Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor.

Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa+/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.

Hearing aid use and adherence: A systematic review of the literature concerning the socioeconomic and psychological influences on hearing aid use and barriers to use

The current hearing health situation in the United States does not provide adequate support to individuals with hearing loss. More research is needed to give more support to these individuals. By conducting a systematic review of relevant literature from 1990 to present, I identified many factors that influence an individual's use of hearing aids. There are two research questions in this study: 1. Does the provision of screening and access to hearing aids decrease the negative effects of hearing loss? 2. Why is it difficult for people with hearing loss to adapt to and use hearing aids? The population of interest was adults (>18 years old) with hearing loss. Factors that influenced use of hearing aids for this population included age, gender, socioeconomic status, education, perceived severity of hearing loss, cost of hearing aids, screening, perceived benefit, stigmatization, perceived control, cognitive capability, personality, and social support. Research suggests that more efficient screening of at-risk individuals and the provision of better access to these individuals would prevent many of the negative effects of hearing loss.^

Gene disruption of p27Kip1 allows cell proliferation in the postnatal and adult organ of Corti

Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B., et al. (1995) Science 267, 1024–1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27Kip1 is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27Kip1-gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27Kip1-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

Recovery of hearing and vocal behavior after hair-cell regeneration

Postmitotic hair-cell regeneration in the inner ear of birds provides an opportunity to study the effect of renewed auditory input on auditory perception, vocal production, and vocal learning in a vertebrate. We used behavioral conditioning to test both perception and vocal production in a small Australian parrot, the budgerigar. Results show that both auditory perception and vocal production are disrupted when hair cells are damaged or lost but that these behaviors return to near normal over time. Precision in vocal production completely recovers well before recovery of full auditory function. These results may have particular relevance for understanding the relation between hearing loss and human speech production especially where there is consideration of an auditory prosthetic device. The present results show, at least for a bird, that even limited recovery of auditory input soon after deafening can support full recovery of vocal precision.

Caracterização do potencial evocado auditivo cortical P1-N1-P2 em crianças com estimulação bimodal

Introdução: O implante coclear (IC) amplamente aceito como forma de intervenção e (re) habilitação nas perdas auditivas severas e profundas nas diversas faixas etárias. Contudo observa-se no usuário do IC unilateral queixas como localização e compreensão sonora em meio ao ruído, gerado pelo padrão anormal de estimulação sensorial. A fim de fornecer os benefícios da audição binaural, é preconizado a estimulação bilateral, seja por meio do IC bilateral ou com a adaptação de um aparelho de amplificação sonora individual (AASI) contralateralmente ao IC. Esta última condição é referida como estimulação bimodal, quando temos, concomitantemente dois modos de estimulação: Elétrica (IC) e acústica (AASI). Não há dados suficientes na literatura voltados à população infantil que esclareça ou demonstre o desenvolvimento do córtex auditivo na audição bimodal. Ressalta-se que não foram encontrados estudos em crianças. Objetivo: Caracterizar o PEAC complexo P1, N1 P2 em usuários da estimulação bimodal e verificar se há correlação com testes de percepção de fala. Metodologia: Estudo descritivo de séries de casos, com a realização do PEAC em cinco crianças usuárias da estimulação bimodal, a partir da metodologia proposta por Ventura (2008) utilizando o sistema Smart EP USB Jr da Intelligent Hearing Systems. Foi utilizado o som de fala /da/, apresentado em campo livre. O exame será realizado em três situações: Somente IC, IC e AASI e somente AASI. A análise dos dados dos potenciais corticais foi realizada após a marcação da presença ou ausência dos componentes do complexo P1-N1-P2 por dois juízes com experiência em potenciais evocados. Resultados: Foi obtida a captação do PEAC em todas as crianças em todas as situações de teste, além do que foi possível observar a correlação destes com os testes de percepção auditiva da fala. Foi possível verificar que o registro dos PEAC é um procedimento viável para a avaliação da criança com estimulação bimodal, porém, ainda não há dados suficientes quanto a utilização deste para a avaliação e indicação do IC bilateral.

Surdez súbita : a marcha diagnóstica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Hearing conservation.

"OSHA 3074."

