Refine
Year of publication
Document Type
- Article (30)
- Preprint (1)
- Working Paper (1)
Has Fulltext
- yes (32)
Is part of the Bibliography
- no (32)
Keywords
- Aurora A (2)
- BCL6 (2)
- Primary cilium (2)
- adipose-derived mesenchymal stem cells (2)
- differentiation (2)
- focal adhesion (2)
- invasion (2)
- migration (2)
- primary cilium (2)
- trophoblast (2)
Institute
- Medizin (23)
- Geowissenschaften (7)
- Erziehungswissenschaften (1)
HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor.
Background: Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP.
Methods/Design: The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (<15 versus ≥15 g/L) and the study site is planned. In this multicenter national study, patients are recruited in at least 13 centers throughout Germany. The key inclusion criterion is the presence of a NOD2 risk variant in patients with decompensated liver cirrhosis. The most important exclusion criteria are current SBP or previous history of SBP and any long-term antibiotic prophylaxis. The primary endpoint is overall survival after 12 months of treatment. Secondary objectives are to evaluate whether the frequencies of SBP and other clinically relevant infections necessitating antibiotic treatment, as well as the total duration of unplanned hospitalization due to cirrhosis, differ in both study arms. Recruitment started in February 2014.
Discussion: Preventive strategies are required to avoid life-threatening infections in patients with liver cirrhosis, but unselected use of antibiotics can trigger resistant bacteria and worsen outcome. Thus, individualized approaches that direct intervention only to patients with the highest risk are urgently needed. This trial meets this need by suggesting stratified prevention based on genetic risk assessment. To our knowledge, the INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms.
Trial registrations: German Clinical Trials Register DRKS00005616. Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26. Registered 26 January 2015.
Background: Obesity impairs a variety of cell types including adipose-derived mesenchymal stem cells (ASCs). ASCs are indispensable for tissue homeostasis/repair, immunomodulation, and cell renewal. It has been demonstrated that obese ASCs are defective in differentiation, motility, immunomodulation, and replication. We have recently reported that some of these defects are linked to impaired primary cilia, which are unable to properly convey and coordinate a variety of signaling pathways. We hypothesized that the rescue of the primary cilium in obese ASCs would restore their functional properties.
Methods: Obese ASCs derived from subcutaneous and visceral adipose tissues were treated with a specific inhibitor against Aurora A or with an inhibitor against extracellular signal-regulated kinase 1/2 (Erk1/2). Multiple molecular and cellular assays were performed to analyze the altered functionalities and their involved pathways.
Results: The treatment with low doses of these inhibitors extended the length of the primary cilium, restored the invasion and migration potential, and improved the differentiation capacity of obese ASCs. Associated with enhanced differentiation ability, the cells displayed an increased expression of self-renewal/stemness-related genes like SOX2, OCT4, and NANOG, mediated by reduced active glycogen synthase kinase 3 β (GSK3β).
Conclusion: This work describes a novel phenomenon whereby the primary cilium of obese ASCs is rescuable by the low-dose inhibition of Aurora A or Erk1/2, restoring functional ASCs with increased stemness. These cells might be able to improve tissue homeostasis in obese patients and thereby ameliorate obesity-associated diseases. Additionally, these functionally restored obese ASCs could be useful for novel autologous mesenchymal stem cell-based therapies.
