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1.
Otol Neurotol ; 45(6): e483-e489, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38865725

RESUMO

OBJECTIVE: To evaluate the effects of related factors on long-term speech perception and quality-of-life (QoL) outcomes in postlingual deaf Mandarin-speaking adult cochlear implant (CI) recipients and to assess any differences between tone language and other intonation language CI adult users. STUDY DESIGN: Retrospective cases review. SETTING: Tertiary referral center. PATIENTS: Forty-five adult CI recipients (48 implanted ears). MAIN OUTCOME MEASURES: Post-CI outcomes were evaluated after follow-ups of more than 24 months using speech perception tests and QoL questionnaires. We analyzed the related factors affecting CI outcomes. RESULTS: A shorter duration of profound deafness was predictive factors for better post-CI speech perception. Earlier implantation and better performance of vowel scores were predictive of better subjective improvements in social and emotional life. Post-CI vowel scores of over 56% indicated promising improvements in QoL. CONCLUSION: Shorter duration of deafness could have better post-CI speech perception. Post-CI vowel scores instead of monosyllable words have the more potential to predict the QoL in Mandarin-speaking adult CI recipients.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Idioma , Qualidade de Vida , Percepção da Fala , Humanos , Percepção da Fala/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Surdez/cirurgia , Surdez/psicologia , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Adulto Jovem , Inquéritos e Questionários
2.
Trends Hear ; 28: 23312165241256721, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773778

RESUMO

This study aimed to investigate the role of hearing aid (HA) usage in language outcomes among preschool children aged 3-5 years with mild bilateral hearing loss (MBHL). The data were retrieved from a total of 52 children with MBHL and 30 children with normal hearing (NH). The association between demographical, audiological factors and language outcomes was examined. Analyses of variance were conducted to compare the language abilities of HA users, non-HA users, and their NH peers. Furthermore, regression analyses were performed to identify significant predictors of language outcomes. Aided better ear pure-tone average (BEPTA) was significantly correlated with language comprehension scores. Among children with MBHL, those who used HA outperformed the ones who did not use HA across all linguistic domains. The language skills of children with MBHL were comparable to those of their peers with NH. The degree of improvement in audibility in terms of aided BEPTA was a significant predictor of language comprehension. It is noteworthy that 50% of the parents expressed reluctance regarding HA use for their children with MBHL. The findings highlight the positive impact of HA usage on language development in this population. Professionals may therefore consider HAs as a viable treatment option for children with MBHL, especially when there is a potential risk of language delay due to hearing loss. It was observed that 25% of the children with MBHL had late-onset hearing loss. Consequently, the implementation of preschool screening or a listening performance checklist is recommended to facilitate early detection.


Assuntos
Linguagem Infantil , Auxiliares de Audição , Perda Auditiva Bilateral , Desenvolvimento da Linguagem , Humanos , Masculino , Pré-Escolar , Feminino , Perda Auditiva Bilateral/reabilitação , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Bilateral/fisiopatologia , Perda Auditiva Bilateral/psicologia , Percepção da Fala , Estudos de Casos e Controles , Correção de Deficiência Auditiva/instrumentação , Resultado do Tratamento , Pessoas com Deficiência Auditiva/reabilitação , Pessoas com Deficiência Auditiva/psicologia , Índice de Gravidade de Doença , Compreensão , Audição , Audiometria de Tons Puros , Fatores Etários , Limiar Auditivo , Testes de Linguagem
3.
Eur Arch Otorhinolaryngol ; 281(6): 3265-3268, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409582

RESUMO

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial disease that affects various systems in the body, particularly the brain, nervous system, and muscles. Among these systems, sensorineural hearing loss is a common additional symptom. METHODS: A 42-year-old female patient with MELAS who experienced bilateral profound deafness and underwent bilateral sequential cochlear implantation (CIs). Speech recognition and subjective outcomes were evaluated. RESULTS: Following the first CI follow-up, the patient exhibited improved speech recognition ability and decided to undergo the implantation of the second ear just two months after the initial CI surgery. The second CI also demonstrated enhanced speech recognition ability. Subjective outcomes were satisfactory for bilateral CIs. CONCLUSIONS: MELAS patients receiving bilateral CIs can attain satisfactory post-CI speech recognition, spatial hearing, and sound qualities.


