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Item 10 Jahre Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren in Gießen: Tätigkeiten und Erfahrungen(2022) Glebe, Dieter; Lehmann, Felix; Goldmann, Nora; Giese, Annika; Hida, Yassine; Gerlich, Wolfram H.; Ziebuhr, John; Slanina, Heiko; Schüttler, Christian G.Item 10 Jahre Screening auf Frühgeborenenretinopathie (2009–2019)(2023) Busik, Valentina; Lorenz, Birgit; Mais, Christine; Jäger, Melanie; Friedburg, Christoph; Andrassi-Darida, Monika; Ehrhardt, Harald; Hubert, MechthildHintergrund: Die Frühgeborenenretinopathie („retinopathy of prematurity“ [ROP]) zählt in Deutschland und weltweit zu den häufigsten Erblindungsursachen im Kindesalter; ein adäquates Screening ist essenziell. Der telemedizinische Ansatz mit objektiver Dokumentation des Netzhautbefundes eröffnet die Möglichkeit, untersucherunabhängig alle ROP-Stadien sicher zu diagnostizieren, wenn die Befundung durch ein ROP-geschultes Augenärzteteam erfolgt. Ziel der Arbeit: 10-Jahres-Vergleich des ROP-Screenings an 2 deutschen Level-1-Perinatalzentren: universitär und vor Ort vs. nichtuniversitär und telemedizinisch. Material und Methoden: Retrospektive Analyse der Screeninguntersuchungen stratifiziert nach Gestationsalter (GA), Geburtsgewicht (GG), Geschlecht, Mehrlingsgeburten, ROP-Zeitpunkt, Behandlungsbedürftigkeit, -zeitpunkt und Untersuchungshäufigkeit. Ergebnisse: Von 2009 bis 2019 wurden 1191 Frühgeborene gescreent, davon 29 Externe. Bei den verbleibenden 1162 wurden 3713 Netzhautuntersuchungen durchgeführt; 34 % hatten eine ROP, 5,4 % wurden behandelt (Gießen 3,7 %, Siegen 7,2 %). Mittleres GA war 28,9 SSW (± 2,5), mittleres GG 1155 g (± 417,5). Die Zahl der ROP-Diagnosen stieg in Gießen um 227,3 % und in Siegen um 111,1 % aufgrund zunehmender Zahlen der betreuten Kinder. Diskussion: Die vergleichende Analyse bestätigte national und international steigende ROP-Screening-Untersuchungen und Kinder mit akuter ROP. Das telemedizinische Screening war dem Vor-Ort-Screening gleichwertig und sicher. Mit beiden Screeningmethoden wurden alle Behandlungsbedürftigen zeitgerecht erkannt. Kein Kind mit einem GA > 29 SSW benötigte eine Behandlung, analog zu Ergebnissen des schwedischen Registers. Im deutschen ROP-Register waren aber einzelne Frühgeborene mit einem GA ≥ 30 SSW behandlungsbedürftig.Item 3D In Vitro Models: Novel Insights into Idiopathic Pulmonary Fibrosis Pathophysiology and Drug Screening(2022) Vazquez-Armendariz, Ana Ivonne; Barroso, Margarida Maria; El Agha, Elie; Herold, SusanneItem 3D-analysis of unwanted tooth movements despite bonded orthodontic retainers: a pilot study(2020) Klaus, Katharina; Xirouchaki, Faidra; Ruf, SabineItem 8p23.1 duplication syndrome: narrowing of critical interval to 1.80 Mbp(2014) Weber, Axel; Köhler, Angelika; Hahn, Andreas; Müller, UlrichBACKGROUND: A 3.68 Mbp duplication of 8p23.1 defines the 8p23.1 duplication syndrome. The main features of this syndrome are developmental delay and/or learning problems. RESULTS: Here we present a patient with a 1.80 Mbp duplication in 8p23.1 and characteristic signs and symptoms of the syndrome, including delay of motor and speech development and intellectual disability. DISCUSSION: The case indicates that genes within this interval, in particular dosage sensitive genes SOX7 and TNKS1, and possibly MIR124-1 and MIR598 as well suffice to cause the pathognomonic features of the 8p23.1 duplication syndrome.Item A 20:1 synergetic mixture of cafedrine\/theodrenaline accelerates particle transport velocity in murine tracheal epithelium via IP3 receptor-associated calcium release(2023) Schmidt, Götz; Rienas, Gerrit; Müller, Sabrina; Edinger, Fabian; Sander, Michael; Koch, Christian; Henrich, MichaelBackground: Mucociliary clearance is a pivotal physiological mechanism that protects the lung by ridding the lower airways of pollution and colonization by pathogens, thereby preventing infections. The fixed 20:1 combination of cafedrine and theodrenaline has been used to treat perioperative