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Background: Familial Meniere's disease (FMD) is a rare polygenic disorder of the inner ear. Mutations in the connexin gene family, which encodes gap junction proteins, can also cause hearing loss, but their role in FMD is largely unknown. Methods: We retrieved exome sequencing data from 94 individuals in 70 Meniere's disease (MD) families. Through gene burden analysis, we calculated the enrichment of rare variants (allele frequency < 0.05) in connexins genes in FMD individuals compared with the reference population. The connexin monomer and the homomeric connexon structural models were predicted using AlphaFold2 and HDOCK. RT-qPCR and immunofluorescence were done in mice cochleae to identify expression of the mouse ortholog candidate gene Gjd3. Results: We found an enrichment of rare missense variants in the GJD3 gene when comparing allelic frequencies in FMD (N = 94) with the Spanish reference population (OR = 3.9[1.92–7.91], FDR = 2.36E-03). In the GJD3 sequence, we identified a rare haplotype (TGAGT) composed of two missense, two synonymous, and one downstream variant. This haplotype was found in five individuals with FMD, segregating in three unrelated families with a total of ten individuals; and in another eight MD individuals. GJD3 encodes the gap junction protein delta 3, also known as human connexin 31.9 (Cx31.9). The protein model predicted that the NP_689343.3:p.(His175Tyr) missense variant could modify the interaction between connexins and the connexon assembly, affecting the homotypic GJD3 gap junction between cells. Our studies in mice revealed that Gjd3—encoding Gjd3 or mouse connexin 30.2 (Cx30.2)—was expressed in the organ of Corti and vestibular organs, particularly in the tectorial membrane, the base of inner and outer hair cells and the nerve fibers. Conclusions: The present results describe a novel association between GJD3 and FMD, providing evidence that FMD is related to changes in the inner ear channels, and supporting a new role of tectorial membrane proteins in MD. [ABSTRACT FROM AUTHOR]

Background: Progress in medical education is reflected in healthcare quality and patient satisfaction. However, there are still gaps in knowledge regarding the patients' expectations of general practitioners (GPs), even though patients' interactions with GPs are among the most frequent in healthcare. Accordingly, this study investigated the qualities desired by adults in GPs, intending to include them in future medical humanization education to enhance the patients' experience. Methods: Using an online survey, 1057 respondents (52.8% female; mean age, 46.55 years old, SD 16.03) were asked to rate 15 statements on a scale of 1 to 10 regarding desirable characteristics of general practitioners. In addition to the respondents' high regard for their GP's ongoing education and sincerity in conveying both positive and negative information, the findings suggest that the socio-demographic attributes of the respondents influence their expectations of GPs. Results: Women had higher overall expectations than men. In addition, those who reported higher satisfaction with their lives and recent healthcare users had higher expectations of GPs than those who were dissatisfied. The youngest group of respondents exhibited the lowest expectations of the GPs' attributes, except for their greater willingness to engage in discussions with GPs regarding personal or professional issues, compared with the older groups. Conclusions: The information presented in this work can be utilized during medical students' humanization training and physicians' continuing education. The knowledge gained should enhance GPs' awareness of the distinctions in patients' expectations, enabling them to adapt their approach and services to align with their patients' unique needs, expectations, and experiences. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated the presence of resident immune cells in the healthy inner ear. Aim: This scoping review aimed to systematize this knowledge by collecting the data on resident immune cells in the inner ear of different species under steady-state conditions. Methods: The databases PubMed, MEDLINE (Ovid), CINAHL (EBSCO), and LIVIVO were used to identify articles. Systematic reviews, experimental studies, and clinical data in English and German were included without time limitations. Results: The search yielded 49 eligible articles published between 1979 and 2022. Resident immune cells, including macrophages, lymphocytes, leukocytes, and mast cells, have been observed in various mammalian inner ear structures under steady-state conditions. However, the physiological function of these cells in the healthy cochlea remains unclear, providing an opportunity for basic research in inner ear biology. Conclusions: This review highlights the need for further investigation into the role of these cells, which is crucial for advancing the development of therapeutic methods for treating inner ear disorders, potentially transforming the field of otolaryngology and immunology. [ABSTRACT FROM AUTHOR]

Tinnitus is a phantom percept of noise heard only by the affected person. The principal problem of persons suffering from tinnitus is the inability to deflect their attention from the phantom sound, resulting in insomnia and problems with concentration, followed by significant health issues. To date, no therapy would relieve patients from the phantom sound. Instead, commonly used therapeutic approaches for tinnitus aim primarily at the reduction of tinnitus-induced distress and are based on various tinnitus habituation methods. Our project aims to quench the tinnitus percept using an implant. To develop such an implant, this research group joined the INTAKT network initiated by the German Federal Ministry of Education and Research and dedicated to the development of smart implants. During this still ongoing, prospective clinical study, the efficacy of two protocols using electrical stimulation is assessed for tinnitus silencing. The electrical stimulation used in the presented study is non-invasive and applied on three consecutive days in the form of short sessions. In a sample of 48 subjects, following three stimulation sessions, 48% of patients reported a significant reduction of tinnitus loudness; 10% reported a brief increase of tinnitus loudness, and 42% stated no change. In one case, the first course of stimulation led to the total distinguishing of tinnitus. On average, the stimulation did not affect the grade of tinnitus-induced distress during the time of measurement. Our current results prompt us to broaden our investigations, expand the subject sample, and further optimize the stimulation conditions.

Tinnitus is a phantom sound perceived only by the affected person. Although the causes for tinnitus may be very diverse (e.g. hearing loss, cardiovascular diseases, diabetes, Meniere’s disease, otosclerosis), they all lead to pathological activation of the auditory pathway. Cochlear implants are electronic inner ear prostheses used to restore the hearing abilities of hard of hearing people. It has been noticed that the cochlear implants not only enable hearing but also reduce tinnitus that usually accompanies deafness and hearing loss. One of the likely mechanisms behind the latter phenomena is thought to be the unknown properties of electrical stimulus. This project was designed as a proof of concept for a device, which would be sending the tinnitus-suppressing electrical signal. To achieve this, the project was split into a preclinical part using experimental animals (guinea pigs) and a clinical trial part with tinnitus patients. In the preclinical part, together with Inomed Medizintechnik GmbH, we are testing the physical design and biocompatibility of anti-tinnitus implant. In the clinical part of the project, we use an electrical stimulation in the ear canal, through the eardrum (tinnitus patients), or via cochlear implant in a sample of cochlear implant patients (pre- and post-implantation). We ask the patients to mark the loudness of their tinnitus on a visual scale from 1 to 10 before, during and after routine electrical stimulation and quality of the tinnitus The results obtained during our preclinical and clinical testing as well as future plans will be presented and discussed.