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Hearing Research May 2024The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of...
The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited. Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (P) and scala tympani (P) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (P) across the basilar membrane - known to be closely related to the hearing sensation - was calculated as the complex difference between P and P. With air conduction stimulation, both P and Pincreased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for P compared to P. The P, in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement. With bone conduction, the average within-specimen effects were less than 5 dB for either P, P or P. The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction. This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement.
PubMed: 38850830
DOI: 10.1016/j.heares.2024.109049 -
Folia Morphologica Jun 2024Mastoid pneumatization is subject to numerous influencing factors including race, sex, and surrounding structures of the middle ear. This study aims to determine the...
BACKGROUND
Mastoid pneumatization is subject to numerous influencing factors including race, sex, and surrounding structures of the middle ear. This study aims to determine the mastoid air cell system (MACS) volume and its relationship with middle ear structures, and the influence of sex.
MATERIALS AND METHODS
A cross-sectional study was performed analyzing computed tomography (CT) scans in which MACS volume and the Estachian tube length (ETL) were visible. MACS volume, ETL, and width and height of the aditus ad antrum were obtained.
RESULTS
A total of 100 CT were included with a mean age of 38.5 ± 15.3 years, of which 56 were women and 44 were men. The mean right and left MACS volume were 5.43 ± 3.15 cm³ and 5.54 ± 3.43 cm3 respectively , with a ETL of 24.55 ± 3.07 mm in right side and 24.24 ± 2.60 mm on left side. A aditus ad antrum width of 2.98 ± 0.65 in right and 2.98 ± 0.58 on the left and height of 4.51 ± 1.05 and 4.32 ± 0.85, on right and left side respectively. There were statistical differences between sexes in left ETL, and in MACS volume bilaterally. A low positive correlation between aditus ad antrum height and MACS volume was identified.
CONCLUSIONS
Mastoid pneumatization was bigger in men than women. There was a low positive correlation between mastoid volume and ETL on both sides, and a significant correlation between right mastoid volume and aditus ad antrum height. This could lead us to believe that the length of ETL does not affect the pneumatization of MACS.
PubMed: 38842073
DOI: 10.5603/fm.100190 -
Investigative Ophthalmology & Visual... Jun 2024The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using... (Observational Study)
Observational Study
PURPOSE
The purpose of this study was to evaluate self-reported functional vision (FV) and the impact of vision loss in patients with USH2A-associated retinal degeneration using a patient-reported outcome (PRO) measure, the Michigan Retinal Degeneration Questionnaire (MRDQ), to correlate MRDQ scores with well-established visual function measurements.
DESIGN
An observational cross-sectional study (n = 93) of participants who had Usher Syndrome Type 2 (USH2, n = 55) or autosomal recessive non-syndromic retinitis pigmentosa (ARRP; n = 38) associated with biallelic variants in the USH2A gene.
METHODS
The study protocol was approved by all ethics boards and informed consent was obtained from each participant. Participants completed the MRDQ at the 48-month study follow-up visit. Disease duration was self-reported by participants. One-way ANOVA was used to compare subgroups (clinical diagnosis, age, disease duration, and full-field stimulus threshold [FST] Blue-Red mediation) on mean scores per domain. Spearman correlation coefficients were used to assess associations between MRDQ domains and visual/retinal function assessments.
RESULTS
Of the study sample, 58% were female participants and the median disease duration was 13 years. MRDQ domains were sensitive to differences between subgroups of clinical diagnosis, age, disease duration, and FST Blue-Red mediation. MRDQ domains correlated with static perimetry, microperimetry, full-field stimulus testing, and best-corrected visual acuity (BCVA).
CONCLUSIONS
Self-reported FV measured by the MRDQ, when applied to USH2 and ARRP participants, had good distributional characteristics and correlated well with visual function tests. MRDQ adds a new dimension of understanding on vision-related functioning and establishes this PRO tool as an informative measure in evaluating USH2A outcomes.
Topics: Humans; Female; Male; Cross-Sectional Studies; Middle Aged; Visual Acuity; Extracellular Matrix Proteins; Adult; Self Report; Usher Syndromes; Surveys and Questionnaires; Retinal Degeneration; Aged; Young Adult; Quality of Life; Adolescent; Retinitis Pigmentosa
PubMed: 38833260
DOI: 10.1167/iovs.65.6.5 -
Translational Vision Science &... Jun 2024Deep learning architectures can automatically learn complex features and patterns associated with glaucomatous optic neuropathy (GON). However, developing robust...
PURPOSE
Deep learning architectures can automatically learn complex features and patterns associated with glaucomatous optic neuropathy (GON). However, developing robust algorithms requires a large number of data sets. We sought to train an adversarial model for generating high-quality optic disc images from a large, diverse data set and then assessed the performance of models on generated synthetic images for detecting GON.
