A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.

Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.

Signaling pathways regulating the immune function of cochlear supporting cells and their involvement in cochlear pathophysiology.

The inner ear, including the cochlea, used to be regarded as an immune-privileged site because of its immunologically isolated environment caused by the blood-labyrinthine barrier. Cochlear resident macrophages, which originate from the yolk sac or fetal liver during the embryonic stage and are maintained after birth, are distributed throughout various regions of the cochlear duct. Intriguingly, these cells are absent in the organ of Corti, where hair cells (HCs) and supporting cells (SCs) are located, except for a limited number of ionized calcium-binding adapter molecule 1 (Iba1)-positive cells. Instead, SCs exert glial functions varying from a quiescent to an emergency state. Notably, SCs acquire the nature of macrophages and begin to secrete inflammatory cytokines during viral infection in the organ of Corti, which is ostensibly unprotected owing to the lack of general resident macrophages. This review provides an overview of both positive and negative functions of SCs enabled to acquire macrophage phenotypes upon viral infection focusing on the signaling pathways that regulate these functions. The former function protects HCs from viral infection by inducting type I interferons, and the latter function induces HC death by necroptosis, leading to sensorineural hearing loss. Thus, SCs play contradictory roles as immune cells with acquired macrophage phenotypes; thereby, they are favorable and unfavorable to HCs, which play a pivotal role in hearing function.

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq.

BACKGROUND: The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. METHODS: We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. RESULTS: Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. CONCLUSION: Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL.

Bi-allelic variants in the mitochondrial RNase P subunit PRORP cause mitochondrial tRNA processing defects and pleiotropic multisystem presentations.

Human mitochondrial RNase P (mt-RNase P) is responsible for 5' end processing of mitochondrial precursor tRNAs, a vital step in mitochondrial RNA maturation, and is comprised of three protein subunits: TRMT10C, SDR5C1 (HSD10), and PRORP. Pathogenic variants in TRMT10C and SDR5C1 are associated with distinct recessive or x-linked infantile onset disorders, resulting from defects in mitochondrial RNA processing. We report four unrelated families with multisystem disease associated with bi-allelic variants in PRORP, the metallonuclease subunit of mt-RNase P. Affected individuals presented with variable phenotypes comprising sensorineural hearing loss, primary ovarian insufficiency, developmental delay, and brain white matter changes. Fibroblasts from affected individuals in two families demonstrated decreased steady state levels of PRORP, an accumulation of unprocessed mitochondrial transcripts, and decreased steady state levels of mitochondrial-encoded proteins, which were rescued by introduction of the wild-type PRORP cDNA. In mt-tRNA processing assays performed with recombinant mt-RNase P proteins, the disease-associated variants resulted in diminished mitochondrial tRNA processing. Identification of disease-causing variants in PRORP indicates that pathogenic variants in all three subunits of mt-RNase P can cause mitochondrial dysfunction, each with distinct pleiotropic clinical presentations.

Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss.

Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.

Luteolin inhibits the JAK/STAT pathway to alleviate auditory cell apoptosis of acquired sensorineural hearing loss based on network pharmacology, molecular docking, molecular dynamics simulation, and experiments in vitro.

PURPOSE: The study aimed to explore the mechanisms of luteolin in acquired sensorineural hearing loss (SNHL) through network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. METHODS: First, the practices of network pharmacology were used to obtain the intersecting targets of luteolin and acquired SNHL, construct the PPI (Protein-Protein Interaction) network, conduct GO and KEGG enrichments, and establish luteolin-acquired SNHL-target-pathway network, aiming to gain the core targets and pathways. Then, the affinity between the core targets and luteolin was verified by molecular docking. Moreover, molecular dynamics (MD) simulation was applied to simulate the binding between targets and luteolin. Finally, with the HEI-OC1 cell line, some molecular biology techniques were adopted to verify the pharmacological actions of luteolin and the significance of the pathway from KEGG enrichment in luteolin-protecting auditory cell damage related to acquired SNHL. RESULTS: 14 intersecting targets were obtained, and the 10 core targets were further verified through molecular docking and MD simulation to get 5 core targets. The JAK/STAT was selected as the critical pathway through KEGG enrichment. Luteolin could dose-dependently alleviate auditory cell apoptosis by inhibiting the JAK/STAT pathway, confirmed by a series of experiments in vitro. CONCLUSION: This study manifested that luteolin could reduce acquired SNHL-related auditory cell apoptosis through the JAK/STAT pathway, which provided a new idea for acquired SNHL pharmacological treatment.

