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"text": "\n139952\nTestosterone to dihydrotestosterone ratio as a new biomarker for an adverse metabolic phenotype in the polycystic ovary syndrome.\n\nMünzker, J\n\nHofer, D\n\nTrummer, C\n\nUlbing, M\n\nHarger, A\n\nPieber, T\n\nOwen, L\n\nKeevil, B\n\nBrabant, G\n\nLerchbaum, E\n\nObermayer-Pietsch, B\n\nBeiträge in Fachzeitschriften\nISI:000353350900071\n25387259.0\n10.1210/jc.2014-2523\nNone\nPolycystic ovary syndrome (PCOS) is a heterogeneous disease with many different aspects, including hyperandrogenism and metabolic disturbances. Clinical phenotypes show different patterns of steroid hormones that have been investigated to some extent.\n This study intended to determine the role of the testosterone (TT) to dihydrotestosterone (DHT) ratio (TT/DHT ratio) in PCOS patients and to further assess the correlation of this ratio with hormonal, anthropometric, and metabolic parameters.\n Serum samples of 275 premenopausal PCOS patients fulfilling Rotterdam criteria and 35 BMI-matched, premenopausal, healthy controls were analyzed for testosterone, DHT, dehydroepiandrosterone (DHEA), and androstenedione using liquid chromatography/mass spectrometry.\n We measured total levels of testosterone and DHT and calculated unbound hormone levels as well as the ratio of testosterone to DHT. Further, impaired glucose tolerance, basal and stimulated serum insulin levels, metabolic syndrome and insulin resistance according to the homeostatic model assessment (HOMA-IR) were assessed.\n PCOS patients showed significantly higher levels of TT (P < .001), free testosterone (P < .001), and free DHT (P < .001) compared to healthy controls. The TT/DHT ratio was significantly higher in PCOS patients (P < .001). No difference was found for total DHT levels (P = .072). In PCOS patients alone, the TT/DHT ratio was significantly higher in obese patients (P < .001) and patients with metabolic syndrome (P < .001), impaired glucose tolerance (IGT) (P < .001) or insulin resistance (P < .001). Significant correlations of the TT/DHT ratio with various adverse anthropometric, hormonal, lipid and liver parameters and parameters of glucose metabolism were found.\n Our data provide evidence for a strong link between a high TT/DHT ratio and an adverse metabolic phenotype in PCOS patients. This correlation was only found in PCOS patients, suggesting the TT/DHT ratio to be a new biomarker for an adverse metabolic phenotype in PCOS patients.\n\nLerchbaum, Elisabeth\n\nObermayer-Pietsch, Barbara\n\nPieber, Thomas\n\nTrummer, Christian\n\n\n"
},
{
"text": "\n141090\nThe need for more workshops in laparoscopic surgery and surgical anatomy for European gynaecological oncology trainees: a survey by the European Network of Young Gynaecological Oncologists.\n\nManchanda, R\n\nHalaska, MJ\n\nPiek, JM\n\nGrabowski, JP\n\nHaidopoulos, D\n\nZapardiel, I\n\nGultekin, M\n\nVranes, B\n\nDallaku, K\n\nBossart, M\n\nEuropean Network of Young Gynecological Oncologists (ENYGO)\n\nBeiträge in Fachzeitschriften\nISI:000330373600025\n23792606.0\n10.1097/IGC.0b013e31829703b0\nNone\nThe objective of this study was to highlight the relative preference of European gynecologic oncology trainees for workshops that could support and supplement their training needs.\n A Web-based survey was sent to 900 trainees on the European Network of Young Gynaecological Oncologists database in November 2011. Respondents were asked to rate a 13-item questionnaire (using a 1- to 5-point Likert scale) on workshop topics they felt would most benefit their training requirements. Free text space for additional topics was also provided. Descriptive analysis was used to describe the mean scores reported for different items. A complete linkage hierarchical cluster analysis with Dendron plot was used to assess any clustering of data, and Cronbach α was used to assess the internal reliability of the questionnaire.\n One hundred ninety trainees from 37 countries responded to the survey, giving a 21% response rate. The 3 most important topics reported were laparoscopic surgery; surgical anatomy, and imaging techniques in gynecologic oncology. The Dendron plot indicated 4 different clusters of workshops (research related skills, supportive ancillary skills, related nonsurgical subspecialties, and core surgical skills) reflecting different competencies trainees need to meet. There was no significant association between individual country of training and workshop preference. The mean duration of the workshop preferred by 71% of respondents was 2 days. Cronbach α of the 13-item questionnaire was 0.78, which suggests good internal consistency/reliability.\n This report for the first time highlights the relative importance and significance European trainees attach to some of their training needs in gynecologic oncology. Laparoscopic surgery, surgical anatomy, and imaging appear to be the 3 areas of greatest need. The European Society of Gynaecological Oncology, other national specialist societies, and institutions should direct additional training efforts at these areas.\n\nLaky, Rene Walter\n\n\n"
},
{
"text": "\n152770\nLarge-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci (vol 90, pg 410, 2012)\n\nSaxena, R\n\nElbers, CC\n\nGuo, YR\n\nPeter, I\n\nGaunt, TR\n\nMega, JL\n\nLanktree, MB\n\nTare, A\n\nCastillo, BA\n\nLi, YR\n\nJohnson, T\n\nBruinenberg, M\n\nGilbert-Diamond, D\n\nRajagopalan, R\n\nVoight, BF\n\nBalasubramanyam, A\n\nBarnard, J\n\nBauer, F\n\nBaumert, J\n\nBhangale, T\n\nBohm, BO\n\nBraund, PS\n\nBurton, PR\n\nChandrupatla, HR\n\nClarke, R\n\nCooper-DeHoff, RM\n\nCrook, ED\n\nDavey-Smith, G\n\nDay, IN\n\nde Boer, A\n\nde Groot, MCH\n\nDrenos, F\n\nFerguson, J\n\nFox, CS\n\nFurlong, CE\n\nGibson, Q\n\nGieger, C\n\nGilhuijs-Pederson, LA\n\nGlessner, JT\n\nGoel, A\n\nGong, Y\n\nGrant, SFA\n\nGrobbee, DE\n\nHastie, C\n\nHumphries, SE\n\nKim, CE\n\nKivimaki, M\n\nKleber, M\n\nMeisinger, C\n\nKumari, M\n\nLangaee, TY\n\nLawlor, DA\n\nLi, MY\n\nLobmeyer, MT\n\nMaitland-van der Zee, AH\n\nMeijs, MFL\n\nMolony, CM\n\nMorrow, DA\n\nMurugesan, G\n\nMusani, SK\n\nNelson, CP\n\nNewhouse, SJ\n\nO'Connell, JR\n\nPadmanabhan, S\n\nPalmen, J\n\nPatel, SR\n\nPepine, CJ\n\nPettinger, M\n\nPrice, TS\n\nRafelt, S\n\nRanchalis, J\n\nRasheed, A\n\nRosenthal, E\n\nRuczinski, I\n\nShah, S\n\nShen, HQ\n\nSilbernagel, G\n\nSmith, EN\n\nSpijkerman, AWM\n\nStanton, A\n\nSteffes, MW\n\nThorand, B\n\nTrip, M\n\nvan der Harst, P\n\nvan der A, DL\n\nvan Iperen, EPA\n\nvan Setten, J\n\nvan Vliet-Ostaptchouk, JV\n\nVerweij, N\n\nWolffenbuttel, BHR\n\nYoung, T\n\nZafarmand, MH\n\nZmuda, JM\n\nBoehnke, M\n\nAltshuler, D\n\nMcCarthy, M\n\nKao, WHL\n\nPankow, JS\n\nCappola, TP\n\nSever, P\n\nPoulter, N\n\nCaulfield, M\n\nDominiczak, A\n\nShields, DC\n\nBhatt, DL\n\nZhang, L\n\nCurtis, SP\n\nDanesh, J\n\nCasas, JP\n\nvan der Schouw, YT\n\nOnland-Moret, NC\n\nDoevendans, PA\n\nDorn, GW\n\nFarrall, M\n\nFitzGerald, GA\n\nHegele, AHR\n\nHingorani, AD\n\nHofker, MH\n\nHuggins, GS\n\nIllig, T\n\nJarvik, GP\n\nJohnson, JA\n\nKlungel, OH\n\nKnowler, WC\n\nKoenig, W\n\nMarz, W\n\nMeigs, JB\n\nMelander, O\n\nMunroe, PB\n\nMitchell, BD\n\nBielinski, SJ\n\nRader, DJ\n\nReilly, MR\n\nRich, SS\n\nRotter, JI\n\nSaleheen, D\n\nSamani, NJ\n\nSchadt, EE\n\nShuldiner, AR\n\nSilverstein, R\n\nKottke-Marchant, K\n\nTalmud, PJ\n\nWatkins, H\n\nAsselbergs, FW\n\nde Bakker, PIW\n\nMcCaffery, J\n\nWijmenga, C\n\nSabatine, MS\n\nWilson, JG\n\nReiner, A\n\nBowden, DW\n\nHakonarson, H\n\nSiscovick, DS\n\nKeating, BJ\n\nBeiträge in Fachzeitschriften\nISI:000302833400022\nNone\n10.1016/j.ajhg.2012.03.001\nNone\nNone\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n156591\nLow-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner.\n\nBosche, B\n\nMolcanyi, M\n\nRej, S\n\nDoeppner, TR\n\nObermann, M\n\nMüller, DJ\n\nDas, A\n\nHescheler, J\n\nMacdonald, RL\n\nNoll, T\n\nHärtel, FV\n\nBeiträge in Fachzeitschriften\nISI:000389378100001\n27999548.0\n10.3389/fphys.2016.00593\nPMC5138228\nLithium at serum concentrations up to 1 mmol/L has been used in patients suffering from bipolar disorder for decades and has recently been shown to reduce the risk for ischemic stroke in these patients. The risk for stroke and thromboembolism depend not only on cerebral but also on general endothelial function and health; the entire endothelium as an organ is therefore pathophysiologically relevant. Regardless, the knowledge about the direct impact of lithium on endothelial function remains poor. We conducted an experimental study using lithium as pharmacologic pretreatment for murine, porcine and human vascular endothelium. We predominantly investigated endothelial vasorelaxation capacities in addition to human basal and dynamic (thrombin-/PAR-1 receptor agonist-impaired) barrier functioning including myosin light chain (MLC) phosphorylation (MLC-P). Low-dose therapeutic lithium concentrations (0.4 mmol/L) significantly augment the cholinergic endothelium-dependent vasorelaxation capacities of cerebral and thoracic arteries, independently of central and autonomic nerve system influences. Similar concentrations of lithium (0.2-0.4 mmol/L) significantly stabilized the dynamic thrombin-induced and PAR-1 receptor agonist-induced permeability of human endothelium, while even the basal permeability appeared to be stabilized. The lithium-attenuated dynamic permeability was mediated by a reduced endothelial MLC-P known to be followed by a lessening of endothelial cell contraction and paracellular gap formation. The well-known lithium-associated inhibition of inositol monophosphatase/glycogen synthase kinase-3-β signaling-pathways involving intracellular calcium concentrations in neurons seems to similarly occur in endothelial cells, too, but with different down-stream effects such as MLC-P reduction. This is the first study discovering low-dose lithium as a drug directly stabilizing human endothelium and ubiquitously augmenting cholinergic endothelium-mediated vasorelaxation. Our findings have translational and potentially clinical impact on cardiovascular and cerebrovascular disease associated with inflammation explaining why lithium can reduce, e.g., the risk for stroke. However, further clinical studies are warranted.\n\n\n"
},
{
