Efficient ultra-broadband emitter is realized by using lanthanide ion doping coupled with “DPs-in-glass composite” (DiG) structure. The synergy of self-trapped exciton together with the energy transition induce this ultra-broadband emission emerge. 2Ag(In/Bi)Cl6 lead-free double perovskite (DP) coupled with “DPs-in-glass composite” (DiG) structure. The synergy of self-trapped exciton together with the energy transition induces this ultra-broadband emission emerge.Efficient ultra-broadband emitter is realized by using multi-Ln-doped Cs Traditional ultra-broadband light sources generally include halogen tungsten lamps (HTLs)3, super-luminescent diodes (SLDs)4, ultra-broadband semiconductor lasers (UBSLs)5, laser-driven light sources (LDLSs)6, super-continuum light sources (SCLSs)7, etc. However, many shortcomings still exist, such as spectral instability, high electrical consumption, short lifetime, substantial heat generation, and noncompactness. Hence, alternative ultra-broadband light sources with outstanding optical and structural properties are highly demanded.Ultra-broadband emitter is critical to advancing the applications of light sensing, spectrum analysis, and life sciences imaging, et al. With the development of high-capacity optical data communications and ultra-precision metrology10, making them as the promising monochromatic bright emitters. However, toxicity and poor material stabilities of traditional lead perovskites impede their further commercialization11. Accordingly, lead-free halide double perovskites (DPs) have drawn increasing attention recently owing to their fascinating optical properties and excellent stabilities. In particular, lanthanide (Ln3+) ion doping to tailor the optical or electrical properties of DPs has been well documented, aiming for their applications in white LED, NIR-LED, scintillator, anti-counterfeiting, and X-ray detecting12. The progresses leverage the opportunity to realize ultra-broadband emission using Ln3+-doped DPs, which has never been explored.Metal halide perovskites have attracted widespread attention due to their outstanding optoelectronic properties2AgInCl6 DPs, by combining the self-trapped exciton (STE) and extra luminescence channel induced by Ln3+ doping13 : Cs2AgInCl6) exhibit both visible STE and multiple NIR Ln3+ 4f-4f emissions under excitation14, which enables ultra-broadband emission  in Csg13 Fig. . In partion Fig. . Energy 3+  thus induce ultra-broadband continuous luminescence. As shown in Fig. 3+ activators need to be doped into DPs host, but the energy transfer and cross-relaxation processes among them typically led to the energy loss via non-radiative relaxation, resulting in quenched Ln3+ emissions in the multi-doped DPs17. To solve the problem, they constructed a unique DPs-in-glass (DiG) monolithic composite to confine different Ln3+ dopants and avoid their interaction. Specifically, Nd:Cs2AgInCl6, Yb/Er: Cs2AgInCl6 and Yb/Tm:Cs2AgInCl6 DPs were dispersed into an inorganic glass matrix by low temperature co-sintering. The above bottom-up strategy endows the prepared Ln3+-doped DiG with an improved PLQY of 40% and superior long-term stability.The synergy of STE broadband emission (400–800 nm) and narrowband NIR emissions from Ln13.The DiG was then coupled with commercial 350 nm UV chip to fabricate lighting devices, representing the record ultra-broadband light source covering spectral region from 400 to 2000 nm with full width at half maxima (FWHM) of ~365 nm Fig. . Further3+-doped DPs to realize efficient ultra-broadband emitters. The strategy certainly will attract widespread attention from the whole community, and facilitate their application in various fields such as multi-functional lighting, optical communication, and nondestructive spectral analysis. The lanthanide-doped lead-free DPs thus represent a promising candidate for next generation ultra-broadband light sources.The brand-new strategy conceived by Chen et al. thus provides a powerful toolbox to tailoring multi-Ln


Many environmental factors, such as noise, chemicals, and heavy metals, are mostly produced by human activities and easily induce acquired hearing loss. Organophosphorus pesticides (OPs) constitute a large variety of chemicals and have high usage with potentiate damage to human health. Moreover, their metabolites also show a serious potential contamination of soil, water, and air, leading to a serious impact on people's health. Hearing loss affects 430 million people , bringing a heavy burden to individual patients and their families and society. However, the potential risk of hearing damage by OPs has not been taken seriously. In this study, we summarized the effects of OPs on hearing loss from epidemiological population studies and animal experiments. Furthermore, the possible mechanisms of OP-induced hearing loss are elucidated from oxidative stress, DNA damage, and inflammatory response. Overall, this review provides an overview of OP exposure alone or with noise that leads to hearing loss in human and experimental animals. According to the latest World Health Organization (WHO) report, hearing loss currently affects more than 1.5 billion people in the world, accounting for 20% of the global population. About 1.16 billion people present mild hearing loss, while 430 million people  have moderate to severe or greater hearing loss   , 31. A c < 0.05) . A prosp < 0.05) . From a  < 0.05) . In a cr < 0.05) . In a de < 0.05) . Among t < 0.05) . A study < 0.05) . Taken tExcessive noise exposure is one of the most common causes of hearing loss. It has been verified that the synergistic combination effect of OPs and noise exposure could result in more severe damage to the auditory system , 40. GuiExposure to OPs during embryonic life could cause neurodevelopmental toxicity, resulting in persistent brain neurotransmitter metabolism disorders, cognitive–behavioral abnormalities, and structural–morphological damage to brain tissue, as well as a negative impact on the auditory system. In a cohort study of Chinese infants, the ABR analysis of hearing in 9-month-old infants found that those prenatally exposed to multiple pesticides had a longer central conduction time, wave V latency, and negative effects on myelin-related gene expression, function, and myelination in the brain and the auditory system early in life . A studyTo sum up, hearing damage can occur in the OP-exposed population, especially in the occupational population, presenting as hearing difficulties, persistent bilateral tinnitus, higher prevalence of hearing abnormalities, significantly increased incidence of hearing abnormalities, significant changes or dysfunction of the peripheral and central auditory system, increased high-frequency hearing thresholds, permanent SNHL, and alterations in vestibular structures. The combined exposure to OPs and occupational noise can exacerbate the degree of hearing loss in workers. Low-level pesticide exposures  in pregnant women and young children showed neurodevelopmental toxicity and abnormalities in ABR. These results mean that OP exposure is associated with adverse health effects for the auditory system in population studies.p < 0.025) increase in daily hearing tests at 6 levels between 500 and 16,000 Hz after being exposed to 0.1 mg/kg of parathion for 148 days (p = 0.0569) was observed for the variable saccule. These results emphasize that OPs have neuro-ototoxic potential, but the dose and duration of exposure that are considered safe cannot be determined at this time ((2.35) = 7.87; p = 0.002), and the amplitude of the DPOAE drop was well related to the severity of neuropathological consequences. Cochlear histology analysis showed that the alteration was present in spiral ganglion rather than the hair cells of Corti in the soman-exposed group. The nucleus of the damaged spiral ganglion was sometimes invisible or occurred strongly retracted and surrounded by large vacuoles  and pro-inflammatory cytokines can move into hair cells (HCs), thus activating extrinsic and intrinsic apoptotic cascade responses. These responses cause mitochondrial dysfunction, which promotes the activation of the apoptotic cascade . AlthougCarassius auratus), short-term exposure to the highly toxic monocrotophos resulted in the suppression of glutathione peroxidase (GPx) activity, increasing malondialdehyde (MDA) content, and generation of large amounts of ROS in a short duration, which in turn caused oxidative damage to DNA bases and telomeric DNA (Danio rerio (Rhamdia quelen) ruptured the blood–brain barrier (BBB), elevated brain ROS and brain lipid peroxides, reduced brain cell viability, and caused brain oxidative damage  production and exhausted antioxidant defenses . If the eric DNA . In the eric DNA . In mouseric DNA . Moreoveio rerio . In SH-Sio rerio . CPF couio rerio . Subchroio rerio . The effio rerio . Exposure damage . Five OPe damage . It is evia activation of the DNA fragmentation factor enzyme. Apoptosis-inducing factors could translocate to the nucleus to damage the genomic DNA  α, which promotes a robust inflammatory response and activation of the downstream pro-apoptotic signaling pathway. High levels of interleukin 1 beta (IL-1β) have also been detected in cochlea, promoting the formation of a pyroptosome or inflammasome that mediates caspase-1-dependent cell death roptosis .2O2) production and TNF  . CPF act and TNF .The cohort research of two distinct populations from Pakistan and Cameroon found that the levels of IL-6, IL1-β, and TNF-α in chronically OP-exposed groups were higher than those in the non-exposed group, with a statistically significant increase. The paraoxyglucose Paraoxonase 1 (PON1), a serum esterase/lactonase, played a key role in the hydrolysation of various OPs. The catalytic ability of PON1 was mainly affected by rs662 and rs854560 single-nucleotide polymorphisms (SNPs). It was found that, in exposed individuals of both populations, rs662 SNP risk genotype had a causative association with acetylcholinesterase (AChE), PON1 activity levels, and pro-inflammatory biomarkers  . In all,OP insecticides have great advantages in pest control due to their low cost, high performance, and broad spectrum. However, they also increase insecticide resistance, pose a risk to human health, pollute the environment, and so on. About 3 million poisoning cases and approximately 250,000 deaths occur annually worldwide because of pesticides, where most of the deaths are caused by OPs . NumerouBy reviewing the papers about epidemiological population studies, we concluded that hearing damage could occur in the OP-exposed population, especially in the occupational population. With ABR and OAE testing on humans, both peripheral and central auditory systems appear to be dysfunctional. However, population-based studies are limited in several ways. OPs are the largest and most diverse types of pesticides, so it is difficult to locate which OPs would be responsible for hearing loss in population studies. Moreover, the sources of OP exposure are varied and complex. It is difficult to assess the dose arising from environmental and occupational exposure . OPs arein vitro. The House Ear Institute-Organ of Corti 1 (HEI-OC1) represents a common progenitor for auditory cells and expresses several markers such as prestin, connexin 26, and myosin7a. The HEI-OC1 cell line is proposed as a useful model to investigate the biological responses associated with auditory cells (Danio rerio) is a useful auditory research model owing to its detailed perception of sound and easy accession of its lateral line. The zebrafish lateral line is an easy-to-screen putative ototoxic in vivo for understanding ototoxic mechanisms and developing protective agents. However, unlike auditory cell lines, each neuromast of zebrafish lateral line contains HCs and supporting cells, and each HC receives both afferent and efferent innervation  release, and caspase-3 activation. Involved signaling pathways may include the upregulated expression of inflammatory cytokines and chemokines, as well as the generation of oxidative stress . These ery cells . Currentry cells . Also, iry cells . In addiervation .In summary, there is an association between hearing loss and OP exposure. This review recapitulates the main mechanisms of hearing loss caused by OPs including oxidative stress, DNA damage, and inflammation. It can provide a novel consideration for future studies of environmental pollutants in SNHL. OP exposure is a long-term and underlying process, so their effects may be imperceptible in a timely manner. Therefore, appropriate hearing protection measures should be brought forward, including short-interval audiometric examinations, efficient hearing protectors, and intervention by anti-inflammatory and antioxidant drugs.MSZ and MH: data collection and original draft. JYZ and RC: funding acquisition and writing-review and editing. RC: conceptualization and supervision. All authors contributed to the article and approved the submitted version.This work was supported by the Zhejiang Provincial Natural Science Foundation of China under Grant number LQ20B070006 and the National Natural Science Foundation of China (Grant Number 22106034).