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This study uses a 3-D representation of the cochlear fluid to extend the results of a recent paper [Sisto, Belardinelli, and Moleti (2021b). J. Acoust. Soc. Am. 150, 4283–4296] in which two hydrodynamic effects, pressure focusing and viscous damping of the BM motion, both associated with the sharp increase in the wavenumber in the peak region, were analyzed for a 2-D fluid, coupled to a standard 1-D transmission-line WKB approach to cochlear modeling. The propagation equation is obtained from a 3-D fluid volume conservation equation, yielding the focusing effect, and the effect of viscosity is represented as a correction to the local 1-D admittance. In particular, pressure focusing amplifies the BM response without modifying the peak admittance, and viscous damping determines the position of the response peak counteracting focusing, as sharp gradients of the velocity field develop. The full 3-D WKB formalism is necessary to represent satisfactorily the behavior of the fluid velocity field near the BM-fluid interface, strictly related to viscous losses. As in finite element models, a thin layer of fluid is effectively attached to the BM due to viscosity, and the viscous force associated with the vertical gradient of the fluid vertical velocity acts on the BM through this layer.

In a previous study, we observed: (i) significant hearing function impairment, assessed with pure tone audiometry and distortion product otoacoustic emissions, in patients with Parkinson’s disease, compared with a matched control group, and (ii) lateralization of the hearing dysfunction, worse on the side affected by more pronounced Parkinson’s disease motor symptoms. This study investigates the association between the basal ganglia dopamine transporter availability and the hearing function in Parkinson’s disease patients, focusing also on the lateralization of both dysfunctions, with respect to that of the motor symptoms, and introducing a further distinction between patients with left-sided and right-sided predominant motor symptoms. Patients with right-handed Parkinson’s disease with a recent estimation of 123I-FP-CIT striatal uptake were audiologically tested with pure tone audiometry and distortion product otoacoustic emissions. Thirty-nine patients were included in the study. A statistically significant association was found, in the left-side predominant group only, between the distortion product otoacoustic emission levels and the contralateral dopamine transporter availability, and between the hearing threshold and the dopamine transporter availability difference between the ipsi- and the contralateral sides. The hearing impairment lateralization correlated to the motor symptom asymmetry was found significant only in the left-side predominant patients. The association between hearing function and basal ganglia dopamine transporter availability supports the hypothesis that the peripheral hearing function decline associated with dopamine depletion is involved in Parkinson’s disease development, with a significant difference between patients with left- and right-sided predominant motor symptoms. These findings also suggest that peripheral hearing function evaluation and its lateralization could be key elements for subtyping the disease.

This paper discusses the role of two-dimensional (2-D)/three-dimensional (3-D) cochlear fluid hydrodynamics in the generation of the large nonlinear dynamical range of the basilar membrane (BM) and pressure response, in the decoupling between cochlear gain and tuning, and in the dynamic stabilization of the high-gain BM response in the peak region. The large and closely correlated dependence on stimulus level of the BM velocity and fluid pressure gain [Dong, W., and Olson, E. S. (2013). Biophys. J. 105(4), 1067-1078] is consistent with a physiologically oriented schematization of the outer hair cell (OHC) mechanism if two hydrodynamic effects are accounted for: amplification of the differential pressure associated with a focusing phenomenon, and viscous damping at the BM-fluid interface. The predictions of the analytical 2-D Wentzel-Kramers-Brillouin (WKB) approach are compared to solutions of a 3-D finite element model, showing that these hydrodynamic phenomena yield stable high-gain response in the peak region and a smooth transition among models with different effectiveness of the active mechanism, mimicking the cochlear nonlinear response over a wide stimulus level range. This study explains how an effectively anti-damping nonlinear outer hair cells (OHC) force may yield large BM and pressure dynamical ranges along with an almost level-independent admittance.

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.

