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Evaluation of Retinal Nerve Fiber Layer and Macular Ganglion Cell Layer Thickness in Relation to Optic Disc Size
No full textTo investigate whether optic nerve ganglion cell amount is dependent on optic disc size, this trial analyzes the correlation between Bruch’s membrane opening area (BMOA) and retinal nerve fiber layer (RNFL) thickness as well as macular ganglion cell layer thickness (mGCLT). Additionally, differences in RNFL and mGCLT regarding various optic disc cohorts are evaluated. This retrospective, monocentric study included 501 healthy eyes of 287 patients from the University Hospital Münster, Germany, who received macular and optic disc optical coherence tomography (OCT) scans. Rank correlation coefficients for clustered data were calculated to investigate the relationship between BMOA and thickness values of respective retinal layers. Furthermore, these values were compared between different optic disc groups based on BMOA. Statistical analysis did not reveal a significant correlation between BMOA and RNFL thickness, nor between BMOA and mGCLT. However, groupwise analysis showed global RNFL to be significantly decreased in small and large discs in comparison to medium discs. This was not observed for global mGCLT. This study extends existing normative data for mGCLT taking optic disc size into account. While the ganglion cell amount represented by the RNFL and mGCLT seemed independent of BMOA, mGCLT was superior to global RNFL in displaying optic nerve integrity in very small and very large optic discs
grenzenlos.:Beiträge zu den Niederlanden und den deutsch-niederländischen Beziehungen
No full textDas Zentrum für Niederlande-Studien (ZNS) der Universität Münster ist das akademische Expertise-Zentrum für Niederlande-Forschung und deutsch-niederländische Beziehungen in Europa. Es vermittelt wesentliche Kompetenzen und Kenntnisse durch seine Aktivitäten in den Bereichen Lehre, Forschung und Wissenstransfer. Im Rahmen der Publikationsreihe grenzenlos behandeln die Mitarbeiter:innen des ZNS und externe Expert:innen Fragestellungen aus verschiedenen Fachdisziplinen. Die deutsch-, niederländisch- oder englischsprachigen Texte sollen dazu beitragen, das Wissen über und das Verständnis für die Niederlande und die deutsch-niederländischen Beziehungen zu erhöhen
Humoral signatures of MOG-antibody-associated disease track with age and disease activity
No full textMyelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated disease (MOGAD) is an inflammatory demyelinating disease of the CNS. Although MOG is encephalitogenic in different mammalian species, the mechanisms by which human MOG-specific Abs contribute to MOGAD are poorly understood. Here, we use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral immune responses in 123 patients with MOGAD. We show that age is a major determinant for MOG-antibody-related immune signatures. Unsupervised clustering additionally identifies two dominant immunological endophenotypes of MOGAD. The pro-inflammatory endophenotype characterized by increased binding affinities for activating Fcγ receptors (FcγRs), capacity to activate innate immune cells, and decreased frequencies of galactosylated and sialylated immunoglobulin G (IgG) glycovariants is associated with clinically active disease. Our data support the concept that FcγR-mediated effector functions control the pathogenicity of MOG-specific IgG and suggest that FcγR-targeting therapies should be explored for their therapeutic potential in MOGAD
Implementation of an antimicrobial stewardship programme in three regional hospitals in the south-east of Liberia: lessons learned
No full textBackground: Antimicrobial stewardship (AMS) programmes can improve the use of antimicrobial agents. However, there is limited experience in the implementation of such programmes in low- and middle-income countries (LMICs). Objectives: To assess the effect of AMS measures in south-east Liberia on the quality of antimicrobial use in three regional hospitals. Methods: A bundle of three measures (local treatment guideline, training and regular AMS ward rounds) was implemented and quality indicators of antimicrobial use (i.e. correct compounds, dosage and duration) were assessed in a case series before and after AMS ward rounds. Primary endpoints were (i) adherence to the local treatment guideline; (ii) completeness of the microbiological diagnostics (according to the treatment guideline); and (iii) clinical outcome. The secondary endpoint was reduction in ceftriaxone use. Results: The majority of patients had skin and soft tissue infections (n = 108) followed by surgical site infections (n = 72), pneumonia (n = 64), urinary tract infection (n = 48) and meningitis (n = 18). After the AMS ward rounds, adherence to the local guideline improved for the selection of antimicrobial agents (from 34.5% to 61.0%, P < 0.0005), dosage (from 15.2% to 36.5%, P < 0.0005) and duration (from 13.2% to 31.0%, P < 0.0005). In total, 79.7% of patients (247/310) had samples sent for microbiological analysis. Overall, 92.3% of patients improved on Day 3 (286/310). The proportion of patients receiving ceftriaxone was significantly reduced after the AMS ward rounds from 51.3% to 14.2% (P < 0.0005). Conclusions: AMS measures can improve the quality of antimicrobial use in LMICs. However, long-term engagement is necessary to make AMS programmes in LMICs sustainable