"text": "\n167164\nNetwork Analysis to Risk Stratify Patients With Exercise Intolerance\n\nOldham, WM\n\nOliveira, RKF\n\nWang, RS\n\nOpotowsky, AR\n\nRubins, DM\n\nHainer, J\n\nWertheim, BM\n\nAlba, GA\n\nChoudhary, G\n\nTornyos, A\n\nMacRae, CA\n\nLoscalzo, J\n\nLeopold, JA\n\nWaxman, AB\n\nOlschewski, H\n\nKovacs, G\n\nSystrom, DM\n\nMaron, BA\n\nBeiträge in Fachzeitschriften\nISI:000429102200014\n29437835.0\n10.1161/CIRCRESAHA.117.312482\nPMC5924425\n\n\nRationale:\n\n\nCurrent methods assessing clinical risk due to exercise intolerance in cardiopulmonary disease patients rely on a small subset of traditional variables. Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking.\n\nObjective:\n\nUse unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance.\n\nMethods and Results:\n\nData from 738 consecutive patients referred for invasive cardiopulmonary exercise testing (iCPET) at a single center (2011-2015) were analyzed retrospectively (derivation cohort). A correlation network of iCPET parameters was assembled using |r|>0.5. From an exercise network of 39 variables (i.e., nodes) and 98 correlations (i.e., edges) corresponding to P<9.5e-46for each correlation, we focused on a subnetwork containing peak rate of oxygen consumption (pVO2) and 9 linked nodes. K-mean clustering based on these ten variables identified 4 novel patient clusters characterized by significant differences in 44 of 45 exercise measurements (P<0.01). Compared to a probabilistic model including 23 independent predictors of pVO2and pVO2itself, the network model was less redundant and identified clusters that were more distinct. Cluster assignment from the network model was predictive of subsequent clinical events. For example, a 4.3-fold (P<0.0001; 95% CI, 2.2-8.1) and 2.8-fold (P=0.0018; 95% CI, 1.5-5.2) increase in hazard for age- and pVO2-adjusted all-cause 3-year hospitalization, respectively, were observed between the highest vs. lowest risk clusters. Using these data, we developed the first risk-stratification calculator for patients with exercise intolerance. When applying the risk calculator to patients in twoindependent iCPET cohorts (Boston, USA and Graz, Austria), we observed a clinical risk profile that paralleled the derivation cohort.\n\nConclusions:\n\nNetwork analyses were used to identify novel exercise groups and develop a point-of-care risk calculator. These data expand the range of useful clinical variables beyond pVO2that predict hospitalization in patients with exercise intolerance.\n\nKovacs, Gabor\n\nOlschewski, Horst\n\nTornyos, Adrienn\n\n\n"
},
{
"text": "\n175620\nBlood Biomarkers of Heart Failure and Hypercoagulation to Identify Atrial Fibrillation-Related Stroke.\n\nKneihsl, M\n\nGattringer, T\n\nBisping, E\n\nScherr, D\n\nRaggam, R\n\nMangge, H\n\nEnzinger, C\n\nFandler-Höfler, S\n\nEppinger, S\n\nHermetter, C\n\nBucnik, B\n\nPoltrum, B\n\nNiederkorn, K\n\nFazekas, F\n\nBeiträge in Fachzeitschriften\nISI:000478838200064\n31216968.0\n10.1161/STROKEAHA.119.025339\nNone\nBackground and Purpose- Occult atrial fibrillation (AF) causes a relevant proportion of initially cryptogenic stroke (CS), but prolonged rhythm monitoring is difficult to apply to all such patients. We hypothesized that blood biomarkers indicating heart failure (NT-proBNP [N-terminal pro-brain natriuretic peptide]) and hypercoagulability (D-dimer, AT-III [antithrombin-III]) were associated with AF-related stroke and could serve to predict the likelihood of AF detection in CS patients early on. Methods- Over a 1-year period, we prospectively applied a defined etiologic work-up to all ischemic stroke patients admitted to our stroke unit. If no clear stroke cause was detected (CS), patients underwent extended in-hospital cardiac rhythm monitoring (≥72 hours). Blood to determine biomarker levels was drawn within 24 hours after admission. Results- Of 429 patients, 103 had AF-related stroke. Compared with noncardiac stroke patients (n=171), they had higher NT-proBNP (1867 versus 263 pg/ml) and D-dimer levels (1.1 versus 0.6 µg/ml), and lower AT-III concentration (89% versus 94%). NT-proBNP ≥505 pg/ml distinguished AF-related from noncardiac stroke with a sensitivity of 93% and a specificity of 72%. D-dimer and AT-III cutoffs had lower sensitivities (61% and 53%) and specificities (58% and 69%) for AF-related stroke. Of all initially 143 CS patients, 14 were diagnosed with AF during in-hospital monitoring. The preidentified NT-proBNP cutoff ≥505 pg/ml correctly predicted AF in 12 of them (86%, negative predictive value: 98%), while D-dimer and AT-III cutoffs were noncontributory. Conclusions- This study supports the association of NT-proBNP and to a lesser extent of hypercoagulation markers with AF-related stroke. NT-proBNP seems helpful in selecting CS patients for immediate extended cardiac rhythm monitoring to detect occult AF whereby levels <505 pg/ml seem to have a high-negative predictive value.\n\nBisping, Egbert Hubertus\n\nEnzinger, Christian\n\nEppinger, Sebastian\n\nFandler-Höfler, Simon\n\nFazekas, Franz\n\nGattringer, Thomas\n\nKneihsl, Markus\n\nMangge, Harald\n\nRaggam, Reinhard Bernd\n\nScherr, Daniel\n\n\n"
},
{
"text": "\n179204\nUrinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health.