Dispersed DNA variants underlie hearing loss in South Florida's minority population.

BACKGROUND: We analyzed the genetic causes of sensorineural hearing loss in racial and ethnic minorities of South Florida by reviewing demographic, phenotypic, and genetic data on 136 patients presenting to the Hereditary Hearing Loss Clinic at the University of Miami. In our retrospective chart review, of these patients, half self-identified as Hispanic, and the self-identified racial distribution was 115 (86%) White, 15 (11%) Black, and 6 (4%) Asian. Our analysis helps to reduce the gap in understanding the prevalence, impact, and genetic factors related to hearing loss among diverse populations. RESULTS: The causative gene variant or variants were identified in 54 (40%) patients, with no significant difference in the molecular diagnostic rate between Hispanics and Non-Hispanics. However, the total solve rate based on race was 40%, 47%, and 17% in Whites, Blacks, and Asians, respectively. In Non-Hispanic Whites, 16 different variants were identified in 13 genes, with GJB2 (32%), MYO7A (11%), and SLC26A4 (11%) being the most frequently implicated genes. In White Hispanics, 34 variants were identified in 20 genes, with GJB2 (22%), MYO7A (7%), and STRC-CATSPER2 (7%) being the most common. In the Non-Hispanic Black cohort, the gene distribution was evenly dispersed, with 11 variants occurring in 7 genes, and no variant was identified in 3 Hispanic Black probands. For the Asian cohort, only one gene variant was found out of 6 patients. CONCLUSION: This study demonstrates that the diagnostic rate of genetic studies in hearing loss varies according to race in South Florida, with more heterogeneity in racial and ethnic minorities. Further studies to delineate deafness gene variants in underrepresented populations, such as African Americans/Blacks from Hispanic groups, are much needed to reduce racial and ethnic disparities in genetic diagnoses.

Two novel heterozygous exonic deletions lead to Chanarin-Dorfman syndrome in a patient with congenital ichthyosis, sensorineural hearing loss, and liver dysfunction.

Chanarin-Dorfman syndrome is an autosomal recessively inherited disorder characterized by ichthyosis, sensorineural hearing loss, and hepatic dysfunction. We report on a 60-year-old female of Venezuelan descent who presented with congenital ichthyosis, progressive sensorineural hearing loss, and liver cirrhosis. We identify a heterozygous copy number deletion involving exon 1 and another heterozygous deletion involving exon 3 of the ABHD5 gene. Exon 2 is preserved. Both deletions were confirmed with RT-PCR. RNAseq from peripheral blood shows a reduction of ABHD5 expression overall and an absence of exon 3 expression, confirming the deleterious effects of the identified deletions. We present exonic deletions as a potentially common type of ABHD5 variation.

ACOX1 gain-of-function variation in a 10-years-old patient responsive to immunomodulating therapy.

A heterozygous gain-of-function variant in the acyl-CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10-year-old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition.

Three-dimensional heavily T2-weighted FLAIR in the detection of blood-labyrinthine barrier leakage in patients with sudden sensorineural hearing loss: comparison with T1 sequences and application of deep learning-based reconstruction.

OBJECTIVE: Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement. METHODS: Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared. RESULTS: Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5 days after presentation (63.38 vs. 41.85, p = 0.019). CONCLUSION: 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period. CLINICAL RELEVANCE STATEMENT: Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction. KEY POINTS: • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information.

Establishing multifactorial risk factors for adult-onset hearing loss: A systematic review with topic modelling and synthesis of epidemiological evidence.

