Expression of AQP-10, -11 and -12 in the rat stria vascularis.

BACKGROUND: Water homeostasis is essential for inner ear function. Several aquaporins (AQPs), which are water transport proteins in the cell or plasma membrane, have been reported in the lateral wall of the rat inner ear (cochlea). However, the presence of AQP-10, -11 and -12 has not been reported in the rat stria vascularis (SV) to date. AIMS/OBJECTIVES: We have aimed to clarify the expression of AQP-10, -11 and -12 in the cochlea lateral wall. MATERIALS AND METHODS: Using Wistar rats, we examined the expression of AQP-10, -11 and -12 in the cochlea lateral wall using molecular approaches and immunohistochemistry. RESULTS: AQP-11 was molecular biologically expressed, but the expression of AQP-10 and -12 was not observed. Immunohistochemically, AQP-11 was diffusely localized in the basal cells and marginal cells of the rat SV but was not expressed at the apical site of marginal cells with double staining. The expression of AQP-10 and -12 was not observed. CONCLUSIONS AND SIGNIFICANCE: Only AQP-11 was expressed in the basal cells and marginal cells, but it was not expressed at the apical site of marginal cells. Based on this study, AQP-11 may not have an important role in water flux between the perilymph and endolymph.

Surgical results of 29 ears with congenital middle ear anomalies; Microscopic vs. endoscopic ear surgery.

OBJECTIVE: Although congenital middle ear anomalies include various types of ossicular anomalies, all of these can be treated by ossiculoplasty or stapes surgery. Transcanal endoscopic ear surgery (TEES) is a minimally invasive surgical method for middle ear disease with an excellent surgical view that has been widely adopted worldwide. To determine the efficacy of TEES for middle ear anomalies, we describe the surgical results and compare the hearing outcomes between patients treated by TEES and microscopic ear surgery (MES). METHODS: A total of 39 ears with congenital middle ear anomalies were treated surgically at the University Hospital of Kochi Medical School between January 2011 and December 2021. In total, 29 ears of 23 patients were included in the study. Demographics, type of anomaly, surgical methods, pre- and postoperative hearing thresholds, and surgical complications were investigated by retrospective chart review. RESULTS: Of the 29 ears, 11 were treated by MES and 18 were treated by TEES. There were no differences in sex, age, preoperative hearing thresholds, or rate of stapes surgery between the two groups. The mean air-bone gap improvement was 20.6 dB in the MES group and 28.8 dB in the TEES group; these values were not significantly different. The median operation time was not significantly different between the MES and TEES groups (125 and 130 min, respectively). The improvements of air conduction in class 1 and 2 (stapes surgery) and class 3 (ossiculoplasty) cases were also not different between the groups. CONCLUSIONS: TEES achieved comparable hearing outcomes to MES without postauricular or endaural incisions. Further, class 1 and 2 anomalies demonstrated hearing improvement similar to class 3 without major complications. Since the surgical field limited around the ossicular chain, coupled with the fact that the middle ear anomaly itself does not exhibit inflammation leading to unfavorable bleeding, TEES is a feasible surgical procedure for all types of congenital ossicular anomalies.

Integration of motion information in illusory motion perceived in stationary patterns.

Illusory motion is a phenomenon in which stationary images with repeating luminance gradient patterns appear to be moving. In this study, we conducted experiments focusing on illusory motion to verify the hypothetical rule that velocity information, extracted from local luminance patterns, is integrated by summation in visual information processing. This rule is based on the hypothesis of velocity integration, and could estimate perceived velocity of stimulus. The summation rule was evaluated by a psychophysical experiment. Our results showed that the summation rule unbiasedly predicted perceived velocity, suggesting that an algorithm for integrating velocity information in illusory motion is based on the summation rule. These results would contribute to understanding of the spatial integration of local motion signals in visual information processing.

Botulinum Toxin Therapy for Spasmodic Dysphonia in Japan: The History and an Update.

Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic laryngeal muscles. SD is classified into three types: adductor SD (AdSD), abductor SD (AbSD), and mixed SD. Of these, AdSD accounts for 90-95% of disease; younger females are predominantly affected. Botulinum toxin injection into the laryngeal muscles is safe, minimally invasive, and very effective. Here, we review the history of clinical research for SD conducted in Japan. The first use of botulinum toxin injection therapy to treat SD in Japan was by Kobayashi et al. in 1989. The group developed an objective mora (syllable) method to evaluate SD severity. Recently, we conducted a placebo-controlled, randomized, double-blinded clinical trial of botulinum toxin therapy for AdSD and an open-label trial for AbSD to obtain the approval of such therapy by the Japanese medical insurance system. The mora method revealed significant voice improvement and the evidence was of high quality. Additionally, a clinical trial of type 2 thyroplasty using titanium bridges confirmed the efficacy and safety of such therapy. These studies broadened the SD treatment options and have significantly benefited patients.

Optimistic reinforcement learning by forward Kullback-Leibler divergence optimization.

This paper addresses a new interpretation of the traditional optimization method in reinforcement learning (RL) as optimization problems using reverse Kullback-Leibler (KL) divergence, and derives a new optimization method using forward KL divergence, instead of reverse KL divergence in the optimization problems. Although RL originally aims to maximize return indirectly through optimization of policy, the recent work by Levine has proposed a different derivation process with explicit consideration of optimality as stochastic variable. This paper follows this concept and formulates the traditional learning laws for both value function and policy as the optimization problems with reverse KL divergence including optimality. Focusing on the asymmetry of KL divergence, the new optimization problems with forward KL divergence are derived. Remarkably, such new optimization problems can be regarded as optimistic RL. That optimism is intuitively specified by a hyperparameter converted from an uncertainty parameter. In addition, it can be enhanced when it is integrated with prioritized experience replay and eligibility traces, both of which accelerate learning. The effects of this expected optimism was investigated through learning tendencies on numerical simulations using Pybullet. As a result, moderate optimism accelerated learning and yielded higher rewards. In a realistic robotic simulation, the proposed method with the moderate optimism outperformed one of the state-of-the-art RL method.

Motion illusion-like patterns extracted from photo and art images using predictive deep neural networks.

In our previous study, we successfully reproduced the illusory motion perceived in the rotating snakes illusion using deep neural networks incorporating predictive coding theory. In the present study, we further examined the properties of the network using a set of 1500 images, including ordinary static images of paintings and photographs and images of various types of motion illusions. Results showed that the networks clearly classified a group of illusory images and others and reproduced illusory motions against various types of illusions similar to human perception. Notably, the networks occasionally detected anomalous motion vectors, even in ordinally static images where humans were unable to perceive any illusory motion. Additionally, illusion-like designs with repeating patterns were generated using areas where anomalous vectors were detected, and psychophysical experiments were conducted, in which illusory motion perception in the generated designs was detected. The observed inaccuracy of the networks will provide useful information for further understanding information processing associated with human vision.

Robust Stochastic Gradient Descent With Student-t Distribution Based First-Order Momentum.

Remarkable achievements by deep neural networks stand on the development of excellent stochastic gradient descent methods. Deep-learning-based machine learning algorithms, however, have to find patterns between observations and supervised signals, even though they may include some noise that hides the true relationship between them, more or less especially in the robotics domain. To perform well even with such noise, we expect them to be able to detect outliers and discard them when needed. We, therefore, propose a new stochastic gradient optimization method, whose robustness is directly built in the algorithm, using the robust student-t distribution as its core idea. We integrate our method to some of the latest stochastic gradient algorithms, and in particular, Adam, the popular optimizer, is modified through our method. The resultant algorithm, called t-Adam, along with the other stochastic gradient methods integrated with our core idea is shown to effectively outperform Adam and their original versions in terms of robustness against noise on diverse tasks, ranging from regression and classification to reinforcement learning problems.

Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.

Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.

Changes during medical treatments before adenotonsillectomy in children with obstructive sleep apnea.