METHODS
A total of 17,060 (6874 glaucomatous and 10,186 healthy) fundus images were used to train deep convolutional generative adversarial networks (DCGANs) for synthesizing disc images for both classes. We then trained two models to detect GON, one solely on these synthetic images and another on a mixed data set (synthetic and real clinical images). Both the models were externally validated on a data set not used for training. The multiple classification metrics were evaluated with 95% confidence intervals. Models' decision-making processes were assessed using gradient-weighted class activation mapping (Grad-CAM) techniques.
RESULTS
Following receiver operating characteristic curve analysis, an optimal cup-to-disc ratio threshold for detecting GON from the training data was found to be 0.619. DCGANs generated high-quality synthetic disc images for healthy and glaucomatous eyes. When trained on a mixed data set, the model's area under the receiver operating characteristic curve attained 99.85% on internal validation and 86.45% on external validation. Grad-CAM saliency maps were primarily centered on the optic nerve head, indicating a more precise and clinically relevant attention area of the fundus image.
CONCLUSIONS
Although our model performed well on synthetic data, training on a mixed data set demonstrated better performance and generalization. Integrating synthetic and real clinical images can optimize the performance of a deep learning model in glaucoma detection.
TRANSLATIONAL RELEVANCE
Optimizing deep learning models for glaucoma detection through integrating DCGAN-generated synthetic and real-world clinical data can be improved and generalized in clinical practice.
Topics: Deep Learning; Humans; Optic Disk; Optic Nerve Diseases; ROC Curve; Glaucoma; Female; Male; Middle Aged; Algorithms
PubMed: 38829624
DOI: 10.1167/tvst.13.6.1 -
Microbiology Spectrum Jul 2024The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA)...
The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2-9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6-17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity ( = 28/35) for HPV16 and HPV33 and a specificity of 97% ( = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% ( = 17/20), while in samples with <750 µL plasma, it was 73% ( = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material.IMPORTANCEHPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.
Topics: Humans; DNA, Viral; Papillomavirus Infections; Cell-Free Nucleic Acids; Polymerase Chain Reaction; Oropharyngeal Neoplasms; Papillomaviridae; Female; Sensitivity and Specificity; Male; Middle Aged; Aged; Human papillomavirus 16; Human Papillomavirus Viruses
PubMed: 38829114
DOI: 10.1128/spectrum.00024-24 -
SAGE Open Medical Case Reports 2024This report presents a rare case of bronchogenic adenocarcinoma with initial metastasis in the external auditory canal. The patient, a 64-year-old man with a history of...
This report presents a rare case of bronchogenic adenocarcinoma with initial metastasis in the external auditory canal. The patient, a 64-year-old man with a history of bladder urothelial carcinoma, initially presented with a persistent right otitis externa. Otoscopic examination revealed a mass obstructing the right external auditory canal. The temporal bone computed tomography scan revealed a mass that completely obstructed the right external auditory canal and extended into the middle ear. A biopsy showed a poorly differentiated adenocarcinoma of bronchogenic origin, confirmed by positive immunohistochemical staining for cytokeratin 7 and Thyroid transcription factor-1. Further imaging revealed a large tumor mass in the lung involving the mediastinum and parenchyma, along with carcinomatous lymphangitis and cerebral metastasis. Histopathological examination of the primary lung tumor confirmed a poorly differentiated adenocarcinoma with similar features to the metastasis in the external auditory canal. The tumor was staged as T4N2M1c, and the patient underwent local external-beam radiation therapy with chemotherapy.
PubMed: 38828381
DOI: 10.1177/2050313X241258155 -
PloS One 2024Vision and hearing impairments are highly prevalent and have a significant impact on physical, psychological and social wellbeing. There is a need for accurate,...
INTRODUCTION
Vision and hearing impairments are highly prevalent and have a significant impact on physical, psychological and social wellbeing. There is a need for accurate, contemporary national data on the prevalence, risk factors and impacts of vision and hearing loss in Australian adults.
OBJECTIVES
The Australian Eye and Ear Health Survey (AEEHS) aims to determine the prevalence, risk factors and impacts of vision and hearing loss in both Aboriginal and Torres Strait Islander and non-Indigenous older adults.