Introduction: This study presents our online-teaching material within the k-MED project (Knowledge in Medical Education) at the university of Marburg. It is currently organized in five e-learning modules: cytogenetics, chromosomal aberrations, formal genetics, fundamentals of molecular diagnostics, and congenital abnormalities and syndromes. These are basic courses intended to do the educational groundwork, which will enable academic teachers to concentrate on more sophisticated topics during their lectures. Methods: The e-learning modules have been offered to a large group of about 3300 students during four years at the Faculty of Medicine in Marburg. The group consists of science students (human biology) and medical students in the preclinical or the clinical period, respectively. Participants were surveyed on acceptance by evaluating user-tracking data and questionnaires. Results and Conclusion: Analysis of the evaluation data proofs the broad acceptance of the e-learning modules during eight semesters. The courses are in stable or even increasing use from winter term 2005/06 until spring term 2009. Conclusion: Our e-learning-model is broadly accepted among students with different levels of knowledge at the Faculty of Medicine in Marburg. If the e-learning courses are maintained thoroughly, minor adaptations can increase acceptance and usage even furthermore. Their use should be extended to the medical education of technical assistances and nurses, who work in the field of human genetics. Keywords: Human genetics, e-Learning, evaluation, multimedia
Einleitung: Die vorliegende Studie beschreibt unser Online-Lehrmaterial Humangenetik im Zusammenhang mit dem k-MED-Projekt (Knowledge in Medical Education) an der Philipps-Universität Marburg. Es besteht aus fünf E-Learning-Modulen: Zytogenetik, Chromosomenstörungen, Formalgenetik, Grundlagen der molekularen Diagnostik sowie Kongenitale Abnormitäten und Fehlbildungssyndrome. Diese E-Module sollen ein einheitliches Wissensniveau der Studierenden gewährleisten und die Dozenten in der Präsenzlehre entlasten. Methoden: Die fünf E-Learning-Module Humangenetik wurden auf freiwilliger Basis einer großen Personengruppe von ca. 3300 Studierenden am Fachbereich Humanmedizin der Universität Marburg über eine Dauer von vier Jahren angeboten. Die Teilnehmer bestanden aus Naturwissenschaftlern (Humanbiologie) im 5. Fachsemester und Studierenden der Humanmedizin, die sich entweder in der Vorklinik (1. Semester) oder im klinischen Studienabschnitt (7./8. Semester) befanden. Von diesen wurden Daten zur Akzeptanz in Form von Usertrackingdaten und klausur-begleitenden Fragebögen erhoben. Ergebnisse und Schlussfolgerung: Die Evaluation zeigte eine breite Akzeptanz unserer Lehrmodule über einen Zeitraum von acht Semestern. Obwohl das Angebot freiwillig ist, werden die Online-Kurse Humangenetik konstant oder sogar in zunehmendem Maße zwischen Wintersemester 2005/06 und Sommersemester 2009 genutzt. Fazit: Unser E-Learning-Modell Humangenetik wird von Studierenden aus unterschiedlichen Semestern und Studiengängen am Fachbereich Humanmedizin gut angenommen und genutzt. Bei sorgfältiger Pflege der Online-Kurse steigern moderate Anpassungen sowohl Akzeptanz als auch Benutzungshäufigkeit in signifikanter Weise. Die Anwendung der E-Learning Module erscheint uns auch in der Ausbildung von MTAs oder Pflegekräften sinnvoll, um ein ausreichendes Grundwissen in Humangenetik zu gewährleisten. Schlüsselwörter: Humangenetik, Evaluation, Multimedia, E-Learning
In den letzten Jahrhunderten kam es regelmäßig zur aktiven oder passiven Einbringung von Pflanzenarten in die mitteleuropäische Flora. Dieser Zuwachs wurde von JÄGER (1988) eingehend beschrieben. Umfangreiche Analysen aktueller Publikationen liegen den zusammenfassenden Darstellungen von KOWARIK (2003) und PYŠEK et al. (2002) zu Grunde. Während JÄGER (1988) bei seiner Analyse der Einschleppungs- und Einbürgerungsentwicklung noch von einem Schwerpunkt im 19. Jahrhundert und einem allmählichen Rückgang der Einbürgerungszahlen neuer Pflanzenarten ausgeht, deutet die starke Zunahme von Neueinbürgerungen seit den 1990er Jahren auf einen noch drastischeren Florenwandel in Mitteleuropa als im 19. Jh. geschehen hin. Mögliche Ursachen sind neben den immensen Veränderungen der Landnutzung und dem Klimawandel insbesondere die wesentlich verbesserten globalen und regionalen Transport- und Austauschmöglichkeiten.
Emotional instability, difficulties in social adjustment, and disinhibited behavior are the most common symptoms of the psychiatric comorbidities in juvenile myoclonic epilepsy (JME). This psychopathology has been associated with dysfunctions of mesial-frontal brain circuits. The present work is a first direct test of this link and adapted a paradigm for probing frontal circuits during empathy for pain. Neural and psychophysiological parameters of pain empathy were assessed by combining functional magnetic resonance imaging (fMRI) with simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In JME patients, we observed reduced neural activation of the anterior cingulate cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy for pain in patients. At the same time, pupil dilation was positively related to neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally showed reduced functional connectivity with the primary and secondary somatosensory cortex, areas fundamentally implicated in processing the somatic cause of another's pain. Our results provide first evidence that alterations of mesial-frontal circuits directly affect psychosocial functioning in JME patients and draw a link of pupil dynamics with brain activity during emotional processing. The findings of reduced pain empathy related activation of the ACC and AI and aberrant functional integration of the ACC with somatosensory cortex areas provide further evidence for this network's role in social behavior and helps explaining the JME psychopathology and patients' difficulties in social adjustment.
Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients.
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.