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Cave-adapted animals evolve a suite of regressive and constructive traits that allow survival in the dark. Most studies aiming at understanding cave animal evolution have focused on the genetics and environmental underpinnings of regressive traits, with special emphasis on vision loss. Possibly as a result of vision loss, other non-visual sensory systems have expanded and compensated in cave species. For instance, in many cave-dwelling fish species, including the blind cavefish of the Mexican tetra, Astyanax mexicanus, a major non-visual mechanosensory system called the lateral line, compensated for vision loss through morphological expansions. While substantial work has shed light on constructive adaptation of this system, there are still many open questions regarding its developmental origin, synaptic plasticity, and overall adaptive value. This review provides a snapshot of the current state of knowledge of lateral line adaption in A. mexicanus, with an emphasis on anatomy, synaptic plasticity, and behavior. Multiple open avenues for future research in this system, and how these can be leveraged as tools for both evolutionary biology and evolutionary medicine, are discussed.

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OBJECTIVE: To investigate the effect of peroxynitrite on the cultured cochlear hair cells of C57BL/6 P3 mice in vitro as well as the role of Wnt3a, as an activator of the canonical Wnt signaling pathway, underlying the action of such an oxidative stress. METHODS: The in vitro primary cultured cochlear hair cells were subjected to l00 µM peroxynitrite and l00 µM peroxynitrite +25 ng/mL Wnt3a for 24 h, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy. RESULTS: The number of surviving hair cells was significantly reduced in the 100 µM peroxynitrite group, while it was significantly higher in the Wnt3a + peroxynitrite treated group compared with the peroxynitrite treated group. The transmission electron microscopy showed that exposure to peroxynitrite induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, while Wnt3a clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. CONCLUSION: These results indicated that peroxynitrite could cause oxidative damage to the cochlear hair cells, and low concentrations of Wnt3a has a protective effect against oxidative damage. LEVEL OF EVIDENCE: Level 2.

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Abstract Objective To investigate the effect of peroxynitrite on the cultured cochlear hair cells of C57BL/6 P3 mice in vitro as well as the role of Wnt3a, as an activator of the canonical Wnt signaling pathway, underlying the action of such an oxidative stress. Methods The in vitro primary cultured cochlear hair cells were subjected to l00 μM peroxynitrite and l00 μM peroxynitrite +25 ng/mL Wnt3a for 24 h, the cell survival and morphological changes were examined by immunofluorescence and transmission electron microscopy. Results The number of surviving hair cells was significantly reduced in the 100 μM peroxynitrite group, while it was significantly higher in the Wnt3a + peroxynitrite treated group compared with the peroxynitrite treated group. The transmission electron microscopy showed that exposure to peroxynitrite induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, while Wnt3a clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. Conclusion These results indicated that peroxynitrite could cause oxidative damage to the cochlear hair cells, and low concentrations of Wnt3a has a protective effect against oxidative damage. Level of evidence: Level 2.

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Abstract Objective: The present study aimed to perform a morphological and morphometric analysis of cochlear structures of C57BL/6J mice receiving oral melatonin for a 12-month period. Methods: 32 male C57BL/6J were divided into control and melatonin groups. Control received saline and ethanol solution and melatonin group, 50 μL of 10 mg of melatonin/kg/day orally for a 12-month period. After de experiment the animals were sacrificed into a 40% concentration of CO2 chamber, and the blades were morphological and morphometrically analyzed. Results: The melatonin group revealed a higher median density of viable cells (45 ± 10.28 cells/100 μm2, 31-73, vs. 32 ± 7.47 cells/100 μm2, 25-48). The median area of stria vascularis was 55.0 ± 12.27 cells/100 μm2 (38-80) in the control, and 59.0 ± 16.13 cells/100 μm2 (40-134) in the melatonin group. The morphometric analysis of the spiral ligament reveals a higher median of total viable neurons in the melatonin (41 ± 7.47 cells/100 μm2, 27-60) than in the control group (31 ± 5.68 cells/100 μm2, 21-44). Conclusion: Although melatonin is a potent antioxidant, it does not completely neutralize the occurrence of presbycusis; however, it may delay the onset of this condition. Level of evidence: 3.

