The Expression Levels of MicroRNAs Differentially Expressed in Sudden Sensorineural Hearing Loss Patients' Serum Are Unchanged for up to 12 Months after Hearing Loss Onset.

Sudden sensorineural hearing loss (SSNHL) is an acquired idiopathic hearing loss. Serum levels of small, non-coding RNAs and microRNAs (miRNAs) miR-195-5p/-132-3p/-30a-3p/-128-3p/-140-3p/-186-5p/-375-3p/-590-5p are differentially expressed in SSNHL patients within 28 days of hearing loss onset. This study determines if these changes persist by comparing the serum miRNA expression profile of SSNHL patients within 1 month of hearing loss onset with that of patients 3-12 months after hearing loss onset. We collected serum from consenting adult SSNHL patients at presentation or during clinic follow-up. We matched patient samples drawn 3-12 months after hearing loss onset (delayed group, n = 9 patients) by age and sex to samples drawn from patients within 28 days of hearing loss onset (immediate group, n = 14 patients). We compared the real-time PCR-determined expression levels of the target miRNAs between the two groups. We calculated the air conduction pure-tone-averaged (PTA) audiometric thresholds in affected ears at the initial and final follow-up visits. We undertook inter-group comparisons of hearing outcome status and initial and final PTA audiometric thresholds. There was no significant inter-group difference in miRNA expression level, hearing recovery status and initial and final affected ear PTA audiometric thresholds.

A systematic review and meta-analysis of extratympanic electrocochleography in Ménière's disease diagnosis.

Objective: Determine whether a combination of electrocochleography determined summating/action potential (SP/AP) ratio and other audiological measurements has greater sensitivity and specificity than that achieved with electrocochleography SP/AP ratio alone in diagnosing definite Ménière's Disease. Design: Systematic review and meta-analysis. Study sample: Pubmed, Cochrane Library, and Web of Science were searched using search terms "electrocochleography", "ECochG, ,"ECoG", "Ménière's Disease", and "Idiopathic Endolymphatic Hydrops". Inclusion criteria were extratympanic electrocochleography methodology, English language publication between January 2002 and December 2017, and the 1995 American Academy of Otolaryngology and Head and Neck Surgery Ménière's disease diagnostic criteria. Five articles satisfied inclusion criteria and were sufficiently detailed for aggregate quantitative analysis of SP/AP ratio (315 subjects) and combination audiological measures (113 subjects). Results: The diagnostic sensitivity and specificity of the SP/AP amplitude ratio was 47.6% and 83.8% and of combination diagnostic measures 63.5% and 89.3%, respectively. Point estimates of sensitivity (p = 0.248) and specificity (p = 0.969) and the summary Receiver Operator Characteristic Curve (p = 0.407) were not statistically significant. Conclusion: Statistically, combination diagnostic measures do not result in greater accuracy of definite Ménière's disease diagnosis compared to the SP/AP amplitude ratio alone. However, given the small sample size further studies are recommended to arrive at a definitive conclusion.

WITHDRAWN: Grommets (ventilation tubes) for recurrent acute otitis media in children.

BACKGROUND: This is an update of a Cochrane review first published in The Cochrane Library in Issue 4, 2008 and previously updated in 2011.Acute suppurative otitis media is one of the most common infectious diseases in childhood. Recurrent acute otitis media is defined for the purposes of this review as either three or more acute infections of the middle ear cleft in a six-month period, or at least four episodes in a year. Strategies for managing the condition include the assessment and modification of risk factors where possible, repeated courses of antibiotics for each new infection, antibiotic prophylaxis and the insertion of ventilation tubes (grommets). OBJECTIVES: To establish whether grommet insertion reduces the frequency of episodes of recurrent acute otitis media and the proportion of symptomatic children. SEARCH METHODS: The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2014, Issue 10); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 6 November 2014. SELECTION CRITERIA: Randomised controlled trials comparing grommet insertion versus control (antibiotics/other treatments/no treatment) for recurrent acute otitis media in children aged from 0 to 16 years. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies. Three authors independently assessed study quality and extracted data. We synthesised data descriptively. MAIN RESULTS: Two randomised controlled trials with a total of 148 participants are included in this review. The overall risk of bias in the studies is unclear.The first study randomised 95 children to grommets or control (antibiotic treatment of acute otitis media episodes). For the primary outcome, this study showed that grommet insertion leads to a mean reduction of 1.5 episodes of acute otitis media in the first six months after treatment. In six months of follow-up significantly more children in the grommet group had no episodes of acute otitis media (P value < 0.001). Complications of surgery included grommet blockage with acute otitis media requiring re-operation within six months in 3/54 children who underwent grommet insertion. Adverse effects were not documented in the control group. The following pre-defined secondary outcomes were not reported: change in symptom scores for otalgia or otorrhoea, alteration in the frequency of otalgia or otorrhoea, and number of days at nursery or school lost secondary to acute otitis media.The second study reported on 53 of 68 children who were randomised to grommet insertion or six months of once a day sulfamethoxazole and trimethoprim antibiotic prophylaxis. There was no significant difference in the primary outcome, number of episodes of acute otitis media, during the six-month follow-up between grommet insertion and antibiotic treatment groups (64.5% in the surgical group versus 45.4% in the antibiotic group had no recurrence, P value = 0.4). Two participants underwent grommet re-insertion to replace extruded tubes during the follow-up period. The only other adverse effect reported was the development of a skin rash in two patients in the medical group. Other pre-defined secondary outcome measures were not reported. The study has a high risk of bias and the results should be interpreted cautiously. AUTHORS' CONCLUSIONS: Grommets significantly increase the number of acute otitis media-free children in the first six months after insertion compared to children who receive no treatment. Grommet insertion maybe of equivalent efficacy to once a day antibiotic prophylaxis. Further research is required to confirm the advantage of grommets over no treatment, investigate the effect beyond six months, compare grommet effectiveness against alternative active treatments and confirm the low risk of adverse effects compared to no treatment and all active treatments in recurrent acute otitis media. In the interim clinicians should consider the possible adverse effects of grommet insertion and alternative treatments before recommending surgery.

