Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading cause of disability. Here, We used a two-sample Mendelian randomization approach using pooled statistics from genome-wide association studies of ISSHL (1491 cases, 196,592 controls) and depression (23,424 cases, 192,220 controls) in European populations. This study investigated the bidirectional relationship between single nucleotide polymorphisms associated with depression and ISSHL using inverse variance weighting.Additional sensitivity analyses, such as Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, were performed to assess the reliability of the findings. Significant causal association between genetic susceptibility to ISSHL and depression in a random-effects IVW approach (OR = 1.037, 95% CI = 1.004-1.072, P = 0.030). In contrast, genetic depression was not risk factors for ISSHL (OR = 1.134, 95% CI = 0.871-1.475, P = 0.350). After validation by different MR methods and the sensitivity analysis, all of the above results are consistent. The evidence we have gathered suggests a causal relationship between ISSHL and depression. The presence of the former induces or further exacerbates the latter, whereas a similar situation does not exist when the latter is an influencing factor.

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.

Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual stimulation in not only the auditory cortex, but also in the visual and audiovisual cortices. In the present study, we used an established model of loud noise exposure in rats to examine, for the first time, whether the crossmodal plasticity in the audiovisual cortex that occurs following a relatively mild degree of hearing loss emerges solely from altered intracortical processing or if thalamocortical changes also contribute to the crossmodal effects. Using a combination of an established pharmacological \'cortical silencing\' protocol and current source density analysis of the laminar activity recorded across the layers of the audiovisual cortex (i.e., the lateral extrastriate visual cortex, V2L), we observed layer-specific changes post-silencing in the strength of the residual visual, but not auditory, input in the noise exposed rats with mild hearing loss compared to rats with normal hearing. Furthermore, based on a comparison of the laminar profiles pre- versus post-silencing in both groups, we can conclude that noise exposure caused a re-allocation of the strength of visual inputs across the layers of the V2L cortex, including enhanced visual-evoked activity in the granular layer; findings consistent with thalamocortical plasticity. Finally, we confirmed that audiovisual integration within the V2L cortex depends on intact processing within intracortical circuits, and that this form of multisensory processing is vulnerable to disruption by noise-induced hearing loss. Ultimately, the present study furthers our understanding of the contribution of intracortical and thalamocortical processing to crossmodal plasticity as well as to audiovisual integration under both normal and mildly-impaired hearing conditions.

BACKGROUND: The cochlear implant (CI) is effective for rehabilitating patients with severe to profound sensorineural hearing loss. However, its placement and use have been associated with various complications, such as those affecting the vestibular system. The objective of this study was to compare vestibular function using the video head impulse test (vHIT) in pediatric patients before and after CI placement.
METHODS: A descriptive and retrospective study was conducted. The outcomes of 11 pediatric patients of both sexes with a history of profound hearing loss were evaluated. The results of vestibular-ocular reflex (VOR) gain, saccades, asymmetry, Pérez Rey (PR) index, and VOR/saccade ratio for both ears obtained by the vHIT test before and after CI placement were compared.
RESULTS: Of the 11 patients evaluated, the VOR gain showed that 81.8% had normal function, 18.2% had hypofunction, and no patients had hyperfunction before implantation. No statistically significant differences were found when compared with post-implant off and post-implant on conditions (p > 0.05). The extracted variables, asymmetry, PR index, and the VOR/saccades ratio also showed no statistically significant differences between the pre- and post-implant conditions, whether off or on.
CONCLUSIONS: The vestibular function of pediatric patients did not show significant changes before and after CI placement. The vHIT test is a valuable tool for assessing vestibular function and could be considered a criterion for surgical and rehabilitation decisions in patients undergoing CI placement.
UNASSIGNED: El implante coclear es un dispositivo eficaz para la rehabilitación de pacientes con hipoacusia neurosensorial severa a profunda. Sin embargo, su colocación y uso se ha asociado a diversas complicaciones, entre ellas a nivel del sistema vestibular. El objetivo del presente estudio fue comparar la función vestibular mediante la prueba de videoimpulso cefálico (vHIT) de pacientes pediátricos antes y después de la colocación del implante coclear.
UNASSIGNED: Se llevó a cabo un estudio descriptivo y retrospectivo. Se evaluaron los resultados de 11 pacientes pediátricos de ambos sexos con antecedente de hipoacusia profunda. Se compararon los resultados de ganancia del VOR, sacadas, asimetría, índice PR así como la relación VOR/sacadas para ambos oídos obtenidos mediante la prueba vHIT antes y después de la colocación del implante coclear.
RESULTS: De los 11 pacientes evaluados, la ganancia del VOR mostró que el 81.8% tenía normofunción, 18.2% hipofunción y ningún paciente hiperfunción antes del implante. Al compararlo con la ganancia post implante apagado y post implante encendido no se encontraron diferencias estadísticamente significativas (p > 0.05). Las variables sacadas, asimetría, índice PR así como la relación VOR/sacadas tampoco mostraron diferencias estadísticamente significativas entre las condiciones pre y pos implante ya sea apagado o encendido.
CONCLUSIONS: La función vestibular de pacientes pediátricos no mostró cambios significativos previo y posterior a la colocación del implante coclear. La prueba vHIT es una herramienta útil que permite evaluar la función vestibular y que podría considerarse como criterio para tomar decisiones quirúrgicas en pacientes que se encuentran en protocolo para implante coclear.

