TY - JOUR A1 - Juergens, Lukas A1 - Bieniussa, Linda A1 - Voelker, Johannes A1 - Hagen, Rudolf A1 - Rak, Kristen T1 - Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice JF - Histochemistry and Cell Biology N2 - The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing. KW - tubulin-binding cofactors KW - tubulin KW - development KW - cochlea KW - posttranslational modifications KW - hearing Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234852 SN - 0948-6143 VL - 154 ER - TY - JOUR A1 - Friedrich, Maximilian U. A1 - Schneider, Erich A1 - Buerklein, Miriam A1 - Taeger, Johannes A1 - Hartig, Johannes A1 - Volkmann, Jens A1 - Peach, Robert A1 - Zeller, Daniel T1 - Smartphone video nystagmography using convolutional neural networks: ConVNG JF - Journal of Neurology N2 - 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. KW - digital medicine KW - nystagmus KW - eye movement disorders KW - videooculography KW - computer vision KW - telemedicine KW - precision medicine Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324526 VL - 270 IS - 5 ER - TY - JOUR A1 - Bahmer, Andreas A1 - Gupta, Daya Shankar T1 - Role of Oscillations in Auditory Temporal Processing: A General Model for Temporal Processing of Sensory Information in the Brain? JF - Frontiers in Neuroscience N2 - We review the role of oscillations in the brain and in the auditory system showing that the ability of humans to distinguish changes in pitch can be explained as a precise analysis of temporal information in auditory signals by neural oscillations. The connections between auditory brain stem chopper neurons construct neural oscillators, which discharge spikes at various constant intervals that are integer multiples of 0.4 ms, contributing to the temporal processing of auditory cochlear output. This is subsequently spatially mapped in the inferior colliculus. Electrophysiological measurements of auditory chopper neurons in different species show oscillations with periods which are integer multiples of 0.4 ms. The constant intervals of 0.4 ms can be attributed to the smallest synaptic delay between interconnected simulated chopper neurons. We also note the patterns of similarities between microcircuits in the brain stem and other parts of the brain (e.g., the pallidum, reticular formation, locus coeruleus, oculomotor nuclei, limbic system, amygdala, hippocampus, basal ganglia and substantia nigra), dedicated to the processing of temporal information. Similarities in microcircuits across the brain reflect the importance of one of the key mechanisms in the information processing in the brain, namely the temporal coupling of different neural events via coincidence detection. KW - canonical microcircuits KW - cochlear nucleus KW - locus coerulus KW - limbic system KW - amygdala KW - hippocampus KW - basal ganglia KW - substantia nigra Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196087 SN - 1662-453X VL - 12 IS - 793 ER - TY - JOUR A1 - Greiser, Eberhard M. A1 - Greiser, Karin Halina A1 - Ahrens, Wolfgang A1 - Hagen, Rudolf A1 - Lazszig, Roland A1 - Maier, Heinz A1 - Schick, Bernhard A1 - Zenner, Hans Peter T1 - Risk factors for nasal malignancies in German men: the South-German Nasal cancer study JF - BMC Cancer N2 - Background: There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. Methods: A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Wurttemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. Results: Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). Conclusions: Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only. KW - paranasal sinuses KW - case-control study KW - nasal snuff KW - nasopharyngeal carcinoma KW - sinonasal cancer KW - occupational exposures KW - cigarette smoking KW - Univted-States KW - maxillary sinus KW - wood dust KW - formaldehyde KW - cavity KW - nasal cancer KW - smoking KW - hardwood dust KW - asbestos KW - organic solvents KW - insecticides KW - nasal spray KW - nasal lavage Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133365 VL - 12 IS - 506 ER - TY - JOUR A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Risk factors for children requiring adenotonsillectomy and their impact on postoperative complications: a retrospective analysis of 2000 patients JF - Anaesthesia N2 - Adenotonsillectomies are commonly performed procedures and sleep‐disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri‐operative complications in children requiring adenotonsillectomy, we performed a retrospective