Grommets (ventilation tubes) for recurrent acute otitis media in children.

BACKGROUND: Acute otitis media (AOM) is one of the most common childhood illnesses. While many children experience sporadic AOM episodes, an important group suffer from recurrent AOM (rAOM), defined as three or more episodes in six months, or four or more in one year. In this subset of children AOM poses a true burden through frequent episodes of ear pain, general illness, sleepless nights and time lost from nursery or school. Grommets, also called ventilation or tympanostomy tubes, can be offered for rAOM. OBJECTIVES: To assess the benefits and harms of bilateral grommet insertion with or without concurrent adenoidectomy in children with rAOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL; MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 4 December 2017. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing bilateral grommet insertion with or without concurrent adenoidectomy and no ear surgery in children up to age 16 years with rAOM. We planned to apply two main scenarios: grommets as a single surgical intervention and grommets as concurrent treatment with adenoidectomy (i.e. children in both the intervention and comparator groups underwent adenoidectomy). The comparators included active monitoring, antibiotic prophylaxis and placebo medication. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Primary outcomes were: proportion of children who have no AOM recurrences at three to six months follow-up (intermediate-term) and persistent tympanic membrane perforation (significant adverse event). Secondary outcomes were: proportion of children who have no AOM recurrences at six to 12 months follow-up (long-term); total number of AOM recurrences, disease-specific and generic health-related quality of life, presence of middle ear effusion and other adverse events at short-term, intermediate-term and long-term follow-up. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: Five RCTs (805 children) with unclear or high risk of bias were included. All studies were conducted prior to the introduction of pneumococcal vaccination in the countries' national immunisation programmes. In none of the trials was adenoidectomy performed concurrently in both groups.Grommets versus active monitoringGrommets were more effective than active monitoring in terms of:- proportion of children who had no AOM recurrence at six months (one study, 95 children, 46% versus 5%; risk ratio (RR) 9.49, 95% confidence interval (CI) 2.38 to 37.80, number needed to treat to benefit (NNTB) 3; low-quality evidence);- proportion of children who had no AOM recurrence at 12 months (one study, 200 children, 48% versus 34%; RR 1.41, 95% CI 1.00 to 1.99, NNTB 8; low-quality evidence);- number of AOM recurrences at six months (one study, 95 children, mean number of AOM recurrences per child: 0.67 versus 2.17, mean difference (MD) -1.50, 95% CI -1.99 to -1.01; low-quality evidence);- number of AOM recurrences at 12 months (one study, 200 children, one-year AOM incidence rate: 1.15 versus 1.70, incidence rate difference -0.55, 95% -0.17 to -0.93; low-quality evidence).Children receiving grommets did not have better disease-specific health-related quality of life (Otitis Media-6 questionnaire) at four (one study, 85 children) or 12 months (one study, 81 children) than those managed by active monitoring (low-quality evidence).One study reported no persistent tympanic membrane perforations among 54 children receiving grommets (low-quality evidence).Grommets versus antibiotic prophylaxisIt is uncertain whether or not grommets are more effective than antibiotic prophylaxis in terms of:- proportion of children who had no AOM recurrence at six months (two studies, 96 children, 60% versus 35%; RR 1.68, 95% CI 1.07 to 2.65, I2 = 0%, fixed-effect model, NNTB 5; very low-quality evidence);- number of AOM recurrences at six months (one study, 43 children, mean number of AOM recurrences per child: 0.86 versus 1.38, MD -0.52, 95% CI -1.37 to 0.33; very low-quality evidence).Grommets versus placebo medicationGrommets were more effective than placebo medication in terms of:- proportion of children who had no AOM recurrence at six months (one study, 42 children, 55% versus 15%; RR 3.64, 95% CI 1.20 to 11.04, NNTB 3; very low-quality evidence);- number of AOM recurrences at six months (one study, 42 children, mean number of AOM recurrences per child: 0.86 versus 2.0, MD -1.14, 95% CI -2.06 to -0.22; very low-quality evidence).One study reported persistent tympanic membrane perforations in 3 of 76 children (4%) receiving grommets (low-quality evidence).Subgroup analysisThere were insufficient data to determine whether presence of middle ear effusion at randomisation, type of grommet or age modified the effectiveness of grommets. AUTHORS' CONCLUSIONS: Current evidence on the effectiveness of grommets in children with rAOM is limited to five RCTs with unclear or high risk of bias, which were conducted prior to the introduction of pneumococcal vaccination. Low to very low-quality evidence suggests that children receiving grommets are less likely to have AOM recurrences compared to those managed by active monitoring and placebo medication, but the magnitude of the effect is modest with around one fewer episode at six months and a less noticeable effect by 12 months. The low to very low quality of the evidence means that these numbers need to be interpreted with caution since the true effects may be substantially different. It is uncertain whether or not grommets are more effective than antibiotic prophylaxis. The risk of persistent tympanic membrane perforation after grommet insertion was low.Widespread use of pneumococcal vaccination has changed the bacteriology and epidemiology of AOM, and how this might impact the results of prior trials is unknown. New and high-quality RCTs of grommet insertion in children with rAOM are therefore needed. These trials should not only focus on the frequency of AOM recurrences, but also collect data on the severity of AOM episodes, antibiotic consumption and adverse effects of both surgery and antibiotics. This is particularly important since grommets may reduce the severity of AOM recurrences and allow for topical rather than oral antibiotic treatment.

