TY - JOUR A1 - Trudzinski, Franziska C. A1 - Minko, Peter A1 - Rapp, Daniel A1 - Fähndrich, Sebastian A1 - Haake, Hendrik A1 - Haab, Myriam A1 - Bohle, Rainer M. A1 - Flaig, Monika A1 - Kaestner, Franziska A1 - Bals, Robert A1 - Wilkens, Heinrike A1 - Muellenbach, Ralf M. A1 - Link, Andreas A1 - Groesdonk, Heinrich V. A1 - Lensch, Christian A1 - Langer, Frank A1 - Lepper, Philipp M. T1 - Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis JF - Annals of Intensive Care N2 - Background Even though bleeding and thromboembolic events are major complications of extracorporeal membrane oxygenation (ECMO), data on the incidence of venous thrombosis (VT) and thromboembolism (VTE) under ECMO are scarce. This study analyzes the incidence and predictors of VTE in patients treated with ECMO due to respiratory failure. Methods Retrospective analysis of patients treated on ECMO in our center from 04/2010 to 11/2015. Patients with thromboembolic events prior to admission were excluded. Diagnosis was made by imaging in survivors and postmortem examination in deceased patients. Results Out of 102 screened cases, 42 survivors and 21 autopsy cases [mean age 46.0 ± 14.4 years; 37 (58.7 %) males] fulfilling the above-mentioned criteria were included. Thirty-four patients (54.0 %) underwent ECMO therapy due to ARDS, and 29 patients (46.0 %) with chronic organ failure were bridged to lung transplantation. Despite systemic anticoagulation at a mean PTT of 50.6 ± 12.8 s, [VT/VTE 47.0 ± 12.3 s and no VT/VTE 53.63 ± 12.51 s (p = 0.037)], VT and/or VTE was observed in 29 cases (46.1 %). The rate of V. cava thrombosis was 15/29 (51.7 %). Diagnosis of pulmonary embolism prevailed in deceased patients [5/21 (23.8 %) vs. 2/42 (4.8 %) (p = 0.036)]. In a multivariable analysis, only aPTT and time on ECMO predicted VT/VTE. There was no difference in the incidence of clinically diagnosed VT in ECMO survivors and autopsy findings. Conclusions Venous thrombosis and thromboembolism following ECMO therapy are frequent. Quality of anticoagulation and ECMO runtime predicted thromboembolic events. " KW - Pulmonary Embolism KW - Inferior Vena Cava KW - Venous Thrombosis KW - Fresh Freeze Plasma KW - Extracorporeal Membrane Oxygenation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164455 VL - 6 ER - TY - JOUR A1 - Palladino, Viola Stella A1 - Chiocchetti, Andreas G. A1 - Frank, Lukas A1 - Haslinger, Denise A1 - McNeill, Rhiannon A1 - Radtke, Franziska A1 - Till, Andreas A1 - Haupt, Simone A1 - Brüstle, Oliver A1 - Günther, Katharina A1 - Edenhofer, Frank A1 - Hoffmann, Per A1 - Reif, Andreas A1 - Kittel-Schneider, Sarah T1 - Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD JF - Journal of Clinical Medicine N2 - The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics. KW - ADHD KW - hiPSC KW - PARK2 KW - mitochondria KW - disease modelling Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220074 SN - 2077-0383 VL - 9 IS - 12 ER - TY - JOUR A1 - Gershberg, Jana A1 - Fennel, Franziska A1 - Rehm, Thomas H. A1 - Lochbrunner, Stefan A1 - Würthner, Frank T1 - Anti-cooperative supramolecular polymerization: a new K\(_2\)-K model applied to the self-assembly of perylene bisimide dye proceeding via well-defined hydrogen-bonded dimers JF - Chemical Science N2 - A perylene bisimide dye bearing amide functionalities at the imide positions derived from amino acid L-alanine and a dialkoxy-substituted benzyl amine self-assembles into tightly bound dimers by π-π-stacking and hydrogen bonding in chloroform. In less polar or unpolar solvents like toluene and methylcyclohexane, and in their mixtures, these dimers further self-assemble into extended oligomeric aggregates in an anti-cooperative process in which even numbered aggregates are highly favoured. The stepwise transition from dimers into oligomers can not be properly described by conventional K\(_2\)-K model, and thus a new K\(_2\)-K aggregation model has been developed, which interpretes the present anti-cooperative supramolecular polymerization more appropriately. The newly developed K\(_2\)-K model will be useful to describe self-assembly processes of a plethora of other π-conjugated molecules that are characterized by a favored dimer species. KW - π–π Stacking KW - nucleation elongation KW - upramolecular polymerization process KW - dimerization KW - K2–K model Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191428 VL - 7 IS - 3 ER - TY - THES A1 - Frank, Franziska T1 - Veränderung der Ranvier’schen Schnürringarchitektur