OBJECTIVES: The severity of pediatric obstructive sleep apnea (OSA) can vary from mild to very severe (AHI ≥ 30 events/h) with the seasons. The efficacy of medical treatment has been investigated in cases of mild and moderate pediatric OSA, but not in severe cases thoroughly. METHODS: Our prospective cohort study involved 205 children who visited our outpatient clinic between December 2014 and May 2020. We performed home sleep tests after the initial visit, and then polysomnography after optimizing the control of rhinitis, sinusitis, adenoid hypertrophy, and tonsillitis by using medical treatments. RESULTS: The respective proportions of patients who improved to obstructive AHI (O-AHI) < 1/h or who proceeded to surgery were 43.4% and 62.3% in mild cases; 43.3% and 52.2% in moderate cases; 30.2% and 68.4% in severe cases; and 0.0% and 100% in very severe cases. Additionally, nadir SaO2 improved significantly between before and after medical treatment in both O-AHI < 1/h and O-AHI ≥ 1/h patients (respectively p < 0.0001, p = 0.0009). The lowest nadir SaO2 before medical treatment was 74% in patients in whom O-AHI was normalized after medical treatments. CONCLUSION: Medical treatment instituted before a surgical decision is made can provide substantial benefits and avoid unnecessary surgery if there is time for such treatments. In contrast, it may be difficult to normalize the O-AHI in pediatric patients with very severe OSA or a nadir SaO2 of less than 74% by medical treatment.

Post-treatment clinical course following botulinum toxin injection therapy for adductor spasmodic dysphonia: Analysis of data from a placebo-controlled, randomized, double-blinded clinical trial in Japan.

OBJECTIVE: Botulinum toxin (BT) therapy is a first-line treatment for spasmodic dysphonia (SD). However, a detailed chronological course and clinical factors that affect the therapeutic effect have been vague. In this study, we analyzed the data from our placebo-controlled, randomized, double-blinded parallel-group comparison/open-label clinical trial of BT (Botox) to clarify these. METHODS: A total of 22 patients with abductor SD (ADSD) were enrolled. The female-to-male ratio was 20:2 with a mean age of 40.0 ± 10.3 years and a median duration of symptoms of 7.5 years. The therapeutic effect was evaluated based on the change in the number of aberrant morae (phonemes), GRBAS scale, Voice Handicap Index (VHI), and Visual Analogue Scale (VAS). RESULTS: The change in the number of aberrant morae peaked at 2 weeks and lasted for 12 weeks in the BT group with significance (P < .01) compared to the placebo group. Objective improvement (number of aberrant morae and [S] element in GRBAS) preceded subjective improvement (VHI and VAS). The change in number of aberrant morae and VHI showed a significant correlation (P < .01). The changes in the number of aberrant morae, VHI, and VAS in younger subjects were greater than in older subjects. Patients who presented with post-treatment breathy hoarseness or dysphagia showed better therapeutic effects. CONCLUSIONS: BT therapy was effective for ADSD based on both objective and subjective assessments. Improvements in subjective parameters were delayed compared to objective measures due to post-treatment breathy hoarseness. However, this adverse event was believed to reflect the treatment effect. LEVEL OF EVIDENCE: 1b.

Cartilage tympanoplasty for recurrent cholesteatoma using a single sliced cartilage graft: Our experience in 14 ears.

Our procedure may provide a useful alternative in cases where previous surgeries have failed to eradicate the cholesteatoma.

t-soft update of target network for deep reinforcement learning.

This paper proposes a new robust update rule of target network for deep reinforcement learning (DRL), to replace the conventional update rule, given as an exponential moving average. The target network is for smoothly generating the reference signals for a main network in DRL, thereby reducing learning variance. The problem with its conventional update rule is the fact that all the parameters are smoothly copied with the same speed from the main network, even when some of them are trying to update toward the wrong directions. This behavior increases the risk of generating the wrong reference signals. Although slowing down the overall update speed is a naive way to mitigate wrong updates, it would decrease learning speed. To robustly update the parameters while keeping learning speed, a t-soft update method, which is inspired by Student-t distribution, is derived with reference to the analogy between the exponential moving average and the normal distribution. Through the analysis of the derived t-soft update, we show that it takes over the properties of the Student-t distribution. Specifically, with a heavy-tailed property of the Student-t distribution, the t-soft update automatically excludes extreme updates that differ from past experiences. In addition, when the updates are similar to the past experiences, it can mitigate the learning delay by increasing the amount of updates. In PyBullet robotics simulations for DRL, an online actor-critic algorithm with the t-soft update outperformed the conventional methods in terms of the obtained return and/or its variance. From the training process by the t-soft update, we found that the t-soft update is globally consistent with the standard soft update, and the update rates are locally adjusted for acceleration or suppression.

The prevalence and clinical features of spasmodic dysphonia: A review of epidemiological surveys conducted in Japan.

