CDKL5) gene, encoding a kinase essential for normal brain development and function, are responsible for CDD. Zebrafish is an accepted biomedical model for the study of several genetic diseases and has many advantages over other models. Therefore, this work aimed to characterize the phenotypic, behavioral, and molecular consequences of the Cdkl5 protein disruption in a cdkl5 mutant zebrafish line (sa21938). cdkl5sa21938 mutants displayed a reduced head size, suggesting microcephaly, a feature frequently observed in CDD individuals. Double staining revealed shorter craniofacial cartilage structures and decrease bone mineralization in cdkl5 homozygous zebrafish indicating an abnormal craniofacial cartilage development and impaired skeletal development. Motor behavior analysis showed that cdkl5sa21938 embryos had less frequency of double coiling suggesting impaired glutamatergic neurotransmission. Locomotor behavior analysis revealed that homozygous embryos swim shorter distances, indicative of impaired motor activity which is one of the main traits of CCD. Although no apparent spontaneous seizures were observed in these models, upon treatment with pentylenetetrazole, seizure behavior and an increase in the distance travelled were observed. Quantitative PCR showed that neuronal markers, including glutamatergic genes were dysregulated in cdkl5sa21938 mutant embryos. In conclusion, homozygous cdkl5sa21938 zebrafish mimic several characteristics of CDD, thus validating them as a suitable animal model to better understand the physiopathology of this disorder.CDKL5 deficiency disorder (CDD) is a rare neurodevelopmental condition characterized primarily by seizures and impairment of cognitive and motor skills. Additional phenotypes include microcephaly, dysmorphic facial features, and scoliosis. Mutations in cyclin-dependent kinase-like 5 ( However, a variety of additional features have also been observed including microcephaly, scoliosis, bruxism, and distinctive facial features2. Despite the severity of the disease, the mechanisms responsible for its onset remain unclear.CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental condition characterized primarily by early-onset seizures, which generally begin in the first months of life and impairment of cognitive and motor skills 3. Human CDLK5 is encoded by a single-copy gene located on the X chromosome and although the disorder is essentially observed in heterozygous females due to dominant X-linked mutations, the most severe phenotypes are observed in males2. CDKL5 is a ubiquitous protein mainly expressed in the brain, testes and thymus and found both in the cytoplasm and in the nucleus, where it co-localizes with nuclear speckles4. It has a kinase catalytic activity responsible for its autophosphorylation as well as the phosphorylation of amphiphysin 1, its first identified substrate5. CDKL5 can also mediate MeCP2 phosphorylation, suggesting a molecular link between CDKL5 disorder and MeCP2-associated Rett syndrome6. More recently, CDKL5 was shown to interact with Shootin1 and contribute to the regulation of neuronal polarization7.The disorder is associated with a loss of cyclin-dependent kinase-like 5 (CDKL5) function due to a variety of mutations, but the link between the type or location of mutations and symptoms is not clearly understoodCdkl5 knockout (KO) do not completely reproduce the human CDKL5 phenotype makes the use of alternative models such as zebrafish mutant lines even more interesting. Indeed, as referred in a recent review, despite all the advantages of rodent models, none of the available mutant Cdkl5 mouse models develop early-onset seizures, a central feature of this syndrome in humans8. In contrast, it was recently shown that zebrafish, upon treatment with pentylenetetrazole (PTZ) can develop seizures, allowing researchers to investigate the molecular basis of this phenotype9.Although mammalian models suggest a potential for reversibility, there are no approved therapies yet and standard treatments do not provide substantial symptom relief. The development of alternative and/or complementary model organisms that may accelerate the development of therapeutic approaches should therefore be contemplated to gain valuable insights in this field. The fact that the existing mouse models for 10 and shares many physiological processes with humans including a large structural and functional conservation between zebrafish and human genes11. Zebrafish has a single cdkl5 gene and two alternative splice variants, similar to human CDKL5, were recently identified. Variant 1 is mainly expressed in the brain, while variant 2 is ubiquitously expressed12. Although the function and mode of action of Cdkl5 in fish have not been investigated, previous studies conducted in our laboratory showed that cdkl5 expression in zebrafish is in accordance with its known localization in humans13. Also, zebrafish cdkl5 structural organization, flanking genomic regions, and putative transcription factor binding sites located in its promoter region appear to be highly conserved when compared to its human ortholog13. The corresponding proteins also show a high degree of sequence conservation, particularly in the catalytic domains required for phosphorylation13. These data support the suitability of zebrafish as a valid model to investigate CDKL5 deficiency disorder.Zebrafish is a suitable biomedical model that has been established as a genetically manipulable systemcdkl5sa21938) expressing a mutant form of Cdkl5, in terms of their morphological and behavior phenotype as well as their molecular alterations. The