MicroRNA expression is associated with auditory dysfunction in workers exposed to ototoxic solvents and noise.

This study is part of a project on early hearing dysfunction induced by combined exposure to volatile organic compounds (VOCs) and noise in occupational settings. In a previous study, 56 microRNAs were found differentially expressed in exposed workers compared to controls. Here, we analyze the statistical association of microRNA expression with audiometric hearing level (HL) and distortion product otoacoustic emission (DPOAE) level in that subset of differentially expressed microRNAs. The highest negative correlations were found; for HL, with miR-195-5p and miR-122-5p, and, for DPOAEs, with miR-92b-5p and miR-206. The homozygous (mut) and heterozygous (het) variants of the gene hOGG1 were found disadvantaged with respect to the wild-type (wt), as regards the risk of hearing impairment due to exposure to VOCs. An unsupervised artificial neural network (auto contractive map) was also used to detect and show, using graph analysis, the hidden connections between the explored variables. These findings may contribute to the formulation of mechanistic hypotheses about hearing damage due to co-exposure to noise and ototoxic solvents.

Hearing Aids Performance in Hypobaric Environments.

OBJECTIVE: High altitudes imply exposure to a decreased ambient air pressure. Such a situation may also alter the performance of acoustic transducers using vibrating diaphragms due to air rarefaction. This study aimed at analyzing the performance at high altitude of hearing aids (HAs) where mechano-electric and electro-mechanic transducers are used. METHODS: A hypobaric chamber was used to perform two separated experimental sessions. In the first one two commercial models of HAs were exposed to a simulated altitude of 25,000 ft (7620 m) and to a subsequent rapid decompression profile, with a rapid climb (< 3 s) from 8000 (2438 m) to 25,000 ft. The second session separately analyzed the performance of microphone and receiver at an altitude of 9000 and 15,000 ft (2743 and 4572 m). Before and after the first session, the HAs were tested with an electronic ear while a dedicated recording system was used in the second session. RESULTS: No HA damage or dysfunction was detected during the first session. In the second one, the microphone showed a mild decrease of its output, while the receiver exhibited a much higher reduction of its output. CONCLUSION: Our findings highlight the safe use of HAs even under extreme environmental pressure changes. For altitudes exceeding 10,000 ft (3048 m), a recalibration of the HAs output via a dedicated program may be suggested. Lucertini M, Sanjust F, Manca R, Cerini L, Lucertini L, Sisto R. Hearing aids performance in hypobaric environments. Aerosp Med Hum Perform. 2021; 92(9):738743.

Distortion product otoacoustic emission sensitivity to different solvents in a population of industrial painters.

Objective: To evaluate the ototoxic effect of the exposure to different organic solvents and noise using distortion product otoacoustic emissions (DPOAEs).Design: The exposure to different solvents was evaluated by measuring, before and at the end of the work-shift, the urinary concentrations of solvent metabolites used as dose biomarkers. The urinary concentrations of DNA and RNA oxidation products were also measured as biomarkers of oxidative damage. The simultaneous exposure to noise was also evaluated. DPOAEs and pure tone audiometry (PTA) were used as outcome variables, and were correlated to the exposure variables using mixed effect linear regression models.Study sample: Seventeen industrial painters exposed to a solvent mixture in a naval industry. A sample size of 15 was estimated from previous studies as sufficient for discriminating small hearing level and DPOAE level differences (5 dB and 2 dB, respectively) at a 95% confidence level.Results: Statistically significant associations were found between the DPOAE level and the urinary dose biomarkers and the oxidative damage biomarkers. DPOAE level and the logarithm of the metabolite concentration showed a significant negative correlation.Conclusions: DPOAE are sensitive biomarkers of exposure to ototoxic substances and can be effectively used for the early detection of hearing dysfunction.

Lack of Significant Audiometric Changes Under Hypobaric Hypoxia at 15,000 ft.