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Objective: To determine the circadian influence on sound sensitivity produced by temporal hearing deprivation in healthy normal human subjects. Design: Participants underwent bilateral earplugging before completion of anthropometry, the author's developed questionnaire, the Hamilton Anxiety and Depression Inventory, pure tone audiometry (PTA), stapedial reflex thresholds (SRT), distortion products otoacoustic emissions input/output (DPOAE-I/O), and uncomfortable loudness levels (ULLs). Afterward, the participants were randomly divided into group A, starting at 8:00 a.m. and finishing at 8:00 p.m., and group B, starting at 4:00 p.m. and ending at 4:00 a.m. Serum cortisol levels and audiological test results were obtained at the beginning and end of the session and 24-h free urinary cortisol levels were measured. Study sample: Thirty healthy volunteers. Results: PTA was 2.68 and 3.33 dB HL in groups A and B, respectively, with no statistical difference between them. ULLs were significantly lower in group A compared to group B, with an average of 8.1 dB SPL in group A and 3.3 dB SPL in group B (p < 0.0001). A SRT shift was observed in group A, with no difference in group B, and a night shift in DPOAE-I/O in group B. Conclusions: Reduced loudness tolerance is demonstrated during daytime hearing deprivation in contrast to nighttime; this may be due to increased central gain in the awake cortex.

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OBJECTIVE: The present study aimed to perform a morphological and morphometric analysis of cochlear structures of C57BL/6J mice receiving oral melatonin for a 12-month period. METHODS: 32 male C57BL/6J were divided into control and melatonin groups. Control received saline and ethanol solution and melatonin group, 50 µL of 10 mg of melatonin/kg/day orally for a 12-month period. After de experiment the animals were sacrificed into a 40% concentration of CO2 chamber, and the blades were morphological and morphometrically analyzed. RESULTS: The melatonin group revealed a higher median density of viable cells (45 ±â€¯10.28 cells/100 µm2, 31-73, vs. 32 ±â€¯7.47 cells/100 µm2, 25-48). The median area of stria vascularis was 55.0 ±â€¯12.27 cells/100 µm2 (38-80) in the control, and 59.0 ±â€¯16.13 cells/100 µm2 (40-134) in the melatonin group. The morphometric analysis of the spiral ligament reveals a higher median of total viable neurons in the melatonin (41 ±â€¯7.47 cells/100 µm2, 27-60) than in the control group (31 ±â€¯5.68 cells/100 µm2, 21-44). CONCLUSION: Although melatonin is a potent antioxidant, it does not completely neutralize the occurrence of presbycusis; however, it may delay the onset of this condition.

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Background: In several non-mammalian species, auditory receptors undergo cell renewal after damage. This has raised hope of finding new options to treat human sensorineural deafness. Uncertainty remains as to the triggering mechanisms and whether hair cells are regenerated even under normal conditions. In the present investigation, we explored the auditory organ in the crocodile to validate possible ongoing natural hair cell regeneration. Materials and Methods: Two male Cuban crocodiles (Crocodylus rhombifer) and an adult male African Dwarf crocodile (Osteolaemus tetraspis) were analyzed using transmission electron microscopy and immunohistochemistry using confocal microscopy. The crocodile ears were fixed in formaldehyde and glutaraldehyde and underwent micro-computed tomography (micro-CT) and 3D reconstruction. The temporal bones were drilled out and decalcified. Results: The crocodile papilla basilaris contained tall (inner) and short (outer) hair cells surrounded by a mosaic of tightly connected supporting cells coupled with gap junctions. Afferent neurons with and without ribbon synapses innervated both hair cell types. Supporting cells occasionally showed signs of trans-differentiation into hair cells. They expressed the MAFA and SOX2 transcription factors. Supporting cells contained organelles that may transfer genetic information between cells, including the efferent nerve fibers during the regeneration process. The tectorial membrane showed signs of being replenished and its architecture being sculpted by extracellular exosome-like proteolysis. Discussion: Crocodilians seem to produce new hair cells during their life span from a range of supporting cells. Imposing efferent nerve fibers may play a role in regeneration and re-innervation of the auditory receptors, possibly triggered by apoptotic signals from wasted hair cells. Intercellular signaling may be accomplished by elaborate gap junction and organelle systems, including neural emperipolesis. Crocodilians seem to restore and sculpt their tectorial membranes throughout their lives.