overall goal is to provide a new model organism to further investigate the Cdkl5 signaling pathway and mechanisms that lead to CDKL5 deficiency disorder and ultimately, contribute to the identification of therapeutic targets to treat or relief symptoms of CDD.The main objective of this study was to characterize a stable zebrafish model (cdkl5 zebrafish line (sa21938) generated through the Zebrafish Mutation Project by ENU mutagenesis of males was characterized in this work.CDKL5 loss-of-function in humans is known to be responsible for the CDKL5 deficiency disorder phenotype. To investigate the effect of Cdkl5 loss-of-function, a mutant cdkl5 has two splice variants encoding two proteins with 1039 and 1080 amino acids (aa), consisting of an N-terminal catalytic domain and a C-terminal region containing two nuclear localization signals and one nuclear export signal. cdkl5sa21938 mutants have a nonsense mutation in exon 11 of the cdkl5 gene  were genotyped to find heterozygous cdkl5sa21938 mutants and then in-crossed to obtain homozygous zebrafish. Sequencing results confirmed the existence of the three possible resulting genotypes  and homozygous (cdkl5−/−) mutants were characterized throughout the first days of development. No severe morphological defects were observed in the mutants compared to wild-type embryos during the initial stages of development , associated with Rett syndrome, is a chromatin-associated protein that binds to methylated CpG sites of genes, regulating their activity19. It was demonstrated that MECP2 represses CDKL5 transcription and that CDKL5 can phosphorylate MECP220. MECP2 is also known to affect the activity of BDNF (Brain-derived neurotrophic factor) which is an important regulator of neuronal development and function22. Interestingly, studies showed that CDKL5 regulates neuronal morphogenesis through a mechanism involving BDNF-Rac1 signaling6. In our study, levels of bdnf and mecp2 were equally significantly increased in cdkl5 heterozygous and homozygous mutant embryos compared to the WT embryos , a major mediator of dopamine effects with diverse functions such as cognition, movement, learning and memory, was found increased in the striatum of Mecp2 mutant mice25. Our results showed that levels of mef2ca and drd2a were also significantly increased but only in the homozygous embryos  in their study. In our study, an overall decrease in bone mineralization was observed in homozygous cdkl5 mutants in comparison to wild-type larvae at 14 dpf. Altogether, these results indicate that Cdkl5 is needed for both normal cartilage craniofacial development and skeletal development. The presence of skeletal deformities in adult mutant fish should be evaluated to further elucidate the Cdkl5 role in bone formation.CDKL5 has been suggested to have a potential role in bone metabolism. A recent study showed that it was hypermethylated in all the osteoporotic participants37, the motor behavior of cdkl5sa21938 mutants was investigated. No differences were observed in the frequency of spontaneous single contractions, that is the earliest embryonic motor behavior, between cdkl5sa21938 mutants and wild-type embryos. Spontaneous coiling is driven by excitatory activity in the spinal cord and it is only dependent on the electrical coupling of the neuronal network. Subsequently, as chemical neurotransmission develops, mature locomotion is achieved16. Our results indicate that excitation in the spinal cord is not affected by Cdkl5 loss-of-function. The double coiling represents a transition behavior between single coiling and swimming activity driven by chemical glutamatergic and glycinergic neurotransmission16. cdkl5sa21938 embryos showed a reduced percentage of double coiling suggesting that Cdkl5 deficiency results in abnormal glutamatergic neurotransmission. Locomotor behavior analysis revealed that the swimming activity was reduced in cdkl5 homozygous embryos, which covered a shorter swimming distance. Accordingly, a significant decrease in distance swum by the homozygous mutant was also reported by Serrano et al.35. The available works using CDKL5 KO mice showed contradictory behavioral results among them, with both hypoactivity and hyperactivity reported in these studies38. Altogether, these results suggest that Cdkl5 ablation in zebrafish causes impairment in their motor activity, following what was observed in individuals with CCD that have impaired motor skills such as delayed or impaired walking.Motor dysfunction is a prominent feature of CDKL5 deficiency disorder. Since zebrafish is recognized as a valuable model to study genetically linked motor defects and behaviors observed in neurodevelopmental human diseasescdkl5 embryos showed a slight but significant reduced thigmotaxis. These results may suggest that embryos with defective Cdkl5 have anxiety behavioral alterations or could be sensitive to the tactile stimuli represented by the wall of the well, a behavior that resembles the autistic features in CDD individuals. In accordance, Wang et al. reported a decreased anxiety-related behavior and autistic-like behavior in Cdkl5 KO mice30.The thigmotaxis behavior used to evaluate the level of anxiety was also investigated. Homozygous cdkl5sa21938 zebrafish embryos, at least through the analysis of the mutant fish swimming behavior with the tested conditions (5 min of tracking and 5 dpf zebrafish). Nevertheless, we cannot affirm that the cdkl5sa21938 mutant does not have spontaneous seizures. The absence of spontaneous seizures could be simply because of the parameters used, such as the age of the fish and the time of tracking used for the