BACKGROUND: This systematic review explores the multifaceted nature of risk factors contributing to adult-onset HL. The objective was to synthesise the most recent epidemiological evidence to generate pooled proportional incidences for the identified risk factors. METHODS: We conducted an extensive search of electronic databases (MEDLINE, EMBASE, and psychINFO) for studies providing epidemiological evidence of risk factors associated with hearing loss. Topic modelling using Latent Dirichlet Allocation (LDA) was first conducted to determine how many risk factor themes were available from the papers. Data were analysed by calculating the pooled proportional incidence using a meta-analysis of proportions. RESULTS: From the 72 studies reviewed, six key risk factor themes emerged through LDA topic modelling. The review identified ototoxicity, primarily caused by cancer treatments and antibiotics, infectious diseases like COVID-19, occupational noise exposure, lifestyle factors, health conditions, biological responses, and age progression as significant risk factors for HL. The highest proportional incidence was found with cancer-related ototoxicity at 55.4% (95%CI: 39.0-70.7), followed closely by ototoxicity from infectious diseases at 50.0% (95%CI: 28.5-71.5). This high proportional incidence suggests the need to explore less destructive therapies and proactively monitor hearing function during treatments. CONCLUSIONS: The findings of this review, combined with the synthesis of epidemiological evidence, enhance our understanding of hearing loss (HL) pathogenesis and highlight potential areas for intervention, thereby paving the way for more effective prevention and management of adult-onset hearing loss in our ageing global population.

The neurological core features of the infantile-onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family.

AIM: Biallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features. METHODS: Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy-associated genes yielded negative results. RESULTS: Whole-exome sequencing analysis identified the homozygous substitution c.256C>T (p.Gln86Ter) in the PTRH2 gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic. At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug-resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy. INTERPRETATION: Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.

Cardiovascular Risk Factors, Cerebral Small Vessel Disease, and Subsequent Risk of Stroke in Patients with Idiopathic Sudden Sensorineural Hearing Loss: Systematic Review and Meta-Analyses of the Current Literature.

Vascular involvement in the pathophysiology of idiopathic sudden sensorineural hearing loss (iSSNHL) has been previously proposed. The objective of this study was to perform a systematic review of the current literature and conduct meta-analyses to evaluate associations between cardiovascular risk factors, cerebral small vessel disease, and subsequent stroke after presentation with iSSNHL. Three systematic literature reviews and meta-analyses were conducted using PubMed, Embase, and CINAHL. All studies investigating associations between iSSNHL and the cardiovascular risk factors: body mass index (BMI), diabetes mellitus, hyperlipidemia, hypertension, medical history of myocardial infarction (MI), smoking, the degree of white matter hyperintensities, and incidence of stroke were included. Adhering to the PRISMA guidelines, two independent reviewers reviewed the articles and assessed risk of bias. The cardiovascular risk factors of abnormal BMI, diabetes, hypertension, total cholesterol, low-density lipoprotein cholesterol, and a medical history of MI were significantly associated with iSSNHL. The adjusted hazard ratio of a higher degree of white matter hyperintensities was 0.70 (95% CI 0.44, 1.12). Patients with iSSNHL showed a higher risk of stroke compared to controls, with hazard ratios ranging from 1.22 up to 4.08. Several cardiovascular risk factors are more frequently present in patients with iSSNHL than in the general population. The degree of white matter hyperintensities does not appear to be increased in patients with iSSNHL, while the risk of stroke following ISSNHL is increased. Prospective studies with larger study populations are needed to confirm the associations between generalized cardiovascular disease and iSSNHL and to assess whether these patients benefit from cardiovascular risk management to prevent future cardiovascular and cerebrovascular disease.

Vertebrobasilar System Laterality and Idiopathic Sudden Sensorineural Hearing Loss.

INTRODUCTION: The etiology of idiopathic sudden sensorineural hearing loss (ISSNHL) remains elusive, with vascular compromise as a proposed cause. This study aimed to explore the correlation between the vertebrobasilar vascular system laterality (VBVSL) and ISSNHL laterality. METHODS: We conducted a retrospective analysis of consecutive patients diagnosed with ISSNHL from 2015 to 2020. The VBVSL pattern was established via magnetic resonance imaging scans by a neuroradiologist. ISSNHL occurring contralaterally to the basilar artery (BA) curvature or ipsilaterally to the dominant vertebral artery (VA) was designated as a "positive match," with all other scenarios classified as a "negative match." RESULTS: Our study included 191 ISSNHL patients (median age 57 years, 89 males, 93 right ears). The majority of patients did not exhibit a positive match between ISSNHL laterality and the sides of BA curvature or dominant VA (28.8% and 36.6% for BA and VA, respectively). Notably, VA-positive match patients were significantly older than VA-negative match patients (59 vs. 53 years, p = 0.043), with a similar trend observed in BA-positive match compared to BA-negative match (59 vs. 54.5 years, p = 0.057). However, there was no significant difference in any other clinical, audiometric, or outcome factors between the positive and negative match groups. CONCLUSION: The findings suggest no association between VBVSL and ISSNHL laterality. Furthermore, patients in the positive match group did not exhibit distinct clinical or audiometric features compared to those without a match.