\n\nMasania, J\n\nFaustmann, G\n\nAnwar, A\n\nHafner-Giessauf, H\n\nRajpoot, N\n\nGrabher, J\n\nRajpoot, K\n\nTiran, B\n\nObermayer-Pietsch, B\n\nWinklhofer-Roob, BM\n\nRoob, JM\n\nRabbani, N\n\nThornalley, PJ\n\nBeiträge in Fachzeitschriften\nISI:000502070900006\n31827677.0\n10.1155/2019/4851323\nPMC6885816\nGlycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen. We recruited 200 human subjects with early-stage health decline and healthy controls. Urinary amino acid metabolites were determined by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. Machine learning was applied to optimise and validate algorithms to discriminate between study groups for potential diagnostic utility. Urinary analyte changes were as follows: impaired metabolic health-increased N \nε\n -carboxymethyl-lysine, glucosepane, glutamic semialdehyde, and pyrraline; impaired vascular health-increased glucosepane; and impaired renal health-increased BCAAs and decreased N \nε\n -(γ-glutamyl)lysine. Algorithms combining subject age, BMI, and BCAAs discriminated between healthy controls and impaired metabolic, vascular, and renal health study groups with accuracy of 84%, 72%, and 90%, respectively. In 2-step analysis, algorithms combining subject age, BMI, and urinary N \nε\n -fructosyl-lysine and valine discriminated between healthy controls and impaired health (any type), accuracy of 78%, and then between types of health impairment with accuracy of 69%-78% (cf. random selection 33%). From likelihood ratios, this provided small, moderate, and conclusive evidence of early-stage cardiovascular, metabolic, and renal disease with diagnostic odds ratios of 6 - 7, 26 - 28, and 34 - 79, respectively. We conclude that measurement of urinary glycated, oxidized, crosslinked, and branched-chain amino acids provides the basis for a noninvasive health screen for early-stage health decline in metabolic, vascular, and renal health.\n Copyright © 2019 Jinit Masania et al.\n\nHafner-Giessauf, Hildegard Elisabeth\n\nObermayer-Pietsch, Barbara\n\nTiran, Beate\n\n\n"
},
{
"text": "\n179372\nEtiology and Outcome of Candidemia in Neonates and Children in Europe: An 11-year Multinational Retrospective Study.\n\nWarris, A\n\nPana, ZD\n\nOletto, A\n\nLundin, R\n\nCastagnola, E\n\nLehrnbecher, T\n\nGroll, AH\n\nRoilides, E\n\nAndersen, CT\n\nArendrup, MC\n\nArsenijevic, VA\n\nBianchini, S\n\nvon Both, U\n\nChmelnik, M\n\nControzzi, T\n\nEmonts, M\n\nEsposito, S\n\nFerreras-Antolin, L\n\nHenriet, S\n\nIosifidis, E\n\nIrwin, A\n\nKopsidas, J\n\nLagrou, K\n\nLyall, H\n\nCasteleiro, AM\n\nMesini, A\n\nOlbrich, P\n\nPaulus, S\n\nLausch, KR\n\nSoler-Palacin, P\n\nSpyridis, N\n\nStrenger, V\n\nTheodoraki, M\n\nWolfs, T\n\nEUROCANDY Study Group\n\nBeiträge in Fachzeitschriften\nISI:000509535000010\n31725552.0\n10.1097/INF.0000000000002530\nPMC7208278\nData on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia.\n All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients' demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality.\n One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8-2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed.\n This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.\n\nStrenger, Volker\n\n\n"
},
{
"text": "\n183993\nReal-World Experience With a Paclitaxel-Coated Balloon in Critical Limb Ischemia: 24-Month Subgroup Outcomes of BIOLUX P-III.\n\nBrodmann, M\n\nMoscovic, M\n\nWang, JCC\n\nNano, G\n\nDahm, J\n\nZeller, T\n\nChristensen, JK\n\nKeirse, K\n\nGhotbi, R\n\nCorpataux, JM\n\nTepe, G\n\nBeiträge in Fachzeitschriften\nISI:000577447400018\n32950415.0\n10.1016/j.jcin.2020.06.059\nNone\nThe aim of the BIOLUX P-III (A Prospective, International, Multi-Centre, Post-Market All-Comers Registry to Assess the Clinical Performance of the Passeo-18 Lux Paclitaxel Releasing Balloon Catheter in Infrainguinal Arteries - III) registry was to collect real-world data on the Passeo-18 Lux paclitaxel-coated balloon.\n Critical limb ischemia (CLI) is a severe condition associated with high morbidity and mortality. Prospective data are needed to provide further insights on drug-eluting devices.\n BIOLUX P-III is a prospective, post-market, all-comers registry assessing the safety and performance of the Passeo-18 Lux. Clinical information was collected at 6, 12, and 24 months. The authors report 24-month outcomes of the CLI subgroup with patients in Rutherford classes 4 to 6.\n The CLI subgroup included 328 patients with 422 lesions. Patients were 71.1 ± 10.5 years of age, and 61.0% had diabetes. Femoropopliteal lesions were present in 53.8% (n = 227), below-the-knee lesions were present in 27.0% (n = 114), and lesions were moderate or heavily calcified in 45.0% (n = 190). Major adverse events, defined as 30-day device- or procedure-related mortality, major target limb amputation, and clinically driven target lesion revascularization, occurred in 9.8% of patients through 6 months, in 14.9% through 12 months, and in 19.4% through 24 months. Clinically driven target lesion revascularization occurred in 4.4%, 8.5%, and 12.1%, major amputation in 4.9%, 5.2%, and 6.1%, and mortality in 8.1%, 11.1%, and 20.1%, respectively. Predictors of mortality were age ≥75 years and higher Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class, and higher Rutherford class was associated with increased mortality and amputation rates.\n In a large, multimorbid patient population with complex lesions and CLI, the safety and performance of the Passeo-18 Lux paclitaxel-coated balloon has been confirmed, with low rates of major amputation and target lesion revascularization.\n Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.\n\nBrodmann, Marianne\n\n\n"
},
{
