@article{LinzBrandsKertelsetal.2021, author = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte}, title = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {48}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {12}, issn = {1619-7070}, doi = {10.1007/s00259-021-05422-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246}, pages = {3951-3960}, year = {2021}, abstract = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.}, language = {en} } @article{SprinzlMageleSchoergetal.2023, author = {Sprinzl, Georg Mathias and Magele, Astrid and Schoerg, Philipp and Hagen, Rudolf and Rak, Kristen and Kurz, Anja and Van de Heyning, Paul and Calvino, Miryam and Lassaletta, Luis and Gavil{\´a}n, Javier}, title = {A novel representation of audiological and subjective findings for acoustical, bone conduction and direct drive hearing solutions}, series = {Journal of Personalized Medicine}, volume = {13}, journal = {Journal of Personalized Medicine}, number = {3}, issn = {2075-4426}, doi = {10.3390/jpm13030462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311210}, year = {2023}, abstract = {Background: The benefit of hearing rehabilitation is often measured using audiological tests or subjective questionnaires/interviews. It is important to consider both aspects in order to evaluate the overall benefits. Currently, there is no standardized method for reporting combined audiological and patient reported subjective outcome measures in clinical practice. Therefore, this study focuses on showing the patient's audiological, as well as subjective outcomes in one graph using data from an existing study. Method: The present paper illustrated a graph presenting data on four quadrants with audiological and subjective findings. These quadrants represented speech comprehension in quiet (unaided vs. aided) as WRS\% at 65 dB SPL, speech recognition in noise (unaided vs. aided) as SRT dB SNR, sound field threshold (unaided vs. aided) as PTA\(_4\) in dB HL, wearing time and patient satisfaction questionnaire results. Results: As an example, the HEARRING graph in this paper represented audiological and subjective datasets on a single patient level or a cohort of patients for an active bone conduction hearing implant solution. The graph offered the option to follow the user's performance in time. Conclusion: The HEARRING graph allowed representation of a combination of audiological measures with patient reported outcomes in one single graph, indicating the overall benefit of the intervention. In addition, the correlation and consistency between some results (e.g., aided threshold and aided WRS) can be better visualized. Those users who lacked performance benefits on one or more parameters and called for further insight could be visually identified.}, language = {en} } @phdthesis{Bieniussa2024, author = {Bieniussa, Linda Ilse}, title = {Different effects of conditional Knock-Out of Stat3 on the sensory epithelium of the Organ of Corti}, doi = {10.25972/OPUS-35143}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351434}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die Cochlea von S{\"a}ugetieren nimmt Schall als Reaktion auf Vibrationen an frequenzabh{\"a}ngigen Positionen entlang des Cochlea-Kanals wahr. Die sensorischen {\"a}ußeren Haarzellen, die von St{\"u}tzzellen umgeben sind, wirken als Signalverst{\"a}rker, indem sie ihre Zelll{\"a}nge ver{\"a}ndern k{\"o}nnen. Dies wird als Elektromotilit{\"a}t bezeichnet. Um eine korrekte elektrische {\"U}bertragung bei mechanischen Kr{\"a}ften zu gew{\"a}hrleisten, ist ein gewisser Widerstand des sensorischen Epithels eine Voraussetzung f{\"u}r die fehlerfreie Weiterleitung von H{\"o}rinformationen. Dieser Widerstand wird durch Mikrotubuli und deren posttranslationalen Modifikationen in den St{\"u}tzzellen des sensorischen Epithels der Cochlea gew{\"a}hrleistet. Stat3 ist ein Transkriptionsfaktor, der an verschiedenen Phosphorylierungsstellen, sowie je nach Zelltyp und aktiviertem Signalweg an vielen zellul{\"a}ren Prozessen wie Differenzierung, Entz{\"u}ndung, Zell{\"u}berleben und Mikrotubuli-Dynamik beteiligt ist. W{\"a}hrend Stat3 ein breites Spektrum an intrazellul{\"a}ren Funktionen hat, stellte sich die Frage, wie und ob Stat3 in den Zellen des Cortischen Organ einen Einfluss auf den H{\"o}rprozess hat. Um dies zu testen, wurde das Cre/loxp-System verwendet, um Stat3 in den {\"a}ußeren Haarzellen oder den St{\"u}tzzellen entweder vor oder nach H{\"o}rbeginn von M{\"a}usen konditional auszuschalten. Um das H{\"o}rverm{\"o}gen zu erfassen, wurden DPOAE- und ABR-Messungen durchgef{\"u}hrt, w{\"a}hrend molekulare und morphologische Untersuchungen mittels Sequenzierung und Immunhistochemie durchgef{\"u}hrt wurden. Eine konditioneller Knock-Out von Stat3 vor und nach dem Beginn des H{\"o}rens in {\"a}ußeren Haarzellen f{\"u}hrt zu leichten H{\"o}rsch{\"a}den, w{\"a}hrend Synapsen, Nervenfasern und Mitochondrien nicht betroffen waren. Die Analyse der Sequenzierung von {\"a}ußeren Haarzellen aus M{\"a}usen mit konditionellem Knock-Out vor dem Beginn des H{\"o}rens ergab eine St{\"o}rung der zellul{\"a}ren Hom{\"o}ostase und der extrazellul{\"a}ren Signale. Ein konditioneller Knock-Out von Stat3 in den {\"a}ußeren Haarzellen nach Beginn des H{\"o}rens f{\"u}hrte zu einem fr{\"u}h-entz{\"u}ndlichen Signalweg mit erh{\"o}hter Zytokinproduktion und der Hochregulierung des NF-κB-Wegs. In den St{\"u}tzzellen f{\"u}hrte ein kondioneller Knock-Out von Stat3 nur nach dem Beginn des H{\"o}rens zu einer H{\"o}rbeeintr{\"a}chtigung. Synapsen, Nervensoma und -fasern waren jedoch von einem konditionellen Knock-Out von Stat3 in St{\"u}tzzellen nicht betroffen. Dennoch war die detyronisierte Modifikation der Mikrotubuli ver{\"a}ndert, was zu einer Instabilit{\"a}t der St{\"u}tzzellen, insbesondere der Phalangealforts{\"a}tze, f{\"u}hrte, was wiederum zu einer Instabilit{\"a}t des Epithels w{\"a}hrend des H{\"o}rvorgangs f{\"u}hrte. Zusammenfassend l{\"a}sst sich sagen, dass ein konditioneller Knock-Out von Stat3 in Zellen des Cortischen Organs zu einer H{\"o}rst{\"o}rung f{\"u}hrte. W{\"a}hrend ein konditioneller Knock-Out in {\"a}ußeren Haarzellen eine erh{\"o}hte Zytokinproduktion zur Folge hatte, verloren die St{\"u}tzzellen ihre Zellstabilit{\"a}t aufgrund einer verminderten detyronisierten Modifikation der Mikrotubuli. Insgesamt deuten die Ergebnisse darauf hin, dass Stat3 ein wichtiges Protein f{\"u}r die H{\"o}rleistung ist. Es sind jedoch weitere Untersuchungen des molekularen Mechanismus erforderlich, um die Rolle von Stat3 in den Zellen des Corti-Organs zu verstehen.}, subject = {Audiologie}, language = {en} } @article{FriedrichSchneiderBuerkleinetal.2023, author = {Friedrich, Maximilian U. and Schneider, Erich and Buerklein, Miriam and Taeger, Johannes and Hartig, Johannes and Volkmann, Jens and Peach, Robert and Zeller, Daniel}, title = {Smartphone video nystagmography using convolutional neural networks: ConVNG}, series = {Journal of Neurology}, volume = {270}, journal = {Journal of Neurology}, number = {5}, doi = {10.1007/s00415-022-11493-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324526}, pages = {2518-2530}, year = {2023}, abstract = {Background Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances. Methods A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the "two one-sample t-test" (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation. Results ConVNG tracking accuracy reached 9-15\% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms' precision was inferior to VOG. Conclusions ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.}, language = {en} } @phdthesis{Skornicka2024, author = {Skornicka, Johannes}, title = {Analyse des modulierenden Effekts von pegyliertem IGF-1 (pegIGF-1) auf die H{\"o}rfunktion von pmn-M{\"a}usen}, doi = {10.25972/OPUS-34912}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349125}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die Maus mit progressiver motorischer Neuropathie (PMN) ist ein Modell f{\"u}r eine vererbte motorische Neuropathie mit progressiver Neurodegeneration. Die Degeneration der Axone geht mit homozygoten Mutationen des TBCE- Gens einher, das f{\"u}r das Tubulin-Chaperon-E- Protein kodiert. TBCE ist f{\"u}r die korrekte Dimerisierung von Alpha- und Beta-Tubulin verantwortlich. Auffallend ist, dass die PMN-Maus nach dem normalen Beginn des H{\"o}rens auch einen progressiven H{\"o}rverlust entwickelt, der durch die Degeneration des H{\"o}rnervs und den Verlust der {\"a}ußeren Haarzellen (OHC) gekennzeichnet ist. Die Entwicklung dieser neuronalen und cochle{\"a}ren Pathologie ist Wirkung von peg-IGF-1 auf das auditorische System durch Behandlung ab dem 15. postnatalen Tag (p15). Die histologische Analyse ergab positive Auswirkungen auf die OHC-Synapsen der medialen olivocochle{\"a}ren (MOC) neuronalen Fasern und eine kurzfristige Abschw{\"a}chung des OHC-Verlustes. Peg-IGF-1 war in der Lage, die Desorganisation der OHC-Synapsen bedingt wiederherzustellen und die Bereitstellung von cholinerger Acetyltransferase in den Pr{\"a}synapsen aufrechtzuerhalten. Zur Beurteilung der auditorischen Funktion wurden frequenzspezifische Hirnstammreaktionen und otoakustische Emissionen mit Verzerrungsprodukten bei Tieren mit p21 und p28 aufgezeichnet. Trotz der positiven Auswirkungen auf die MOC-Fasern und die OHC konnte jedoch keine Wiederherstellung des H{\"o}rverm{\"o}gens erreicht werden. Die vorliegende Arbeit zeigt, dass die synaptische Pathologie der efferenten MOC-Fasern in PMN-M{\"a}usen eine besondere Form der "efferenten auditorischen Neuropathie" darstellt. Peg-IGF-1 zeigte eine otoprotektive Wirkung, indem es die Degeneration von OHCs und efferenten Synapsen verhinderte. Es sind jedoch verst{\"a}rkte Anstrengungen zur Optimierung der Behandlung erforderlich, um nachweisbare Verbesserungen der H{\"o}rleistung zu erzielen.}, subject = {Cochlea}, language = {de} } @article{EngertSpahnBieniussaetal.2023, author = {Engert, Jonas and Spahn, Bjoern and Bieniussa, Linda and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes}, title = {Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body}, series = {Life}, volume = {13}, journal = {Life}, number = {5}, issn = {2075-1729}, doi = {10.3390/life13051188}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319387}, year = {2023}, abstract = {The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.}, language = {en} } @article{StefanakisBasslerWalczuchetal.2023, author = {Stefanakis, Mona and Bassler, Miriam C. and Walczuch, Tobias R. and Gerhard-Hartmann, Elena and Youssef, Almoatazbellah and Scherzad, Agmal and St{\"o}th, Manuel Bernd and Ostertag, Edwin and Hagen, Rudolf and Steinke, Maria R. and Hackenberg, Stephan and Brecht, Marc and Meyer, Till Jasper}, title = {The impact of tissue preparation on salivary gland tumors investigated by Fourier-transform infrared microspectroscopy}, series = {Journal of Clinical Medicine}, volume = {12}, journal = {Journal of Clinical Medicine}, number = {2}, issn = {2077-0383}, doi = {10.3390/jcm12020569}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304887}, year = {2023}, abstract = {Due to the wide variety of benign and malignant salivary gland tumors, classification and malignant behavior determination based on histomorphological criteria can be difficult and sometimes impossible. Spectroscopical procedures can acquire molecular biological information without destroying the tissue within the measurement processes. Since several tissue preparation procedures exist, our study investigated the impact of these preparations on the chemical composition of healthy and tumorous salivary gland tissue by Fourier-transform infrared (FTIR) microspectroscopy. Sequential tissue cross-sections were prepared from native, formalin-fixed and formalin-fixed paraffin-embedded (FFPE) tissue and analyzed. The FFPE cross-sections were dewaxed and remeasured. By using principal component analysis (PCA) combined with a discriminant analysis (DA), robust models for the distinction of sample preparations were built individually for each parotid tissue type. As a result, the PCA-DA model evaluation showed a high similarity between native and formalin-fixed tissues based on their chemical composition. Thus, formalin-fixed tissues are highly representative of the native samples and facilitate a transfer from scientific laboratory analysis into the clinical routine due to their robust nature. Furthermore, the dewaxing of the cross-sections entails the loss of molecular information. Our study successfully demonstrated how FTIR microspectroscopy can be used as a powerful tool within existing clinical workflows.