analysis. Thus, the behavior of mutants at older stages of development should be further analyzed, and the time of tracking could be increased. Electroencephalographic records should also be performed to investigate the epileptic phenotype. Interestingly, Serrano et al. identified the existence of spontaneous seizures in cdkl5 zebrafish mutants through live imaging of the brain by using a transgenic line expressing a genetically-encoded calcium indicator. This represents an advantage over the existent Cdkl5 mouse models that do not exhibit spontaneous seizures at initial developmental stages30. Nevertheless, our results showed that after treatment with a seizure-inducing drug, a seizure behavior was achieved by the homozygous fish, with an increase in their swimming activity. And that increase was significantly greater in the homozygous mutants compared to the wild-type fish thus, indicating higher susceptibility to seizures. This could be valuable to identify epileptic mechanisms affected by Cdkl5 loss-of-function in CDD. The latency, number of seizures, seizure times and the interval between seizures should also be investigated to better characterize the epileptic events.Although early-onset seizures are a central characteristic of CDKL5 deficiency disorder, spontaneous seizures were not apparent in cdkl5sa21938 embryos. The genes bdnf, mecp2 mef2ca and drd2a were upregulated in homozygous embryos. BDNF is crucial for the central nervous system development, and studies show that it is involved in epileptogenesis. Although there are contradictory data, some studies indicate that higher levels of BDNF induce epilepsy39. MECP2 is a methyl-CpG-binding protein important for appropriate neuronal development. In vivo studies showed that mice overexpressing MECP2 develop seizures and are less active40, therefore the presence of higher levels of this gene in mutant embryos provides further evidence for the presence of abnormal neuronal development/function. Since our results suggested an impairment of the glutamatergic neurotransmission in the cdkl5sa21938 mutants, we also analyzed the expression of glutamatergic-related genes, including the NMDA receptor grin1b, the AMPA receptor grin2a, the metabotropic receptor grm1b, and the glutamate transporter slc1a1. These genes were all overexpressed in the cdkl5sa21938 mutants, confirming that the glutamatergic pathway is affected. The connection between the dysregulation of expression of the analyzed genes and the observed phenotype should be further investigated, and the expression of additional genes should be analyzed to identify the molecular basis of the disease, for instance by performing RNA-seq.To shed light on the molecular pathways affected by defective Cdkl5, the expression levels of brain-related genes were examined in the mutant cdkl5sa21938 zebrafish recapitulate a number of characteristics of CDKL5 deficiency disorder, such as the presence of microcephaly, craniofacial dysmorphic features, and locomotor behavior defects. Therefore, this work provides evidence that validates the use of this model organism to further study CDKL5 function and associated molecular pathways, in order to better understand the physiopathology of CDD. Furthermore, it represents a suitable in vivo model for the first-line screening of small-molecule libraries for total/partial rescue of phenotypes mimicking CDKL5 deficiency disorder.In conclusion, our data show that homozygous https://arriveguidelines.org). This study was approved by the Portuguese Direção-Geral de Alimentação e Veterinária (authorization no. 0421/2021). Animal handling and experimentation were performed by qualified operators. All efforts were made to minimize pain, distress, and discomfort. Experiments were terminated  whenever adverse effects were observed.All procedures involving zebrafish experimentation were performed in accordance with the EU and Portuguese legislation for animal experimentation and welfare  and in compliance with ARRIVE guidelines (cdkl5sa21938 zebrafish line generated by Stemple lab41 was obtained from EZRC. Adult wild-type (WT) zebrafish (AB strain) and cdkl5sa21938 mutant zebrafish were maintained in a recirculating system at controlled room temperature (28 °C) and kept under a 14 h light -10 h dark cycle. For the reproductions, adult females were separated from males with plastic dividers in breeding boxes the night before spawning. The next day, they were allowed to spawn naturally. The embryos were raised in E3 medium with 0.1% methylene blue to avoid fungal contamination and staged according to the morphological scheme described by Kimmel et al.42. Dead or undeveloped embryos were removed daily. For the experiments using the cdkl5sa21938 mutant line, heterozygous embryos were obtained by crossing adults F3 homozygous mutants with AB wild-type zebrafish; homozygous embryos were obtained by incross adults F3 homozygous mutants, and AB wild-type zebrafish was used as control.Mutant cdkl5 fragment flanking the mutation was amplified by polymerase chain reaction (PCR) from 50 ng of gDNA using specific primers (Table To extract genomic DNA (gDNA), adult zebrafish were anesthetized in tricaine methanesulfonate (MS222) solution 168 mg/L), and the tail fin was clipped and incubated at 95 °C in 25 μl alkaline lysis buffer containing 25 mM NaOH and 0.2 mM EDTA. After dissolution, 25 μl of neutralization buffer (40 mM Tris–HCl. pH = 8) was added. Then, the 68 mg/L, cdkl5 mutants was visualized and photographed at different developmental stages using a Leica MZ10F stereomicroscope. Parameters including body length, head length and