CoCl2 -simulated hypoxia potentiates the osteogenic differentiation of fibroblasts derived from tympanosclerosis by upregulating the expression of BMP-2.

Tympanosclerosis (TS) is a result of long-standing middle ear inflammation characterized by fibroblasts ossification. Fibrosis is the last revertible stage in the progress of middle ear inflammation to TS. It was hypothesized that chronic hypoxia could be modulating fibrosis, which in turn additionally further aggravated hypoxia via decreasing oxygen diffusion. However, the effects of hypoxia on osteoinductive activity of fibroblasts have not been explored. Herein, we purposed to explore the role of hypoxia in osteogenic differentiation of fibroblasts derived from TS. The expression of bone morphogenetic protein-2 (BMP-2), hypoxia-inducible factor-1α (HIF-1α), and Vimentin in the human surgical specimens of tympansclerosis was investigated by immunofluorescent staining. Furthermore, cultured fibroblasts were stratified into the following study groups: control, 25, 50, and 100 µM cobaltous chloride (CoCl2 ) group. BMP-2, as well as HIF-1α levels of expression were detected via western blotting and immunofluorescence analysis. We found that the expression of BMP-2 and HIF-1α was significantly upregulated in TS tissues and these fibroblasts, which was vimentin positive surrounding sclerotic plaques, were also expressing HIF-1α positive. The results also demonstrated that CoCl2 treatment increased nuclear HIF-1α protein level in the fibroblast. Furthermore, treatment with CoCl2 significantly increased BMP-2 expression and remarkably elevated alkaline phosphatse activity and the mineralized nodules area. These data illustrate that hypoxia may play an osteogenic role in TS fibroblasts via the elevated expression of a possible osteogenic factor, BMP-2.

Segregation of competing speech in adults and children with normal hearing and in children with cochlear implants.

Children with normal hearing (CNH) have greater difficulty segregating competing speech than do adults with normal hearing (ANH). Children with cochlear implants (CCI) have greater difficulty segregating competing speech than do CNH. In the present study, speech reception thresholds (SRTs) in competing speech were measured in Chinese Mandarin-speaking ANH, CNH, and CCIs. Target sentences were produced by a male Mandarin-speaking talker. Maskers were time-forward or -reversed sentences produced by a native Mandarin-speaking male (different from the target) or female or a non-native English-speaking male. The SRTs were lowest (best) for the ANH group, followed by the CNH and CCI groups. The masking release (MR) was comparable between the ANH and CNH group, but much poorer in the CCI group. The temporal properties differed between the native and non-native maskers and between forward and reversed speech. The temporal properties of the maskers were significantly associated with the SRTs for the CCI and CNH groups but not for the ANH group. Whereas the temporal properties of the maskers were significantly associated with the MR for all three groups, the association was stronger for the CCI and CNH groups than for the ANH group.

Sound localization, speech and tone recognition for stimuli presented from the rear in bilateral cochlear implant users.

OBJECTIVE: To assess any differences in spatial listening ability of cochlear implant recipients when using both or only one of two bilateral cochlear implants (BCIs) for stimuli originating from behind the subject. DESIGN: Twelve loudspeakers were placed in the rear horizontal plane of the subjects to test the sound localisation performance of BCI users and normal-hearing listeners (NHLs) with or without interfering noise. Stimuli were presented via two rear loudspeakers simultaneously during the speech recognition test. In the tone recognition test, another anechoic chamber was used with stimuli presenting from a loudspeaker behind the participants. STUDY SAMPLE: Twenty-seven NHLs and eleven BCI users. RESULTS: Average root-mean-square (RMS) error for the bilateral condition was significantly lower than that for the right and left cochlear implant (CI) conditions with or without interfering noises (p < 0.05). Average speech or tone recognition scores for the bilateral condition and the right and left CI conditions were not statistically significant (p > 0.05). CONCLUSION: Sound localisation with BCIs was significantly more accurate than with either implant alone. Speech and tone recognition scores were not better with two compared to those of one activated implant. Given the small number of subjects, the results should be considered as preliminary.

Tinnitus impairs segregation of competing speech in normal-hearing listeners.