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Professional musicians are often exposed to high noise levels and thus face the risk of noise-induced hearing loss. Yet, adoption rates for hearing protection among musicians are low. Previous surveys indicate that the chief concern is the effect of hearing protection use on performance. However, few studies have investigated actual changes in performance when wearing hearing protection. We report an experiment investigating differences in pianists’ performance and experience with and without hearing protection. We compare the effect of foam earplugs and musician earplugs, designed to preserve sound quality with a flat frequency response. The analysis revealed that participants performed overall more loudly with the foam earplugs than with the musician earplugs, and in turn performances with the musician earplugs were louder than the open condition, indicating a compensatory effect. However, this effect was stronger for novel excerpts than for familiar excerpts. No effect was observed on dynamic range. Furthermore, we observed an acclimatization effect, whereby the effect of hearing protection use, observed on the first performance, decreased on the second performance. In terms of experience, participants reported changes in coloration, difficulties gauging dynamics and articulation, and increased effort required when performing with hearing protection. These effects were more pronounced when wearing the foam earplugs, and the participants reported finding the musician earplugs more comfortable to wear and play with. In conclusion, hearing protection use affects pianists’ performance particularly in terms of dynamics and their experience more so in terms of coloration. But the effects are less marked for familiar pieces and after repetition, suggesting that pianists can quickly adjust their playing when playing familiar pieces with hearing protection. Professional musicians are often exposed to noise levels that exceed occupational exposure limits and thus face the risk of noise-induced hearing loss . While tIn addition to rate, the questionnaire studies cited above also investigate musicians’ perspectives with regard to the advantages and challenges of hearing protection use. The main barrier to adoption is the potential effect of wearing hearing protection on musical performance. Among instrumentalists, the chief complaint was the inability to assess the sound of their own instrument, followed by difficulties hearing others, leading to problems of balance and intonation in ensemble settings . In one More specifically, musicians report distortions of timbre and dynamics . These cWhile these studies indicate that the chief barrier is concern over the effect of hearing protection on performance, the fact remains that some musicians do choose to wear hearing protection—and consistently so. What factors compel certain musicians to wear hearing protection despite concerns over performance?One common finding among these studies is higher rate of hearing protection use among musicians with existing hearing complaints . While iDifferent rates of use are consistently noted among players of different instruments . This inWhile qualitative studies are an important aspect in incorporating musician perspectives into education initiatives and development of technology, another complementary approach is to investigate measurable changes in performance with and without earplugs through acoustic analysis. This approach has been taken in an industry setting when studying the effect of earplugs on speech production but few studies have done so with musician performance.In the context of speech production, two main effects have been documented: the Lombard effect and the occlusion effect. The Lombard effect is a well-documented phenomenon whereby speakers increase their level of speech relative to increased environmental noise. The occlusion effect is another phenomenon whereby self-generated sounds  are perceived to be of increased loudness when the ears are covered. The ability to adjust speech levels to noise has been shown to be affected by use of hearing protectors whereby the level of speech produced in noise while wearing hearing protectors is lower compared to speech in noise without hearing protection . HoweverTurning to the effect of hearing protection use on musician performance, a finding analogous to the Lombard effect was reported in choral singers  with a 1With instrumentalists, spectral analyses of musicians’ performances with and without earplugs with various instruments were conducted in solo and ensemble settings . SpecifiA third study  comparedA fourth recent study  investigWhile few in number, the above studies lay the foundation for further research into the measurable changes in musical performance with and without hearing protection. This is not to say that quantitative measures are somehow more valid than subjective experience of performance. For example, if acoustic analysis reveals no difference but musicians report greater effort required to perform with hearing protection, this increased effort could present a barrier to consistent use. Thus, both qualitative and quantitative aspects are needed to better understand the effect of hearing protection on performance.With the aim of better understanding the effect of hearing protection use on musical performance, this study has four objectives. First, we investigate pianists’ attitudes toward hearing protection, with a detailed questionnaire on auditory health practices and attitude toward hearing protection. Second, we explore changes in performance with and without hearing protection while controlling for instrument (piano) and performance context (solo). Specifically, we compare the loudness and dynamic range of solo performances recorded by the same pianists under three conditions: without hearing protection, while wearing musician earplugs and while wearing foam earplugs. Third, we investigate acclimatization to hearing protection by comparing first-time and second-time performances. Fourth, we investigate pianists’ experience while performing with and without hearing protection with a short questionnaire administered after each trial.Seventeen pianists with more than 10 years of musical training were recruited through the mailing lists of the McGill University Schulich School of Music and the Centre for Interdisciplinary Music, Media and Technology. They received $15 CAD for their participation and took home both pairs of hearing protectors tested.Participants were first asked to fill out a questionnaire on their auditory health practices. Then, the participants were instructed to play three excerpts under three different hearing conditions: namely, an open condition without hearing protection, while wearing foam earplugs, and while wearing musician earplugs, for a total of 9 trials per participant . Participants performed on a Yamaha upright Disklavier Mark III, which recorded their performance as MIDI data. The order of the hearing conditions was counterbalanced across participants. The order of presentation for the 3 excerpts was fixed, starting with the most familiar, played from memory, to the least familiar, in a sight-reading task (see details below). After each trial, participants filled out a short post-trial questionnaire on their experience. The entire session lasted about an hour.The excerpts were selected as follows:•0: Participants were instructed to prepare a short excerpt of their choice, under 2 minutes, before the study. They played this first excerpt from memory. This was designed to provide the participants with maximum familiarity with this excerpt. Selections included pieces by Bach, Mozart, Haydn, Schumann, Schubert, Gershwin, Scriabin, Einaudi and Veloso.E•1: Participants were instructed to sight-read the first 24 bars from the Prelude No. 15, opus 38 by Frederic Chopin. This excerpt was chosen as a common excerpt of medium difficulty from the standard repertoire, and participants were expected to have heard or played it before. This was designed to provide the participants with an intermediate level of familiarity with this excerpt.E•2: The participants were instructed to sight-read the first 17 bars from the Nocturne No. 3 by Francis Poulenc. This excerpt, also of medium difficulty, was chosen because it is a lot less common. This was designed to provide the participants with a low level of familiarity with this excerpt.E0 excerpt under each of the three protection conditions. This was done to investigate a potential acclimatization whereby participants might be less affected by the hearing protection on their second try. The experimental design is represented in Furthermore, a subset of 11 participants was asked to repeat each performance of the familiar EWe tested two types of earplugs, namely foam earplugs and musician earplugs. The foam earplugs were standard roll-down slow-recovery foam 3 M 1,100, widely available at a cost of around 1$ per pair, with an advertised Noise Reduction Rating (NRR) of 29 dB (when properly inserted). The musician earplugs used were flange Etymotic ER-20 earplugs, at a cost of $20 per pair, with an advertised attenuation of 20 dB but an official NRR of 12 dB. Frequency-specific attenuation, as provided by the manufacturers, as shown in A general auditory health questionnaire was administered when participants first arrived. The questionnaire consisted of 31 Likert scales and 3 open-ended questions. It was adapted to the musical setting from a previous survey with industry workers  and tran0), all reported being somewhat familiar with E1 and all reported never having played E2 before.Seventeen music students , all currently enrolled at the Schulich School of Music of McGill University, participated in the experiment. They were aged 18 to 37 (mean age 24). Twelve studied piano performance (mostly at the graduate level), either classical or jazz, while the remaining 5 played piano as their secondary instrument. They reported an average of 17 years of musical training and 3.4 hours of daily practice. All participants had prepared a short excerpt to play from memory (EN = 4), hypersensitivity to loud sounds (N = 3), pain related to noise exposure (N = 1), and some form of hearing loss (N = 1). Yet only 9 (out of 17) participants reported using hearing protection, but only very occasionally and mostly when studying (N = 6), attending events or parties with amplified music (N = 6), being exposed to loud noises  (N = 6), or sleeping (N = 1). Four participants reported using hearing protection in the context of group rehearsals while one other participant reported using it for individual practices but not for group practices. While most participants (14 out of 17) reported that both their own instrument and others’ instruments were loud, they also reported that most musicians did not wear hearing protection, and that playing music with hearing protection was less fun. Furthermore, 13 found hearing protection uncomfortable, and five participants reported being worried that wearing hearing protection would make them look unprofessional.All participants reported some concern over their auditory health, and 12 participants (out of 17) reported taking measures to protect their auditory health, such as moving away from loud sounds, avoiding loud live music, and limiting headphone volume. Seven participants reported auditory health issues, specifically tinnitus , for each of the three excerpts in each of three conditions. We represented velocity over time over the entire duration of each excerpt for each trial. An example of this representation is shown in From each participant’s MIDI data, we extracted individual note velocity, used as a measure of loudness in previous studies , excluding repeated excerpts. A two-way repeated measures ANOVA was performed to evaluate the effect of the hearing protection condition on loudness over three different excerpts. There were significant effects of condition  and excerpt  as well as a statistically significant interaction between condition and excerpt on velocity . Therefore, the effect of the hearing protection condition was analyzed separately for each of the three excerpts using one-way repeated ANOVAs for each excerpt with condition as a factor. The effect of condition was significant for all three excerpts  but no other effects were observed. The results, shown in To further investigate the effect of hearing protection on performance, we evaluated the effect on dynamic range, defined as the difference between the loudest and softest note for each trial. A two-way repeated measures ANOVA was performed to evaluate the effect of hearing protection condition on dynamic range over three different excerpts. A significant main effect of excerpt was observed  and repetition  as well as an interaction effect of condition × repetition on note velocity .To investigate acclimatization, we only considered the familiar excerpt (E0) which was performed twice in each condition by 11 participants  = 27.91, p < 0.001 for first time, F = 21.4, p < 0.001 for the second time]. Further analyzing differences for the first-time performance, post-hoc tests  revealed significant differences between Open and Foam conditions as well as between Foam and Musician conditions (both p < 0.001) but no significant difference between Open and Musician conditions (p = 0.25). For the second performance, post-hoc tests revealed a significant difference between Foam and Musician conditions (p = 0.004) but no significant differences between Open and Musician (p = 0.8) or between Foam and Open conditions (p = 0.06). In other words, on the second performance, no significant differences were observed between the open condition and the two hearing protection conditions. Indeed, as shown in Therefore, the effect of the hearing protection condition was analyzed separately using one-way repeated ANOVAs for each repetition with condition as a factor. The effect of condition was significant for both repetition conditions [The effect on experience was investigated through the post-trial questionnaire analysis. The free-form answers to the sound quality question were grouped into four broad themes using an inductive content analysis. Specifically, the first and last author first segmented free-format responses into individual mentions and independently categorized them into themes emerging from the constant comparison method . They thOverall, the difficulties and discomfort level were higher when wearing foam earplugs than musician earplugs, as can be seen from the distribution of negative and positive mentions.p < 0.0001). Similarly, the sound was perceived as significantly boomier (2.6 out of 5) with foam earplugs than with musician earplugs (1.9 out of 5) (p < 0.001). In terms of overall experience, participants reported a strong preference for the open conditions (4.5. out of 5) and their intention to use or buy either type of hearing protection was low (2.1 out of 5).The analysis of the Likert scales was in line with the qualitative results. Indeed, the overall satisfaction level was significantly lower for foam earplugs (2.6 out of 5) than musician earplugs (3.4 out of 5) , difficulties gauging dynamics and articulation, and additional effort required. These disadvantages could be even more problematic in an ensemble context, particularly to hear subtle cues  and finer adjustments needed to achieve ensemble blend.Although our participants generally disliked playing with earplugs, they were more comfortable with the musician earplugs than with the foam earplugs. Being aware that one type of protection was designed for musicians might have affected their perception. It is understandable that unacclimatized musicians would feel discomfort when first playing with earplugs, but it is encouraging that their experience was more positive when wearing musician earplugs. This provides support for the use of musician earplugs and encourages further technological initiatives aimed at preserving musicians’ auditory health.Compared with previous studies on hearing protection in industry workplaces see . This suOur experiment revealed that participants played more loudly when wearing hearing protection, and this effect was stronger when they wore foam earplugs than musician earplugs. This indicates a compensatory effect whereby participants increased the loudness of their playing to compensate for the level attenuation caused by the earplugs. This is further supported by the fact that participants played at the loudest level with the foam earplugs, which have greater attenuation. However, this is in contradiction with previous studies where musicians, usually singers or brass players, instead played more quietly when wearing hearing protection . This diAs previous research  had obseOur study further reveals the importance of another factor affecting hearing protection use, namely the degree of familiarity with the music performed and/or the task at hand. Indeed, in our experiment with pianists, the effects of wearing hearing protection were less marked when playing familiar excerpts from memory than when sight-reading novel excerpts. This finding suggests that the compensatory effect that caused the participants to play more loudly with hearing protection was moderated by familiarity with the piece they were playing. This could be attributed to the fact that pianists performing familiar pieces play more confidently, rely less on the auditory feedback and more on muscle memory than when sight-reading. But this also suggests that musicians working on familiar pieces, as in the context of practicing standard repertoire, could be somewhat protected from the negative effects of wearing hearing protection. Since some protection is better than none, this finding could encourage musicians to wear hearing protection in musical contexts where they feel more at ease, even if they remain reluctant to do so in higher stakes environments. Finally, the lesser effect of hearing condition for the familiar excerpt could also be related to the fact that it was played more loudly than less familiar excerpts, at a level at which hearing protection might be less efficient.Our findings also suggest an acclimatization effect whereby the differences in loudness across hearing protection conditions which were observed during the first performance were no longer significant on the second performance. In other words, the compensatory effect disappeared on the first repetition, after only a few minutes of wearing hearing protection. This suggests that musicians could have the ability to quickly adapt to wearing earplugs, which could lead to a reduction of the negative effects of hearing protection after prolonged use. Furthermore, if musicians can easily adapt their playing when wearing hearing protection after a short training period (as they do when playing with a practice mute), they may be able to use earplugs in certain conditions  and opt out for other situations . Alternatively, in ensemble settings where they might be exposed to higher levels, they could practice  with hearing protection ahead of time, in order to prepare for group performances where protection is most needed. Future research is needed to determine the extent to which musicians can learn to adjust to different hearing protection conditions.Our investigation was limited to a particular instrument (piano) and performance context (solo). Given that the effects of hearing protection in performance differ across instrument types, the results may not generalize to other musical contexts. Furthermore, there are reasons to believe that different instrument types may be affected very differently by hearing protection use, particularly because of the occlusion effect which only applies to embodied sound generation. Conducting similar research with a wide range of instrument types, while accounting for the method of sound production, would allow us to reconcile conflicting research findings across studies with different instruments.Additionally, performance in an ensemble context is likely to be more affected by hearing protection use. Indeed, the Lombard effect, which predicts that speakers raise their voice in louder environments, could apply to music performance in ensemble contexts. In other words, performers wearing earplugs would play softer because of the sound level attenuation of the surrounding environment. This might counterbalance or at least reduce the compensatory effect observed in this study, where solo musicians played more loudly when wearing earplugs.Future research is also needed to investigate whether the beneficial effects of familiarity and acclimatization also apply in the context of ensemble playing. Musicians are at a greater risk of noise-induced hearing loss in ensemble contexts, yet they are also more reluctant to use hearing protection in such contexts. Testing these effects of familiarity and acclimatization in ensemble settings could encourage musicians to persevere through the initial challenges encountered when wearing hearing protection. This could contribute to raising the rate of use of hearing protection devices in orchestral contexts.In their responses, our participants very clearly favored the musician earplugs over the foam ones. It would be important to examine whether musicians would react even more favorably to custom-made earplugs that fit the morphology of their ear with a pre-specified attenuation level. This could encourage hesitant musicians to invest in such devices. Additionally, the attenuation of the earplugs used in this study (in the 20–30 dB range) is perhaps too large for certain musical contexts, particularly for smaller ensembles and quieter instrument types. Certain musicians may get sufficient hearing protection with lower attenuation earplugs while suffering less from the negative effects that come with wearing earplugs. Having a range of attenuation options for musicians to choose from, along with research to inform that choice, could also go a long way to encourage more widespread use.Another promising path towards the wide-spread adoption of hearing protection devices lies in a new trend of musicians considering earplugs as potential practicing tools. Indeed, a previous study reported on the use of earplugs as a “performance enhancer”; that is, a tool used by performers to distance themselves from their sound in order to mimic the sound environment of larger concert halls in their practice rooms . Such apOverall, this study contributes to the small yet growing body of literature aiming to increase understanding of the factors influencing hearing protection use among musicians. While we observed a compensatory effect of wearing hearing protection on overall loudness, this effect disappeared after only one repetition, and was less pronounced with familiar excerpts and with musician earplugs. These results suggest that musicians can quickly learn to adjust their playing when wearing earplugs, even if their experience might be negatively affected. Our findings highlight the need for education campaigns about the effects of hearing protection so that musicians can balance the pros and cons to prevent noise-induced hearing loss without compromising the quality of their performance.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by McGill Research Ethics Board II. The patients/participants provided their written informed consent to participate in this study.AB, CG, and SB conceived and planned the experiment. EB analyzed the data under the guidance of CG and AB. EB wrote the manuscript with support from CG, AB, and SB. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