head width were measured using ImageJ software.Phenotype of zebrafish 43. Briefly, zebrafish were incubated with double stain solution  overnight at room temperature under agitation. The pigmentation was removed by exposing the zebrafish to a bleaching solution of 1.5% H2O2 and 1% KOH for 20 min. Then, the tissue was cleared using successive changes of glycerol and KOH solution. Stained zebrafish were visualized and imaged using a stereomicroscope (Leica MZ10F). Several craniofacial parameters, such as ceratohyal angle (Ch-a), ceratohyal length (Ch-l), palatoquadrate length (Pq-l), ceratohyal cartilage length (CCL) and lower jaw length (LJL) were measured using Image J.Zebrafish with 5 dpf and 14 dpf were collected and sacrificed with a lethal dose of anesthesia (MS222). After washing twice with phosphate-buffered saline (PBS), zebrafish were fixed overnight in 4% paraformaldehyde . They were washed twice with PBS and dehydrated in increasing ethanol series. Acid-free double staining was performed following Walker and Kimmel protocolcdkl5 mutant zebrafish was characterized through several parameters and compared to wild-type or control fish. The rate of spontaneous coiling contractions was analyzed at 25 h post-fertilization (hpf). For that, embryos were dechorionated and placed in a 12-well plate filled with 2 ml of water. After 1 h of habituation each fish was recorded for 2 min using a stereomicroscope.The motor behavior of To monitor the spontaneous swimming activity, embryos with 5 days post-fertilization (dpf) were randomly placed in a 24-well plate filled in with 2 ml of water. Homogeneous illumination was provided, and swimming motor behavior was monitored for 5 min using the ZANTIKS apparatus. Parameters such as distance travelled, thigmotaxis and swimming patterns were analyzed. Embryos that did not swim were excluded from the analysis. To investigate thigmotactic behavior, wells were divided into two zones: an inner circular region (radius 4.5 mm) and an outer circular region (radius 8 mm); and the time spent by the embryos in each region was assessed.Embryos’ behavior was also analyzed after treatment with PTZ, a seizure-inducing drug. For that, the water from each well was removed and 2 ml of PTZ solution  was added. After 10 min, swimming behavior was recorded for 5 min using the ZANTIKs apparatus.cdkl5sa21938 mutant embryos with 5 dpf were collected, sacrificed with a lethal concentration of anesthesia (MS22), and washed twice with PBS. Total RNA was extracted using NZYol (NZYTech) according to the manufacturer’s instructions and its quality was accessed through electrophoresis in an agarose gel stained with GreenSafe (NZYTech). At least three biological replicates were obtained from individual experiments. For reverse transcription, 1 µg of total RNA was subjected for 30 min at 37 °C to RQ1 RNase-free DNase (Promega) and cDNA was synthesized by the Moloney murine leukemia virus reverse transcriptase (Invitrogen) using an oligo-dT primer.Pools of approximately 30 –∆∆Ct and normalized using β-actin as reference gene , 0.4 μM of each forward and reverse gene-specific primers and 2 μl of cDNA (1:10 dilution). Gene-specific primers are listed in Table p < 0.05.Statistical analysis was performed using Prism 5 (GraphPad Software). Data normality was assessed using Kolmogorov–Smirnov test. Normally distributed data are presented as mean ± SD and significant differences were determined through one-way analysis of variance (ANOVA) followed by Tukey’s post-test for three groups and t-test with Welch correction for two groups. Data failing the normality test are presented as median with the interquartile region (boxplot) and significant differences were determined through Kruskal–Wallis followed by Dunn multiple comparisons test for three groups and Mann–Whitney test for two groups. The Chi-square test was used to analyze the occurrence of mineralized caudal fin rays. Differences were considered statistically significant for


Hearing loss is the most common form of sensory impairment in humans, affecting people of all ages. The most recent Global Burden of Disease Study revealed that deafness is the fourth leading cause of years lived with disability and its prevalence continues to grow. Deafness has serious negative consequences for the individual and society, such as difficulties in communication leading to social isolation and withdrawal. It affects mental health and wellbeing, causing depression and anxiety. It is a barrier to independent living and has been linked to dementia. The primary clinical management intervention for people with hearing loss is hearing aids, but not all people with a measurable form of hearing loss could use a hearing aid. The majority (80%) of adults aged 55–74 years, who would benefit from a hearing aid, do not use them. Furthermore, many people who are issued a hearing aid do not wear it . AlthougOver the last three decades, the cochlear implant (CI) has become the most successful sensory prosthesis worldwide for the rehabilitation of severe to profound deafness, as it provides open-set speech understanding in majority of the patients, and some patients with CI can also use the telephone . Since tDespite the huge clinical success of the CI, clinicians still continue to face the challenge of expanding CI indications to allow more people who cannot receive the benefits of conventional hearing aids to be able to receive CI and of optimizing the outcomes in CI users with inner ear or auditory nerve anomalies. A large body of research demonstrating the efficacy of MEI/BCI devices and their clinical safety and