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Different effects of conditional Knock-Out of Stat3 on the sensory epithelium of the Organ of Corti
(2024)
The mammalian cochlea detects sound in response to vibration at frequency-dependent positions along the cochlea duct. The sensory outer hair cells, which are surrounded by supporting cells, act as a signal amplifier by changing their cell length. This is called electromotility. To ensure correct electrical transmission during mechanical forces, a certain resistance of the sensory epithelium is a prerequisite for correct transduction of auditory information. This resistance is managed by microtubules and its posttranslational modification in the supporting cells of the sensory epithelium of the cochlea. Stat3 is a transcription factor, with its different phosphorylation sites, is involved in many cellular processes like differentiation, inflammation, cell survival and microtubule dynamics, depending on cell type and activated pathway. While Stat3 has a wide range of intracellular roles, the question arose, how and if Stat3 is involved in cells of the organ of Corti to ensure a correct hearing.
To test this, Cre/loxp system were used to perform conditional Knock-Out (cKO) of Stat3 in outer hair cells or supporting cells either before hearing onset or after hearing onset. Hearing performances included DPOAE and ABR measurements, while molecular were performed by sequencing. Additionally, morphological examination was used by immunohistochemistry and electron microscopy.
A cKO of Stat3 before and after hearing onset in outer hair cells leads to hearing impairments, whereas synapses, nerve fibers and mitochondria were not affected. Bulk sequencing analyzation of outer hair cells out of cKO mice before hearing onset resulted in a disturbance of cellular homeostasis and extracellular signals. A cKO of Stat3 in the outer hair cells after hearing onset resulted in inflammatory signaling pathway with increased cytokine production and upregulation of NF-kb pathway. In supporting cells, cKO of Stat3 only after hearing onset resulted in a hearing impairment. However, synapses, nerve soma and fibers were not affected of a cKO of Stat3 in supporting cells. Nevertheless, detyronisated modification of microtubules were altered, which can lead to an instability of supporting cells during hearing.
In conclusion, Stat3 likely interact in a cell-specific and function-specific manner in cells of the organ of Corti. While a cKO in outer hair cells resulted in increased cytokine production, supporting cells altered its stability due to decreased detyronisated modification of microtubules. Together the results indicated that Stat3 is an important protein for hearing performances. However, additional investigations of the molecular mechanism are needed to understand the role of Stat3 in the cells of the organ of Corti.
Surgical management of lateral neck abscesses in children: a retrospective analysis of 100 cases
(2023)
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.
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.
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.
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.
Automated analysis of the inner ear anatomy in radiological data instead of time-consuming manual assessment is a worthwhile goal that could facilitate preoperative planning and clinical research. We propose a framework encompassing joint semantic segmentation of the inner ear and anatomical landmark detection of helicotrema, oval and round window. A fully automated pipeline with a single, dual-headed volumetric 3D U-Net was implemented, trained and evaluated using manually labeled in-house datasets from cadaveric specimen (N = 43) and clinical practice (N = 9). The model robustness was further evaluated on three independent open-source datasets (N = 23 + 7 + 17 scans) consisting of cadaveric specimen scans. For the in-house datasets, Dice scores of 0.97 and 0.94, intersection-over-union scores of 0.94 and 0.89 and average Hausdorf distances of 0.065 and 0.14 voxel units were achieved. The landmark localization task was performed automatically with an average localization error of 3.3 and 5.2 voxel units. A robust, albeit reduced performance could be
attained for the catalogue of three open-source datasets. Results of the ablation studies with 43 mono-parametric variations of the basal architecture and training protocol provided task-optimal parameters for both categories. Ablation studies against single-task variants of the basal architecture showed a clear performance beneft of coupling landmark localization with segmentation and a dataset-dependent performance impact on segmentation ability.
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.
Seed amplification assays (SAA) are becoming commonly used in synucleinopathies to detect α-synuclein aggregates. Studies in Parkinson’s disease (PD) and isolated REM-sleep behavior disorder (iRBD) have shown a considerably lower sensitivity in the olfactory epithelium than in CSF or skin. To get an insight into α-synuclein (α-syn) distribution within the nervous system and reasons for low sensitivity, we compared SAA assessment of nasal brushings and skin biopsies in PD (n = 27) and iRBD patients (n = 18) and unaffected controls (n = 30). α-syn misfolding was overall found less commonly in the olfactory epithelium than in the skin, which could be partially explained by the nasal brushing matrix exerting an inhibitory effect on aggregation. Importantly, the α-syn distribution was not uniform: there was a higher deposition of misfolded α-syn across all sampled tissues in the iRBD cohort compared to PD (supporting the notion of RBD as a marker of a more malignant subtype of synucleinopathy) and in a subgroup of PD patients, misfolded α-syn was detectable only in the olfactory epithelium, suggestive of the recently proposed brain-first PD subtype. Assaying α-syn of diverse origins, such as olfactory (part of the central nervous system) and skin (peripheral nervous system), could increase diagnostic accuracy and allow better stratification of patients.
Salivary gland tumors (SGTs) are a relevant, highly diverse subgroup of head and neck tumors whose entity determination can be difficult. Confocal Raman imaging in combination with multivariate data analysis may possibly support their correct classification. For the analysis of the translational potential of Raman imaging in SGT determination, a multi-stage evaluation process is necessary. By measuring a sample set of Warthin tumor, pleomorphic adenoma and non-tumor salivary gland tissue, Raman data were obtained and a thorough Raman band analysis was performed. This evaluation revealed highly overlapping Raman patterns with only minor spectral differences. Consequently, a principal component analysis (PCA) was calculated and further combined with a discriminant analysis (DA) to enable the best possible distinction. The PCA-DA model was characterized by accuracy, sensitivity, selectivity and precision values above 90% and validated by predicting model-unknown Raman spectra, of which 93% were classified correctly. Thus, we state our PCA-DA to be suitable for parotid tumor and non-salivary salivary gland tissue discrimination and prediction. For evaluation of the translational potential, further validation steps are necessary.
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.