Background Painters are exposed to different substances, among which volatile organic compounds. Similar Exposure Groups (SEG) should be identified according to the European Standard EN:689/2019 to perform representative measurements of exposure. This approach was applied to 15 ship painters. Methods Two SEGs were identified considering environment and application technique: 6 spray painters (group A) working inside a hangar and 9 roller painters (group B) working on the ship. Gaseous toluene, xylenes, acetone, ethylacetate, n-butyl acetate, ethylbenzene and benzene were collected using Radiello samplers and determined by GC/MS. Results The ratios between each exposure value and the corresponding occupational exposure limit (Italian for toluene, xylenes, acetone, ethylbenzene, and benzene; German for ethylacetate and n-butyl acetate) were below 0.5 for Group A and well below 0.1 for Group B. Considering the common neurotoxic effect, workers’ exposure was also evaluated for the additive contribution of each component to the mixture. The mixture exposure index resulted 1.01 for spray painters and 0.09 for roller painters. Short Discussion/Conclusions Considering single substances, exposure levels were below the limits for both groups; when the mixture exposure is assessed, it reaches the mixture occupational limit for group A (spray) while it remains well below for group B (rollers). Results confirm that environment features and application techniques significantly affect the exposure levels, that are to be monitored on a SEG basis, and that considering the exposure to the mixture is crucial in order to orient the medical surveillance to prevent the neurotoxic effect in spray painters.

Distortion product otoacoustic emission (DPOAE) levels plotted as a function of stimulus frequency ratio demonstrate a bandpass shape. This bandpass shape is narrower at higher frequencies compared to lower frequencies and thus has been thought to be related to cochlear mechanical tuning. However, the frequency- and level-dependence of these functions above 8 kHz is largely unknown. Furthermore, how tuning estimates from these functions are related to behavioral tuning is not fully understood. From experiment 1, we report DPOAE level ratio functions (LRF) from seven normal-hearing, young-adults for f(2) = 0.75-16 kHz and two stimulus levels of 62/52 and 52/37 dB FPL. We found that LRFs became narrower as a function of increasing frequency and decreasing level. Tuning estimates from these functions increased as expected from 1-8 kHz. In experiment 2, we compared tuning estimates from DPOAE LRF to behavioral tuning in 24 normal-hearing, young adults for 1 and 4 kHz and found that behavioral tuning generally predicted DPOAE LRF estimated tuning. Our findings suggest that DPOAE LRFs generally reflect the tuning profile consistent with basilar membrane, neural, and behavioral tuning. However, further investigations are warranted to fully determine the use of DPOAE LRF as a clinical measure of cochlear tuning.

Uncertainties regarding the generation mechanism and source of human stimulus frequency otoacoustic emissions (SFOAEs), as well as the possible generation of artifacts, have previously restricted the use of SFOAEs in clinical settings for assessing cochlear function. Over the years, advanced time-frequency analysis of SFOAEs, using models of SFOAE delays as a function of frequency, have been implemented in an effort to isolate the long-latency (LL) component of SFOAEs—improving the signal-to-noise ratio and the artifact rejection as noteworthy byproducts. In order to test the hypothesis that behavioral measures and SFOAE LL component both reflect the activity of limited cochlear regions, the relationship between SFOAE LL component and behavioral measures was investigated. SFOAEs, behavioral thresholds and psychophysical tuning curves (PTCs) were measured for probe frequencies centered around 0.75, 1, 2, 4, 8, 10, 12.5 and 14 kHz. Stimulus levels for PTCs (10 dB SL) and SFOAEs (10, 20 and 30 dB SL) were referenced to behavioral thresholds at each frequency. Using the same in situ calibration technique using Thevenin-equivalent source parameters, behavioral thresholds and SFOAE-estimated thresholds from input-output functions of the SFOAE LL component were strongly correlated. Furthermore, there was a strong correlation between SFOAE-based and psychophysical tuning estimates.