Needle aspiration versus incision and drainage for the treatment of peritonsillar abscess.

BACKGROUND: Peritonsillar abscess is a common infection presenting as a collection of pus in the peritonsillar area. The condition is characterised by a severe sore throat, difficulty in swallowing and pain on swallowing, fever and malaise, and trismus. Needle aspiration and incision and drainage are the two main treatment modalities currently used in the treatment of this condition. The effectiveness of one versus the other has not been clearly demonstrated and remains an area of debate. OBJECTIVES: To assess the effectiveness and risks of needle aspiration versus incision and drainage for the treatment of peritonsillar abscess in older children (eight years of age or older), adolescents and adults. SEARCH METHODS: The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 7); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 August 2016. SELECTION CRITERIA: Randomised controlled trials comparing needle aspiration with incision and drainage. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were recurrence rate (proportion of patients needing repeat intervention) and adverse effects associated with the intervention. Secondary outcomes were time to resumption of normal diet, complications of the disease process and symptom scores. We used GRADE to assess the quality of evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included 11 studies (674 participants). The risk of bias was high or unclear in all of the included studies. All studies compared needle aspiration to incision and drainage.All but one of the 11 studies reported on the primary outcome of recurrence. When we pooled data from the 10 studies the recurrence rate was higher in the needle aspiration group compared with incision and drainage: risk ratio (RR) 3.74 (95% confidence interval (CI) 1.63 to 8.59; 612 participants). We detected moderate heterogeneity in this analysis (I2 = 48%). In interpreting the pooled result it is important to note that the evidence for this outcome was of very low quality.None of the other outcomes (adverse effects of the intervention, time to resumption of normal diet, complications of the disease process and symptom scores) were consistently measured across all studies.Only three studies reported on adverse effects/events associated with the intervention and only one such event in a single patient was reported (post-procedure bleeding following incision and drainage: 1/28, 3.6%) (very low-quality evidence). Time to resumption of normal diet was compared in two studies; neither found an obvious difference between needle aspiration and incision and drainage (very low-quality evidence).Only three studies stated that they would report complications of the disease process. In these three studies, the only complication reported was admission to hospital for dehydration in two patients who underwent incision and drainage (2/13, 6.7%). Symptom scores were measured in four studies; three evaluated pain using different scales and one other symptoms. The data could not be pooled in a meta-analysis. Two studies evaluating procedural pain reported this to be lower in the needle aspiration groups. One study found comparable rates of pain resolution at five days post-intervention between groups. The quality of the evidence for symptom scores was very low. AUTHORS' CONCLUSIONS: Although a number of studies have sought to evaluate whether or not needle aspiration or incision and drainage is more effective in patients with peritonsillar abscess, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain. Very low-quality evidence suggests that incision and drainage may be associated with a lower chance of recurrence than needle aspiration. There is some very low-quality evidence to suggest that needle aspiration is less painful.

A pilot randomized controlled trial comparing bismuth iodine paraffin paste external ear pack and no ear pack after middle ear surgery.