case‐control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95%CI 2.1–7.1), low body weight (OR 2.6, 95%CI 1.5–4.4), obstructive sleep apnoea (OR 2.4, 95%CI 1.5–3.8), pre‐existing craniofacial or syndromal disorders (OR 2.3, 95%CI 1.4–3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95%CI 4.7–13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre‐operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra‐operative complications. KW - adenotonsillectromy KW - monotoring KW - obstructive sleep apnoea KW - paediatrics KW - retrospective KW - risk factors Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204787 VL - 74 IS - 12 ER - TY - JOUR A1 - Stelzig, Yvonne A1 - Jacob, Roland A1 - Mueller, Joachim T1 - Preliminary speech recognition results after cochlear implantation in patients with unilateral hearing loss: a case series JF - Journal of Medical Case Reports N2 - Introduction Cochlear implants known to provide support in individuals with bilateral hearing loss may also be of great benefit for individuals with unilateral hearing loss. This case report demonstrates the positive effects of cochlear implantation on speech understanding in noise conditions in patients with unilateral hearing loss and normal hearing on the contralateral side. To the best of our knowledge, the data presented here are from the first few cases to receive a cochlear implant for unilateral hearing loss. Case presentation Four Caucasian German men, two aged 48 and the others aged 51 and 57 years old, with post-lingual unilateral hearing loss and normal hearing on the contralateral side were implanted with a cochlear implant. All our patients were members of the German army. Before and after implantation, they were given a battery of speech tests in different hearing conditions to assess the effect of unilateral cochlear implantation on speech understanding in noise conditions. Test results showed that all patients benefited from unilateral cochlear implantation, particularly in terms of speech understanding in noise conditions. Conclusions Unilateral cochlear implantation might be a successful treatment method for patients with unilateral hearing loss not benefiting from alternative treatment options. The results of this case report open up the field of cochlear implantation for expanded criteria and new areas of research. KW - medicin Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141722 VL - 5 IS - 343 ER - TY - JOUR A1 - Meyer, Till Jasper A1 - Gerhard-Hartmann, Elena A1 - Lodes, Nina A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Steinke, Maria A1 - Hackenberg, Stephan T1 - Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors JF - PLoS One N2 - 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. KW - Head and neck cancers KW - salivary gland tumors KW - salivary glands KW - cancers and neoplasms KW - malignant tumors KW - lipids KW - raman spectroscopy KW - surgical oncology Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264736 VL - 16 IS - 9 ER - TY - JOUR A1 - Polat, Bülent A1 - Kaiser, Philipp A1 - Wohlleben, Gisela A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Scheich, Matthias A1 - Malzahn, Uwe A1 - Fischer, Thomas A1 - Vordermark, Dirk A1 - Flentje, Michael T1 - Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer JF - BMC Cancer N2 - Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact. KW - perioperative changes KW - osteopontin KW - TGFβ1 KW - head and neck cancer KW - survival Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157529 VL - 17 IS - 6 ER - TY - JOUR A1 - Bieniussa, Linda A1 - Kahraman, Baran A1 - Skornicka, Johannes A1 - Schulte, Annemarie A1 - Voelker, Johannes A1 - Jablonka, Sibylle A1 - Hagen, Rudolf A1 - Rak, Kristen T1 - 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 JF - Frontiers in Neurology N2 - 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. KW - cochlea KW - microtubules KW - MOC fibers KW - hearing loss KW - pegylated insulin-like growth factor 1 KW - outer hair cell (OHC) KW - motor neuropathy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276669 SN - 1664-2295 VL - 13 ER - TY - JOUR A1 - Engert, Jonas A1 - Spahn, Bjoern A1 - Bieniussa, Linda A1 - Hagen, Rudolf A1 - Rak, Kristen A1 - Voelker, Johannes T1 - Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body JF - Life N2 - 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. KW - neurosphere KW - auditory pathway KW - neural stem cell potential Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319387 SN - 2075-1729 VL - 13 IS - 5 ER -