The present paper extrapolates quantitative data for ozone virucidal activity on the basis of the available scientific literature data for a safe and effective use of ozone in the appropriate cases and to explore the safety measures developed under the stimulus of the current emergency situation. Ozone is a powerful oxidant reacting with organic molecules, and therefore has bactericidal, virucidal, and fungicidal actions. At the same time, it is a toxic substance, having adverse effects on health and safety. Its use is being proposed for the disinfection of workplaces’ and public places’ atmosphere, and for disposable masks and personal protective equipment disinfection for reuse, with particular reference to the COVID-19 pandemic outbreak. Ozone can be generated in situ by means of small, compact ozone generators, using dried ambient air as a precursor. It should be injected into the room that is to be disinfected until the desired ozone concentration is reached; after the time needed for the disinfection, its concentrations must be reduced to the levels required for the workers’ safety. The optimal use of ozone is for air and surface disinfection without human presence, using a concentration that is effective for the destruction of viruses, but not high enough to deteriorate materials.

Graphical abstract, Highlights • Exposure to volatile organic compounds represents a threat for workers' health and safety, even using protective equipment. • Spray-painting exposure is at higher risk than roller-painting. • Exposure to organic solvents may induce DNA and RNA oxidation, urine metabolite excretion and miRNA up- or down-regulation. • miR-589-5p and miR-941, miR-146b-3p and miR-27a-3p have been identified as potential biomarkers of effect in exposed workers. • KEGG pathway analysis showed that miRNA-1, related to lung cancer, is significantly downregulated in exposed workers., 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.

Acoustic Diagnostics is an Italian Space Agency (ASI) biomedical experiment exploiting the diagnostic potential of otoacoustic emissions (OAEs) to monitor the astronauts’ hearing health on board the International Space Station (ISS). It is being performed (July 2019–April 2020) on the ISS, in the framework of the BEYOND mission, sponsored by European Space Agency (ESA). A dedicated instrument for measuring distortion product OAE (DPOAE) in a noisy environment was designed by University of Rome Tor Vergata and INAIL. Aerospace Logistics Technology Engineering Company (ALTEC) took care of the payload development, mechanical, thermal and electromagnetic tests, verification, and acceptance. Two astronauts were subjected, before leaving for their mission on the ISS, to the DPOAE test, along with a full set of audiological tests (Baseline Data Collection, BDC), especially designed at University of Roma La Sapienza and Campus Bio-Medico. An identical DPOAE apparatus was used five times on board the ISS to test the two astronauts. Finally, a post-flight BDC was performed, few days after return to Earth. Preliminary analysis demonstrated that the payload was able to record DPOAEs on board the ISS with very low instrumental noise level, despite the high noise level of the ISS environment. ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country, provides access to the ISS as a laboratory in space. The utilization support services are provided, thanks to a contract, awarded by ASI, to ARGOTEC/Telespazio (UTISS Team).

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...

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.

Human health is influenced by various factors; these include genetic inheritance, behavioral lifestyle, socioeconomic and environmental conditions, and public access to care and therapies in case of illness, with the support of the national health system. All these factors represent the starting point for the prevention and promotion of a healthy lifestyle. However, it is not yet clear to what extent these factors may actually affect the health of an entire population. The exposures to environmental and occupational factors are several, most of which might be poorly known, contributing to influencing individual health. Personal habits, including diet, smoking, alcohol, and drug consumption, together with unhealthy behaviors, may inevitably lead people to the development of chronic diseases, contributing to increasing aging and decreasing life expectancy. In this article, we highlight the role of susceptibility biomarkers, i.e., the genetic polymorphisms of individuals of different ethnicities, with particular attention to the risk factors in the response to specific exposures of Europeans. Moreover, we discuss the role of precision medicine which is representing a new way of treating and preventing diseases, taking into account the genetic variability of the individual with each own clinical history and lifestyle.

