochemical, and sonographic data. Results: HCV genotypes 1, 2, 3, 4, and 5 were found in 74.8, 2.8, 16, 5.2, and 0.4% of the patients. Most frequent subtypes were 1b (54%), 1a (15.6%), and 3a (15.6%). Patients with genotype 1 (mean, 52.8 years) or 2 (mean, 51.0 years) were significantly older than patients with genotype 3 (mean. 37.2 years) or genotype 4 (mean, 37.2 years). Patients with subtype 1b (mean, 58.1 years) were significantly older than patients with subtype la (mean, 40.8 years) or 3a (mean, 37.5 years). The main sources of HCV infection were intravenous drug abuse in 30.0% of all patients (genotype 1 in 53.3%; genotype 3 in 40%) or transfusion of blood and blood products in 21.6% of all patients (genotype 1 in 83.4%). The source of transmission, however, remained unknown in 44.8% of all patients. The prevalence of genotype 1 was significantly higher in patients with long duration (more than 20 years) of CHC. In none of the patients with genotype 2 or 3, duration of CHC for more than 20 years was observed. The prevalence of genotype 4 was significantly higher in patients with short duration (less than 10 years) of CHC. Liver cirrhosis was diagnosed in 13.6% of all patients (97.1% of patients with genotype 1). Patients with liver cirrhosis were significantly older compared to asymptomatic patients (mean, 63.8 vs. 51.3 years). Conclusion: HCV subtype 1b was found to be the main subtype in the investigated population and is currently the major contributor to liver cirrhosis. Patients infected with subtype 1a, however, are at comparable risk for development of liver cirrhosis. In future. subtype 3a and genotype 4 may also become an increasing problem. (C) 2001 Elsevier Science B.V. All rights reserved.\n\n\n"
},
{
"text": "\n154918\nThe Baby Moves prospective cohort study protocol: using a smartphone application with the General Movements Assessment to predict neurodevelopmental outcomes at age 2 years for extremely preterm or extremely low birthweight infants.\n\nSpittle, AJ\n\nOlsen, J\n\nKwong, A\n\nDoyle, LW\n\nMarschik, PB\n\nEinspieler, C\n\nCheong, J\n\nBeiträge in Fachzeitschriften\nISI:000391303200144\n27697883.0\n10.1136/bmjopen-2016-013446\nPMC5073614\nInfants born extremely preterm (EP; <28 weeks' gestation) and/or with extremely low birth weight (ELBW; <1000 g birth weight) are at increased risk for adverse neurodevelopmental outcomes. However, it is challenging to predict those EP/ELBW infants destined to have long-term neurodevelopmental impairments in order to target early intervention to those in most need. The General Movements Assessment (GMA) in early infancy has high predictive validity for neurodevelopmental outcomes in preterm infants. However, access to a GMA may be limited by geographical constraints and a lack of GMA-trained health professionals. Baby Moves is a smartphone application (app) developed for caregivers to video and upload their infant's general movements to be scored remotely by a certified GMA assessor. The aim of this study is to determine the predictive ability of using the GMA via the Baby Moves app for neurodevelopmental impairment in infants born EP/ELBW.\n This prospective cohort study will recruit infants born EP/ELBW across the state of Victoria, Australia in 2016 and 2017. A control group of normal birth weight (>2500 g birth weight), term-born (≥37 weeks' gestation) infants will also be recruited as a local reference group. Parents will video their infant's general movements at two time points between 3 and 4 months' corrected age using the Baby Moves app. Videos will be scored by certified GMA assessors and classified as normal or abnormal. Parental satisfaction using the Baby Moves app will be assessed via survey. Neurodevelopmental outcome at 2 years' corrected age includes developmental delay according to the Bayley Scales of Infant and Toddler Development-III and cerebral palsy diagnosis.\n This study was approved by the Human Research and Ethics Committees at the Royal Children's Hospital, The Royal Women's Hospital, Monash Health and Mercy Health in Melbourne, Australia. Study findings will be disseminated via peer-reviewed publications and conference presentations.\n Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.\n\nEinspieler, Christa\n\nMarschik, Peter\n\n\n"
},
{
"text": "\n166431\nWhat Is the Relationship of Fear Avoidance to Physical Function and Pain Intensity in Injured Athletes?\n\nFischerauer, SF\n\nTalaei-Khoei, M\n\nBexkens, R\n\nRing, DC\n\nOh, LS\n\nVranceanu, AM\n\nBeiträge in Fachzeitschriften\nISI:000431410600023\n29480885.0\n10.1007/s11999.0000000000000085\nPMC6260093\nFear avoidance can play a prominent role in maladaptive responses to an injury. In injured athletes, such pain-related fear or fear avoidance behavior may have a substantial influence on the recovery process. Specifically, it may explain why some are able to reach their preinjury abilities, whereas others are unable to return to sport.\n (1) Is fear avoidance in athletes associated with decreased physical function after injury? (2) To what degree is fear avoidance associated with athletes' pain intensity?