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Abstract Introduction Distortion product otoacoustic emissions (DPOAE) and their suppression may be considered useful in monitoring cochlear function and the efferent auditory pathway inhibitory effect. Nonetheless, the establishment of reliable parameters of response variations is of great importance. Objectives To verify the replicability of test and retest in the research of the inhibitory effect of the efferent pathway using contralateral suppressing stimulus during DPOAE recording for clinical applicability. Methods Cross-sectional study with 48 volunteers, aged 18 to 30 years, with normal audiometric thresholds. The procedures included were audiometric and immittance measures to overrule any conductive or sensorineural conditions and DPOAE recordings without and with contralateral suppression with a 60 dBHL white noise. Distortion product otoacoustic emissions amplitudes were analyzed and compared in both conditions with Wilcoxon test, and the Spearman correlation test was used to assess test-retest reliability. Results The comparative analysis showed differences between amplitudes in test and retest conditions only in 1,500 Hz for DPOAE measures with all other tested frequencies showing no differences, and no difference was observed in all recorded frequencies in the test and retest comparison for DPOAE suppression. The degree of correlation between test and retest of DPOAE amplitude was good at 6,000 Hz and strong (r > 0.880) at the other frequencies. For DPOAE with suppression, all frequencies presented strong correlation between test and retest: 1,500 Hz (r = 0.880), 2,000 Hz (r = 0.882), 3,000 Hz (r = 0.940), and 6,000 Hz (r = 0.957). Conclusions The study found good replicability in contralateral suppression of DPOAE with potential clinical applicability, and we recommend conducting the test from 2000Hz to higher frequencies for more reliable results.

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Introduction Distortion product otoacoustic emissions (DPOAE) and their suppression may be considered useful in monitoring cochlear function and the efferent auditory pathway inhibitory effect. Nonetheless, the establishment of reliable parameters of response variations is of great importance. Objectives To verify the replicability of test and retest in the research of the inhibitory effect of the efferent pathway using contralateral suppressing stimulus during DPOAE recording for clinical applicability. Methods Cross-sectional study with 48 volunteers, aged 18 to 30 years, with normal audiometric thresholds. The procedures included were audiometric and immittance measures to overrule any conductive or sensorineural conditions and DPOAE recordings without and with contralateral suppression with a 60 dBHL white noise. Distortion product otoacoustic emissions amplitudes were analyzed and compared in both conditions with Wilcoxon test, and the Spearman correlation test was used to assess test-retest reliability. Results The comparative analysis showed differences between amplitudes in test and retest conditions only in 1,500 Hz for DPOAE measures with all other tested frequencies showing no differences, and no difference was observed in all recorded frequencies in the test and retest comparison for DPOAE suppression. The degree of correlation between test and retest of DPOAE amplitude was good at 6,000 Hz and strong (r > 0.880) at the other frequencies. For DPOAE with suppression, all frequencies presented strong correlation between test and retest: 1,500 Hz (r = 0.880), 2,000 Hz (r = 0.882), 3,000 Hz (r = 0.940), and 6,000 Hz (r = 0.957). Conclusions The study found good replicability in contralateral suppression of DPOAE with potential clinical applicability, and we recommend conducting the test from 2000Hz to higher frequencies for more reliable results.

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Abstract Introduction Tinnitus is the perception of sound in the absence of external sound stimulation. There is a general agreement that it is a direct consequence of irreversible and permanent cochlear damage. Objectives The present work is designed to study the distortion product otoacoustic emissions (DPOAEs) in tinnitus patients with normal hearing in comparison with normal hearing control and to study any possible correlation between DPOAEs recording and patients' complaints. Methods The present study included 80 subjects divided into 2 groups: Control group: consisted of 30 normal-hearing adults not complaining of tinnitus and Study group: consisted of 50 normal-hearing adults complaining of tinnitus. The methodology includes full audiological history, otoscopic examination, basic audiological evaluation, DPOAEs including both DP-gram and DPOAEs input/output functions. Results Basic audiological evaluation showed within normal hearing sensitivity in both groups, however, with significant higher hearing thresholds in tinnitus patients at all frequency ranges. The Tinnitus Handicap Inventory Questionnaire showed mean scores of 35.2 ± 16.9 in the study group. The DP-gram showed higher amplitudes in the control group when compared with tinnitus patients. The DPOAEs input-output functions at different frequencies (1, 2, 4 and 6kHz) also showed higher amplitudes at all frequencies and different input levels. The slope of the I/O function tends to be steeper in tinnitus cases. Conclusion Patients with tinnitus might have neural dysfunction at either the level of the cochlea, as shown in reduced DPOAE levels, and changes in the normal DP-I/O function recorded in the present work.