To pilot a substantive randomized control trial comparing post-operative external ear canal pack with no ear pack after middle ear surgery, 32 adults undergoing primary posterior bony canal wall preserving middle ear surgery were randomized to have either a bismuth iodoform paraffin paste pack or no ear pack post-operatively. Outcome measures included clinician- and patient-recorded visual analogue scale scores for ear signs and symptoms at 3 weeks and 3 months and audiometric findings at 3 months post-operatively. There was no statistically significant inter-group difference in 3-week clinician and patient cumulative scores for ear signs and symptoms. There was also no significant difference in graft take rate, appearance of ear canals and audiometric results in either group at 3 months. No difference in ear symptoms, clinician findings or hearing was demonstrated between patients with a post-operative pack compared to those without a pack following middle ear surgery in this pilot study.

Acquired sensorineural hearing loss, oxidative stress, and microRNAs.

Hearing loss is the third leading cause of human disability. Age-related hearing loss, one type of acquired sensorineural hearing loss, is largely responsible for this escalating global health burden. Noise-induced, ototoxic, and idiopathic sudden sensorineural are other less common types of acquired hearing loss. The etiology of these conditions is complex and multi-factorial involving an interplay of genetic and environmental factors. Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss. Short non-coding RNA sequences known as microRNAs (miRNAs) have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response. Sensory hair cell death is a central histopathological finding in sensorineural hearing loss. As these cells do not regenerate in humans, it underlies the irreversibility of human age-related hearing loss. Ovid EMBASE, Ovid MEDLINE, Web of Science Core Collection, and ClinicalTrials. gov databases over the period August 1, 2018 to July 31, 2023 were searched with "hearing loss," "hypoxamiRs," "hypoxia," "microRNAs," "ischemia," and "oxidative stress" text words for English language primary study publications or registered clinical trials. Registered clinical trials known to the senior author were also assessed. A total of 222 studies were thus identified. After excluding duplicates, editorials, retractions, secondary research studies, and non-English language articles, 39 primary studies and clinical trials underwent full-text screening. This resulted in 11 animal, in vitro, and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review. MiRNAs miR-34a and miR-29b levels increase with age in mice. These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1-alpha (SIRT1/PGC-1α), SIRT1/p53, and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis. Furthermore, hypoxia and oxidative stress had a similar adverse apoptotic effect, which was inhibited by resveratrol and a myocardial inhibitor-associated transcript, a miR-29b competing endogenous mRNA. Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice - an effect that was corrected by inner ear stem cell-derived exosomes. There is ongoing work seeking to determine if these findings can be effectively translated to humans.

Candidate odours for a short form odorant identification test.

Measurement of olfactory function is difficult and despite the availability of validated olfactory tests these are not in common use in general clinical practice. The mismatch between self-reported olfactory function and objective test response is well known, thus the need for adequate assessment of olfaction is not disputed. We aimed to determine which if any odour in a commercially available olfactory test could be identified by 70 % or more of normal subjects with a view to developing a shortened screening test for use in general otolaryngology and non-specialist clinics in the United Kingdom. Hospital staff and medical students, under 50 years of age were recruited. The tests were undertaken in a quiet room of neutral odour. Subjects were asked to self-identify 12 odorants presented consecutively and to record how strongly they perceived the odorants on a 4-point scale. One hundred and four participants correctly identified the odorant in 466 (37.3 %) of the 1,248 individual odorant identification tests. Peppermint, fish and coffee odours were identified by 88.5, 79.8 and 69.7 % of participants, respectively, without the advantage of a choice of name prompt. These supra-threshold test odour stimuli were perceived as present in all of the individual odour identification tests, but correct identification of the test odour was very much lower for the other nine test stimuli. Peppermint, fish and coffee are odours that should be evaluated further for inclusion in a short form olfactory identification test in a British population.

Vestibular rehabilitation potential of commercially available virtual reality video games.

BACKGROUND: Peripheral vestibular disorders affect 2.8-6.5% of people. Standard treatment is vestibular rehabilitation therapy, and virtual reality (VR) could improve outcomes. The objective of this study was to identify the commercially available VR video game that is most congruent to vestibular rehabilitation therapy. METHODS: A term search "virtual reality racing" was performed on the App Store in March 2022. Results were screened for free point-of-view racing games compatible with Android and iOS devices. An investigator was filmed playing each game and videos were distributed to 237 physiotherapists. Physiotherapists completed a survey of 5-point Likert scale questions that assessed the video games vestibular rehabilitation potential. Survey responses were analyzed using Friedman Two-Way ANOVA (alpha = 0.05) and paired samples sign test with Bonferroni correction. RESULTS: The search yielded 58 games, 4 were included. Forty physiotherapists participated. VR Tunnel Race (VRTR) and VR Real World Bike Racing (VRWBR) had the greatest vestibular rehabilitation potential (median global scores = 18.00). VRTR replicated habituation exercises significantly (p < 0.001) better than Derby VR, and VRWBR replicated physiotherapist-prescribed exercises significantly (p < 0.001) better than VR X-Racer. There were no discernable significant differences between VRWBR and VRTR. CONCLUSIONS: VRTR and VRWBR are the most congruent VR games to standard vestibular rehabilitation. VRWBR is preferable to VRTR with respect to ease of use and the ability to alter the amount of optokinetic stimulation. Prospective studies are needed to confirm the efficacy of these videos games and to determine if they could be used as solitary treatments. TRIAL REGISTRATION: Not applicable.