Assuntos
Implante Coclear , Implantes Cocleares , Síndrome MELAS , Humanos , Feminino , Adulto , Síndrome MELAS/complicações , Implante Coclear/métodos , Perda Auditiva Neurossensorial/cirurgia , Perda Auditiva Neurossensorial/etiologia , Percepção da Fala
4.
Acta Otolaryngol ; 144(1): 44-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38400594

RESUMO

BACKGROUND: With advances in cochlear implant (CI) technology, prelingual deaf adults may experience improved speech perception and quality of life (QoL). It is still a challenge for Mandarin-speaking CI user with tone recognition due to CI technology focused on intonation language. OBJECTIVES: To evaluate the long-term post-CI auditory performance and social-emotional benefits in prelingual deaf Mandarin-speaking adults and the difference between them and post-lingual deaf adults. MATERIAL AND METHODS: Fifty-five adult implanted ears were included (forty-six postlingual deaf group; nine prelingual deaf group). Post-CI long-term outcomes were using vowels, consonants, disyllabic words, Mandarin monosyllable words, categories of audiology performance, speech intelligibility rating, subjective social-emotional questionnaires. RESULTS: Post-CI auditory performance and speech intelligibility of prelingual deafness adults was significantly inferior to that of those with postlingual deafness. However, both groups presented improved social-emotional benefits, with no significant difference between both groups. CONCLUSIONS: Adult CI recipients who deaf before the age of 4 can experience benefits in social-emotional life functioning, regardless of their limited auditory performance and speech intelligibility. Therefore, prelingual Mandarin-speaking deaf adults, especially those using oral communication, can be considered as relative indications for cochlear implantation. SIGNIFICANCE: To clarify and validate the benefits among Mandarin-speaking prelingual deaf adult recipients.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Percepção da Fala , Adulto , Humanos , Qualidade de Vida , Surdez/cirurgia , Surdez/reabilitação
5.
Am J Otolaryngol ; 44(4): 103876, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37084611

RESUMO

PURPOSE: Although previous studies have shown the efficacy of cochlear implants (CIs) in older adults, no study written in English has focused on Mandarin-speaking older recipients. Mandarin is a tonal language, it is hard to lip-read and tone recognition for CI users. This study aimed to evaluate the long-term post-CI outcomes in Mandarin-speaking older adults and the difference between them and younger recipients. MATERIALS AND METHODS: Forty-six post-lingually deafened adults were included. Speech perception tests (vowel, consonant, disyllable words, Mandarin monosyllable recognition test, and categories of audiology performance were evaluated) and psychosocial scale were evaluated. RESULTS: There were no significant differences between older and younger recipients in post-CI open-set speech perception. However, older recipients had significantly lower social and total scores in the subjective questionnaire than younger recipients. In both duration of deafness less than seven years and hearing years in life over 92.6 %, older recipients had no less capable speech perception than in younger. CONCLUSION: Mandarin-speaking older recipients can improve not only speech perception but also psychosocial benefits. Well hearing experience may confer an advantage to older recipients, despite their older implanted age. These results can help provide pre-CI consultation guidelines for older Mandarin-speaking recipients.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Percepção da Fala , Humanos , Idoso , Implante Coclear/métodos , Surdez/cirurgia , Idioma
6.
J Clin Med ; 11(14)2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35887909

RESUMO

The value of kinematic data for skill assessment is being investigated. This is the first virtual reality simulator developed for liver surgery. This simulator was coded in C++ using PhysX and FleX with a novel cutting algorithm and used a patient data-derived model and two instruments functioning as ultrasonic shears. The simulator was evaluated by nine expert surgeons and nine surgical novices. Each participant performed a simulated metastasectomy after training. Kinematic data were collected for the instrument position. Each participant completed a survey. The expert participants had a mean age of 47 years and 9/9 were certified in surgery. Novices had a mean age of 30 years and 0/9 were certified surgeons. The mean path length (novice 0.76 ± 0.20 m vs. expert 0.46 ± 0.16 m, p = 0.008), movements (138 ± 45 vs. 84 ± 32, p = 0.043) and time (174 ± 44 s vs. 102 ± 42 s, p = 0.004) were significantly different for the two participant groups. There were no significant differences in activating the instrument (107 ± 25 vs. 109 ± 53). Participants considered the simulator realistic (6.5/7) (face validity), appropriate for education (5/7) (content validity) with an effective interface (6/7), consistent motion (5/7) and realistic soft tissue behavior (5/7). This study showed that the simulator differentiates between experts and novices. Simulation may be an effective way to obtain kinematic data.

