-
Molecular Therapy : the Journal of the... Jan 2024Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region...
Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region of the stereocilia, and mutations in TPRN cause hereditary hearing loss through an unknown mechanism. Here, using biochemistry and dual stimulated emission depletion microscopy imaging, we show that the TPRN, together with its binding proteins CLIC5 and PTPRQ, forms concentric rings in the taper region of stereocilia. The disruption of TPRN rings, triggered by the competitive inhibition of the interaction of TPRN and CLIC5 or exogenous TPRN overexpression, leads to stereocilia degeneration and severe hearing loss. Most importantly, restoration of the TPRN rings can rescue the damaged auditory function of Tprn knockout mice by exogenously expressing TPRN at an appropriate level in HCs via promoter recombinant adeno-associated virus (AAV). In summary, our results reveal highly structured TPRN rings near the taper region of stereocilia that are crucial for stereocilia function and hearing. Also, TPRN ring restoration in stereocilia by AAV-Tprn effectively repairs damaged hearing, which lays the foundation for the clinical application of AAV-mediated gene therapy in patients with TPRN mutation.
Topics: Animals; Humans; Mice; Deafness; Hearing; Hearing Loss; Mice, Knockout; Proteins; Receptor-Like Protein Tyrosine Phosphatases, Class 3; Stereocilia
PubMed: 37952086
DOI: 10.1016/j.ymthe.2023.11.011 -
Molecular Therapy : the Journal of the... Sep 2023Hearing loss is a common disorder affecting nearly 20% of the world's population. Recently, studies have shown that inner ear gene therapy can improve auditory function...
Hearing loss is a common disorder affecting nearly 20% of the world's population. Recently, studies have shown that inner ear gene therapy can improve auditory function in several mouse models of hereditary hearing loss. In most of these studies, the underlying mutations affect only a small number of cell types of the inner ear (e.g., sensory hair cells). Here, we applied inner ear gene therapy to the Ildr1 (Ildr1) mouse, a model of human DFNB42, non-syndromic autosomal recessive hereditary hearing loss associated with ILDR1 variants. ILDR1 is an integral protein of the tricellular tight junction complex and is expressed by diverse inner ear cell types in the organ of Corti and the cochlear lateral wall. We simultaneously applied two synthetic adeno-associated viruses (AAVs) with different tropism to deliver Ildr1 cDNA to the Ildr1 mouse inner ear: one targeting the organ of Corti (AAV2.7m8) and the other targeting the cochlear lateral wall (AAV8BP2). We showed that combined AAV2.7m8/AAV8BP2 gene therapy improves cochlear structural integrity and auditory function in Ildr1 mice.
Topics: Humans; Animals; Mice; Receptors, Cell Surface; Deafness; Hearing Loss; Disease Models, Animal; Genetic Therapy
PubMed: 37481704
DOI: 10.1016/j.ymthe.2023.07.014 -
BMC Public Health Aug 2023Pain is a common reason for seeking out healthcare professionals and support services. However, certain populations, such as people with deafness, may encounter...
BACKGROUND
Pain is a common reason for seeking out healthcare professionals and support services. However, certain populations, such as people with deafness, may encounter difficulties in effectively communicating their pain; on the other side, health care professionals may also encounter challenges to assess pain in this specific population.
AIMS
To describe (a) the state of the research in the field of pain assessment in individuals with deafness; (b) instruments validated; and (b) strategies facilitating the pain communication or assessment in this population.
METHODS
A systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were performed, searching Medline, CINAHL, Scopus, Embase and PsycInfo databases, from their initiation to July 2023. Primary and secondary studies, involving adults with deafness and investigating pain assessment and communication difficulties, facilitators, or barriers, were eligible. The included studies were assessed in their methodological quality with the Quality Assessment for Diverse Studies tool; data extraction and the narrative synthesis was provided by two researchers.
RESULTS
Five studies were included. Two were validation studies, while the remaining were a case report, a case study and a qualitative study. The interRAI Community Health Assessment and the Deafblind Supplement scale have been validated among people with deafness by reporting few psychometric properties; in contrast, instruments well established in the general population (e.g. Visual Analogue Scale) have been assessed in their usability and understandability among individuals with deafness, suggesting their limitations. Some strategies have been documented as facilitating pain communication and assessment: (a) ensuring inclusiveness (the presence of family members as mediators); (b) ensuring the preparedness of healthcare professionals (e.g. in sign language); and (c) making the environment friendly to this population (e.g. removing masks).
CONCLUSIONS
The research regarding pain in this population is in its infancy, resulting in limited evidence. In recommending more research capable of establishing the best pain assessment instrument, some strategies emerged for assessing pain in which the minimum standards of care required to offer to this vulnerable population should be considered.