}, language = {en} } @article{HackenbergMeyerHaefneretal.2022, author = {Hackenberg, Stephan and Meyer, Till Jasper and H{\"a}fner, Johannes and Scheich, Matthias and St{\"o}th, Manuel and Al-Tinawi, Fadi and Neun, Tilmann and Mlynski, Robert and Hagen, Rudolf and Scherzad, Agmal}, title = {Surgical management of tympanojugular paragangliomas using the flexible CO\(_2\) laser}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {12}, doi = {10.1007/s00405-022-07416-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324164}, pages = {5623-5630}, year = {2022}, abstract = {Purpose Surgery is a standard therapy for tympanojugular paragangliomas (TJP). Maintaining the quality of life (QoL) requires functional preservation. The flexible CO\(_2\) laser allows contact-free tumor removal. This retrospective study compares the postoperative functional outcomes of TJP surgery with and without the flexible CO\(_2\) laser. Methods Between 2005 and 2019, 51 patients with TJP were surgically treated at a tertiary hospital. Until 2012, 17 patients received conventional surgery. Thereafter, the flexible laser was used in 34 patients. Tumor extend, pre- and postoperative cranial nerve function, and complications were compared between the groups. Results The cohort consisted of 33 class A and B tumors and 18 class C and D tumors. Preoperative embolization was performed in 17 cases. Class C/D TJP were usually removed via an infratemporal fossa type A approach. Gross total tumor removal was achieved in 14/18 class C/D tumors. 3/51 patients suffered from long-term partial or complete facial palsy. No differences in post-therapeutic cranial nerve function or complications were noted between the conventional and laser group. One recurrence was observed after complete tumor resection. Conclusion The flexible CO\(_2\) laser was shown to be a safe and effective alternative to conventional bipolar cauterization, which is appreciated by the surgeon in these highly vascularized tumors. Both techniques allowed a high tumor control rate and good long-term results also from a functional point of view.}, language = {en} } @article{TecleHackenbergScheichetal.2023, author = {Tecle, Nyat-Eyob and Hackenberg, Stephan and Scheich, Matthias and Scherzad, Agmal and Hagen, Rudolf and Gehrke, Thomas}, title = {Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases}, series = {European Journal of Pediatrics}, volume = {182}, journal = {European Journal of Pediatrics}, number = {1}, doi = {10.1007/s00431-022-04676-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324179}, pages = {431-438}, year = {2023}, abstract = {Cervical abscesses are relatively common infections in pediatric patients. There is an ongoing debate about the necessity and time point of surgical drainage. The identification of a focus of infection might play an important role in facilitating a therapeutic decision. In a retrospective study, 100 pediatric patients aged 1-18 years who underwent incision and drainage of a lateral cervical abscess at our institution were analyzed. Patients were divided into two groups based on whether a focus of infection could be identified or not. Data collection included patient characteristics, microbiological results, antibiotic regimen, and clinical course. A focus of infection was found in 29\% (29/100) of the patients, most frequently in the tonsils. A causative microorganism was found in 75\% (75/100) of all patients, with Staphylococcus aureus and Streptococcus pyogenes being the most common pathogens. All patients received an empiric antibiotic therapy in addition to surgery. Antibiotic medication was changed in 31\% in both groups (9/29 with a focus of infection and 22/71 without a focus of infection) during therapy. Children without an identified focus of infection generally were younger and had more comorbidities reducing immune response while also showing differences in the pathogens involved. There were no complications associated to surgery or antibiotic therapy in any of the patients involved. Conclusion: Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding the microorganisms involved. But the focus of infection seems not to have an impact on patient's outcome. What is Known: • Neck abscesses are a relatively common disease in the pediatric population and may cause serious complications. • Therapy in general consists of intravenous antibiotics with or without surgery. What is New: • The focus identification has no impact on patient's outcome. • Children with an identified focus of infection show several differences compared to those with isolated lateral abscesses, especially regarding their medical history, age, and the microorganisms involved.}, language = {en} } @article{MertensAndriesKurzetal.2022, author = {Mertens, Griet and Andries, Ellen and Kurz, Anja and Tȧvora-Vieira, Dayse and Calvino, Miryam and Amann, Edda and Anderson, Ilona and Lorens, Artur}, title = {Towards a consensus on an ICF-based classification system for horizontal sound-source localization}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {12}, issn = {2075-4426}, doi = {10.3390/jpm12121971}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297319}, year = {2022}, abstract = {The study aimed to develop a consensus classification system for the reporting of sound localization testing results, especially in the field of cochlear implantation. Against the background of an overview of the wide variations present in localization testing procedures and reporting metrics, a novel classification system was proposed to report localization errors according to the widely accepted International Classification of Functioning, Disability and Health (ICF) framework. The obtained HEARRING_LOC_ICF scale includes the ICF graded scale: 0 (no impairment), 1 (mild impairment), 2 (moderate impairment), 3 (severe impairment), and 4 (complete impairment). Improvement of comparability of localization results across institutes, localization testing setups, and listeners was demonstrated by applying the classification system retrospectively to data obtained from cohorts of normal-hearing and cochlear implant listeners at our institutes. The application of our classification system will help to facilitate multi-center studies, as well as allowing better meta-analyses of data, resulting in improved evidence-based practice in the field.}, language = {en} } @phdthesis{Noyalet2023, author = {Noyalet, Laurent}, title = {Untersuchung der "Vestibular aqueduct" Morphologie bei Patienten mit H{\"o}rminderung und Morbus Meni{\`e}re am W{\"u}rzburger Patientenkollektiv}, doi = {10.25972/OPUS-32942}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-329423}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Trotz langj{\"a}hriger klinischer Erfahrung, vielen Untersuchungen und Studien, ist die korrekte Diagnosestellung eines Morbus Meni{\`e}re immer noch schwierig. Diagnostische Mittel sind vor allem eine ausf{\"u}hrliche Anamnese, die ECOG, Tonaudiogramm und der Ausschluss anderer Innenohrerkrankungen. Betroffene erleiden h{\"a}ufig Schwindelanf{\"a}lle, Tinnitus, Ohrdruck und verlieren an H{\"o}rverm{\"o}gen. Der progressive Verlauf dieser Erkrankung l{\"a}sst sich meist nur verlangsamen. H{\"a}ufig startet die Therapie funktionserhaltend-medikament{\"o}s mit Betahistin und Antiemetika, im weiteren Verlauf sind meist operative Eingriffe wie die Saccotomie n{\"o}tig. Dabei wird der Saccus endolymphaticus aufgesucht, geschlitzt und mittels Silikondreieck offengehalten, um damit eine Entlastung des endolymphatischen Systems zu schaffen. Zeigt sich nur wenig Besserung kann destruierend fortgefahren werden. Hierbei sind vor allem die Gentamycin-Therapie und die Neurektomie oder Labyrinthektomie Mittel der Wahl. Diese Untersuchung hatte das Ziel eine weitere diagnostische Methode zu finden, um die MM-Diagnose zu sichern und eine Prognose in Bezug auf die Therapie mittels Saccotomie zu liefern. Im Fokus stand hierbei der vestibul{\"a}re Aqu{\"a}dukt, welcher bereits in vielen Arbeiten auff{\"a}llig in Form und Lage bei MM-Patienten gewesen war. Vor allem der Bezug des Aqu{\"a}duktes zu den Bogeng{\"a}ngen und dessen L{\"a}nge wurden in der vorliegenden Studie genauer betrachtet. Dies geschah durch Messungen anhand von CT-Bildern. Der Winkel zwischen den Bogeng{\"a}ngen und dem VA und die L{\"a}nge des VA wurde gemessen und ausgewertet. Dies wurde zur Best{\"a}tigung der Methode, sowohl an menschlichen Felsenbeinpr{\"a}paraten mit qualitativ unterschiedlichen CT-Aufnahmen als auch an Patienten durchgef{\"u}hrt. Dabei konnte man keine signifikanten Unterschiede innerhalb der verschiedenen CT-Aufnahmen der Felsenbeinpr{\"a}parate feststellen. Mit Best{\"a}tigung der Reliabilit{\"a}t dieser Methode wurden dann Patienten untersucht. Dabei wurden zwei Gruppen gebildet, Nicht-MM- und MM-Patienten. Die Nicht-MM bestanden aus Patienten mit einem Akustikusneurinom der Gegenseite oder einem Cochlea-Implantat, welche keinen MM aufwiesen. Die MM-Patienten wurden alle mit einer Saccotomie behandelt und hatten damit einen gesicherten MM. Die Auswertung der Messergebnisse stellte dar, dass bei MM-Betroffenen die L{\"a}nge mit durchschnittlich 7,9 mm im Vergleich mit Nicht-Betroffenen-VA (9,5 mm), signifikant reduziert war. Auch die Ergebnisse der Winkelmessung zeigte bei allen Bogeng{\"a}ngen signifikante Unterschiede. Um die Ergebnisse der Winkelmessung besser zu kategorisieren, wurde der VA-Score erstellt. Dieser vereinigt die Ergebnisse der drei Bogeng{\"a}nge zu einem Wert von 1 bis 8. Auch hier erwiesen sich die MM-Patienten als auff{\"a}llig, da sich diese im VA-Score 2 mit 44\% h{\"a}uften. Im Gegensatz dazu waren die Ergebnisse der nicht Erkrankten breiter verteilt. Zur weiteren Auswertung z{\"a}hlten außerdem die anamnestischen Daten und der Verlauf der Saccotomie. Dadurch konnte der Erfolg der Behandlung bestimmt und diese mit den Untersuchungen des VA des jeweiligen Patienten korreliert werden. Dabei stellte sich heraus, dass vor allem bei VA mit hohen Winkeln und sehr kurzen VA die Erfolgsquote geringer war. Damit k{\"o}nnte also ein Zusammenhang zwischen Form und Lage des VA und Therapie bestehen. Um dies sicher zu best{\"a}tigen, braucht es noch mehr Patienten und eine klinisch zugelassene Software, die diese Messungen durchf{\"u}hren kann. Hierbei ist vor allem eine gute Bildgebung des Innenohrs wichtig, um den VA optimal messen zu k{\"o}nnen. Um die Messungen schnell und zuverl{\"a}ssig durchf{\"u}hren zu k{\"o}nnen, w{\"a}re eine Software, welche die Messungen automatisch durchf{\"u}hren kann, ein m{\"o}glicher Ansatz. Die ausf{\"u}hrliche Voruntersuchung wird jedoch weiterhin notwendig sein, um MM sicher zu diagnostizieren.}, subject = {Meni{\`e}re-Krankheit}, language = {de} } @phdthesis{Hunsmann2005, author = {Hunsmann, Esther L.