The Benefit of Bimodal Hearing and Beamforming for Cochlear Implant Users.

INTRODUCTION: Cochlear implantation is the standard treatment for severe to profound hearing loss. While cochlear implant (CI) users can communicate effectively in quiet environments, speech understanding in noise remains challenging. Bimodal hearing, combining a CI in one ear and a hearing aid (HA) in the other, has shown advantages over unilateral electrical hearing, especially for speech understanding in noisy conditions. Beamforming is a technique used to improve speech understanding in noise by detecting sound direction and enhancing frontal (speech) sounds while attenuating background noise. One specific beamformer, Stereozoom, combines signals from microphones in both ears to create a focused beam toward the front resulting in a binaural beamformer (BB), in order to improve speech intelligibility in noise for bilateral and bimodal CI users. METHODS: A prospective crossover study involving 17 bimodal CI users was conducted, and participants were tested with various device configurations (CI, HA, CI + HA) with and without BB. Speech recognition testing with the Dutch/Flemish matrix test was performed in a sound-attenuated booth with diffuse noise to simulate realistic listening conditions. RESULTS: The results showed a statistically significant benefit of bimodal hearing over the CI configuration and showed a statistical significant benefit of BB for the CI and CI + HA configuration. The benefit of BB in the HA configuration was not statistically significant probably due to the higher variance. The benefit of BB in the three configurations did not differ statistically significant. CONCLUSION: In conclusion, bimodal hearing offers advantages for speech understanding in noise for CI users. BB provides a benefit in various device configurations, leading to improved speech intelligibility when speech comes from the front in challenging listening environments.

Changes in temporal lobe activation during a sound stimulation task in patients with sensorineural tinnitus: a multi-channel near-infrared spectroscopy study.

BACKGROUND: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. METHODS: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. RESULTS: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. CONCLUSIONS: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.

Serum lipid metabolism characteristics and potential biomarkers in patients with unilateral sudden sensorineural hearing loss.

BACKGROUND: Glycerophospholipids (GPLs) are essential for cell membrane structure and function. Sphingomyelin and its metabolites regulate cell growth, apoptosis, and stress responses. This study aimed to investigate lipid metabolism in patients experiencing sudden sensorineural hearing loss across all frequencies (AF-SSNHL). METHODS: The study included 60 patients diagnosed with unilateral AF-SSNHL, among whom 30 patients had a level of hearing improvement ≥ 15 dB after 6 months of follow-up. A propensity score-matched (2:1) control group was used. Liquid chromatography‒mass spectrometry based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the lipids change. The "lipidome" R package and weighted gene co-expression network analysis (WGCNA) were utilised to assess the lipids' structural features and the association between lipids and hearing. RESULTS: Lipidomics successfully differentiated the AF-SSNHL group from the control group, identifying 17 risk factors, mainly including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and related metabolites. The ratios of lysophosphatidylcholine/PC, lysophosphatidylethanolamine/PE, and lysodimethylphosphatidylethanolamine/PE were upregulated, while some glycerophospholipid (GPL)-plasmalogens were downregulated in the AF-SSNHL group, indicating abnormal metabolism of GPLs. Trihexosylceramide (d34:1), PE (18:1e_22:5), and sphingomyelin (d40:3) were significantly different between responders and nonresponders, and positively correlated with hearing improvement. Additionally, the results of the WGCNA also suggested that partial GPL-plasmalogens were positively associated with hearing improvement. CONCLUSION: AF-SSNHL patients exhibited abnormally high blood lipids and pronounced GPLs metabolic abnormalities. Sphingolipids and GPL-plasmalogens had an association with the level of hearing improvement. By understanding the lipid changes, clinicians may be able to predict the prognosis of hearing recovery and personalize treatment approaches.

Japanese spotted fever complicated by acute sensorineural hearing loss.