Improving reproducibility in animal research by splitting the study population into several 'mini-experiments'
No full textIn light of the hotly discussed 'reproducibility crisis', a rethinking of current methodologies appears essential. Implementing multi-laboratory designs has been shown to enhance the external validity and hence the reproducibility of findings from animal research. We here aimed at proposing a new experimental strategy that transfers this logic into a single-laboratory setting. We systematically introduced heterogeneity into our study population by splitting an experiment into several 'mini-experiments' spread over different time points a few weeks apart. We hypothesised to observe improved reproducibility in such a 'mini-experiment' design in comparison to a conventionally standardised design, according to which all animals are tested at one specific point in time. By comparing both designs across independent replicates, we could indeed show that the use of such a 'mini-experiment' design improved the reproducibility and accurate detection of exemplary treatment effects (behavioural and physiological differences between four mouse strains) in about half of all investigated strain comparisons. Thus, we successfully implemented and empirically validated an easy-to-handle strategy to tackle poor reproducibility in single-laboratory studies. Since other experiments within different life science disciplines share the main characteristics with the investigation reported here, these studies are likely to also benefit from this approach
Incidence and predictors of left atrial appendage thrombus on transesophageal echocardiography before elective cardioversion
No full textGuidelines recommend transesophageal echocardiography (TEE) before cardioversion in thrombogenic arrhythmias when the requirement of ≥ 3 weeks of anticoagulation is not met. Current data to support this approach, especially with direct oral anticoagulants (DOAC), are scarce. We analyzed consecutive elective pre-cardioversion TEE in a high-volume electrophysiology center for the occurrence of left atrial appendage (LAA) thrombi or reduced LAA flow velocity. Possible predictors were recorded and compared in a multivariate logistic regression analysis. Consecutive pre-cardioversion TEE in 512 patients (148 female, median age 69 years) were included. In all patients, indication for TEE was either intake of anticoagulation < 3 weeks before cardioversion or uncertain adherence to the prescribed anticoagulation regimen. Of the 512 TEE, 19 (3.7%) depicted a LAA thrombus. An additional 41 patients (8.0%) showed either a reduced LAA flow velocity (≤ 20 cm/s), LAA sludge, or both. In a multivariate logistic regression analysis, QRS width on admission 12-lead ECG emerged as a possible predictor of LAA thrombus and reduced LAA flow (p = 0.008). Noteworthy, a high CHA2DS2-VASc score was not associated with an increased risk of reduced LAA emptying velocity and LAA thrombi were even found in patients with a CHA2DS2-VASc score of 0 (n = 1) and 1 (n = 1). The presence of LAA thrombus before an elective cardioversion is a rare event in the age of direct oral anticoagulants. However, LAA thrombi occurred even in supposed low-risk individuals according to the CHA2DS2-VASc score. QRS width may aid in identifying patients at risk of reduced LAA flow velocity
Increased Intrathecal B and Plasma Cells in Patients With Anti-IgLON5 Disease:A Case Series
No full textBackground and Objectives: Despite detection of autoantibodies, anti-IgLON5 disease was historically considered a tau-associated neurodegenerative disease, with limited treatment options and detrimental consequences for the patients. Observations in increasing case numbers hint toward underlying inflammatory mechanisms that, early detection provided, open a valuable window of opportunity for therapeutic intervention. We aimed to further substantiate this view by studying the CSF of patients with anti-IgLON5. Methods: We identified 11 patients with anti-IgLON5 from our database and compared clinical, MRI, and CSF findings with a cohort of 20 patients with progressive supranuclear palsy (PSP) (as a noninflammatory tauopathy) and 22 patients with functional neurologic disorder. Results: Patients with anti-IgLON5 show inflammatory changes in routine CSF analysis, an increase in B-lymphocyte frequency, and the presence of plasma cells in comparison to the PSP-control group and functional neurologic disease controls. Patients with intrathecal plasma cells showed a clinical response to rituximab. Discussion: Our findings indicate the importance of inflammatory mechanisms, in particular in early and acute anti-IgLON5 cases, which may support the use of immune-suppressive treatments in these cases. The main limitation of the study is the small number of cases due to the rarity of the disease
A Machine Learning Based Downscaling Approach to Produce High Spatio-Temporal Resolution Land Surface Temperature of the Antarctic Dry Valleys from MODIS Data