}, title = {Sprachverstehen im St{\"o}rl{\"a}rm mit dem Hochmair-Schulz-Moser (HSM)-Satztest : audiometrische Normwerte junger Erwachsener bei binaural alternierender Sprachdarbietung mit Einsteckh{\"o}rern}, doi = {10.25972/OPUS-32932}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-329327}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2005}, abstract = {Sprachaudiometrische Untersuchungen sind Voraussetzung f{\"u}r die korrekte Verordnung und Anpassung von H{\"o}rger{\"a}ten und Cochlea-Implantaten sowie der arbeitsmedizinischen Begutachtung von Minderungen der Erwerbsf{\"a}higkeit. Um das Kommunikationsverm{\"o}gen im l{\"a}rmbelasteten Alltag zu pr{\"u}fen, eignen sich Sprachverst{\"a}ndlichkeitsmessungen im St{\"o}rschall. In dieser Arbeit sollten mit dem HSM-Satztest Normwerte zum Sprachverstehen im St{\"o}rl{\"a}rm an jungen Erwachsenen f{\"u}r Messungen an H{\"o}rgesch{\"a}digten ermittelt werden. Junge Erwachsene sind i.d.R. maximal konzentrations- und leistungsf{\"a}hig sowie normal h{\"o}rend. Ferner wurde {\"u}berpr{\"u}ft, inwiefern sich das individuelle Antwortverhalten der Probanden und die Position der Satzgruppe auf das Sprachverstehen auswirken. Dreißig Probanden beiderlei Geschlechts im Alter von 20 bis 29 Jahren wurden zwischen beiden Ohren wechselnd digital aufgezeichnete, sinnvolle S{\"a}tze in St{\"o}rschallpegeln von 60 und 80 dB dargeboten. Die getrennte Betrachtung der Ergebnisse bei 60 und 80 dB St{\"o}rschall zeigte f{\"u}r den Bereich der Sprachverst{\"a}ndlichkeitsschwelle ein signifikant besseres Sprachverstehen bei 80 dB St{\"o}rschall. Hier war ein geringerer Sprachschallpegel zum f{\"u}nfzigprozentigen Sprachverst{\"a}ndnis erforderlich. Außerdem war bei gleichem Signal- Rausch-Abstand das prozentuale Verst{\"a}ndnis h{\"o}her. Die Befunde mit der binaural alternierenden Darbietung des HSM-Tests best{\"a}tigen entsprechende Vermutungen fr{\"u}herer Untersuchungen von H{\"o}rger{\"a}tetr{\"a}gern und {\"a}lteren Normalh{\"o}renden. Daher wurde nicht ein Artefakt des hier verwendeten Versuchsaufbaus gemessen. Forsches Antwortverhalten zeigte eine leichte, jedoch nicht signifikante Tendenz zu besser bewertetem Sprachverst{\"a}ndnis. Unterschiede im Sprachverst{\"a}ndnis in Abh{\"a}ngigkeit von der Position der Satzgruppe konnten nicht festegestellt werden. Die Definition der Norm mit diesem Testansatz, der Alltagsbedingungen im Labor simuliert, ist eine wesentliche Voraussetzung f{\"u}r pr{\"a}zise Diagnostik von H{\"o}rst{\"o}rungen und ihre optimierte Behandlung.}, language = {de} } @phdthesis{Ilgen2023, author = {Ilgen, Lukas}, title = {Ermittlung cochle{\"a}rer L{\"a}ngen- und Winkelmaße mittels Flachdetektor-Volumen-Computertomographie - Evaluation der Anwendung sekund{\"a}rer Rekonstruktionen}, doi = {10.25972/OPUS-32794}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327945}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {F{\"u}r die Cochlea-Implantat-Versorgung ist die Kenntnis der individuellen Anatomie der H{\"o}rschnecke im perioperativen Kontext essenziell, um ein suffizientes audiologisches Resultat sicherzustellen. Ein akkurates Verfahren hierf{\"u}r stellt die 3D multiplanare Rekonstruktion (3D-curved MPR) in Schnittbildgebung dar. Notwendige Voraussetzung ist jedoch eine hinreichende Bildqualit{\"a}t. In dieser Arbeit wurde das Augenmerk auf die sekund{\"a}re Rekonstruktion von Prim{\"a}rdatens{\"a}tzen der Flachdetektor-Volumen-Computertomographie (fpVCTSECO) gerichtet. Diese bietet n{\"a}mlich die M{\"o}glichkeit, die Bildqualit{\"a}t zu steigern, ohne jedoch eine als kritisch einzusch{\"a}tzende Dosissteigerung in Kauf nehmen zu m{\"u}ssen. Es konnte gezeigt werden, dass es f{\"u}r die Messung der L{\"a}nge von 2 Schneckenwindungen (2TL), der gesamten cochle{\"a}ren L{\"a}nge (CDL) und dem Winkelmaß (AL) mittels 3D-curved MPR in der fpVCT keinen signifikanten Unterschied gegen{\"u}ber der Mehrschicht-CT gibt. In beiden Modalit{\"a}ten wurden alle drei Parameter gegen{\"u}ber der Referenzbildgebung micro-CT deutlich untersch{\"a}tzt. Durch die fpVCTSECO war es m{\"o}glich, die Genauigkeit der Messungen zu steigern und den Werten der Referenz anzun{\"a}hern. Lediglich f{\"u}r AL muss eine geringf{\"u}gige systematische Untersch{\"a}tzung beachtet werden. Postoperativ zeigte sich mit einliegendem Elektrodentr{\"a}ger f{\"u}r 2TL eine ebenso pr{\"a}zise Messung wie pr{\"a}operativ ohne. Jedoch wurde die CDL um circa 0,5 - 0,7 mm untersch{\"a}tzt. Urs{\"a}chlich hierf{\"u}r d{\"u}rften vor allem Metallartefakte gewesen sein. Auch wenn die 3D-curved MPR in Kombination mit der fpVCTSECO postoperativ zur Visualisierung der r{\"a}umlichen Beziehung von Elektrodentr{\"a}ger, Modiolus und oss{\"a}rer lateraler Wand sehr gut geeignet war, so muss sich der Einfluss dieser Diskrepanz f{\"u}r die audiologische Anpassung in Zukunft erst noch zeigen.}, subject = {Cochlea}, language = {de} } @phdthesis{Ludwig2023, author = {Ludwig, Elena Maria}, title = {Eine retrospektive Analyse laryngealer Vorl{\"a}uferl{\"a}sionen sowie deren Verlauf und Progressionsrisiko}, doi = {10.25972/OPUS-32796}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327966}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Hinter dem makroskopischen Bild einer Leukoplakie der Stimmlippen k{\"o}nnen sich verschiedene histopathologische Diagnosen, wie Hyper- oder Parakeratosen, unterschiedliche Dysplasieschweregrade oder ein invasives Karzinom, verbergen. Die Diagnose wird durch Exzision und histopathologische Beurteilung gestellt, gefolgt von einer Einteilung je nach Klassifikationssystem. Die existierenden Klassifikationssysteme sind in ihrer Aussagekraft bez{\"u}glich des Progressionsrisikos der verschiedenen Vorl{\"a}uferl{\"a}sionen und der daraus resultierenden Behandlungsempfehlung eingeschr{\"a}nkt. Die neue Einteilung der WHO aus dem Jahr 2017 unterscheidet „low-grade" Dysplasien (ehemals Epithelhyperplasien und leichte Dysplasie) von „high-grade" Dysplasien (ehemals m{\"a}ßige- und schwergradige Dysplasien einschließlich des Carcinoma in situ). In der vorliegenden Arbeit wurden insgesamt 392 Patienten mit laryngealen Vorl{\"a}uferl{\"a}sionen aus der Klinik und Poliklinik f{\"u}r Hals-, Nasen- und Ohrenheilkunde des Universit{\"a}tsklinikums W{\"u}rzburg untersucht. Es waren insbesondere M{\"a}nner im Durchschnittsalter von 59,9 Jahren betroffen. Zudem wird ein Raucheranteil von 85,1 \% beschrieben. Im Verlauf entwickelten 57 Patienten (14,5\%) ein invasives Karzinom. Mit steigendem Dysplasieschweregrad konnte eine zunehmende Entartungstendenz beobachtet werden. Patienten mit der initialen Diagnose einer Hyper- oder Parakeratose ohne Dysplasie (5,6\%) bzw. einer leichtgradigen Dysplasie (8,9\%) wiesen ein signifikant geringeres Entartungsrisiko auf als Patienten mit h{\"o}hergradigen dysplastischen Ver{\"a}nderungen (p<0,001). M{\"a}ßiggradige (41\%) und schwergradige Dysplasien (43,5\%) bzw. Carcinomata in situ (54,5\%) wiesen ein vergleichbar hohes Progressionsrisiko auf. M{\"a}ßige Dysplasien wurden in bisherigen Arbeiten bez{\"u}glich ihres Entartungsrisikos eher untersch{\"a}tzt und oftmals mit den leichtgradigen Dysplasien in einer Gruppe zusammengefasst. Die aktuell erhobenen Daten weisen jedoch auf ein h{\"o}her als urspr{\"u}nglich angenommenes Entartungsrisiko hin, sodass aufgrund des hohen Progressionsrisikos die Aufnahme in die Kategorie der „high-grade" Dysplasien gerechtfertigt scheint. Es l{\"a}sst sich zudem beobachten, dass der Zeitraum in dem sich aus einer schwergradigen Dysplasie (45 Wochen) bzw. einem Carcinoma in situ (66,2 Wochen) ein Larynxkarzinom entwickelt, k{\"u}rzer ist als der der m{\"a}ßigen Dysplasien (117,1 Woche). Weitere Studien sind erforderlich, um die neu gewonnen Erkenntnisse zu validieren, das neue Klassifikationssystem der WHO 2017 in die klinische Praxis zu integrieren und ein besseres Verst{\"a}ndnis der zugrunde liegenden Pathomechanismen zu entwickeln.}, subject = {Kehlkopf}, language = {de} } @phdthesis{EiterverhSeidl2023, author = {Eiter [verh. Seidl], Rafael}, title = {Untersuchungen zum Einfluss von Wundsekret auf Zellvermehrung, Chemoresistenzentwicklung, Zellzyklus und die Induktion einer Epithelial-mesenchymalen Transition in Tumorzellen von Kopf und Hals}, doi = {10.25972/OPUS-32678}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326782}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Tumore von Kopf und Hals gehen weiterhin mit einer schlechten Prognose einher. Im Rahmen einer operativen Therapie tritt Wundsekret (WS) aus, welches der Wundheilung dient. Dieses kann in Kontakt mit Tumorzellen bzw. Resttumor in der Wunde kommen. Im Rahmen der vorliegenden Arbeit wurde die Frage nach dem Einfluss von Wundsekret auf Zellvermehrung, Chemoresistenzentwicklung, den Zellzyklus und die Induktion einer Epithelial-mesenchymalen Transition (EMT) in Tumorzellen von Kopf und Hals gestellt. Hierf{\"u}r wurde das WS von Tag1 und das WS von Tag 2 im Dotblot auf seine Zytokinzusammensetzung analysiert. Zwei Tumorzelllinien von Kopf und Hals, FaDu und HlaC78, wurden mit WSTag1 und WSTag2 behandelt und untersucht, welche Effekte das WS auf die Zellen hat. Verwendet wurden ein Proliferationsassay, eine Zellzyklusuntersuchung und Apoptosetestung mittels FACS, eine PCR, ein Spheroidmodell und die Lichtmikroskopie. Im WS wurden erh{\"o}hte Konzentrationen verschiedener Zytokine, insbesondere von IL-6, nachgewiesen. Gezeigt werden konnte eine gesteigerte Proliferationsrate der Tumorzellen unter WS-Behandlung, jedoch keine ver{\"a}nderte Verteilung der Zellzyklusphasen. In HlaC78-Zellen konnte eine vermehrte Vitalit{\"a}t nach Cisplatinbehandlung nachgewiesen werden. In beiden Tumorzelllinien fand sich eine vermehrte Exprimierung von Snail 1, Snail 2 und Vimentin. E-Cadherin wurde vermindert exprimiert. Twist und N-Cadherin wiesen keine Ver{\"a}nderungen auf. Es zeigte sich eine vermehrte Migration der Tumorzellen in die Umgebung. Die Zellen wiesen nach Behandlung mit WS vermehrt mesenchymale Zeichen auf. Es konnte kein Unterschied der Auswirkungen einer Behandlung mit WSTag1 im Vergleich zu einer Behandlung mit WSTag2 festgestellt werden. Insgesamt scheint WS in Tumorzellen von Kopf und Hals einen EMT-artigen Prozess in Gang zu setzen, also eine partial EMT (pEMT). Als m{\"o}gliche Ausl{\"o}ser dieser Ver{\"a}nderungen kommen die im WS nachgewiesenen Zytokine und v. a. IL-6 in Frage.}, subject = {Wundheilung}, language = {de} } @article{TopsakalAgrawalAtlasetal.2022, author = {Topsakal, Vedat and Agrawal, Sumit and Atlas, Marcus and Baumgartner, Wolf-Dieter and Brown, Kevin and Bruce, Iain A. and Dazert, Stefan and Hagen, Rudolf and Lassaletta, Luis and Mlynski, Robert and Raine, Christopher H. and Rajan, Gunesh P. and Schmutzhard, Joachim and Sprinzl, Georg Mathias and Staecker, Hinrich and Usami, Shin-ichi and Van Rompaey, Vincent and Zernotti, Mario and Heyning, Paul van de}, title = {Minimally traumatic cochlear implant surgery: expert opinion in 2010 and 2020}, series = {Journal of Personalized Medicine}, volume = {12}, journal = {Journal of Personalized Medicine}, number = {10}, issn = {2075-4426}, doi = {10.3390/jpm12101551}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-288196}, year = {2022}, abstract = {This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.