It remains unclear how to effectively treat rare cases of sudden and recurrent hearing losses which might coincidently follow vaccination. We report the first case, to our knowledge, of systemic and local steroid administration to successfully treat sudden and recurrent left-ear hearing loss, respectively, following a second dose of the BNT162b2 COVID-19 mRNA vaccination which inflammatory response potentially affected an existing left intralabyrinthine schwannoma in a young male patient. This case highlights the importance and timing of intratympanic steroid treatment strategies to suppress the progressive symptoms and restore hearing to a stable condition, and therefore avoid permanent hearing loss which would otherwise demand a surgical removal of the schwannoma to improve vertigo and reconstitute artificial hearing. To combat the COVID-19 pandemic, mRNA vaccines have been widely administered as one of the most effective approaches to protect from SARS-CoV-2 infections and/or severe disease.A man in his 20s with normal vital records and blood pressure was referred to the ear, nose and throat (ENT) clinic for two times of sudden hearing losses of the left ear within three months following the second dose of COVID-19 vaccination. The oral steroids became ineffective for the recurrent hearing loss after initial effects to improve from the first hearing loss . He expeBased on the patient’s report, we tracked back the timeline of his symptoms, tests, and treatment trials and found a possible association with his COVID-19 mRNA vaccination, the second dose of which was administered on day 0 prior to his first sudden hearing loss of the left ear on day 1 . SubsequUnfortunately, 1 week later starting on day 31, the patient suffered from a second left-ear hearing loss with no response to the immediately resumed, 5-day cetirizine treatment, leading to impaired left ear hearing from most of the frequency range by day 44 , using tThe patient was referred for videonystagmography test on day 76 which showed that the left ear had 93% weakness in the caloric testing and 50% directional preponderance to the right . Trackin10.1136/bcr-2022-249316.supp1Supplementary data10.1136/bcr-2022-249316.supp2Supplementary data10.1136/bcr-2022-249316.supp3Supplementary dataConsidering Meniere’s disease does not normally present with sudden hearing loss neither progressive hearing loss after oral steroid treatment, we hypothesised that an inflammatory response might be triggered by the second dose of COVID-19 mRNA vaccination and associated with two times of hearing losses. However, additional factors associated with the hearing loss needed to be determined.A gadolinium-enhanced MRI was then performed at ENT on day 94, identifying a mass of about 6 × 4 mm labyrinthine schwannoma in the left vestibule . The imaThe patient showed progressive left ear hearing loss on day 103 . To iden10.1136/bcr-2022-249316.supp4Supplementary dataSuspecting an inflammatory response against the labyrinthine schwannoma following the two-dose vaccination, an intratympanic steroid injection of dexamethasone (10 mg/mL) was given once on day 103 by the ENT doctor to completely fill the left middle ear. Three days after the first local steroid treatment (day 106), the patient reported disappearance of the left ear ringing and buzzing. The hearing test revealed an average of 20 dB improvement in the left ear hearing on day 111  need to be followed, this case demonstrates that when oral steroids lose effects on persistent and progressive hearing loss, advanced examination for possible organic diseases as well as timely and intensive immune suppression via intratympanic injections to the local microenvironment are necessary for a full recovery. It is critical for young patients to prevent permanent hearing loss and avoid possible surgical interventions. These data also suggest that vaccinated patients who suffer from inflammatory reactions and adverse effects should seek cautious evaluations, close symptomatic monitoring and strategic immune-suppressive treatment.Clinicians should distinguish sensorineural hearing loss from conductive hearing loss. A sudden hearing loss is defined as a loss that occurs within a 72-hour period.Audiometric evaluation should be obtained within the first 2 weeks of the occurrence to prove the hearing loss.MRI is obtained to rule out retrocochlear involvement.The patient is offered corticosteroid, either oral or intratympanic.When I first heard I had a tumour in the left ear, I was completely shocked and started to search online for any possible explanation and treatment. There was no such information available, so I felt helpless. I had prepared for permanent loss of my left ear hearing. After experiencing all the up and downs along with all the tests and treatment trials, I am extremely grateful for the final improvements. The submission and ultimate publication of this case report will absolutely help similar patients in the future.This is a rare case of two sudden, recurrent progressive hearing losses which have immediately followed the second dose of COVID-19 vaccination and coincided with detection of labyrinthine schwannoma.Effective communications between the patient and a multidisciplinary team including otolaryngologist, virologists and cancer immunologists for differential diagnosis with MRI are pivotal to identify the association with COVID-19 vaccination and schwannoma.Following the ear, nose and throat guidelines, implementation of the intratympanic steroid injection approach is effective to mitigate the local aggressive inflammatory response and ultimately restore the hearing.


Apraxia is a cognitive-motor planning disorder that expresses itself as an inability to perform purposeful and skilled movements in the absence of sensory or motor loss and hampers patients' ability to perform activities of daily living (ADL). ADL is a set of everyday tasks required for personal care and independent living, executed through a complex interaction between sensorimotor integration and motor learning. We have designed a ‘Strategy training’ program for apraxia patients by reviewing the existing clinical trial literature on the above-said topic per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Strategy training is an evidence-based standardized occupational therapy program to improve ADL in apractic patients by teaching them a variety of compensatory strategies to combat impairment and improve activity performance. Three basic steps of strategy training include: 1) initiation-development of an action plan, 2) execution-performance of the plan, and 3) control-assessment and result of action performed. The patient group suggested for strategy training comprises post-stroke (past 20 weeks) apraxia patients aged 40-90 years of both genders, highly motivated and fit to perform ADL. After preliminary assessment, ‘strategy training’ will be specifically executed through an exclusively visual feedback approach in which apraxia patients learn eight ADLs in 8 weeks (three sessions of 30 minutes/week for 8 weeks). They practice two ADLs for 15 minutes each in every session, thus a total of six sessions will be allocated to learn two ADLs simultaneously followed by the next set of ADLs. Strategy training for brushing teeth is described in detail to show how each step of this training program is implemented for a specific ADL. As this strategy training program is based on individual care, attention, and augmenting motivational aspects, it is expected to teach patients compensatory strategies to learn and perform ADL more smoothly, swiftly, and most importantly independently. The program is not aimed at treating clinical motor symptoms of apraxia per se but to help patients function more independently post apractic motor impairment. IntroductionApraxia’ DiseaseApraxia’ stems from Greek which means ‘without action’ and clinically manifests as decreased ability to do purposeful skilled movements ,2 . ‘LimActivities of Daily Living (ADL)ADL is a set of everyday tasks required for personal care and independent living. It is classified as 1) domestic ADLs, 2) extra-domestic ADLs, and 3) physical self-maintenance (PSM), most commonly, tasks such as bathing, dressing, toileting, grooming, and eating [ADL on five one-dimensional classification taxonomies: 1) Muscular involvement continuum: ADL involves both gross skills  and fine skills . It depends on the specific type of ADL. 2) Environmental influences continuum: ADL are closed motor skills that are performed in predictable environment with full control of both initiation of action and timing of movements. 3) Continuity continuum: ADL are serial discrete skills linked together in a movement sequence and perform in a specific order. 4) Pacing continuum: ADL are self  as the learner can control the speed, timing, and rate of skill. 5) Complexity continuum: ADL constitute a simple skill as a small amount of information is processed with fewer decisions to take while performing the skill .ADL on gentile’s 2D taxonomy: This approach implies that our every action is a result of complex interaction between the performer, task, and the environment. Specific type of ADL decides which grid of Gentile’s 2D taxonomy is suitable. Overall, for any ADL, from an ‘environmental viewpoint’, stationary regulatory conditions persist with internal variability absent/present allocating either row 1 or 2 to it. From an ‘action function’ perspective, body remains stable or moves with 1) ‘no’ object manipulation (column A) or 2) object manipulations (column B). Thus, depending upon the ADL type, scores are allocated from (1A-2D); e.g., brushing teeth (1B), from lying on bed to chair (1C), and so forth .Fitts and Posner’s three-stage model, Dynamical System Model: In ‘strategy training’, two new ADL are practiced every session for a total of six consecutive sessions every 2 weeks (3 sessions/week). This means that a patient typically moves from ‘cognitive’ stage to ‘associative’ stage (Fitts and Posner’s 3-stage model) or from ‘novice’ to ‘advance’  by the end of the second week. However, strategy training does not provide specific guidelines for change in instructional technique with patient learning keeping these models’ transition perspective in mind .Strategy Training‘Strategy training’ is an evidence-based standardized occupational therapy program originally designed by Van Heugten to supplement the existing rehabilitation program for apraxia in stroke patients . The maiObjectivesThe current systematic review is aimed to focus on ‘strategy training’ and construct a practice session design for apraxia patients to perform PSM ADL to lead a hassle-free living post-stroke.MethodsData Sources, Searches, and Article SelectionThe reporting of this review was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search for this review has been limited to electronic databases  and was searched employing the keywords:  AND (apraxia) AND (activities of daily living). Additionally, we’ve looked into the reference list of trials and reviews identified in the final analysis. Our search was limited to English language studies published between inception and Sept 2021. A detailed step-wise description of the searched methodology is depicted in Figure Patient CharacteristicsThe patient group suggested for ‘strategy training’ comprises apraxia patients aged 40-90 years of both genders . Per the anthropometric measurements, strategy training will not specifically take the weight of the patient into