Older people with hearing impairment: A literature review of the spouse's perspective

Spouses of older people with hearing impairment frequently urge their hearing impaired partners to seek help for their hearing difficulties. Only a minority of individuals with hearing impairment are self-motivated, with the majority of clients, especially older clients, presenting at audiology clinics under the persuasion or influence of their spouse or significant other. This highlights the important role that spouses play in initiating aural rehabilitation and indicates that spouses of older people with hearing impairment may become so frustrated with their partners' hearing loss that they are often the primary reason why the hearing impaired person presents for audiological services. To date, however, the number of studies addressing the effect of hearing loss on significant others is limited. Those studies that have investigated the effect of hearing impairment on families are commonly focused on the person with the impairment and most commonly, the significant other has merely been used as a proxy to describe the perceived problems of his or her spouse. Further, there has been no systematic indepth investigation of the needs of spouses of older people with hearing impairment, including the effect of retirement and the increase in time spent together, with the majority of studies focusing primarily on younger spouses of workers affected by noise-induced hearing loss. The cumulative effect of experiencing many years of hearing difficulties with a partner may also influence the extent to which older spouses are affected by hearing impairment. The primary purpose of this article is therefore to critically review the existing literature on the effects of hearing impairment on spouses. It will also provide a rationale for the importance of this topic as a clinical issue and suggest some future directions for research in this area.

Hearing sensitivity and bone mineral density in older adults: the Health, Aging and Body Composition Study

Bone mineral density (BMD) may be associated with hearing loss in older adults. Demineralization of the cochlear capsule has been associated with hearing loss in those with Paget's disease of the bone and otosclerosis. Osteoporosis may also result in cochlear capsule demineralization. We hypothesized that lower hip BMD and lower heel ultrasound measurements would be associated with hearing loss in a population-based sample of 2,089 older black and white men and women. Bone parameters and hearing function were measured at the fourth clinical follow-up visit. Audiometric threshold testing was used to measure air- and bone-conduction hearing sensitivity. BMD of the hip and its subregions was measured using dual-energy X-ray absorptiometry. Calcaneal bone measurements [broadband ultrasound attenuation (BUA), speed of sound (SOS) and the quantitative ultrasound index (QUI)] were obtained using heel ultrasound. After adjusting for known hearing loss risk factors, no association was found between hearing and any of the bone measurements in whites and black women. In black men, however, lower hip BMD was associated with higher odds of hearing loss; for each standard deviation decrease in total hip BMD, the odds of hearing loss were 1.41 (95% confidence interval 1.08, 1.83), 1.39 (95% CI 1.07, 1.82) for femoral neck BMD and 1.65 (95% CI 1.26, 2.16) for trochanter BMD. Conductive hearing loss was associated with lower heel ultrasound measurements, though only among white men. The results of this study are mixed and inconclusive. Lower BMD of the hip and its subregions was associated with hearing loss among black men, but not among whites or black women. Lower measurements on heel ultrasound were associated with conductive hearing loss, though only among white men. These results suggest that axial and appendicular bone parameters may be modestly associated with hearing loss in older men, but not in women.

Hearing and vision:the age old problem

Opticians and audiologists tend to see the same people. Many factors that are associated with poorer vision, whether hereditary, pre-natal, or post-natal, are also associated with poorer hearing. The most common factor is simply old age. According to the Royal National Institute for Deaf People (RNID), more than half of all people aged over 60 have some degree of hearing loss and are gradually losing their hearing as part of the ageing process – a process known as presbycusis.

Help-seeking for medically unexplained hearing difficulties:a qualitative study

Aims - Up to 10% of audiology patients report diffi culties hearing speech in noise even though clinical investigation reveals normal hearing thresholds, in other words, no evidence of physical pathology. The diagnostic category applied to these patients is known as King-Kopetzky Syndrome (KKS). This study aimed to gather descriptions of patients' experiences of the clinical encounter involving their KKS diagnosis and analyse the themes of help-seeking, as part of a larger study into the process of coping with medically unexplained hearing diffi culties. Method - A qualitative approach was employed, comprising unstructured interviews in the homes of 25 patients who had attended audiology services (and received a diagnosis of KKS) in Bath and Cardiff. Thematic analysis of transcripts was undertaken, infl uenced by grounded theory techniques. Findings - Informants characterized the clinical encounter as either negative or positive. Negative consultations were those in which patients' illness claims were dismissed and as such not validated. Positive encounters were typifi ed by the provision of meaningful information that reconciled clinical information with the patients' experiences of hearing loss. Conclusion - Successful management of medically unexplained illnesses requires the adoption of a patient-centred approach, rather than focusing on the absence of observable pathology