}, language = {en} } @phdthesis{Voelker2023, author = {V{\"o}lker, Christine Irma Annikki}, title = {In-vitro-Analyse der Maturation und Interaktion neuronaler Stammzellen des Nucleus Cochlearis der Ratte}, doi = {10.25972/OPUS-32317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323173}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Im Jahre 2011 wurden erstmals neuronale Stammzellen (NSCs) im Nucleus Cochlearis (N.C.) der Ratte beschrieben (Rak et al. 2011). Um diese Zellen besser zu charakterisieren, war das Ziel der vorliegenden Arbeit, die NSCs des N.C. im Hinblick auf ihre Maturation und Interaktion in neuronalen Netzwerken sowie auf die M{\"o}glichkeiten nichtinvasiver Beeinflussung dieser Zellen zu untersuchen und diese mit prim{\"a}ren Neuronen des N.C. zu vergleichen. F{\"u}r die Untersuchungen waren intrazellul{\"a}re Calcium-Ionen (Ca2+) von besonderem Interesse, da diese {\"u}ber spannungsgesteuerte Ca2+-Kan{\"a}le (VGCCs) und deren Spontanoszillationen indirekt die Aktivit{\"a}t und Differenzierung der Neurone widerspiegeln k{\"o}nnten. F{\"u}r die Analyse wurden N.C.s von P6 Ratten mikroskopisch pr{\"a}pariert und nach Dissoziation in Einzelzellen die NSCs f{\"u}r 8 Wochen in Stammzellmedium kultiviert oder direkt als prim{\"a}re Neurone im Stammzellmedium ausplattiert. Zur Vorbereitung der Untersuchungen fand eine Kultivierung der jeweiligen Zellen f{\"u}r 4 Tage in Differenzierungsmedium statt. Anschließend wurden sie f{\"u}r Calcium-Imaging-Messungen mit dem Ca2+-sensitiven Fluorophor Oregon Green BAPTA-1 beladen. Zum einen wurde eine Analyse der Grundaktivit{\"a}ten innerhalb der Zellareale und im neuronalen Netzwerk im Verlauf der Maturation durchgef{\"u}hrt. Zum anderen fand am Tag 4 der Zelldifferenzierung (DIF d4) eine Untersuchung der qualitativen und quantitativen Verteilung von VGCCs {\"u}ber die Zugabe der Ca2+-Kanalinhibitoren Nifedipin, ω-Conotoxin MVIIC, Kurtoxin und SNX-482 statt. In jedem Fall wurden die Zellen anschließend mit PFA fixiert und immunzytologisch untersucht. Zudem wurde eine Markierung der VGCCs mit dem Antik{\"o}rper anti-Ca2+-Channel-(1 Subunit)-Pan vorgenommen. Innerhalb der Ergebnisse konnte eine Abh{\"a}ngigkeit der neuronalen Reifung von der Zellaktivit{\"a}t in Form von Ca2+-Str{\"o}men nachgewiesen werden. Hierf{\"u}r zeigte sich urs{\"a}chlich eine Variation im qualitativen und quantitativen Vorkommen von VGCCs und in ihrer Spontanaktivit{\"a}t innerhalb der Zellareale im Verlauf der neuronalen Maturation. NSCs zeigten ein {\"a}hnliches Verhalten wie prim{\"a}r kultivierte Neurone - sowohl bez{\"u}glich ihres Aktivit{\"a}tsmusters w{\"a}hrend der Differenzierung als auch bez{\"u}glich ihrer M{\"o}glichkeit der Inhibierung, was auf eine {\"a}hnliche Expression von VGCCs hinweisen k{\"o}nnte. Die h{\"o}chste Aktivit{\"a}t zeigte sich in beiden F{\"a}llen bei DIF d4. Die neurogene Nische, welche in der Literatur sowohl bei Ratten (Rak et al. 2011) als auch bei M{\"a}usen (Volkenstein et al. 2013) im N.C. nachweisbar war, k{\"o}nnte somit zur Analysierung pathologischer Prozesse sowie auch zu deren Behandlung in Betracht gezogen werden. Zusammenfassend konnte in der vorliegenden Dissertation eine Charakterisierung des N.C. der H{\"o}rbahn in elektrophysiologischer und biochemischer Hinsicht erreicht werden. Die Ans{\"a}tze dieser Arbeit k{\"o}nnten in Zukunft zu Therapieoptionen der H{\"o}rrehabilitation auf dieser Ebene beitragen.}, subject = {Nucleus cochlearis anterior}, language = {de} } @article{RakVoelkerTaegeretal.2019, author = {Rak, Kristen and V{\"o}lker, Johannes and Taeger, Johannes and Bahmer, Andreas and Hagen, Rudolf and Albrecht, Urs-Vito}, title = {Medizinische Apps in der HNO-Heilkunde}, series = {Laryngorhinootologie}, volume = {98}, journal = {Laryngorhinootologie}, number = {S 01}, doi = {10.1055/a-0740-4866}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224948}, pages = {S253-S289}, year = {2019}, abstract = {The implementation of mobile information and communication technology in the field of health services, e.g. in the form of apps, is becoming increasingly important. Unfortunately, the necessary quality criteria are often mising. Thus, it seems important, that in addition to an app controlling authority highly qualified health care professionals participate in the development of these applications. For reasons of liability, however, the physician must exercise great caution in the selection and recommendation of medical apps, especially considering, that only a few apps are certified as medical devices. There are a large number of medical apps on the market, with only a small proportion being assigned to the field of otorhinolaryngology. The areas of audiology, sleep medicine and allergology are most frequently represented. Althouhgh there is increasing scientific work on this topic in the field of otorhinolaryngology, there is a lack of scientific evidence of contents and results, as is generally the case of medical apps. However, there are other possibilities for users to rate medical apps regarding defined qualitiy criteria such as functionality, scientific integrity, but also data privacy. None of the apps assessed by such a evaluation tool met all the required quality criteria, but the applied instrument helped to better assess the application. However, it was possible to consider the quality criteria in the developmental process of an medical app for the field of otorhinolaryngoglogy. In summary, the present work provide a comprehensive insight into the topic "Apps in Otorhinolaryngology" with the aim to use these modern aids in a beneficial way.}, language = {de} } @article{KoepingShehataDielerSchneideretal.2018, author = {K{\"o}ping, Maria and Shehata-Dieler, Wafaa and Schneider, Dieter and Cebulla, Mario and Oder, Daniel and M{\"u}ntze, Jonas and Nordbeck, Peter and Wanner, Christoph and Hagen, Rudolf and Schraven, Sebastian P.}, title = {Characterization of vertigo and hearing loss in patients with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {13}, journal = {Orphanet Journal of Rare Diseases}, doi = {10.1186/s13023-018-0882-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222818}, year = {2018}, abstract = {Background Fabry Disease (FD) is an X-linked hereditary lysosomal storage disorder which leads to a multisystemic intralysosomal accumulation of globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ involvement, patients commonly complain about vestibulocochlear symptoms like high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data especially on vertigo remain scarce. The aim of this study was to examine the prevalence and characteristics of vertigo and hearing loss in patients with FD, depending on renal and cardiac parameters and get hints about the site and the pattern of the lesions. Methods Single-center study with 57 FD patients. Every patient underwent an oto-rhino-laryngological examination as well as videonystagmography and vestibular evoked myogenic potentials (VEMPs) and audiological measurements using pure tone audiometry and auditory brainstem response audiometry (ABR). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results More than one out of three patients (35.1\%) complained about hearing loss, 54.4\% about vertigo and 28.1\% about both symptom. In 74\% a sensorineural hearing loss of at least 25 dB was found, ABR could exclude any retrocochlear lesion. Caloric testing showed abnormal values in 71.9\%, VEMPs were pathological in 68\%. A correlation between the side or the shape of hearing loss and pathological vestibular testing could not be revealed. Conclusions Hearing loss and vertigo show a high prevalence in FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as well as central nervous pathologies cause vertigo. Thus, both the site of lesion and the pathophysiological patterns seem to differ.}, language = {en} } @article{NoyaletIlgenBuerkleinetal.2022, author = {Noyalet, Laurent and Ilgen, Lukas and B{\"u}rklein, Miriam and Shehata-Dieler, Wafaa and Taeger, Johannes and Hagen, Rudolf and Neun, Tilmann and Zabler, Simon and Althoff, Daniel and Rak, Kristen}, title = {Vestibular aqueduct morphology and Meniere's disease - development of the vestibular aqueduct score by 3D analysis}, series = {Frontiers in Surgery}, volume = {9}, journal = {Frontiers in Surgery}, issn = {2296-875X}, doi = {10.3389/fsurg.2022.747517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312893}, year = {2022}, abstract = {Improved radiological examinations with newly developed 3D models may increase understanding of Meniere's disease (MD). The morphology and course of the vestibular aqueduct (VA) in the temporal bone might be related to the severity of MD. The presented study explored, if the VA of MD and non-MD patients can be grouped relative to its angle to the semicircular canals (SCC) and length using a 3D model. Scans of temporal bone specimens (TBS) were performed using micro-CT and micro flat panel volume computed tomography (mfpVCT). Furthermore, scans were carried out in patients and TBS by computed tomography (CT). The angle between the VA and the three SCC, as well as the length of the VA were measured. From these data, a 3D model was constructed to develop the vestibular aqueduct score (VAS). Using different imaging modalities it was demonstrated that angle measurements of the VA are reliable and can be effectively used for detailed diagnostic investigation. To test the clinical relevance, the VAS was applied on MD and on non-MD patients. Length and angle values from MD patients differed from non-MD patients. In MD patients, significantly higher numbers of VAs could be assigned to a distinct group of the VAS. In addition, it was tested, whether the outcome of a treatment option for MD can be correlated to the VAS.}, language = {en} } @article{BieniussaKahramanSkornickaetal.2022, author = {Bieniussa, Linda and Kahraman, Baran and Skornicka, Johannes and Schulte, Annemarie and Voelker, Johannes and Jablonka, Sibylle and Hagen, Rudolf and Rak, Kristen}, title = {Pegylated insulin-like growth factor 1 attenuates hair cell loss and promotes presynaptic maintenance of medial olivocochlear cholinergic fibers in the cochlea of the progressive motor neuropathy mouse}, series = {Frontiers in Neurology}, volume = {13}, journal = {Frontiers in Neurology}, issn = {1664-2295}, doi = {10.3389/fneur.2022.885026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276669}, year = {2022}, abstract = {The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.}, language = {en} } @article{HerrmannMuellerGraffKaulitzetal.2022, author = {Herrmann, David P. and M{\"u}ller-Graff, Franz-Tassilo and Kaulitz, Stefan and Cebulla, Mario and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-17732-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300197}, year = {2022}, abstract = {This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion.}, language = {en} } @article{RadeloffWeissHagenetal.2021, author = {Radeloff, Katrin and Weiss, Dorothee and Hagen, Rudolf and Kleinsasser, Norbert and Radeloff, Andreas}, title = {Differentiation behaviour of adipose-derived stromal cells (ASCs) seeded on polyurethane-fibrin scaffolds in vitro and in vivo}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {8}, issn = {2227-9059}, doi = {10.3390/biomedicines9080982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245030}, year = {2021}, abstract = {Adipose-derived stromal cells (ASCs) are a promising cell source for tissue engineering and regenerative medicine approaches for cartilage replacement. For chondrogenic differentiation, human (h)ASCs were seeded on three-dimensional polyurethane (PU) fibrin composites and induced with a chondrogenic differentiation medium containing TGF-ß3, BMP-6, and IGF-1 in various combinations. In addition, in vitro predifferentiated cell-seeded constructs were implanted into auricular cartilage defects of New Zealand White Rabbits for 4 and 12 weeks. Histological, immunohistochemical, and RT-PCR analyses were performed on the constructs maintained in vitro to determine extracellular matrix (ECM) deposition and expression of specific cartilage markers. Chondrogenic differentiated constructs showed a uniform distribution of cells and ECM proteins. RT-PCR showed increased gene expression of collagen II, collagen X, and aggrecan and nearly stable expression of SOX-9 and collagen I. Rabbit (r)ASC-seeded PU-fibrin composites implanted in ear cartilage defects of New Zealand White Rabbits showed deposition of ECM with structures resembling cartilage lacunae by Alcian blue staining. However, extracellular calcium deposition became detectable over the course of 12 weeks. RT-PCR showed evidence of endochondral ossification during the time course with the expression of specific marker genes (collagen X and RUNX-2). In conclusion, hASCs show chondrogenic differentiation capacity in vitro with the expression of specific marker genes and deposition of cartilage-specific ECM proteins. After implantation of predifferentiated rASC-seeded PU-fibrin scaffolds into a cartilage defect, the constructs undergo the route of endochondral ossification.