Postdemokratie und Citizenship Gratzer, Julia Magdalena; Reiter, Katrin
Magazin erwachsenenbildung.at,
2010
11
Journal Article
Recenzirano
Inwiefern nehmen StaatsbürgerInnen ihr demokratisches Recht auf Gestaltung ihres Lebens wahr und können realpolitisch ihr eigenes Leben und damit auch gesellschaftliche Strukturen mitgestalten? Was ...heißt, politisch verantwortlich zu handeln, und wo bzw. wie beginnt politisches Handeln überhaupt? Sind wir bereits an die Grenzen der Demokratie gestoßen? Colin Crouch zufolge haben wir die demokratischen Grenzen bereits überschritten und befinden wir uns in einer postdemokratischen Zeit, in der die politischen Verhandlungen hinter verschlossenen Türen stattfinden und Wahlen eher fadenscheinig abgehalten werden - es eben nicht mehr die StaatsbürgerInnen sind, von denen das Recht ausgeht, obzwar im ersten Artikel der Österreichischen Bundesverfassung steht: "Österreich ist eine demokratische Republik. Ihr Recht geht vom Volk aus". In diesem Spannungsfeld zwischen Demokratie, Postdemokratie und ihrem Verhältnis zu StaatsbürgerInnen bewegten sich die in diesem Beitrag vorgestellten Vorträge, Workshops und Diskussionen der Tagung "Postdemokratie und Citizenship" am Bundesinstitut für Erwachsenenbildung in Strobl 2010. (Verl.).
Current guidelines for the diagnosis of acute myocardial infarction (AMI), among other criteria, also require a rise and/or fall in cardiac troponin (cTn) levels. It is unknown whether absolute or ...relative changes in cTn have higher diagnostic accuracy and should therefore be preferred.
In a prospective, observational, multicenter study, we analyzed the diagnostic accuracy of absolute (Δ) and relative (Δ%) changes in cTn in 836 patients presenting to the emergency department with symptoms suggestive of AMI. Blood samples for the determination of high-sensitive cTn T and cTn I ultra were collected at presentation and after 1 and 2 hours in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing AMI was significantly higher for 2-hour absolute (Δ) versus 2-hour relative (Δ%) cTn changes (area under the receiver operating characteristic curve 95% confidence interval, high-sensitivity cTn T: 0.95 0.92 to 0.98 versus 0.76 0.70 to 0.83, P<0.001; cTn I ultra: 0.95 0.91 to 0.99 versus 0.72 0.66 to 0.79, P<0.001). The receiver operating characteristic curve-derived cutoff value for 2-hour absolute (Δ) change was 0.007 μg/L for high-sensitivity cTn T and 0.020 μg/L for cTn I ultra (both cutoff levels are half of the 99th percentile of the respective cTn assay). Absolute changes were superior to relative changes in patients with both low and elevated baseline cTn levels.
Absolute changes of cTn levels have a significantly higher diagnostic accuracy for AMI than relative changes, and seem therefore to be the preferred criteria to distinguish AMI from other causes of cTn elevations.
URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00470587.
To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without ...acute myocardial infarction (AMI).
In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays.
Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value.
RING-between-RING (RBR) E3s contain RING1 domains that are structurally similar yet mechanistically distinct from canonical RING domains. Both types of E3 bind E2∼ubiquitin (E2∼Ub) via their RINGs ...but canonical RING E3s promote closed E2∼Ub conformations required for direct Ub transfer from the E2 to substrate, while RBR RING1s promote open E2∼Ub to favor Ub transfer to the E3 active site. This different RING/E2∼Ub conformation determines its direct target, which for canonical RING E3s is typically a substrate or substrate-linked Ub, but is the E3 active-site cysteine in the case of RBR-type E3s. Here we show that a short extension of HHARI RING1, namely Zn2+-loop II, not present in any RING E3s, acts as a steric wedge to disrupt closed E2∼Ub, providing a structural explanation for the distinctive RING1-dependent conformational restriction mechanism utilized by RBR E3s.
•HHARI RING1 Zn2+-loop II extension disrupts closed conformation of E2∼Ubs•A crystal structure shows open UbcH7∼Ub binding RING1 of auto-inhibited HHARI•HHARI UBA-L domain has Ub binding properties
Dove et al. show that RING1 domains found in RING-between-RING (RBR) E3s, like HHARI, use Zn2+-loop II to disrupt closed E2∼Ub, resulting in open E2∼Ub that favor Ub transfer to the E3 active site. The work places the mechanism of RBR E3s-mediated Ub transfer on structural footing.
To introduce blood normalization for myocardial T1 values at magnetic resonance (MR) imaging and to evaluate regional differences between systolic and diastolic myocardial T1 values in healthy ...subjects.
