RepoMed (Medizinische Hochschule Hannover)
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"Of mice and men": the relevance of Cometin and Erythropoietin origin for its effects on murine spiral ganglion neuron survival and neurite outgrowth in vitro
Get PDFNeurotrophic factors (NTF) play key roles in the survival of neurons, making them promising candidates for therapy of neurodegenerative diseases. In the case of the inner ear, sensorineural hearing loss (SNHL) is characterized over time by a degeneration of the primary auditory neurons, the spiral ganglion neurons (SGN). It is well known that selected NTF can protect SGN from degeneration, which positively influences the outcome of cochlear implants, the treatment of choice for patients with profound to severe SNHL. However, the outcome of studies investigating protective effects of NTF on auditory neurons are in some cases of high variability. We hypothesize that the factor origin may be one aspect that affects the neuroprotective potential. The aim of this study was to investigate the neuroprotective potential of human and mouse Erythropoietin (EPO) and Cometin on rat SGN. SGN were isolated from neonatal rats (P 2-5) and cultured in serum-free medium. EPO and Cometin of mouse and human origin were added in concentrations of 0.1, 1, and 10 ng/mL and 0.1, 1, and 10 μg/mL, respectively. The SGN survival rate and morphology, and the neurite outgrowth were determined and compared to negative (no additives) and positive (brain-derived neurotrophic factor, BDNF) controls. A neuroprotective effect of 10 μg/mL human Cometin comparable to that obtained with BDNF was observed in the SGN-culture. In contrast, mouse Cometin was ineffective. A similar influence of 10 μg/mL human and mouse and 1 μg/mL human Cometin on the length of regenerated neurites compared to BDNF was also detected. No other Cometin-conditions, and none of the EPO-conditions tested had neuroprotective or neuritogenic effects or influenced the neuronal morphology of the SGN. The neuroprotective effect of 10 μg/mL human Cometin on SGN indicates it is a potentially interesting protein for the supportive treatment of inner ear disorders. The finding that mouse Cometin had no effect on the SGN in the parallel-performed experiments underlines the importance of species origin of molecules being screened for therapeutic purpose
Investigation of OCTA Biomarkers in Fabry Disease: a Long Term Follow-Up of Macular Vessel Area Density and Foveal Avascular Zone Metrics
Get PDFIntroduction Retinal microvasculature is known to be altered in patients with Fabry disease (FD). We aimed to investigate the long-term changes in macular microvasculature and explore a reliable retinal biomarker for treatment monitoring in FD. Methods Prospective study of 26 eyes with FD followed up to 48 months (mean 24, range 8-48). OCT angiography (OCTA) images (2.9 × 2.9 mm) were obtained using Heidelberg Spectralis II at baseline and follow-up. Macular vessel area density (VAD, %) was measured in three layers: superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) in three peri-macular circular sectors (c1, c2, c3). Additionally, foveal avascular zone (FAZ) area (mm2) and horizontal and vertical diameters (µm) were assessed. Results VAD decreased over time in SVP, ICP (in sectors c2 and c3) and DCP (all sectors) (p < 0.04). VAD reduction was predominantly seen in treated FD patients. FAZ and horizontal diameters increased at follow-up in FD patients compared to baseline (p ≤ 0.025). Correlation analysis showed a moderate to strong negative correlation between VAD of SVP and DCP in the innermost circle and FAZ in treated patients (r = - 0.6; p < 0.0001). Conclusions This is the first long-term follow-up OCTA study in FD to our knowledge. A decrease in VAD, pronounced in the peripheral circle and deeper layers, as well as an enlargement of the FAZ could be observed over time. These changes reflect the vascular remodelling during the course of the disease. Interestingly, the reduction of VAD was more pronounced in treated patients. This could be a result of enzyme replacement therapy and could be potentially used as a reliable biomarker for monitoring the treatment of the disease. A baseline examination of VAD and FAZ before treatment initiation is meaningful. Larger studies are needed to establish the use of VAD and FAZ as biomarkers for treatment monitoring
How do parents access, appraise, and apply health information on early childhood allergy prevention? A focus group and interview study.