bei Patienten mit diabetischer Neuropathie T1 - Disruption of the nodal architecture in patients with diabetic neuropathy N2 - In der Krankheitsentstehung der diabetischen Neuropathie wird die paranodale Demyelinisierung als ein möglicher Pathomechanismus diskutiert, wobei Studien mit Gewebeproben von Patienten aufgrund der Invasivität limitiert sind. In der vorliegenden Studie wurden periphere Nervenfasern in Hautbiopsien von Patienten mit diabetischer Neuropathie und in Patienten mit Diabetes mellitus ohne Neuropathie untersucht. Ziel war es, nodale und paranodale Veränderungen, wie eine Dispersion der paranodalen Proteine Caspr und Neurofascin oder der nodalen Na-Kanäle, zu detektieren und die Proben auf verlängerte Ranvier`sche Schnürringe zu untersuchen. Es wurde die Hypothese überprüft, dass paranodale Demyelinisierungen bei Patienten mit diabetischer Neuropathie in Hautbiopsien, als minimal-invasive Methode, nachweisbar sind. Hautproben von Patienten mit Diabetes mellitus ohne Neuropathie sollten zudem in einem frühen Krankheitsstadium untersucht werden. Für die Untersuchung konnten 35 Patienten mit einer diabetischen Neuropathie, 17 Patienten mit Diabetes mellitus und 31 Kontrollen eingeschlossen werden. Immunfluoreszenzfärbungen mit Antikörpern gegen Caspr, Neurofascin und Natrium-Kanälen wurden zur Analyse der Ranvier`schen Schnürringarchitektur durchgeführt und ausgewertet. Eine erhöhte Anzahl an verlängerten Schnürringen, als Zeichen einer segmentalen Demyelinisierung, konnte in den Patienten mit diabetischer Neuropathie aber auch in Patienten mit Diabetes mellitus nachgewiesen werden. Weiterhin waren vermehrt Veränderungen der paranodalen Proteine, wie eine Dispersion von Caspr und Neurofascin in den Proben des Fingers der Patienten mit diabetischer Neuropathie sowie eine Dispersion von Neurofascin im Unterschenkel in beiden Patientengruppen nachweisbar. Interessanterweise waren einzelne Veränderungen auch in den gesunden Kontrollen auffindbar. Veränderungen der Schnürringarchitektur lassen sich mithilfe der Hautbiopsie nachweisen und quantifizieren. Nodale und paranodale Veränderungen weisen auf demyelinisierende Prozesse in Patienten mit diabetischer Neuropathie hin und finden sich auch bereits in einem frühen Krankheitsstadium. N2 - During the course of diabetic neuropathy, paranodal demyelination has been discussed as a possible mechanism, although studies with tissue samples from patients are limited due to its invasiveness. In the present study, peripheral nerve fibers were examined in skin biopsies from patients with diabetic neuropathy and in patients with diabetes mellitus without neuropathy. The aim was to detect nodal and paranodal changes, such as a dispersion of the paranodal proteins Caspr and Neurofascin or the nodal sodium channels, and to examine the samples for elongated nodes of Ranvier. The hypothesis was tested that paranodal demyelination in patients with diabetic neuropathy can be detected in skin biopsies as a minimally invasive method. Skin samples from patients with diabetes mellitus without neuropathy should also be examined at an early stage of the disease. 35 patients with diabetic neuropathy, 17 patients with diabetes mellitus and 31 controls could be included in the study. Immunofluorescence staining with antibodies against Caspr, Neurofascin and sodium channels were carried out and evaluated in order to analyze the architecture of nodes of Ranvier. An increased number of elongated nodes, as a sign of segmental demyelination, could be demonstrated in patients with diabetic neuropathy, but also in patients with diabetes mellitus. An increased number of changes in paranodal proteins, such as a dispersion of Caspr and Neurofascin in the samples of the finger of the patients with diabetic neuropathy and a dispersion of Neurofascin in the lower leg in both patient groups, were detectable. Interestingly, alterations of the nodal architecture could also be found in healthy controls. A disruption of the architecture of the node of Ranvier can be detected and quantified using skin biopsies. Nodal and paranodal alterations indicate demyelinating processes in patients with diabetic neuropathy and are also found at an early stage of the disease. KW - Ranvier-Schnürring KW - Diabetische Neuropathie KW - Diabetes mellitus KW - Hautbiopsie KW - skin biopsy KW - Caspr KW - Neurofascin KW - Caspr KW - Neurofascin KW - node of Ranvier KW - diabetic neuropathy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219668 