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Introduction Tinnitus is the perception of sound in the absence of external sound stimulation. There is a general agreement that it is a direct consequence of irreversible and permanent cochlear damage. Objectives The present work is designed to study the distortion product otoacoustic emissions (DPOAEs) in tinnitus patients with normal hearing in comparison with normal hearing control and to study any possible correlation between DPOAEs recording and patients' complaints. Methods The present study included 80 subjects divided into 2 groups: Control group: consisted of 30 normal-hearing adults not complaining of tinnitus and Study group: consisted of 50 normal-hearing adults complaining of tinnitus. The methodology includes full audiological history, otoscopic examination, basic audiological evaluation, DPOAEs including both DP-gram and DPOAEs input/output functions. Results Basic audiological evaluation showed within normal hearing sensitivity in both groups, however, with significant higher hearing thresholds in tinnitus patients at all frequency ranges. The Tinnitus Handicap Inventory Questionnaire showed mean scores of 35.2 ± 16.9 in the study group. The DP-gram showed higher amplitudes in the control group when compared with tinnitus patients. The DPOAEs input-output functions at different frequencies (1, 2, 4 and 6kHz) also showed higher amplitudes at all frequencies and different input levels. The slope of the I/O function tends to be steeper in tinnitus cases. Conclusion Patients with tinnitus might have neural dysfunction at either the level of the cochlea, as shown in reduced DPOAE levels, and changes in the normal DP-I/O function recorded in the present work.

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RESUMO Objetivo avaliar o efeito da variação da intensidade de estimulação sobre as respostas das emissões otoacústicas produto de distorção em indivíduos com perda auditiva neurossensorial, utilizando um protocolo de gradiente de fase das emissões. Métodos estudo observacional transversal. Participaram 38 indivíduos com diagnóstico de perda auditiva neurossensorial de grau leve, moderado ou severo. Foram realizadas anamnese, meatoscopia, audiometria tonal liminar, logoaudiometria, imitanciometria, emissões otoacústicas produto de distorção e emissões otoacústicas residuais. As emissões otoacústicas residuais foram coletadas com o equipamento Echodia, modelo Elios®. O protocolo utilizado permite a variação dos parâmetros frequência e intensidade e as respostas são analisadas por meio do teste do Gradiente de Fase. As respostas registradas nas emissões residuais foram consideradas como "presente", "ausente" e "artefato", considerando a variação da fase em função de f1. Resultados Foram incluídas 72 orelhas. Houve diferença estatisticamente significativa nas frequências de 1300 Hz e 2000 Hz, ao comparar os resultados das emissões residuais. Ao correlacionar o resultado da audiometria e a intensidade de estimulação que evocou a emissão residual, houve correlação positiva para as frequências de 1000 Hz e 4000Hz. O "artefato" foi registrado, principalmente, nas frequências mais agudas: 56,2% em 3000 Hz e 58,2% em 4000 Hz. A emissão otoacústica residual presente foi registrada em 18,6% em 1000 Hz, 13,4% em 2000 Hz, 6,3% em 3000 Hz e 7,5% em 4000 Hz. Conclusão o aumento da intensidade de estimulação no exame de emissões pode auxiliar no estudo das células ciliadas residuais, desde que seja utilizado um protocolo capaz de diferenciar respostas fisiológicas de artefatos.

ABSTRACT Purpose To study the effect of stimulation intensity variation on the responses of distortion products in subjects with sensorineural hearing loss using a new protocol to register the otoacoustic emissions. Methods This is a cross-sectional observational study. The following procedures were performed: anamnesis, otoscopy, pure tone audiometry, speech audiometry, tympanometry, distortion product and residual otoacoustic emissions. The residual DPOAE were collected with the Echodia equipment, Elios®. The protocol that was developed allows the variation of frequency and intensity parameters and the responses are analyzed by phase gradient test. Responses recorded in residual otoacoustic emissions were considered "present", "absent" or "artifact". Results The total included ears was 72. On residual otoacoustic emissions test, at a frequency of 1300Hz and 2000Hz, there was statistically significant difference. By analyzing the average found in the audiometry and the results of residual emissions, only the frequency of 1300Hz showed a statistically significant association in all groups. By correlating the results of the audiometry and the stimulation intensity used to evoke the residual emission, there was positive correlation for the frequencies of 1000Hz and 4000Hz. The "artifact" was mostly recorded in the higher frequencies: 56.2% in 3000Hz and 58.2% in 4000 Hz. Residual EOAPD present was recorded as 18.6% at 1000Hz, 13.4% at 2000Hz, 6.3% at 3000Hz and 7.5% at 4000Hz. Conclusion The increased stimulation intensity in the otoacoustic emissions test can aid in the study of residual outer hair cells, as long as a protocol is used to check the correctness of the responses.