Get PDFBackground When parents want to make health-related decisions for their child, they need to be able to handle health information from a potentially endless range of sources. Early childhood allergy prevention (ECAP) is a good example: recommendations have shifted from allergen avoidance to early introduction of allergenic foods. We investigated how parents of children under 3 years old access, appraise and apply health information about ECAP, and their respective needs and preferences. Methods We conducted 23 focus groups and 24 interviews with 114 parents of children with varied risk for allergies. The recruitment strategy and a topic guide were co-designed with the target group and professionals from public health, education, and medicine. Data were mostly collected via video calls, recorded and then transcribed verbatim. Content analysis according to Kuckartz was performed using MAXQDA and findings are presented as a descriptive overview. Results Parents most frequently referred to family members, friends, and other parents as sources of ECAP information, as well as healthcare professionals (HCPs), particularly pediatricians. Parents said that they exchanged experiences and practices with their peers, while relying on HCPs for guidance on decision-making. When searching for information online, they infrequently recalled the sources used and were rarely aware of providers of "good" health information. While parents often reported trying to identify the authors of information to appraise its reliability, they said they did not undertake more comprehensive information quality checks. The choice and presentation of ECAP information was frequently criticized by all parent groups; in particular, parents of at-risk children or with a manifested allergy were often dissatisfied with HCP consultations, and hence did not straightforwardly apply advice. Though many trusted their HCPs, parents often reported taking preventive measures based on their own intuition. Conclusion One suggestion to react upon the many criticisms expressed by parents regarding who and how provides ECAP information is to integrate central ECAP recommendations into regular child care counseling by HCPs-provided that feasible ways for doing so are identified. This would assist disease prevention, as parents without specific concerns are often unaware of the ECAP dimension of issues such as nutrition
Generation of an induced pluripotent stem cell line, ZIPi021-A, from fibroblasts of a Prader-Willi syndrome patient with maternal uniparental disomy (mUPD)
Get PDFPrader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by loss of paternal expression of imprinted genes on chromosome 15q11-q13. We established a human induced pluripotent stem cell line (hiPSC), ZIPi021-A, from fibroblasts of a 4-year-old female PWS patient with the subtype of maternal uniparental disomy (mUPD). The generated hiPSC line was transgene-free, expressed pluripotency markers and showed the ability to differentiate into all three germ layers in vitro. The ZIPi021-A hiPSC line could be used as a cellular model for PWS in humans
Vena cava thrombosis after congenital diaphragmatic hernia repair: multivariate analysis of potential risk factors
Get PDFDie Rolle von Heparanase 1 und Heparanase 2 in der Degradierung der endothelialen Glykokalyx beim septischen Schock
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Automated Classification of Free-Text Radiology Reports: Using Different Feature Extraction Methods to Identify Fractures of the Distal Fibula
No full textZiel: Radiologische Befundtexte enthalten häufig Freitext, was eine strukturierte Datenauswertung erschwert. Natural language processing (NLP)-Techniken wandeln Freitext in maschinenlesbare Dokumentenvektoren um, die für die Entwicklung zuverlässiger, skalierbarer Methoden zur Datenanalyse wichtig sind. Ziel dieser Studie war, unstrukturierte Röntgenbefunde nach Frakturen der distalen Fibula zu klassifizieren und die beste Text-Mining-Methode zu finden. Material & Methoden: Zur Erstellung eines eigenen deutschsprachigen Befunddatensatzes wurden mittels einer dedizierten Suchmaschine Sprunggelenks-Röntgenbilder identifiziert und die entsprechenden Befunde manuell nach Frakturen der distalen Fibula sortiert. Anhand der Daten wurde eine Machine Learning Pipeline erstellt, die die Textrepräsentationsmethoden Bag-of-Words (BOW), Term Frequency-Inverse Document Frequency (TF-IDF), Principal Component Analysis (PCA), Non-Negative Matrix Factorization (NMF), Latent Dirichlet Allocation (LDA) und Document Embedding (doc2vec) implementierte. Die extrahierten Dokumentvektoren wurden zum Trainieren von neuronalen Netzen (NN), Support Vector Machines (SVM) und logistischer Regression (LR) verwendet, um distale Fibulafrakturen zu erkennen. Die Ergebnisse wurden mittels Kreuztabellen bzgl. der Accuracy (acc) und der area under the curve (AUC) verglichen. Ergebnisse: Insgesamt wurden 3268 Röntgenbefunde inkludiert, von denen 1076 eine distale Fibulafraktur beschrieben. Der Vergleich der Textdarstellungsmethoden zeigte, dass BOW die besten Ergebnisse erzielte (AUC=0,98; acc=0,97), gefolgt von TF-IDF (AUC=0,97; acc=0,96), NMF (AUC=0,93; acc=0,92), PCA (AUC=0,92; acc=0,9), LDA (AUC=0,91; acc=0,89) und doc2vec (AUC=0,9; acc=0,88). Im Vergleich der Klassifikatoren erwiesen sich die NN (AUC=0,91) gegenüber SVM (AUC=0,87) und LR (AUC=0,85) als überlegen. Schlussfolgerung: Eine automatisierte Klassifikation von unstrukturierten Befunden von Sprunggelenksaufnahmen kann zuverlässig Frakturen der distalen Fibula erkennen. Eine besonders geeignete Methode zur Feature Extraction ist das BOW-Modell. Kernaussagen: Ziel war die automatisierte Klassifizierung unstrukturierter Röntgenbefunde entsprechend distaler Fibulafrakturen. Eine zuverlässige Detektion von distalen Fibulafrakturen ist durch das automatisierte Klassifizierungssystem gewährleistet. Eine besonders geeignete Methode zur Feature Extraction ist das BOW-Model. Please note: Due to de-duplication and anonymization, the number of radiology reports published in this dataset differs from the original study dataset. The CSV file is encoded in UTF-8 with default quoting ('"'). The file may be read as intended with Python pandas version 1.4.4 read_csv method with default parameters
Lipidation of small GTPase Cdc42 as regulator of its physiological and pathophysiological functions.
Get PDFThe protein cell division cycle 42 (Cdc42) is a small GTPase of the Rho family regulating a plethora of physiological functions in a tissue, cell and subcellular-specific manner via participating in multiple signaling pathways. Since the corresponding signaling hubs are mainly organized along the cellular membranes, cytosolic proteins like Cdc42 need to be properly targeted and held at the membrane. Here, lipid modifications come into play: Cdc42 can be associated with membranes by different lipid anchors including prenylation (Cdc42-prenyl) and palmitoylation (Cdc42-palm). While Cdc42-prenyl is ubiquitously expressed, Cdc42-palm splicing variant in mainly expressed in the brain. Mechanisms underlying Cdc42 lipidation as well as its regulation are the main topic of this review. Furthermore, we will discuss the functional importance of Cdc42 lipid modifications with the focus on the role of different lipids in regulating defined Cdc42 functions. Finally, we will provide an overview of the possible implementation of Cdc42 lipidation in pathological conditions and different diseases