HDR syndrome is a rare disease characterized by hypoparathyroidism, deafness, and renal dysplasia. An autosomal dominant disease caused by heterozygous pathogenic GATA3 variants, the penetrance of each associated condition is variable. Literature reviews have provided some answers, but many questions remain, in particular what the relationship is between genotype and phenotype. The current study examines 28 patients with HDR syndrome combined with an exhaustive review of the literature. Some conditions such as hearing loss are almost always present, while others described as rare initially, do not seem to be so rare after all (genital malformations and basal ganglia calcifications). By modeling pathogenic GATA3 variants found in HDR syndrome, we found that missense variations appear to always be located in the same area (close to the two Zinc Finger domain). We describe new pathogenic GATA3 variants, of which some seem to always be associated with certain conditions. Many audiograms were studied to establish a typical audiometric profile associated with a phenotype in HDR. As mentioned in the literature, hearing function should always be assessed as early as possible and follow up of patients with HDR syndrome should include monitoring of parathyroid function and vesicoureteral reflux in order to prevent complications.

OBJECTIVE: Hearing impairment affects a small but significant percentage of newborns (0.1-0.4%). Newborn hearing screening (NHS) is recommended for early detection and treatment. The implementation of NHS can vary among countries. In this study, we present the methodology, organization, and technical requirements of NHS. This study analyzed results from a tertiary hospital, identified issues, and proposed solutions.
METHODS: In the studied region, there are five maternity hospitals and a perinatal intensive care center and in 2020, there were 5,864 live births. Screening is performed at three levels. The first screening is conducted on the 2nd-3rd day of a newborn\'s life in a maternity hospital, the first rescreening on the 3rd-6th week at a relevant ENT department, and the second rescreening on the 3rd-6th month of life at the regional screening center where the central database is also held.
RESULTS: In the studied region, 5,793 out of 5,864 (98.79%) newborns received NHS in 2020. Of these, 120 (2.07%) were tested positive on their first screening. Ninety-four patients (78.3%) of those attended the ENT department for a first rescreening. Thirty-four patients (0.59% of total) were tested positive again and referred to the regional screening center. Out of the 27 patients who attended the second rescreening, four (0.07% of the total) were ultimately diagnosed with hearing impairment.
CONCLUSIONS: Our study found that newborn hearing screening (NHS) in our region achieved a high compliance rate of 98.8% for initial screenings in 2020. However, challenges remain in the rescreening process due to data management issues, inter-regional cooperation, and public awareness. The recent implementation of mandatory screenings, updated guidelines, and a centralized database is expected to enhance the effectiveness of NHS. Further research is needed to evaluate these improvements.

UNASSIGNED: Sensorineural hearing loss (SNHL) is the most common form of sensory deprivation and is often unrecognized by patients, inducing not only auditory but also nonauditory symptoms. Data-driven classifier modeling with the combination of neural static and dynamic imaging features could be effectively used to classify SNHL individuals and healthy controls (HCs).
UNASSIGNED: We conducted hearing evaluation, neurological scale tests and resting-state MRI on 110 SNHL patients and 106 HCs. A total of 1,267 static and dynamic imaging characteristics were extracted from MRI data, and three methods of feature selection were computed, including the Spearman rank correlation test, least absolute shrinkage and selection operator (LASSO) and t test as well as LASSO. Linear, polynomial, radial basis functional kernel (RBF) and sigmoid support vector machine (SVM) models were chosen as the classifiers with fivefold cross-validation. The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity and accuracy were calculated for each model.
UNASSIGNED: SNHL subjects had higher hearing thresholds in each frequency, as well as worse performance in cognitive and emotional evaluations, than HCs. After comparison, the selected brain regions using LASSO based on static and dynamic features were consistent with the between-group analysis, including auditory and nonauditory areas. The subsequent AUCs of the four SVM models (linear, polynomial, RBF and sigmoid) were as follows: 0.8075, 0.7340, 0.8462 and 0.8562. The RBF and sigmoid SVM had relatively higher accuracy, sensitivity and specificity.
UNASSIGNED: Our research raised attention to static and dynamic alterations underlying hearing deprivation. Machine learning-based models may provide several useful biomarkers for the classification and diagnosis of SNHL.