An exploration of the perspectives of help-seekers prescribed hearing aids

Aim - This pilot study uses qualitative methods to learn about the psycho-social needs of people who seek help with hearing loss. Background - There has been some emphasis in health policy to reduce the number of appointments required between assessment of hearing loss and fitting of hearing aids. This may respond to audiological needs but may not address the psycho-social needs. This study piloted a phenomenological approach to identify the patient's perspective. Methods - A phenomenological approach was taken to provide description of patient perspectives. Findings - Six patients reported that help-seeking was primarily influenced by the need to appease social partners and to improve hearing performance. Hearing aids were not regarded as acceptable treatments. Conclusions - Service providers need to consider the psycho-social consequences of hearing-aid issue alongside audiological needs.

Effects of real -time captioning and sign language interpreting on the learning of college students who are deaf or hard of hearing

College personnel are required to provide accommodations for students who are deaf and hard of hearing (D/HoH), but few empirical studies have been conducted on D/HoH students as they learn under the various accommodation conditions (sign language interpreting, SLI, real-time captioning, RTC, and both). Guided by the experiences of students who are D/HoH at Miami-Dade College (MDC) who requested RTC in addition to SLI as accommodations, the researcher adopted Merten’s transformative-emancipatory theoretical framework that values perceptions and voice of students who are D/HoH. A mixed methods design addressed two research questions: Did student learning differ for each accommodation? What did students experience while learning through accommodations? Participants included 30 students who were D/HoH (60% women). They represented MDC’s majority minority population: 10% White (non-Hispanic), 20% Black (non-Hispanic, including Haitian/Caribbean), 67% Hispanic, and 3% other. Hearing loss, ranged from severe-profound (70%) to mild-moderate (30%). All were able to communicate with American Sign Language: Learning was measured while students who were D/HoH viewed three lectures under three accommodation conditions (SLI, RTC, SLI+RTC). The learning measure was defined as the difference in pre- and post-test scores on tests of the content presented in the lectures. Using repeated measure ANOVA and ANCOVA, confounding variables of fluency in American Sign Language and literacy skills were treated as covariates. Perceptions were obtained through interviews and verbal protocol analysis that were signed, videotaped, transcribed, coded, and examined for common themes and metacognitive strategies. No statistically significant differences were found among the three accommodations on the learning measure. Students who were D/HoH expressed thoughts about five different aspects of their learning while they viewed lectures: (a) comprehending the information, (b) feeling a part of the classroom environment, (c) past experiences with an accommodation, (d) individual preferences for an accommodation, (e) suggestions for improving an accommodation. They exhibited three metacognitive strategies: (a) constructing knowledge, (b) monitoring comprehension, and (c) evaluating information. No patterns were found in the types of metacognitive strategies used for any particular accommodation. The researcher offers recommendations for flexible applications of the standard accommodations used with students who are D/HoH.

Transgenic Expression of Endothelin Receptor-B Rescues the Aganglionosis Phenotype of Piebald Lethal Mice

Neural crest cells (NCC) are a unique population of cells in vertebrates that arise between the presumptive epidermis and the dorsal most region of the neural tube. During neurulation, NCC migrate to many regions of the body to give rise to a wide variety of cell types. NCC that originate from the neural tube at the levels of somite 1-7 colonize the gut and give rise to the enteric ganglia. The endothelin signaling pathway has been shown to be crucial for proper development of some neural crest derivatives. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene exhibit similar phenotypes characterized by hypopigmentation, hearing loss, and megacolon. Thesephenotypes are due to lack of melanocytes in the skin, inner ear and enteric ganglia in the distal portion of the colon, respectively. It is well established that Ednrb is required early during the embryonic development for normal innervation of the gut. However, it is not clear if Ednrb acts on enteric neuron precursor cells or in pre-committed NC precursors. Additionally, it is controversial whether the action of Ednrb is cell autonomous or non- autonomous. We generated transgenic mice that express Ednrb under the control of the Nestin second intron enhancer (Nes) which drives expression to pre-migrating NCC. These mice were crosses to the spontaneous mouse mutant piebald lethal, which carriers a null mutation in Ednrb and exhibits enteric aganglionosis. The Nes-Ednrb was capable of rescuing the aganglianosis phenotype of piebald lethal mutants demonstrating that expression of Ednrb in pre-committed precursors is sufficient for normal enteric ganglia development. This study provides insight in early embryonic development of NCC and could eventually have potential use in cellular therapies for Hirschsprung's disease.