\n In a cross-sectional study, we recruited injured athletes-defined as patients with sports-related injury, weekly engagement in sport activities, participation in competitive events as part of a team or club, self-identification as an athlete, and a desire to return to sport after recovery-from an orthopaedic sports medicine center at a major urban university hospital. Of 130 approached patients, 102 (84% men; mean ± SD age 25 ± 8.5 years) met the inclusion criteria. Participants completed a demographic questionnaire, the Athlete Fear Avoidance Questionnaire, which assesses injury-related fear and avoidance behavior specifically in an athletic population, the Pain Catastrophizing Scale, the Hospital Anxiety and Depression Scale, and two Patient-Reported Outcomes Measurement Information System measures: Physical Function Computerized Adaptive Testing (CAT) and Pain Intensity CAT.\n After controlling for age, injury region (upper versus lower extremity), catastrophic thinking, and emotional distress, we found that an increase in athletes' fear avoidance was associated with a decrease in physical function (b = -0.32; p = 0.002). The model explained 30% of the variation in physical function with 7.3% explained uniquely by fear avoidance. After controlling for initial appointment/followup, surgery for the current condition, multiple pain conditions, history of prior sport-related injury/surgery, pain medication prescription, catastrophic thinking, and emotional distress, athletes' fear avoidance was not associated with pain (b = -0.14; p = 0.249). The model explained 40% of the variation in pain intensity and pain catastrophizing (b = 0.30; p = 0.001) uniquely explained 7.1% of this variation.\n In injured athletes, fear avoidance is independently associated with decreased physical function, whereas pain catastrophizing is associated with high pain intensity. Both level of an athlete's fear avoidance and catastrophic thinking about pain should be accounted for in clinical interventions aimed at helping athletes improve recovery and return to sport.\n Level II, prognostic study.\n\nFischerauer, Stefan Franz\n\n\n"
},
{
"text": "\n184252\nEvaluation of Myocardial Gene Expression Profiling for Superior Diagnosis of Idiopathic Giant-Cell Myocarditis and Clinical Feasibility in a Large Cohort of Patients with Acute Cardiac Decompensation.\n\nEscher, F\n\nPietsch, H\n\nAleshcheva, G\n\nWenzel, P\n\nFruhwald, F\n\nStumpf, C\n\nWestermann, D\n\nBauersachs, J\n\nEnseleit, F\n\nRuschitzka, F\n\nNägele, H\n\nLaugwitz, KL\n\nHaake, H\n\nFrey, N\n\nBrachmann, J\n\nHuber, K\n\nBraun-Dullaeus, RC\n\nBergmann, MW\n\nStrotmann, J\n\nGrönefeld, G\n\nKrülls-Münch, J\n\nWestenfeld, R\n\nSkurk, C\n\nLandmesser, U\n\nPieske, B\n\nGross, UM\n\nMorawietz, L\n\nSchultheiss, HP\n\nBeiträge in Fachzeitschriften\nISI:000580689600001\n32825201.0\n10.3390/jcm9092689\nPMC7563288\nThe diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 ± 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed; this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy.\n\nFruhwald, Friedrich\n\n\n"
},
{
"text": "\n103676\nContinuous 24 h monitoring of changes in intraocular pressure with the wireless contact lens sensor Triggerfish™. First results in patients].\n\nFaschinger, C\n\nMossböck, G\n\nBeiträge in Fachzeitschriften\nISI:000283506200004\n20535482.0\n10.1007/s00347-010-2198-4\nNone\nBackground. For many years researchers have been striving for a non-invasive 24 h continuous method of ambulatory intraocular pressure monitoring. A wireless device with a contact lens sensor is now on the market for clinical use, which is not a quantitative measurement of the intraocular pressure but is at least a recording of qualitative changes. These changes of corneal curvature due to changes of the intraocular pressure result in a distinct profile which gives information about fluctuations of the intraocular pressure, the behaviour during supine sleeping time and the 24 h efficacy of glaucoma therapy. We investigated the practicability and tolerability of this device. Method. The sensor is embedded in a soft silicone contact lens and consists of 4 strain gauges. Additionally there is an antenna made out of gold and a microchip. A second antenna is fixed around the eye which sends impulses to the microchip and receives data from the microchip. The data are sent to a recorder via a wire. Measurements are made for 90 s every 8.5 min resulting in 144 measurements within 24 h. Of the 4 strain gauges 2 sense changes in the corneal curvature due to changes of the intraocular pressure. This device was used in 11 patients with ocular hypertension or glaucoma. Results. The result of the 24 h continuous measurement is a pressure profile which may be flat, fluctuating and with no, some or many spikes. We describe 2 examples of profiles from patients with glaucoma. The changes in the profiles were mostly during the sleeping hours in a supine position. Due to the lack of validation of the results it is not known if intermittent spikes are true spikes or artefacts. Practicability was simple and tolerability was reported to be good by all patients. Conclusions. For the first time a practicable, well tolerated, non-invasive device for continuous 24 h monitoring of changes of the corneal curvature due to changes of the intraocular pressure is available. It is not a direct measurement of the intraocular pressure. The resulting profile gives additional information about the behaviour of the intraocular pressure, especially during out-of-office times and night times. Disadvantages are the high cost of the contact lens sensor and the lack of validation of the results and reproducibility in patients.\n\nFaschinger, Christoph\n\n\n"
}
]
}