The zero crossings of basilar-membrane (BM) responses to clicks are nearly independent of stimulus intensity. This work explores the constraints that this invariance imposes on one-dimensional nonlinear cochlear models with two degrees of freedom (2DoF). The locations of the poles and zeros of the BM admittance, calculated for a set of linear models in which the strength of the active force is progressively decreased, provides a playground for evaluating the behavior of a corresponding nonlinear model at increasing stimulus levels. Mathematical constraints on the model parameters are derived by requiring that the poles of the admittance move horizontally in the s-plane as the active force is varied. These constraints ensure approximate zero-crossing invariance over a wide stimulus level range in a nonlinear model in which the active force varies as a function of the local instantaneous BM displacement and velocity. Two different 2DoF models are explored, each capable of reproducing the main qualitative characteristics of the BM response to tones (i.e., the tall and broad activity pattern at low stimulus levels, the large gain dynamics, and the partial decoupling between gain and phase). In each model, the motions of the two masses are compared with response data from animal experiments.

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.

Graphical abstract, Highlights • Circulating miRNAs can be used as sensitive biomarkers of low dose exposure to organic solvents at workplace. • The miRNA response to organic chemicals elucidates molecular mechanisms occurring after specific occupational exposures. • Associations between miRNAs, dose and oxidative stress biomarkers contribute to prevent and promote workers’ health., 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.

This study aimed to identify sensitive and noninvasive biomarkers of early cyto-genotoxic, oxidative and inflammatory effects for exposure to volatile organic compounds (VOCs) in shipyard painters. On 17 (11 spray and 6 roller) painters (previously characterized for VOCs exposure to toluene, xylenes, ethylbenzene, ethyl acetate) and on 18 controls, we performed buccal micronucleus cytome (BMCyt) assay, Fpg-comet assay on lymphocytes, detection of urinary 8-oxoGua (8-oxo-7,8-dihydroguanine), 8-oxodGuo (8-oxo-7,8-dihydro-2′-deoxyguanosine) and 8-oxoGuo (8-oxo-7,8-dihydroguanosine), and cytokines release on serum. We found induction of cyto-genotoxicity by BMCyt assay and inflammatory effects (IL-6 and TNFα) in roller painters exposed to lower VOC concentrations than spray painters. In contrast, in both worker groups, we found direct and oxidative DNA damage by comet assay (with slightly higher oxidative DNA damage in roller) and significant increase of 8-oxoGuo and decrease of 8-oxodGuo and 8-oxoGua in respect to controls. The cyto-genotoxicity observed only on buccal cells of roller painters could be related to the task’s specificity and the different used protective equipment. Although limited by the small number of subjects, the study shows the usefulness of all the used biomarkers in the risk assessment of painters workers exposed to complex mixtures.

The mammalian cochlea achieves its remarkable sensitivity, frequency selectivity, and dynamic range by spatially segregating the different frequency components of sound via nonlinear processes that remain only partially understood. As a consequence of the wave-based nature of cochlear processing, the different frequency components of complex sounds interact spatially and nonlinearly, mutually suppressing one another as they propagate. Because understanding nonlinear wave interactions and their effects on hearing appears to require mathematically complex or computationally intensive models, theories of hearing that do not deal specifically with cochlear mechanics have often neglected the spatial nature of suppression phenomena. Here we describe a simple framework consisting of a nonlinear traveling-wave model whose spatial response properties can be estimated from basilar-membrane (BM) transfer functions. Without invoking jazzy details of organ-of-Corti mechanics, the model accounts well for the peculiar frequency-dependence of suppression found in two-tone suppression experiments. In particular, our analysis shows that near the peak of the traveling wave, the amplitude of the BM response depends primarily on the nonlinear properties of the traveling wave in more basal (high-frequency) regions. The proposed framework provides perhaps the simplest representation of cochlear signal processing that accounts for the spatially distributed effects of nonlinear wave propagation. Shifting the perspective from local filters to non-local, spatially distributed processes not only elucidates the character of cochlear signal processing, but also has important consequences for interpreting psychophysical experiments.