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Noise-induced hearing loss has gained relevance as one of the most common forms of hearing impairment. The anatomical correlates of hearing loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about the physiological aspects of damaged, surviving cells. Here we addressed the functional consequences of noise exposure on the capacity of inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice of either sex at postnatal day (P) 15-16 were exposed to 1-12 kHz noise at 120 dB sound pressure level (SPL), for 1 h. Exocytosis was measured by tracking changes in membrane capacitance (ΔCm) from IHCs of the apical cochlea. Upon IHC depolarization to different membrane potentials, ΔC m showed the typical bell-shaped curve that mirrors the voltage dependence of Ca2+ influx, in both exposed and unexposed cells. Surprisingly, from IHCs at 1-day after exposure (d.a.e.), we found potentiation of exocytosis at the peak of the bell-shaped curve. The increase in exocytosis was not accompanied by changes in whole-cell Ca2+ influx, suggesting a modification in coupling between Ca2+ channels and synaptic vesicles. Consistent with this notion, noise exposure also changed the Ca2+-dependence of exocytosis from linear to supralinear. Noise exposure did not cause loss of IHCs, but did result in a small reduction in the number of IHC-SGN synapses at 1-d.a.e. which recovered by 14-d.a.e. In contrast, a strong reduction in auditory brainstem response wave-I amplitude (representing synchronous firing of SGNs) and distortion product otoacoustic emissions (reflecting outer hair cell function) indicated a profound hearing loss at 1- and 14-d.a.e. To determine the role of glutamate release in the noise-induced potentiation of exocytosis, we evaluated vesicular glutamate transporter-3 (Vglut3) knock-out (KO) mice. Unlike WT, IHCs from Vglut3 KO mice showed a noise-induced reduction in ΔC m and Ca2+ influx with no change in the Ca2+-dependence of exocytosis. Together, these results indicate that traumatic noise exposure triggers changes of IHC synaptic function including a Vglut3-dependent potentiation of exocytosis.

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The role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong cnr2 expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Cav1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.

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INTRODUCTION: The toxic substances present in cigarette smoke can damage cochlea hair cells. This effect has been investigated by measuring otoacoustic emissions. OBJECTIVE: To investigate the impact of stimuli on otoacoustic emissions, comparing neonates with and without exposure to cigarette smoke during pregnancy. METHODS: Transient-evoked otoacoustic emissions, evoked by a click stimulus, and distortion product otoacoustic emissions, evoked by two tones tests were conducted in both ears, using an Interacoustic TITAN device. The study included 105 neonates divided into two groups: a study group, comprising 47 neonates exposed to smoke during pregnancy; and a control group comprized of 58 neonates who were not exposed. All participants had normal neonatal hearing screening. RESULTS: No statistical differences in distortion product otoacoustic emissions response levels were found between the groups. In the transient-evoked otoacoustic emissions tests lower response levels were observed in the study group than the control group in frequency band analysis of the right ear, with statistically significant differences in signals and signal-noise ratio (except at 1kHz). CONCLUSION: The impact of smoking exposure could be analyzed through transient-evoked otoacoustic emissions in neonates. The group effect of smoke exposure during pregnancy was evidenced by a reduction in transient-evoked otoacoustic emissions levels. This same effect was not observed for the analyses performed on distortion product otoacoustic emissions levels.

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NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.