shortfalls has been published to date. Despite their clinical potential, they have not been widely used in clinical practice at present, especially in the case of MEI. Only a few centers in the world routinely consider them when counseling patients who are hearing impaired.The current Research Topic edition included seven timely articles covering a wide range of scientific topics associated with auditory implantable devices. It offers an in-depth look at some of the most relevant issues related to their clinical use. Two articles discussed the challenges posed by cochlear implantation, and five articles reviewed some of the newest research outcomes on active implantable devices in the middle ear.Jenkins et al., the authors examined the existing evidence on the use of round window stimulation to manage patients with mixed hearing loss, while active vibration of the ossicular chain/or stapes is not an option due to existing ear diseases. They elegantly reviewed the basic and clinical research on the mechanism of direct round window membrane stimulation and the validation of its clinical use. The authors recognized the early pioneering research of Colletti et al.  follow-up study in which 43 patients implanted with one fully implantable active middle ear implant from a single center were included in the present study. The study found that, after the initial 4 years of post-implantation, some of the patients showed a significant worsening of bone conduction threshold relative to the baseline threshold in the implanted ear as well as a significant decrease when comparing the implanted ear to the contralateral non-implanted ear. The authors attributed the asymmetrical deterioration of the bone conduction threshold to greater energy delivery to the inner ear over time through direct coupling of the device to the stapes. Despite the deterioration of hearing in the implanted ears, the functional gain observed at the initial activation remained constant at follow-up, suggesting an extension of the efficacy of this device in more severe forms of sensorineural hearing loss.Continuing along the lines of the fully implantable active middle ear implant, Frohlich et al. described and analyzed VSB-evoked auditory brainstem response (ABR) wave-V intensity-latency functions to coupling efficiency, response thresholds, and coupling modality [oval window (OW) placement vs. incus placement and round window (RW) placement]. They found no correlation between VSB-evoked ABR wave-V intensity-latency functions and coupling efficiency, and there is a rather large variance of individual wave-V latencies at the threshold level. However, the slopes of the intensity-latency function were observed to converge to a steady-state latency of 7–8 ms at the stimulation levels between 30 dB and more above the ABR threshold. The authors suggest that the saturation in VSB-evoked ABR wave-V latencies most likely occurred due to the limited dynamic range of the audio processor used for signal transmission so that the analysis of VSB-evoked intensity-latency functions can be useful for the objective assessment of a patient's dynamic range with the Soundbridge, with vibroplasty-evoked ABR threshold being an objective indicator of coupling efficacy.Two articles looked at two different aspects of the floating mass transducer vibroplasties of the Vibrant Soundbridge (VSB). Seiwerth et al. reported their study on the influence of VSB and Bone bridge implantation on patients' balance function. They found that 50% of patients with an optimally turned VSB or Bonebridge BCI had a subjectively positive effect on postural control, despite an improvement that could only be shown objectively in a walking task in the trunk sway measurement and in individual changes in stability in a force plate measurement.Under the hypothesis that auditory cues may contribute to postural control in addition to visual, proprioceptive, and vestibular information, Wei et al. examined the challenges posed by CI in patients with cochlear common cavity anomalies. Using the multiplanar volume reconstruction (MPVR) techniques to reconstruct postoperative computed tomography (CT) of the temporal bone, they analyzed the correlation of the distance between each electrode and the cavity wall, programming parameters, and performance outcomes. The authors conclude that the shorter the distance between the individual electrode and the common cavity wall, the lower the maximum comfortable level of stimulation, which in turn appears to promote better speech outcomes despite the shorter distance between the individual electrodes and the cavity wall and increases the incidence of facial nerve stimulation.In their study, Benitez et al. reported the outcomes of CI in postlingually deafened children and adults with single-sided deafness (SSD). The results of the study showed that cochlear implantation in postlingually deafened adults and children with SSD can achieve a speech perception outcome comparable to cochlear implementation in conventional candidates. Improvements in the spatial hearing were also observed in those patients with short-term deafness.In summary, it is our opinion that this collection of articles will provide readers with a better understanding of some challenging issues associated with auditory implants, promote future research in this field, and provide clinicians with better information while making decisions about offering these devices to patients and/or optimizing these devices to rehabilitate hearing loss.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.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.