7.
Int J Pediatr Otorhinolaryngol ; 157: 111141, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35461145

RESUMO

OBJECTIVE: This investigation was to ascertain the performance of the UNHS in Taiwan. METHODS: The predefined questionnaire was delivered on the phone in 2016. The descriptive analysis was applied to the research data. 941 neonates in birth cohorts 2013-2014 who were documented as a bilateral referral in the national UNHS tracking system were targeted. The respondents were either caregivers or family members. RESULTS: 40.3% of 941 children were lost to follow-up, and 66.24% of 363 children were diagnosed with SNHL. 45.15% of 163 children used hearing amplification device(s). 77.46% of hearing amplification device users and 7.51% of non-users participated in the auditory training courses. By six months of age, 38.51% and 22.58% of children diagnosed with bilateral SNHL commenced the hearing amplification device fitting and the auditory training courses, respectively. CONCLUSIONS: More efforts are needed to enhance the performance of the UNHS to achieve national goals stated in the 2014 Taiwan UNHS Revised Guidelines and the well-known benchmarks set by the JCIH in 2007. The development of an electronic tracking system for storing and sharing information on the follow-up on children with congenital hearing loss was as significant as the improvements in the understanding of early hearing detection and intervention of the public and stakeholders.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Adulto , Criança , Surdez/diagnóstico , Surdez/epidemiologia , Seguimentos , Audição , Transtornos da Audição/diagnóstico , Perda Auditiva Bilateral , Perda Auditiva Neurossensorial/epidemiologia , Testes Auditivos , Humanos , Recém-Nascido , Triagem Neonatal , Taiwan
8.
Ear Hear ; 43(4): 1198-1207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34974475

RESUMO

OBJECTIVES: Recessive variants in the MYO15A gene constitute an important cause of sensorineural hearing impairment (SNHI). However, the clinical features of MYO15A-related SNHI have not been systemically investigated. This study aimed to delineate the hearing features and outcomes in patients with pathogenic MYO15A variants. DESIGN: This study recruited 40 patients with biallelic MYO15A variants from 31 unrelated families. The patients were grouped based on the presence of N-terminal domain variants (N variants). The longitudinal audiological data and for those undergoing cochlear implantation, the auditory and speech performance with cochlear implants, were ascertained and compared between patients with different genotypes. RESULTS: At the first audiometric examination, 32 patients (80.0%) presented with severe to profound SNHI. Patients with at least one allele of the N variant exhibited significantly better hearing levels than those with biallelic non-N variants (78.2 ± 23.9 dBHL and 94.7 ± 22.8 dBHL, respectively) (p = 0.033). Progressive SNHI was observed in 82.4% of patients with non-profound SNHI, in whom the average progression rate of hearing loss was 6.3 ± 4.8 dBHL/year irrespective of the genotypes. Most of the 25 patients who underwent cochlear implantation exhibited favorable auditory and speech performances post-implantation. CONCLUSIONS: The hearing features of patients with biallelic pathogenic MYO15A variants are characterized by severe to profound SNHI, rapid hearing progression, and favorable outcomes with cochlear implants. Periodic auditory monitoring is warranted for these patients to enable early intervention.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Percepção da Fala , Surdez/cirurgia , Audição , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/cirurgia , Testes Auditivos , Humanos , Miosinas/genética , Resultado do Tratamento
9.
Hear Res ; 413: 108135, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33288323