BACKGROUND: The aim of this study was pure tone audiometry (PTA) evaluation in normal individuals exposed to hypobaric hypoxia, taking into account the influence of air rarefaction on sound transmission via a standard earphone.METHODS: The study was conducted in a hypobaric chamber using a standard audiometer and a TDH-39P earphone whose performance at altitudes was analyzed in a previous research. Eight male volunteers underwent PTA testing at ground level and at 15,000 ft under normoxia (via an oxygen mask) and after 20 min of hypoxia. Auditory threshold at 500, 1000, 2000, and 4000 Hz was recorded from the right ear while monitoring arterial oxygen saturation (Sao2). The PTA data obtained at high altitude were corrected according to a specific recalibration table.RESULTS: During hypoxia, a significant threshold shift was observed only at 4000 Hz, with respect to ground level recording, for the sole not-corrected data. At the same frequency a significant threshold shift was also observed between the ground level recording and normoxia at 15,000 ft, confirming the presence of a hypobaric effect not related to hypoxia. After the recalibration procedure, this hearing impairment was not significant. No correlation with Sao2 levels was observed.DISCUSSION: The mild and not significant presence of high altitude-induced PTA derangements in healthy normal individuals was documented, although a stimulus recalibration was needed for a correct interpretation of our data.Lucertini M, Lancia S, Sanjust F, Guadagno AG, Lucertini L, Sisto R. Lack of significant audiometric changes under hypobaric hypoxia at 15,000 ft. Aerosp Med Hum Perform. 2020; 91(1):32-36.

High Altitude Performance of Loudspeakers and Potential Impact on Audiometric Findings.

BACKGROUND: The evaluation of how air rarefaction can affect a loudspeaker performance at altitude implies the need for characterization of earphones during hypobaric conditions. The aim of this study was phonometric analysis at different altitudes of the acoustic output of a widely used earphone model, along with its consequences on audiological investigations conducted under such environmental conditions.METHODS: The transfer function of a TDH-39P earphone was analyzed with an artificial ear under nine different altitude levels, from sea level up to 35,000 ft, inside a hypobaric chamber. A specific phonometric system not sensitive to environmental pressure changes was used. Other potentially confounding factors, such as environmental temperature and humidity, were continuously monitored.RESULTS: No relevant temperature or humidity changes were detected. The sound pressure level generated by the earphone under hypobaric conditions was found considerably affected by air density changes. These data produced a correction table aiming at recalibrating the earphone's output at each audiometric octave test frequency within the 250-8000 Hz range. Quite different characteristics of response were observed at different audiometric frequencies. Such findings were particularly evident for altitudes exceeding 12,000 ft.DISCUSSION: The development of a frequency-selective and altitude-related correction factor for acoustic stimuli is an essential aspect when hearing threshold measurements in hypobaric environments are performed.Lucertini M, Botti T, Sanjust F, Cerini L, Autore A, Lucertini L, Sisto R. High altitude performance of loudspeakers and potential impact on audiometric findings. Aerosp Med Hum Perform. 2019; 90(7):655-659.

Circulating microRNAs as potential biomarkers of occupational exposure to low dose organic solvents.

Circulating microRNAs (miRNAs) have been recently acknowledged as novel and non-invasive biomarkers of exposure to environmental and occupational hazardous substances. This preliminary study investigates the potential role of blood miRNAs as molecular biomarkers of exposure to the most common organic solvents (ethylbenzene, toluene, xylene) used in the shipyard painting activity. Despite the low number of recruited workers, a two-tail standard Students' test with Holm-Bonferroni adjusted p-value shows a significant up-regulation of two miRNAs (miR_6819_5p and miR_6778_5p) in exposed workers with respect to controls. A correlation analysis between miRNA, differentially expressed in exposed workers and in controls and urinary dose biomarkers i.e. methylhyppuric acid (xylenes metabolite), phenylglyoxylic and mandelic acid (ethylbenzene metabolites) S-benzyl mercapturic acid (toluene metabolite) and S-phenylmercapturic acid (benzene metabolite) measured at the end of the work-shift, allowed the identification of high correlation (0.80-0.99) of specific miRNAs with their respective urinary metabolites. MiRNA_671_5p correlated with methylhippuric, S-phenylmercapturic and S-benzyl mercapturic acid while the miRNA best correlating with the phenylglioxylic acid was miRNA_937_5p. These findings suggest miRNA as sensitive biomarkers of low dose exposure to organic chemicals used at workplace. Urinary DNA and RNA repair biomarkers coming from the oxidation product of guanine have been also associated to the different miRNAs. A significant negative association was found between 8-oxo-7,8-dihydroguanine (8-oxoGua) urinary concentration and miR_6778_5p. The findings of the present pilot study deserve to be tested on a larger population with the perspective of designing a miRNA based test of low dose exposure to organic solvents.

