The DNA methylation inhibitor RG108 protects against noise-induced hearing loss

Background Noise-induced hearing loss represents a commonly diagnosed type of hearing disability, severely impacting the quality of life of individuals. The current work is aimed at assessing the effects of DNA methylation on noise-induced hearing loss. Methods Blocking DNA methyltransferase 1 (DNMT1) activity with a selective inhibitor RG108 or silencing DNMT1 with siRNA was used in this study. Auditory brainstem responses were measured at baseline and 2 days after trauma in mice to assess auditory functions. Whole-mount immunofluorescent staining and confocal microcopy of mouse inner ear specimens were performed to analyze noise-induced damage in cochleae and the auditory nerve at 2 days after noise exposure. Results The results showed that noise exposure caused threshold elevation of auditory brainstem responses and cochlear hair cell loss. Whole-mount cochlea staining revealed a reduction in the density of auditory ribbon synapses between inner hair cells and spiral ganglion neurons. Inhibition of DNA methyltransferase activity via a non-nucleoside specific pharmacological inhibitor, RG108, or silencing of DNA methyltransferase-1 with siRNA significantly attenuated ABR threshold elevation, hair cell damage, and the loss of auditory synapses. Conclusions This study suggests that inhibition of DNMT1 ameliorates noise-induced hearing loss and indicates that DNMT1 may be a promising therapeutic target. Graphical abstract

Sensorineural hearing loss in tubotympanic variety of chronic suppurative otitis media

Objectives: To determine whether chronic suppurative otitis media(CSOM) can cause Sensorineural hearing loss(SNHL) and to note its degree and its relation to duration of disease. Methods: This was a cross sectional study which was carried out in the departments of Otolaryngology and Head-Neck Surgery of Dhaka Medical College Hospital during the period of April’2012 to March’2013. A total number of 76 patients having unilateral CSOM were included in this study age ranging from 6 to 59 years after exclusion of other possible causes of SNHL such as meningitis, head injury, previous ear surgery and chronic noise exposure. The use of unilateral CSOM cases provided a contralateral ear to serve as a control. Bone conduction threshold elevation between diseased and control ear was considered as the indicator of inner ear damage. Results: In this series, CSOM was seen to be associated with sensorineural hearing loss. Significant threshold elevation was observed in relation to disease duration. Here bone conduction measurement in all frequencies (500Hz,1000Hz,2000Hz and 4000Hz) in diseased and uninvolved contralateral side showed elevation of bone conduction in diseased side and this elevation was significantly higher (p<0.001). The average bone conduction loss at 4kHz was higher than the average at the speech frequency range. Conclusion: This study suggests that CSOM can cause significant bone conduction threshold elevation and it should be considered when managing this problem. Early detection and prompt treatment may limit this potential handicap. Bangladesh J Otorhinolaryngol; April 2016; 22(1): 26-30

Prospective Study of Dietary Patterns and Hearing Threshold Elevation

We conducted a prospective study of dietary patterns and longitudinal change in audiometric hearing thresholds among 3,135 women (mean age = 59 years) in the Nurses’ Health Study II (2012–2018). Diet adherence scores for the Dietary Approaches to Stop Hypertension (DASH) and Alternate Mediterranean (AMED) diets and the Alternate Healthy Eating Index 2010 (AHEI-2010) were calculated using validated food-frequency questionnaires. Baseline and 3-year follow-up hearing sensitivities were assessed by pure-tone audiometry at 19 US sites. We used multivariable-adjusted logistic regression models to examine independent associations between diet adherence scores and risk of ≥5 dB elevation in the pure-tone average (PTA) of low-frequency (LPTA0.5,1,2 kHz), mid-frequency (MPTA3,4 kHz), and high-frequency (HPTA6,8 kHz) hearing thresholds. Higher adherence scores were associated with lower risk of hearing loss. Compared with the lowest quintile of DASH score, the multivariable-adjusted odds ratios for mid-frequency and high-frequency threshold elevation in the highest quintile were 0.71 (95% confidence interval (CI): 0.55, 0.92; P for trend = 0.003) and 0.75 (95% CI: 0.59, 0.96; P for trend = 0.02); for AMED and AHEI scores, for mid-frequency threshold elevation, they were 0.77 (95% CI: 0.60, 0.99; P for trend = 0.02) and 0.72 (95% CI: 0.57, 0.92; P for trend = 0.002). Nonsignificant inverse associations were observed for high-frequency threshold elevation. There were no significant associations between adherence scores and low-frequency threshold elevation. Our findings indicate that eating a healthy diet might reduce the risk of acquired hearing loss.