The spatial extent of the cochlear region that actually contributes to the DPOAE signal measured in the ear canal may be evaluated experimentally using interference tones or computed numerically using nonlinear cochlear models. A nonlinear transmission-line cochlear model is used in this study to evaluate whether the recently reported nonlinear behavior of the reticular lamina (RL) over a wide basal region may be associated with generation of a significant distortion product otoacoustic emission (DPOAE) component. A two-degrees-of-freedom 1-D nonlinear model was used as discussed by Sisto et al. (2019), in which each local element consists of two coupled oscillators, roughly representing the basilar membrane (BM) and the RL. In this model, the RL shows a strongly nonlinear response over a wide region basal to the characteristic place, whereas the BM response is linear outside the narrow peak region. Such a model may be considered as that using the minimal number of degrees of freedom necessary to separately predict the motion of the BM and RL, while preserving important cochlear symmetries, such as the zero-crossing invariance of the impulse response. In the numerical simulations, the RL nonlinearity generates indeed a large intracochlear distortion product source, extended down to very basal cochlear regions. Nevertheless, due to the weak and indirect coupling between the RL motion and the differential fluid pressure in the basal part of the traveling wave path, no significant contribution from this mechanism is predicted by the model to the generation of the DPOAE signal that is eventually measured in the ear canal.

Volatile organic compounds (VOCs) are present in several working activities. This work is aimed at comparing oxidative stress and DNA damage biomarkers to specific VOCs in the occupational exposure of painters. Dose-response relationships between biomarkers of oxidative stress and of dose were studied. Unmetabolized VOCs and their urinary metabolites were analyzed. Urinary Methylhyppuric acids (MHIPPs, xylenes metabolite), Phenylglyoxylic and Mandelic acid (PGA, MA ethylbenzene metabolites), S-Benzylmercapturic acid (SBMA, toluene metabolite), and S-Phenylmercapturic acid (SPMA, benzene metabolite) were quantified at the end of work-shift. Oxidative stress was determined by: urinary excretion of 8-oxodGuo, 8-oxoGua and 8-oxoGuo and direct/oxidative DNA damage in blood by Fpg-Comet assay. Multivariate linear regression models were used to assess statistical significance of the association between dose and effect biomarkers. The regressions were studied with and without the effect of hOGG1 and XRCC1 gene polymorphisms. Statistically significant associations were found between MHIPPs and both 8-oxoGuo and oxidative DNA damage effect biomarkers measured with the Comet assay. Oxidative DNA damage results significantly associated with airborne xylenes and toluene, whilst 8-oxodGuo was significantly related to urinary xylenes and toluene. Direct DNA damage was significantly associated to SBMA. XRCC1 wild-type gene polymorphism was significantly associated with lower oxidative and total DNA damage with respect to heterozygous and mutant genotypes. The interpretation of the results requires some caution, as the different VOCs are all simultaneously present in the mixture and correlated among them.

Background Although styrene is an established ototoxic agent at occupational exposure levels, the mechanisms of styrene toxicity in the auditory system are still unclear. Objectives The aim of this study was to identify the consequences of styrene chronic exposure in cochlear structures, looking for the mechanisms of ototoxicity of this organic compound and focusing on cell targets and oxidative stress/inflammatory processes. Methods Male adult Wistar rats were exposed to styrene (400 mg/kg by gavage for 5 days/week, 3 consecutive weeks). Hearing loss was evaluated by measuring auditory brainstem responses (ABR), morphological analysis were performed to evaluate hair cell and spiral ganglion neuron survival, as well as synaptic damage. Analysis of apoptotic (p53) and inflammatory (NF-κB, TNF-α, IL-1β and IL-10) mediators were performed by immunofluorescence analysis and western blot. Results Styrene ototoxic effects induced a hearing loss of about 35–40 dB. Immunofluorescence and western blotting analyses demonstrated that styrene administration induced redox imbalance and activated inflammatory processes, targeting sensory hair cell and neural dysfunction by a cross-talk between oxidative and inflammatory mediators. Discussion Major findings connect styrene ototoxicity to an interplay between redox imbalance and inflammation, leading to the intriguing assumption of a mixed sensory and neural styrene-induced ototoxicity. Thus, in a clinical perspective, data reported here have important implications for styrene risk assessment in humans.