"text": "\n186779\nIterative image reconstruction techniques for CT coronary artery calcium quantification: comparison with traditional filtered back projection in vitro and in vivo.\n\nSchindler, A\n\nVliegenthart, R\n\nSchoepf, UJ\n\nBlanke, P\n\nEbersberger, U\n\nCho, YJ\n\nAllmendinger, T\n\nVogt, S\n\nRaupach, R\n\nFink, C\n\nSaam, T\n\nBamberg, F\n\nNikolaou, K\n\nApfaltrer, P\n\nBeiträge in Fachzeitschriften\nNone\n24471388.0\n10.1148/radiol.13130233\nNone\nTo investigate in vitro and in vivo the use of image-based and raw data-based iterative reconstruction algorithms for quantification of coronary artery calcium by using the Agatston score and subsequent cardiac risk stratification.\n In vitro data were obtained by using a moving anthropomorphic cardiac phantom containing calcium inserts of different concentrations and sizes. With institutional review board approval and HIPAA compliance, coronary calcium imaging data of 110 consecutive patients (mean age ± standard deviation, 58.2 years ± 9.8; 48 men) were reconstructed with filtered back projection (FBP), iterative reconstruction in image space (IRIS), and sinogram-affirmed iterative reconstruction (SAFIRE). Image noise was measured and the Agatston score was obtained for all reconstructions. Assignment to Agatston scores and percentile-based cardiac risk categories was compared. Statistical analysis included the Cohen κ coefficient and Friedman and Wilcoxon testing.\n In vitro, mean Agatston scores ± standard deviation for FBP (638.9 ± 9.6), IRIS (622.7 ± 15.2), and SAFIRE (631.4 ± 17.6) were comparable (P = .30). The smallest phantom calcifications were more frequently detected when iterative reconstruction techniques were used. The Agatston scores in the patient cohort were not significantly different among FBP, IRIS, and SAFIRE in paired comparisons (median Agatston score [25th and 75th percentiles]: 76.0 [20.6, 243.9], 76.4 [22, 249.3], and 75.7 [21.5, 49.1], respectively; P = .20 each). Comparison of categorization based on Agatston score percentiles showed excellent agreement for both IRIS and SAFIRE with FBP (κ = 0.975 [0.942-1.00] and κ = 0.963 [0.922-1.00], respectively). The mean effective dose was 1.02 mSv ± 0.51. Mean image noise was significantly (P < .001) higher with FBP than that with iterative reconstructions.\n In comparison with FBP, iterative reconstruction techniques do not have a profound effect on the reproducible quantification of coronary calcium according to Agatston score and subsequent cardiac risk classification, although risk reclassification may occur in a small subset of subjects.\n ©RSNA, 2013\n\nApfaltrer, Paul\n\n\n"
},
{
"text": "\n186926\nAltered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder.\n\nJenewein, J\n\nErni, J\n\nMoergeli, H\n\nGrillon, C\n\nSchumacher, S\n\nMueller-Pfeiffer, C\n\nHassanpour, K\n\nSeiler, A\n\nWittmann, L\n\nSchnyder, U\n\nHasler, G\n\nBeiträge in Fachzeitschriften\nISI:000390293300007\n27641312.0\n10.1016/j.jpain.2016.09.002\nPMC5580085\nThere is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age- and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects' hand. A designation of 'CS-' was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of 'CS+' was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS-, and a low-temperature stimulus induced less subjective pain after CS- than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments.\n This study provides new insights into the pathogenesis of chronic pain in patients with PTSD. The findings may help to develop new treatment strategies for this highly prevalent comorbidity in PTSD.\n Copyright © 2016 American Pain Society. All rights reserved.\n\nJenewein, Josef\n\n\n"
},
{
"text": "\n187324\nVitamin D deficiency in critically ill COVID-19 ARDS patients.\n\nNotz, Q\n\nHerrmann, J\n\nSchlesinger, T\n\nKranke, P\n\nSitter, M\n\nHelmer, P\n\nStumpner, J\n\nRoeder, D\n\nAmrein, K\n\nStoppe, C\n\nLotz, C\n\nMeybohm, P\n\nBeiträge in Fachzeitschriften\nNone\n33745749.0\n10.1016/j.clnu.2021.03.001\nPMC7937427\nVitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS).\n This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1, 5-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding.\n A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1, 5-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1, 5-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048).\n The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1, 5-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.\n Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.\n\nAmrein, Karin\n\n\n"
},
{
"text": "\n187547\nSurgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.\n\nBanys-Paluchowski, M\n\nGasparri, ML\n\nde Boniface, J\n\nGentilini, O\n\nStickeler, E\n\nHartmann, S\n\nThill, M\n\nRubio, IT\n\nDi Micco, R\n\nBonci, EA\n\nNiinikoski, L\n\nKontos, M\n\nKaradeniz Cakmak, G\n\nHauptmann, M\n\nPeintinger, F\n\nPinto, D\n\nMatrai, Z\n\nMurawa, D\n\nKadayaprath, G\n\nDostalek, L\n\nNina, H\n\nKrivorotko, P\n\nClasse, JM\n\nSchlichting, E\n\nAppelgren, M\n\nPaluchowski, P\n\nSolbach, C\n\nBlohmer, JU\n\nKühn, T\n\nThe Axsana Study Group, T\n\nBeiträge in Fachzeitschriften\nISI:000638347000001\n33805367.0\n10.3390/cancers13071565\nPMC8037995\nIn the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).\n\nPeintinger, Florentia\n\n\n"
},
{