}, language = {en} } @article{MoratinIckrathScherzadetal.2021, author = {Moratin, Helena and Ickrath, Pascal and Scherzad, Agmal and Meyer, Till Jasper and Naczenski, Sebastian and Hagen, Rudolf and Hackenberg, Stephan}, title = {Investigation of the immune modulatory potential of zinc oxide nanoparticles in human lymphocytes}, series = {Nanomaterials}, volume = {11}, journal = {Nanomaterials}, number = {3}, issn = {2079-4991}, doi = {10.3390/nano11030629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234016}, year = {2021}, abstract = {Zinc oxide nanoparticles (ZnO-NP) are commonly used for a variety of applications in everyday life. In addition, due to its versatility, nanotechnology supports promising approaches in the medical sector. NP can act as drug-carriers in the context of targeted chemo- or immunotherapy, and might also exhibit autonomous immune-modulatory characteristics. Knowledge of potential immunosuppressive or stimulating effects of NP is indispensable for the safety of consumers as well as patients. In this study, primary human peripheral blood lymphocytes of 9 donors were treated with different sub-cytotoxic concentrations of ZnO-NP for the duration of 1, 2, or 3 days. Flow cytometry was performed to investigate changes in the activation profile and the proportion of T cell subpopulations. ZnO-NP applied in this study did not induce any significant alterations in the examined markers, indicating their lack of impairment in terms of immune modulation. However, physicochemical characteristics exert a major influence on NP-associated bioactivity. To allow a precise simulation of the complex molecular processes of immune modulation, a physiological model including the different components of an immune response is needed.}, language = {en} } @phdthesis{Engert2022, author = {Engert, Jonas}, title = {Untersuchung neuronaler Stammzellen des Colliculus inferior der Ratte im zeitlichen Verlauf}, doi = {10.25972/OPUS-28264}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282642}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Neural stem cells (NSCs) have been recently identified in the inferior colliculus (IC). These cells are of particular interest, as no casual therapeutic options for impaired neural structures exist. This research project aims to evaluate the neurogenic potential in the rat IC from early postnatal days until adulthood. The IC of rats from postnatal day 6 up to 48 was examined by neurosphere assays and histological sections. In free-floating IC cell cultures, neurospheres formed from animals from early postnatal to adulthood. The amount of generated neurospheres decreased in older ages and increased with the number of cell line passages. Cells in the neurospheres and the histological sections stained positively with NSC markers (Doublecortin, Sox-2, Musashi-1, Nestin, and Atoh1). Dissociated single cells from the neurospheres differentiated and were stained positively for the neural lineage markers β-III-tubulin, glial fibrillary acidic protein, and myelin basic protein. In addition, NSC markers (Doublecortin, Sox-2, CDK5R1, and Ascl-1) were investigated by qRT-PCR. In conclusion, a neurogenic potential in the rat IC was detected and evaluated from early postnatal days until adulthood. The identification of NSCs in the rat IC and their age-specific characteristics contribute to a better understanding of the development and the plasticity of the auditory pathway and might be activated for therapeutic use.}, subject = {Colliculus inferior}, language = {de} } @article{RadeloffRamosTiradoHaddadetal.2021, author = {Radeloff, Katrin and Ramos Tirado, Mario and Haddad, Daniel and Breuer, Kathrin and M{\"u}ller, Jana and Hochmuth, Sabine and Hackenberg, Stephan and Scherzad, Agmal and Kleinsasser, Norbert and Radeloff, Andreas}, title = {Superparamagnetic iron oxide particles (VSOPs) show genotoxic effects but no functional impact on human adipose tissue-derived stromal cells (ASCs)}, series = {Materials}, volume = {14}, journal = {Materials}, number = {2}, issn = {1996-1944}, doi = {10.3390/ma14020263}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222970}, year = {2021}, abstract = {Adipose tissue-derived stromal cells (ASCs) represent a capable source for cell-based therapeutic approaches. For monitoring a cell-based application in vivo, magnetic resonance imaging (MRI) of cells labeled with iron oxide particles is a common method. It is the aim of the present study to analyze potential DNA damage, cytotoxicity and impairment of functional properties of human (h)ASCs after labeling with citrate-coated very small superparamagnetic iron oxide particles (VSOPs). Cytotoxic as well as genotoxic effects of the labeling procedure were measured in labeled and unlabeled hASCs using the MTT assay, comet assay and chromosomal aberration test. Trilineage differentiation was performed to evaluate an impairment of the differentiation potential due to the particles. Proliferation as well as migration capability were analyzed after the labeling procedure. Furthermore, the labeling of the hASCs was confirmed by Prussian blue staining, transmission electron microscopy (TEM) and high-resolution MRI. Below the concentration of 0.6 mM, which was used for the procedure, no evidence of genotoxic effects was found. At 0.6 mM, 1 mM as well as 1.5 mM, an increase in the number of chromosomal aberrations was determined. Cytotoxic effects were not observed at any concentration. Proliferation, migration capability and differentiation potential were also not affected by the procedure. Labeling with VSOPs is a useful labeling method for hASCs that does not affect their proliferation, migration and differentiation potential. Despite the absence of cytotoxicity, however, indications of genotoxic effects have been demonstrated.}, language = {en} } @article{ScherzadMeyerKleinsasseretal.2020, author = {Scherzad, Agmal and Meyer, Till and Kleinsasser, Norbert and Hackenberg, Stephan}, title = {Erratum: Scherzad, A., et al. Molecular mechanisms of zinc oxide nanoparticle-induced genotoxicity short running title: Genotoxicity of ZnO NPs. Materials 2017, 10, 1427}, series = {Materials}, volume = {13}, journal = {Materials}, number = {23}, issn = {1996-1944}, doi = {10.3390/ma13235462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219440}, year = {2020}, abstract = {No abstract available}, language = {en} } @phdthesis{Kretzer2022, author = {Kretzer, Katharina}, title = {Einfluss der Form elektrischer Impulse auf die intracochle{\"a}re neuronale Antwort bei Cochlea-Implantat-Tr{\"a}gern: triphasische Pulse mit anodischer und kathodischer zweiter Phase}, doi = {10.25972/OPUS-28165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281650}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Vorliegende Arbeit besch{\"a}ftigte sich mit der Verbesserung von Defiziten der elektrischen Stimulation durch Cochlea Implantate (CI) mit alternativen Pulsformen. Dabei wurde mit elektrophysiologischen und psychophysikalischen Methoden untersucht, wie sich die Pulsformen auf die Effektivit{\"a}t der Stimulation auswirken. Es wurden pr{\"a}zisions-triphasische Pulse (pTP) mit anodischer und kathodischer zweiter Phase anhand der Daten von elf Probanden untersucht. Im Rahmen der objektiven elektrophysiologischen Messung wurde mit den unterschiedlichen Formen des pTP an drei unterschiedlichen Kontaktpositionen auf den CI-Elektrodentr{\"a}gern stimuliert, und die St{\"a}rke der jeweils evozierten neuronalen Antwort aufgezeichnet. Der subjektive psychophysikalische Test diente dazu, die pulsformspezifischen H{\"o}rschwellen zu bestimmen und wurde an zwei unterschiedlichen Kontakten auf den CI-Elektrodentr{\"a}gern durchgef{\"u}hrt. Dabei erzielten pTP, welche eine symmetrisch-triphasische Pulsform aufwiesen, geringere neuronale Antwortst{\"a}rken und h{\"o}here H{\"o}rschwellen als die pTP, die einer biphasischen Pulsform glichen. Diejenigen pTP, die biphasischen Pulsen mit anodischer erster Phase glichen, erzielten dabei die h{\"o}chsten neuronalen Antwortst{\"a}rken und die niedrigsten H{\"o}rschwellen.}, subject = {Cochlear-Implantat}, language = {de} } @article{KleinsasserWiestScherzadetal.2021, author = {Kleinsasser, N. and Wiest, F. and Scherzad, A. and Ickrath, P. and Poier, N. and Hackenberg, S.}, title = {Untersuchungen zum Sch{\"a}digungspotenzial durch den Konsum von E-Zigaretten: In-vitro-Exposition von humanen Nasenschleimhautzellen mit Propylenglykol im Air-Liquid-Interface}, series = {HNO}, volume = {69}, journal = {HNO}, doi = {10.1007/s00106-021-00998-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280329}, pages = {952-960}, year = {2021}, abstract = {Hintergrund Die E‑Zigarette erfreut sich in den letzten Jahren zunehmender Beliebtheit. Die Frage nach der Toxizit{\"a}t ist jedoch noch nicht eindeutig gekl{\"a}rt, und es herrscht global Unsicherheit im Umgang mit der E‑Zigarette. Ziel Ziel der vorliegenden Arbeit war es, Propylenglykol, ein Hauptbestandteil der Liquide, in Bezug auf m{\"o}gliche akute Entz{\"u}ndungsreaktionen, zyto- und genotoxische Auswirkungen auf humane Nasenschleimhautzellen zu untersuchen. Material und Methoden Die Nasenschleimhautzellen wurden von zehn Probanden im Air-Liquid-Interface kultiviert und anschließend mit unterschiedlichen Konzentrationen des Propylenglykols bedampft. Die Analyse erfolgte mittels Trypanblau-Test, Comet-Assay, Mikrokerntest und IL-6- und IL-8-Sandwich-ELISA. Ergebnis Der Trypanblau-Test zeigte keine Reduktion der Vitalit{\"a}t. Im Sandwich-ELISA konnte kein Anstieg der IL-6- und IL-8-Konzentrationen nachgewiesen werden. Im Comet-Assay zeigte das Olive Tail Moment eine Sch{\"a}digung im Vergleich zur Negativkontrolle in allen untersuchten Konzentrationen. Zudem zeigte sich eine dosisabh{\"a}ngige Sch{\"a}digung. Im Mikrokerntest konnte ein Unterschied zwischen dem Reinstoff und der Negativkontrolle gefunden werden. Schlussfolgerung Es zeigten sich m{\"o}glicherweise reparable DNS-Sch{\"a}digungen im Comet-Assay. Im Mikrokerntest konnten diese nur in der Reinstoffkonzentration best{\"a}tigt werden. Es sollte ein restriktiver Umgang mit der E‑Zigarette erfolgen, bis insbesondere Langzeitstudien vorliegen. Zudem ist eine eindeutige Deklaration der Inhaltsstoffe der Liquide durch die Hersteller zu fordern, um weitergehende Sch{\"a}digungspotenziale untersuchen zu k{\"o}nnen.}, language = {de} } @article{RadeloffRadeloffTiradoetal.2019, author = {Radeloff, Katrin and Radeloff, Andreas and Tirado, Mario Ramos and Scherzad, Agmal and Hagen, Rudolf and Kleinsasser, Norbert H. and Hackenberg, Stephan}, title = {Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells}, series = {Materials}, volume = {12}, journal = {Materials}, number = {1823}, doi = {10.3390/ma12111823}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224779}, pages = {1-14}, year = {2019}, abstract = {Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.