Purpose The phase delay of stimulus frequency otoacoustic emissions (SFOAEs) has been proposed as a noninvasive, objective, and fast source for estimating cochlear mechanical tuning. However, the implementation of SFOAEs clinically has been thwarted by the gaps in understanding of the stability of SFOAE delay-based tuning estimates and their relationship to behavioral measures of tuning. Therefore, the goals of this study were (a) to investigate the relationship between delay-based tuning estimates from SFOAEs and simultaneously masked psychophysical tuning curves (PTCs) and (b) to assess the across- and within-session repeatability of tuning estimates from behavioral and OAE measures. Method Three sets of behavioral and OAE measurements were collected in 24 normal-hearing, young adults for two probe frequencies, 1 and 4 kHz. For each participant, delay-based tuning estimates were derived from the phase gradient of SFOAEs. SFOAE-based and behavioral estimates of tuning obtained using the fast-swept PTC paradigm were compared within and across sessions. Results In general, tuning estimates were sharper at 4 kHz compared to 1 kHz for both PTCs and SFOAEs. Statistical analyses revealed a significant correlation between SFOAE delay-based tuning and PTCs at 4 kHz, but not 1 kHz. Lastly, SFOAE delay-based tuning estimates showed better intra- and intersession repeatability compared to PTCs. Conclusions SFOAE phase-gradient delays reflect aspects of cochlear mechanical tuning, in that a frequency dependence similar to that of basilar membrane tuning was observed. Furthermore, the significant correlation with PTCs at 4 kHz and the high repeatability of SFOAE-based tuning measures offer promise of an objective, nonbehavioral assay of tuning in human ears.

In the last decade, animal studies highlighted the sensitivity of hearing function to lack of specific cochlear dopamine receptors, while several studies on humans reported association between hearing loss and Parkinson’s disease, partially recovered after levodopa administration in de novo patients. Taken together, these observations suggest investigating the possible use of cochlear function outcome variables, particularly, otoacoustic emissions, as sensitive biomarkers of Parkinson’s disease. Any lateralization of hearing dysfunction correlated with Parkinson’s disease lateralization would (i) further confirm their association and (ii) provide a disease-specific differential outcome variable. Differential indicators are particularly useful for diagnostic purposes, because their effectiveness is not limited by physiological inter-subject fluctuations of the outcome variable. Recent advances in the acquisition and analysis techniques of otoacoustic emissions suggest using them for evaluating differential cochlear damage in the two ears. In this study, we quantitatively evaluated hearing function in a population of subjects with Parkinson’s disease, to investigate the occurrence of hearing loss, and, particularly, whether hearing dysfunction shows lateralization correlated with motor symptoms. Pure tone audiometry and distortion product otoacoustic emissions were used as outcome variables in 80 patients (mean age 65 ± 9 years) and 41 controls (mean age 64 ± 10 years). An advanced customized acquisition and analysis system was developed and used for otoacoustic testing, which guarantees response stability independent of probe insertion depth, and has the sensitivity necessary to accurately assess the low levels of otoacoustic response typical of elderly subjects. To our knowledge, this is the first study introducing the distinction between ipsilateral and contralateral ear, with respect to the body side more affected by Parkinson’s disease motor symptoms. Significant asymmetry was found in the auditory function, as both otoacoustic responses and audiometric hearing levels were worse in the ipsilateral ear. Significantly worse hearing function was also observed in patients with Parkinson’s disease compared to controls, confirming previous studies. Several pathophysiological mechanisms may be hypothesized to explain asymmetric cochlear damage in Parkinson's disease, including the impairment of dopamine release and the involvement of extra-dopaminergic circuits, with the cholinergic pathway as a likely candidate. The observed asymmetry in the audiological response of patients with Parkinson’s disease suggests that lateralization of hearing dysfunction could represent a specific non-motor signature of the disease. The possible diagnostic use of cochlear dysfunction asymmetry as a specific biomarker of Parkinson’s disease deserves further investigation, needing a more precise quantitative assessment, which would require a larger sample size., Hearing function was evaluated in 80 subjects with Parkinson’s disease, by means of pure tone audiometry and distortion product otoacoustic emissions. Significant auditory asymmetry was found, as parameters were worse on the body side more affected by motor symptoms. Also, patients showed worse auditory function when compared to controls., Graphical Abstract Graphical Abstract