OBJECTIVES: Spasmodic dysphonia (SD) is a rare disease and its epidemiological status is unclear. This review aimed to explore the current prevalence and clinical features of SD in Japan. METHODS: We reviewed Japanese surveys of SD and compared them to surveys reported from other countries. We focused on SD prevalence, clinical features (SD type, sex and age), and treatment modalities. RESULTS: The SD prevalence in Japan was 3.5-7.0/100,000, similar to that in Rochester (NY, USA) and Iceland. Adductor SD predominated (90-95%) and females were four-fold more likely to be affected than males. Mean age at onset was approximately 30 years in Japan. Several years elapsed from onset to diagnosis. The most frequent treatment was botulinum toxin injection, and surgical intervention, particularly type 2 thyroplasty is becoming more popular. CONCLUSIONS: Our review demonstrated some differences of clinical features of SD in Japan compared with other countries, such as a greater female predominance and younger age of onset. Many physicians and patients may be unfamiliar with the clinical features of SD leading to delayed of diagnosis. Therefore, we proposed diagnostic criteria to facilitate early diagnosis and an appropriate choice of treatment modalities.

Comprehensive Detection of Respiratory Bacterial and Viral Pathogens in the Middle Ear Fluid and Nasopharynx of Pediatric Patients With Acute Otitis Media.

BACKGROUND: Acute otitis media (AOM) is a common ear infection caused by respiratory viruses and bacteria of the nasopharynx. The present study aimed to detect various respiratory viruses and bacteria in middle ear fluid (MEF) and nasopharyngeal aspirates (NPA) using polymerase chain reaction (PCR). METHODS: We collected MEF and NPA samples from 122 pediatric patients with AOM. Real-time PCR detected 11 types of respiratory viruses (respiratory syncytial virus A/B, parainfluenza virus 1/2/3, human metapneumovirus, influenza virus A/B, adenovirus, human bocavirus and rhino virus) and 7 types of bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Streptococcus pyogenes, Legionella pneumophila and Moraxella catarrhalis). MEF specimens were also examined using bacterial culture. RESULTS: At least 1 respiratory viral or bacterial pathogen was detected in MEF of 120 cases (98%) by viral and bacterial PCR and of 93 cases (76%) by viral PCR and bacterial culture. Respiratory viruses were detected in NPA of 84 cases (69%) and MEF of 67 cases (55%). The most common virus detected in MEF was respiratory syncytial virus (21%), followed by parainfluenza virus (15%). All the viruses present in MEF were also detected in NPA specimens. Bacteria were detected by PCR in MEF of 109 cases (89%); H. influenzae was the most frequently detected (65%). CONCLUSIONS: In many cases, pediatric AOM was found to constitute a respiratory polymicrobial infection. Multiplex PCR was useful to detect multiple respiratory viruses and bacteria in AOM. To understand intractable AOM, further studies regarding the clinical features of each viral and bacterial coinfection are required.

Verbal abuse during pregnancy increases frequency of newborn hearing screening referral: The Japan Environment and Children's Study.

BACKGROUND: Verbal abuse during pregnancy has a greater impact than physical and sexual violence on the incidence of postnatal depression and maternal abuse behavior towards their children. In addition, exposure of children (aged 12 months to adolescence) to verbal abuse from their parents exerts an adverse impact to the children's auditory function. However, the effect of verbal abuse during pregnancy on fetal auditory function has not yet been thoroughly investigated. OBJECTIVE: The objective of the study was to examine the relationship between intimate partner verbal abuse during pregnancy and newborn hearing screening (NHS) referral, which indicates immature or impaired auditory function. PARTICIPANTS AND SETTING: The Japan Environment and Children's Study is an ongoing nationwide population-based birth-cohort study designed to determine environmental factors during and after pregnancy that affect the development, health, or wellbeing of children. Pregnant women living in 15 areas of Japan were recruited between January 2011 and March 2014. METHODS: Multiple imputation for missing data was performed, followed by multiple logistic regression using 16 confounding variables. RESULTS: Of 104,102 records in the dataset, 79,985 mother-infant pairs submitted complete data for questions related to verbal and physical abuse and the results of NHS. Of 79,985 pregnant women, 10,786 (13.5%) experienced verbal abuse and 978 (1.2%) experienced physical abuse. Of 79,985 newborns, 787 (0.98%) received a NHS referral. Verbal abuse was significantly associated with NHS referral (adjusted odds ratio: 1.44; 95% confidence interval: 1.05-1.98). CONCLUSIONS: Verbal abuse should be avoided during pregnancy to preserve the newborn's auditory function.