This prospective study (ClinicalTrials.gov identification number, NCT01728597) was approved by the institutional review board, and volunteer informed consent was obtained. Forty healthy subjects (20 women; age range, 20-35 years) underwent electrocardiographically gated 1.5-T MR imaging. A modified Look-Locker inversion recovery sequence was used to acquire myocardial T1 maps in systole and diastole. Regional T1 values were evaluated in 16 myocardial segments; blood T1 was derived from the blood pool in the center of the left ventricular cavity. Linear regression slopes between myocardial and blood T1 values were used to normalize myocardial T1 to the mean blood T1 of the study population. Mean T1 values were compared by using the t test, with P < .05 considered to indicate a significant difference.
Mean myocardial T1 (984 msec ± 28 standard deviation in diastole, 959 msec ± 21 in systole) and all segmental T1 values between diastole and systole differed significantly (P < .001). Blood T1 correlated well with segmental myocardial T1 (R = 0.73 for diastole, R = 0.72 for systole). After normalization to blood T1, significant sex differences in myocardial T1 disappeared and variances in mean myocardial T1 decreased. Blood-normalized diastolic and systolic myocardial T1 values correlated strongly with each other on segmental (r = 0.72) and global (r = 0.89) levels. Subregional myocardial T1 distribution characteristics in diastole were similar to those in systole.
In normal myocardium, diastolic and systolic myocardial T1 values differ significantly but correlate strongly. Blood normalization eliminates sex differences in myocardial T1 values and reduces their variability.
T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Herein, we investigated whether heart-specific T cells exert salutary or ...detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class-II-restricted epitopes, we found that myosin heavy chain alpha (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in mice. Transferred MYHCA614-629-specific CD4+ T (TCR-M) cells selectively accumulated in the myocardium and mediastinal lymph nodes (med-LN) of infarcted mice, acquired a Treg phenotype with a distinct pro-healing gene expression profile, and mediated cardioprotection. Myocardial Treg cells were also detected in autopsies from patients who suffered a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in MI-patients. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence showing that MI-context induces pro-healing T cell autoimmunity in mice and confirms the existence of an analogous heart/med-LN/T cell axis in MI patients.
Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the ...noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development.
•Human mutations in KATNB1, encoding katanin p80, cause severe microlissencephaly•Katanin p80 is required for embryogenesis and neocortical development•Katnb1 null mice display few cortical progenitors and nearly absent neurons•Loss of katanin p80 causes excess centrioles and cilia, and disrupts Shh signaling
Hu et al. identify human mutations in KATNB1, encoding the p80 subunit of microtubule-severing complex katanin, as a cause of microlissencephaly and show that katanin p80 regulates centriole and cilia duplication, and Shh signaling during neocortical development.
We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 ...years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.
Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been ...identified. In this study, we show that serotonin (5-hydroxytryptamine 5-HT) stored in platelets strongly induces extracellular matrix synthesis in interstitial fibroblasts via activation of 5-HT(2B) receptors (5-HT(2B)) in a transforming growth factor β (TGF-β)-dependent manner. Dermal fibrosis was reduced in 5-HT(2B)(-/-) mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT(2B) also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis. Consistently, mice deficient for TPH1, the rate-limiting enzyme for 5-HT production outside the central nervous system, showed reduced experimental skin fibrosis. These findings suggest that 5-HT/5-HT(2B) signaling links vascular damage and platelet activation to tissue remodeling and identify 5-HT(2B) as a novel therapeutic target to treat fibrotic diseases.
Abstract Objective The study objective was to compare the incidence and prognosis of acute myocardial infarction when using high-sensitivity cardiac troponin assays instead of a standard cardiac ...troponin assay for the diagnosis of acute myocardial infarction. Methods In a prospective international multicenter study, we enrolled 1124 consecutive patients presenting with suspected acute myocardial infarction. Final diagnoses were adjudicated by 2 independent cardiologists 2 times using all available clinical information: first using standard cardiac troponin levels and second using high-sensitivity cardiac troponin T levels for adjudication. Patients were followed up for a mean of 19 ± 9 months. Results The use of high-sensitivity cardiac troponin T instead of standard cardiac troponin resulted in an increase in the incidence of acute myocardial infarction from 18% to 22% (242 vs 198 patients), a relative increase of 22%. Of the 44 additional acute myocardial infarctions, 35 were type 1 acute myocardial infarctions and 9 were type 2 acute myocardial infarctions. This was accompanied by a reciprocal decrease in the incidence of unstable angina (unstable angina, 11% vs 13%). The most pronounced increase was observed in patients adjudicated with cardiac symptoms of origin other than coronary artery disease with cardiomyocyte damage (83 vs 31 patients, relative increase of 268%). Cumulative 30-month mortality rates were 4.8% in patients without acute myocardial infarction, 16.4% in patients with a small acute myocardial infarction detected only by high-sensitivity cardiac troponin T but not standard cardiac troponin, and 23.9% in patients with a moderate/large acute myocardial infarction according to standard cardiac troponin assays and high-sensitivity cardiac troponin T ( P < .001). Conclusions The introduction of high-sensitivity cardiac troponin assays leads to only a modest increase in the incidence of acute myocardial infarction. The novel sensitive assays identify an additional high-risk group of patients with increased mortality, therefore appropriately classified with acute myocardial infarction (Advantageous Predictors of Acute Coronary Syndromes Evaluation; NCT00470587 ).
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