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RESUMO Objetivo Avaliar a função coclear de trabalhadores marítimos Offshore e Onshore de uma empresa naval da cidade do Rio de Janeiro e estimar a magnitude de associação entre a exposição ocupacional ao ruído e/ou substâncias químicas e alterações na função coclear. Método Neste estudo, foram avaliados trabalhadores marítimos entre 20-49 anos, de ambos os gêneros, sem queixas auditivas, distribuídos em dois grupos: o Grupo Offshore, que operam em alto mar com exposição ocupacional; e o Grupo Onshore, que operam em escritórios sem exposição ocupacional. Para avaliação da função coclear, foram realizados os exames de emissões otoacústicas evocadas por estímulo transiente (EOAT) e por produto de distorção (EOAPD). Resultados As respostas das EOAT e EOAPD foram, em média, menores no Grupo Offshore, para todas as frequências analisadas. A proporção de falhas observadas também foi maior no grupo de exposição (Offshore), tanto no critério geral quanto por frequência específica, principalmente para as frequências mais agudas de cada teste, 4 kHz para EOAT e 6 kHz para EOAPD. Conclusão Os resultados sugerem que a exposição a ruído e/ou a substâncias químicas pode contribuir significativamente para alterações da função coclear de trabalhadores marítimos, mesmo antes de manifestarem queixas auditivas.

ABSTRACT Purpose To evaluate the cochlear function of offshore and onshore seafaring workers of a naval company in the city of Rio de Janeiro and to estimate the degree of association between occupational exposure to noise and/or chemical substances and alteration in cochlear function. Methods This study evaluated seafaring workers aged 20 to 49, of both genders, without auditory symptoms, divided into two groups: the Offshore Group, operating in the high seas with occupational exposure; and the Onshore Group, operating in offices without occupational exposure. Exams were performed to evaluate cochlear function, including transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE). Results The TEOAE and DPOAE responses were on average lower in the Offshore Group, for all frequencies analyzed. The proportion of failures observed was also higher in the exposure group (Offshore), for general response and specific frequency, mainly for the frequencies of 4 kHz for TEOAE and 6 kHz for DPOAE. Conclusion The results suggest that exposure to noise and/or chemical substances can contribute to alterations in cochlear function in seafarers even without manifesting auditory symptoms.

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The expansion and pruning of ion channel families has played a crucial role in the evolution of nervous systems. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels with distinct roles in synaptic transmission at the neuromuscular junction, the central and peripheral nervous system, and the inner ear. Remarkably, the complement of nAChR subunits has been highly conserved along vertebrate phylogeny. To ask whether the different subtypes of receptors underwent different evolutionary trajectories, we performed a comprehensive analysis of vertebrate nAChRs coding sequences, mouse single-cell expression patterns, and comparative functional properties of receptors from three representative tetrapod species. We found significant differences between hair cell and neuronal receptors that were most likely shaped by the differences in coexpression patterns and coassembly rules of component subunits. Thus, neuronal nAChRs showed high degree of coding sequence conservation, coupled to greater coexpression variance and conservation of functional properties across tetrapod clades. In contrast, hair cell α9α10 nAChRs exhibited greater sequence divergence, narrow coexpression pattern, and great variability of functional properties across species. These results point to differential substrates for random change within the family of gene paralogs that relate to the segregated roles of nAChRs in synaptic transmission.

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ABSTRACT Purpose: to verify the functioning of the outer hair cells and the medial efferent olivocochlear system, and the integrity of the auditory pathways in the brainstem up to the auditory cortex, in aphasic individuals. Methods: the sample comprised 20 individuals - 10 without aphasia and 10 with it, aged from 21 to 58 years. The procedures used were the research of the otoacoustic emissions by a transient stimulus with and without noise, and the cognitive potential (tone-burst and speech stimuli). The findings were analyzed based on descriptive statistics. Results: the suppression effect was more present in individuals without aphasia when compared with the aphasic ones. In the cognitive potential, the mean latency values of P3 was within normality standards, with a higher latency in the individuals presented with aphasia for the tone-burst stimulus in both ears. A statistically significant difference of the P3-N2 amplitude was observed for the tone-burst stimulus, comparing the ears in both groups, and for speech stimulus only to the left ear in both groups. Conclusions: aphasic individuals did not present significant differences regarding suppression of the otoacoustic emissions. As for the cognitive potential, the aphasic individuals presented higher latency values when compared to those with no aphasia.