Effects of cochlear synaptopathy on spontaneous and sound-evoked activity in the mouse inferior colliculus

ABSTRACTTinnitus and hyperacusis are life-disrupting perceptual abnormalities that are often preceded by acoustic overexposure. Animal models of overexposure have suggested a link between these phenomena and neural hyperactivity, i.e. elevated spontaneous rates (SRs) and sound-evoked responses. Prior work has focused on changes in central auditory responses, with less attention paid to the exact nature of the associated peripheral damage. The demonstration that acoustic overexposure can cause cochlear nerve damage without permanent threshold elevation suggests this type of peripheral damage may be a key elicitor of tinnitus and hyperacusis in humans with normal audiograms. We addressed this idea by recording responses in the mouse inferior colliculus (IC) following a bilateral, neuropathic noise exposure. Two wks post-exposure, mean SRs were unchanged in mice recorded while awake, or under anesthesia. SRs were also unaffected by more intense, or unilateral exposures. These results suggest that neither neuropathy nor hair cell loss are sufficient to raise SRs in the IC, at least in mice. However, it’s not clear whether our mice had tinnitus. Tone-evoked rate-level functions at the CF were steeper following exposure, specifically in the region of maximal neuropathy. Furthermore, suppression driven by off-CF tones and by ipsilateral noise were also reduced. Both changes were especially pronounced in neurons of awake mice. These findings align with prior reports of elevated acoustic startle in neuropathic mice, and indicate that neuropathy may initiate a compensatory response in the central auditory system leading to the genesis of hyperacusis.

Effect of Endolymphatic Hydrops on Sound Transmission in Live Guinea Pigs Measured with a Laser Doppler Vibrometer

Objective. This study aimed at describing the mechanism of hearing loss in low frequency and the different dynamic behavior of the umbo, the stapes head, and the round window membrane (RWM) between normal guinea pigs and those with endolymphatic hydrops (EH), using a laser Doppler vibrometer (LDV).Methods. Cochlear sections were stained with hematoxylin and eosin (HE) to evaluate the hydropic ratio (HR). Auditory brainstem responses (ABR) and whole-mount immunostaining were measured. Displacement of the umbo, stapes head, and RWM in response to ear-canal sound was evaluated using a LDV.Results. Mean HR values in EH model of all the turns are larger than the control group. The ABR threshold of the EH group was significantly higher than that of the control. Strong positive correlation was found between HR at apical turn and ABR threshold elevation at 1000 Hz and at subapical turn and ABR threshold elevation at 2000 Hz. FITC-phalloidin immunostaining of the cochlear basilar membrane in the apical, subapical, and suprabasal turns showed missing and derangement stereocilia of third-row outer hair cells. The umbo, stapes head, and RWM displacement in ears with EH was generally lower than that of normal ears. The EH-induced differences in stapes head and RWM motion were significant at 0.5 kHz.Conclusion. The LDV results suggested that the higher inner ear impedance in EH affected the dynamic behavior of the two opening windows of the cochlea and then reduced the vibration of the ossicular chain by increasing the afterload, resulting in acoustic dysfunction. The vibration reduction mainly occurred at low frequencies, which has related with the morphology changes of the apical and subapical turns in EH model.

Unusual cause for pacemaker threshold elevation

Pacing threshold is an important entity which should be tested during pacemaker follow up. Abnormal elevation of pacing threshold would end up with early exhaustion of pacemaker battery. In this report, we described a patient with an unusual cause for threshold elevation. Learning objective: Pacemaker follow-up has its own routines. Telecardiogram is one of them, however it is mostly underrated nowadays. Our objective is to teach value of this quick and inexpensive test for pacemaker patients. DOI: http://dx.doi.org/10.3126/ajms.v6i1.10801 Asian Journal of Medical Sciences Vol.6(1) 2015 106-107

A multi-proxy approach to assessing isolation basin stratigraphy from the Lofoten Islands, Norway

This study takes a comprehensive approach to characterizing the isolation sequence of Heimerdalsvatnet, a coastal lake in the Lofoten Islands, northern Norway. We use established methods and explore new techniques to assess changes in marine influence. Bathymetric and sub-bottom profiles were acquired to examine basin-wide sedimentation and a 5.8 m sediment core spanning the last 7800 cal yr BP was analyzed. We measured magnetic susceptibility, bulk organic matter properties, molecular biomarkers, diatom assemblages, and elemental profiles acquired by scanning X-ray fluorescence. These characteristics of the sediment reflect detailed changes in salinity and water column conditions as the lake was progressively isolated. Three distinct litho/chemo-stratigraphic units represent a restricted marine phase (7800–6500 cal yr BP), a transitional phase characterized by intermittent marine influence (6500–4900 cal yr BP), and complete isolation and freshwater sedimentation (4900 cal yr BP to present). Although there are uncertainties in the estimate of the threshold elevation of the lake, the timing of these phases generally corresponds with previous interpretations of the local relative sea-level history. This record captures sea-level regression following the Tapes transgression and supports the interpretation of a subsequent sea-level stillstand, dated in Heimerdalsvatnet from 6500 to 4900 cal yr BP.