Many tinnitus patients report difficulties understanding speech in noise or competing talkers, despite having "normal" hearing in terms of audiometric thresholds. The interference caused by tinnitus is more likely central in origin. Release from informational masking (more central in origin) produced by competing speech may further illuminate central interference due to tinnitus. In the present study, masked speech understanding was measured in normal hearing listeners with or without tinnitus. Speech recognition thresholds were measured for target speech in the presence of multi-talker babble or competing speech. For competing speech, speech recognition thresholds were measured for different cue conditions (i.e., with and without target-masker sex differences and/or with and without spatial cues). The present data suggest that tinnitus negatively affected masked speech recognition even in individuals with no measurable hearing loss. Tinnitus severity appeared to especially limit listeners' ability to segregate competing speech using talker sex differences. The data suggest that increased informational masking via lexical interference may tax tinnitus patients' central auditory processing resources.

Ligand-Activated Peroxisome Proliferator-Activated Receptor ß/δ Facilitates Cell Proliferation in Human Cholesteatoma Keratinocytes.

Cholesteatoma is characterized by both the overgrowth of hyperkeratinized squamous epithelium and bone erosion. However, the exact mechanism underlying the hyperproliferative ability of cholesteatoma remains unknown. In this study, we investigated PPAR ß/δ expression in human surgical specimens of cholesteatoma and analyzed its functional role as a regulator of epithelial keratinocyte hyperproliferation. We found that the expression of PPAR ß/δ was significantly upregulated in cholesteatoma and ligand-activated PPAR ß/δ markedly promoted the proliferation of cholesteatoma keratinocytes. Furthermore, we showed that PPAR ß/δ activation increased PDK1 expression and decreased PTEN generation, which led to increased phosphorylation of AKT and GSK3ß and increased the expression level of Cyclin D1. Overall, our data suggested that the proliferating effect of PPAR ß/δ on the cholesteatoma keratinocytes was mediated by the positive regulation of the PDK1/PTEN/AKT/GSK3ß/Cyclin D1 pathway. These findings warranted further investigation of PPAR ß/δ as a therapeutic target for recurrent or residual cholesteatoma.

Factors Affecting Bimodal Benefit in Pediatric Mandarin-Speaking Chinese Cochlear Implant Users.

OBJECTIVES: While fundamental frequency (F0) cues are important to both lexical tone perception and multitalker segregation, F0 cues are poorly perceived by cochlear implant (CI) users. Adding low-frequency acoustic hearing via a hearing aid in the contralateral ear may improve CI users' F0 perception. For English-speaking CI users, contralateral acoustic hearing has been shown to improve perception of target speech in noise and in competing talkers. For tonal languages such as Mandarin Chinese, F0 information is lexically meaningful. Given competing F0 information from multiple talkers and lexical tones, contralateral acoustic hearing may be especially beneficial for Mandarin-speaking CI users' perception of competing speech. DESIGN: Bimodal benefit (CI+hearing aid - CI-only) was evaluated in 11 pediatric Mandarin-speaking Chinese CI users. In experiment 1, speech recognition thresholds (SRTs) were adaptively measured using a modified coordinated response measure test; subjects were required to correctly identify 2 keywords from among 10 choices in each category. SRTs were measured with CI-only or bimodal listening in the presence of steady state noise (SSN) or competing speech with the same (M+M) or different voice gender (M+F). Unaided thresholds in the non-CI ear and demographic factors were compared with speech performance. In experiment 2, SRTs were adaptively measured in SSN for recognition of 5 keywords, a more difficult listening task than the 2-keyword recognition task in experiment 1. RESULTS: In experiment 1, SRTs were significantly lower for SSN than for competing speech in both the CI-only and bimodal listening conditions. There was no significant difference between CI-only and bimodal listening for SSN and M+F (p > 0.05); SRTs were significantly lower for CI-only than for bimodal listening for M+M (p < 0.05), suggesting bimodal interference. Subjects were able to make use of voice gender differences for bimodal listening (p < 0.05) but not for CI-only listening (p > 0.05). Unaided thresholds in the non-CI ear were positively correlated with bimodal SRTs for M+M (p < 0.006) but not for SSN or M+F. No significant correlations were observed between any demographic variables and SRTs (p > 0.05 in all cases). In experiment 2, SRTs were significantly lower with two than with five keywords (p < 0.05). A significant bimodal benefit was observed only for the 5-keyword condition (p < 0.05). CONCLUSIONS: With the CI alone, subjects experienced greater interference with competing speech than with SSN and were unable to use voice gender difference to segregate talkers. For the coordinated response measure task, subjects experienced no bimodal benefit and even bimodal interference when competing talkers were the same voice gender. A bimodal benefit in SSN was observed for the five-keyword condition but not for the two-keyword condition, suggesting that bimodal listening may be more beneficial as the difficulty of the listening task increased. The present data suggest that bimodal benefit may depend on the type of masker and/or the difficulty of the listening task.