Several areas of human knowledge are evolving rapidly. Otorhinolaryngology is one of them: endoscopic surgery, cochlear implants, and robotic surgery are now a reality.Until a few years ago, we faced difficulties obtaining an early diagnosis and treating infants born with hearing impairment (HI). Diagnostic advances, including otoacoustic emission, auditory brainstem response (ABR), steady-state potentials – as well as therapeutic advances with digital amplification devices, cochlear implants, implantable prostheses, etc. – have completely changed the prognosis for children with HI. Nowadays, thanks to technological advances, we can guarantee a completely normal life for these infants.The main contemporary challenges for professionals working with children exhibiting language delay are related to diseases that have no available laboratory tests to establish the diagnosis and no surgical or clinical treatment to change its evolution. The prognosis depends on establishing the diagnosis as soon as possible and on the right specific speech therapy. In this scenario, the two most significant diseases are autistic spectrum disorder (ASD) and specific language disorder (SLD).Upon learning of this subject, perhaps many otorhinolaryngologists wonder: “Where are these children, for I do not see them?” Certainly, they are being seen in these same professionals’ offices, because these are highly prevalent diseases, although they are not being diagnosed.The various disciplines studying language development in children – such as speech therapy, developmental pediatrics, psychiatry, and pediatric neurology – are finding an increased incidence of ASD. The 2014 report of CDC (Center for Disease Control) relates an ASD incidence of 1:68 for 8-year-old children, five times more frequent in males (1:42) than in females (1:189).Regarding SLD, the NIH  states that this disease affects about 7–8% of preschool children and that in 50–70% of cases there is at least one relative suffering the same disturbance.In Brazil, no epidemiological studies on ASD and SLD have been conducted, but it is possible that the Brazilian rates are similar to those of the United States.Hearing represents the world's largest information gateway. But having normal hearing thresholds is not enough: we need to process and recognize the auditory information in a quick and correct way.Through electrophysiological tests, such as ABR with speech stimuli, we can identify children with auditory processing disorder which may present reading and writing learning difficulties in their early years of life.In most cases, patients with language delay or learning disability are initially seen by an otorhinolaryngologist for suspected HI.What should be the role of the otorhinolaryngologist in these cases? Every time we see a child with language delay and with normal hearing, we must think that, by simply stating that the exam is normal, that everything is fine, and that the child should talk soon, we may be delaying the correct diagnosis and losing a few months of great neuroplasticity.A more thorough assessment, followed by a proper guidance, can dramatically change the future of a child.Similarly, it is important to investigate the auditory processing of those children with learning disabilities, for without an accurate diagnosis, they can waste years with inadequate and ineffective therapies.For many years, otolaryngologists treated hearing problems in the cochlea. But thanks to ABR, hearing also can be assessed in the brain stem. Today, we must be prepared to assess hearing in the brain. Mismatch Negativity (MMN), P300, ABR with speech stimuli, and behavioral assessments of auditory processing offer much information that can assist in the diagnosis and therapeutic management of patients with oral or written language disorders and normal hearing thresholds.For those who are interested in these topics, the ABORL has been offering the Extensive Training Course in Phoniatry for two years.The author declares no conflicts of interest.


