The perception of the pitch of a harmonic complex tone missing its fundamental frequency was investigated in patients with unilateral sensorineural low-frequency hearing loss. Using a two-alternative forced choice adaptive method and an adjustment technique, patients matched the pitch of a complex tone consisting of the 3rd-7th or 3rd-10th harmonics, with a pure tone. Component frequencies were chosen such that they would fall within the intact portion of the patient's damaged ear, but whose fundamental frequency would fall within the damaged frequency area. Pitch matches were made monaurally and binaurally, with and without low-pass filtered noise. Results indicated that the patients tended to match the pitch of the lacking fundamentals to the complexes even though the frequency of the residue pitch fell within the range of elevated pure tone thresholds. It is concluded that information regarding the residue pitch is not mediated by cochlear nerve fibers with characteristic frequencies corresponding to the fundamental. Temporal cues carried by fibers with characteristic frequencies corresponding to the partials within the complex stimulus are most likely involved in pitch perception. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

The purpose of this investigation was (1) to perform hearing screening tests on 100 youths who are classified as delinquent; (2) to evaluate more completely the hearing of those who fail the hearing screening tests in order to determine the nature and severity of the losses; and (3) to determine whether or not any significant number of the youths tested demonstrate nonorganic components in their reported audiometric thresholds.

Background: Pure-tone, air-conduction audiograms notched at 4000 Hz have long been considered the signature configuration for noise-induced hearing loss even though there is an extensive literature that does not mesh with this simple explanation. There are many reports of notched audiograms from individuals with no history of noise exposure and, conversely, reports of audiograms with no notches from individuals with a history of noise exposure. Recent reports increasingly suggest that unilateral 4000 Hz notches are common. The prevalence of notched audiograms at 4000 Hz is dependent on the definition of the notch and the population under study. Purpose: To examine the prevalence and characteristics of audiograms that are notched at 4000 Hz. Research Design: Retrospective, descriptive. Study Sample: The participants were 3430 veterans evaluated in the Audiology Clinic at the VA Medical Center, Mountain Home, Tennessee. The mean age was 62.3 yr. Data Collection and Analyses: The data were collected in the course of a 60 min, routine audiological evaluation. In addition to pure-tone audiometry, a history, otoscopy, speech audiometry in quiet and in noise, and aural-acoustic immittance measures were included in the clinic protocol but were not evaluated in this report. A notch was defined when the 4000 Hz threshold minus the 2000 Hz threshold and the 4000 Hz threshold minus the 8000 Hz threshold both were ≥10 dB. Results: Overall the mean LE (left ear) thresholds at 2000, 3000, and 4000 Hz were at hearing levels 2-3 dB higher than the hearing levels for the corresponding mean RE (right ear) thresholds; the differences were significant. A notched audiogram was observed in 40.6% of the participants in at least one ear with 15.4% having bilateral notches, 28.8% LE notches, and 27.1% RE notches. Unilateral 4000 Hz notches were almost twice as prevalent as bilateral 4000 Hz notches. Viewed as a function of age, notched audiograms were most common (∼35% of the participants) in the 40 and 50 yr groups with a diminishing prevalence in the 60-80 yr groups. The mean notch depth at 4000 Hz was consistently 20-26 dB across the seven age groups. In comparison to the thresholds of the audiograms that were not notched, the thresholds of the audiograms with 4000 Hz notches (1) at 250-2000 Hz were at hearing levels 2-3 dB lower, (2) at 3000 and 4000 Hz were at hearing levels 8-17 dB higher, and (3) at 8000 Hz were at hearing levels 3-4 dB lower; the threshold differences were significant at all frequencies for both ears. Conclusions: The data suggest that unilateral, 4000 Hz notched audiograms are as common or more common than bilateral notched audiograms and that unilateral notched audiograms are equally common for the LE and RE. The prevalence and characteristics of 4000 Hz notched audiograms in this veteran sample are similar to those observed in the population as a whole.