RESUMO

Hearing loss, the most common sensory abnormality, is caused by the death of or damage to inner ear hair cells. Genetic mutations are the main cause of hearing loss. We used nex-generation sequencing data released by the Taiwan Biobank to investigate the GJB2 mutation spectrum in 1517 patients. We compared hearing function in Taiwanese patients with nonsyndromic hearing loss (NSHL) caused by the two most common GJB2 mutations c.109G>A (p.V37I) and c.235delC. We extracted DNA from the oral mucosa of patients with NSHL and performed Sanger sequencing to confirm the genotype. Of 240 patients with NSHL, we identified 25 with GJB2 c.109G>A and 9 with GJB2 c.235delC mutations, after excluding patients aged >10 years, in whom hearing loss may have been caused due to age-related degeneration. We investigated genotype-phenotype correlations in patients harboring GJB2 c.109G>A and c.235delC mutations. Furthermore, we described the GJB2 mutation spectrum in the Taiwanese population and identified the role of homozygous and heterozygous GJB2 mutations associated with hearing phenotypes in patients with NSHL. Thus, our study provides insights into the complexity of GJB2 genetics. Our data indicate that GJB2 c.109G>A heterozygotes had poorer hearing than did homozygotes. The mechanism underlying the more severe phenotype in heterozygotes and whether the phenotype is caused by GJB2 heterozygotes or compound heterozygotes warrant future investigation.


Assuntos
Perda Auditiva , Conexina 26/genética , Análise Mutacional de DNA , Genótipo , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Humanos , Mutação , Fenótipo
10.
Hear Res ; 413: 108254, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34020824

RESUMO

Mesenchymal stem cells (MSCs) can be isolated from different tissue origins, such as the bone marrow, the placenta, the umbilical cord, adipose tissues, and skin tissues. MSCs can secrete anti-inflammatory molecules and growth factors for tissue repair and remodeling. However, the ability of skin-derived MSCs (SMSCs) to repair cochlear damage and ameliorate hearing loss remains unclear. Cisplatin is a commonly used chemotherapeutic agent that has the side effect of ototoxicity due to inflammation and oxidative stress. This study investigated the effects of SMSCs on cisplatin-induced hearing loss in mice. Two independent experiments were designed for modeling cisplatin-induced hearing loss in mice, one for chronic toxicity (4 mg/kg intraperitoneal [IP] injection once per day for 5 consecutive days) and the other for acute toxicity (25 mg/kg IP injection once on day one). Three days after cisplatin injection, 1 × 106 or 3 × 106 SMSCs were injected through the tail vein. Data on auditory brain responses suggested that SMSCs could significantly reduce the hearing threshold of cisplatin-injected mice. Furthermore, immunohistochemical staining data suggested that SMSCs could significantly ameliorate the loss of cochlear hair cells, TUNEL-positive cells and cleaved caspase 3-positive cells in cisplatin-injected mice. Neuropathological gene analyses revealed that SMSCs treatment could downregulate the expression of cochlear genes involved in apoptosis, autophagy, chromatin modification, disease association, matrix remodeling, oxidative stress, tissue integrity, transcription, and splicing and unfolded protein responses. Additionally, SMSCs treatment could upregulate the expression of cochlear genes affecting the axon and dendrite structures, cytokines, trophic factors, the neuronal skeleton and those involved in carbohydrate metabolism, growth factor signaling, myelination, neural connectivity, neural transmitter release, neural transmitter response and reuptake, neural transmitter synthesis and storage, and vesicle trafficking. Results from TUNEL and caspase 3 staining further confirmed that cisplatin-induced apoptosis in cochlear tissues of cisplatin-injected mice could be reduced by SMSCs treatment. In conclusion, the evidence of the effects of SMSCs in favor of ameliorating ototoxicity-induced hearing loss suggests a potential clinical application.


Assuntos
Antineoplásicos , Perda Auditiva , Células-Tronco Mesenquimais , Administração Intravenosa , Animais , Antineoplásicos/metabolismo , Cisplatino/metabolismo , Cisplatino/toxicidade , Cóclea/patologia , Células Ciliadas Auditivas Externas/patologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/metabolismo , Perda Auditiva/prevenção & controle , Células-Tronco Mesenquimais/metabolismo , Camundongos
11.
Artigo em Inglês | MEDLINE | ID: mdl-34767509

RESUMO

Three cochlear implant (CI) sound coding strategies were combined in the same signal processing path and compared for speech intelligibility with vocoded Mandarin sentences. The three CI coding strategies, biologically-inspired hearing aid algorithm (BioAid), envelope enhancement (EE), and fundamental frequency modulation (F0mod), were combined with the advanced combination encoder (ACE) strategy. Hence, four singular coding strategies and four combinational coding strategies were derived. Mandarin sentences with speech-shape noise were processed using these coding strategies. Speech understanding of vocoded Mandarin sentences was evaluated using short-time objective intelligibility (STOI) and subjective sentence recognition tests with normal-hearing listeners. For signal-to-noise ratios at 5 dB or above, the EE strategy had slightly higher average scores in both STOI and listening tests compared to ACE. The addition of EE to BioAid slightly increased the mean scores for BioAid+EE, which was the combination strategy with the highest scores in both objective and subjective speech intelligibility. The benefits of BioAid, F0mod, and the four combinational coding strategies were not observed in CI simulation. The findings of this study may be useful for the future design of coding strategies and related studies with Mandarin.


