@article{GrubeKoenneckeWalteretal.2013, author = {Grube, Maike Miriam and Koennecke, Hans-Christian and Walter, Georg and Meisel, Andreas and Sobesky, Jan and Nolte, Christian Hans and Wellwood, Ian and Heuschmann, Peter Ulrich}, title = {Influence of Acute Complications on Outcome 3 Months after Ischemic Stroke}, series = {PLOS ONE}, volume = {8}, journal = {PLOS ONE}, number = {9}, issn = {1932-6203}, doi = {10.1371/journal.pone.0075719}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128362}, pages = {e75719}, year = {2013}, abstract = {Background: Early medical complications are potentially modifiable factors influencing in-hospital outcome. We investigated the influence of acute complications on mortality and poor outcome 3 months after ischemic stroke. Methods: Data were obtained from patients admitted to one of 13 stroke units of the Berlin Stroke Registry (BSR) who participated in a 3-months-follow up between June 2010 and September 2012. We examined the influence of the cumulative number of early in-hospital complications on mortality and poor outcome (death, disability or institutionalization) 3 months after stroke using multivariable logistic regression analyses and calculated attributable fractions to determine the impact of early complications on mortality and poor outcome. Results: A total of 2349 ischemic stroke patients alive at discharge from acute care were included in the analysis. Older age, stroke severity, pre-stroke dependency and early complications were independent predictors of mortality 3 months after stroke. Poor outcome was independently associated with older age, stroke severity, pre-stroke dependency, previous stroke and early complications. More than 60\% of deaths and poor outcomes were attributed to age, pre-stroke dependency and stroke severity and in-hospital complications contributed to 12.3\% of deaths and 9.1\% of poor outcomes 3 months after stroke. Conclusion: The majority of deaths and poor outcomes after stroke were attributed to non-modifiable factors. However, early in-hospital complications significantly affect outcome in patients who survived the acute phase after stroke, underlining the need to improve prevention and treatment of complications in hospital.}, language = {en} } @article{MuranyiMalkuschMuelleretal.2013, author = {Muranyi, Walter and Malkusch, Sebastian and M{\"u}ller, Barbara and Heilemann, Mike and Kr{\"a}usslich, Hans-Georg}, title = {Super-Resolution Microscopy Reveals Specific Recruitment of HIV-1 Envelope Proteins to Viral Assembly Sites Dependent on the Envelope C-Terminal Tail}, series = {PLoS Pathogens}, volume = {9}, journal = {PLoS Pathogens}, number = {2}, doi = {10.1371/journal.ppat.1003198}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131235}, pages = {e1003198}, year = {2013}, abstract = {The inner structural Gag proteins and the envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) traffic independently to the plasma membrane, where they assemble the nascent virion. HIV-1 carries a relatively low number of glycoproteins in its membrane, and the mechanism of Env recruitment and virus incorporation is incompletely understood. We employed dual-color super-resolution microscopy visualizing Gag assembly sites and HIV-1 Env proteins in virus-producing and in Env expressing cells. Distinctive HIV-1 Gag assembly sites were readily detected and were associated with Env clusters that always extended beyond the actual Gag assembly site and often showed enrichment at the periphery and surrounding the assembly site. Formation of these Env clusters depended on the presence of other HIV-1 proteins and on the long cytoplasmic tail (CT) of Env. CT deletion, a matrix mutation affecting Env incorporation or Env expression in the absence of other HIV-1 proteins led to much smaller Env clusters, which were not enriched at viral assembly sites. These results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env\((\Delta CT)\) appears to be randomly incorporated. The observed Env accumulation surrounding Gag assemblies, with a lower density on the actual bud, could facilitate viral spread in vivo. Keeping Env molecules on the nascent virus low may be important for escape from the humoral immune response, while cell-cell contacts mediated by surrounding Env molecules could promote HIV-1 transmission through the virological synapse.}, language = {en} } @article{WiedmannHeuschmannHillmannetal.2014, author = {Wiedmann, Silke and Heuschmann, Peter U. and Hillmann, Steffi and Busse, Otto and Wiethoelter, Horst and Walter, Georg M. and Seidel, Guenter and Misselwitz, Bjoern and Janssen, Alfred and Berger, Klaus and Burmeister, Christoph and Matthias, Christine and Kolominsky-Rabas, Peter and Hermanek, Peter}, title = {The Quality of Acute Stroke Care-an Analysis of Evidence-Based Indicators in 260 000 Patients}, series = {Deutsches {\"A}rzteblatt International}, volume = {111}, journal = {Deutsches {\"A}rzteblatt International}, number = {45}, issn = {1866-0452}, doi = {10.3238/arztebl.2014.0759}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114747}, pages = {759-765}, year = {2014}, abstract = {Background: Stroke patients should be cared for in accordance with evidence-based guidelines. The extent of implementation of guidelines for the acute care of stroke patients in Germany has been unclear to date. Methods: The regional quality assurance projects that cooperate in the framework of the German Stroke Registers Study Group (Arbeitsgemeinschaft Deutscher Schlaganfall-Register, ADSR) collected data on the care of stroke patients in 627 hospitals in 2012. The quality of the acute hospital care of patients with stroke or transient ischemic attack (TIA) was assessed on the basis of 15 standardized, evidence-based quality indicators and compared across the nine participating regional quality assurance projects. Results: Data were obtained on more than 260 000 patients nationwide. Intravenous thrombolysis was performed in 59.7\% of eligible ischemic stroke patients patients (range among participating projects, 49.7-63.6\%). Dysphagia screening was documented in 86.2\% (range, 74.8-93.1\%). For the following indicators, the defined targets were not reached for all of Germany: antiaggregation within 48 hours, 93.4\% (range, 86.6-96.4\%); anticoagulation for atrial fibrillation, 77.6\% (range, 72.4-80.1\%); standardized dysphagia screening, 86.2\% (range, 74.8-93.1\%); oral and written information of the patients or their relatives, 86.1\% (range, 75.4-91.5\%). The rate of patients examined or treated by a speech therapist was in the target range. Conclusion: The defined targets were reached for most of the quality indicators. Some indicators, however, varied widely across regional quality assurance projects. This implies that the standardization of care for stroke patients in Germany has not yet been fully achieved.}, language = {en} } @article{DongBoeppleThieletal.2023, author = {Dong, Meng and B{\"o}pple, Kathrin and Thiel, Julia and Winkler, Bernd and Liang, Chunguang and Schueler, Julia and Davies, Emma J. and Barry, Simon T. and Metsalu, Tauno and M{\"u}rdter, Thomas E. and Sauer, Georg and Ott, German and Schwab, Matthias and Aulitzky, Walter E.}, title = {Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions}, series = {Cells}, volume = {12}, journal = {Cells}, number = {5}, issn = {2073-4409}, doi = {10.3390/cells12050807}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311030}, year = {2023}, abstract = {Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air-liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.}, language = {en} }