Japanese spotted fever is an emerging rickettsiosis caused by Rickettsia japonica and is characterized by high fever, rash, and eschar formation. Other symptoms are often vague and nonspecific and include headaches, nausea, vomiting, and myalgia. We present a case of a 46-year-old woman with Japanese spotted fever, complicated by transient bilateral sensorineural hearing loss and presenting cutaneous IgM/IgG immune complex vasculitis. The patient was admitted with a history of several days of high fever, generalized skin erythema, and hearing impairment. Laboratory findings revealed thrombocytopenia and elevated liver enzyme and C-reactive protein levels. Pure-tone audiometry revealed bilateral sensorineural hearing loss, and a skin biopsy revealed leukocytoclastic vasculitis with deposition of C3 and IgM on the vessel walls. Under the tentative diagnosis of rickettsiosis, scrub typhus, or Japanese spotted fever, the patient was treated with minocycline, and her symptoms improved within approximately 10 days. A definitive diagnosis was made on the basis of a serological test showing increased antibody levels against Rickettsia japonica. Japanese spotted fever can cause transient sensorineural hearing loss, a rare complication that presents with cutaneous IgM/IgG immune complex vasculitis.

"Repository of Cochlear Implant Information:" A Multi-Institutional REDCap Database.

PURPOSE: To describe the creation of a multi-center cochlear implant database as a template for future medical database design. The first clinical question examined was the association between BMI on cochlear implant surgical time and postoperative outcome. MATERIALS AND METHODS: A retrospective repository in REDCap, named the "Repository of Cochlear Implant Information" (ROCII), was created and collected de-identified data on patients who underwent cochlear implantation. Data was exported and stratified into three BMI groupings (<25, 25.0-29.9, ≥ 30.0). Differences in surgical time and AZBio Sentence Test postoperative score changes were analyzed using the mixed-effect model. RESULTS: The mean BMI (n = 145) was 28.52, and the mean surgical time was 128.9 min. The BMI < 25 reference group (n = 50) and the BMI 25.0-29.9 group (n = 50) had an identical mean surgical time of 127.5 min. The BMI ≥30.0 group (n = 45) had a mean surgical time of 132 min, however this difference was not statistically significant when compared to the reference group (p = 0.4727). The mean AZBio postoperative score change (n = 74) was 63.32. The BMI < 25 reference group (n = 29) had a mean postoperative change of 56.66. The BMI 25.0-29.9 group (n = 22) and BMI ≥30.0 group (n = 23) had mean postoperative changes of 61.32 and 73.65 respectively, however these differences were not statistically significant compared to the reference group (p = 0.5847, 0.0637). CONCLUSION: BMI did not have a significant association with surgical time or postoperative outcome and therefore should not be a contraindication for implantation. ROCII will facilitate a deeper understanding of the evaluation process, outcomes, and patient experience of cochlear implantation across institutions. LEVEL OF EVIDENCE: Level 1.

Efficacy of intratympanic steroid therapy for severe and profound sudden sensorineural hearing loss.

BACKGROUND: Intratympanic steroids (ITS) in treating sudden sensorineural hearing loss (SSNHL) have become more widespread. AIM: This study investigates whether ITS treatment provides additional benefits when combined with systemic steroids (SS) in patients with severe and profound SSNHL. MATERIALS AND METHODS: Patients diagnosed with severe and profound SSNHL were divided into two groups: SS group and SS combined with ITS group. Pure-tone audiometry was performed before and three months after treatment completion. The pure-tone average (PTA), frequency-specific hearing gains, and average values were compared between the groups. RESULTS: The study included 57 patients (27 SS, 30 ITS), with a mean age of 50.09 ± 15.56. Before treatment: SS PTA 84.40 ± 15 dB HL, ITS 87.50 ± 9.38 dB HL (p = 0.36). After treatment: SS 62.2 ± 23.13 dB HL, ITS 65.17 ± 12.19 dB HL (p = 0.55). Average hearing gain: SS 22.19 ± 13.81 dB HL, ITS 22.33 ± 12.24 dB HL (p = 0.96). Frequency-specific gains were similar (p > 0.05). SS group: 12 slight improvement, 10 no improvement, 3 partial, 2 complete recovery. ITS group: 23 slight improvement, 6 no improvement, 1 partial. CONCLUSION: In our study, combining ITS with SS treatment did not provide additional benefits in treating severe and profound SSNHL.