Regulators of G-protein signaling (RGS) are a multifunctional and highly diverse group of proteins that negatively regulate G-protein coupled receptor (GPCR) signaling pathways. The common mechanism of RGS is to act as GTPase accelerating proteins (GAP) to accelerate the hydrolysis of active GTP bound G proteins and terminate the actions of the associated GPCR. In addition to the traditional function of inhibiting G-protein signaling, recent studies have highlighted the role of RGS proteins in modulating GPCRs in GAP-independent way. There are more than 30 RGS proteins, and depending upon cell/tissue type, they interact and associate with different G proteins and GPCRs to modulate various physiological functions. RGS17, a member of the RGS-RZ subfamily, commonly targets GTP bound Gαz, Gαi, and Gαo for hydrolysis and signal termination. RGS17 is abundantly expressed in the central nervous system and is highly associated with opioid, dopamine and cannabinoid receptors in the brain. RGS17 is also upregulated in many malignant tumors such as lung, prostate and breast cancers. Analysis of whole cochlea transcriptome data from our lab revealed higher levels of RGS17 in the cochlea after cisplatin treatment. This highlights a possible role of RGS17 (and probably other RGS proteins) in cisplatin ototoxicity. Activation of endogenous, otoprotective GPCRs such as adenosine (A1AR) and cannabinoid (CB2) receptor is beneficial for promoting protection against cisplatin-induced hearing loss. Taking all this together, the underlying hypothesis for this study is that cisplatin could possibly mediate ototoxicity by increasing the expression of RGS17, which reduces the otoprotective effect of endogenous receptors such as cannabinoid receptor 2. The main objective of the study is to examine the expression and function of RGS17 in the cochlea and determine if inhibition of RGS17 could protect against cisplatin ototoxicity.The expression of RGS17 was observed in the both in vitro and in vivo models of cochlear cell types. Immunofluorescence study, western blot analysis, and RT-qPCR results showed the presence of RGS17 in UB\OC-1, as well as Wistar rat cochlea; expression levels increased after cisplatin treatment. To determine the role of RGS17 in hearing, first, it was overexpressed in the cochlea using adenoviral vector that was found to significantly increase ABR threshold shifts and decrease ABR Wave I amplitude. Conversely, knockdown of RGS17 (by siRGS17) decreased cisplatin-induced elevations in ABR thresholds along with increased wave I amplitude and latency. Furthermore, siRGS17 pretreatment prevented cisplatin-mediated synapse loss at inner hair cells. This indicates inhibition of RGS17 can preserve the functional and physiological integrity of the cochlea, which is essential for hearing. Cochleae that were treated with siRGS17, followed by cisplatin, showed fewer TUNEL-positive cells and reduced loss of Outer hair cells (OHC) as compared to cisplatin-treated rats. Moreover, overexpression of RGS17 increased the ratio of the transcription factors, pSTAT1/pSTAT3, which may indicate initiation of the apoptotic pathway. Moreover, UB\OC-1 cells treated with Celastrol, a RGS17 inhibitor, showed an increase in cell viability against cisplatin toxicity. In addition to apoptosis, overexpression of RGS17 also elevated ROS production and oxidative stress. But, the inhibition of RGS17 attenuated the cisplatin-induced increase in transcripts for oxidative and inflammatory stress markers, such as NOX3, iNOS, KIM1, TNF-α, and COX2, whereas the mRNA level of antioxidant genes such as Nrf2 and SOD2 were increased. Activation of CB2 via JWH-015 (a CB2 agonist) prior to cisplatin administration significantly reduced the cisplatin-induced elevated levels of RGS17, while knockdown of CB2 increased RGS17 expression in the cochlea. siRGS17 treatment boosted endogenous CB2R-Gα expression. Additionally, cisplatin decreased the expression of Gαi/o and Gαz in vitro, but the activation of CB2 increased the expression of these G proteins. Furthermore, JWH-015 treatment alleviated RGS17-dependent cell death. This study suggests that RGS17 could serve as a mediator of cisplatin ototoxicity by reducing the duration of active CB2R-G protein signaling, which normally suppresses cochlear oxidative stress, inflammation and hair cell apoptosis, and thereby preserves normal hearing. These data also indicate the existence of tonic reciprocal inhibition between RGS17 and CB2 mediated via the G proteins. Thus, we propose that RGS17 inhibitors could serve as an effective treatment against cisplatin ototoxicity when used alone and can potentiate the actions of CB2 agonists when used in combination therapy against cisplatin-induced hearing loss.