Effect of Tinnitus and Duration of Deafness on Sound Localization and Speech Recognition in Noise in Patients With Single-Sided Deafness.

Patients with single-sided deafness (SSD) often experience poor sound localization, reduced speech understanding in noise, reduced quality of life, and tinnitus. The present study aims to evaluate effects of tinnitus and duration of deafness on sound localization and speech recognition in noise by SSD subjects. Sound localization and speech recognition in noise were measured in 26 SSD and 10 normal-hearing (NH) subjects. Speech was always presented directly in front of the listener. Noise was presented to the deaf ear, in front of the listener, or to the better hearing ear. Tinnitus severity was measured using visual analog scale and Tinnitus Handicap Inventory. Relative to NH subjects, SSD subjects had significant deficits in sound localization and speech recognition in all listening conditions ( p < .001). For SSD subjects, speech recognition in noise was correlated with mean hearing thresholds in the better hearing ear ( p < .001) but not in the deaf ear. SSD subjects with tinnitus performed poorer in sound localization and speech recognition in noise than those without tinnitus. Shorter duration of deafness was associated with greater tinnitus and sound localization difficulty. Tinnitus visual analog scale and Tinnitus Handicap Inventory were highly correlated; the degree of tinnitus was negatively correlated with sound localization and speech recognition in noise. Those experiencing noticeable tinnitus may benefit more from cochlear implantation than those without; subjective tinnitus reduction may be correlated with improved sound localization and speech recognition in noise. Subjects with longer duration of deafness demonstrated better sound localization, suggesting long-term compensation for loss of binaural cues.

Effects of age and duration of deafness on Mandarin speech understanding in competing speech by normal-hearing and cochlear implant children.

Due to poor perception of fundamental frequency (F0) cues that are important for lexical tone perception and talker segregation, pediatric Chinese cochlear implant (CI) users may be especially susceptible to informational masking. Here, speech recognition thresholds (SRTs) were measured in steady noise or competing speech in Mandarin-speaking CI and normal-hearing (NH) children. CI children were more susceptible to informational masking and were unable to use F0 cues to segregate talkers. SRTs were significantly correlated with chronological age in NH children and with duration of deafness in CI children, suggesting that auditory deprivation may limit developmental processes important for talker segregation.

Effect of spatial separation and noise type on sentence recognition by Mandarin-speaking cochlear implant users.

OBJECTIVES: To investigate the effects of spatial separation and noise type on sentence recognition by unilateral Mandarin-speaking cochlear implant (CI) users and normal-hearing (NH) listeners. METHOD: Twenty-two unilateral Mandarin-speaking CI users and six NH listeners participated in this study. Speech reception thresholds were measured for three noise types (steady state noise, speech babble, and music). Sentences from the Mandarin Speech Perception test were presented directly in front of the listener (0°). Noise was presented from one of the five speaker locations: -90°, -45°, 0°, +45°, and +90°. RESULTS: Overall, CI performance was significantly poorer than NH performance for all spatial separation and noise type conditions. NH listeners performed best with music and poorest with steady noise. CI users performed best with steady noise, and poorest with babble. Performance was significantly affected by noise location and noise type. There was no significant difference in head shadow effects among the different noise types for CI users. CONCLUSIONS: Performance was much poorer in CI than in NH listeners for all noise types and spatial separations. Noise type differently affected unilateral CI users and NH listeners. The limited spectral resolution in CI users did not appear to affect head shadow.