A two-degrees-of-freedom nonlinear cochlear model [Sisto, Shera, Altoè, and Moleti (2019). J. Acoust. Soc. Am. 146, 1685-1695] correctly predicts that the reticular lamina response is nonlinear over a wide basal region. Numerical simulations of suppression tuning curves agree with a recent experiment [Dewey, Applegate, and Oghalai (2019). J. Neurosci. 39, 1805-1816], supporting the idea that the strong susceptibility of the reticular lamina response to suppression by high-frequency tones does not imply that the total traveling wave energy builds-up in correspondingly basal regions. This happens because the reticular lamina is the lightest element of a coupled-oscillators system, only indirectly coupled to the differential pressure.

The catalytic conversion of carbon dioxide to synthetic CH4 was studied on five Ni/YSZ samples, with the same nickel loading (10 wt%) but different Ni particle size. The catalysts, prepared by different methods, were characterized combining morphological (BET, TEM), structural (XRD, in-operando XAS), electronic (XPS, in-operando XANES) analysis and H2-TPR experiments. The results showed that catalytic activity and CH4 selectivity depended on size and morphology of Ni particles, and that type and amount of deposited carbon strongly depended on Ni0 morphology. The kinetic measurements revealed that both H2 and CO2 reactants were activated on Ni sites, and that YSZ support was not directly involved in the reaction mechanism. The most efficient catalyst was that prepared by wet impregnation with Ni(EDTA)2− complex due to the high Ni0 dispersion.This catalyst showed low amount of carbon and remarkable stability over time on stream. In-operando XAS showed that it did not undergo deactivation by Ni0 → Ni2+ oxidation using high CO2 concentration, thus it is applicable in dynamic conditions like those typical in the energy storage from renewable sources process.

Aim: The occupational biomonitoring of exposures to carcinogens is carried out by measuring dose (metabolites) and susceptibility biomarkers (gene polymorphisms) in two biological matrices: urine for metabolite detection and blood for genotyping. Blood is the most common substrate but has some disadvantages including: invasiveness of the harvesting technique; need of specialized staff and equipment; and high infection risk. Methods & results: We propose our in-house approach using urine as single sample in 20 volunteers for simultaneous detection of dose and susceptibility biomarkers in order to verify efficacy and feasibility. Conclusion: Despite the low number of subjects, interindividual and gender variability in DNA yield, urine genomic DNA is a valuable source for gene polymorphism studies when blood samples are not available. [Formula: see text]

This present study is devoted to investigate the vibration transmissibility of the elbow along the forearm direction as a function of hand grip force. The vibration was from 6 to 500 Hz, which was generated on a single-axis electric shaker. It was transmitted to the elbow from an instrumented handle fixed on the shaker through the hand-arm system. 34 healthy adults participated in the measurement experiment. Each of them applied a constant grip force while maintaining the forearm in horizontal direction with a 90° elbow angle. The grip force was controlled in terms of the percent maximum voluntary contraction and three levels (20%, 30% and 40%) most frequently observed at workplaces were used in the experiment. A laser vibrometer was used to measure the vibration on the bony surface of the elbow along the forearm direction. The measured vibration transmissibility spectrum was expressed in an equal frequency band with a resolution of less than 1 Hz. This study found that increasing the grip force did not significantly change the first resonant peak at 8 Hz but it increased the second resonant frequency and the vibration transmissibility at higher frequencies. Relevance to industry The effect of the grip force on the elbow vibration transmissibility can be used to enhance the understanding of the vibration-induced disorders. The force-specific transmissibility can also be used as a frequency-weighting factor to quantify the exposure. They may help improve the method for the risk assessment of vibration-induced elbow injuries and disorders.