"text": "\n65915\nInfluence of low molecular weight heparin compared to conventional heparin for anticoagulation during haemodialysis on low density lipoprotein subclasses.\n\nWiemer, J\n\nWinkler, K\n\nBaumstark, M\n\nMärz, W\n\nScherberich, JE\n\nBeiträge in Fachzeitschriften\nISI:000179668600032\n12454238.0\n10.1093/ndt/17.12.2231\nNone\nBACKGROUND: In haemodialysis (HD) patients, low density lipoprotein (LDL) particle distribution is characterized by a higher proportion of more atherogenic dense LDL. Though clinical studies showed favourable effects of low molecular weight (LMW) heparin compared to standard heparin on triglycerides (TG) and cholesterol (CH) in HD patients with hypertriglyceridaemia, it is not known if LMW heparin influences LDL subfraction pattern. Thus, the aim of this pilot study was to investigate if a switch to LMW heparin influences LDL subfractions and apolipoproteins. METHODS: Ten outpatients with fasting TG >230 mg/dl in the chronic HD programme on heparin for anticoagulation (AC) were switched to dalteparin (80 IU/kg body weight as a bolus). Blood samples were drawn for CH, TG, LDL-CH, HDL-CH, apolipoproteins (apo), very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and LDL subclasses at the beginning and after 12 months of therapy. Lipoproteins were isolated by preparative ultracentrifugation. Total LDL were fractionated into six density classes by equilibrium density gradient ultracentrifugation [(density in kg/l): LDL-1 1.019-1.031, LDL-2 1.031-1.034, LDL-3 1.034-1.037, LDL-4 1.037-1.040, LDL-5 1.040-1.044, LDL-6 1.045-1.063]. CH and TG were determined enzymatically, apolipoproteins by turbidimetry. RESULTS: In eight patients suitable for evaluation cholesterol decreased from 241 to 202 (P<0.05) and TG from 557 to 278 mg/dl (P<0.01), whereas LDL-CH and HDL-CH did not change significantly. A 28.2% decrease of VLDL (P<0.01) and a 19.3% decrease of IDL (P<0.05) paralleled by a significant drop of apoB were observed. Buoyant LDL subclasses increased (LDL-2, +34.3% and LDL-3, +20.3%) whereas dense LDL (LDL-5, -13.4% and LDL-6, -33.1%) decreased (P<0.05 for LDL-6). The ratio of buoyant LDL to dense LDL increased from 0.46+/-0.28 to 0.72+/-0.33 (P<0.05). CONCLUSION: In hypertriglyceridaemic HD patients, dalteparin improved metabolism of TG-rich lipoproteins, increased buoyant LDL and decreased potentially atherogenic dense LDL. Preservation of lipoprotein lipase by LMW heparin may be a possible mechanism to explain our findings.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n73628\nS-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia.\n\nHallström, S\n\nFranz, M\n\nGasser, H\n\nVodrazka, M\n\nSemsroth, S\n\nLosert, UM\n\nHaisjackl, M\n\nPodesser, BK\n\nMalinski, T\n\nBeiträge in Fachzeitschriften\nISI:000253622100010\n18006447.0\n10.1093/cvr/cvm052\nNone\nAIMS: Uncoupled endothelial nitric oxide synthase (eNOS) is a major contributor to vascular reactive oxygen species generation in ischaemia/reperfusion (I/R) injury. Supplementation of NO by the novel NO donor S-nitroso human serum albumin (S-NO-HSA) may inhibit uncoupling of eNOS (feedback inhibition). METHODS AND RESULTS: Pigs (n = 14; 33.1 +/- 1.7 kg) were continuously monitored for heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and coronary flow (CF). Infusion of either human serum albumin (n = 8; controls) or S-NO-HSA (n = 6) lasted 60 min (0.1 micromol/kg/h) starting 15 min prior to ischaemia. After clamping the aorta under cardiopulmonary bypass (CPB), the hearts underwent 15 min of warm, unprotected ischaemia (37 degrees C). Reperfusion lasted 150 min (30 min under CPB; 15 min weaning; additional 105 min reperfusion). In biopsies from non-ischaemic hearts and myocardial biopsies taken after 150 min of reperfusion, high-energy phosphates were measured and the calcium ionophore-stimulated release of NO, superoxide, and peroxynitrite (ONOO(-)) were monitored with nanosensors. Compared with non-ischaemic hearts, the NO level decreased from 930 +/- 25 to 600 +/- 15 nmol/L (P < 0.001) while the superoxide level increased from 45 +/- 5 to 110 +/- 10 nmol/L (P < 0.001) after ischaemia. S-NO-HSA restored the NO level to 825 +/- 20 nmol/L, shifted favourably the [NO]/[ONOO(-)] balance (a marker of eNOS uncoupling) from 1.36 +/- 0.06 (ischaemia) to 3.59 +/- 0.18, significantly improved CF (65 +/- 10 vs. control, 43 +/- 5 mL/min, P < 0.05), MAP (57 +/- 5 vs. 39 +/- 3 mm Hg, P < 0.01), LVSP (106 +/- 5 vs. 81 +/- 4 mm Hg, P < 0.01) and phosphocreatine (PCr) content (41.5 +/- 7.3 vs. 18.0 +/- 5.6 micromol/g protein; P < 0.01) at 150 min of reperfusion. CONCLUSION: Long-lasting release of NO by S-NO-HSA prevented uncoupling of eNOS and thereby improved systolic and diastolic function, myocardial perfusion, and the energetic reserve of the heart after I/R injury.\n\nHallström, Seth\n\n\n"
},
{
"text": "\n81842\nAngiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium.\n\nKockskämper, J\n\nKhafaga, M\n\nGrimm, M\n\nElgner, A\n\nWalther, S\n\nKockskämper, A\n\nvon Lewinski, D\n\nPost, H\n\nGrossmann, M\n\nDörge, H\n\nGottlieb, PA\n\nSachs, F\n\nEschenhagen, T\n\nSchöndube, FA\n\nPieske, B\n\nBeiträge in Fachzeitschriften\nISI:000259301600014\n18503051.0\n10.1093/cvr/cvn126\nPMC2614393\nAims Stretch is an important regulator of atrial function. The functional effects of stretch on human atrium, however, are poorly understood. Thus, we characterized the stretch-induced force response in human atrium and evaluated the underlying cellular mechanisms. Methods and results Isometric twitch force of human atrial trabeculae (n = 252) was recorded (37 C, 1 Hz stimulation) following stretch from 88 (L88) to 98% (L98) of optimal length. [Na(+)](i) and pH(i) were measured using SBFI and BCECF epifluorescence, respectively. Stretch induced a biphasic force increase: an immediate increase [first-phase, Frank-Starting mechanism (FSM)] to similar to 190% of force at L88 followed by an additional slower increase [5-10 min; stow force