The first two years of life are critical for the acquisition and development of hearing and speaking skills.This prospective study aims to verify the performance of infants with cleft lip and palate (CLP) with and without risk factors for hearing (RFH) in the verbal recognition test (VRT).The parents of 100 infants (9 to 18 months of age) with CLP were interviewed to investigate the presence of RFH and to sort out the characteristics of the study groups. All infants underwent VRT.Otologic diseases, lack of breastfeeding, parental smoking, upper airway insufficiency, stay in an incubator, and family history of hearing impairment were the most frequent RFH. Eighty-five infants had RFH, among which 40% had altered VRT results; fifteen did not have any RFH and 73% performed as expected for their age range in the VRT. There was no significant difference (p=0.326) between groups. Fifty-four infants had history of otitis media (OM), among which 31% had altered VRT results; forty-six had no history of OM and performed as expected for their age range in the VRT; Statistically significant difference (p=0.000) was found.Other risk factors for hearing aside CLP were found. Infants with and without history of RFH performed similarly in the VRT. The presence of otologic diseases significantly interfered with the VRT. The first two years of life are considered to be a critical period for the acquisition and development of auditory and language skills.Since the first weeks of life, a series of skills related to perception can be observed in infants. As is the case for other sensory organs, the vestibule is functional at birth. Infants are therefore able to locate sources of sound. However, starting at the third week of life, infants do not stay focused as they hear a soundHowever, pre, intra, and post-natal disturbances may compromise a child's development. Damages inflicted upon the auditory sensory system will modify the way a child receives input, thus changing the nature of the intellectual and biopsychosocial experience he or she will have.The Joint Committee on Infant Hearing listed a series of risk indicators to identify the children at a higher risk of having hearing impairment.Longitudinal follow-up of infants at risk for developmental disorders is fundamental, as the first year of life represents a significant transition in the evolution of human beings, a time when the most important changes and evolutionary leaps take place.Considering therefore that the first year of life is critical in hearing development, that familiar voices are among the stimuli that best promote reliable responses from infants, and that congenital malformation is an important risk indicator for hearing and others, we decided to carry out a prospective study on the verbal recognition skills of infants with cleft lift and palate, with and without risk factors for hearing.This study aims to verify the performance of infants with cleft lip and palate, with and without history of risk factors for hearing, tested for verbal recognition.This study was approved by the Ethics Research Committee of our institution under permit 319/2004-UEPCEP. One hundred infants with ages ranging between nine and eighteen months were randomly enrolled in this prospective study. All infants included in this study had congenital cleft lip and palate and had undergone at least one lip or palate repair surgery. Nine infants had only their upper lips involved, sixty-eight had their upper lips and entire palates (soft and hard) involved, and twenty-three had only their palates (soft and hard) involved. This study was done in 2004 and 2005.The parents of all infants were interviewed6 to check for hearing risk factors and split the infants into groups.All parents read an Informative Letter and signed a Free Informed Consent Term.All infants were examined for verbal recognition as proposed by Azevedo- Level 1:‘Waive goodbye!’, ‘Throw me a kiss!’, ‘Clap your hands!’ - for 9-12 month old infants.- Level 2:‘Where's mommy?’, ‘Where's your pacifier?’, ‘Where's your shoe?’ - for 12-15 month old infants.- Level 3:‘Where's your hair?’, ‘Where's your hand?’, ‘Where are your feet?’- for 15-18 month old infants.The following verbal cues were used:All responses were observed by an examiner and sorted as normal or altered. Normal response means the infant responded to the verbal cue expected for his or her age group, while altered means unresponsiveness.Group A:infants with risk factors for hearing impairment.Group B:infants without risk factors for hearing impairment.Two groups were formed as a result of the interviews with the parents:Statistical analysis was carried out using the chi-square test. A five percent threshold was adopted to refute the null hypothesis (Ho).After interviewing the parents of 100 infants, we found that 85 of the children had at least one risk factor for hearing impairment (Group A). The remaining fifteen were not reported for any hearing impairment risk factor (Group B). Statistical analysis pointed presence of ear disease (e.g.: otitis media) as the only risk factor with significant impact on the results of verbal recognition testing when compared to the other reported risk factors .Chart 3DThe Joint Committee on Infant Hearing (2000) stresses, among others, the presence of craniofacial malformations such as cleft lip and palate as a risk factor for hearing impairment. This study emphasized other risk factors found in the infants with cleft lip and palate .4Otitis media is the most commonly diagnosed pediatric condition, affecting an estimated 70% of all children.8 Craniofacial malformations, specifically cleft lip and palate, establish a direct connection between the nasal and oropharyngeal cavities and the opening of the Eustachian tube. Therefore, Eustachian tube disorders affecting this population also present themselves as a risk factor for the development of secretory otitis media.Evidences show that breastfeeding, especially when offered at least until the infant's sixth month of life, reduces the chance of otitis media, as the development of the face muscles and introduction of immunoglobulins act as protection mechanisms.Exposure to tobacco smoke may lead to increased risk of respiratory disease (upper airway infections) and secretory otitis media among infants. Epidemiological findings and isolated studies point to increased prevalence and higher incidence of otitis media among children exposed to tobacco smoke. As the number of cases of respiratory infection in parents and infants increases, the more likely the episodes of otitis media become.Exposure of newborns to intense noise in incubators7 and presence of diseases or conditions that require incubator stays longer than 48 hours4 are important risk factors for hearing loss that were also found in the group of infants enrolled in this study.Epidemiological data suggests that congenital hearing loss occurs in one of every one thousand live births, with half of the cases having genetic origins.Maternal drug and alcohol abuse, low weight at birth, intrauterine infection, consanguine parents, and immune disease were some of the risk factors identified in this study, however with a prevalence rate below 3%.Alcoholic drinks ingested by pregnant women go through the placenta barrier and expose the fetus to the same concentrations of alcohol found in the mother's bloodstream. Thus, as metabolism and elimination of substances is slower in the fetus, fetal exposure is dramatically increased.Individuals with cleft lip and/or palate are more likely to have very low weight at birth, however without establishing a direct relationship with prematurityIntrauterine infections including toxoplasmosis, measles, cytomegalovirus, herpes, and syphilis, have been pointed as relevant risk factor for hearing impairment and accounted for various degrees and patterns of hearing loss.Significant associations between consanguine parents and cleft lip and palate have been described in the literature36Although Group A presents more altered results in the verbal recognition test, Group B had more responses within the level expected for the infants’ ages as proposed by Azevedo (1991)7 . As no sWhen statistically analyzing the impact of each risk factor on the verbal recognition test results, ear disease – otitis media, in the case – was the only risk factor bearing significant impact on the results of the verbal recognition test when compared to all other present factors.History of ear disease as a risk factor for hearing impairment in the infants with cleft lip and palate analyzed in this study was the indicator that most impacted the performance of infants in the verbal recognition test. The deleterious impact on speech and language development introduced by the presence of otitis media has been mentioned in a number of studies.38This study allowed the identification of other risk factors for hearing loss aside from congenital malformation. The performance of infants with and without history of risk factors for hearing loss was not different in the verbal recognition test. Presence of ear disease had statistically significant impact on verbal recognition test results.