Assuntos
Implantes Cocleares , Percepção da Fala , Humanos , Ruído , Razão Sinal-Ruído , Inteligibilidade da Fala
12.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206364

RESUMO

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.


Assuntos
Doenças Cocleares/etiologia , Doenças Cocleares/terapia , Exossomos/metabolismo , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/citologia , Animais , Antineoplásicos/efeitos adversos , Terapia Biológica , Biomarcadores , Cisplatino/efeitos adversos , Doenças Cocleares/patologia , Modelos Animais de Doenças , Exossomos/transplante , Células Ciliadas Auditivas Externas/patologia , Perda Auditiva/etiologia , Perda Auditiva/metabolismo , Perda Auditiva/terapia , Imunofenotipagem , Camundongos , MicroRNAs/genética , Proteômica/métodos , Resultado do Tratamento
13.
J Int Adv Otol ; 17(3): 275-277, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100756

RESUMO

Cochlear implantation is a reliable and safe tool to rehabilitate patients with severe-to-profound sensorineural hearing loss, who get limited benefits from traditional hearing aids. Electrode misplacement is a rare but significant problem that fails to provide benefits and may cause injury to the nearby structures. We present a case that underwent mastoidectomy first to remove cholesteatoma, followed by cochlear implantation with electrode misplacement into the petrous area, with sustained hearing benefits and without any injury to the surrounding structures.


Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva Neurossensorial , Eletrodos Implantados , Audição , Perda Auditiva Neurossensorial/cirurgia , Humanos
14.
Acta Otolaryngol ; 140(6): 497-500, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32186232

RESUMO

Background: Many studies have focused on the suppressive effects of cochlear implants (CIs) on loudness of tinnitus.Aims/objective: This study aimed to examine the effects of CIs and their activation on changes in loudness and tinnitus and explore other factors associated with this effect.Material and methods: We recruited 26 CI recipients according to specific criteria. Participants asked to complete tinnitus questionnaires, while the CI was kept on and at 30 min after the CI was turned off. Tinnitus improvement after CI was tested using Wilcoxon signed rank tests, and correlation was tested using Spearman's rank correlation coefficients and multiple linear regression.Results: After CI, tinnitus reduced from 62% to 46%. Total and partial reduction in tinnitus was seen in 76% subjects with pre-CI tinnitus. However, 6% of the subjects had tinnitus since birth, and none showed worsening tinnitus. The average THI score while the CI on was significantly lower than that CI off.Conclusions: Post-CI tinnitus improvement was seen in 76% of those with pre-CI tinnitus; however, the low risk of new or aggravating tinnitus should be considered, and reasonable expectations for tinnitus reduction should be built into the pre-CI assessment.


Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva/cirurgia , Zumbido/prevenção & controle , Adulto , Feminino , Perda Auditiva/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Zumbido/complicações , Zumbido/diagnóstico , Resultado do Tratamento , Adulto Jovem
15.
Stem Cell Res ; 42: 101692, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31896484

RESUMO

Hearing loss is the most common disorder in the sensory system. Mutations in GJB2 have been reported to be very common in sensorineural hearing loss patients. In this report, we generated an induced pluripotent stem cell (iPSC) line, MMCi001-A, from the peripheral blood mononuclear cells of a 4-year-old male hearing loss patient carrying GJB2 pV37I mutation by using the Sendai virus delivery system. The generated iPSCs were demonstrated to express pluripotent markers and be differentiated into three germ layers in vitro and in vivo. This GJB2-pV37I iPSCs is valuable for studying the pathogenic mechanisms and drug discovery of hearing loss.