Apnea hypopnea indices categorized by REM/NREM sleep and sleep positions in 100 children with adenotonsillectomy for obstructive sleep apnea disease.

OBJECTIVES: In pediatric obstructive sleep apnea (OSA), the relationship between rapid eye movement sleep and upper airway collapse, and between sleep position and airway dimensions are well known. However, the interrelations between these factors and the obstructive apnea hypopnea index (O-AHI) have not been thoroughly investigated. METHODS: A retrospective study including 100 children who underwent adenotonsillectomy between March 2010 and July 2017. Total O-AHI was divided into four subcategories by sleep stage and position. RESULTS: Preoperatively 14 of 47 mild cases of OSA (1 ≤ total O-AHI) and 17 of 18 moderate (5 ≤ total O-AHI) had time showing severe apnea (10 ≤ subcategorized O-AHI). Twenty-two of 24 severe cases (10 ≤ total O-AHI) exhibited very severe apnea (30 ≤ subcategorized O-AHI). All 11 very severe cases (30 ≤ total O-AHI) experienced more than 50 apnea events per hour in at least one of the O-AHI subcategories. After surgery, 23 of 70 cases classified as completely resolved (total O-AHI < 1) still had mild apnea in the O-AHI subcategories, and six of 13 cases who continued to experience apnea events had moderate-to-severe apnea. Seventeen cases worsened in the O-AHI subcategories, and total O-AHI deteriorated in two cases of the 17. The amount of REM sleep and use of the supine position increased significantly postoperatively in the quartile groups with the lowest baseline values (p < 0.0001). CONCLUSIONS: When an unexpected AHI value is encountered, the O-AHI subcategories may be informative regarding the indications for surgery and evaluating the efficacy thereof.

The gray scale value of ear tissues undergoing volume-rendering high-resolution cone-beam computed tomography.

OBJECTIVE: When the thresholds for VR reconstruction from multi-slice CT images are changed, problems develop when assessing pathologies in the absence of standardized thresholds. The advantages of CBCT include lower radiation exposure compared with other techniques and better visualization of small ear structures. However, a disadvantage is that the scanner provides unstandardized gray scale values, thus not CT numbers (Hounsfield units, HU). METHODS: We analyzed 88 sets of volume data obtained from temporal bones. The gray scale values were measured in aerated areas (two sites), along the ossicular chain (four sites) and in a bone area (one site) in the external and middle ears, and in soft tissue areas (five sites) and bone areas (two sites) in the inner ear. RESULTS: The standard male and female gray scale values were 2448-2970 and 2585-3091 for the aerated areas, 3248-4945 and 3359-5223 for the ossicular chains, 3368-4109 and 3371-4147 for soft tissues, and 4790-5776 and 5044-5959 for bone, respectively. Sex significantly affected the values (p<0.05). Significant differences between aerated areas and ossicular chains, and between soft tissues and bone, were evident (all p<0.0001). CONCLUSION: Volume-rendering (VR) images obtained by cone-beam computed tomography (CBCT) can be standardized simply by using fixed thresholds.

Single field-of-view tomographic imaging of 3D impurity emission distribution in magnetized edge plasma of LHD.

A new tomographic scheme is proposed for reconstructing three dimensional (3D) impurity emission distributions from two dimensional (2D) measurements with a single field-of-view in the magnetized edge plasma in a Large Helical Device (LHD). The 2D image is obtained with a multi-channel fiber array spectrometer, which views the entire region of the edge stochastic magnetic layer of LHD, including divertor plates, divertor legs, the stochastic layer, and the last closed flux surface. The scheme introduces new regularization terms in the Lagrangian function, based on the transport feature in magnetized plasma that the transport parallel to the magnetic field lines is much faster than the transport across the magnetic field, thus assuming smooth distribution in the parallel direction. The scheme is benchmarked with the test data of 3D distribution in the measurement volume, where the effectiveness of the various regularization terms is surveyed and feasibility of the scheme is confirmed. The new scheme is applied to the experimental data in LHD for carbon impurity emissions of C1+ and C3+, where the obtained distributions are discussed taking into account the plasma wall interaction and charge dependence of ionization potentials.