hypotension or hypotensive states due to emergency situations since the 1960s. Because mucociliary clearance is impaired during mechanical ventilation and critical illness, the present study aimed to evaluate the influence of cafedrine/theodrenaline on mucociliary clearance. Material and Methods: The particle transport velocity (PTV) of murine trachea preparations was measured as a surrogate for mucociliary clearance under the influence of cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone. Inhibitory substances were applied to elucidate relevant signal transduction cascades. Results: All three applications of the combination of cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone induced a sharp increase in PTV in a concentration-dependent manner with median effective concentrations of 0.46 µM (consisting of 9.6 µM cafedrine and 0.46 µM theodrenaline), 408 and 4 μM, respectively. The signal transduction cascades were similar for the effects of both cafedrine and theodrenaline at the murine respiratory epithelium. While PTV remained at its baseline value after non-selective inhibition of β-adrenergic receptors and selective inhibition of β1 receptors, cafedrine/theodrenaline, cafedrine alone, or theodrenaline alone increased PTV despite the inhibition of the protein kinase A. However, IP3 receptor activation was found to be the pivotal mechanism leading to the increase in murine PTV, which was abolished when IP3 receptors were inhibited. Depleting intracellular calcium stores with caffeine confirmed calcium as another crucial messenger altering the PTV after the application of cafedrine/theodrenaline. Discussion: Cafedrine/theodrenaline, cafedrine alone, and theodrenaline alone exert their effects via IP3 receptor-associated calcium release that is ultimately triggered by β1-adrenergic receptor stimulation. Synergistic effects at the β1-adrenergic receptor are highly relevant to alter the PTV of the respiratory epithelium at clinically relevant concentrations. Further investigations are needed to assess the value of cafedrine/theodrenaline-mediated alterations in mucociliary function in clinical practice.Item A comparative clinical study on the transfer accuracy of conventional and digital implant impressions using a new reference key-based method(2021) Schmidt, Alexander; Rein, Peter Engelbert; Wöstmann, Bernd; Schlenz, Maximiliane AmelieItem A comparative study on the lipidome of normal knee synovial fluid from humans and horses(2021) Kosinska, Marta Krystyna; Eichner, Gerrit; Schmitz, Gerd; Liebisch, Gerhard; Steinmeyer, JürgenItem A cross-sectional survey on knowledge and attitudes of Greek dentists regarding molar incisor hypomineralisation diagnosis and treatment(2022) Seremidi, Kyriaki; Amend, Stefanie; Krämer, Norbert; Gizani, SotiriaBackground: Molar Incisor Hypomineralisation (MIH) remains a challenge for clinicians underlining the gap in the literature regarding the condition. The study aimed to record knowledge and attitudes of Greek dentists regarding diagnosis and treatment of MIH and correlate findings with non-dental characteristics. Methods: It is a cross-sectional study based on a questionnaire consisting of 37 multiple-choice questions. Data regarding diagnosis, aetiopathogenesis, and clinical management of MIH were collected from active members of three Greek Dental Associations. Chi-square and student’s t-test were used to correlate responses with practitioners’ characteristics and odds ratios calculated to evaluate differences on treatment of MIH-affected teeth (p < 0.05). Results: From the 360 participants (response rate = 94%), 185 were general dental practitioners (GDPs) and 175 dental specialists (59 paediatric dentists (PDs), 38 orthodontists and 78 of other specialties).MIH was commonly encountered as a clinical problem, with GDPs reporting genetics and fluoride intake as common aetiological factors at significantly higher percentages as compared to PDs (p < 0.05). Permanent molars and incisors (44%) were the teeth most commonly