Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis : a cross-sectional multicentre international study with experimental animal model

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n=983), recurrent AP (RAP, n=270) and CP (n=62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5+was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3+do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.Peer reviewe

Sleeping Beauty transposon-based system for cellular reprogramming and targeted gene insertion in induced pluripotent stem cells.

The discovery of direct cell reprogramming and induced pluripotent stem (iPS) cell technology opened up new avenues for the application of non-viral, transposon-based gene delivery systems. The Sleeping Beauty (SB) transposon is highly advanced for versatile genetic manipulations in mammalian cells. We established iPS cell reprogramming of mouse embryonic fibroblasts and human foreskin fibroblasts by transposition of OSKM (Oct4, Sox2, Klf4 and c-Myc) and OSKML (OSKM + Lin28) expression cassettes mobilized by the SB100X hyperactive transposase. The efficiency of iPS cell derivation with SB transposon system was in the range of that obtained with retroviral vectors. Co-expression of the miRNA302/367 cluster together with OSKM significantly improved reprogramming efficiency and accelerated the temporal kinetics of reprogramming. The iPS cells displayed a stable karyotype, and hallmarks of pluripotency including expression of stem cell markers and the ability to differentiate into embryoid bodies in vitro. We demonstrate Cre recombinase-mediated exchange allowing simultaneous removal of the reprogramming cassette and targeted knock-in of an expression cassette of interest into the transposon-tagged locus in mouse iPS cells. This strategy would allow correction of a genetic defect by site-specific insertion of a therapeutic gene construct into 'safe harbor' sites in the genomes of autologous, patient-derived iPS cells

The Europeanization of Social Democracy in East Central Europe

'The Europeanization of social democratic parties in the new member states has reached a turning point with accession, especially in relation to the upcoming elections to the European Parliament (EP) in June 2004. At the same time, domestically the social construction of democracy is high on the agenda in East Central Europe (ECE) after a long decade of political and economic transformation which has brought the region to the stage of democratic consolidation. The ECE countries have arrived at a crossroads: in parallel with EU accession they must decide what kind of public sector they will create, almost from scratch, and how a new democratic state will be built. This paper focuses on the present situation of social democracy in ECE, particularly in respect of the connection between social interests and political parties in the Europeanization process. It tries to combine a bottom-up and a top-down approach, presenting the attempts of leftist party elites to solve social problems and represent societal interests on the one hand, and describing the forms and intensity of popular pressure from below on the other. The formation of political parties in ECE, indeed, has been to a great extent an elite-dominated process and the party elites have used several forms of political marketing to attract voter support without a meaningful social response. It is equally true that the ECE parties - at least in their rhetoric and mostly before elections - have tried to satisfy their constituencies' demands, so to some extent they have had to pursue social interest-driven politics. However, the main influence on ECE party formation has been the example of the Western European party system: only those have survived that could fit into the pre-existing party-types with an 'EU license', that is, have received an 'accreditation' from the West. This paper focuses on the changes in the external role and internal structure of left-wing parties in ECE, contrasting between external and internal Europeanization, also in respect of the painful road from politics to policy, that is, from ideologically-driven political battles to concrete policy-making processes. Our conclusion is that despite particular efforts to solve the problems of those who have lost out from systemic change and EU accession, the challenges they have faced have brought hard times for the Left everywhere in ECE, indicating a difficult start for social democracy in the westernmost part of the 'East,' namely Central Europe.' (extract)Die Europaeisierung der sozialdemokratischen Parteien in den neuen Mitgliedsstaaten hat mit dem Beitritt und besonders den Wahlen zum Europaeischen Parlament einen Wendepunkt erreicht. Gleichzeitig steht auf nationaler Ebene der soziale Aufbau der Demokratie nach einer langen Zeit politischer und oekonomischer Transformation an der Spitze der Tagesordnung in Mittel- und Osteuropa (ECE). Die ECE-Laender muessen sich mit dem Beitritt zur EU entscheiden, wie der oeffentliche Sektor ausgestaltet sein soll und wie ein neuer demokratischer Staat aufgebaut werden kann. Der vorliegende Beitrag konzentriert sich auf die Sozialdemokratie in den ECE-Laendern unter besonderer Beruecksichtigung der Beziehungen zwischen sozialen Interessen und politischen Parteien waehrend des Europaeisierungsprozesses. Der Autor verbindet dabei die Positionen der Parteielite und der Parteibasis. (ICDUebers)German title: Die Europaeisierung der Sozialdemokratie in OstmitteleuropaAvailable from Friedrich-Ebert-Stiftung e.V. Abt. Internationale Politikanalyse, Bonn (DE) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Ungarn zwischen zentralistischer Mehrheitsdemokratie und europaeischer Mehrebenendemokratie

'Der Sieg der Rechten, der frueher liberalen Jungdemokraten (FIDESZ) bei den Wahlen von 1998 veraenderte den Stil, in dem in Ungarn Politik betrieben wird. Die Machtuebernahme durch die FIDESZ spitzte die unvermeidlichen neuen und scharfen Widersprueche der politischen und wirtschaftlichen Transformation noch weiter zu. Trotz aller zentralistischer Tendenzen der 'FIDESZ-Welt' steht Ungarn in Mitteleuropa dennoch den Demokratien westlichen Typs am naechsten, und die Europaeisierung ist nicht nur gelungen, sondern hat in diesem Regierungszyklus sogar Fortschritte gemacht. Vom so oft zitierten Zusammenbruch der ungarischen Demokratie kann also keine Rede sein, auch deshalb nicht, weil fuer eine autoritaere Restauration, vereinfacht ausgedrueckt, fuer eine Jahrzehnte waehrende Konsolidierung a la Bethlen wie zu Beginn der zwanziger Jahre weder die externen, noch die internen Bedingungen vorhanden sind. Heute vollzieht sich vielmehr die mit grossem Laerm betriebene Etablierung der neuen Elite, die fuer Ungarn sehr kostspielig ist. Schlimmer und noch kostspieliger als die Etablierung einer neuen Elite ist nur noch, wenn die rechte, alternative Elite immer wieder auseinander bricht, wie in Polen. Am schlimmsten ist die Situation wohl in Tschechien oder der Slowakei, wo bislang noch keine einzige lebensfaehige politische Elite die Buehne betreten hat und Parteienfragmente die politische Arena bedecken. So ist die Politikverdrossenheit der Bevoelkerung in Tschechien und der Slowakei nicht weiter verwunderlich.' (Autorenreferat)SIGLEAvailable from http://library.fes.de/fulltext/id/01245.htm / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Hadron thermodynamics from imaginary chemical potentials

We use 4stout improved staggered lattice data at imaginary chemical potentials to calculate fugacity expansion coefficients in finite temperature QCD. We discuss the phenomenological interpretation of our results within the hadron resonance gas (HRG) model, and the hints they give us about the hadron spectrum. We also discuss features of the higher order coefficients that are not captured by the HRG. This conference contribution is based on our recent papers [1, 2].

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

© 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975)

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes