We tested whether sensitivity to acoustic spectrotemporal modulations can be observed from reaction times for normal-hearing and impaired-hearing conditions. In a manual reaction-time task, normal-hearing listeners had to detect the onset of a ripple (with density between 0–8 cycles/octave and a fixed modulation depth of 50%), that moved up or down the log-frequency axis at constant velocity (between 0–64 Hz), in an otherwise-unmodulated broadband white-noise. Spectral and temporal modulations elicited band-pass filtered sensitivity characteristics, with fastest detection rates around 1 cycle/oct and 32 Hz for normal-hearing conditions. These results closely resemble data from other studies that typically used the modulation-depth threshold as a sensitivity criterion. To simulate hearing-impairment, stimuli were processed with a 6-channel cochlear-implant vocoder, and a hearing-aid simulation that introduced separate spectral smearing and low-pass filtering. Reaction times were always much slower compared to normal hearing, especially for the highest spectral densities. Binaural performance was predicted well by the benchmark race model of binaural independence, which models statistical facilitation of independent monaural channels. For the impaired-hearing simulations this implied a “best-of-both-worlds” principle in which the listeners relied on the hearing-aid ear to detect spectral modulations, and on the cochlear-implant ear for temporal-modulation detection. Although singular-value decomposition indicated that the joint spectrotemporal sensitivity matrix could be largely reconstructed from independent temporal and spectral sensitivity functions, in line with time-spectrum separability, a substantial inseparable spectral-temporal interaction was present in all hearing conditions. These results suggest that the reaction-time task yields a valid and effective objective measure of acoustic spectrotemporal-modulation sensitivity. Human speech and other complex sounds in the natural environment are typically dynamic signals that rapidly change in amplitude over both time and frequency. Fluctuations in the temporal domain provide information about the rhythm of speech, such as syllable and word boundaries, whereas variations in the spectral domain are essential for formant and voice pitch perception . SensitiSpectrotemporal dynamic ripples have been introduced in psychoacoustics to investigate the spectrotemporal modulation sensitivity of auditory perception. Ripples are broadband noise stimuli that are modulated sinusoidally in amplitude over time and/or frequency . RipplesIn the present study we used manual reaction times to construct the spectrotemporal modulation transfer function (stMTF), rather than the conventionally used modulation detection or discrimination thresholds. Research in monkeys shows that reaction times systematically depend on acoustic modulation rates . SeveralFurthermore, reaction times allow for testing the presence or absence of binaural integration based on monaural responses, by comparing binaural reaction times against the prediction of a so-called “race model”. In such a model, the signals from either ear compete independently to reach the detection threshold, so that the response latency is determined by the winner of an independent parallel race between the two ears . Due to We tested whether reaction times are an objective measure having convergent validity of auditory sensitivity to moving ripples with various spectrotemporal modulations for normal-hearing listeners. We assessed the extent of separability of joint spectrotemporal sensitivity and investigated how binaural listening affected modulation sensitivity compared to monaural listening conditions by comparing the data with the race-model prediction. As a validation of our reaction-time paradigm, we also collected data under more challenging impaired-hearing simulations that are known to affect temporal and spectral sensitivity  and binaSix listeners participated in this study , none of whom reported a history of auditory deficits. All listeners had normal hearing (< 20 dB HL) in both ears from 125 to 8000 Hz. Except for two of the authors, listeners were naïve to the purpose of the experiments. We included the data from the two authors as they were highly similar to the data from the naïve listeners  and excluding those data did not appreciably affect the results and conclusions. The study was approved by the Local Ethics Committee of the Radboud University Nijmegen (protocol number 40327.091.12).Listeners were seated in an acoustically shielded sound chamber. Stimuli were presented through TDH 39 headphones . For sound processing and data acquisition we used Tucker Davis Technologies System 3 . Stored sounds were sent via the PC to a real-time processor (RP2.1) at a sampling rate of 48,828.125 Hz, and passed through a programmable attenuator (PA5). Stimuli were set at a comfortable, well-audible loudness of 65 dB(A) .t is time (s), if frequency (Hz) of the i-th harmonic, and i-th frequency was determined by i = 0–127. All harmonic tones had the same amplitude, effectively yielding the same spectrum as white noise.Dynamic ripples were created in MATLAB  as described by t is time (s), ω is the ripple velocity (Hz) and The spectrotemporal envelope determined the ripple fluctuations in amplitude over time and/or frequency:Together the carrier and the modulator formed the dynamic ripple in our experiments as follows:Cochlear-implant vocoder simulations were created using a previously described method by Litvak et al.  that modWe used 6 vocoder channels to simulate hearing via a cochlear implant, as cochlear-implant users are typically unable to effectively utilize information from all available cochlear-implant channels . Normal-Hearing-aid simulations were generated by using a fourth-order Butterworth low-pass filter with a cut-off at 500 Hz, mimicking residual hearing in the lower frequencies present in the bimodal cochlear implant users of our previous studies  period of silence between each trial. If the button was pressed before ripple onset, the trial was reiterated, but no more than 4 times. The outcome measure of the experiment was the listener's manual reaction time, which was defined as the time between the onset of the ripple and the moment the button was pressed.We tested five different listening conditions; acoustic stimuli were presented 1) monaurally , 2) monaurally via cochlear-implant vocoder , 3) monaurally via hearing-aid simulation , 4) binaurally , 5) binaurally via bimodal cochlear implant and hearing-aid simulation . In monaural conditions, both ears were tested separately. In the bimodal condition, cochlear implant and hearing aid were tested in both the right and left ear in different sessions. We did not test the binaural unimodal listening conditions (cochlear implant-cochlear implant or hearing aid-hearing aid). Each stimulus was presented 5 times in each listening condition. A complete data set thus contained a total of 6120 stimuli, which were split in 12 sessions of 30–40 min, each containing 510 trials. Sessions were distributed over 6 days of two sessions each. Ripples and conditions were presented in pseudo-randomized order.Because of time constraints, data collection was not fully completed in the four naïve listeners. Two naïve listeners completed 11 out of 12 sessions, with all ripples measured at least twice. The other two listeners completed 9 out of 12 sessions .st to 500th trial compared to the first 100 trials, yielding a P value of a two-sided permutation t-test of 0.815; changes in mean reaction times varied between −27 to + 21 ms across listening conditions, all of which did not reach significance [P > 0.323]). This observation indicates that procedural learning effects did not confound the reaction-time data.The four naïve listeners performed one training session under normal hearing conditions prior to the recording sessions, to become familiarized with the ripple stimuli and experimental procedures. We observed no systematic change in the average reaction times during the training session for these four listeners, or over the time course of the experimental sessions for all six listeners . Non-responses were found in 10% of the trials under normal-hearing conditions and in 46% of the trials of the hearing-impaired conditions . We do not explicitly account for the percentage of non-responses but note that in our analyses a higher number of non-responses would yield a median promptness (reaction time) closer to 1/3 s−1 (3 s). The non-modulated sound (velocity 0 Hz and density 0 cycles/octave) served as a catch stimulus, to determine the guess  rate of the participant. The guess rate varied from 7% for binaural normal hearing, to 21% for monaural hearing-aid listening, with the average guess rate across conditions at 12%.Data analysis was performed with custom-written MATLAB software. Reaction times generally show a skewed distribution with an extended tail towards longer reaction times. To obtain normally distributed data , the reaω. Similarly, we determined the temporal modulation transfer function tMTF, F, we calculated the mean promptness per ripple to construct a two-dimensional spectrotemporal modulation transfer function ω, Ω) = F(ω)·Σ·G(Ω). In case of a fully separable stMTF, the spectral and temporal components are independent of each other and the total of all 136 spectrotemporal responses can be expressed by the vectorial outer product of a single temporal F1(ω) (17 components) and spectral G1(Ω) (8 components) modulation transfer function, as follows:σ1 the largest singular value.To analyze the degree of separability of the stMTF, we applied singular value decomposition (SVD) for all listening conditions. SVD transforms the stMTF into two unitary matrices containing temporal and spectral singular vectors, respectively, and a rectangular diagonal matrix that contains the singular values: stMTF the cumulative probability function (CDF) of an observed reaction time τ at time t; M1 and M2 represent monaurally-presented stimuli . We estimated the cumulative probability density functions (CDF) from the promptness values. The race model CDF was constructed from the two monaural CDFs according to Equation  were observed at  ± 32,  ± 32,  ± 16,  ± 16,  ± 8 Hz, respectively. The longer response times to pure amplitude modulations under impaired-hearing conditions clearly implicate increased difficulty in the detection of temporal modulations. Differences in response times between binaural and monaural listening will be considered in more detail below with race-model predictions. Responses to upward (<0 Hz) and downward (>0 Hz) moving ripples were very similar; correlation coefficients between the responses to up- and downward ripples were between 0.91–0.99 for all listening conditions.We will first elaborate on how reaction times reflect the detection of temporal-only modulations . For theFor the static ripples , the promptness as a function of density resembled a low-pass characteristic, at least for the binaural and monaural normal-hearing conditions (Responses made for the cochlear-implant simulation (light green diamonds) resembled a band-pass filter characteristic with a cutoff around 0.75 cycles/octave and responses in the hearing-aid condition (dark green triangles) followed a band-pass characteristic with its highest promptness around 1–2 cycles/octave. Bimodal responses (pink squares) resembled the best values of the cochlear-implant and hearing-aid conditions. Overall, the impact of hearing-impairment simulation on reaction times was generally larger for the spectral modulations  than forsupplemental Figure S1-6 for individual stMTFs) per ripple density (abscissa) and velocity (ordinate). Deep red colors correspond to high spectral-temporal sensitivity, dark blue colors to low sensitivity . The results for pure amplitude-modulated stimuli (cf. ω = 0 Hz.muli cf.  are at tmuli cf.  are foun−1) than in the monaural condition (−1). Combined spectrotemporal modulation sensitivity for both listening conditions resembled a two-dimensional band-pass for both density and velocity, with fastest reaction times around velocities of ± 8–16 Hz and densities around 0.75–1 cycles/octave . The ripples were well detectable up to and including 4 cycles/octave.Ripple detection in the binaural normal-hearing condition  was fast−1 for cochlear implant, hearing aid, and bimodal vocoder, respectively). Temporal modulation sensitivity again showed a band-pass filter characteristic with fastest detection rates around ± 16 Hz. Cochlear-implant simulations (−1) were elicited to −16 Hz amplitude-modulated sounds (Ω = 0 cycles/octave). Ripple detection with the cochlear-implant vocoder became impossible for densities exceeding 0.75 cycles/octave. Of all hearing conditions, listeners reacted slowest for the hearing-aid simulations (−1). However, in contrast to the cochlear-implant condition, higher densities of up to 4 cycles/octave could still be detected if temporal modulation rates were not too fast (>16 Hz). A local dip in promptness exists for ripples with a density around 0.5 cycles/octave.The stMTFs for the impaired-hearing simulations –E were dulations  mainly r−1 at  = ). For high spectral modulation frequencies, the bimodal condition was comparable to the hearing-aid condition; for low spectral modulations it followed the cochlear-implant condition.The bimodal simulation resembled a conjunction of the cochlear-implant and hearing-aid simulation results, seemingly exhibiting a “best of both worlds” principle  with resα1 .We assessed the degree of separability of the stMTF into a pure temporal and spectral component through singular value decomposition (SVD) using the separability index Equation ) and theEquation ) to deteEquation ) and of Equation ). If the1 for the various hearing conditions. The first-order reconstruction of the stMTF yielded purely orthogonal patterns in the matrix, resulting from the full-separability assumption. For both normal hearing conditions, the separability index α1 was high , which suggests that the variability in the normal-hearing stMTFs can be captured quite well with a first-order approximation  and 0.97 . Now, the responses to the amplitude-modulated sounds seemed to be accounted for as well.The central row of ximation  and thatximation ). Notablα1 = 0.89). The first-order reconstructions were worse for the hearing-aid and bimodal conditions , suggesting a considerable inseparable spectrotemporal component to the responses of these two listening conditions. Incorporating the first two SVD components improved reconstructions  compared to normal hearing, as expected from the impaired signal processing of the simulations. Although the separability of the stMTF into a spectral and temporal component was high for both the normal-hearing and for the cochlear-implant simulated data, the inseparable second-order spectrotemporal component was still substantial, with a value between 7–10%. For the bimodal and especially the hearing-aid conditions, inseparability was larger by about 16 and 28%. For all ripples, binaural and bimodal reaction-time performance was comparable to the prediction of the benchmark race model of statistical facilitation, suggesting independent detection of two monaural signals, rather than true binaural integration.Constructing the stMTF based on reaction times is a fairly new approach that has been introduced so far only in monkey research , 2014. STo evaluate our reaction-time test under more challenging listening situations, we manipulated the ripple stimuli using hearing-aid and cochlear-implant simulations. Both simulations made it substantially harder to detect ripple modulations and even impossible for certain parameters, eliciting much longer reaction times compared to monaural normal hearing for all ripples. Bimodal hearing exhibited a “best-of-both-worlds” effect, following the fastest unimodal condition, which was the cochlear-implant condition for spectral modulations below 0.75 cycles/octave, and the hearing aid for higher spectral modulations . An impr−1 for the well-detectable rates below 16 Hz. In these studies, hearing-impaired listeners performed in between normal hearing and cochlear-implant users. Our hearing-aid simulation, however, showed longer reaction times for temporal modulations (at 0 cycles/octave) compared to the cochlear implant condition. It should be emphasized that our hearing-aid condition was based on a worst-case-scenario, simulating very little residual hearing, whereas hearing thresholds of the hearing-impaired listeners in the study of Other studies have shown a 5–10 dB reduction in the temporal-modulation detection threshold for cochlear-implant users compared to normal hearing , whereasImpaired spectral modulation sensitivity with a cochlear implant is a likely result of its band-pass filtering mechanism that limits the spectral information to a set number of spectral bands. To get insights in the mechanism of combining input at both ears, we used race models to test whether monaural responses could predict binaural performance. For normal-hearing conditions, faster reaction times were elicited when stimuli were presented binaurally compared to monaural presentation . BinauraBimodal responses were also as fast as the race model , suggestIn contrast to our results, several studies have shown reaction times to stimuli that exceeded the predictions based on statistical facilitation. However, these studies typically involved responses to multisensory stimuli, or to the dichotic presentation of two spectrally distinct sounds . Like thMeasuring the stMTF is typically a time-consuming process, for which it would be valuable to know whether the two-dimensional function is simply the product of a temporal and spectral component. A large degree of separability of spectrotemporal sensitivity has been found for normal-hearing listeners and cochlear-implant users . Our datAs can be appreciated from the observable differences between the single and two-component reconstructions , the secWe believe that a reaction-time paradigm could provide an alternative novel hearing test. This test potentially provides a description of acoustic sensitivity that is potentially closer to speech perception accuracy than pure-tone audiometry. Here, we demonstrated the convergent validity of the test by showing that the stMTF obtained from reaction times resemble the stMTFs obtained from standard detection thresholds . Earliersupplemental Figures S1-6) and separability indices with narrow confidence intervals . An advantage over a modulation-detection threshold paradigm is that stimuli can be presented at supra-threshold levels, allowing for a relatively easy task, potentially suitable for clinical assessments, and for studies with children, or with experimental animals. This is supported by the fact that we did not observe procedural learning effects during the experiments.The test is reliable across listeners, yielding highly similar stMTFs  or music. In fact, one can think of developing a framework that relates the sensitivity to the spectrotemporal modulations of the moving ripples to the recognition and pitch accuracy of speech materials such as phonemes and words . While bNumerous studies have shown that non-acoustic aspects, such as attention and reward expectation, could affect the spectrotemporal receptive fields of cells in primary auditory cortex . It woulReaction times are a valid objective measure for ripple sensitivity. The joint spectrotemporal transfer function closely resembled data from earlier studies that used modulation detection thresholds. Responses to spectrotemporal modulated ripples could be reconstructed by using the first two components of singular value decomposition, suggesting significant spectrotemporal inseparability, especially for the hearing-aid and bimodal listening conditions. We further found that binaural and simulated bimodal reaction times could be predicted from statistical facilitation induced by a race of independent monaural inputs.Click here for additional data file.Supplemental material, sj-docx-1-tia-10.1177_23312165221127589 for Reaction Time Sensitivity to Spectrotemporal Modulations of Sound by Lidwien C. E. Veugen, A. John van Opstal and Marc M. van Wanrooij in Trends in Hearing


Speech understanding disorders in the elderly may be due to peripheral or central auditory dysfunctions. Asymmetry of results in dichotic testing increases with age, and may reflect on a lack of inter-hemisphere transmission and cognitive decline.Aim: To investigate auditory processing of aged people with no hearing complaints.Study design: clinical prospective.Materials and Methods: Twenty-two voluntary individuals, aged between 55 and 75 years, were evaluated. They reported no hearing complaints and had maximal auditory thresholds of 40 dB HL until 4 KHz, 80% of minimal speech recognition scores and peripheral symmetry between the ears. We used two kinds of tests: speech in noise and dichotic alternated dissyllables (SSW). Results were compared between males and females, right and left ears and between age groups.Results: There were no significant differences between genders, in both tests. Their Left ears showed worse results, in the competitive condition of SSW. Individuals aged 65 or older had poorer performances than those aged 55 to 64.Conclusion: Central auditory tests showed worse performance with aging. The employment of a dichotic test in the auditory evaluation setting in the elderly may help in the early identification of degenerative processes, which are common among these patients. The increase in life expectancy is responsible for the growth in the elderly population throughout the world and, consequently, it has brought about different health care needs. Health care professionals who follow this population must understand the changes that happen with aging, and hearing is among them. Sensorineural hearing loss is a consequence of aging and it is one of the most prevalent chronic conditions affecting senior citizens, behind only arthritis and hypertensionPresbycusis is defined as hearing loss associated with aging, arising from the summation of factors which cause physiological degeneration. The changes stemming from aging involve mainly the inner ear and the central auditory pathways. This hearing loss happens to individuals starting in their fifth decades of lives, and the hearing sensitivity changes affect mainly the high frequencies. Structural changes to the auditory nerve and the central auditory pathways are associated with aging and cause important drawbacks in speech recognitionThe central structures, both the brainstem as well as the brain cortex are affecting the aged population. There can be a general loss of neurons, blood flow reduction, and reduction in glucose metabolism and oxygen consumptionThe prevalence of AP disorders increase significantly with aging. Differences between the ears, non-existent in the young population, increase with age. Such asymmetry can be justified by the progressive deterioration of the corpus callosum because of aging, causing a drop in the inter-hemispheric transfer efficiencyMore recent studies have considered that the age-related drop in cognitive functions, such as working memory, selective attention and information processing speed, have an important impact on the speech of elderly peopleThus, speech understanding problems in the elderly population may be caused by peripheral hearing loss, auditory processing (AP) disorders or drop in cognitive skills.Speech recognition difficulties increase when the signal is distorted, and the most common condition in these cases is the speech signal distortion by another competitive signal. Speech recognition in the presence of noise, dichotic competition and temporal processing are factors which may compromise speech understanding in the elderlyThere is a greater result variability concerning temporal processing in the elderly, in other words, such difficulty does not affect everyone in the same wayBecause of the large variability in the results found assessing the hearing in elderly patients, numerous authors have carried out studies with the aim of investigating the central hearing in this population, using auditory processing tests.The effects of aging in the execution of dichotic tests in individuals with symmetrical sensorineural hearing loss were studied in 30 young and elderly individuals. The tests used were the digits, vowel-consonant and the recognition of low redundancy phrases. The results show a worse performance in all these tests among the elderly. There was a poorer performance in the left side hearing when compared to the right side for the same group, showing the effects of chronological age in dichotic hearing testsQuintero et al. (2002) compared the performance of elderly individuals with normal hearing ones and those with symmetrical sensorineural hearing loss - characteristic of presbycusis, by means of disyllable recognition test in a dichotic task (SSW). They assessed 100 elderly individuals with ages varying between 60 and 79 years. The SSW test results showed an increase in the mean number of errors for most of the conditions assessed in the study group, and a greater percentage of errors when competitive noise was present, and the competitive left side was the condition with the greatest number of errors. The authors concluded that the sensorineural hearing loss is not a determining factor; however, it is a worsening factor of the difficulty in speech intelligibility in the elderlyPinheiro and Pereira, in 2004, carried out a study to characterize the verbal and non-verbal sounds interaction in elderly individuals with and without hearing loss, using Sound Location in Five Directions, Binaural Fusion and Pediatric Sentences Identification (PSI) tests. They assessed 110 normal hearing elderly and those with moderately severe sensorineural hearing loss. The results showed that only the Binaural Fusion test was changed in the population investigated, pointing to losses in the recognition of physically distorted verbal soundsA revision study on the masking of language information by competitive speech sounds concluded that elderly adults may have more interference in competitive speech when compared to young adults, with a need for a signal/noise ratio about 2.8dB higher than that for young people in speech recognition in the presence of competitive speechA retrospective survey was carried out in order to compare the Speech with Noise test performance of 55 elderly individuals. They analyzed performance in the SRI and Speech with Noise tests. The noise presentation resulted in a negative impact for the elderly without hearing loss. The authors concluded that the performance in the speech test cannot be justified only through their tonal thresholdsA study with the goal of analyzing the central auditory function efficiency in elderly patients who reported not having hearing difficulties assessed 40 patients with mean age of 68.2 years, without history of neurological disorders. The following tests were carried out: Synthetic Sentences Identification with ipsilateral competitive message (PSI), frequency pattern and SSW. The statistical analysis for the SSW test showed a statistically significant difference between the mean values of the percentage of correct answers under the RC and LC conditions. The authors argued that the changes arising from aging happen to the entire auditory nervous system, and they concluded that the prevalence of central hearing abnormalities show inefficiencies of the auditory function, even in elderly patients who report good hearingThe interference of different background noises in the speech processing of elderly individuals was studied assessing 24 individuals with symmetrical bilateral sensorineural hearing loss, with ages varying between 56 and 83 years. Word recognition tests in the presence of background noise were employed. The results show that with aging, individuals have lower capability of using the modulated noise intervals to recognize speechIn an attempt to establish which factors determine faster speech recognition in the elderly, the authors employed compressed speech tests in young and elderly patients alike. The data obtained suggest that information processing problems involve auditory and non-auditory areas. Information processing reduction is part of the problem senior citizens have to sustain speech understanding in situations when the signal is distortedOne study which investigated speech understanding in the elderly in the presence of competitive noise, by means of functional magnetic resonance, concluded that young adults proved to be more efficient in the hearing cortical areas  while the elderly have a more diffuse neural network involving frontal and ventral cerebral regionsThe conclusions of the aforementioned studies point to a worsening in the auditory processing of the elderly population, especially regarding speech in the presence of competitive noise and in dichotic hearing tests. They also indicate that there are difficulties in the speech recognition of the elderly, regardless of peripheral hearing loss. Nonetheless, the studies vary considerably in regards of the applied auditory processing test and the degree of sensorineural hearing loss accepted in the sample make up.With the aim of better understanding the auditory difficulties of the elderly population, this study investigated the auditory performance of elderly patients without auditory complaints in two auditory processing tests.This project was submitted to the Ethics in Research Committee of the institution where it was carried out, and it was approved under protocol # 8952/2004. All participants signed the free and informed consent form.We assessed 22 volunteers aged between 55 and 75 years, without hearing complaints. Besides the lack of complaints, the other criteria used to include patients in the sample were: no changes seen upon ear inspection; mild sensorineural hearing loss - at most, and symmetrical below 4000Hz; Speech Recognition Index (SRI) greater than 80% and no neurologic disorders or severe chronic diseases.The patients were submitted to a brief interview in order to confirm the sample inclusion factors, as well as ear inspection and tonal air conduction audiometry in the frequencies of 250 and 8000 Hz. For those patients with air hearing thresholds above 25 dB hearing level (HL), we carried out a bone transmission threshold test in the frequencies of 500 to 4000 Hz. Following that, we investigated the Speech Recognition Threshold (SRT), in order to confirm the air conduction threshold and the speech recognition index (SRI), done at 40 dB sensation level (SL), with the CD from the Central Auditory Processing Assessment Handbook, volume 1  The procedures used for study were the Speech with Noise test and the Alternate Dissyllable Dichotic (SSW) test.White Noise was presented ipsilateral in the signal to noise ratio of +5dB. The patients were instructed to repeat the words they heard and ignore the competitive noise.The Speech under Noise test was carried out using the D3 and D4 lists and the track 2 from the aforementioned CDIn order to perform the SSW tests, we used the track 6 from volume 2 of the Central Auditory Processing Assessment Handbook CDWe used the Madsen, Midimate 622 audiometer during the entire assessment.The results obtained were statistically analyzed by using the SAS® 9.1 software from PROC NLMIXED, in which we used the non-linear regression model with mixed effects. The analysis's goal was to compare genders, ears and age groups in the performance of the auditory processing tests..For all the calculations, the significance level was set at 5% Of the 22 individuals evaluated, 12 were females and 10 were males. Their ages varied between 55 and 75 years, and the mean age was 62.82 years, with a standard deviation of 6.23.The descriptive analysis of the tonal thresholds obtained from the population under study is presented on Data on Analyzing We used as normality criteria for the hearing processing tests, the patterns described in the literatureThe descriptive comparison between genders for the Speech under Noise and SSW tests, with the ears grouped is presented on (p = 0.23), SSW- non-competitive condition (p = 0.99) and SSW - competitive condition (p = 0.18).The statistical analysis did not show gender differences for any of the three situations analyzed, in other words, speech with noise Observing On p value < 0.01. The comparison between the right and left ears for the speech under noise test had p = 0.25 and for the SSW non-competitive, p= 0.39.The application of the comparative tests showed a statistical difference for the ears only in the competitive condition for the SSW test, and Considering the degenerative process arising from aging, which impairs performance in dichotic hearing tasks, and in the fact that the population studied had age distribution involving two decades of life, we chose do carry out statistical analysis of this population distributed in two age groups, in other words, one group with age varying between 55 and 64 years, called Group 1; and another group with ages between 65 and 75 years, called Group 2.Following, we present the results from the statistical analysis of the same population, with a new distribution. Group 1 (G1), made up of 14 individuals with mean age of 58.64 years; and group 2 (G2), with 8 individuals with mean age of 70.12 years.The SSW test descriptive analysis in the competitive and non-competitive conditions according to groups G1 and G2 and right and left ears are depicted on Also in 0.01), which leads us to conclude that G2 (elderly) had the worst results.The comparative analysis did not show statistically significant difference between the groups in the non-competitive conditions for the SSW test. Nonetheless, for the competitive condition we obtained a statistical difference between the groups . The statistical comparison of G1 ears, seen on (p = 0.09).In the comparison between the right and left ears from each group, we found a statistically significant difference only for G2 ((p = 0.01), once again pointing to better results in G1, when compared to G2.The comparison of the same ear between groups showed a statistically significant difference for the left ear (p < 0.01). When we compared the right and left ears within each group, we found a statistically significant difference for G2 only (p = 0.01). When we compared the same ear between the groups we found a statistically significant difference (p < 0.01), in which the right ear performance was worse for the higher age group.The comparison between age groups showed a statistical difference for the speech under noise test -As of the fifth decade of life, people begin to suffer the effects of aging on the central and peripheral auditory systems. Nonetheless, the differences arising from the body and/or the communication needs of each individual, make these progressive difficulties to be perceived very differently by peopleTo try to find people older than 60 years of age with hearing thresholds below 25 dB HL is not an easy task. Many who came and denied hearing and oral understanding differences had a descending-type hearing loss, even initially. Thus, it was very difficult to find a group of people in this age range without an air conduction threshold higher than 25 dB HL. Such fact made us abandon this initial criterion of sample composition and made us accept people with thresholds up to 40 dB HL in frequencies of 500 to 4,000Hz, as long as they did not report hearing difficulties.In our study, of the 22 individuals assessed, only 9 (40%) had thresholds higher than 25dB HL in all the frequencies bilaterally, 6 (27%) of them were below 65 years and only 3 (13%) were older than 65 years.Other studies involved elderly individuals without auditory complaints to make up the sample and also found the same difficulty. Sanchez et al. (2008), studied 40 elderly individuals and found only 20% of them with thresholds within normal parameters for all the frequenciesQuintero et al. (2002) found 50 people in the age range between 60 and 79 years with thresholds in all the frequencies of the audiogram lower than or equal to 5 dB HL. This study concluded that the sensorineural hearing loss cannot be considered a determining factor of the difficulties in speech intelligibility in the elderly in noisy or reverberating environmentsThe speech recognition index (SRI) above 80% in all the participants in the study justifies the absence of complaints as to speech inteligibility-Of all that has been said, we notice that peripheral hearing loss, even gradual, is not perceivable, since it starts in the elderly population and is in agreement with the extensive literature on the topicKnowing that the prevalence of auditory processing disorders grows with agingAs far as gender is concerned, we did not find performance differences for the tests studied. Other studies involving speech-under-noise testsInsofar as the differences between ears are concerned, we found asymmetry, in other words, a worse performance for the left ear only in the SSW competitive condition.The interaural differences increase with age and can be justified by the structural and cognitive models-The structural model proposed by Kimura (1961), justifies the perception asymmetry as follows: the information presented to the right ear travels directly to the left hemisphere. During dichotic stimulation, the ipsilateral auditory pathways are suppressed favoring the contralateral ones, which have a greater number of fibers. The left ear disadvantage is a product of the greater verbal information transmission time in this ear, since it has to be moved from the right hemisphere for its processing in the left hemisphere, through the corpus callosum. Therefore, the left ear requires greater corpus callosum participation in order to be efficient in language information processing. In the case of the elderly, this central nervous system structure suffers the natural deterioration of aging and its performance drops, causing the ear asymmetry hereby observedbottom-up). On left-side hearing (dichotic task), the stimuli are naturally suppressed by stimuli in the right ear. In order to serve the need for directing listening to the left, it is necessary to have a greater activation and involvement of the cognitive function (top-down). Since these functions deteriorate with aging, the ear asymmetry can be seen during dichotic tests given to the elderly-The cognitive model emphasizes the importance of attention, working memory and information processing speed in the dichotic hearing tasks. Because of the left hemispheric dominance for speech processing, most people have dominance as to the stimuli heard on the right side, which allows them to predominantly use a more automatic acoustic processing of the stimuli  seems to corroborate what is published in the literature, and it can be considered a reflex of aging.The separation of this same population in two age groups brought us new evidence that the advancement of age makes the sound signal processing deteriorate, since the comparisons between the younger group (G1) and the elderly (G2) have statistically significant differences in the two tests investigated, both in the monotic as in the dichotic tasks. Such findings bring us back to the existence of neuronal losses which are common to agingIn the SSW non-competitive test, a situation in which one hears a word alone, without any type of sound competition, the performance from the participants of the two groups was similar and with correct answers indexes close to those from young adultsThe aforementioned information makes us consider that: age-related changes happen to the entire central nervous auditory system; the prevalence of auditory changes show the inefficiency of the central auditory functions even in elderly people without complaintsThe last discussion to which the data from this study refer to is the worse right ear performance in the speech test with noise in both groups (G1 and G2). The literature states that there is a worsening in the speech intelligibility of the elderly when exposed to noisy environmentsAge caused a worsening in the performance of the elderly in the Speech-under-noise and alternate disyllable dichotic (SSW) tests, regardless of a hearing complaint.The left ear has a worse performance when compared to the right one in dichotic tests, which can be associated to central auditory pathway and cognitive functions deterioration associated with aging.The introduction of the dichotic test to the audiological battery of tests in the elderly with and without peripheral auditory loss may contribute to the identification of the degenerative process and, consequently, for the creation of intervention strategies before they interfere in the communication skills of these individuals.


Past five years of age, the main complaint of children who are hard of hearing is that they have difficulty in learning.Compare these results to suspected hearing loss, through triage with the exams of evoked otoacoustic emissions (EOAE) transients (TEOAE) and by distortion product (DPEOAE), using data from audiometric exams; observe which of the procedures of EOAE better respond to school children triage.To evaluate 451 school children, grade one students, from the public schools in São Luís. At school, otoscopic exams with the removal of wax and the TEOAE and DPEOAE exams were also carried on all school children. Audiometry and acoustic impedance were performed on the children who presented alterations at any point during the TEOAE and/or DPEOAE exams.Transversal- Prospective.18.6% had ear wax. As for the TEOAE and DPEOAE triage, no significant statistic difference was found when comparing the results of the exams which failed only in the TEOAE and DOEOAE with audiometric exam data, nonetheless, when comparing this failure data to both of these exams there was a significant difference (p<0.05).Both EOAE procedures responded well to the hearing triage in school children. Hearing problems may be missed by parents and teachers; therefore it is important to systematize educational, preventive and hearing loss curative programs in order to mitigate and/or to avoid possible auditory sequelae that may impair the person's school performanceHearing assessment can be carried out by means of objective tests, such as otoacoustic emissions (OAE), immittance studies, and subjective tests such as tonal and vocal audiometry.OAE is a low intensity sound energy which is amplified by the contraction of cochlear outer hair cells, which may be detected in the external ear canal. They were discovered in 197 by the hearing biophysics professor Dr. David T. Kemp from the University College, in London. They can be classified in: spontaneous - if recorded in the external acoustic meatus in the absence of sound stimuli; evoked - when energy is recorded in the external ear canal in response to a sound stimulusEvoked otoacoustic emissions (EOAE) are classified in transient (TEOAE) - evoked by a brief sound stimulus, usually a broad spectrum click that encompasses a wide range of frequencies; distortion product (DPOAE) - evoked by two pure simultaneous tones (f1 and f2) that through intermodulation produce a distortion product response (2f1- f2); stimulus-frequency (SFEOAE) - evoked by a continuous and low intensity signal, these are less used clinically because their recording brings about much technical difficulties and the testing time is longerEOAE are recorded in most normal hearing individuals, regardless of age and gender. Its presence indicates that the cochlea is intact, and it may tell if the hearing of a given ear is within normal ranges. Screening with otoacoustic emissions present less false positives and less false negatives. It is a fast, reliable and non-invasive test; therefore making it the ideal test for screening purposesMiddle ear immittance study - immitanciometry - offers a large number of practical applications. It provides somewhat accurate information about the health of the tympano-ossicular apparatus, enabling the differential diagnosis among purely sensorineural, conductive and mixed hearing lossAudiometry is the method that introduces this Idea of metrics in audiology. Its goal is to establish the hearing threshold in each frequency. The electrical audiometer emits pure sounds of known and variable frequencies, usually between 125 and 8,000 hertz (Hz), at the same time, for each sound type, it produces known and variable intensitiesOur study tried to assess auditory alterations in school aged children through two otoacoustic emission procedures, in order to avoid, as much as possible, false positive and false negative values, and also be able to observe which of the two procedures would be better to screen school aged-children, since we found in the literature only five papers discussing the use of otoacoustic emissions in the auditory screening of school-aged childrenThis study was carried out after being authorized by the Ethics in Research Committee (CEP) of the University Hospital (protocol # 0795/04) and the Secretaria Municipal de Educação em São Luís  - MA .We held a cross-sectional prospective and observational study in school-aged children of the first grade from 19 elementary schools of the São Luiz Public Education System, from August 1st through December 15 of 2005. We randomly selected 19 schools from the 52 public elementary schools of the São Luís urban area, and from each school we randomly selected 30 students, making up a total of 16,122 children from the 1st grade of the public elementary school system of São Luiz, data were collected at the Municipal Secretariat of Education of São Luiz.First, we arranged with the schools’ principals to deliver a letter with authorization from the Municipal Secretariat of Education. At this point we explained them the importance of that research Project and we asked if we could use the library or a study room with the minimum possible noise level in order to carry out the hearing tests.The Otorhinolaryngologist performed an otoscopic exam (Heine Otoscope), to check for alterations in the external ear canal and the ear drum.Ear wax was removed for a better performance of the otoacoustic emissions test. When the children had hard or impacted ear wax, the parents or guardians were instructed to drop a wax softening solution in their ears for about seven days and later the wax was removed.After otoscopy and recording of the findings, the children were submitted to evoked otoacoustic emissions, commonly used in the clinical setting . Standard equipment software was used in order to record the emissions, both the transient and the distortion product.After hearing screening through otoacoustic emissions, the students who failed the exam at any point were referred to audiometric exam. For such evaluations, a sound treated booth from Vibrasom was used, and a GSI68 audiometer, calibrated in July of 2005 and an AZ7 immitanciometry device from Inter Acustics, calibrated in July of 2005.Audiogram findings interpretation, as well as the characterization of clinical findings regarding the type of hearing loss were based on the criteria established by Russo and SantosThe values were presented in integers and relative numbers. The statistical analysis was carried out by the chi-squared test, with the Yates correction when necessary, and by the Fisher's exact test, considered significant when p < 0.05.We assessed 454 school-aged children between 6 and 11 years of age, 219 (48.0%) were females and 235 (52.0%) were males.The otoscopic exam was carried out in 908 ears, of which 169 (18.6%) had impacted wax, and they all used wax softening ear drops for later ear washing and otoacoustic emission test, according to Of the 451 school aged-children submitted to otoacoustic exam - since in three of them it was not possible to remove the wax, 402 (89.0%) did not show alterations and 49 (11.0%) had some uni or bilateral failure, 232 were males with 31 (7.0%) alterations, and 219 were females, with 18 (4.0%) of alterations, there were no significant difference between the genders (p > 0.05), according to When we analyzed the tests considering ear alterations, 818 (90.6%) ears passed and 84 (9.4%) ears failed transient otoacoustic exams (TEOAE); and in the ears that went through distortion product otoacoustic emissions (DPOAE), we observed 849 (94.0%) ears that passed and 53 (6.0%) ears that failed this type of emission, according to Of the 32 (3.9%) ears that failed, only the TEOAE were submitted to audiometry, and we found 9 (1.0%) with auditory alterations and 23 (2.9%) with normal audiometric exam. There was only 1 (0.1%) ear that failed DPOAE metric exams, the most frequent alteration found was the conductive type, in 56 ears (92.0%), followed by the sensorineural and the mixed types. The differences between these frequencies were significant (p < 0.05). We did not only, and when submitted to audiometry this ear presented normal values. When we compare the 52 (6.0%) exams that showed failure in both procedures (TOAE+DPOAE) they all had altered audiometry .Graph 1RIn comparing results from the audiometries of children who failed only the TOAE, with those who failed both procedures (TOAE+DPOAE), we found a statistically significant difference (p < 0.05).In comparing results from the audiometries of children who failed only distortion product otoacoustic emission with those who failed only DPOAE, with data from the audiometries, there were no statistically significant differences (p < 0.05).When we compared the tests that failed only TOAEs with those that failed only the DPOAEs, with audiometric tests, there was no statistically significant difference (p > 0.05).As to the types of hearing loss found in the audio-observe any alterations between the hearing loss and the ear side (p > 0.05). Both sides presented similar frequencies in the same alterations, according to Evoked otoacoustic emissions are recorded from all individuals whose auditory thresholds are better than 20-30 dB HL, its presence may confirm cochlear integrity, establishing whether the otoacoustic activity of a given ear is within normal limits, and the occasional lack of otoacoustic emissions in normal ears may happen in special clinical situations, caused by anatomical alterations in the external auditory canal, or in the middle ear, or to problems associated with the equipment or the excess of environmental noiseAccording to the literature, transitory otoacoustic emissions (TOAE) are recorded in about 90% of the individuals with normal hearing and are more effective in the range of 1000 to 4000 Hz and with people with hearing levels between 0 and 25 dB HLFrazzaWe observed that a greater impediment to acquiring otoacoustic emissions in this paper was longer response times or no response at all, depending on the noise level and the child's breathing.We did not find significant differences in relation to gender, and this is different from the research carried out by Dell’Aringa et al.In relation to distortion product otoacoustic emissions (DPOAE), they are found in almost 100% of normal individuals; however, it is possible to observe a response in people with sensorineural hearing loss up to 45dB HLDell’Aringa et al.We found a rate of 85 ears (9.4%) which failed the EOAE and this rate drops to 61 (6.8%) when we compare it with the results from audiometric tests. We found 2.5% of false positives in TOAEs; and 0.1% of false negatives in DPOAE.When we do a statistical comparison between the exams that failed only the TOAE and DPOAE with the results from audiometric exams we did not find any significant difference. However, when compared to the ears that failed both types of otoacoustic emissions (TOAE+DPOAE) with data from the audiometric exams we found significant differences.We found 18.6% of ear wax in the school aged children. When the wax was excessive and impacted, it can cause considerable hearing loss in humans. The rate of children with ear wax in the literature varies between 12 and 52%In relation to the hearing loss seen in school-aged children after audiometry, we observed a higher rate of conductive hearing loss, in agreement with the literatureWe showed that transient and distortion product otoacoustic emissions enable us to identify sensorineural and conductive hearing loss and, therefore, both one and the other can be considered as a procedure of choice for hearing screening in school-aged children.


COMT and hearing loss has not been reported previously in nationally representative population-based studies. A regression linear model was used to estimate associations between the allele/genotype of COMT and self-reported hearing loss based on 13,403 individuals from Wave IV of the Add Health study, a nationally representative sample of multiethnic U.S. young adults. The inverse variance-weighted effect magnitude was estimated using a genetic meta-analysis model. The “A” allele frequency of rs6480 (a missense variant in COMT) was 0.44. The prevalence of hearing loss was 7.9% for individuals with the “A” allele and 6.5% for those with the “G” allele. The “A” allele was significantly associated with increased hearing loss (p = 0.01). The prevalence of hearing loss was 6.0%, 7.2%, and 8.7% for individuals with GG, AG, and AA genotypes, respectively, which was consistent with a genetic additive model. The genotypic association model showed that rs4680 was significantly associated with increased hearing loss (p = 0.006). A missense variant of rs4680 in COMT was significantly associated with increased hearing loss among young adults in a multi-racial/ethnic U.S. population-based cohort.Hearing loss is a major public problem with a heritability of up to 70%. Catechol-O-methyltransferase (COMT) encodes an enzyme that is highly expressed in sensory hair cells of the inner ear. The association between  Hearing loss is a major public health problem with an estimated 1.57 billion people worldwide with hearing loss in 2019, accounting for one in five people. It was the third largest cause of global years lived with disabilities (YLD) and the leading cause of global YLDs for adults older than 70 years ,4,5,6. TThe etiology of hearing loss is multifactorial and includes genetic factors, environmental factors, and their interaction. Many genetic variants are associated with hearing loss ,9. The hCOMT) allele is nonsynonymous with a guanine (G) to adenine (A) substitution in the DNA nucleotide sequence resulting in a valine  to methionine (Met) amino acid substitution. rs4680 G > A influences COMT enzyme activity , which catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines that play a key role in auditory function [COMT has been associated with cisplatin-induced hearing loss in children [www.internationalgenome.org). The association between rs4680 and hearing loss has not been reported previously in population-based studies.We examine the association of hearing loss with selected allelic haplotypes. For example, catechol-O-methyltransferase (COMT) encodes an enzyme that is involved in the inactivation of catecholamine neurotransmitters and is highly expressed in sensory hair cells of the inner ear . COMT hafunction . A genetchildren ,17. BothThe self-reported hearing loss questions in the Add Health Study provide a useful measure for genetic studies ,11,18. IThis study was based on data collected from Add Health, an ongoing, nationally representative longitudinal study, which covered the social, behavioral, and biological linkages in health and developmental trajectories from early adolescence into adulthood . The adoThe question was, “Which statement best describes your hearing without a hearing aid or other assistive devices? Response options: 1. Excellent; 2. Good; 3. A little trouble; 4. Moderate hearing trouble; 5. A lot of trouble; 6. Deaf.” Hearing loss was defined by any of the following four responses: “a little trouble”, “moderate hearing trouble”, “a lot of trouble”, and “deaf”.https://addhealth.cpc.unc.edu/documentation/user-guides/ (accessed on 19 October 2022).Biological specimens  in Wave IV of the Add Health study were collected from a large, nationally representative sample of young adults by trained and certified field interviewers. Salivary buccal cell lysis and DNA stabilization were performed in the field and shipped to a central lab for DNA extraction, genotyping, and archiving . The col® OpenArray® or Illumina BeadXperss® GoldenGate® platform. The Hardy Weinberg equilibrium (HWE) was evaluated for each allele genotype in race/ethnicity-specific strata. HWE p value < 0.05 and Minor Allele frequency (MAF) < 0.01 were used for QC.All SNP assays were conducted on either an Applied Biosystems TaqManTo evaluate the association between hearing loss and the SNP allele/genotype, a logistic regression model was performed, adjusting for sex, age, family income, smoking status, and education levels. Three genetic models  were used to evaluate the genotypic association, respectively. The association testing was performed by racial/ethnic groups. Before the logistic regression, we examined the data for influential observations and the presence of variance inflation. No influential observations or multicollinearity was found. The R package of meta was used for meta-analysis with an inverse variance-weighed fixed effects method  in combihttps://zhanggroup.org//I-TASSER/, accessed on 19 October 2022) [From a paradigm of protein sequence-to-structure-to-function, we uploaded translated sequences (amino acid sequences) to the I-TASSER online server (er 2022) ,27,28 toer 2022) . PyMol [er 2022)  was usedp < 0.001). The prevalence of hearing loss in males was significantly higher than in females. Participants with a higher education had a significantly lower prevalence of hearing loss (p < 0.001), and, concomitantly, those with a lower household income had a significantly higher prevalence of hearing loss .A total of 13,403  adults were included in the study . The preMinor allele frequencies (MAF) were 0.45 (“A”), 0.26 (“A”), and 0.29 (“T”) for rs4680, rs1800497, and rs12945042, respectively. The prevalence of hearing loss for individuals who carried minor alleles was higher than for individuals who carried major alleles  for rs46COMT) was significantly associated with a higher prevalence of hearing loss (β (95% CI) = 0.13 , p = 0.010, The rs4680  is a missense variant from a guanine (G) to adenine (A) substitution in the DNA nucleotide sequence resulting in a valine  to methionine (Met) amino acid substitution at the position 158. I-TASSER predicted the possible protein structure based on an amino acid sequence with V158M. The predicted protein structure was different from the wild type a–c with COMT, Gene ID: 1312) is associated with an increased prevalence of hearing loss.Add Health is an ongoing, nationally representative longitudinal study of social, behavioral, and biological factors in health and developmental trajectories from early adolescence into adulthood. The participants in Wave IV were 24–32 years old. We analyzed associations between hearing loss and three measured single nucleotide polymorphisms (SNPs) in three candidate genes. We found that rs4680  is nonsynonymous with a guanine (G) to adenine (A) substitution in the DNA nucleotide sequence resulting in a valine  to methionine (Met) amino acid substitution. rs4680 G > A influences COMT enzyme activity  [COMT variant, rs4818, which has an association with cisplatin-induced hearing loss and confers an 11-to-18-fold reduction in COMT protein levels due to alterations in the mRNA secondary structure [2~0.70 [nner ear . In addictivity) ,32. A mactivity) . An enzyctivity) . Two intctivity) . The haptructure . The mis [2~0.70 . This su [2~0.70 .Following the discovery of genetic association, function studies are a critical next step. Based on the sequence-to-structure-to-function paradigm, I-TASSER was developed as an online platform for protein structure and function prediction . The ideCOMT. Importantly, the self-reported hearing loss question used in the Add Health study is identical to the phrasing of the question on reported hearing loss that is used and analyzed in other major U.S. population-based health surveys [One potential limitation of this study is that self-reported hearing loss was used to estimate the association with a missense variant in  surveys . In popu surveys . InvestiIn summary, we analyzed data from Wave IV of Add Health, a population-based longitudinal cohort study, and identified a missense variant, rs4680 G > A, which was significantly associated with an increased prevalence of hearing loss. Compared to the wild type, this missense variant led to a protein structure change that may cause hearing loss through an increase in S-adenosylmethionine levels resulting from a reduced COMT activity.


With the rapidly aging world population, Japan has many older people with difficulties in maintaining oral health. This study aimed to investigate the relationship between dietary hardness score and performance of activities of daily living (ADL) of 90‐year‐old individuals in rural areas of Japan.A total of 236 individuals (64 men and 172 women) aged 90 years in Mitsugi town, Hiroshima, Japan, were included. Assessment of oral status and survey of ADL were performed. The association of ADL with dietary hardness score and the number of remaining teeth was determined.The mean dietary hardness score was 8.3 ± 2.6. Eighty individuals showed independence in ADL, whereas 156 individuals showed dependence. Logistic regression analysis, adjusted for potential confounding factors, showed that dietary hardness score was associated with ADL status but not the number of remaining teeth.Our findings suggest that a low dietary hardness score is associated with dependence on ADL in 90‐year‐old individuals. Severe decay or tooth stump was not included in the remaining teeth.The following factors were considered possible confounders influencing dietary hardness score, the number of remaining teeth, and ADL: participants' sex (men or women), smoking history (smoker or nonsmoker), dry mouth , and mouth rinsing (possible or impossible).2.5t‐test. Categorical data were analyzed using Fisher's exact test or χ2 test. After the data were adjusted for various confounding factors such as sex, smoking, dry mouth, and mouth rinse status, we calculated odds ratios and 95% confidence intervals for dependent ADL status using logistic regression analysis. All collected data were analyzed using JMP Pro 13 . The level of significance was set at p = .05.All data are presented as mean ± standard deviation. Differences in continuous data were analyzed using Student's 3± 9.2. The mean dietary hardness score was 8.3 ± 2.6. ADL status was identified in all participants: 80 were independent and 156 were dependent. The mean dietary hardness score was 9.4 ± 1.6 in independent participants and 7.7 ± 2.9 in dependent participants, and it was significantly different in independent than in dependent participants (p < .001). Individuals with high dietary hardness scores were more likely to be independent of ADL .The mean number of remaining teeth was 8.3 Logistic regression analysis showed that high dietary hardness score was negatively related to dependent ADL status after adjustment for possible confounding factors Table . The pre4This study investigated the relationship between oral status  and ADL status among 90‐year‐old individuals. We found that dietary hardness score based on subjective assessment was related to the ability to perform ADL. A previous study suggested that poor dentition may be related to the deterioration of the systemic health of aged individuals  and physical ability were associated in an 80‐year‐old population (Takata, Ansai, Awano, Sonoki et al., Potential limitations of this study should be noted. First, we could not include multiple variables because of the small number of participants. Our surveys were performed in a rural area in Japan; hence, it was difficult to recruit more 90‐year‐old participants. More participants should be recruited in future studies to prevent sampling bias. Second, further studies are needed to assess the association between dental status and nutrition. Finally, data on some important factors related to mastication, such as temporomandibular joint disease, periodontitis, and denture status, were not included. Further studies should include these factors.5In conclusion, self‐assessed dietary hardness score, and not the number of remaining teeth, was associated with ADL status in 90‐year‐old individuals.The authors declare no conflict of interest.Supplementary information.Click here for additional data file.


The goal of this study is to investigate the effects of HGT on the growth performance, immune function, and antioxidant capacity of yellow-feather broilers. From our findings, the supplementation of HGT in the diet of broilers has no adverse impact on their growth performance, and the diet supplemented with 450 mg/kg HGT is found to improve immune and antioxidant functions of broilers.Tannins were traditionally considered as anti-nutritional factors in poultry production. Recent studies found that the addition of hydrolyzed gallotannin (HGT) could improve animal health; however, the proper dosage of HGT in chickens’ diet is still unknown. Hence, our study aims to recommend its optimal dose by exploring the effects of HGT from Chinese gallnuts on the growth performance, immune function, and antioxidant capacity of yellow-feather broilers. A total of 288 male yellow-feather broilers (34.10 ± 0.08 g) were randomly allocated to four diet treatments, the basal diet with 0 (CON), 150, 300, and 450 mg/kg HGT for 63 days, respectively, with six replications per treatment and 12 birds per replication. The growth performance, slaughter performance, immune organ index, liver antioxidant-related indicators, and serum immune-related factors were evaluated. Results show that HGT supplementation did not influence the growth performance of broilers, but the diets supplemented with 300 and 450 mg/kg HGT increased the semi-eviscerated rate. Furthermore, HGT increased the content of liver T-AOC and the ratio of GSH/GSSG, which can protect against oxidative damage of birds. Additionally, supplementing HGT raised the contents of serum IL-10, IL-4, IL-6, IgA, and IgM. In conclusion, diet supplemented with 450 mg/kg HGT may be the optimal to the health of yellow-feather broilers on the whole. Over the past decades, antibiotics have been used as feed additives in poultry production to promote growth performance and gut health . HoweverEimeria spp. oocyst excretion and an anti-inflammatory effect on the small intestine were observed after dietary supplementation of a mix of chestnut and quebracho tannins in the rabbit diet [Tannins are secondary metabolites produced by plants and consist of two forms, hydrolysable and condensed tannins . Hydrolybit diet . As for bit diet  reportedbit diet  revealedThe one-day-old yellow-feather broilers employed in this research were offered by WENS Foodstuff Group Co., Ltd. . The HGT product was provided by Fengjiu Biotechnology Co., Ltd.  and the content of available HGT is 50%, with rice hull as the carrier. Feedstuffs for the broiler diet were offered by Fujian Jinhualong Feed Co., Ltd. . The experiment was carried out in the Poultry Experimental Station of Fujian Agriculture and Forestry University. All management and experimental procedures followed the animal care protocols approved by the Fujian Agriculture and Forestry University Animal Care and Use Ethics Committee . A single-factor completely random test was conducted in this research. A total of 288 one-day-old male broilers (34.10 ± 0.08 g) were randomly allocated into four groups: (1) corn–soybean-based diet (CON), (2) CON diet supplemented with 150 mg/kg HGT, (3) CON diet supplemented with 300 mg/kg HGT, and (4) CON diet supplemented with 450 mg/kg HGT, with six replications per group and 12 birds per replication. The doses of HGT were selected according to several previous reports and the recommended dose of the manufacturer ,15,16. T2/bird) with 23 h of light and 1 h of dark in a day, and ad libitum feeding and water intake. The temperature was 35 °C initially and then lowered by 2–3 °C weekly, gradually decreasing to 22 °C until the end of the trial. Additionally, the poultry units were well-ventilated. Immunization with Infectious Avian Influenza Vaccine on Day 5 and vaccination against Newcastle disease on Day 10 and Day 20 were conducted. Meanwhile, the health and mental status of the chickens were observed daily.The diet composition and nutrient levels of basal diets are shown in Each replication was weighed on Day 1 and Day 63 and feed intake was recorded every day. Average daily gain average (ADG), daily feed intake (ADFI), and feed conversion ratio (FCR) were calculated for 1–63 d.g for 10 min to collect serum samples, which were stored at −20 °C until analysis. The liver samples were collected and stored at −80 °C for antioxidant-related indicator detection. Two broilers from each replication were sacrificed after 12-h fasting on Day 63 to detect slaughter performance and immune organ index. One broiler from each replication was chosen to detect the antioxidant and immune function. The blood was collected from the basilic vein, left at room temperature for 2 h, then centrifuged at 1450× The sacrificed birds were manually dissected to determine dressing percentage, semi-eviscerated yield, eviscerated yield, breast muscle yield, and thigh muscle yield. All indexes were calculated as follows: (1) dressing percentage (%) = dressed weight (g)/live weight (g) × 100%; (2) semi-eviscerated yield (%) = semi-eviscerated weight (g)/live weight (g) × 100%; (3) eviscerated yield (%) = eviscerated weight (g)/live weight (g) × 100%; (4) breast muscle yield = breast muscle weight (g)/eviscerated weight (g) × 100%; and (5) thigh muscle yield (%) = thigh muscle weight (g)/eviscerated weight (g) × 100%.The immune organs of 63-day-old broilers, such as spleen, thymus, and bursa of Fabricius, were also collected and weighted. The calculation formula of the immune organ index was as follows: immune organs indexes (%) = immune organ weight (g)/live weight (g) × 100%.g for 20 min at 4 °C. Finally, supernatant was collected for measuring the concentration of total protein using a BCA protein quantitative kit purchased from New cell § Molecular Biotech Co., Ltd. . The contents of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), and oxidized glutathione (GSSG) were determined by available assay kits from Enzymatic Biotechnology Co., Ltd. , and the ratio of GSH/GSSG was calculated to evaluate glutathione redox status. The absorbance was detected by the iMark™ Microplate Absorbance Reader .The liver was isolated on an ice tray, fully homogenized with cold PBS (pH = 7.4), with a weight-to-volume ratio of 1:80, and then centrifuged at 1000× The levels of immunoglobulin (IgA and IgM) and the concentration of Interleukin-10 (IL-10), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interferon-gamma (IFN-γ) in serum were measured using ELISA kits purchased from Enzymatic Biotechnology Co., Ltd. , and the absorbance was detected by the iMark™ Microplate Absorbance Reader . p ≤ 0.05.The raw data were preliminarily processed by Excel 2019 software. The experimental data were analyzed via one way-ANOVA analysis. Duncan’s multiple comparison was conducted to analyze the differences between groups by using the SPSS 25.0 software. The linear and quadratic comparisons were applied to determine the dose effect of HGT on broilers. Significant difference exists when The effect of HGT on the growth performance of broilers is presented in p ≤ 0.05). Additionally, the semi-eviscerated rate linearly increased with an increasing dietary HGT level (p = 0.004). However, dressing percentage, total evisceration yield, leg muscle yield, and breast muscle yield were not significantly different between groups.The effect of HGT on slaughter performance is presented in As shown in p ≤ 0.05). HGT supplementations of 150 or 300 mg/kg could obviously increase liver GSH/GSSG (p ≤ 0.05). However, there were no special effects of HGT treatment on the contents of liver SOD, GSH-PX, GSH, CAT, and MDA.The effect of HGT on the liver antioxidant function is presented in p ≤ 0.05), and IL-10 content linearly increased with an increasing dietary HGT level (p = 0.001). Additionally, the contents of serum IL-4, IL-6, IgA, and IgM in birds supplemented with 450 mg/kg HGT were higher than the CON group (p ≤ 0.05), and linearly increased with an increasing dietary HGT level (p ≤ 0.05).The effect of HGT on serum immune-related factors is presented in Traditionally, tannins were defined as anti-nutritional factors in poultry production and had negative effects on the digestibility of nutrients and the growth performance of broilers . HoweverSlaughter performance is an important index to assess the production performance of livestock and poultry. High abdominal fat content of broilers has a negative effect on the processing of meat products and the purchase desire of consumers . Based oThymus, spleen, and bursa of Fabricius are important immune organs for poultry, and their organ indexes can reflect the growth and development status and immune function to some extent . Both thMycobacterium, thereby effectively alleviating the inflammatory response of mice [Cytokines play an important role in regulating immune responses. IL-1β and IFN-γ are proinflammatory cytokines produced by a variety of immune cells . IL-10 i of mice . Further of mice . Similar of mice  demonstr of mice ,35,36.Immunoglobulins are a category of immunoactive molecules binding specifically to antigens and removing them by sedimentation and phagocytosis. In the domestic chicken, immunoglobulins mainly include IgG, IgA, and IgM . 250 andE. tenella infection.The antioxidant capacity can reflect the bodily function to scavenge free radicals accumulated in cells and tissues to avoid oxidative damage . The antThe antioxidant role of phenolic compounds mainly benefits from their reductive properties, which enable them to act as reducing agents, proton donors, and singlet oxygen quenchers . As a kiTo conclude, dietary supplementation with 450 mg/kg of HGT had a positive impact on the slaughter performance of yellow-feather broilers. No differences were detected on growth performance; however, some beneficial changes in liver antioxidant capacity and immune function were observed. All the results indicate that HGT might be a new functional additive on yellow-feather broiler production.