A randomized controlled trial evaluating the effects of motivational interviewing in new hearing aid users (MI-HAT): study protocol for a randomized controlled trial.

BACKGROUND: Hearing loss is the third leading global cause of disability and is associated with poorer quality of life. Hearing aids are often recommended for hearing loss; however, hearing aid uptake and use rates are perpetually low. Motivational interviewing (MI) is a patient-centered counseling aimed at addressing the desire in the patient to change their behavior. The aim of this study is to investigate the impact of one-on-one MI sessions on hearing aid use among new adult users. METHODS: A multi-center, prospective, randomized patient-blind controlled trial with a pre- and post-tests design. New hearing aid users ≥ 18 years of age will be recruited from Vancouver, Canada. They will be randomly assigned to a treatment or control group. The treatment group will attend a one-on-one MI session hosted by a practicing MI therapist in addition to standard in-person audiological care. The control group will receive standard in-person audiological care. Data is collected at baseline and at 1, 3, 6, and 12 months' follow-ups. The primary outcomes are data-logged hearing aid use hours and patient-reported outcomes as measured by the International Outcome Inventory for Hearing Aids questionnaire. Associations between intervention and hearing aid use hours and self-reported outcome measures will be assessed. DISCUSSION: This trial is designed to evaluate the efficacy of one-on-one MI in improving hearing aid use in new adult users in the short and long terms. Results will contribute to the evidence on whether MI counseling has an effect on hearing aid use and may guide future clinical practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT04673565 . Registered on 17 December 2020.

Adult porcine (Sus scrofa) derived inner ear cells: Characteristics in in-vitro cultures.

There is a need for an animal model that closely parallels human cochlea gestational development. This study aims to document porcine inner ear anatomy, and in vitro porcine derived inner ear cell culture characteristics. Twenty-four temporal bone were harvested from 12 adult pigs (Sus scrofa). Six were formalin fixed and their maximal diameters were measured. The cochlea duct length was determined by the insertion length of a Nucleus 22 cochlear implant in two bones. Four formalin fixed bones were sectioned for histology. Cochlear and vestibular tissues were harvested from non-fixed bones, cultured and characterized at different passages (P). Gene and protein expression of multipotent stem/progenitor (Nestin and Sox2), inner ear hair (Myosin VIIa, Prestin) and supporting (Cytokeratin 18 and Vimentin) cell markers were determined. The porcine cochlea was a 3.5 turn spiral. There was a separate vestibular compartment. The cochlear mean maximal diameter and height was 7.99 and 3.77 mm, respectively. Sphere forming cells were identified on phase-contrast microscopy. The relative mRNA expression levels of KRT18, MYO7A and SLC26A5 were significantly positively correlated in cochlear cultures; and MYO7A and SLC26A5; SOX2 and KRT18; NES and SLC26A5 genes were positively correlated in vestibular cultures (p = .037, Spearman correlation [τ] = .900). Inner ear sensory and stem cell characteristics persist in passaged porcine inner ear cells. Further work is required to establish the usefulness of porcine inner ear cell cultures to the study of human inner ear disorders.

The role of hypoxia-associated miRNAs in acquired sensorineural hearing loss.

Introduction: Sensorineural hearing loss (SNHL) is a prevalent sensory deficit presenting commonly as age-related hearing loss. Other forms of SNHL include noise-induced and sudden SNHL. Recent evidence has pointed to oxidative stress as a common pathogenic pathway in most subtypes of acquired SNHL. MicroRNAs (miRNAs) are small non-coding RNA sequences that suppress target mRNA expression and affect downstream processes. Many studies have shown that miRNAs are integral biomolecules in hypoxia-adaptive responses. They also promote apoptosis in response to oxidative stress resulting in SNHL. Our hypothesis is that miRNAs are involved in the pathophysiological responses to hypoxia and oxidative stress that result in SNHL. This study reviews the evidence for hypoxia-adaptive miRNAs (hypoxamiRs) in different types of acquired SNHL and focuses on miRNAs involved in hypoxia driven SNHL. Methods: Electronic bibliographic databases PubMed, Ovid MEDLINE, Ovid EMBASE, and Web of Science Core Collection were searched independently by two investigators for articles published in English from the inception of individual databases to the end of July 2020. The text word or medical subject heading searches of all fields, titles, abstracts, or subject headings depending on the database were undertaken with combinations of the words "microRNAs", "hypoxia", "hypoxamiRs", "oxidative stress", "ischemia" and "hearing loss". The reference lists of studies meeting the inclusion criteria were searched to identify additional relevant studies. The inclusion criteria included relevant clinical studies with human subjects, animals, and in vitro experiments. The risk of bias was assessed using the Cochrane risk of bias assessment tool for human studies and the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) a risk of bias assessment tool for animal model and in vitro studies. Results: A total of 15 primary articles were selected for full text screening after excluding duplicates, reviews, retracted articles, and articles not published in English. All nine articles meeting the study inclusion criteria were from animal or in vitro model studies and were assessed to be at low risk of bias. miRNAs miR-34a and miR-29b were reported to be involved in SNHL in inner ear cell models exposed to oxidative stress. Signaling pathways Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1-alpha (SIRT1/PGC-1α), SIRT1/p53, and SIRT1/hypoxia-inducible factor 1-alpha (HIF-1α) were identified as underlying pathways involved in acquired SNHL. Conclusion: There is evidence that miR-34a and -29b are involved in hypoxia-driven and other causes of oxidative stress-related acquired SNHL. Further studies are required to determine if these findings are clinically applicable.

MicroRNA Signature and Cellular Characterization of Undifferentiated and Differentiated House Ear Institute-Organ of Corti 1 (HEI-OC1) Cells.

MicroRNAs (miRNAs) regulate gene expressions and control a wide variety of cellular functions. House Ear Institute-Organ of Corti 1 (HEI-OC1) cells are widely used to screen ototoxic drugs and to investigate cellular and genetic alterations in response to various conditions. HEI-OC1 cells are almost exclusively studied under permissive conditions that promote cell replication at the expense of differentiation. Many researchers suggest that permissive culture condition findings are relevant to understanding human hearing disorders. The mature human cochlea however consists of differentiated cells and lacks proliferative capacity. This study therefore aimed to compare the miRNA profiles and cellular characteristics of HEI-OC1 cells cultured under permissive (P-HEI-OC1) and non-permissive (NP-HEI-OC1) conditions. A significant increase in the level of expression of tubulin ß1 class VI (Tubb1), e-cadherin (Cdh1), espin (Espn), and SRY (sex determining region Y)-box2 (Sox2) mRNAs was identified in non-permissive cells compared with permissive cells (P < 0.05, Kruskal-Wallis H test, 2-sided). miR-200 family, miR-34b/c, and miR-449a/b functionally related cluster miRNAs, rodent-specific maternally imprinted gene Sfmbt2 intron 10th cluster miRNAs (-466a/ -467a), and miR-17 family were significantly (P < 0.05, Welch's t-test, 2-tailed) differentially expressed in non-permissive cells when compared with permissive cells. Putative target genes were significantly predominantly enriched in mitogen-activated protein kinase (MAPK), epidermal growth factor family of receptor tyrosine kinases (ErbB), and Ras signaling pathways in non-permissive cells compared with permissive cells. This distinct miRNA signature of differentiated HEI-OC1 cells could help in understanding miRNA-mediated cellular responses in the adult cochlea.

Hyperbaric Oxygen Therapy for Patients With Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-analysis.

Importance: Sudden sensorineural hearing loss (SSNHL) is an acute, usually unilateral deficit. Systemic and intratympanic steroids are accepted treatments. Although evidence suggests that hyperbaric oxygen therapy (HBOT) may be beneficial, it is not widely offered. Objectives: To review and evaluate recent evidence of the association of HBOT with hearing outcomes in SSNHL and to determine if HBOT should be a single or part of a combination treatment regimen. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, Web of Science, CAB, ICTRP, Google Scholar, Clinicaltrials.gov, and ISRCTN databases were searched for randomized controlled trials (RCTs) published in English from January 1, 2000, and April 30, 2020. Study Selection: Prospective RCTs involving only adult participants (≥18 years) with SSNHL and comparing HBOT, as a single or combination therapy, with control therapies, such as steroids and/or placebo. Only RCTs that used the American Academy of Otolaryngology-Head and Neck Surgery's diagnostic criteria for SSNHL were included. Data Extraction and Synthesis: Data were extracted independently by 2 researchers. A fixed-effects model was used for analysis and performed from November 30, 2020, to May 20, 2021. Main Outcomes and Measures: The mean difference in absolute hearing gain recorded by pure-tone audiometric (PTA) thresholds averaged across 4 low (0.5, 1, 2, and 3 or 4 kHz) or 3 high (3 or 4, 6, and 8 kHz) frequencies was the primary outcome. The secondary outcomes were the odds ratio of hearing recovery defined as a hearing gain of ≥10 decibels (dB) in PTA average and treatment-related adverse effects. Results: Of the 826 records initially identified, 358 duplicates and 451 articles were excluded based on article type, title, and abstract. The full texts of 17 articles were reviewed, of which 14 were excluded because they were either not prospective RCTs (11 articles), the participants were less than 18 years old (2 articles), or the PTA was not reported at frequencies of interest (1 article). Three prospective RCTs with a total of 88 participants who received HBOT in the intervention groups and 62 participants who received only medical therapy in the control groups were studied. The intergroup difference in mean absolute hearing gain (mean difference, 10.3 dB; 95% CI, 6.5-14.1 dB; I2 = 0%) and the odds ratio of hearing recovery (4.3; 95% CI, 1.6-11.7; I2 = 0%) favored HBOT over the control therapy. Conclusions and Relevance: In this systematic review and meta-analysis, HBOT as part of a combination treatment was significantly associated with improved hearing outcomes in patients with SSNHL over control treatments. Trial Registration: PROSPERO Identifier: CRD42020193191.