Assuntos
Conexinas/metabolismo , Perda Auditiva/genética , Células-Tronco Pluripotentes Induzidas/metabolismo , Animais , Linhagem Celular , Pré-Escolar , Conexina 26 , Humanos , Masculino , Taiwan
16.
Cell Death Dis ; 9(4): 437, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29740017

RESUMO

Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry-positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles. To model the molecular and stereociliary structural changes involved in HC dysfunction in SHL, we further used ATOH1/RFX1/RFX3 to differentiate HC-like cells from the iPSCs from patients with myoclonus epilepsy associated with ragged-red fibres (MERRF) syndrome, which is caused by A8344G mutation of mitochondrial DNA (mtDNA), and characterised by myoclonus epilepsy, ataxia and SHL. Compared with isogenic iPSCs, MERRF-iPSCs possessed ~42-44% mtDNA with A8344G mutation and exhibited significantly elevated reactive oxygen species (ROS) production and CAT gene expression. Furthermore, MERRF-iPSC-differentiated HC-like cells exhibited significantly elevated ROS levels and MnSOD and CAT gene expression. These MERRF-HCs that had more single cilia with a shorter length could be observed only by using a non-TF method, but those with fewer stereociliary bundle-like protrusions than isogenic iPSCs-differentiated-HC-like cells could be further observed using ATOH1/RFX1/RFX3 TFs. We further analysed and compared the whole transcriptome of M1ctrl-HCs and M1-HCs after treatment with ATOH1 or ATOH1/RFX1/RFX3. We revealed that the HC-related gene transcripts in M1ctrl-iPSCs had a significantly higher tendency to be activated by ATOH1/RFX1/RFX3 than M1-iPSCs. The ATOH1/RFX1/RFX3 TF-driven approach for the differentiation of HC-like cells from iPSCs is an efficient and promising strategy for the disease modelling of SHL and can be employed in future therapeutic strategies to treat SHL patients.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular , Células Ciliadas Auditivas Internas/metabolismo , Síndrome MERRF/patologia , Fatores de Transcrição de Fator Regulador X/genética , Fator Regulador X1/genética , Adolescente , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Catalase/genética , Catalase/metabolismo , Cílios/fisiologia , DNA Mitocondrial/genética , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Feminino , Células Ciliadas Auditivas Internas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Síndrome MERRF/complicações , Miosina VIIa/genética , Miosina VIIa/metabolismo , Mutação Puntual , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição de Fator Regulador X/metabolismo , Fator Regulador X1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
17.
Stem Cell Res ; 25: 245-249, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29174977

RESUMO

Sensorineural hearing loss (SNHL) is a prevalent form of deafness commonly arising from damage to the cochlear sensory hair cells and degeneration of the spiral ganglion neurons. In this study, Sendai virus was used to generate an induced pluripotent stem cell (iPSC) line from a 39-year-old female patient diagnosed with severe-to-profound, non-syndromic SNHL. The patient also carries a A1555G mutation in the mitochondrial 12S ribosome RNA gene (MTRNR1). This iPSC line was verified to express pluripotent markers, possess normal karyotype, harbor the specific mutation and demonstrated the capacity to differentiate into three germ layers.


Assuntos
DNA Mitocondrial/genética , Perda Auditiva Neurossensorial/genética , Células-Tronco Pluripotentes Induzidas/citologia , Mutação Puntual , RNA Ribossômico/genética , Adulto , Linhagem Celular , Células Cultivadas , DNA Mitocondrial/metabolismo , Feminino , Perda Auditiva Neurossensorial/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo
18.
Int J Pediatr Otorhinolaryngol ; 95: 57-62, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28576534

RESUMO

OBJECTIVE: To examine whether behavioral pure-tone audiometry (PTA) thresholds in children can be accurately estimated from the corresponding infants' click-evoked auditory brainstem response (ABR) thresholds through a retrospective review of data from a universal newborn hearing screening (UNHS) program in Taiwan. METHOD: According to medical records from Mackay Memorial Hospital, Taipei Hospital District, 45,450 newborns received hearing screening during January 1999-December 2011. Among these newborns, 104 (82, both ears; 22, one ear; total, 186 ears) received regular follow-up and were recruited as subjects. The relationship between infant click-evoked ABR thresholds and the corresponding child PTA thresholds was determined through Pearson correlation coefficient and linear regression analyses. RESULTS: The correlation coefficient between click-evoked ABR thresholds and behavioral PTA thresholds at the average of frequencies of 1-4 and 2-4 kHz was 0.76 and 0.76, respectively. Linear regression analysis showed that behavioral audiometry thresholds at the average of frequencies of 1-4 and 2-4 kHz were accurately estimated from click-evoked ABR thresholds in 57% and 58% children, respectively. CONCLUSION: Click-evoked ABR testing is a reliable tool to cautiously estimate behavioral PTA thresholds at the average of frequencies of 1-4 and 2-4 kHz. For accurately performing hearing aid fitting and auditory rehabilitation in congenitally deaf infants, a combination of frequency-specific tone-burst ABR and click-evoked ABR should be used.