consideration while training, however, overweight and obese individuals have generalized difficulty in learning a few ADL tasks . Typically, less flexible than healthy individuals as immobility/less mobility due to stroke reduces flexibility. A clinical diagnosis of stroke (ischemic stroke or hemorrhagic stroke in the past 20 weeks) and apraxia . ‘Strategy training’ is designed with a thought that apraxia patients learn ADL as naïve sensorimotor learners. The therapist making them perform ADL should be fully acquainted with the patient’s language.Specifics of ‘Strategy Training’ TaskOnly the patient and therapist will be present at the time of training because ADL are typically performed alone even by normal healthy individuals. This will also avoid undue anxiety which may creep in in the presence of others that hampers overall learning. Strategy training will help participants learn ADL slowly over time. The training will include visual, auditory, and tactile stimuli to learn ADL, however, the reliance will be more on visual stimuli just like a normal individual. The training will be given utilizing the same objects a person will use after training to perform ADL in the future. ADL may be modified or simplified impromptu depending upon the patient’s response to learning, e.g., while brushing teeth, toothbrush and toothpaste will be placed in the order of use, with lid of toothpaste open in order to reduce coordination requirements .Environmental Factors in ‘Strategy Training’Strategy training will be carried out in a closed predictable environment where a learner has full control over his actions and timing of movements. Each ADL will be performed in a different environment depending upon the ADL itself, e.g., brushing teeth in a bathroom, combing hair in a dressing room, and so forth. Only the patient and therapist will be present at the time of training because ADL are typically performed alone even by normal healthy individuals. Strategy training for all the ADL is practiced in either a bedroom, living room, or bathroom in a thermoneutral environment (75°F) in a bright day or artificial light. The idea is to train the participant in the same environment where he will use his skill in future. The instructor will make sure that the participant will be encouraged  and no disruptions take place  throughout the training session.Practice DesignPreliminary assessment:It will be done through choice of activity, assessment of the level of disabilities in ADL, and utilizing Barthel Index. 1) Choice of activity : ActivitOverview of practice design Figure : Two ADLDetailed steps of practice design: A detailed elaboration of the steps of strategy training with ‘brushing teeth’ as an example quoted for each step is shown in Table DiscussionThe discussion will elaborate motor learning factors that surround and influence ‘strategy training’ for apraxia.Augmented FeedbackA combination of audio and visual feedback will be given to the participant after every ADL in the allocated 15 minutes time during each session. After the task, the recorded ADL will be shown to the patient and a verbal feedback on result (KR), performance (KP), and suggestions to improve will be given while watching the video with the patient. However, strategy training does not provide specific guidelines for change in this AF frequency with patient learning.ModellingObservational learning implies learning by watching and imitating another individual (model) and this is strongly implied during both ‘initiation of activity’ (therapist ‘mimic/demonstrate part of task himself’) and ‘execution of activity’ (therapist mimics activity to assist the patient).Verbal CuesAkin to modeling, verbal cues strongly influence strategy training for ADL both during ‘initiation of activity’  and ‘execution of activity’ . Attention cueing will be tried sometimes to make sure that the participant is paying maximal attention to a specific aspect of the skill while performing it as a whole. For example, while brushing teeth the learner will be focusing mostly on transferring paste onto the brush. The instructor will make sure that the participant will be encouraged  while performing the task.Distribution of Practice and Contextual InterferenceAlthough ‘strategy training’ does not follow ‘blocked practice’ entirely (2 ADL at a time are used instead of 1), however, it is heavily inclined toward this approach as two ADL will be selected every two weeks and each ADL will be practiced for 15 minutes during the 30 minutes session every day. With a total of three sessions scheduled for a week, a total of six sessions will be employed for practicing two ADL. This will be followed by choosing another set of two new ADL for the next 2 weeks and so on. In contrast to ‘random practice’ this approach works better in acquisition (short-term) than retention (long-term). ‘Strategy training’ is low in contextual interference as different ADL are not mixed well while practicing and there is adherence to a set of two ADL at a time.Part vs Whole PracticeTypically, as a task, ADLs are high in organization which means that subcomponents of the task/ADL are interdependent, i.e., performance of each part heavily depends upon the preceding component. They are low in complexity with not many subcomponents making up the skill. As a result, strategy training for ADL will focus on the whole practice instead of part practice.Variability and Specificity of PracticeTypically, ‘strategy training’ works on ‘constant practice’ schedule and will not vary the conditions of practice much during practice as all ADL will be practiced in the same environment  where the learned skill will be used in future, and this approach alike ‘distribution of practice’ works well in acquisition (short-term) than retention and transfer (long-term). Although, some variability is seen after completion of eight ADL with one ADL learning somewhat influence the learning of another ADL . ‘Strategy training’ follows the ‘specificity of practice’ principle strongly and all ADL will be practiced in the same testing conditions  where the learned skill will be used in the future.LimitationsThe major limitation of this review are 1) the availability of only a few articles (2017-2020) that specifically address strategy training in apraxia patients, 2) all the research on ‘strategy training’ in apraxia patients is confined to western Europe constraining the generalizability of its findings, and 3) alluding ‘strategy training’ is limited in scope in terms of its conceptualization to post-stroke patients’ capacity to perform PCM ADL.Since this ‘strategy training’ program is based on individual care, attention, and scientific augmentation of general motivational aspects, it is expected to teach patients compensatory strategies to learn and perform ADL more smoothly, swiftly, and most importantly ‘independently’. This program is not aimed at treating clinical motor symptoms of apraxia per se but to help patients function more independently post apractic motor impairment. However, occupational therapists may observe a sort of ‘ceiling effect’ during ‘strategy training’-patients who perform ADL rather independently before the program may not exhibit much progress. As such, there remains a need to determine how long ‘strategy training’ will sustain post-therapy in apraxia patients, keeping in mind their gradual-worsening of motor impairment with advancing age. Based on the limited existing literature, despite the everlasting presence of apraxia this therapy program is anticipated to wane off motor impairments associated with ADL and help enable these patients to function in a more autonomous fashion.


The association between the treatment of transverse maxillary deﬁciency and the recovery of hearing and voice functions has gained attention in recent years.This prospective controlled trial aimed to evaluate the effects of rapid maxillary expansion on hearing and voice function in children with non-cleft lip palate and bilateral cleft lip palate with transverse maxillary deficiencyt-test was used for comparisons of mean values of T0 and T2 voice parameters within both groups.53 patients  requiring rapid maxillary expansion for correction of narrow maxillary arches were recruited for this trial. Eight sub-groups were established based on the degree of hearing loss. Pure-tone audiometric and tympanometric records were taken for each subject at four different time periods. The first records were taken before rapid maxillary expansion (T0), the second after expansion (T1) , the third after three months (T2)  and the fourth at the end of retention period (T3) . ANOVA and Tukey HSD post-hoc tests were used for data analysis. Additionally, voice analysis was done using an updated PRAAT software program in a computerized speech lab at T0 and T2. A paired-sampleRapid maxillary expansion treatment produced a significant increase in the hearing levels and middle ear volumes of all non-cleft and bilateral cleft lip palate patients with normal hearing levels and with mild conductive hearing loss, during the T0–T1, T1–T2, T0–T2, and T0–T3 observation periods (p < 0.05). The significant increase was observed in right middle ear volumes during the T0–T1, T0–T2 and T0–T3 periods in non-cleft patients with moderate hearing loss. For voice analysis, significant differences were observed only between the T0 and T2 mean fundamental frequency (F0) and jitter percentage (p < 0.05) in the non-cleft group. In the cleft group, no significant differences were observed for any voice parameter between the T0 and T2 periods.Correction of the palatal anatomy by rapid maxillary expansion therapy has a beneficial effect on both improvements in hearing and normal function of the middle ear in both non-cleft and bilateral cleft lip palate patients. Similarly, rapid maxillary expansion significantly influences voice quality in non-cleft patients, with no significant effect in BCLP patients. Transverse maxillary deficiencies represent a significant component of all malocclusions among both cleft lip palate and non-cleft lip palate orthodontic patients. Mouth breathing, digit and pacifier sucking, and atypical swallowing have been ascribed as the myriad causative factors of maxillary width deficiency, often resulting in detrimental effects on the dentofacial pattern.Estimates from the World Health Organization reveal that hearing loss is a globally prevalent public health problem with a sizeable number of populations (approx. 