Inner ear organoids: progress and outlook, with a focus on the vascularization.

The inner ear is a complex organ that encodes sound, motion, and orientation in space. Given the complexity of the inner ear, it is not surprising that treatments are relatively limited despite the fact that, in 2015, hearing loss was the fourth leading cause of years lived with disability worldwide. Inner ear organoid models are a promising tool to advance the study of multiple aspects of the inner ear to aid the development of new treatments and validate drug-based therapies. The blood supply of the inner ear plays a pivotal role in growth, maturation, and survival of inner ear tissues and their physiological functions. This vasculature cannot be ignored in order to achieve a truly in vivo-like model that mimics the microenvironment and niches of organ development. However, this aspect of organoid development has remained largely absent in the generation of inner ear organoids. The current review focuses on three-dimensional inner ear organoid and how recent technical progress in generating in vitro vasculature can enhance the next generation of these models.

Effect of Physician Consultation on Satisfaction With Hearing Aid Use: A Randomized Clinical Trial.

Importance: Hearing loss is one of the most common chronic disabilities in older adults, yet reported rates of users' satisfaction with hearing aids are low. Some believe that physicians can provide patients who are pursuing a hearing aid fitting an impartial opinion that will improve hearing aid satisfaction. Objective: To determine whether a physician consultation increased or decreased patients' satisfaction with hearing aids compared with patients undergoing hearing aid fitting with a dispensing audiologist alone. Design, Setting, and Participants: This multicenter, parallel-group, standard regimen-controlled, randomized clinical trial was conducted in offices of audiologists, family physicians, and a hospital-based neurotologist in Vancouver, British Columbia, Canada, and recruited participants from July 2016 to December 2020 with a 3-month postintervention follow-up. The final data analysis was conducted on March 25, 2022. Adult first-time hearing aid users with averaged sensorineural hearing losses of more than 25 dB were prospectively allocated by random number generation to control and intervention groups. Participants were excluded from analysis if they did not attend follow-up or complete the study questionnaire. Interventions: Control participants were followed up solely by their dispensing audiologist. The intervention group attended a single structured visit with a physician in addition to their audiologist's determined follow-up. Main Outcomes and Measures: Primary outcome: hearing aid satisfaction 3 months postfitting as measured by the Satisfaction with Amplification in Daily Life (SADL) questionnaire. Secondary outcome: number of returned hearing aids. Prerecruitment null hypothesis: no intergroup difference in postfitting hearing aid satisfaction. Intergroup difference in mean SADL questionnaire scores analyzed by effect size and the Student t test and proportion of returned hearing aids by the Fischer exact test. Results: A total of 133 participants (mean [SD] age, 70.9 [8.5] years; 64 women [48.1%]) were recruited. Of these, 51 randomized to the control group (mean [SD] age, 71.7 [8.3] years; 28 women [54.9%]) and 42 to the physician intervention (mean [SD] age, 69.9 [7.6] years; 17 women [40.5%]) had results that were analyzed. There was no clinically meaningful intergroup difference in participants' SADL scores (control: mean [SD] score, 5.33 [0.72]; physician consultation: mean [SD] score, 5.35 [0.61]), the mean difference of 0.02 (95% CI, -0.25 to 0.29), or returned hearing aids (control, 1; physician consultation, 0). Conclusions and Relevance: The results of this randomized clinical trial suggest that a physician consultation that is focused on hearing change does not alter a patient's satisfaction with hearing aids 3 months postfitting. Trial Registration: ClinicalTrials.gov Identifier: NCT02842905.

Bacterial lipoproteins differentially regulate human primary and memory CD4+ T and B cell responses to pneumococcal protein antigens through Toll-like receptor 2.

BACKGROUND: Bacterial lipoproteins (BLPs) are expressed across a range of bacteria and are able to activate Toll-like receptor 2 (TLR-2). BLPs enhance immune responses in naive individuals and have therefore been tested as candidate vaccine adjuvants. It is not known whether BLPs affect any preexisting immunity (eg, memory cell response in primed individuals). Colonization with pneumococcus (PNC), which primes for memory cell response, is common in young children. METHODS: We studied effects of BLPs on memory and primary B and CD4+ T cell responses to pneumococcal proteins using adenoidal cells from children. RESULTS: Although BLPs enhanced the primary antibody responses seen in some children with no detectable nasal PNC, BLPs unexpectedly reduced the memory antibody responses in children with positive nasal culture results. Likewise, BLPs augmented the naive but inhibited the memory antigen-driven CD4+ T cell response. The downregulation of the memory responses was associated with increases in interleukin 10 and inducible costimulatory molecule expression, as well as a decrease in CD28 expression in memory CD4+ T cells; all were blocked by anti-TLR2 and anti-B7h antibodies. Augmentation of naive CD4+ T cell proliferation was blocked by anti-B7.2. CONCLUSION: Differential regulation of primary and memory responses by BLPs through TLR2 may have important implications for therapeutic and vaccination strategies against bacterial infection.