Topics: Adult; Humans; Communication; Deafness; Narration; Pain; Pain Measurement
PubMed: 37608263
DOI: 10.1186/s12889-023-16535-5 -
Journal of Diabetes Investigation Dec 2023Mitochondrial dysfunction causes maternally inherited deafness and diabetes (MIDD). Herein, we report improved glycemic control in a 47-year-old Japanese woman with MIDD...
Mitochondrial dysfunction causes maternally inherited deafness and diabetes (MIDD). Herein, we report improved glycemic control in a 47-year-old Japanese woman with MIDD using imeglimin without major adverse effects. Biochemical tests and metabolome analysis were performed before and after imeglimin administration. Blood glucose level fluctuations were determined. Sulfonylureas, dipeptidyl peptidase-4 inhibitors (DPP4is), and sodium glucose transporter-2 inhibitors (SGLT2i) were administered to evaluate the efficacy of their combination with imeglimin. Imeglimin decreased the HbA1c and ammonia levels and increased the time-in-range, C-peptide reactivity, and glucagon level. Elevated citrulline and histamine levels were decreased by imeglimin. The hypoglycemic effect was not enhanced by imeglimin when combined with sulfonylurea or DPP4i, but the blood glucose level was improved when combined with SGLT2i. Imeglimin improved glucose concentration-dependent insulin secretion and maximized the insulin secretory capacity by improving mitochondrial function and glutamine metabolism and urea circuit abnormalities by promoting glucagon secretion. Imeglimin could improve glycemic control in MIDD.
Topics: Female; Humans; Middle Aged; Diabetes Mellitus, Type 2; Blood Glucose; Glucagon; Glycemic Control; Maternal Inheritance; Hypoglycemic Agents; Deafness; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37715448
DOI: 10.1111/jdi.14085 -
Otolaryngologic Clinics of North America Oct 2023The external auditory canal is a highly specialized skin appendage whose primary purpose is to provide a pathway for the transmission of sound to the tympanic membrane... (Review)
Review
The external auditory canal is a highly specialized skin appendage whose primary purpose is to provide a pathway for the transmission of sound to the tympanic membrane and beyond. It is also a frequent source of symptoms for our patients. Sources of pain, hearing loss, tinnitus, itching, and other sensations can be inferred from an appropriate history. This should be followed by a thorough cleaning of the ear, so that a thorough examination can be performed.
Topics: Humans; Ear Canal; Tympanic Membrane; Deafness; Sound; Tinnitus
PubMed: 37558611
DOI: 10.1016/j.otc.2023.06.011 -
International Journal of Audiology Jul 2024There has been a major growth in global health networks in recent decades to address health issues including tobacco use, alcohol abuse, and maternal mortality. Most...
There has been a major growth in global health networks in recent decades to address health issues including tobacco use, alcohol abuse, and maternal mortality. Most conditions that incur high costs have provoked networks of advocates working to mitigate the impact, increase investment in research, and establish campaigns. Global health networks often work simultaneously across policy, knowledge creation, and advocacy. Until recently there has been limited activity in global health networks and advocacy addressing hearing loss and deafness which has contributed to its relatively low visibility with policymakers compared to other health conditions. This discussion paper reports on a global consultation that explored the views of advocacy groups and individuals on advocacy for the management of hearing loss, and cochlear implantation (CI). It focussed on stakeholders' views of current advocacy endeavours, opportunities and barriers, and the possible development of a global advocacy network to improve access to cochlear implantation and the supporting services. The subsequent development of a global health network, the Cochlear Implant International Community of Action (CIICA) is discussed and the conditions necessary for the successful development of health networks are explored. This paper will be of interest to those wishing to understand the factors influencing the development of health networks and advocacy.
Topics: Humans; Cochlear Implants; Cochlear Implantation; Health Policy; Global Health; Deafness; Health Services Accessibility; Policy Making; Persons With Hearing Impairments
PubMed: 37560826
DOI: 10.1080/14992027.2023.2231634 -
Medicina (Kaunas, Lithuania) Nov 2023There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur... (Review)
Review
There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.
Topics: Humans; Neurobiology; Polyphenols; Cochlea; Aging; Deafness
PubMed: 38004094
DOI: 10.3390/medicina59112045 -
Cochlear Implants International Nov 2023Identify and evaluate the effectiveness of methods for improving postoperative cochlear implant (CI) hearing performance in subjects with single-sided deafness (SSD) and... (Review)
Review
OBJECTIVE
Identify and evaluate the effectiveness of methods for improving postoperative cochlear implant (CI) hearing performance in subjects with single-sided deafness (SSD) and asymmetric hearing loss (AHL).
DATA SOURCES
Embase, PubMed, Scopus.
REVIEW METHODS
Systematic review and narrative synthesis. English language studies of adult CI recipients with SSD and AHL reporting a postoperative intervention and comparative audiometric data pertaining to speech in noise, speech in quiet and sound localization were included.