affected, with yellow/brown demarcated opacities (68%) the most common clinical feature with PDs reporting them in a significantly higher percentage (p < 0.05). Dentists with specialisation, dentists that treat > 10 children per week and children with MIH-affected teeth had a 2–5.5 times greater probability to report difficulty achieving sufficient anaesthesia and hypersensitivity problems (p < 0.001). Agreement between GDPs’ and dental specialists’ views was found on less invasive treatment of anterior lesions. Non-PDs reported bulk-fill restorations and onlays as the ideal treatment of severely-affected posterior teeth, as compared to PDs that preferred preformed metal crowns (p < 0.05). Multivariate logistic regression analysis revealed that the age of the clinician, years of experience and number of children treated per week were the factors significantly associated with the decision for the treatment of only severely-affected posterior MIH teeth. Conclusions: Most participants had encountered MIH-affected teeth in their clinical practice and were able to recognize main aetiological factors and clinical findings related to the condition. Nevertheless, their knowledge regarding treatment is limited.Item A Microfluidic System for Simultaneous Raman Spectroscopy, Patch-Clamp Electrophysiology, and Live-Cell Imaging to Study Key Cellular Events of Single Living Cells in Response to Acute Hypoxia(2021) Knoepp, Fenja; Wahl, Joel; Andersson, Anders; Kraut, Simone; Sommer, Natascha; Weissmann, Norbert; Ramser, KerstinItem A New Type of Chronic Wound Infection after Wisdom Tooth Extraction: A Diagnostic Approach with 16S-rRNA Gene Analysis, Next-Generation Sequencing, and Bioinformatics(2020) Böttger, Sebastian; Zechel-Gran, Silke; Streckbein, Philipp; Knitschke, Michael; Hain, Torsten; Weigel, Markus; Wilbrand, Jan-Falco; Domann, Eugen; Howaldt, Hans-Peter; Attia, SamehItem A Novel Insertion in the Hepatitis B Virus Surface Protein Leading to Hyperglycosylation Causes Diagnostic and Immune Escape(2023) Lehmann, Felix; Slanina, Heiko; Roderfeld, Martin; Roeb, Elke; Trebicka, Jonel; Ziebuhr, John; Gerlich, Wolfram H.; Schüttler, Christian G.; Schlevogt, Bernhard; Glebe, DieterChronic hepatitis B virus (HBV) infection is a global health threat. Mutations in the surface antigen of HBV (HBsAg) may alter its antigenicity, infectivity, and transmissibility. A patient positive for HBV DNA and detectable but low-level HBsAg in parallel with anti-HBs suggested the presence of immune and/or diagnostic escape variants. To support this hypothesis, serumderived HBs gene sequences were amplified and cloned for sequencing, which revealed infection with exclusively non-wildtype HBV subgenotype (sgt) D3. Three distinct mutations in the antigenic loop of HBsAg that caused additional N-glycosylation were found in the variant sequences, including a previously undescribed six-nucleotide insertion. Cellular and secreted HBsAg was analyzed for N-glycosylation in Western blot after expression in human hepatoma cells. Secreted HBsAg was also subjected to four widely used, state-of-the-art diagnostic assays, which all failed to detect the hyperglycosylated insertion variant. Additionally, the recognition of mutant HBsAg by vaccine- and natural infection-induced anti-HBs antibodies was severely impaired. Taken together, these data suggest that the novel six-nucleotide insertion as well as two other previously described mutations causing hyperglycosylation in combination with immune escape mutations have a critical impact on in vitro diagnostics and likely increase the risk of breakthrough infection by evasion of vaccineinduced immunity.Item A novel model of a biomechanically induced osteoarthritis-like cartilage for pharmacological in vitro studies(2021) Sauerland, Katrin; Wolf, Amela; Schudok, Manfred; Steinmeyer, JürgenItem A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab-refractory iNHL (COMPLEMENT A + B study)(2021) Rummel, Mathias J.; Janssens, Ann; MacDonald, David; Keating, Mary-Margaret; Zaucha, Jan