42 million people) more than three years of age being affected by it. Approximately, 28–38% of the children are affected by middle ear disorders with far-reaching adverse impacts on their psychosocial, esthetic, orofacial, academic and overall development.Patients with Cleft Lip and Palate (CLP) usually encounter a multitude of lifelong challenges due to the constrained growth of the upper jaw; and frequently manifest speech, orthodontic, hearing and dental problems.The anatomical and physiological integrity of the hearing system exhibits a strong interrelationship with the acquisition and development of verbal language and speech.Substantial changes produced by Rapid Maxillary Expansion (RME) may change the oral, nasal, and pharyngeal tissue form, thereby contributing to improved respiration and correction of a dental cross-bite. In growing patients with CHL and associated maxillary deficiency, the orthopedic effect of RME may aid in improving hearing owing to a restoration of normal functioning of the pharyngeal ostia of the Eustachian tubes.16Although the association and correlation between the treatment of transverse maxillary constriction and the unexpected therapeutic recovery of auditory functions have been widely documented in the literature, a recent systematic review by Fagundes et al.20However, to the best of our knowledge, no studies have been performed that investigated the interventional effect of maxillary expansion on the improvement of both speech and hearing functions among non-cleft lip palate and cleft lip palate patients presenting with varying degree of hearing ability patterns. Thus, this prospective controlled trial aimed to evaluate the effects of RME among age-matched non-cleft patients and non-syndromic Bilateral Cleft Lip Palate (BCLP) patients requiring maxillary expansion as one of the treatment modalities for adjunctive correction or improvement of hearing and voice function.The present study was conducted as an Inter-Hospital research project involving two University Centers. Approval for the study was obtained from the Institutional Ethical Committee vide Appx ‘A’ to O/o Institutional Permission letter nº 15965/56th; and the present clinical study was registered at the Institutional Health Care Registry, Research and Referral Center, vide ADC/Pers/RKM/2017 dated 11 Feb 2017. Written informed consent was obtained from the parents of all patients after explaining the details of the study. Based on the significance level of alpha 0.05 and at least 80 percent power with an allowable error of 15%, 53 patients within the age group of 9–13 years  were recruited for the study. The patients were divided into two groups: Group I consisted of 26 non-cleft patients  requiring maxillary expansion for correction of transverse maxillary constriction; and Group II comprised 27 BCLP patients  requiring maxillary expansion for correction of maxillary constriction and arch collapse.Patients enrolled for this prospective study met the following inclusion criteria in cleft groups: (1) Presence of transverse maxillary deficiency; (2) bilateral posterior cross-bite, (3) lip and palatal repair in early childhood only with no subsequent surgical interventions, (4) no history of previous orthodontic treatment, (5) high degree of cooperation. The inclusion criteria for the noncleft control group were: (1) Angle’s Class I occlusion with bilateral posterior crossbite, (2) no history of previous orthodontic treatment and (3) internally motivated and cooperative. Exclusion criteria were as follows for both groups: (1) History of orthodontic treatment, (2) history of nasal or pharyngeal surgery, (3) presence of nasorespiratory and allergic symptoms (3) presence of systemic disease; (4) craniofacial anomalies and syndromic cases, and (5) presence of cerumen, tympanic membrane perforation and/or other possible alterations as confirmed by otoscopic examination.Based on the classification of degree of hearing loss,Before the commencement of the RME procedure, the hearing levels of each patient were evaluated by an otorhinolaryngologist by means of pure-tone audiograms and tympanograms. RME was performed using bonded Hyrax expander , activated twice a day, one turn in the morning and one in the evening (0.5 mm/day), for 7–14 days until necessary expansion for each subject was accomplished with complete elimination of posterior crossbite Figs.  and 4a–cFollowing the standardized protocols proposed by Munhoz et al.,Acoustic voice samples were recorded from all patients at T0 i.e. before RME, and at T2 i.e. at the end of 3 months stabilization phase, without the appliance in the mouth. All voice samples were recorded in a quiet room using a high-quality unidirectional condenser microphone brand Shure, model SM-58, on a desktop computer . The microphone was positioned at a constant 10 cm distance from the mouth in a 45° to 90° off-axis position.The hearing records (audiograms and tympanograms) and voice recordings were blocked and randomized for assessment by well-trained evaluator. This helped ensure blinding, thereby eliminating the influence of cognitive bias on the results in the assessments.Following acoustic parameters were analyzed and compared between T0 and T2:Mean fundamental frequency : representing the number of vibrations of the vocal fold per second;Jitter percentage (pitch perturbation): representing short-term (cycle-to-cycle) deviation in the fundamental frequency of a signal/deviation from true periodicity of a presumably periodic signalShimmer percentage (amplitude perturbation): representing the variability of the peak-to-peak amplitude between adjacent cycles of vocal fold vibrationsHarmonic-to-noise ratio : quantifying the amount of additive noise in the voice signal.Data were processed using SPSS software for Windows . The Kolmogorov-Smirnov statistic was used to verify the normality of data distribution. Descriptive statistics (including means and standard deviations) for the pure-tone threshold measurements (at the investigated frequencies), and for tympanometric measurements for each ear were calculated at each of the four measurement periods separately. The data regarding the hearing levels, middle ear volume, and static compliance values were evaluated using the analysis of variance (ANOVA) test. Tukey HSD post-hoc test was applied to determine at which periods the measurement changes were significant.t-test. Tests of significance were two-tailed, and the minimum level of the statistical significance was set at p < 0.05.The speech parameters of the non-cleft and cleft groups were evaluated independently between T0 and T2 periods using paired samples p <  0.05)  a. Signif<  0.05) . However<  0.05)  and S7.FIn cleft group patients with normal hearing levels, statistically significant hearing improvements were observed from the T0 to T1, T0 to T2 and T0 to T3 periods in both ears. (p = 0.000) in right middle ear volume during the T1–T3 period in Group IIa (Table S16).In Group Ia, right middle ear volume showed statistically significant improvement during the following observation periods: T0–T1, T1–T2 and T0–T3; while the improvements in left middle ear volume were not statistically significant  and S14.Both Group Ib and Group IIb samples showed a statistically significant increase in both the right and left middle ear volumes with no significant change in static compliance values (Table S14). In Group Ib, significant change in middle ear volume was observed during the T0–T1 and T0–T3 periods in right ear and during the T1–T2 period in the left ear (Table S17). Both right and left middle ear volumes in Group IIb also showed significant increases during the T0–T1, T0–T2 and T0–T3 periods (Table S18). In Group Ic, significant mean differences were observed only for right middle ear volumes during the T0–T1, T0–T2 and T0–T3 observation periods; while the middle ear volume changes in group IIc samples were statistically insignificant  and S14.p < 0.05; As for the voice analysis, means of different voice parameters at T0 and T2 periods are depicted in Correction of transverse maxillary deficiency by arch expansion is considered to be one of the foremost important steps in the rehabilitation of any orthodontic and dentofacial deformity, both in non-cleft and cleft lip palate affected constrictions. Owing to combination of favourable dentofacial and craniofacial treatment effects,29In the present study, we used bonded Hyrax expander with occlusal acrylic coverage because of its advantages of allowing greater skeletal expansion, more parallel movement of the anchor teeth and the two maxillary halves, and long-term stability as compared to the conventional expanders.As for the methods of hearing evaluation, a pure-tone audiogram is considered a vital tool for the subjective assessment of hearing levels and for measuring the level of recognition of pure-tone sounds at different frequencies.Objective audiometric assessment using tympanometry provides valuable quantitative information about the compliance or mobility of the tympanic membrane, the presence of fluid in the middle ear, mobility and pressure within the middle ear system, ET dysfunctions and ear canal volume. Measurement of the static compliance of the tympanic membrane and of the volume of the tympanic cavity by the use of tympanograms proves beneficial in determining the changes in stiffness of the tympanic membrane, reduction of the middle ear effusion, and volumetric changes in the middle ear cavity.The results of the present study highlight that all non-cleft and cleft subjects with normal hearing levels and with mild conductive hearing loss, selected for palatal expansion showed significant improvements in hearing levels during the T0–T1, T1–T2, T0–T2, and T0–T3 observation periods. However, improvements in hearing after maxillary expansion did not show a further significant increase but were retained during the T1–T2 and T2–T3 observation periods. Despite general consensus regarding the positive effects of RME on hearing levels, conflicting reports exist in literature regarding the maintenance of hearing improvements over a period of time; with few authorsHowever, the cleft group and the non-cleft group patients with moderate to severe hearing loss did not show statistically significant hearing improvement during the observation period from T0–T1 to T2–T3, except for the significant improvements in left ear during T0–T1, T0–T2 and T0–T3 periods in non-cleft group patients exhibiting moderate hearing loss.Regarding the results of the tympanometric evaluation, middle ear volumes of both the non-cleft and cleft group patients with normal hearing levels and mild hearing loss showed considerable improvement during all the observation periods. Similar findings were also reported in the study of Kilic et al.These findings are in accordance with those of Handzik-Cuk et al.In a three-dimensional finite element analysis of ET function under normal and pathological conditions, Sheer et al.Tunçbilek et al.Fagundes et al.Measurements of vocal extension profile, fundamental frequency, perturbation index (jitter and shimmer) and harmonics-to-noise ratio are the most important vocal acoustic parameters having clinical implications.For examining voice quality, Harmonic-to-Noise Ratios (HNR) were obtained for vowels in the conversation, conversation-repetition, and the first and second sentence repetition samples using PRAAT software. Normalization of the HNR values (nHNR) was done using the duration of the measured vowel portions. All the voice recordings were blocked and randomized for assessment to eliminate the influence of cognitive bias on the results in the assessments.Due to lowered and backward positioning of the tongue during phonation of the /a/ vocal, the closure and constriction in the center of the vocal tract do not occur as in the other voices. Additionally, since the/a/sound also constitutes the phonological core of many syllables,Regarding the effects of RME on speech, the results of the present study are difficult to compare to previous investigations since objective studies assessing the influence of RME on vocal function in subjects with bilateral cleft palate are relatively non-existent. Moreover, heterogeneity in methodology, mixed patient groups and non-unified surgical techniques make comparison of speech results of different studies difficult. Flynn et al.In the current study, after appliance removal, the cleft group showed a statistically insignificant decrease in mean F0 frequency. Contrary to the results of Gonzalez et al.Macari et al.As for the limitations of the study, a non-expanded control group with posterior cross-bite was not constituted due to ethical reasons for denying the benefits of timely correction of functional crossbite. Furthermore, the results of the present study should be extrapolated with caution and a greater number of randomized trials can be planned and conducted in different populations with larger sample size and involving long follow-up periods to further validate the findings. Moreover future studies can take benefit of advanced diagnostic AID such as video-otoscopy for instrumental observation of the external auditory tube and the tympanic membrane.This study showed that the correction of the palatal anatomy by RME therapy had a positive and statistically significant effect on improvements in hearing and function of the middle ear in both non-cleft and bilateral cleft lip palate patients with normal hearing levels and with mild conductive hearing loss. Similarly, RME significantly influenced voice quality in non-cleft patients, with no significant effect in bilateral cleft lip palate patients.The authors declare no conflicts of interest.