RESULTS
32 studies met criteria for full text review and 6 (n = 81) met final inclusion criteria. Interventions were categorized as: formal auditory training, programming techniques, or hardware optimization. Formal auditory training (n = 10) found no objective improvement in hearing outcomes. Experimental CI maps did not improve audiologic outcomes (n = 9). Programed CI signal delays to improve synchronization demonstrated improved sound localization (n = 12). Hardware optimization, including multidirectional (n = 29) and remote (n = 11) microphones, improved sound localization and speech in noise, respectively.
CONCLUSION
Few studies meeting inclusion criteria and small sample sizes highlight the need for further study. Formal auditory training did not appear to improve hearing outcomes. Programming techniques, such as CI signal delay, and hardware optimization, such as multidirectional and remote microphones, show promise to improve outcomes for SSD and AHL CI users.
Topics: Adult; Humans; Cochlear Implantation; Hearing Loss, Unilateral; Speech Perception; Treatment Outcome; Hearing Loss; Cochlear Implants; Sound Localization; Deafness
PubMed: 37490782
DOI: 10.1080/14670100.2023.2239512 -
The Journal of Neuroscience : the... Jul 2023Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple...
Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of "normal" age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction. Structure-function correlation analyses in mice across the lifespan showed that the age-dependent increase in macrophage activation in the stria vascularis is associated with a decline in auditory sensitivity. High-resolution imaging analysis of macrophage activation in middle-aged and aged mouse and human cochleas, along with transcriptomic analysis of age-dependent changes in mouse cochlear macrophage gene expression, support the hypothesis that aberrant macrophage activity is an important contributor to age-dependent strial dysfunction, cochlear pathology, and hearing loss. Thus, this study highlights the SV as a primary site of age-related cochlear degeneration and aberrant macrophage activity and dysregulation of the immune system as early indicators of age-related cochlear pathology and hearing loss. Importantly, novel new imaging methods described here now provide a means to analyze human temporal bones in a way that had not previously been feasible and thereby represent a significant new tool for otopathological evaluation. Age-related hearing loss is a common neurodegenerative disorder affecting communication and quality of life. Current interventions (primarily hearing aids and cochlear implants) offer imperfect and often unsuccessful therapeutic outcomes. Identification of early pathology and causal factors is crucial for the development of new treatments and early diagnostic tests. Here, we find that the SV, a nonsensory component of the cochlea, is an early site of structural and functional pathology in mice and humans that is characterized by aberrant immune cell activity. We also establish a new technique for evaluating cochleas from human temporal bones, an important but understudied area of research because of a lack of well-preserved human specimens and difficult tissue preparation and processing approaches.
Topics: Male; Middle Aged; Female; Humans; Animals; Mice; Aged; Stria Vascularis; Quality of Life; Cochlea; Presbycusis; Deafness; Macrophages; Inflammation
PubMed: 37268417
DOI: 10.1523/JNEUROSCI.2234-22.2023 -
European Archives of... Oct 2023Assess the outcomes in patients who underwent cochlear implant (CI) for single-sided deafness (SSD).
OBJECTIVES
Assess the outcomes in patients who underwent cochlear implant (CI) for single-sided deafness (SSD).
METHODS
All patients affected by SSD who underwent CI at Gruppo Otologico, Piacenza, from October 2012 to May 2022 with at least 6 months of follow-up were selected in the study group. The analysis included subjective and objective measures performed pre-operative and up to 24 months after surgery. Hearing threshold on both sides was evaluated with a weighted four-frequency average (PTA [0.5 kHz + 1 kHz + 2 kHz + 4 kHz]/4) on pure tone audiometry and speech audiometry (Speech Discrimination Score, SDS). The Speech Spatial and Qualities of Hearing scale (SSQ Questionnaire) for binaural hearing benefits and sound localization, the Tinnitus Handicap Inventory Questionnaire (THI) and Dizziness Handicap Inventory Questionnaire (DHI) were used for subjective assessment.
RESULTS
Data from 138 patients, 69 males and 69 females, (mean age 49 years, range 17-77 years) underwent CI for SSD were examined. Single-sided hearing deprivation average before undergoing CI surgery was 2.5 years (range 3 months-35 years). There was a significant reduction of THI and DHI scores compared to pre-operative scores alongside a referred improvement in social, physical, and emotional well-being through the SSQ questionnaire.
CONCLUSIONS
To the best of our knowledge, this paper descried the largest cohort of SSD who underwent CI in a single institution. According to our findings CI in patients affected by SSD represents a valuable tool for an overall improvement of tinnitus and dizziness but also quality of life, after at least 6 months of follow-up. Further studies are desirable to improve rehabilitation pathways and possibly set new standards of care of this condition.
Topics: Male; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Cochlear Implantation; Tinnitus; Quality of Life; Dizziness; Audiometry, Pure-Tone; Vertigo; Deafness
PubMed: 37029803
DOI: 10.1007/s00405-023-07959-1