ER - TY - JOUR A1 - Wolter, Steffen A1 - Aizezers, Janis A1 - Fennel, Franziska A1 - Seidel, Marcus A1 - Würthner, Frank A1 - Kühn, Oliver A1 - Lochbrunner, Stefan T1 - Size-dependent exciton dynamics in one-dimensional perylene bisimide aggregates JF - New Journal of Physics N2 - The size-dependent exciton dynamics of one-dimensional aggregates of substituted perylene bisimides are studied by ultrafast transient absorption spectroscopy and kinetic Monte-Carlo simulations as a function of the excitation density and the temperature in the range of 25-90 degrees C. For low temperatures, the aggregates can be treated as infinite chains and the dynamics is dominated by diffusion-driven exciton-exciton annihilation. With increasing temperature the aggregates dissociate into small fragments consisting of very few monomers. This scenario is also supported by the time-dependent anisotropy deduced from polarization-dependent experiments. KW - rotational diffusion KW - spectroscopy KW - dyes KW - annihilation KW - migration KW - films Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135190 VL - 14 IS - 105027 ER - TY - JOUR A1 - Herzberg, Moritz A1 - Scherling, Korbinian A1 - Stahl, Robert A1 - Tiedt, Steffen A1 - Wollenweber, Frank A. A1 - Küpper, Clemens A1 - Feil, Katharina A1 - Forbrig, Robert A1 - Patzig, Maximilian A1 - Kellert, Lars A1 - Kunz, Wolfgang G. A1 - Reidler, Paul A1 - Zimmermann, Hanna A1 - Liebig, Thomas A1 - Dieterich, Marianne A1 - Dorn, Franziska T1 - Late Thrombectomy in Clinical Practice: Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry JF - Clinical Neuroradiology N2 - Background and Purpose To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). Results Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence. KW - late thrombectomy KW - stroke KW - endovascular therapy KW - outcome Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264765 VL - 31 IS - 3 ER - TY - JOUR A1 - Herzberg, Moriz A1 - Dorn, Franziska A1 - Trumm, Christoph A1 - Kellert, Lars A1 - Tiedt, Steffen A1 - Feil, Katharina A1 - Küpper, Clemens A1 - Wollenweber, Frank A1 - Liebig, Thomas A1 - Zimmermann, Hanna T1 - Middle cerebral artery M2 thrombectomy: safety and technical considerations in the German Stroke Registry (GSR) JF - Journal of Clinical Medicine N2 - There is ongoing debate concerning the safety and efficacy of various mechanical thrombectomy (MT) approaches for M2 occlusions. We compared these for MT in M2 versus M1 occlusions. Subgroup analyses of different technical approaches within the M2 MT cohort were also performed. Patients were included from the German Stroke Registry (GSR), a multicenter registry of consecutive MT patients. Primary outcomes were reperfusion success events. Secondary outcomes were early clinical improvement (improvement in NIHSS score > 4) and independent survival at 90 days (mRS 0–2). Out of 3804 patients, 2689 presented with M1 (71%) and 1115 with isolated M2 occlusions (29%). The mean age was 76 (CI 65–82) and 77 (CI 66–83) years, respectively. Except for baseline NIHSS (15 (CI 10–18) vs. 11 (CI 6–16), p < 0.001) and ASPECTS (9 (CI 7–10) vs. 9 (CI 8–10, p < 0.001), baseline demographics were balanced. Apart from a more frequent use of dedicated small vessel stent retrievers (svSR) in M2 (17.4% vs. 3.0; p < 0.001), intraprocedural aspects were balanced. There was no difference in ICH at 24 h (11%; p = 1.0), adverse events (14.4% vs. 18.1%; p = 0.63), clinical improvement (62.5% vs. 61.4 %; p = 0.57), mortality (26.9% vs. 22.9%; p = 0.23). In M2 MT, conventional stent retriever (cSR) achieved higher rates of mTICI3 (54.0% vs. 37.7–42.0%; p < 0.001), requiring more MT-maneuvers (7, CI 2–8) vs. 2 (CI 2–7)/(CI 2–2); p < 0.001) and without impact on efficacy and outcome. Real-life MT in M2 can be performed with equal safety and efficacy as in M1 occlusions. Different recanalization techniques including the use of svSR did not result in significant differences regarding safety, efficacy and outcome. KW - mechanical thrombectomy KW - M2 KW - distal occlusion KW - endovascular therapy KW - aspiration KW - stent retriever KW - outcome Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286052 SN - 2077-0383 VL - 11 IS - 15 ER - TY - JOUR A1 - Breuer, René A1 - Mattheisen, Manuel A1 - Frank, Josef A1 - Krumm, Bertram A1 - Treutlein, Jens A1 - Kassem, Layla A1 - Strohmaier, Jana A1 - Herms, Stefan A1 - Mühleisen, Thomas W. A1 - Degenhardt, Franziska A1 - Cichon, Sven A1 - Nöthen, Markus