RESUMO Objetivos: verificar o funcionamento das células ciliadas externas e do sistema olivococlear eferente medial e a integridade das vias auditivas no tronco encefálico até o córtex auditivo, em indivíduos afásicos. Métodos: a amostra foi composta por 20 indivíduos, sendo 10 indivíduos sem afasia e 10 indivíduos afásicos, com idades entre 21 e 58 anos. Os procedimentos utilizados foram: pesquisa das emissões otoacústicas por estímulo transiente sem e com ruído, e potencial cognitivo (estímulo toneburst e de fala). Os achados foram analisados a partir da estatística descritiva. Resultados: o efeito de supressão esteve mais presente nos indivíduos sem afasia quando comparado com os afásicos. No potencial cognitivo, o valor médio das latências P3, mostrou-se dentro dos padrões da normalidade com maior latência nos indivíduos com afasia para o estímulo toneburst em ambas as orelhas. Observou-se diferença estatisticamente significante da amplitude P3-N2 para o estímulo toneburst, comparando as orelhas em ambos os grupos, e para o estímulo de fala apenas à orelha esquerda em ambos os grupos. Conclusões: indivíduos afásicos não apresentaram diferenças significantes quanto à supressão das emissões otoacústicas. Quanto ao potencial cognitivo, os indivíduos afásicos apresentaram maior valor de latência em relação aos indivíduos sem afasia.

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Abstract Introduction: Mammalian hair cells and auditory neurons do not show regenerative capacity. Hence, damage to these cell types is permanent and leads to hearing loss. However, there is no treatment that re-establishes auditory function. Regenerative therapies using stem cells represent a promising alternative. Objective: This article aims to review the current literature about the main types of stem cells with potential for application in cell therapy for sensorineural hearing loss, the most relevant experiments already performed in animals, as well as the advances that have been recently made in the field. Methods: Research included the databases PubMed/MEDLINE, Web of Science, Science Direct and SciELO, as well as gray literature. Search strategy included the following main terms: "stem cells", "hair cells" and "auditory neurons". Additionally, the main terms were combined with the following secondary terms: "mesenchymal", "iPS", "inner ear", "auditory". The research was conducted independently by three researchers. Results: Differentiation of stem cells into hair cells and auditory neurons has a high success rate, reaching up to 82% for the first and 100% for the latter. Remarkably, these differentiated cells are able to interact with hair cells and auditory neurons of cochlear explants through formation of new synapses. When transplanted into the cochlea of animals with hearing loss, auditory restoration has been documented to date only in deafferented animals. Conclusion: Advances have been more prominent in cases of auditory neuropathy, since partial improvement of auditory nerve conditions through cell-based therapy may increase the number of patients who can successfully receive cochlear implants.

Resumo Introdução: Nos mamíferos, as células ciliadas e os neurônios auditivos não apresentam capacidade regenerativa. Assim, os danos a esses tipos celulares são permanentes e levam à perda auditiva. Contudo, como não há tratamento que restabeleça a função auditiva, as terapias regenerativas utilizando células-tronco representam uma alternativa promissora. Objetivo: Este artigo tem como objetivo revisar a literatura atual sobre os principais tipos de células-tronco com potencial para aplicação em terapia celular para perda auditiva sensorioneural, os experimentos mais relevantes já realizados em animais, bem como os avanços obtidos recentemente nessa área. Método: As pesquisas incluíram as bases de dados PubMed/MEDLINE, Web of Science, Science Direct e SciELO, além da literatura cinza. A estratégia de busca incluiu os seguintes termos principais: "stem cells", "hair cells" e "auditory neurons". Além disso, os termos principais foram combinados com os seguintes termos secundários: "mesenchymal", "iPS", "inner ear" e "auditory". A pesquisa foi realizada de forma independente por três pesquisadores. Resultados: A diferenciação de células-tronco em células ciliadas e neurônios auditivos têm alta taxa de sucesso, chegando a 82% para o primeiro caso e 100% para o segundo. Notavelmente, essas células diferenciadas são capazes de interagir com células ciliadas e neurônios auditivos de explantes cocleares através da formação de novas sinapses. Quando transplantadas para a cóclea de animais com perda auditiva, a restauração da função auditiva foi observada, até o momento, apenas em animais com ablação do VIII nervo craniano. Conclusão: Os avanços têm sido mais proeminentes em casos de neuropatia auditiva. A melhora parcial das condições do nervo auditivo por meio de terapia baseada em células-tronco pode aumentar o número de pacientes candidatos a receber implantes cocleares com sucesso.

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