}, language = {en} } @phdthesis{DerouetgebSchenkelberger2022, author = {Derouet [geb. Schenkelberger], Freya Kwen-Kwes}, title = {Entwicklung optimierter Ankopplungsbedingungen von aktiven Mittelohrimplantaten am runden Fenster}, doi = {10.25972/OPUS-27807}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278079}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Seit Mitte der 90er-Jahre gewinnen aktive Mittelohrimplantate wie die Vibrant sound bridge (VSB) zunehmend an Bedeutung. Sie k{\"o}nnen zur Rehabilitation von Schallleitungs- und Schallempfindungsst{\"o}rungen, sowie kombinierter H{\"o}rst{\"o}rungen indiziert sein. Die Vibrant sound bridge stellt eine Alternative f{\"u}r Patienten dar, bei denen aus verschiedenen Gr{\"u}nden eine Unvertr{\"a}glichkeit gegen{\"u}ber herk{\"o}mmlichen H{\"o}rger{\"a}ten besteht. Bei der Implantation des Floating mass transducers (FMT) am runden Fenster zeigte sich in der Klinik neben einer hohen Revisionsrate von bis zu 15,6 \% eine hohe Varianz der audiologischen Ergebnisse, was auf eine unkontrollierte und mangelnde Ankopplung des Floating mass transducers an das runde Fenster zur{\"u}ckzuf{\"u}hren ist. Erste Ergebnisse der kontrollierten Ankopplung am runden Fenster mit einem Kamin zeigten vielversprechende Ergebnisse. Die suffiziente Fixation des Kamins an der Rundfensternische stellt eine Herausforderung dar. Es bedarf eines Haftvermittlers, der eine suffiziente Verbindung zwischen dem Titankamin und dem darunter befindlichen Knochen am runden Fenster herstellt. Ziel der Dissertation war die Findung einer geeigneten Haftkomponente zur Fixation des Kamins am runden Fenster. Es wurden der Calciumphosphatzement HydroSet® (Fa. Stryker) und der Glasionomerzement Ketac™ Cem (Fa. ESPE 3M™ Deutschland) untersucht. In Anlehnung an DIN 13990-2 wurden nach Einwirkung physikalischen Stresses in Form von Temperatur und Feuchtigkeit die Scherhaftfestigkeit der Titanzylinder an humanen Felsenbeinknochen gemessen. Es zeigte sich eine schwach signifikant bessere Haftung f{\"u}r das Calciumphosphatzement HydroSet®, bei insgesamt geringer Scherhaftfestigkeit beider Zemente im Vergleich mit anderen zahnheilkundlichen Adh{\"a}siven der Literatur.}, language = {de} } @phdthesis{Wagner2022, author = {Wagner, Martin}, title = {Zyto- und Gentoxizit{\"a}t von Zinkoxid-Nanopartikeln in humanen mesenchymalen Stammzellen nach repetitiver Exposition und im Langzeitversuch}, doi = {10.25972/OPUS-27572}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275726}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Zinkoxid-Nanopartikel (ZnO-NP) finden in vielen Produkten des t{\"a}glichen Verbrauchs Verwendung. Daten {\"u}ber die toxikologischen Eigenschaften von ZnO-NP werden kontrovers diskutiert. Die menschliche Haut ist in Bezug auf die ZnO-NP Exposition das wichtigste Kontakt-Organ. Intakte Haut stellt eine suffiziente Barriere gegen{\"u}ber NP dar. Bei defekter Haut ist ein Kontakt zu den proliferierenden Stammzellen m{\"o}glich, sodass diese als wichtiges toxikologische Ziel f{\"u}r NP darstellen. Das Ziel dieser Dissertation war die Bewertung der genotoxischen und zytotoxischen Effekte an humanen mesenchymalen Stammzellen (hMSC) durch niedrig dosierte ZnO-NP nach 24 st{\"u}ndiger Exposition, repetitiven Expositionen und im Langzeitversuch bis zu 6 Wochen. Zytotoxische Wirkungen von ZnO-NP wurden mit 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid-Test (MTT) gemessen. Dar{\"u}ber hinaus wurde die Genotoxizit{\"a}t durch den Comet-Assay bewertet. Zur Langzeitbeobachtung bis zu 6 Wochen wurde die Transmissionselektronenmikroskopie (TEM) verwendet. Zytotoxizit{\"a}t nach 24-st{\"u}ndiger ZnO-NP-Exposition war ab einer Konzentration von 50 µg/ml nachweisbar. Genotoxizit{\"a}t konnten bereits bei Konzentrationen von 1 und 10 µg/ml ZnO-NP beschrieben werden. Wiederholte Exposition verst{\"a}rkte die Zyto-, aber nicht die Genotoxizit{\"a}t. Eine intrazellul{\"a}re NP-Akkumulation mit Penetration der Zellorganelle wurde bei einer Exposition bis zu 6 Wochen beobachtet. Die Ergebnisse deuten auf zytotoxische und genotoxisches Effekte von ZnO-NP hin. Bereits geringe Dosen von ZnO-NP k{\"o}nnen bei wiederholter Exposition toxische Wirkungen hervorrufen sowie eine langfristige Zellakkumulation. Diese Daten sollten bei der Verwendung von ZnO-NP an gesch{\"a}digter Haut ber{\"u}cksichtigt werden.}, subject = {nanoparticle}, language = {de} } @article{RadeloffRadeloffRamosTiradoetal.2020, author = {Radeloff, Katrin and Radeloff, Andreas and Ramos Tirado, Mario and Scherzad, Agmal and Hagen, Rudolf and Kleinsasser, Norbert H. and Hackenberg, Stephan}, title = {Toxicity and functional impairment in human adipose tissue-derived stromal cells (hASCs) following long-term exposure to very small iron oxide particles (VSOPs)}, series = {Nanomaterials}, volume = {10}, journal = {Nanomaterials}, number = {4}, issn = {2079-4991}, doi = {10.3390/nano10040741}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203676}, year = {2020}, abstract = {Magnetic nanoparticles (NPs), such as very small iron oxide NPs (VSOPs) can be used for targeted drug delivery, cancer treatment or tissue engineering. Another important field of application is the labelling of mesenchymal stem cells to allow in vivo tracking and visualization of transplanted cells using magnetic resonance imaging (MRI). For these NPs, however, various toxic effects, as well as functional impairment of the exposed cells, are described. The present study evaluates the influence of VSOPs on the multilineage differentiation ability and cytokine secretion of human adipose tissue derived stromal cells (hASCs) after long-term exposure. Human ASCs were labelled with VSOPs, and the efficacy of the labelling was documented over 4 weeks in vitro cultivation of the labelled cells. Unlabelled hASCs served as negative controls. Four weeks after labelling, adipogenic and osteogenic differentiation was histologically evaluated and quantified by polymerase chain reaction (PCR). Changes in gene expression of IL-6, IL-8, VEGF and caspase 3 were determined over 4 weeks. Four weeks after the labelling procedure, labelled and unlabelled hASCs did not differ in the gene expression of IL-6, IL-8, VEGF and caspase 3. Furthermore, the labelling procedure had no influence on the multidifferentiation ability of hASC. The percentage of labelled cells decreased during in vitro expansion over 4 weeks. Labelling with VSOPs and long-term intracellular disposition probably have no influence on the physiological functions of hASCs. This could be important for the future in vivo use of iron oxide NPs.}, language = {en} } @article{KrausHackenbergShehataDieleretal.2022, author = {Kraus, Fabian and Hackenberg, Stephan and Shehata-Dieler, Wafaa and Hagen, Rudolf}, title = {High-sensitivity FEES\(^{®}\) with the professional image enhancement technology "PIET"}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {1}, issn = {1434-4726}, doi = {10.1007/s00405-021-07067-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266822}, pages = {293-298}, year = {2022}, abstract = {Purpose Flexible endoscopic evaluation of swallowing (FEES\(^{®}\)) is a standard diagnostic tool in dysphagia. The combination of FEES® and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination. The new version of the "professional image enhancement technique" (PIET) provides another image enhancing system. This study investigates the eligibility of PIET in the FEES\(^{®}\) procedure. Methods Both techniques, NBI and PIET, were compared using a target system. Furthermore, the image enhancement during FEES\(^{®}\) was performed and recorded with the two systems during daily routine. Results Performing an image enhancement during FEES\(^{®}\) is possible with both systems PIET and NBI. On the target system, the contrast of the PIET showed a brighter and a more detailed picture. In dysphagia patients, no difference between PIET and NBI was detected. Conclusion PIET proved to be non-inferior to NBI during image enhancement FEES\(^{®}\). So far, image enhancement FEES\(^{®}\) was exclusively connected to NBI. With the PIET system, an alternative endoscopy technology is available for certain indications.}, language = {en} } @article{GehrkeScherzadHagenetal.2022, author = {Gehrke, Thomas and Scherzad, Agmal and Hagen, Rudolf and Hackenberg, Stephan}, title = {Deep neck infections with and without mediastinal involvement: treatment and outcome in 218 patients}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {3}, issn = {1434-4726}, doi = {10.1007/s00405-021-06945-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266814}, pages = {1585-1592}, year = {2022}, abstract = {Purpose Infections of the deep neck, although becoming scarcer due to the widespread use of antibiotics, still represent a dangerous and possibly deadly disease, especially when descending into the mediastinum. Due to the different specialities involved in the treatment and the heterogenous presentation of the disease, therapeutic standard is still controversial. This study analyzes treatment and outcome in these patients based on a large retrospective review and proposes a therapeutic algorithm. Methods The cases of 218 adult patients treated with deep neck abscesses over a 10-year period at a tertiary university hospital were analyzed retrospectively. Clinical, radiological, microbiological and laboratory findings were compared between patients with and without mediastinal involvement. Results Forty-five patients (20.64\%) presented with abscess formation descending into the mediastinum. Those patients had significantly (all items p < 0.0001) higher rates of surgical interventions (4.27 vs. 1.11) and tracheotomies (82\% vs. 3.4\%), higher markers of inflammation (CRP 26.09 vs. 10.41 mg/dl), required more CT-scans (3.58 vs. 0.85), longer hospitalization (39.78 vs 9.79 days) and more frequently needed a change in antibiotic therapy (44.44\% vs. 6.40\%). Multi-resistant pathogens were found in 6.67\% vs. 1.16\%. Overall mortality rate was low with 1.83\%. Conclusion Despite of the high percentage of mediastinal involvement in the present patient collective, the proposed therapeutic algorithm resulted in a low mortality rate. Frequent CT-scans, regular planned surgical revisions with local drainage and lavage, as well as an early tracheotomy seem to be most beneficial regarding the outcome.}, language = {en} } @article{MuellerGraffIlgenSchendzielorzetal.2022, author = {M{\"u}ller-Graff, Franz-Tassilo and Ilgen, Lukas and Schendzielorz, Philipp and Voelker, Johannes and Taeger, Johannes and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {5}, issn = {1434-4726}, doi = {10.1007/s00405-021-06924-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266798}, pages = {2309-2319}, year = {2022}, abstract = {Purpose For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCT\(_{SECO}\)) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. Methods Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCT\(_{SECO}\)) of patients with and without implanted electrodes. Results Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCT\(_{SECO}\) with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCT\(_{SECO}\) compared to MSCT. Conclusion The combination of fpVCT\(_{SECO}\) and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.