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Nils Peters,Esther van Leijsen,Anil M. Tuladhar,Christian Barro,Marek J. Konieczny,Michael Ewers,Philippe Lyrer,Stefan T. Engelter,Jens Kuhle,Marco Duering,Frank-Erik de Leeuw 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.3
Background and Purpose Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) crosssectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally. Methods From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA). Results Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=–0.159; 95% confidence interval [CI], –0.242 to –0.068; P=0.001; executive function β=–0.095; 95% CI, –0.170 to –0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age. Conclusions Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly. Keywords Stroke; Dementia; Small vessel diseases; Neurofilament
Nils Haneklaus,Cristian Cionea,Rony Reuven,David Frazer,Peter Hosemann,Per F. Peterson 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.11
Hybrid friction diffusion bonding (HFDB) is a solid-state bonding process first introduced by Helmholtz-Zentrum Geesthacht to join aluminum tube-to-tube sheet joints of Coil-wound heat exchangers (CWHE). This study describes how HFDB was successfully used to manufacture 316L test samples simulating tube-to-tube sheet joints of stainless steel CWHE for molten salt coolants as foreseen in several advanced nuclear- and thermal solar power plants. Engineering parameters of the test sample fabrication are presented and results from subsequent non-destructive vacuum decay leak testing and destructive tensile pull-out testing are discussed. The bonded areas of successfully fabricated samples as characterized by tube rupture during pull-out tensile testing, were further investigated using optical microscopy and scanning electron microscopy including electron backscatter diffraction.
Schmidt, Nils Ole,Przylecki, Wojciech,Yang, Wendy,Ziu, Mateo,Teng, Yang,Kim, Seung U.,Black, Peter Mcl.,Aboody, Karen S.,Carroll, Rona S. Elsevier 2005 Neoplasia Vol.7 No.6
<P>The transplantation of neural stem cells (NSCs) offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF) is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumor-upregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.</P>
Interference of engineered nanomaterials in flow cytometry: A case study
Bohmer, Nils,Rippl, Alexandra,May, Sarah,Walter, Auré,lie,Heo, Min Beom,Kwak, Minjeong,Roesslein, Matthias,Song, Nam Woong,Wick, Peter,Hirsch, Cordula Elsevier 2018 Colloids and Surfaces B Vol.172 No.-
<P><B>Abstract</B></P> <P>Nanotechnology is regarded as the enabling technology of the 21st century. However, only a relatively small number of nano-enabled medical and healthcare products finally made their way to the market. There are several reasons why such innovative approaches fail in translation, with one key factor being the uncertainty surrounding their safety assessment. Although well described, interference reactions of engineered nanomaterials (ENM) with classical cytotoxicity assays remain a major source of uncertainty.</P> <P>Flow cytometry is a powerful, widely used, <I>in vitro</I> technique. Its readout is based on the detection of refracted laser light and fluorescence signals. It is therefore susceptible to ENM interference. Here we investigated possible interferences of ENM in the Annexin V/propidium iodide (PI) assay, which quantifies apoptotic and necrotic cell populations by flow cytometry.</P> <P>Two case studies were conducted using either silica or gold nanoparticles differing in size, specific surface area and surface chemistry. Both ENM types were found to cause distinct interference reactions at realistic concentrations. Silica particles induced false-positive signals; however only in the absence of a protein corona and in conjunction with a particular fluorophore combination (FITC/PI). In contrast, gold particles led to complex quenching effects which were only marginally influenced by the presence of proteins and occurred for both fluorophore combinations analyzed. We present a versatile spike-in approach which is applicable to all ENM and cell types. It further allows for the identification of a broad range of different interference phenomena, thereby increasing the reliability and quality of flow cytometry and ENM hazard assessment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Silica nanoparticles interfere with propidium iodide in the AnnexinV/PI assay. </LI> <LI> Serum proteins prevent interference of silica nanoparticles. </LI> <LI> Gold nanoparticles quench fluorescence in dependence of their surface chemistry. </LI> <LI> Special designed spike-in controls enable detection of interferences. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Shadi Taheri,Nils Peters,Annaelle Zietz,Berthold Abel,Gordian Hubert,Filip Barinka,Hanni Wiestler,Irena Kovacic,Ralf Linker,Felix Schlachetzki,Roland Backhaus 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.6
Background and Purpose While the clinical hallmarks of transient global amnesia (TGA) are well defined, its pathophysiological causes are poorly understood. Specifically, risk factors for recurrences are yet to be determined. Methods This retrospective study analyzed TGA cases diagnosed and treated within the TEMPiS telestroke network and a university stroke center in Germany. Demographic and clinical data were assessed and characteristics of TGA episodes were recorded, such as season of occurrence, trigger factors, duration, and concomitant symptoms. Follow-up of the potential recurrence of TGA was performed using a standardized questionnaire. Results Overall 109 patients were included (age 64±8 years [mean±SD], 59.6% female). The most common vascular risk factor was arterial hypertension (60.6%), and other concomitant conditions included migraine (11.9%), hypothyroidism (22.9%), and atrial fibrillation (4.6%). The most frequent concomitant clinical feature accompanying the TGA episode at admission was elevated blood pressure (48.6%). Nineteen patients experienced at least one recurrent TGA episode. Migraine and hypothyroidism were only observed in subjects with a single TGA episode without recurrence (migraine: 14.4% without recurrence vs. none in the recurrence group, p=0.02; hypothyroidism: 27.8% without recurrence vs. none in the recurrence group, p=0.009). In contrast, atrial fibrillation was more common in subjects with TGA recurrence (p<0.001). Conclusions Arterial hypertension is prevalent in TGA patients, with elevated blood pressure being the most-frequent concomitant condition. In our cohort, recurrence of TGA occurred in approximately one-fifth of patients. Concomitant conditions such as migraine, hypothyroidism, and atrial fibrillation occurred at different frequencies in the two groups.
Rolf Apweiler,Tim Beissbarth,Michael R Berthold,Nils Blüthge,Yvonne Burmeister,Olaf Dammann,Andreas Deutsch,Friedrich Feuerhake,Andre Franke,Jan Hasenauer,Steve Hoffmann,Thomas Höfer,Peter LM Jansen,L 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails. Based on our analysis of current developments in medicine and healthcare and associated research needs, we emphasize the role of systems medicine as a multilevel and multidisciplinary methodological framework for informed data acquisition and interdisciplinary data analysis to extract previously inaccessible knowledge for the benefit of patients.
David J. Seiffge,Christopher Traenka,Alexandros A. Polymeris,Sebastian Thilemann,Benjamin Wagner,Lisa Hert,Mandy D. Müller,Henrik Gensicke,Nils Peters,Christian H. Nickel,Christoph Stippich,Raoul Sutt 대한뇌졸중학회 2017 Journal of stroke Vol.19 No.3
Background and Purpose Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis(IVT) or endovascular treatment (EVT). Methods This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban(September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage. Results Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment. Conclusions Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.