UNASSIGNED: Early identification of newborns with congenital cytomegalovirus (CMV) is necessary to provide antiviral therapy and other interventions that can improve outcomes. Prior research demonstrates that universal newborn CMV screening would be the most cost-effective approach to identifying newborns who are infected. CMV is not uniformly prevalent, and it is uncertain whether universal screening would remain cost-effective in lower-prevalence neighborhoods. Our aim was to identify geographic heterogeneity in the cost-effectiveness of universal newborn CMV screening by combining a geospatial analysis with a preexisting cost-effectiveness analysis.
UNASSIGNED: This study used the CMV testing results and zip code location data of 96 785 newborns in 7 metropolitan areas who had been tested for CMV as part of the CMV and Hearing Multicenter Screening study. A hierarchical bayesian generalized additive model was constructed to evaluate geographic variability in the odds of CMV. The zip code-level odds of CMV were then used to weight the results of a previously published model evaluating universal CMV screening vs symptom-targeted screening.
UNASSIGNED: The odds of CMV were heterogeneous over large geographic scales, with the highest odds in the southeastern United States. Universal screening was more cost-effective and afforded more averted cases of severe hearing loss than targeted testing. Universal screening remained the most cost-effective option even in areas with the lowest CMV prevalence.
UNASSIGNED: Universal newborn CMV screening is cost-effective regardless of underlying CMV prevalence and is the preferred strategy to reduce morbidity from congenital CMV.

Auditory hair cells (HCs) are the mechanosensory receptors of the cochlea, and HC loss or malfunction can result from genetic defects. Dock4, a member of the Dock180-related protein superfamily, is a guanine nucleotide exchange factor for Rac1, and previous reports have shown that Dock4 mutations are associated with autism spectrum disorder, myelodysplastic syndromes, and tumorigenesis. Here, we found that Dock4 is highly expressed in the cochlear HCs of mice. However, the role of Dock4 in the inner ear has not yet been investigated. Taking advantage of the piggyBac transposon system, Dock4 knockdown (KD) mice were established to explore the role of Dock4 in the cochlea. Compared to wild-type controls, Dock4 KD mice showed significant hearing impairment from postnatal day 60. Dock4 KD mice showed hair bundle deficits and increased oxidative stress, which eventually led to HC apoptosis, late-onset HC loss, and progressive hearing loss. Furthermore, molecular mechanism studies showed that Rac1/β-catenin signaling was significantly downregulated in Dock4 KD cochleae and that this was the cause for the disorganized stereocilia and increased oxidative stress in HCs. Overall, our work demonstrates that the Dock4/Rac1/β-catenin signaling pathway plays a critical role in the maintenance of auditory HCs and hearing function.

BACKGROUND: Sensory information obtained from the visual, somatosensory, and vestibular systems is responsible for regulating postural control, and if damage occurs in one or more of these sensory systems, postural control may be altered.
OBJECTIVE: To evaluate and compare the postural sway velocity between children with normal hearing and with sensorineural hearing loss (SNHL), matched by sex and age group, and to compare the postural sway velocity between children with normal hearing and with SNHL, with and without vestibular dysfunction.
METHODS: Cross-sectional study that evaluated 130 children (65 with normal hearing and 65 with SNHL), of both sexes and aged between 7 and 11 years, from public schools of the city of Caruaru, Pernambuco state, Brazil. The postural sway velocity of the center of pressure (COP) was assessed by a force platform, in two directions, anteroposterior (AP) and mediolateral (ML)), in three positions, namely bipedal support with feet together and parallel (parallel feet (PF)), bipedal support with one foot in front of the other (tandem foot (TF)), and single-leg support (one foot (OF)), evaluated with the eyes open and closed.
RESULTS: Children with SNHL demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, with significant differences in the AP direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.003) and closed (PF: p = 0.050; TF: p = 0.005). The same occurred in the ML direction, with the eyes open (PF: p = 0.001; TF: p = 0.000; OF: p = 0.001) and closed (PF: p = 0.002; TF: p = 0.000). The same occurred in relation to vestibular function, where the children with SNHL with an associated vestibular dysfunction demonstrated greater postural sway velocity compared to children with normal hearing in all the positions evaluated, demonstrating significant differences in the AP direction, with the eyes open (TF: p = 0.001; OF: p = 0.029) and eyes closed (PF: p = 0.036; TF: p = 0.033). The same occurred in the ML direction, with the eyes open (TF: p = 0.000) and with the eyes closed (PF: p = 0.008; TF: p = 0.009).
CONCLUSIONS: Children with SNHL demonstrated greater instability of postural control than children with normal hearing in all the directions assessed. Children with SNHL and an associated vestibular dysfunction demonstrated the greatest instability of postural control in this study.