Search

Cochlear implant (CI) listeners have difficulty understanding speech in complex listening environments. This deficit is thought to be largely due to peripheral encoding problems arising from current spread, which results in wide peripheral filters. In normal hearing (NH) listeners, central processing contributes to segregation of speech from competing sounds. We tested the hypothesis that basic central processing abilities are retained in post-lingually deaf CI listeners, but processing is hampered by degraded input from the periphery. In eight CI listeners, we measured auditory nerve compound action potentials to characterize peripheral filters. Then, we measured psychophysical detection thresholds in the presence of multi-electrode maskers placed either inside (peripheral masking) or outside (central masking) the peripheral filter. This was intended to distinguish peripheral from central contributions to signal detection. Introduction of temporal asynchrony between the signal and masker improved signal detection in both peripheral and central masking conditions for all CI listeners. Randomly varying components of the masker created spectral-variance cues, which seemed to benefit only two out of eight CI listeners. Contrastingly, the spectral-variance cues improved signal detection in all five NH listeners who listened to our CI simulation. Together these results indicate that widened peripheral filters significantly hamper central processing of spectral-variance cues but not of temporal cues in post-lingually deaf CI listeners. As indicated by two CI listeners in our study, however, post-lingually deaf CI listeners may retain some central processing abilities similar to NH listeners.

BACKGROUND: Interleukin-32 (IL-32) is a recently discovered proinflammatory cytokine involved in inflammatory diseases. We investigated the expression of IL-32 and its regulation mechanism in the inflammatory response of patients with Helicobacter pylori (H. pylori) infection. DESIGN AND METHODS: IL-32 mRNA and protein expression in gastric tissues was detected by quantitative real-time PCR and immunohistochemistry. The regulation of IL-32 in human gastric epithelia cell line AGS was investigated by different cytokine stimulation and different H. pylori strain infection. RESULTS: Gastric IL-32 mRNA and protein expression were elevated in patients with H. pylori infection and positively correlated with gastritis. In H. pylori-infected patients, the mRNA level of IL-32 was also correlated with that of proinflammatory cytokines IL-1β and TNF-α. In vitro IL-1β and TNF-α could upregulate IL-32 mRNA and protein level in AGS cells, which was dependent on NF-κB signal pathway. The regulation of IL-32 expression in response to H. pylori-infection could be weakened by using neutralizing antibodies to block IL-1β and TNF-α. Moreover, H. pylori-infected AGS cells also induced IL-32 mRNA and protein expression, which was dependent on CagA. CONCLUSIONS: IL-32 level is elevated in patients with H. pylori infection and its expression is regulated by proinflammatory stimuli, suggesting that IL-32 may play a role in the pathogenesis of H. pylori-related gastritis.

BACKGROUND: In recent years, the PLCE1 rs2274223 polymorphism has been extensively investigated as a potential risk factor for upper gastrointestinal cancers, including squamous cell carcinoma (ESCC) and gastric cancer. However, the results of these studies have been inconsistent. METHODS: A meta-analysis of 13 case-control studies was performed including more than 11,000 subjects with genotyped PLCE1 rs2274223 polymorphisms. Odds ratios (OR) with 95% confidence intervals (CI) were employed to assess the association of the PLCE1 rs2274223 polymorphism with a susceptibility to ESCC or gastric cancer. RESULTS: A statistically significant increase in the risk of ESCC was associated with the PLCE1 rs2274223 polymorphism. This included the homozygous genetic model (OR = 1.46), heterozygous genetic model (OR = 1.25) and allelic genetic model (OR = 1.23). Similar results were consistently found for gastric cancer. In a subgroup analysis, the PLCE1 rs2274223 polymorphism was found to be a very sensitive marker for gastric cardia cancer as shown by the homozygous genetic model (OR = 2.23), heterozygous genetic model(OR = 1.59) and allelic genetic model (OR = 1.47). The risk associations of all of the gastric cardia cancer models were statistically significant. In contrast, none of the genetic models for non-cardia gastric cancer were significant. CONCLUSIONS: In this meta-analysis, the PLCE1 rs2274223 polymorphism was confirmed to have a statistically significant association with an increasing risk of ESCC and gastric cancer. The increase risk was especially observed for gastric cardia cancer.

The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.

BACKGROUND: In mammals, hair cells do not undergo spontaneous regeneration when they are damaged and result in permanent hearing loss. Previous studies in cultured Organ of Corti dissected from neonatal animals have shown that both DAPT (r-secretase inhibitor in the Notch signal pathway) treatment and Atoh1 overexpression can induce supernumerary hair cells. The effects of simultaneous DAPT treatment and Atoh1 over expression in the cells of cultured Organ of Corti from neonatal rats are still obscure. PRINCIPAL FINDINGS: In this study, we set out to investigate the interaction of DAPT treatment and Atoh1 overexpression as well as culture time and the location of basilar fragment isolated form neonatal rat inner ear. Our results showed that DAPT treatment induced more hair cells in the apical turn, while Atoh1 overexpression induced more extra hair cells in the middle turn of the cultured Organ of Corti. When used together, their effects are additive but not synergistic. In addition, the induction of supernumerary hair cells by both DAPT and Atoh1 overexpression is dependent on the treatment time and the location of the cochlear tissue. Moreover, DAPT treatment causes dramatic changes in the orientation of the stereociliary bundles of hair cells, whereas Atoh1 overexpression didn't induce drastic change of the polarity of stereociliary bundles. CONCLUSIONS/SIGNIFICANCE: Taken together, these results suggest that DAPT treatment are much more potent in inducing supernumerary hair cells than Atoh1 overexpression and that the new hair cells mainly come from the trans-differentiation of supporting cells around hair cells. The orientation change of stereociliary bundle of hair cells may be attributed to the insertion of the newly formed hair cells. The immature hair bundles on the newly formed hair cells may also contribute to the overall chaos of the stereociliary bundle of the sensory epithelia.