Shinji Urata’s research while affiliated with The University of Texas Medical Branch at Galveston and other places

Objective With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), the main objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection. Methods Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen. Results There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the vallate papillae taste buds (3–35 dpi) and autonomic ganglia (5–35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2–42 dpi). Conclusion The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the vallate papillae taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Objective To evaluate the morphology of the crista fenestra (CF) using three-dimensional reconstruction based on high-resolution computed tomography (HRCT) and to examine the influence of CF height on the insertion approach used for CI632/532 implants. Study design Retrospective study Setting Tertiary referral center Patients Forty-five ears of 37 patients who received CI632/532 implants were included. Interventions HRCT images were reconstructed into three-dimensional images, and CF structures were identified. The patients were divided into two group based on the insertion approach: round window approach (RW; n = 27) and extended round window approach (eRW; n = 18). To evaluate CF interference, 10 cases in the eRW group in which the sheath or electrode did not pass through the RW before widening the RW niche (nRW group) were specifically included in the analysis. Main outcome measure The identified CF cross-sections were confirmed by HRCT axial sectioning, and CF heights were measured. Results The mean CF height was significantly greater in the nRW group than in the RW group (0.97 vs. 0.78 mm). Conclusion CF was identified using three-dimensional computer graphics (3DCG) and the CF height on the HRCT axial sections. Thus, measuring the CF height using 3DCG reconstruction can facilitate the preoperative selection of the electrode insertion approach.

Objective With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection. Methods Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen. Results There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the circumvallate papillae taste buds (3–35 dpi) and autonomic ganglia (5–35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2–42 dpi). Conclusion The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the circumvallate taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Objective To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires. Study Design Prospective, single-subject randomized, crossover study. Setting Anechoic room inside a university. Patients Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss. Interventions Patients’ baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order. Main Outcome Measures Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, “Abbreviated Profile of Hearing Aid Benefit” (APHAB) and “Speech, Spatial, and Qualities of Hearing Scale” with 12 questions (SSQ-12). Results Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits. Conclusion CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.

Genetic factors significantly influence the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully elucidated. Recent extensive genomic studies implicate the protocadherin related 15 ( PCDH15 ) gene in the onset of psychiatric disorders such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15 . Notably, although PCDH15 is primarily identified as the causative gene for Usher syndrome, which leads to visual and auditory impairments, our Pcdh15 homozygous deletion mice ( Pcdh15 -null) did not show observable structural abnormalities in either the retina or inner ear. However, the Pcdh15 heterozygous deletion mice ( Pcdh15 -het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations aligned with symptoms observed in various psychiatric patients and certain psychiatric disease mouse models. Specifically, the hyperactivity may mirror manic episodes in BD. To achieve a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag ® sensor chips in the animals, enabling continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15 -null exhibited elevated activity and body temperature compared with those of wild-type mice (WT). However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15 -null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15 -deletion mice. Therefore, Pcdh15 -deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

We aimed to investigate whether the degree of hearing loss with GJB2 mutations could be predicted by distinguishing between truncating and non-truncating mutations and whether the genotype could predict the hearing loss level. Additionally, we examined the progression of hearing loss in individuals monitored for over 2 years for an average of 6.9 years. The proportion of truncating mutations was higher in patients with profound and severe hearing loss, but it was not accurate enough to predict the degree of hearing loss. Via genotype analysis, mutations of the p.Arg143Trp variants were associated with profound hearing loss, while mutations of the p.Leu79Cysfs*3 allele exhibited a wide range of hearing loss, suggesting that specific genotypes can predict the hearing loss level. Notably, there were only three cases of progression in four ears, all of which involved the p.Leu79Cysfs*3 mutation. Over the long-term follow-up, 4000 Hz was significant, and there was a trend of progression at 250 Hz, suggesting that close monitoring at these frequencies during follow-up may be crucial to confirm progression. The progression of hearing loss was observed in moderate or severe hearing loss cases at the time of the initial diagnosis, emphasizing that children with this level of hearing loss need regular follow-ups.

Objective To investigate whether machine learning (ML)‐based algorithms, namely logistic regression (LR), random forest (RF), k‐nearest neighbor (k‐NN), and gradient‐boosting decision tree (GBDT), utilizing early post‐onset parameters can predict facial synkinesis resulting from Bell's palsy or Ramsay Hunt syndrome more accurately than the conventional statistics‐based LR. Methods This retrospective study included 362 patients who presented to a facial palsy outpatient clinic. Median follow‐up of synkinesis‐positive and ‐negative patients was 388 (range, 177–1922) and 198 (range, 190–3021) days, respectively. Electrophysiological examinations were performed, and the rate of synkinesis in Bell's palsy and Ramsay Hunt syndrome was evaluated. Sensitivity and specificity were assessed using statistics‐based LR; and electroneurography (ENoG) value, the difference in the nerve excitability test (NET), and scores of the subjective Yanagihara scaling system were evaluated using early post‐onset parameters with ML‐based LR, RF, k‐NN, and GBDT. Results Synkinesis rate in Bell's palsy and Ramsay Hunt syndrome was 20.2% (53/262) and 40.0% (40/100), respectively. Sensitivity and specificity obtained with statistics‐based LR were 0.796 and 0.806, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.87. AUCs measured using ML‐based LR of “ENoG,” “difference in NET,” “Yanagihara,” and all three components (“all”) were 0.910, 0.834, 0.711, and 0.901, respectively. Conclusion ML‐based LR model shows potential in predicting facial synkinesis probability resulting from Bell's palsy or Ramsay Hunt syndrome and has comparable reliability to the conventional statistics‐based LR. Level of Evidence 3.

The three-dimensional stria vascularis (SV) and cochlear blood vessel structure is essential for inner ear function. Here, modified Sca/eS, a sorbitol-based optical-clearing method, was reported to visualize SV and vascular structure in the intact mouse cochlea. Cochlear macrophages as well as perivascular-resident macrophage-like melanocytes were detected as GFP-positive cells of the CX3CR1+/GFP mice. This study's method was effective in elucidating inner ear function under both physiological and pathological conditions.