Arabidopsis thaliana, the most renowned noncrop plant model species, have markedly stimulated studies in other species with different biology. Within the family Brassicaceae, the arctic–alpine Arabis alpina has become a model complementary to Arabidopsis thaliana to study the evolution of life‐history traits, such as perenniality, and ecological genomics in harsh environments. In this review, we provide an overview of the properties that facilitated the rapid emergence of A. alpina as a plant model. We summarize the evolutionary history of A. alpina, including genomic aspects, the diversification of its mating system and demographic properties, and we discuss recent progress in the molecular dissection of developmental traits that are related to its perennial life history and environmental adaptation. From this published knowledge, we derive open questions that might inspire future research in A. alpina, other Brassicaceae species or more distantly related plant families.Many model organisms were chosen and achieved prominence because of an advantageous combination of their life‐history characteristics, genetic properties and also practical considerations. Discoveries made in  Commonly, such a model species is originally adopted to study a very particular biological question in detail, and hence a specific trait may be decisive for choosing the appropriate organism for the given study. Subsequently, such a case model may be further elaborated and eventually serves as a reference for many other taxa and, hence, is commonly recognized as a model species  and their particular trait peculiarities are: Arabidopsis halleri for its heavy‐metal tolerance , the Alpine rockcress, has been established as a complementary model species for ecological genomics and life‐history evolution under harsh abiotic conditions. While evolutionary research on A. alpina had started nearly 60 years ago with taxonomic investigations by Hedberg , which ranges from the eastern Mediterranean and Saharo‐Arabian regions to the Tian Shan and Pamir Mountains  A. alpina and its closest relatives (~10–12 species), (ii) its sister clade including A. nordmanniana , and (iii) the A. auriculata clade  are found within the same phylogenetically unresolved clade. If all of those were included within A. alpina to establish monophyletic entities, subspecies concepts would have to be applied  comprise a well‐defined sister clade of exclusively annuals  Different phylogenetic positioning of tribe Arabideae within Brassicaceae core groups depending on the marker set used, indicating a biological phenomenon rather than an analytical artefact , rendering the genus a fascinating system to investigate the molecular and genomic basis of, for example, parallel vs. convergent evolution. Consequently, future studies will benefit from additional sampling of selected species pairs along the phylogeny of the tribe. Moreover, phylogenomics approaches could be performed in the genus 4Understanding the processes governing mating system evolution is pivotal, because the mating system by large influences the distribution of genetic diversity . Plants from self‐compatible populations have markedly smaller and less scented flowers, less herkogamy (anther–stigma distance) and lower pollen production than plants from outcrossing populations , possibly including different treatments  for its wide‐ranging occurrence and broad ecological niche  and mean probability of reproduction (F0 = 0.5) across populations. Moreover, demographic rates were related to environmental conditions in the populations: with elevation, survival tended to increase, while growth and fecundity tended to decrease. These findings in A. alpina reflect common patterns in life histories of herbaceous plants: small, long‐lived species tend to inhabit high elevations, and vice versa , PERPETUAL FLOWERING2  and TARGET OF EAT2 , PEP1 transcript abundance decreases during cold exposure and plants form flower buds  and provide the proof‐of‐concept data that are often the step remaining to be completed in contemporary studies of adaptation. Moreover, interspecific comparison of trait expression and gene function between mono‐ and polycarpic species within the Arabideae will provide insight into the mechanistic basis of life‐history evolution. One major difference between the two life‐history strategies that awaits further research is that senescence after flowering is restricted to reproductive branches in polycarpic plants, whereas it is global in monocarpic plants. To this end, introgression lines of A. alpina that contain genomic regions of the annual close relative A. montbretiana in a common genetic background have already been developed as a genetic tool (Hyun et al., In summary, comparative physiological studies between 8Arabis alpina is well suited to answer questions related to the adaptation of plants to harsh arctic–alpine environments and the evolution of a perennial life history. However, despite the progress of the past decade, there are still many open questions that await to be addressed. Below, we formulate some avenues that may guide future research in the fields of ecological, evolutionary and molecular genetics in A. alpina and other taxa. Advancement will greatly profit from interweaving the complementary approaches reviewed above, which benefit from the ample resources already available in this model species.In this overview, we demonstrate that 8.1While for some ecologically relevant and naturally variable traits, such as the timing of flowering, the molecular genetic basis is already well understood, other traits still await detailed molecular characterization, for example those regulating frost tolerance through the accumulation of metabolites in leaves (Kolaksazov et al., 8.2A. alpina is an exception to this rule, but only limited information on how A. alpina may benefit from such root associates is available to date. For example, Almario et al. (A. alpina roots and found certain taxa to be dominant on soils with low phosphorus content. Their results indicate microbial support for phosphorus uptake under limiting conditions and suggest that taxa growing on alpine, often nutrient‐poor soils can evolve alternative solutions to the otherwise common mycorrhizal symbiosis. Nevertheless, it remains unclear how common these associations are, whether they lead to co‐adaptations in the involved physiological pathways, and to what degree they influence the evolutionary trajectory of the host plant and contribute to the ability of A. alpina to grow on poor soils as a pioneer species. Here, hypotheses could be developed in relation to the extended phenotype concept (Gugerli et al., A. alpina as a species growing across a broad ecological niche, including gradients of elevation or nutrient availability (Buehler et al., Another key to the adaptive success of plants is their ability to associate with mutualistic organisms. In many taxa, fungi or other microbiota grow on plant roots to form close symbioses. While mycorrhizal associations typically do not occur in Brassicaceae, o et al.  characte8.3A. alpina already provides a solid foundation to build on.The mating system of plants largely evolves in relation to plant–pollinator interactions. Addressing the genetic basis of floral scent variation (Petrén et al., 8.4A. alpina has so far centred on populations from the European Alps, Scandinavia and the Spanish reference accession Pajares, future studies should expand along the species' phylogeography. Accessions from the Anatolian mountains and African sky islands, which represent isolated high‐elevation habitats for A. alpina in today's tropical latitudes (Chala et al., Arabidopsis thaliana after including previously neglected accessions from Africa (Durvasula et al., A. alpina to broaden the environmental perspective provided by such a wide‐ranging taxon.While most of the reviewed research on 8.5A. alpina to closely related sister species within the Arabideae, and to those in other well‐studied genera of the Brassicaceae such as Arabidopsis, Capsella, Boechera, Cardamine and Brassica (Krämer, Biological discoveries can be expanded from  Krämer, . With ev Krämer, , or to w Krämer, .Arabidopsis thaliana, to induce enhanced activity of TEs, which in turn affects gene integrity or the regulation of gene expression. Epigenetic transmission can then lead to an acquired adaptive response in the next generation (Thieme & Bucher, A. alpina to cope with environmental stressors. Here, we see great potential in establishing links between genome‐wide methylation patterns and the pertinent information on the types, activity and distribution of TEs (Choudhury et al., Lessons learnt from an arctic–alpine model system may help pinpoint the genomic particularities that also govern physiological processes in other taxa under stressful conditions (Park et al., 9A. alpina, together with the publicly available genomic resources established in recent years, will serve as a comprehensive basis for future studies in this model for ecological genomics and beyond. With our overview, we demonstrate that A. alpina is a valuable and integrative model system that can join different research fields in plant biology. Together with a suite of other taxa, A. alpina complements research in the genus Arabidopsis, on which a huge array of research still relies, to address alternative evolutionary routes to environmental cues. Additional, intensively studied taxa will enrich the field of evolutionary plant biology and contribute to knowledge about the manifold ways plants cope with their abiotic and biotic environment.Taken together, the marked variation in life‐history traits encountered across the natural range of S.W., M.A., M.C.A., G.C. and F.G. conceived the outline, S.W., M.A., M.C.A., M.A.K. and F.G. wrote the article with contributions from G.C., and all authors read and approved the final version.The authors declare no conflicts of interest.Appendix S1Click here for additional data file.


