Kliche T.,Universitatsklinikum Eppendorf
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2011
In order to identify requirements of quality assurance in this field, a general description of prevention, health promotion and education is outlined, based upon healthcare supply analyses and 158 interviews with experts. Prominent features are, among others, a distinctive heterogeneity and complexity of settings, suppliers, and interventions; supply of coverage is below public health criteria (needs); weak outcome evaluation; competition among suppliers, providers, and political agencies and decision makers; need for intra-and intersectoral coordination; the lack of evidence-based healthcare planning; and hurdles for quality assurance. A structural taxonomy of quality assurance systems is then developed, consisting of three dimensions: validity (quality of information), regularity, and degree of commitment and obligation. In terms of these dimensions, important systems of quality assurance in prevention, health promotion and education in Germany are analyzed. A number of different systems and approaches can be found. However, most of them share questionable validity, regularity, and degree of obligation. Increased commitment on behalf of providers, suppliers, and political institutions and decision makers for the quality of preventive interventions is inevitable in order to raise the performance of prevention and health promotion in Germany to their potential effectiveness. © Springer-Verlag 2011.
Hornig J.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Frob F.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Vogl M.R.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Hermans-Borgmeyer I.,Universitatsklinikum Eppendorf |
And 2 more authors.
PLoS Genetics | Year: 2013
Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented. © 2013 Hornig et al.
Langer F.,Universitatsklinikum Eppendorf
Blood | Year: 2013
Lymphocyte depletion with antithymocyte globulin (ATG) can be complicated by systemic coagulation activation. We found that ATG activated tissue factor procoagulant activity (TF PCA) on monocytic cells more potently than other stimuli that decrypt TF, including cell disruption, TF pathway inhibitor inhibition, and calcium ionophore treatment. Induction of TF PCA by ATG was dependent on lipid raft integrity and complement activation. We showed that ATG-mediated TF activation required complement activation until assembly of the C5b-7 membrane insertion complex, but not lytic pore formation by the membrane attack complex C5b-9. Consistently, induction of TF PCA by ATG did not require maximal phosphatidylserine membrane exposure and was not correlated with the magnitude of complement-induced lytic cell injury. Blockade of free thiols, an inhibitory monoclonal antibody to protein disulfide isomerase (PDI), and the small-molecule PDI antagonist quercetin-3-rutinoside prevented ATG-mediated TF activation, and C5 complement activation resulted in oxidation of cell surface PDI. This rapid and potent mechanism of cellular TF activation represents a novel connection between the complement system and cell surface PDI-mediated thiol-disulfide exchange. Delineation of this clinically relevant mechanism of activation of the extrinsic coagulation pathway during immunosuppressive therapy with ATG may have broader implications for vascular thrombosis associated with inflammatory disorders.
Langer F.,Universitatsklinikum Eppendorf |
Ruf W.,Scripps Research Institute |
Ruf W.,Universitatsmedizin Mainz
Thrombosis and Haemostasis | Year: 2014
Tissue factor (TF), the cellular receptor and cofactor for factor VII/VIIa, initiates haemostasis and thrombosis. Initial tissue distribution studies suggested that TF was sequestered from the circulation and only present at perivascular sites. However, there is now clear evidence that TF also exists as a blood-borne form with critical contributions not only to arterial thrombosis following plaque rupture and to venous thrombosis following endothelial perturbation, but also to various other clotting abnormalities associated with trauma, infection, or cancer. Because thrombin generation, fibrin deposition, and platelet aggregation in the contexts of haemostasis, thrombosis, and pathogen defence frequently occur without TF de novo synthesis, considerable efforts are still directed to understanding the molecular events underlying the conversion of predominantly non-coagulant or cryptic TF on the surface of haematopoietic cells to a highly procoagulant molecule following cellular injury or stimulation. This article will review some of the still controversial mechanisms implicated in cellular TF activation or decryption with particular focus on the coordinated effects of outer leaflet phosphatidylserine exposure and thiol-disulfide exchange pathways involving protein disulfide isomerase (PDI). In this regard, our recent findings of ATP-triggered stimulation of the purinergic P2X7 receptor on myeloid and smooth muscle cells resulting in potent TF activation and shedding of procoagulant microparticles as well as of rapid monocyte TF decryption following antithymocyte globulin-dependent membrane complement fixation have delineated specific PDIdependent pathways of cellular TF activation and thus illustrated additional and novel links in the coupling of inflammation and coagulation. © Schattauer 2014.
Hummel F.C.,Universitatsklinikum Eppendorf
Nervenarzt | Year: 2014
Modern neuroimaging techniques, such as structural and functional magnetic resonance imaging (MRI) and non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) are increasingly used in the neuroscientific research of neurological disorders, such as stroke, tinnitus and movement disorders. These methods offer a non-invasive approach and especially in combination, not only the opportunity to add to the pathophysiological understanding of these disorders but also to provide information about the functional recovery and the natural course of the disease in a predictive way. Based on such knowledge therapeutic approaches can be adapted in a patient-tailored fashion to achieve the best therapeutic effects. Furthermore, these methods might provide additional non-invasive information for neurosurgical interventions reducing perioperative interventional risks.In the present article these aspects will be discussed with a focus on the combination of MRI and TMS especially addressed for the topic of recovery from stroke. © Springer-Verlag Berlin Heidelberg 2014.