response (SFR)] to similar to 120% of the FSM. FSM and SFR were unaffected by gender, age, ejection fraction, and pre-medication with major cardiovascular drugs. There was a positive correlation between the amplitude of the FSM and the SFR. [Na(+)](i) rose by similar to 1 mmol/L and pH(i) remained unchanged during the SFR. Inhibition of Na(+)/H(+)-exchange (3 mu M HOE642), Na(+)/Ca(2+)-exchange (5 mu M KB-R7943), or stretch-activated channels (0.5 mu M, GsMtx-4 and 80 mu M streptomycin) did not reduce the SFR. Inhibition of angiotensin-II (AngII) receptors (5 mu M saralasin and 0.5 mu M PD123319) or pre-application of 0.5 mu M AngII, however, reduced the SFR by similar to 40-60%. Moreover, stretch increased phosphorylation of myosin tight chain 2 (MLC2a) and inhibition of MLC kinase (10 mu M ML-7 and 5 mu M wortmannin) decreased the SFR by similar to 40-85%. Conclusion Stretch elicits a SFR in human atrium. The atrial SFR is mediated by stretch-induced release and autocrine/paracrine actions of AngII and increased myofilament Ca(2+) responsiveness via phosphorylation of MLC2a by MLC kinase.\n\nvon Lewinski, Dirk\n\n\n"
},
{
"text": "\n82483\nAssay of anticancer drugs in tissue culture: comparison of a tetrazolium-based assay and a protein binding dye assay in short-term cultures derived from human malignant glioma.\n\nHaselsberger, K\n\nPeterson, DC\n\nThomas, DG\n\nDarling, JL\n\nBeiträge in Fachzeitschriften\nISI:A1996UR40100014\n8792008.0\n10.1097/00001813-199605000-00014\nNone\nBecause of the methodological difficulties associated with the MTT assay in screening short-term cultures derived from human malignant glioma, a chemosensitivity assay based on the protein staining using sulforhodamine B (SRB) has been optimized for use with these cells. SRB at a fixed dye concentration achieved maximal staining density at 20 min for most cell lines and this intensity was not further increased by using dye concentrations above 0.2%. A delay in staining after fixation did not significantly decrease staining intensity, but delay in dye extraction after fixation and staining did. There was an excellent quantitative and qualitative linear relationship between cell number determined by either the SRB assay or by cell counting, but not with the MTT assay which consistently underestimated the number of cells in assay plates. The MTT assay appeared to be incapable of detecting less than about 150 cells/well, while these small numbers of cell were readily detectable by either cell counting or SRB staining. There was a close correlation between chemosensitivity values derived from the MTT and SRB assays for procarbazine, CCNU and vincristine when the endpoint is taken as either the ID25, ID50 or ID75. The results indicate that the SRB is capable of producing broadly similar results to the MTT assay, but is more sensitive in the detection of small numbers of cells with a linear relationship between cell number and SRB staining intensity over a wide range of cell numbers. It is capable of producing data from short-term cultures from malignant glioma and offers technical advantages over the MTT assay in that plates may safely be stored at certain points during the assay without the need for immediate processing. The SRB assay provides a useful alternative to the MTT assay for determining the sensitivity of short-term cultures of human glioma to cytotoxic drugs.\n\n\n"
},
{
"text": "\n82505\nModulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons.\n\nLirk, P\n\nPoroli, M\n\nRigaud, M\n\nFuchs, A\n\nFillip, P\n\nHuang, CY\n\nLjubkovic, M\n\nSapunar, D\n\nHogan, Q\n\nBeiträge in Fachzeitschriften\nISI:000258168300048\n18633052.0\n10.1213/ane.0b013e31817b7a73\nPMC2872162\nBACKGROUND: Chronic neuropathic pain resulting from neuronal damage remains difficult to treat, in part, because of incomplete understanding of underlying cellular mechanisms. We have previously shown that inward Ca2+ flux (I(Ca)) across the sensory neuron plasmalemma is decreased in a rodent model of chronic neuropathic pain, but the direct consequence of this loss of I(Ca) on function of the sensory neuron has not been defined. We therefore examined the extent to which altered membrane properties after nerve injury, especially increased excitability that may contribute to chronic pain, are attributable to diminished Ca2+ entry. METHODS: Intracellular microelectrode measurements were obtained from A-type neurons of dorsal root ganglia excised from uninjured rats. Recording conditions were varied to suppress or promote I(Ca) while biophysical variables and excitability were determined. RESULTS: Both lowered external bath Ca2+ concentration and blockade of I(Ca) with bath cadmium diminished the duration and area of the after-hyperpolarization (AHP), accompanied by decreased current threshold for action potential (AP) initiation and increased repetitive firing during sustained depolarization. Reciprocally, elevated bath Ca2+ increased the AHP and suppressed repetitive firing. Voltage sag during neuronal hyperpolarization, indicative of the cation-nonselective H-current, diminished with decreased bath Ca2+, cadmium application, or chelation of intracellular Ca2+. Additional recordings with selective blockers of I(Ca) subtypes showed that N-, P/Q, L-, and R-type currents each contribute to generation of the AHP and that blockade of any of these, and the T-type current, slows the AP upstroke, prolongs the AP duration, and (except for L-type current) decreases the current threshold for AP initiation. CONCLUSIONS: Taken together, our findings show that suppression of I(Ca) decreases the AHP, reduces the hyperpolarization-induced voltage sag, and increases excitability in sensory neurons, replicating changes that follow peripheral nerve trauma. This suggests that the loss of I(Ca) previously demonstrated in injured sensory neurons contributes to their dysfunction and hyperexcitability, and may lead to neuropathic pain.\n\n\n"