The association between hearing loss and chronic kidney disease and hemodialysis has been well documented. However, the classification used for the degree of loss may underestimate the actual diagnosis due to specific characteristics related to the most affected auditory frequencies. Furthermore, correlations of hearing loss and hemodialysis time with hearing handicap remain unknown in this population.To compare the results of Lloyd's and Kaplan's and The Bureau Internacional d’Audiophonologie classifications in chronic kidney disease patients, and to correlate the averages calculated by their formulas with hemodialysis time and the hearing handicap.This is an analytical, observational and cross-sectional study with 80 patients on hemodialysis. Tympanometry, speech audiometry, pure tone audiometry and interview of patients with hearing loss through Hearing Handicap Inventory for Adults. Cases were classified according to the degree of loss. The correlations of tone averages with hemodialysis time and the total scores of Hearing Handicap Inventory for Adults and its domains were verified.n = 52) with some degree of disability compared to Lloyd and Kaplan (n = 16). In the group with hemodialysis time of at least 2 years, there was weak but statistically significant correlation of The Bureau Internacional d’Audiophonologie classification average with hemodialysis time (r = 0.363). There were moderate correlations of average The Bureau Internacional d’Audiophonologie classification (r = 0.510) and tritone 2 (r = 0.470) with the total scores of Hearing Handicap Inventory for Adults and with its social domain.86 ears (53.75%) had hearing loss in at least one of the tonal averages in 48 patients who responded to Hearing Handicap Inventory for Adults. The Bureau Internacional d’Audiophonologie classification identified a greater number of cases (r = 0.557 and r = 0.512).The Bureau Internacional d’Audiophonologie classification seems to be more appropriate than Lloyd's and Kaplan's for use in this population; its average showed correlations with hearing loss in patients with hemodialysis time ≥ 2 years and it exhibited moderate levels of correlation with the total score of Hearing Handicap Inventory for Adults and its social domain ( Currently, there are several classification scales of the degree of hearing loss and their formulas consider different hearing frequencies to calculate the tone average. There is not yet consensus on which scale better fits the pattern of hearing loss occurring in patients with chronic kidney disease (CKD) and hemodialysis (HD).The best-known association between CKD and hearing loss is Alport Syndrome which has a genetic cause.10The worldwide prevalence of CKD has increased in recent decades. In 2013, 2.5 million patients were on dialysis in the world, and this number is expected to reach 6.5 million in 2030.Hearing loss can affect quality of life and limits activity or restricts participation in daily activities; according to the World Health Organization (WHO), “hearing handicap” (restriction of participation) refers to the involvement in life situations and shows the individual's adaptation to the environment as a result of hearing loss and disability.Emotional and social damage from hearing impairment are variable and depend on life experiences, expectations related to health, and even on the adaptive capacity of the individual. Thus, people with similar hearing loss can experience different communicative, social and emotional difficulties in daily life and have different perceptions of their quality of life.HHIA Questionnaire (Hearing Handicap Inventory for Adults) is a tool to assess the impact of hearing loss based on the perception of hearing handicap, and among its uses in clinical practice is the ability to assess the impact of a therapeutic measure (e.g. hearing aids) and to identify specific treatment needs.As the hearing loss associated with CKD is more pronounced at high frequencies, the formula used to calculate the tone average can lead to different categorizations. Because of the importance of high frequencies in speech intelligibility, it is necessary to better understand the formula that possibly has associations with time of hemodialysis and with hearing handicap. There were no studies in the literature evaluating hearing handicap in HD patients. Thus, the objectives of this study are: (1) to compare the results of Lloyd and Kaplan and BIAP classifications, (2) to correlate the tonal averages calculated by the formulas used by these two classifications and tritonal formula of high frequencies with hemodialysis time (HT) in groups of patients with either less than 2 years and with at least 2 years of treatment, and finally (3) to correlate these averages with hearing handicap.This is an analytical, observational and cross-sectional study. The sample consisted of 80 patients on HD for at least three months, with ages between 14 and 54 years.The protocol of this research is based on Resolution No. 466/12 of the National Health Council of the Ministry of Health for research with human subjects, and was approved by the Research Ethics Committee with No. 1290310/2015.® brand immittanciometer, model at235 XP, serial number 206331, contralateral TDH39 handset, ipsilateral clinical headset; patients with tympanogram of Jerger type “A” (1970) underwent speech audiometry and Pure Tone Audiometry (PTA) in an audiometric 2 m × 2 m cabin to assess the frequencies of 0.25; 0.5; 1; 2; 4; 6 and 8 kHz with Interacoustics® audiometer, ac33 model, serial number 185994 with bone vibrator b-71, TDH-39 right and left headphones properly calibrated according to standards ISO 389-1 and ISO 389-3; PTA tests, speech audiometry and imitanciometry tests were performed by the same physician in all cases. The following average values were calculated with the formulas: tritone 1 average – Lloyd and Kaplan , quadritonal average – BIAP  and tritonal 2 average . Hearing losses were considered when the threshold of tritonal averages were above 25 dB HL, and BIAP average was above 20 dB HL according to the Lloyd and Kaplan (1978) and BIAP (1997) classifications, respectively. Patients with losses of these averages were interviewed for completing the HHIA that consisted of 25 questions quantifying social (12 questions) and emotional (13 questions) effects arising from hearing loss in individuals younger than 65 years. The respondent is asked to answer “yes”, “sometimes” or “no.” A “yes” answer is worth 4 points, “sometimes” is worth 2 points, and “no” does not get any points. The score ranges from 0 to 100. The classification follows the total score of HHIA: no perception of hearing handicap (0–16%), mild/moderate perception (18–42%) and severe (above 42%) perception.The patients selected were those on regular hemodialysis treatment in the center of nephrology of a hospital with public and private care. Inclusion criteria were: patients with CKD under the age of 55 and on HD for at least 3 months, while the exclusion criteria were: hearing loss of any etiology beginning before the CKD, transplantation, chronic ear infection, exposure to noise, mental disability, and use of ototoxic drugs for more than 1 week. Patients with normal otoscopy underwent tympanometry with an InteracousticsTwo groups of patients were created according to HT: Group I (less than 2 years) and Group II (2 years or longer).The correlations of the three tonal averages with hemodialysis time in Groups I and II were checked. Correlations of the three tonal averages with the total scores of HHIA and their domains were also tested.®. The profile of hearing loss and the perception of hearing handicap were established by applying descriptive statistics techniques, and the results were expressed in the form of tables and illustrative chart. The normality test used was the Shapiro–Wilk. Correlations were performed using bivariate correlation test with degree of linear relationship analyzed by Spearman coefficient. Differences were considered significant for the error value of α = 0.05.Statistical analysis was conducted using the Statistical Package for the Social Sciences – SPSS version 21.0 for WindowsThe sample consisted of 80 patients (160 ears) on HD, 39 men (48.75%) and 41 women (51.25%). Eighty-six ears (53.75%) had hearing loss in at least one of the pure tone averages in 48 patients . The 48 patients responded to HHIA, 28 (58.3%) being male. HD average time was 50.50 (± 41.25) months of the sample and of the patients with hearing loss was 54.25 (± 52) months. The type of loss was sensorineural in all cases, and with greater impairment of high frequencies .Figure 1The total number of ears with losses and the distribution of grades according to Lloyd and Kaplan, BIAP and tritone 2 sensorineural can be seen in The correlation test between tritonal and BIAP averages with HT in Groups I and II was performed. In Group I, no correlation of averages with HT was observed. In Group II, there was a weak, but statistically significant correlation of BIAP average with HT .Table 2CForty-eight HHIA questionnaires were filled and 43.75% had some degree of handicap perception with a total average of 30.50–63.00 .Table 3NThere were moderate correlations, and of tritone 1 average, with the score of the social domain of HHIA, and moderate correlation of quadritonal and tritonal 2 averages with total scores of HHIA and its social domain .Table 4CThere was a slight predominance of females in the sample (51.25%), but men (58.3%) predominated among patients with hearing loss. The average time of HD of patients with loss (54.25 months) was higher than the average sample time (50.50 months).n = 52) with some degree of disability compared to the classification of Lloyd and Kaplan (n = 16) that underestimated the number of cases. It was noted that this figure was even higher if Lloyd and Kaplan parameters were applied for the upper tritonal average . Hearing loss in CKD has the same characteristic of loss in the elderly when a higher incidence of high frequencies occurs; BIAP classification proved to be the one that best represents the degree of hearing loss in this population with losses with this feature.When using BIAP and Lloyd and Kaplan classifications, significant differences were observed in the number of cases classified as to the degree of loss for each of them. BIAP classification identified a larger number of cases  the losses in BIAP average showed correlations with the HT. It follows that after 2 years of treatment, there was a greater impact of factors related to CKD/hemodialysis on hearing function, and this is consistent with other studies that have shown that hearing loss may occur more frequently after 2 years of HD.18Hearing handicap proved to be mild/moderate in most cases with great similarity of scores in their fields.r = 0.30); these data suggest that the classification of Lloyd and Kaplan is limited because it does not reflect the impairment in communicative performance generated by such losses in this population. Total HHIA showed moderate correlations with the averages that consider the high frequencies  and the social domain portion of the HHIA. This illustrates the importance of high frequencies in the intelligibility of words, especially for the social life. Kielinen and Nerbonner = 0.41), but the correlations improved when the averages included 4 kHz in the formula (r = 0.55). Stewart et al.r = 0.678) than the average of the frequencies of 0.5, 1 and 2 kHz (r = 0.550); the same authors state that professionals who use tonal averages calculated from higher frequencies tend to intervene earlier in populations with hearing loss at high frequencies through the use of sound amplification or other auditory rehabilitation procedures such as those using formulas employing 0.5 kHz.No level of correlation of tritonal 1 average with hearing handicap was observed. Lima et al.In patients with hearing loss associated with CKD/hemodialysis the BIAP classification seems to be more suitable since it allows a better categorization regarding the degree of impairment. Its calculated average through the quadritonal formula correlated with the duration of hemodialysis in patients with 2 or more years of treatment, and had moderate correlation with the total score of HHIA and its social domain.The authors declare no conflicts of interest.