}, language = {en} } @article{RajeswaranTavoraVieiraMertensetal.2022, author = {Rajeswaran, Ranjith and Tavora-Vieira, Dayse and Mertens, Griet and Dillon, Margaret and Narayan, Saranya and Kameswaran, Mohan and Kurz, Anja}, title = {Audiological practice and COVID-19: recommendations that audiological centers can use to maintain the safety and quality of service-expert opinion}, series = {European Archives of Oto-Rhino-Laryngology}, volume = {279}, journal = {European Archives of Oto-Rhino-Laryngology}, number = {3}, issn = {1434-4726}, doi = {10.1007/s00405-021-06766-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266774}, pages = {1251-1256}, year = {2022}, abstract = {Purpose Audiology is an essential service for some patient groups and some interventions. This article sets forth experience-based recommendations for how audiological centers can continue to safely and effectively function during COVID-19. Methods The recommendations are the result of panel discussion and are based on the clinical experience of the panelists/authors. Results The recommendations cover which patient groups and which interventions should be treated when and whether this can be performed in the clinic or remotely; how to maintain the safety of workplace via optimizing patient flow within the clinic and the sanitation of rooms and equipment; and overcoming communication challenges that COVID-19 intensifies. Conclusion For essential audiological services to continue under COVID-19, safety measures must be implemented and maintained, and treatment and communication strategies must be adapted to offset communication difficulties due to personal protective equipment (PPE) and social distancing and to bolster patient confidence. In short, it is vital that staff feel safe, that patients either feel the clinic is safe enough to visit or that remote treatment may be an option, and that clinics and patients have a broad agreement on the urgency of any needed service. We hope that these recommendations help clinics effectively accomplish these goals.}, language = {en} } @article{MeyerGerhardHartmannLodesetal.2021, author = {Meyer, Till Jasper and Gerhard-Hartmann, Elena and Lodes, Nina and Scherzad, Agmal and Hagen, Rudolf and Steinke, Maria and Hackenberg, Stephan}, title = {Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors}, series = {PLoS One}, volume = {16}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0257470}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264736}, year = {2021}, abstract = {Background The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT. Methods Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software. Results The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly. Conclusion In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.}, language = {en} } @article{TaegerMuellerGraffLukasetal.2021, author = {Taeger, Johannes and M{\"u}ller-Graff, Franz-Tassilo and Lukas, Ilgen and Schendzielorz, Philipp and Hagen, Rudolf and Neun, Tilman and Rak, Kristen}, title = {Cochlear duct length measurements in computed tomography and magnetic resonance imaging using newly developed techniques}, series = {OTO Open}, volume = {5}, journal = {OTO Open}, number = {3}, doi = {10.1177/2473974X211045312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263922}, pages = {1-8}, year = {2021}, abstract = {Objective Growing interest in measuring the cochlear duct length (CDL) has emerged, since it can influence the selection of cochlear implant electrodes. Currently the measurements are performed with ionized radiation imaging. Only a few studies have explored CDL measurements in magnetic resonance imaging (MRI). Therefore, the presented study aims to fill this gap by estimating CDL in MRI and comparing it with multislice computed tomography (CT). Study Design Retrospective data analyses of 42 cochleae. Setting Tertiary care medical center. Methods Diameter (A value) and width (B value) of the cochlea were measured in HOROS software. The CDL and the 2-turn length were determined by the elliptic circular approximation (ECA). In addition, the CDL, the 2-turn length, and the angular length were determined via HOROS software by the multiplanar reconstruction (MPR) method. Results CDL values were significantly shorter in MRI by MPR (d = 1.38 mm, P < .001) but not by ECA. Similar 2-turn length measurements were significantly lower in MRI by MPR (d = 1.67 mm) and ECA (d = 1.19 mm, both P < .001). In contrast, angular length was significantly higher in MRI (d = 26.79°, P < .001). When the values were set in relation to the frequencies of the cochlea, no clinically relevant differences were estimated (58 Hz at 28-mm CDL). Conclusion In the presented study, CDL was investigated in CT and MRI by using different approaches. Since no clinically relevant differences were found, diagnostics with radiation may be omitted prior to cochlear implantation; thus, a concept of radiation-free cochlear implantation could be established.}, language = {en} } @article{TaegerMuellerGraffNeunetal.2021, author = {Taeger, Johannes and M{\"u}ller-Graff, Franz-Tassilo and Neun, Tilmann and K{\"o}ping, Maria and Schendzielorz, Philipp and Hagen, Rudolf and Rak, Kristen}, title = {Highly precise navigation at the lateral skull base by the combination of flat-panel volume CT and electromagnetic navigation}, series = {Science Progress}, volume = {104}, journal = {Science Progress}, number = {3}, issn = {2047-7163}, doi = {10.1177/00368504211032090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250268}, year = {2021}, abstract = {This study aimed to evaluate the feasibility and accuracy of electromagnetic navigation at the lateral skull base in combination with flat panel volume computed tomography (fpVCT) datasets. A mastoidectomy and a posterior tympanotomy were performed on 10 samples of fresh frozen temporal bones. For registration, four self-drilling titanium screws were applied as fiducial markers. Multi-slice computed tomography (MSCT; 600 µm), conventional flat panel volume computed tomography (fpVCT; 466 µm), micro-fpVCT (197 µm) and secondary reconstructed fpVCT (100 µM) scans were performed and data were loaded into the navigation system. The resulting fiducial registration error (FRE) was analysed, and control of the navigation accuracy was performed. The registration process was very quick and reliable with the screws as fiducials. Compared to using the MSCT data, the micro-fpVCT data led to significantly lower FRE values, whereas conventional fpVCT and secondary reconstructed fpVCT data had no advantage in terms of accuracy. For all imaging modalities, there was no relevant visual deviation when targeting defined anatomical points with a navigation probe. fpVCT data are very well suited for electromagnetic navigation at the lateral skull base. The use of titanium screws as fiducial markers turned out to be ideal for comparing different imaging methods. A further evaluation of this approach by a clinical trial is required.}, language = {en} } @article{GehrkeHackenbergTecleetal.2021, author = {Gehrke, Thomas and Hackenberg, Stephan and Tecle, Nyat and Hagen, Rudolf and Scherzad, Agmal}, title = {Tuberculosis in the Head and Neck: Changing Trends and Age-Related Patterns}, series = {The Laryngoscope}, volume = {131}, journal = {The Laryngoscope}, number = {12}, doi = {10.1002/lary.29668}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257524}, pages = {2701-2705}, year = {2021}, abstract = {Objective To evaluate changing trends in patient collectives, age-related patterns of manifestation, and diagnostic pathways of patients with extrapulmonary head and neck tuberculosis (TB), and to provide strategies to fasten diagnosis in these patients. Study design Case control study. Methods A 10-year retrospective analysis of 35 patients diagnosed with extrapulmonary TB in the head and neck at a tertiary university institution from 2009 to 2019, with special focus on the influence of the patient's age on consideration of TB and clinical patterns. Results The vast majority of patients younger than 40 years had their origin in countries with high TB burden (P = .0003), and TB was considered very early as a differential diagnosis (P = .0068), while most patients older than 40 years were domestic citizens initially suspected for a malignancy, who more often had an underlying immunosuppressive condition (0.0472). Most frequent manifestations in both groups were the lymph nodes, larynx, and oropharynx. Surprisingly, no differences in the rates of open TB or history of TB infection in the family anamnesis were found. Conclusion The two groups of patients found most often are younger patients migrating from regions with high TB burden and elderly domestic patients suffering from immunosuppressive conditions, with the latter often being misdiagnosed as malignancies. TB remains an important but difficult differential diagnosis, due to the initially unspecific symptoms and the great variety in the presentation of manifestations in the head and neck.}, language = {en} } @article{MeyerStoethMoratinetal.2021, author = {Meyer, Till Jasper and St{\"o}th, Manuel and Moratin, Helena and Ickrath, Pascal and Herrmann, Marietta and Kleinsasser, Norbert and Hagen, Rudolf and Hackenberg, Stephan and Scherzad, Agmal}, title = {Cultivation of head and neck squamous cell carcinoma cells with wound fluid leads to cisplatin resistance via epithelial-mesenchymal transition induction}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms22094474}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258722}, year = {2021}, abstract = {Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.}, language = {en} } @article{SivarajanKessieOberwinkleretal.2021, author = {Sivarajan, Rinu and Kessie, David Komla and Oberwinkler, Heike and Pallmann, Niklas and Walles, Thorsten and Scherzad, Agmal and Hackenberg, Stephan and Steinke, Maria}, title = {Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {11}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2021.797491}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253302}, year = {2021}, abstract = {To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC\(^-\). Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.}, language = {en} } @article{VoelkerVoelkerEngertetal.2021, author = {Voelker, Johannes and Voelker, Christine and Engert, Jonas and Goemann, Nikolas and Hagen, Rudolf and Rak, Kristen}, title = {Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells}, series = {Cells}, volume = {10}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells10102802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248482}, year = {2021}, abstract = {Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration.}, language = {en} } @article{IckrathSpruegelBeyersdorfetal.2021, author = {Ickrath, Pascal and Spr{\"u}gel, Lisa and Beyersdorf, Niklas and Scherzad, Agmal and Hagen, Rudolf and Hackenberg, Stephan}, title = {Detection of Candida albicans-Specific CD4+ and CD8+ T Cells in the Blood and Nasal Mucosa of Patients with Chronic Rhinosinusitis}, series = {Journal of Fungi}, volume = {7}, journal = {Journal of Fungi}, number = {6}, issn = {2309-608X}, doi = {10.3390/jof7060403}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239671}, year = {2021}, abstract = {Candida albicans is ubiquitously present, and colonization in the nose and oral cavity is common. In healthy patients, it usually does not act as a pathogen, but in some cases can cause diseases. The influence of C. albicans as a trigger of T cell activation on the pathogenesis of chronic rhinosinusitis (CRS) is controversial, and its exact role is not clear to date. The aim of the present study was to detect and characterize C. albicans-specific CD4+ and CD8+ T cells in patients with CRS, with and without nasal polyps. Tissue and blood samples were collected from patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyps (CRSsNP), and from healthy controls. A peptide pool derived from C. albicans antigen was added to tissue and blood samples. After 6 days, lymphocytes were analyzed by multicolor flow cytometry. Activation was assessed by the intracellular marker Ki-67, and the cytokine secretion was measured. Tissue CD8+ T cells of CRSsNP patients showed a significantly higher proportion of Ki-67+ cells after activation with C. albicans antigen compared to peripheral blood CD8+ T cells. Cytokine secretion in response to C. albicans antigen was similar for all study groups. In this study, C. albicans-specific CD4+ and CD8+ T cells were detected in peripheral blood and mucosal tissue in all study groups. In patients suffering from CRSsNP, C. albicans-specific CD8+ T cells were relatively enriched in the nasal mucosa, suggesting that they might play a role in the pathogenesis of CRSsNP.