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Objetivos: estabelecer o diagnóstico de uma amostra de indivíduos com deficiência auditiva (DA) e comprometimento de outras estruturas anatômicas e/ou sistemas fisiológicos, cadastrados no CEDALVI/HRAC-USP-Bauru; verificar possíveis fatores etiológicos envolvidos e investigar possível correlação do tipo de DA com as diferentes síndromes encontradas. Local: Serviço de Genética Clínica do CEDALVI/HRAC-USP, Bauru-SP. Participantes: 93 indivíduos com DA e comprometimento de outras estruturas anatômicas e/ou sistemas fisiológicos. Intervenções: Avaliação genética-clínica; estudo citogenético; avaliações radiológica, oftalmológica, otorrinolaringológica, audiológica e outras. Resultados: Dos 93 indivíduos, 51 eram do sexo masculino e 42, do feminino. Recorrência familial foi observada em 31 casos e, consangüinidade parental em 8. Na amostra, 25 síndromes gênicas conhecidas, 5 síndromes cromossômicas, 5 quadros de etiologia ambiental e 2 quadros de etiologia heterogênea foram estabelecidos em 87 indivíduos. Em 1 caso, não foi possível definir entre 2 condições gênicas e em 5, não foi possível se chegar a um diagnóstico. Conclusões: a casuística se compôs de síndromes etiologicamente heterogêneas, com maior freqüência de etiologia genética; o tipo de DA nas síndromes gênicas foi condizente com o quadro diagnosticado; 3 indivíduos apresentaram síndromes ambientais clássicas, com diferentes tipos de DA; 2 indivíduos apresentaram quadro clínico, possivelmente decorrente de efeito teratogênico; implicação direta de fatores de risco para DA, na etiologia dessa, nos indivíduos com síndromes gênicas conhecidas sem DA; 1 caso, possivelmente, representa uma síndrome nova de padrão único, de etiologia desconhecida; o aconselhamento genético está na dependência da fase em que se encontra o processo de delineamento das diferentes condições estabelecidas. / Objectives: The purposes of this study were to establish the diagnostic of the individuals with hearing loss and presenting other additional anatomic structures and/or physiologic systems involvement, recorded in the CEDALVI/HRAC-USP-Bauru; to verify possible etiologic factors involved and to investigate a possible correlation of the hearing loss type with the different diagnosis syndromes. Setting: Clinical genetic service of the CEDALVI/HRAC-USP, Bauru- P. Participants: The sample was comprised of 93 individuals with hearing loss and involvement of other anatomic structures and/or physiologic systems. Interventions: Clinical genetic evaluation; cytogenetic study; radiological, ophtalmological, othorinolaryngological, audiologycal evaluation, etc. Results: From the total of the sample, 51 were male and 42 were female. Familial recurrence was observed in 31 cases and parental consanguinity in 8. In the present sample, 25 known genic syndromes, 5 chromosomal syndromes, 5 environmental conditions, and 2 heterogeneous conditions were established in 87 individuals. The diagnosis was not established in 5 individuals and in 1 case it was not possible to define between 2 genic conditions. Conclusions: The casuistic was composed of etiologically heterogeneous syndromes with greater frequency of genetic etiology; the type of hearing loss in the genic syndromes was concordant with the diagnosed condition; 3 individuals presented classic environmental syndromes with different types of hearing loss; 2 individuals presented clinical picture, possibly due to teratogenic effect; hearing impairment related to risk factors of the hearing loss in the individuals with known genic syndromes without hearing loss; probable a new unique-pattern syndrome, of unknown etiology in 1 case; the genetic counseling will depend on the step of delineation process of the different diagnosed condition.