Motivational Interviewing for Hearing Aid Use: A Systematic Meta-Analysis on Its Potential for Adult Patients with Hearing Loss.

PURPOSE: The aim of the study is to conduct a meta-analysis examining the impact of motivational interviewing (MI) on hearing aid (HA) use compared with standard care. RESEARCH DESIGN: The research design is a systematic review and meta-analysis. Cochrane ENT, Central, Medline, Web of Science, ICTRP, and ClinicalTrials.gov electronic databases were searched. Inclusion criteria consisted of randomized controlled trials (RCTs) published between 1988 and 2018 that compared MI to standard care. STUDY SAMPLE: The study sample consists of four RCTs, investigating a total of 176 patients. DATA COLLECTION AND ANALYSIS: RevMan 5.3 and a random effect model were used for analysis. RESULTS: The standardized mean difference in data-logged hours of HA use was not statistically significant (0.34 [95% confidence interval or CI: -0.10, 0.78; p = 0.13]). The mean difference for user-reported outcomes on the International Outcome Inventory-Hearing Aids of 0.41 [CI: -1.00, 1.82; p = 0.57] was also not significant. CONCLUSION: There is no current evidence that MI significantly improves HA use or user-reported outcomes. However, there were limited studies included in this review and further research is indicated.

Virtual and augmented reality in the vestibular rehabilitation of peripheral vestibular disorders: systematic review and meta-analysis.

Vestibular rehabilitation therapy is an established treatment for patients with vestibular dysfunction. Virtual reality (VR) and augmented reality (AR) can be utilised in vestibular rehabilitation. Evidence of the efficacy of VR and AR delivered rehabilitation in patients with peripheral vestibular disorders is reviewed. MEDLINE, EMBASE, CENTRAL, CINAHL, PsychInfo, PsychBITE, OTSeeker, Ei Compendex, IEE, Clinical trials.gov and WebofScience databases were searched. Reduction in vestibular dysfunction symptoms 0-3 months post-intervention was the primary outcome. Secondary outcomes included long-term symptom improvement and side effects. Risk of bias assessment and meta analyses were planned. Five studies meeting eligibility criteria were included. Dizziness Handicap Inventory (DHI) scores 0-3 months post-intervention were reported by four studies. Meta-analysis identified a 1.13 (95% CI, - 1.74, - 0.52) standardized mean difference reduction in DHI in VR and AR treated patients compared to controls. Side effects reported by two studies were reduced by week four of VR intervention. Bias assessment identified DHI scores and side effects to be at high risk or of some concern. Adjunct VR interventions reduced patient DHI significantly more than vestibular rehabilitation alone 0-3 months post-intervention in adult patients diagnosed with unilateral vestibular disease. High quality studies are needed.

microRNAs in sudden hearing loss.

OBJECTIVES: To compare the circulating microRNA (miRNA) expression profiles between sudden sensory neural hearing loss (SSNHL) patients and age-matched normal hearing controls. STUDY DESIGN: Prospective cohort multi-center study. METHODS: Patients presenting within 28 days of onset of SSNHL were prospectively recruited along with contemporaneous age-matched controls. Pooled sera of four patient (n = 09, mean age = 53.0 years; 07, 55.0; 10, 52.9; 10, 51.6) and two control (09, 51.2 and 03, 50.0) groups were assessed using a TaqMan Low Density Array. The patients' sera were also divided into two pools, untreated (04, 57.7) and treated (32, 52.6) for additional analysis. miRNA expression level was derived from cycle threshold (Ct) values normalized to a global mean. Inter-group mean Ct differences with fold changes ≥2.0 and ≤0.5 at P < .05 were considered significant. Bioinformatic databases were used to identify putative target mRNAs or validated genes and their functional annotations. RESULTS: Thirty-six SSNHL patients (mean age 53.0 ± standard deviation (SD) 15.2 years) and 12 controls (50.9 ± 11.9) were studied. Eight miRNAs hsa-miR-590-5p/ -186-5p/ -195-5p/ -140-3p/ -128-3p/ -132-3p/ -375-3p, and -30a-3p were identified as significantly differentially expressed in SSNHL patients. Most of these miRNAs were abundantly identified in the nervous system and the putative target messenger RNAs (mRNAs) were enriched in signaling pathways such as phosphatidyl inositol 3 kinase/protein Kinase B (PI3K/Akt), Ras and mitogen-activated protein kinase (MAPK). CONCLUSION: These findings suggest the possible cellular signaling pathways that underlie the disruption of auditory signal transmission in SSNHL. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:E416-E422, 2020.