},
{
"text": "\n119584\nUltrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes.\n\nFrascione, D\n\nDiwoky, C\n\nAlmer, G\n\nOpriessnig, P\n\nVonach, C\n\nGradauer, K\n\nLeitinger, G\n\nMangge, H\n\nStollberger, R\n\nPrassl, R\n\nBeiträge in Fachzeitschriften\nISI:000303916800001\n22661890.0\n10.2147/IJN.S30617\nPMC3357980\nBackground: Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magnetic and/or paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). MLs have an advantage over free magnetic nanocores, in that various functional groups can be attached to the surface of liposomes for ligand-specific targeting. We have synthesized PEG-coated sterically-stabilized magnetic liposomes (sMLs) containing ultrasmall superparamagnetic iron oxides (USPIOs) with the aim of generating stable liposomal carriers equipped with a high payload of USPIOs for enhanced MRI contrast. Methods: Regarding iron oxide nanoparticles, we have applied two different commercially available surface-coated USPIOs; sMLs synthesized and loaded with USPIOs were compared in terms of magnetization and colloidal stability. The average diameter size, morphology, phospholipid membrane fluidity, and the iron content of the sMLs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence polarization, and absorption spectroscopy, respectively. A colorimetric assay using potassium thiocyanate (KSCN) was performed to evaluate the encapsulation efficiency (EE%) to express the amount of iron enclosed into a liposome. Subsequently, MRI measurements were carried out in vitro in agarose gel phantoms to evaluate the signal enhancement on T1- and T2-weighted sequences of sMLs. To monitor the biodistribution and the clearance of the particles over time in vivo, sMLs were injected in wild type mice. Results: DLS revealed a mean particle diameter of sMLs in the range between 100 and 200 nm, as confirmed by TEM. An effective iron oxide loading was achieved just for one type of USPIO, with an EE% between 74% and 92%, depending on the initial Fe concentration (being higher for lower amounts of Fe). MRI measurements demonstrated the applicability of these nanostructures as MRI probes. Conclusion: Our results show that the development of sMLs is strictly dependent on the physicochemical characteristics of the nanocores. Once established, sMLs can be further modified to enable noninvasive targeted molecular imaging.\n\nAlmer, Gunter\n\nLeitinger, Gerd\n\nMangge, Harald\n\nPrassl, Ruth\n\n\n"
},
{
"text": "\n128556\nCystatin C is independently associated with total and cardiovascular mortality in individuals undergoing coronary angiography. The Ludwigshafen Risk and Cardiovascular Health (LURIC) study.\n\nWoitas, RP\n\nKleber, ME\n\nMeinitzer, A\n\nGrammer, TB\n\nSilbernagel, G\n\nPilz, S\n\nTomaschitz, A\n\nWeihrauch, G\n\nDobnig, H\n\nMärz, W\n\nScharnagl, H\n\nBeiträge in Fachzeitschriften\nISI:000322316900045\n23706287.0\n10.1016/j.atherosclerosis.2013.04.027\nNone\nCystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with mortality. The present analysis prospectively evaluated the associations of cystatin C with all-cause and cardiovascular (CV) mortality in a well-characterized cohort of persons undergoing angiography, but without overt renal insufficiency.\n Cystatin C was available in 2998 persons (mean age: 62.7 ± 10.5 years; 30.3% women). Of those 2346 suffered from coronary artery disease (CAD) and 652 (controls) did not. Creatinine (mean ± SD: 83.1 ± 47.8 vs. 74.1 ± 24.7 μmol/L, p = 0.036) but not Cystatin C (mean ± SD: 1.02 ± 0.44 vs. 0.92 ± 0.26 mg/L, p = 0.065) was significantly higher in patients with CAD. After a median follow-up of 9.9 years, in total 898 (30%) deaths occurred, 554 (18.5%) due to CV disease and 326 (10.9%) due to non-CV causes. Multivariable-adjusted Cox analysis (adjusting for eGFR and established cardiovascular risk factors, lipid lowering therapy, angiographic coronary artery disease, and C-reactive protein) revealed that patients in the highest cystatin C quartile were at an increased risk for all-cause (hazard ratio (HR) 1.93, 95% CI 1.50-2.48) and CV mortality (HR 2.05 95% CI 1.48-2.84) compared to those in the lowest quartile. The addition of cystatin C to a model consisting of established cardiovascular risk factors increased the area under the receiver-operating characteristic curve for CV and all-cause mortality, but the difference was statistically not significant. However, reclassification analysis revealed significant improvement by addition of cystatin C for CV and all-cause mortality (p < 0.001), respectively.\n The concentration of cystatin C is strongly associated with long-term all-cause and cardiovascular mortality in patients referred to coronary angiography, irrespective of creatinine-based renal function.\n Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\nPilz, Stefan\n\nScharnagl, Hubert\n\nSilbernagel, Günther\n\n\n"
}
]
}