Assuntos
Audiometria de Tons Puros/métodos , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Triagem Neonatal/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise de Regressão , Estudos Retrospectivos , Taiwan
19.
Eur Arch Otorhinolaryngol ; 274(5): 2327-2334, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28229293

RESUMO

Age-related hearing loss (ARHL) is postulated to affect dementia. Our study aims to investigate the relationship between ARHL and the prevalence, and 10-year incidence of dementia in the Taiwan National Health Insurance Research Database (NHIRD). We selected patients diagnosed with ARHL from the NHIRD. A comparison cohort comprising of patients without ARHL was frequency-matched by age, sex, and co-morbidities, and the occurrence of dementia was evaluated in both cohorts. The ARHL cohort consisted of 4108 patients with ARHL and the control cohort consisted of 4013 frequency-matched patients without ARHL. The incidence of dementia [hazard ratio (HR), 1.30; 95% confidence interval (CI 1.14-1.49); P = 0.002] was higher among ARHL patients. Cox models showed that being female (HR, 1.34; 95% CI 1.07-1.68), as well as having co-morbidities, including chronic liver disease and cirrhosis, rheumatoid arthritis, hypertension, diabetes mellitus, stroke, head injury, chronic kidney disease, coronary artery disease, alcohol abuse/dependence, and tobacco abuse/dependence (HR, 1.27; 95% CI 1.11-1.45), were independent risk factors for dementia in ARHL patients. We found ARHL may be one of the early characteristics of dementia, and patients with hearing loss were at a higher risk of subsequent dementia. Clinicians should be more sensitive to dementia symptoms within the first 2 years following ARHL diagnosis. Further clinical studies of the relationship between dementia and ARHL may be necessary.


Assuntos
Demência , Presbiacusia , Idoso , Estudos de Coortes , Comorbidade , Demência/diagnóstico , Demência/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Presbiacusia/diagnóstico , Presbiacusia/epidemiologia , Prevalência , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan/epidemiologia
20.
J Formos Med Assoc ; 116(10): 790-797, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28012675

RESUMO

BACKGROUND/PURPOSE: To evaluate the complexity of vestibular-ocular reflex (VOR) in patients with acute unilateral vestibular loss (AUVL) via entropy analysis of head impulses. METHODS: Horizontal head impulse test (HIT) with high-velocity alternating directions was used to evaluate 12 participants with AUVL and 16 healthy volunteers. Wireless electro-oculography and electronic gyrometry were used to acquire eye positional signals and head velocity signals. The eye velocity signals were then obtained through differentiation, band-pass filtering. The approximate entropy of eye velocity to head velocity (RApEn) was used to evaluate chaos property. VOR gain, gain asymmetry ratio, and RApEn asymmetry ratio were also used to compare the groups. RESULTS: For the lesion-side HIT of the patient group, the mean VOR gain was significantly lower and the mean RApEn was significantly greater compared with both nonlesion-side HIT and healthy controls (p < 0.01, one-way analysis of variance). Both the RApEn asymmetry ratio and gain asymmetry ratio of the AUVL group were significantly greater compared with those of the control group (p < 0.05, independent sample t test). CONCLUSION: Entropy and gain analysis of HIT using wireless electro-oculography system could be used to detect the VOR dysfunctions of AUVL and may become effective methods for evaluating vestibular disorders.


Assuntos
Cabeça , Reflexo Vestíbulo-Ocular/fisiologia , Movimentos Sacádicos/fisiologia , Vestíbulo do Labirinto/fisiopatologia , Adulto , Estudos de Casos e Controles , Entropia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Curva ROC , Vertigem/etiologia
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