No full textTo monitor environmental and biological processes, Land Surface Temperature (LST) is a central variable, which is highly variable in space and time. This particularly applies to the Antarctic Dry Valleys, which host an ecosystem highly adapted to the extreme conditions in this cold desert. To predict possible climate induced changes on the Dry Valley ecosystem, high spatial and temporal resolution environmental variables are needed. Thus we enhanced the spatial resolution of the MODIS satellite LST product that is sensed sub-daily at a 1 km spatial resolution to a 30 m spatial resolution. We employed machine learning models that are trained using Landsat 8 thermal infrared data from 2013 to 2019 as a reference to predict LST at 30 m resolution. For the downscaling procedure, terrain derived variables and information on the soil type as well as the solar insolation were used as potential predictors in addition to MODIS LST. The trained model can be applied to all available MODIS scenes from 1999 onward to develop a 30 m resolution LST product of the Antarctic Dry Valleys. A spatio-temporal validation revealed an R2 of 0.78 and a RMSE of 3.32 ∘C. The downscaled LST will provide a valuable surface climate data set for various research applications, such as species distribution modeling, climate model evaluation, and the basis for the development of further relevant environmental information such as the surface moisture distribution
Anti-cancer agent 3-bromopyruvate reduces growth of MPNST and inhibits metabolic pathways in a representative invitro model
No full textBackground: Anticancer compound 3-bromopyruvate (3-BrPA) suppresses cancer cell growth via targeting glycolytic and mitochondrial metabolism. The malignant peripheral nerve sheath tumor (MPNST), a very aggressive, therapy resistant, and Neurofibromatosis type 1 associated neoplasia, shows a high metabolic activity and affected patients may therefore benefit from 3-BrPA treatment. To elucidate the specific mode of action, we used a controlled cell model overexpressing proteasome activator (PA) 28, subsequently leading to p53 inactivation and oncogenic transformation and therefore reproducing an important pathway in MPNST and overall tumor pathogenesis.
Methods: Viability of MPNST cell lines S462, NSF1, and T265 in response to increasing doses (0–120 μM) of 3-BrPA was analyzed by CellTiter-Blue® assay. Additionally, we investigated viability, reactive oxygen species (ROS) production (dihydroethidium assay), nicotinamide adenine dinucleotide dehydrogenase activity (NADH-TR assay) and lactate production (lactate assay) in mouse B8 fibroblasts overexpressing PA28 in response to 3-BrPA application. For all experiments normal and nutrient deficient conditions were tested. MPNST cell lines were furthermore characterized immunohistochemically for Ki67, p53, bcl2, bcl6, cyclin D1, and p21.
Results: MPNST significantly responded dose dependent to 3-BrPA application, whereby S462 cells were most responsive. Human control cells showed a reduced sensitivity. In PA28 overexpressing cancer cell model 3-BrPA application harmed mitochondrial NADH dehydrogenase activity mildly and significantly failed to inhibit lactate production. PA28 overexpression was associated with a functional glycolysis as well as a partial resistance to stress provoked by nutrient deprivation. 3-BrPA treatment was not associated with an increase of ROS. Starvation sensitized MPNST to treatment.
Conclusions: Aggressive MPNST cells are sensitive to 3-BrPA therapy in-vitro with and without starvation. In a PA28 overexpression cancer cell model leading to p53 inactivation, thereby reflecting a key molecular feature in human NF1 associated MPNST, known functions of 3-BrPA to block mitochondrial activity and glycolysis were reproduced, however oncogenic cells displayed a partial resistance. To conclude, 3-BrPA was sufficient to reduce NF1 associated MPNST viability potentially due inhibition of glycolysis which should lead to the initiation of further studies and promises a potential benefit for NF1 patients
Black Transatlantic Literary Studies and the Case of James Baldwin
No full textDer Artikel spricht sich dafür aus, dass die transatlantisch orientierte, literaturwissenschaftliche Forschung sich vermehrt mit den Perspektiven Schwarzer Autoren und Autorinnen beschäftigen und die vielfältigen literarischen Verflechtungen zwischen afroamerikanischen, afrodiasporischen, afrikanischen und afro-europäischen Werken in den Blick nehmen sollte. Anhand der Bezüge zu Europa im Werk James Baldwins werden exemplarisch drei Felder skizziert, die für eine solche Forschung von besonderer Relevanz sind: 1) literarische Bilder von Selbst und Anderen (Imagologie), insbesondere literarische Umkehrungen des weißen kolonialen Blicks auf den Schwarzen "Anderen" im europäischen Kontext; 2) Intertextualität, insbesondere literarische Verflechtungen zwischen afroamerikanischer und afrodeutscher Literatur; und 3) Buchwissenschaft und die Rolle literarischer Archive.The article argues that it is important for Transatlantic Literary Studies to focus more extensively on the perspectives of Black writers from both sides of the Atlantic. It specifically points to the need of studying the manifold literary entanglements between African American, African diasporic, African, and Afro-European works. Using the European connections in the writings of James Baldwin as a case in point, the article draws on three fields of study, which can each be considered as particularly relevant for such an approach: 1) literary images of self and other (imagology), especially literary reversals of the white colonial gaze at the Black "Other" in European contexts; 2) intertextuality, especially literary entanglements between African American and Afro-German literature; 3) book studies and the role of literary archives