Cdkl5-KO male mice and primary hippocampal neurons and found that CDKL5 interacts with gephyrin and collybistin, two crucial organisers of the inhibitory postsynaptic sites. Through molecular and electrophysiological approaches, we demonstrated that CDKL5 loss causes a reduced number of gephyrin puncta and surface exposed γ2 subunit-containing GABAA receptors, impacting the frequency of miniature inhibitory postsynaptic currents, which we ascribe to a postsynaptic function of CDKL5. In line with previous data showing that CDKL5 loss impacts microtubule (MT) dynamics, we showed that treatment with pregnenolone-methyl-ether (PME), which promotes MT dynamics, rescues the above defects. The impact of CDKL5 deficiency on inhibitory neurotransmission might explain the presence of drug-resistant epilepsy and cognitive defects in CDD patients. Moreover, our results may pave the way for drug-based therapies that could bypass the need for CDKL5 and provide effective therapeutic strategies for CDD patients.CDKL5 deficiency disorder (CDD) is an X-linked neurodevelopmental disorder characterised by early-onset drug-resistant epilepsy and impaired cognitive and motor skills. CDD is caused by mutations in cyclin-dependent kinase-like 5 (CDKL5), which plays a well-known role in regulating excitatory neurotransmission, while its effect on neuronal inhibition has been poorly investigated. We explored the potential role of CDKL5 in the inhibitory compartment in  CDKL5) gene cause a severe neurodevelopmental disorder , commonly referred to as CDKL5 deficiency disorder (CDD). CDD patients are characterised by intellectual disability, autistic features and drug-resistant epilepsy that normally manifest within the first three months of age  and incubated overnight at 4 °C with 1 µg of anti-CDKL5 or unrelated IgGs as control. The immunocomplexes were precipitated with protein-G agarose (Life Technologies), washed several times with lysis buffer and analysed by SDS-PAGE and western blotting.2+/Mg2+, followed by incubation with 0.5 mg/mL of Sulfo-NHS-SS-Biotin (Cyanagen). Quenching was performed using HBSS/Ca2+/Mg2+ supplemented with glycine (50 mM) and BSA (0.5%), after which cells were lysed with standard radio-immunoprecipitation assay (RIPA) buffer . After correction for protein content using a BCA protein assay kit (PierceTM), biotinylated proteins were purified on StreptAvidin UltraLink Resin (PierceTM) and resolved by SDS-PAGE and western blotting. Surface expression was evaluated as the ratio between the biotinylated fraction (surface) and the total cell lysate normalised with GAPDH.Biotinylation assays were performed according to previously described protocols ,49 with 2) using the Axopatch 200B amplifier and the pClamp-10 software (Axon Instruments). Recordings were performed in Krebs’-Ringer’s-HEPES (KRH) external solution . Recording pipettes were pulled from glass capillary (World Precision Instrument) using a two-stage puller (Narishige) and had tip resistances of 3–5 MΩ when filled with the intracellular solution . Voltage-clamp recordings were performed at holding potentials of +10 mV. The recorded traces were analysed using Clapfit-pClamp 10 software, after choosing an appropriate threshold. In particular, events that exceeded at least twice the standard deviation of the baseline noise were considered as mIPSCs and included in our analyses.GABA-mediated inhibitory postsynaptic currents in miniature (mIPSCs) were recorded using the patch-clamp technique in the whole cell voltage-clamp configuration in the presence of 1 µM tetrodotoxin  to block the generation of action potentials. Recordings were obtained from primary hippocampal neurons at DIV14 , and all values were expressed as the mean ± SEM. Data that were identified as significant outliers by the software were removed from the datasets. The significance of the western blotting and immunofluorescence results was evaluated using Unpaired Student’s


Beauveria bassiana (Bb) is used to control the red palm weevil (RPW) Rhyncophorus ferrugineus (Oliver). Beuveria bassiana can infect and kill all developmental stages of RPW. We found that a solid formulate of B. bassiana isolate 203 , obtained from naturally infected RPW adults, repels RPW females. Fungi, and entomopathogens in particular, can produce volatile organic compounds (VOCs). VOCs from Bb203 were analyzed using gas chromatography-mass spectrometry (GC-MS). GC-MS identified more than 15 VOCs in B. bassiana not present in uninoculated (control) formulate. Both ethenyl benzene and benzothiazole B. bassiana VOCs can repel RPW females. Our findings suggest that B. bassiana and its VOCs can be used for sustainable management of RPW. They could act complementarily to avoid RPW infestation in palms.The entomopathogenic fungus  Rhynchophorus ferrugineus (Coleoptera: Dryophthoridae) is the most serious insect pest for date palms [Phoenix datylifera L.) and canary palms (Phoenix canariensis Chabaud) are economic palms and important in Spain. These species of palms are most abundantly planted in the main tourist resorts in the Mediterranean coastal region from North to South of Spain .The red palm weevil (RPW), te palms ,2. Date RPW infestations in Alicante Province  now affect the UNESCO heritage palms in the cities of Elche and Alicante, Southeastern Spain. In Spain, the economically feasible method to control RPW is by using pesticides and pheromone traps. Excessive use of insecticides causes development of resistance in insect targets and environmental pollution . The masRPW invasion and spread is due to its searching behaviour for food ,6, matesVolatile organic compounds (VOCs) are carbon-based solids and liquids that enter the gas phase by vaporizing at 20 °C and 0.01 kPa . VOCs apMuscodor vitigenus produces naphthalene, also known as “mothballs,” which are used as insect repellents [Muscodor albus VOCs inhibit Spodoptera exigua egg-hatching and are insecticidal [Cephus cinctus is a major pest of wheat that displays avoidance towards M. vitigenus [Drosophila melanogaster [Fungal VOCs protect stored grains from damage by insects and prevent development of toxicogenic fungi . Insectspellents . Besidescticidal . Wheat sitigenus . The abiitigenus , Isopteritigenus , Hemipteitigenus  and Orthitigenus . VOCs frnogaster .Metarhizium anisopliae, Metarhizium flavoviride, Pandora sp., Isaria fumosorosea, Hirsutella danubiensis, Batkoa sp. and Beauveria bassiana produced a wide profile of secondary metabolites (including VOCs), categorized into groups of aldehydes, ketones, alcohols, esters, acids, terpenes and others [Batkoa sp., Isaria fumosorosea, Metarhiziumanisopliae and Hirsutelladanubiensis) [B. bassiana is able to produce VOCs  with repellency activity against banana weevil (Cosmopolites sordidus) [Different species of entomopathogenic fungi such as d others . Benzenebiensis) . Recent ordidus) . The metordidus)  and someordidus) . Althougordidus) , not allordidus) ,27.Beauveria bassiana from our research group has been successful in reducing the RPW infestation in the field [In Spain, the use of a solid formulation of he field . Pathogehe field ,30. Intehe field , avoid ihe field  and reduhe field .B. bassiana cultures on RPW activity, (ii) to identify VOCs produced by solid formulations of B. bassiana, and (iii) to investigate the effects of VOCs from B. bassiana on RPW behavior. This work provides new tools to develop an integrated pest management system to combat RPW palm infestations.Thus, this work investigates the potential of specific VOCs ,27 from A population of RPW adults were collected in Dolores  using pheromone traps baited with 4-methy-5-nonanol and 4-methyl-5 nonanone . InsectsPhoenix dactylifera were randomly collected at the University of Alicante, (SE Spain). Spines and leaves were removed and the stem was cut into 3 × 2 cm fragments. These cuttings were used for the Y-tube bioassay experiments within 3 h.Palm petioles of B. bassiana strain used in the experiment, Bb 203, was isolated from naturally infected RPW adults in southeast Spain  [B. bassiana petri plate was prepared and collected according to Assensio et al. (2008) [B. bassiana using rice substrate (Oryza sativa) was prepared according to Güerri-Agulló et al. (2010) [Entomopathogenic fungus,  121097)  and is m. (2008) . A solid. (2010) . Y-olfactometers were constructed  for laboP. dactylifera, (ii) solid formulation of entomopathogenic fungi, B. bassiana (iii) the autoclaved rice). Rice (Oryza sativa) was used for the two-choice experiments because it was the substrate of the solid formulation of B. bassiana. A video camera  was used for recording RPW movements in the Y-tube olfactometer. The Y-tube was enclosed within a 40 × 32 × 22 cm plastic box with a window (20 × 10 cm) (Curve plastic Iberia SA) for sample handling.Initial experiments for Y-tube bioassays were performed to observe the ability of RPW females to detect and respond to an attractant  or fungus odor in two-choice experiments. Three series of experiments were performed with 20 insects each. These were tested in a Y-tube olfactometer and recorded for 10 min when insects were given a choice between control arm (nothing) and stimulus arm: (i) fresh palm petiole of 2) analyses to test for significant deviation at p < 0.01 from an expected 1:1 (stimulus:control) response.For each experiment, data obtained on the percentage of responses of adult female RPW to each stimulus versus control arm were subjected to Pearson’s chi-squared  were used as source for VOCs detection. Tenax in Glass TD Tube 7″ for Gerstel  was used as adsorbent resin for trapping VOCs. Tenax tubes were thermally cleaned with Gerstel thermal desorption system (TDS)  prior to use. The mass spectra profile (see below) of thermally-desorbed Tenax columns was used as standard blank control.One-month-old solid formulations of B. bassiana were placed in glass tubes and air flowed for 10 min using an air pump. The end of the glass tube was connected with a thermally cleaned Tenax tube for trapping VOCs from the sample. VOCs from same amounts of uninoculated sterilized rice (control) were collected and trapped as explained. All experiments were repeated three times.From ten to twenty grams of solid formulation of the entomopathogenic fungus Tenax tubes containing VOCs were subjected to thermal Desorption (TDS) as before and split into the analytic device Gas Chromatography (GC)  with a HP5-MS 30 m × 0.25 mm × 0.25 μm Column . The vaporized VOCs from the sample pass into the ionization chamber of a mass spectrometer . VOCs are identified with Wiley 275 Mass Spectral database by comparison with retention times and spectra with those of known standards.B. bassiana VOCs were chosen for Y-tube bioassays to test RPW repulsion activities. The VOCs were tested by two techniques (slow and fast release techniques). Fast chemical release was obtained by injecting 0.5 mL of chemicals at chemical stimuli arm. RPW females (one at time) were released into the opening of the central arm of the Y-tube through and exposed to the two arms: (i) chemical stimuli and (ii) control arms. A total number of 40 healthy RPW females was used for this experiment and 20 RPW were randomly selected for each test with chemical stimuli.In this experiment, ethenyl benzene and benzothiazole identified as main Meanwhile, a modified-method for slow chemical release technique  was alsoRPW females were tested as for fast release chemical tests (see above). All RPW were given 10 min in the Y-tube to make a choice. A negative response or repulsion behaviour was scored when an insect either moved away from chemical stimuli arm or only stayed in the control arm during the test recording. After each test, RPW was removed and the Y-tube was rinsed with soap, n-hexane , and water and finally dried with tissue and filter paper.2) analyses. R studio version 3.1.3 was used to test significant deviation (at p < 0.001 from an expected 1:1 (stimulus:control).For each experiment, data obtained on the percentage responses of RPW adult females to each stimulus versus control arm were subjected to chi-square (Xn = 20) showed attraction to P. dactylifera petioles compared to control arms . Meanwhile the behaviour of RPW females (n = 20) vs. rice and control arms showed no significant differences . Solid formulations of the entomopathogenic fungus B.bassiana on rice grains repel RPW females. In a two-choice experiment between the entomopathogenic fungus, B. bassiana and control arm, RPW females preferred the control arm instead of that with B. bassiana grown in rice   .B. bassiana formulate. RPW females avoided B. bassiana arm and chose the uninoculated rice arm instead (10 min recorded). RPW females recorded for 60 min in a Y-tube avoided B. bassiana cultures (0.083 ± 0.06 min) and chose uninoculated rice instead (35.333 ± 13.172 min)  .B. bassiana cultures. Therefore, these cultures were subjected to VOCs separation and identification by GC-MS. Analysis with this technique for control-blank samples (Tenax) detected only two main peaks (B. bassiana solid formulation) (B. bassiana cultures (B. bassiana formulate (Volatile organic compounds (VOCs) were likely responsible for RPW repulsion to in peaks . Seven pulation) . Eleven cultures . Finallyormulate .B. bassiana formulates  using the fast release technique  and Benzothiazole  in silica gel , used as substrate in the formulation [B. bassiana volatiles [B. bassiana inoculated rice. In our experiment, we identified VOCs produced by entomopathogenic fungus B. bassiana grown on rice. Beauveriabassiana produced identified benzene derivatives, benzene acetaldehyde derivatives, straight even-chain saturated hydrocarbons of 10–12 and 16 carbons, n-Decane, ketones and alcohol groups. These groups of compounds were also found by Crespo et al., 2008 and other important entomopathogenic fungi such as Metarhizium anisopliae, Metarhizium flavoviride, Pandora sp., Isaria fumosorosea, Hirsutella danubiensis, Batkoa sp. and Beauveria bassinet with different number of compositions [B. bassiana samples (10 and 20 g). Styrene/Ethenyl-benzene and Benzothiazole were chosen as low retention time and volatile high retention time volatiles. Both significantly repel RPW females for Y-tube olfactometer assays. Previous studies reveal that styrene reduces attractiveness to pine weevils  of pine twig odor [T. castaneum [B. bassania can act as important repellents against banana weevil (C. sordidus) [R. ferrugineus. Repellent compounds such as turmerone, vanillin, nepetalactone and cinnamic acid are repellents of Tribollium castaneum, another colleoptera [RPW females avoid the entomopathogenic fungus, era spp. ,43, Isopera spp. , Hemipteera spp.  and Orthera spp.  also avoordingly . We notimulation . This dimulation . Variousolatiles . For thiositions . Our reswig odor . Other swig odor . Benzothwig odor  and showastaneum . Recent ordidus) . Our resleoptera . In our leoptera ,49 at a B. bassiana VOCs had reduced mobility after treatments. This insect behaviour suggests that VOCs could have neurotoxicity. A previous study showed that fungal VOCs had neurotoxicity on Drosophila melanogaster, reducing its mobility [B. bassiana have potential and can be used to prevent RPW infestation of palms. Future studies should involve further development of gel dispensers for trapping these VOCs, which should allow their use as RPW repellent in the field.RPW females exposed to mobility . In conc


Acute zonal occult outer retinopathy (AZOOR) is a rare condition primarily affecting the outer retina based on electrophysiologic studies. In addition to characteristic fundus appearance, spectral domain optical coherence tomography and fundus autofluorescence are unique in diagnosing AZOOR. There are a few reports on optical coherence tomography anjiography (OCTA) in AZOOR disease. In this report, we present a case using multimodal imaging including OCTA and treatment response to combined systemic antiviral, antiinflammatory, and immunosuppressive drugs. En-face OCTA outer retinal slab may provide useful tips for diagnosis and treatment response. Acute zonal occult outer retinopathy (AZOOR), first reported by Gass in 1992 , 4]. A . A 4]. AWe have evaluated clinical features of AZOOR in a 64-year-old man using multimodal imaging including optical coherence tomography angiography (OCTA)  and treatment response to combined systemic antiviral and immunsupressive drugs during follow-up.A 64-year-old man presented with sudden onset decrease in vision and photopsia in the right eye since 10 days. Systemic and ocular history was normal. There was no viral infection history preceding the symptoms. The best corrected visual acuity (BCVA) in the patient’s right eye was counting fingers at 2 m and 9/10 in his left eye. There was nuclear sclerosis in both eyes. Fundus examination demonstrated an annular ring of yellowish reflex with an about 4–5 disc diameter at the posterior pole in the right eye Figure 1 . AnterioAlthough AZOOR was first described in 1992 .The fundus view may be normal or damaged at different levels, depending on the stage of the disease and the location of the lesion , 7], , .Supporting the characteristic color fundus images with SD-OCT and FAF images is very important in the diagnosis of AZOOR. OCTA is a non-invasive, innovative technology for imaging the microvasculature of the retina and the choroid. OCTA has been reported to be useful in the diagnosis and understanding of many retinal conditions .There are a few reports on OCTA in AZOOR disease in the literature. In the first report by Levison et al. in 2016 , OCTA waThere are some treatment approaches including observation without any treatment, immunosuppressive agents, systemic or intravitreal steroids, and antiviral therapy, and the results were reported in contradiction to one another , 13], , , 15], , , 17], , . In a stThe predictability of the disease is low due to insufficient data. Referring to recent publications, stabilization has been reported to have occurred within 6 months in the majority of patients , 20]. H. H20]. HThe limitation of the case report is the lack of the anterior chamber or vitreous tap for detecting viral etiology. Although the cause of the disease is unknown, autoimmunity or viral causes are considered in the foreground , 22]. G. G22]. GUndoubtedly, further studies with a longer follow-up and a larger series are needed to reach a conclusion on etiology and treatment. In addition to other diagnostic tools, OCTA can provide lock tips in diagnosis and follow-up in AZOOR.The authors declare that they have no competing interests.