METHODS AND ANALYSIS
The AEEHS is a population-based cross-sectional survey which will include 5,000 participants (3250 non-Indigenous aged 50 years or older and 1750 Aboriginal and Torres Strait Islander people aged 40 years or older) from 30 sites covering urban and rural/regional geographic areas, selected using a multi-stage, random cluster sampling strategy. Questionnaires will be administered to collect data on socio-demographic, medical, ocular and ontological history. The testing battery includes assessment of blood pressure, blood sugar, anthropometry, visual acuity (presenting, unaided, pinhole and best-corrected), refraction, tonometry, slit lamp and dilated eye examination, ocular imaging including optical coherence tomography (OCT), OCT-angiography and retinal photography, and automated visual fields. Audiometry, tympanometry and video otoscopy will also be performed. The primary outcomes are age-standardised prevalence of cause-specific vision and hearing impairment. Secondary outcomes are prevalence of non-blinding eye diseases (including dry eye disease), patterns in health service utilisation, universal health coverage metrics, risk factors for vision and hearing impairment, and impact on quality of life.
Topics: Humans; Cross-Sectional Studies; Australia; Middle Aged; Male; Female; Adult; Hearing Loss; Health Surveys; Aged; Prevalence; Risk Factors; Native Hawaiian or Other Pacific Islander; Vision Disorders
PubMed: 38820367
DOI: 10.1371/journal.pone.0301846 -
JAMA Network Open May 2024Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic...
IMPORTANCE
Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD.
OBJECTIVE
To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea.
DESIGN, SETTING, AND PARTICIPANTS
This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023.
MAIN OUTCOMES AND MEASURES
Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis.
RESULTS
A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis.
CONCLUSIONS AND RELEVANCE
In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.
Topics: Humans; Male; Female; Exome Sequencing; Adult; Prospective Studies; Retinal Diseases; Middle Aged; Republic of Korea; Genetic Testing; Adolescent; Young Adult; Child; High-Throughput Nucleotide Sequencing; Computational Biology
PubMed: 38819824
DOI: 10.1001/jamanetworkopen.2024.14198 -
Frontiers in Neurology 2024Calvarial bone marrow has been found to be central in the brain immune response, being connected to the dura through channels which allow leukocyte trafficking. Temporal...
Calvarial bone marrow has been found to be central in the brain immune response, being connected to the dura through channels which allow leukocyte trafficking. Temporal bone marrow is thought to play important roles in relation to the inner ear, but is still largely uncharacterized, given this bone complex anatomy. We characterized the geometry and connectivity of rat temporal bone marrow using lightsheet imaging of cleared samples and microCT. Bone marrow was identified in cleared tissue by cellular content (and in particular by the presence of megakaryocytes); since air-filled cavities are absent in rodents, marrow clusters could be recognized in microCT scans by their geometry. In cleared petrosal bone, autofluorescence allowed delineation of the otic capsule layers. Within the endochondral layer, bone marrow was observed in association to the cochlear base and vestibule, and to the cochlear apex. Cochlear apex endochondral marrow (CAEM) was a separated cluster from the remaining endochondral marrow, which was therefore defined as "vestibular endochondral marrow" (VEM). A much larger marrow island (petrosal non-endochondral marrow, PNEM) extended outside the otic capsule surrounding semicircular canal arms. PNEM was mainly connected to the dura, through bone channels similar to those of calvarial bone, and only a few channels were directed toward the canal periosteum. On the contrary, endochondral bone marrow was well connected to the labyrinth through vascular loops (directed to the spiral ligament for CAEM and to the bony labyrinth periosteum for VEM), and to dural sinuses. In addition, CAEM was also connected to the tensor tympani fossa of the middle ear and VEM to the endolymphatic sac. Endochondral marrow was made up of small lobules connected to each other and to other structures by channels lined by elongated macrophages, whereas PNEM displayed larger lobules connected by channels with a sparse macrophage population. Our data suggest that the rat inner ear is surrounded by bone marrow at the junctions with middle ear and brain, most likely with "customs" role, restricting pathogen spread; a second marrow network with different structural features is found within the endochondral bone layer of the otic capsule and may play different functional roles.
PubMed: 38817550
DOI: 10.3389/fneur.2024.1386654 -
Stem Cell Research Aug 2024We report the establishment of a human induced pluripotent stem cell (iPSC) line from a 54-year-old male patient with an A1555G mutation in the mitochondrial 12S...
We report the establishment of a human induced pluripotent stem cell (iPSC) line from a 54-year-old male patient with an A1555G mutation in the mitochondrial 12S ribosomal RNA gene (MTRNR1), associated with sensorineural hearing loss. The established iPSC line expressed stemness markers or undifferentiated state markers. We also demonstrated the capacity of the cells to differentiate into the three germ layers, suggesting its pluripotency and utility in the pathological study of sensorineural hearing loss and drug screening for ear disorders.
Topics: Humans; Induced Pluripotent Stem Cells; DNA, Mitochondrial; Male; Middle Aged; Mutation; Cell Differentiation; Cell Line; RNA, Ribosomal; Hearing Loss, Sensorineural; Hearing Loss
PubMed: 38815527
DOI: 10.1016/j.scr.2024.103452