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.

Occupational exposure to volatile organic compounds affects microRNA profiling: Towards the identification of novel biomarkers.

In the framework of a project aimed at finding novel predictive biomarkers of VOCs exposure-related diseases, the effect of exposure to ethylbenzene, toluene, and xylene has been analyzed in a group of painters (spray- and roller-painters) working in the shipyard industry. Airborne levels of solvents were higher in spray- than in roller-painters, and comparable to the Occupational Exposure Limits (OELs), particularly for toluene and xylene. The urinary concentration of each volatile organic compound (VOC) and of the corresponding metabolites were also concurrently measured. A set of oxidative stress biomarkers, i.e., the products of DNA and RNA oxidation, RNA methylation, and protein nitration, were measured, and found significantly higher at the end of the work shift. MicroRNA (MiRNA) expression was analyzed in the VOC-exposed workers and in a control group, finding 56 differentially expressed (DE) miRNAs at a statistically significant level (adjusted p ≤ 0.01). The Receiver-Operating Characteristic curves, computed for each identified miRNA, showed high sensitivity and specificity. A pathway analysis in the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that miRNA-1, which was found downregulated in exposed workers, is involved in the lung cancer oncogenesis. A subset of 10 miRNAs (out of the 56 DE) was selected, including those with the highest correlation to the urinary dose biomarkers measured at the end of work-shift. Multivariate ANOVA analysis showed a statistically significant correlation between the urinary dose biomarkers (both the VOCs urinary concentration and the VOCs' metabolite concentration), and the identified miRNA subset, indicating that the exposure to low VOC doses may be sufficient to activate the miRNA response. Four miRNAs belonging to the subset strongly related to the VOCs and VOCs' metabolites concentration were individuated, miR-589-5p, miR-941, miR-146b-3p and miR-27a-3p, with well-known implications in oxidative stress and inflammation processes.

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.

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.

Attenuation of peak sound pressure levels of shooting noise by hearing protective earmuffs.

Transmission losses (TL) to highly impulsive signals generated by three firearms have been measured for two ear muffs, using both a head and torso simulator and a miniature microphone located at the ear canal entrance (MIRE technique). Peak SPL TL have been found to be well approximated by 40 ms short-L eq TL. This has allowed the use of transmissibilities and correction factors for bone conduction and physiological masking appropriate for continuous noise, for the calculation of REAT-type peak insertion losses (IL). Results indicate that peak IL can be well predicted by estimates based on one-third octave band 40 ms short L eq and manufacturer-declared (nominal) IL measured for continuous noise according to test standards. Such predictions tend to be more accurate at the high end of the range, while they are less reliable when the attenuation is lower. A user-friendly simplified prediction algorithm has also been developed, which only requires nominal IL and one-third octave sound exposure level spectra. Separate predictions are possible for IL in direct and diffuse sound fields, albeit with higher uncertainties, due to the smaller number of experimental data comprising the two separate datasets on which such predictions are based.