}, language = {en} } @phdthesis{Pieper2021, author = {Pieper, Sabrina H.}, title = {Temporal information transfer by electrical stimulation in auditory implants}, doi = {10.25972/OPUS-22388}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223887}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {In deafness, which is caused by the malfunctioning of the inner ear, an implantation of a cochlear implant (CI) is able to restore hearing. The CI is a neural prosthesis that is located within the cochlea. It replaces the function of the inner hair cells by direct electrical stimulation of the auditory nerve fibers. The CI enables many deaf or severe hearing-impaired people to achieve a good speech perception. Nevertheless, there is a lot of potential for further improvements. Compared to normal-hearing listeners rate pitch discrimination is much worse. Rate pitch discrimination is the ability to distinguish the pitch of two stimuli with two different pulse rates. This ability is important for enjoying music as well as speech perception (in noise). Further, the small dynamic range in electrical hearing (compared to normal-hearing listeners) and therefore the small intensity resolution limits the performance of CI users. Both, rate pitch coding and dynamic range were investigated in this doctoral thesis. For the first issue, a pitch discrimination task was designed to determine the just-noticeable-difference (JND) in pitch with 200 and 400 pps as reference. Additionally to the default biphasic pulse (single pulse) the experiment was performed with double pulses. The double pulse consists out of two biphasic pulses directly after each other and a small interpulse interval (IPI) in between. Three different IPIs (15, 50, and 150 µs) were tested. The statistical analysis of JNDs revealed no significant effects between stimulation with single-pulse or double-pulse trains. A follow-up study investigated an alternating pulse train consisting of single and double pulses. To investigate if the 400 pps alternating pulse train is comparable in pitch with the 400 pps single-pulse train, a pairwise pitch comparison test was conducted. The alternating pulse train was compared with single-pulse trains at 200, 300 and 400 pps. The results showed that the alternating pulse train is for most subjects similar in pitch with the 200 pps single-pulse train. Therefore, pitch perception seemed to be dominated by the double pulses within the pulse train. Accordingly, double pulses with different amplitudes were tested. Based on the facilitation effect, a larger neuronal response was expected by stimulating with two pulses with a short IPI within the temporal facilitation range. In other studies, this effect was shown to be maximal in CIs of the manufacturer Cochlear, with first pulse amplitudes set at or slightly below the electrically evoked compound action potential (ECAP) threshold. The second pulse amplitude did not influence the facilitation effect and therefore could be choose at will. Similarly, this effect was tested in this thesis with CIs of the manufacturer MED-EL. Nevertheless, to achieve a proper signal-to-noise ratio, technical issues had to be addressed like a high noise floor, resulting in incorrect determination of the ECAP threshold. After solving this issues, the maximum facilitation effect was around the ECAP threshold as in the previous study with Cochlear. For future studies this effect could be used in a modified double pulse rate pitch experiment with the first pulse amplitude at ECAP threshold and the second pulse amplitude variable to set the most comfortable loudness level (MCL). The last study within this thesis investigated the loudness perception at two different loudness levels and the resulting dynamic range for different interphase-gaps (IPG). A larger IPG can reduce the amplitude at same loudness level to save battery power. However, it was unknown if the IPG has an influence on the dynamic range. Different IPGs (10 and 30 µs) were compared with the default IPG (2.1 µs) in a loudness matching experiment. The experiment was performed at the most comfortable loudness level (MCL) of the subject and the amplitude of half the dynamic range (50\%-ADR). An upper dynamic range was calculated from the results of MCL and 50\%-ADR (therefore not the whole dynamic range was covered). As expected from previous studies a larger IPG resulted in smaller amplitudes. However, the observed effect was larger at MCL than at 50\%-ADR which resulted in a smaller upper dynamic range. This is the first time a decrease of this dynamic range was shown.}, subject = {Cochlear-Implantat}, language = {en} } @phdthesis{Hallak2021, author = {Hallak, Basel}, title = {„Direct Drive Simulation" - Entwicklung spezieller pr{\"a}operativer H{\"o}rtestverfahren vor Implantation aktiver Mittelohrprothesen}, doi = {10.25972/OPUS-24316}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243164}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Einleitung: Die sog. Direct-Drive-Simulation (DDS) bietet Patienten pr{\"a}operativ eine Klangsimulation des "Vibrant Soundbridge®-H{\"o}rens". Ein Floating-Mass-Transducer (FMT) wird auf das Trommelfell oder die rekonstruierte Paukenabdeckung aufgesetzt, wor{\"u}ber den Patienten Testsignale dargeboten werden. Ziel der Arbeit war die Evaluation einer Weiterentwicklung des Tests hin zur DDS-Tonaudiometrie und DDS-Sprachaudiometrie. Bei Best{\"a}tigung der ersten Hypothese, soll dar{\"u}ber hinaus gepr{\"u}ft werden, ob eine Hirnstammaudiometrie (BERA) {\"u}ber den DDS durchgef{\"u}hrt werden kann. Ziel der vorliegenden Arbeit ist es Referenzdaten an einer Population Normalh{\"o}render zu generieren. Zusammenfassung: Sowohl die DDS-Ton- und Sprachaudiometrie als auch die Ableitung einer BERA {\"u}ber den DDS-FMT sind m{\"o}glich. Mit der DDS-BERA besteht nun erstmals die M{\"o}glichkeit eines objektiven DDS-Tests pr{\"a}operativ. Die notwendige Einsch{\"a}tzung der Ankopplungsqualit{\"a}t zur korrekten Interpretation der DDS-BERA l{\"a}sst sich elegant mit Hilfe der DDS-Tonaudiometrie ermitteln.}, subject = {Hals-Nasen-Ohrheilkunde}, language = {de} } @article{KuehnSchoenEdelmannetal.2013, author = {K{\"u}hn, Heike and Sch{\"o}n, Franz and Edelmann, Karola and Brill, Stefan and M{\"u}ller, Joachim}, title = {The Development of Lateralization Abilities in Children with Bilateral Cochlear Implants}, series = {ORL}, volume = {75}, journal = {ORL}, number = {2}, issn = {0301-1569}, doi = {10.1159/000347193}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196375}, pages = {55-67}, year = {2013}, abstract = {Objectives: The purpose of this study was to investigate the development of lateralization skills in children who received bilateral cochlear implants (CIs) in sequential operations. Methods: The lateralization skills of 9 children with a mean age of 4.1 years at the first surgery and 5.5 years at the second surgery were assessed at 3 time intervals. Children were assessed with a 3-loudspeaker setup (front, left and right) at 0.9 years (interval I) and 1.6 years (interval II) after the second implantation, and after 5.3 years of bilateral implant use (interval III) with a 9-loudspeaker setup in the frontal horizontal plane between -90° and 90° azimuth. Results: With bilateral implants, a significant decrease in lateralization error was noted between test interval I (45.0°) and II (23.3°), with a subsequent significant decrease at test interval III (4.7°). Unilateral performance with the CI did not improve significantly between the first 2 intervals; however, there was a bias of responses towards the unilateral side by test interval III. Conclusions: The lateralization abilities of children with bilateral CIs develop in a relatively short period of time (1-2 years) after the second implant. Children appear to be able to acquire binaural skills after bilateral cochlear implantation.}, language = {en} } @article{MatthiesBrillKagaetal.2013, author = {Matthies, Cordula and Brill, Stefan and Kaga, Kimitaka and Morita, Akio and Kumakawa, Kozo and Skarzynski, Henryk and Claassen, Andre and Hui, Yau and Chiong, Charlotte and M{\"u}ller, Joachim and Behr, Robert}, title = {Auditory Brainstem Implantation Improves Speech Recognition in Neurofibromatosis Type II Patients}, series = {ORL}, volume = {75}, journal = {ORL}, number = {5}, issn = {0301-1569}, doi = {10.1159/000350568}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196383}, pages = {282-295}, year = {2013}, abstract = {This prospective study aimed to determine speech understanding in neurofibromatosis type II (NF2) patients following implantation of a MED-EL COMBI 40+ auditory brainstem implant (ABI). Patients (n = 32) were enrolled postsurgically. Nonauditory side effects were evaluated at fitting and audiological performance was determined using the Sound Effects Recognition Test (SERT), Monosyllable-Trochee-Polysyllable (MTP) test and open-set sentence tests. Subjective benefits were determined by questionnaire. ABI activation was documented in 27 patients, 2 patients were too ill for testing and 3 patients were without any auditory perception. SERT and MTP outcomes under auditory-only conditions improved significantly between first fitting and 12-month follow-up. Open-set sentence recognition improved from 5\% at first fitting to 37\% after 12 months. The number of active electrodes had no significant effect on performance. All questionnaire respondents were 'satisfied' to 'very satisfied' with their ABI. An ABI is an effective treatment option in NF2 patients with the potential to provide open-set speech recognition and subjective benefits. To our knowledge, the data presented herein is exceptional in terms of the open-set speech perception achieved in NF2 patients.}, language = {en} } @article{MuellerBrillHagenetal.2012, author = {M{\"u}ller, Joachim and Brill, Stefan and Hagen, Rudolf and Moeltner, Alexander and Brockmeier, Steffi-Johanna and Stark, Thomas and Helbig, Silke and Maurer, Jan and Zahnert, Thomas and Zierhofer, Clemens and Nopp, Peter and Anderson, Ilona}, title = {Clinical Trial Results with the MED-EL Fine Structure Processing Coding Strategy in Experienced Cochlear Implant Users}, series = {ORL}, volume = {74}, journal = {ORL}, number = {4}, issn = {0301-1569}, doi = {10.1159/000337089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196396}, pages = {185-198}, year = {2012}, abstract = {Objectives: To assess the subjective and objective performance of the new fine structure processing strategy (FSP) compared to the previous generation coding strategies CIS+ and HDCIS. Methods: Forty-six adults with a minimum of 6 months of cochlear implant experience were included. CIS+, HDCIS and FSP were compared in speech perception tests in noise, pitch scaling and questionnaires. The randomized tests were performed acutely (interval 1) and again after 3 months of FSP experience (interval 3). The subjective evaluation included questionnaire 1 at intervals 1 and 3, and questionnaire 2 at interval 2, 1 month after interval 1. Results: Comparison between FSP and CIS+ showed that FSP performed at least as well as CIS+ in all speech perception tests, and outperformed CIS+ in vowel and monosyllabic word discrimination. Comparison between FSP and HDCIS showed that both performed equally well in all speech perception tests. Pitch scaling showed that FSP performed at least as well as HDCIS. With FSP, sound quality was at least as good and often better than with HDCIS. Conclusions: Results indicate that FSP performs better than CIS+ in vowel and monosyllabic word understanding. Subjective evaluation demonstrates strong user preferences for FSP when listening to speech and music.}, language = {en} }