Objetivo: Verificar o desempenho de crianças diagnosticadas com deficiência auditiva, de grau leve, condutiva e sensorioneural, no Teste da Habilidade de Atenção Auditiva Sustentada (THAAS) visando constatar se este teste sofre influência da presença de uma deficiência auditiva. Modelo: Estudo do Teste da Habilidade de Atenção Auditiva Sustentada-THAAS em três grupos: grupo 1 (G1) grupo controle, formado por crianças com audição normal; grupo 2 (G2) crianças com deficiência auditiva sensorioneural bilateral de grau leve e grupo 3 (G3) composto por crianças com perda auditiva condutiva bilateral de grau leve. Local: Divisão de Saúde Auditiva ? Hospital de Reabilitação de Aanomalias Craniofaciais ?Universidade de São Paulo (HRAC/USP). Participantes: 90 crianças com idade entre 7 e 11 anos de idade, sendo 30 de cada grupo. Intervenções: Audiometria Tonal Limiar, Imitanciometria e THAAS Resultados: não houve indícios estatisticamente significativos entre sexo e idade, em todos os grupos estudados. Os grupos sensorioneural e condutivo apresentaram desempenho inferior ao grupo controle, em todas as respostas do THAAS. Conclusões: o teste THAAS sofreu influência das perdas auditivas de grau leve, condutivas e sensorioneurais na população estudada, sendo o pior comprometimento para perdas sensorioneurais. / Objective: To verify the performance of children diagnosed with a hearing loss of mild degree, conductive and sensorineural, at Sustained Auditory Attention Ability Test (SAAAT), aiming to observe if this test suffers the influence of the presence of a hearing loss. Model: A study of the Sustained Auditory Attention Ability Test ? SAAAT in three groups: group 1 (G1) control group comprising children with normal hearing, group 2 (G2) children with a bilateral sensorineural hearing loss of a mild degree and group 3 (G3), comprising children with a bilateral conductive hearing loss of a mild degree. Place: Division for Hearing Health ? Craniofacial Anomaly Rehabilitation Hospita, University of São Paulo (HRAC/USP). Participants: 7 to 11 year old children, 30 for each group. Interventions: Pure Tone Audiometry, Immitance Acoustic and SAAAT. Results: There were not any statistically significant indications between sex and age in all studied groups. Sensorineural and conductive groups showed a lower performance related to control group in all answers for SAAAT. Conclusions: SAAAT test suffered the influence of conductive and sensorineural hearing losses of light degree in studied population, the worse compromise occurring for sensorineural losses.

In the future, audiological rehabilitation of adults with hearing loss will be more available, personalized and thorough due to the possibilities offered by the internet. By using the internet as a platform it is also possible to perform the process of rehabilitation in a cost-effective way. With tailored online rehabilitation programs containing topics such as communication strategies, hearing tactics and how to handle hearing aids it might be possible to foster behavioral changes that will positively affect hearing aid users. Four studies were carried out in this thesis. The first study investigated internet usage among adults with hearing loss. In the second study the administration format, online vs. paper- and pencil, of four standardized questionnaires was evaluated. Finally two randomized controlled trials were performed evaluating the efficacy of online rehabilitation programs including professional guidance by an audiologist. The programs lasted over five weeks and were designed for experienced adult hearing-aid users. The effects of the online programs were compared with the effects of a control group. It can be concluded that the use of computers and the internet overall is at least at the same level for people with hearing loss as for the general age-matched population in Sweden. Furthermore, for three of the four included questionnaires, the participants’ scores remained the same across formats. It is however recommended that the administration format remain consistent across assessment points. Finally, results from the two concluding intervention studies provide preliminary evidence that the internet can be used to deliver education and rehabilitation to experienced hearing aid users who report residual hearing problems and that their problems are reduced by the intervention; however the content and design of the online rehabilitation program requires further investigation.

INTRODUCTION: Asymmetrical sensorineural hearing loss [ASNHL] is a common otological complaint. Vestibular schwannoma [VS] is a rare, benign tumor that commonly presents with ASNHL. Magnetic resonance imaging [MRI] is the gold standard in diagnosing VS, but is an expensive imaging modality. Therefore, this meta-analysis evaluates the diagnostic yield of MRI scans in patients with ASNHL to rule out VS. METHODS: A systematic review was performed using a keyword search on the PubMed Database. We excluded articles based on: Non-English, case reports, wrong diagnostic test, solely pediatric subjects, inadequate/unnecessary data, repeated studies, and unclear presenting symptoms. The demographics, definition of ASNHL, and the number and results of MRIs were collected. Positive MRIs were grouped based on differences in interaural hearing loss. RESULTS: 5,783 MRIs on subjects with ASNHL were collected from fourteen studies. 296 MRI scans (5.1%) were positive for VS. 170 positive scans were grouped. In Group A (10+ dB) 11.2% had VS; in Group B (15+ dB at ≥2 frequencies or 20+ dB at 1 frequency) 6.5% had VS, Group C (20+ dB) yielded 5.1% with VS, and Group D (30+ dB) had 0.7% yield of positive VS. CONCLUSION: MRI scans to rule out VS in patients with ASNHL has an extremely low diagnostic yield when assessing subjects on the basis of ASNHL. The degree of ASNHL does not correlate with increased odds of VS diagnosis. Overall, the risk of VS diagnosis in patients with any degree of ASNHL is low.