M. A1 - Karypis, George A1 - Kelsoe, John A1 - Greenwood, Tiffany A1 - Nievergelt, Caroline A1 - Shilling, Paul A1 - Shekhtman, Tatyana A1 - Edenberg, Howard A1 - Craig, David A1 - Szelinger, Szabolcs A1 - Nurnberger, John A1 - Gershon, Elliot A1 - Alliey-Rodriguez, Ney A1 - Zandi, Peter A1 - Goes, Fernando A1 - Schork, Nicholas A1 - Smith, Erin A1 - Koller, Daniel A1 - Zhang, Peng A1 - Badner, Judith A1 - Berrettini, Wade A1 - Bloss, Cinnamon A1 - Byerley, William A1 - Coryell, William A1 - Foroud, Tatiana A1 - Guo, Yirin A1 - Hipolito, Maria A1 - Keating, Brendan A1 - Lawson, William A1 - Liu, Chunyu A1 - Mahon, Pamela A1 - McInnis, Melvin A1 - Murray, Sarah A1 - Nwulia, Evaristus A1 - Potash, James A1 - Rice, John A1 - Scheftner, William A1 - Zöllner, Sebastian A1 - McMahon, Francis J. A1 - Rietschel, Marcella A1 - Schulze, Thomas G. T1 - Detecting significant genotype–phenotype association rules in bipolar disorder: market research meets complex genetics JF - International Journal of Bipolar Disorders N2 - Background Disentangling the etiology of common, complex diseases is a major challenge in genetic research. For bipolar disorder (BD), several genome-wide association studies (GWAS) have been performed. Similar to other complex disorders, major breakthroughs in explaining the high heritability of BD through GWAS have remained elusive. To overcome this dilemma, genetic research into BD, has embraced a variety of strategies such as the formation of large consortia to increase sample size and sequencing approaches. Here we advocate a complementary approach making use of already existing GWAS data: a novel data mining procedure to identify yet undetected genotype–phenotype relationships. We adapted association rule mining, a data mining technique traditionally used in retail market research, to identify frequent and characteristic genotype patterns showing strong associations to phenotype clusters. We applied this strategy to three independent GWAS datasets from 2835 phenotypically characterized patients with BD. In a discovery step, 20,882 candidate association rules were extracted. Results Two of these rules—one associated with eating disorder and the other with anxiety—remained significant in an independent dataset after robust correction for multiple testing. Both showed considerable effect sizes (odds ratio ~ 3.4 and 3.0, respectively) and support previously reported molecular biological findings. Conclusion Our approach detected novel specific genotype–phenotype relationships in BD that were missed by standard analyses like GWAS. While we developed and applied our method within the context of BD gene discovery, it may facilitate identifying highly specific genotype–phenotype relationships in subsets of genome-wide data sets of other complex phenotype with similar epidemiological properties and challenges to gene discovery efforts. KW - bipolar disorder KW - subphenotypes KW - rule discovery KW - data mining KW - genotype-phenotype patterns Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220509 VL - 6 ER - TY - JOUR A1 - Dostál, Jakub A1 - Fennel, Franziska A1 - Koch, Federico A1 - Herbst, Stefanie A1 - Würthner, Frank A1 - Brixner, Tobias T1 - Direct observation of exciton–exciton interactions JF - Nature Communications N2 - Natural light harvesting as well as optoelectronic and photovoltaic devices depend on efficient transport of energy following photoexcitation. Using common spectroscopic methods, however, it is challenging to discriminate one-exciton dynamics from multi-exciton interactions that arise when more than one excitation is present in the system. Here we introduce a coherent two-dimensional spectroscopic method that provides a signal only in case that the presence of one exciton influences the behavior of another one. Exemplarily, we monitor exciton diffusion by annihilation in a perylene bisimide-based J-aggregate. We determine quantitatively the exciton diffusion constant from exciton–exciton-interaction 2D spectra and reconstruct the annihilation-free dynamics for large pump powers. The latter enables for ultrafast spectroscopy at much higher intensities than conventionally possible and thus improves signal-to-noise ratios for multichromophore systems; the former recovers spatio–temporal dynamics for a broad range of phenomena in which exciton interactions are present. KW - energy transfer KW - self-assembly KW - optical spectroscopy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226271 VL - 9 ER -