M.; Davis, Jaclyn; Lasher, Janet; Babanrao Pisal, Chaitali; Izquierdo, Miguel; Friedberg, Jonathan W.Item A point mutation c.473A > G of ITGB3 is responsible for the formation of the Woa human platelet alloantigen(2020) Holzwarth, Sarah T.; Strobel, Julian; Cooper, Nina; Leyh, Jörg; Bayat, Behnaz; Bein, Gregor; Zingsem, Jürgen; Sachs, Ulrich J.Item A rare cause of stroke: fail-implanted venous port catheter system – a case report(2021) Yenigün, Mesut; Braun, Tobias; Vlazák, Alexander; Umscheid, Thomas; Jünemann, Martin; Gerriets, Tibo; Tschernatsch, MarleneItem A Severe Dementia Syndrome Caused by Intron Retention and Cryptic Splice Site Activation in STUB1 and Exacerbated by TBP Repeat Expansions(2022) Reis, Marien Colleen; Patrun, Julia; Ackl, Nibal; Winter, Pia; Scheifele, Maximilian; Danek, Adrian; Nolte, DagmarItem A statistical model of the rate-dependent fracture behavior of dental polymer-based biomaterials(2023) Schrader, Peer; Schmidt, Alexander; Schlenz, Maximiliane A.; Kolling, Stefan; Wöstmann, Bernd; Berlinger, MarcelAn insight into the fracture behavior of dental polymer-based biomaterials is important to reduce safety hazards for patients. The crack-driven fracture process of polymers is largely stochastic and often dependent on the loading rate. Therefore, in this study, a statistical model was developed based on three-point bending tests on dental polymethyl methacrylate at different loading rates. The fracture strains were investigated (two-parameter Weibull distribution (2PW)) and the rate-dependency of the 2PW parameters were examined (Cramér-von Mises test (CvM)), arriving at the conclusion that there could be a limiting distribution for both quasi-static and dynamic failure. Based on these findings, a phenomenological model based on exponential functions was developed, which would further facilitate the determination of the failure probability of the material at a certain strain with a given strain rate. The model can be integrated into finite element solvers to consider the stochastic fracture behavior in simulations.Item A survey to evaluate knowledge, perceptions and attitudes toward COVID-19 vaccinations among rheumatologists in Germany(2021) Hasseli, Rebecca; Pfeil, Alexander; Krause, Andreas; Schulze-Koops, Hendrik; Müller-Ladner, Ulf; Specker, Christof; Hoyer, Bimba; Lorenz, Hanns-Martin; Regierer, Anne; Richter, Jutta; Schmeiser, Tim; Strangfeld, Anja; Voll, Reinhard; Voormann, AnnaItem ABCB4 is frequently epigenetically silenced in human cancers and inhibits tumor growth(2014) Kiehl, Steffen; Herkt, Stefanie C.; Richter, Antje M.; Fuhrmann, Liesa; El-Nikhely, Nefertiti; Seeger, Werner; Savai, Rajkumar; Dammann, Reinhard H.Epigenetic silencing through promoter hypermethylation is an important hallmark for the inactivation of tumor-related genes in carcinogenesis. Here we identified the ATP-binding cassette sub-family B member 4 (ABCB4) as a novel epigenetically silenced target gene. We investigated the epigenetic regulation of ABCB4 in 26 human lung, breast, skin, liver, head and neck cancer cells lines and in primary cancers by methylation and expression analysis. Hypermethylation of the ABCB4 CpG island promoter occurred in 16 out of 26 (62%) human cancer cell lines. Aberrant methylation of ABCB4 was also revealed in 39% of primary lung cancer and in 20% of head and neck cancer tissues. In 37% of primary lung cancer samples, ABCB4 expression was absent. For breast cancer a significant hypermethylation occurred in tumor tissues (41%) compared to matching normal samples (0%, p = 0.002). Silencing of ABCB4 was reversed by 5-aza-2´-deoxycytidine and zebularine treatments leading to its reexpression in cancer cells. Overexpression of ABCB4 significantly suppressed colony formation and proliferation of lung cancer cells. Hypermethylation of Abcb4 occurred also in murine cancer, but was not found in normal tissues. Our findings suggest that ABCB4 is a frequently silenced gene in different cancers and it may act tumor suppressivly in lung cancer.