Intensimetric detection of distortion product otoacoustic emissions with ear canal calibration.

Distortion product otoacoustic emissions (DPOAEs) have been accurately measured with an intensimetric technique, involving simultaneous measure of pressure and velocity in the ear canal, which allows one to correctly calibrate both the input stimuli and the otoacoustic emission (OAE) level. Suitable combinations of standard intensimetric quantities, active intensity and power density [Stanzial, Shiffrer, and Sacchi, J. Acoust. Soc. Am. 131, 269-280 (2012)], are used to equalize the stimuli transmitted to the middle ear, and to estimate the DPOAE level emitted by the eardrum. The DPOAE intensimetric spectra are consistent with those recorded with a high-quality conventional otoacoustic probe with state-of-the-art calibration of both stimulus and OAE response [Charaziak and Shera, J. Acoust. Soc. Am. 141, 515-525 (2017)], demonstrating the applicability of the intensimetric method to OAE measurements.

Distortion product otoacoustic emission generation mechanisms and their dependence on stimulus level and primary frequency ratio.

In this study, a systematic analysis of the dependence on stimulus level and primary frequency ratio r of the different components of human distortion product otoacoustic emissions has been performed, to check the validity of theoretical models of their generation, as regards the localization of the sources and the relative weight of distortion and reflection generation mechanisms. 2f1 - f2 and 2f2 - f1 distortion product otoacoustic emissions of 12 normal hearing ears from six human subjects have been measured at four different levels, in the range [35, 65] dB sound pressure level, at eight different ratios, in the range [1.1, 1.45]. Time-frequency filtering was used to separate distortion and reflection components. Numerical simulations have also been performed using an active nonlinear cochlear model. Both in the experiment and in the simulations, the behavior of the 2f1 - f2 distortion and reflection components was in agreement with previous measurements and with the predictions of the two-source model. The 2f2 - f1 response showed a rotating-phase component only, whose behavior was in general agreement with that predicted for a component generated and reflected within a region basal to the characteristic place of frequency 2f2 - f1, although alternative interpretations, which are also discussed, cannot be ruled out.

Input/output functions of different-latency components of transient-evoked and stimulus-frequency otoacoustic emissions.

The input/output functions of the different-latency components of human transient-evoked and stimulus-frequency otoacoustic emissions are analyzed, with the goal of relating them to the underlying nonlinear dynamical properties of the basilar membrane response. Several cochlear models predict a cubic nonlinearity that would yield a correspondent compressive response. The otoacoustic response comes from different generation mechanisms, each characterized by a particular relation between local basilar membrane displacement and otoacoustic level. For the same mechanism (e.g., reflection from cochlear roughness), different generation places would imply differently compressive regimes of the local basilar membrane dynamics. Therefore, this kind of study requires disentangling these contributions, using suitable data acquisition and time-frequency analysis techniques. Fortunately, different generation mechanisms/places also imply different phase-gradient delays, knowledge of which can be used to perform this task. In this study, the different-latency otoacoustic components systematically show differently compressive response, consistent with two simple hypotheses: (1) all emissions come from the reflection mechanism and (2) the basilar membrane response is strongly compressive in the resonance region and closer to linear in more basal regions. It is not clear if such a compressive behavior also extends to arbitrarily low stimulus levels.

Otoacoustic emissions in time-domain solutions of nonlinear non-local cochlear models.

A nonlinear and non-local cochlear model has been efficiently solved in the time domain numerically, obtaining the evolution of the transverse displacement of the basilar membrane at each cochlear place. This information allows one to follow the forward and backward propagation of the traveling wave along the basilar membrane, and to evaluate the otoacoustic response from the time evolution of the stapes displacement. The phase/frequency relation of the response can be predicted, as well as the physical delay associated with the response onset time, to evaluate the relation between different cochlear characteristic times as a function of the stimulus level and of the physical parameters of the model. For a nonlinear cochlea, simplistic frequency-domain interpretations of the otoacoustic response phase behavior may give inconsistent results. Time-domain numerical solutions of the underlying nonlinear and non-local full cochlear model using a large number (thousands) of partitions in space and an adaptive mesh in time are rather time and memory consuming. Therefore, in order to be able to use standard personal computers for simulations reliably, the discretized model has been carefully designed to enforce sparsity of the matrices using a multi-iterative approach. Preliminary results concerning the cochlear characteristic delays are also presented.