Existing evidence links hearing loss to depressive symptoms, with the extent of association and underlying mechanisms remaining inconclusive. We conducted a cross-sectional study to examine the association of hearing loss with depressive symptoms and explored whether social isolation mediated the association.Eight thousand nine hundred sixty-two participants from Guangzhou Biobank Cohort Study were included. Data on self-reported hearing status, the 15-item Geriatric Depression Scale (GDS-15), social isolation and potential confounders were collected by face-to-face interview.The mean (standard deviation) age of participants was 60.2 (7.8) years. The prevalence of poor and fair hearing was 6.8% and 60.8%, respectively. After adjusting for age, sex, household income, education, occupation, smoking, alcohol use, self-rated health, comorbidities, compared with participants who had normal hearing, those with poor hearing  0.54, 0.94) and fair hearing  had higher scores of GDS-15. After similar adjustment, those with poor hearing (odds ratio (OR) = 2.13, 95% CI 1.65, 2.74) or fair hearing  also showed higher odds of depressive symptoms. The association of poor and fair hearing with depressive symptoms attenuated slightly but not substantially after additionally adjusting for social isolation. In the mediation analysis, the adjusted proportion of the association mediated through social isolation was 9% .Poor hearing was associated with a higher risk of depressive symptoms, which was only partly mediated by social isolation. Further investigation of the underlying mechanisms is warranted.The online version contains supplementary material available at 10.1186/s12877-022-03311-0. Depressive symptoms is the most common mental disorder in older people  and a leHearing loss is another common health problem in older people, leading to communication difficulties. In 2015, more than half of adults in China aged over 60 years were affected by hearing loss . Hearing2 = 83.26%) [Moreover, existing evidence also links hearing loss to depression –14, alth 83.26%) .Hearing loss may lead to communication difficulties, and subsequent feelings of being emotionally isolated and social isolated , 18–20. Hence, we examined the association between hearing loss and depressive symptoms using data from the Guangzhou Biobank Cohort Study (GBCS), a well-designed on-going population-based cohort study of older Chinese . We alsoGBCS is a three-way collaboration among the Guangzhou Twelfth People’s Hospital in Guangzhou and the University of Hong Kong in Hong Kong, China, and the University of Birmingham in UK. Details of the GBCS have been reported elsewhere . BrieflyInformation on hearing impairment was assessed by self-reports at baseline . ParticiDepressive symptoms were assessed by a previously validated Chinese version of the 15-item geriatric depression scale (GDS-15) . The GDSThe potential mediator was social isolation. We used the Berkman-Syme Social Network Index (SNI) with appropriate revision , 33, whiPotential confounders adjusted in the multivariable model were age, sex, socioeconomic position , smoking , 36, alcPearson chi-square test and one-way analysis of variance (ANOVA) were used to compare categorical and continuous variables between groups, respectively. Multivariable linear regression was used to assess the association between hearing loss and GDS-15 scores, reporting adjusted regression coefficient (β) and 95% confidence interval (CI). Logistic regression model was used to assess the association between hearing loss and the presence of depressive symptoms, giving odds ratio (OR) and 95% CI. Mediation analysis was conducted to assess the proportion of the association mediated through social isolation. The “medeff” package in Stata was used to perform mediation analysis. We also performed sensitivity analyses by (1) using different cutoff value of GDS-15 score for the definition of depressive symptoms, and (2) excluding those with hearing aids. Data analysis was done using STATA/SE 15.1.Of 10,088 participants recruited from 2006–2008, after excluding 1,126 (11.2%) participants with missing data, 8,962 participants (74.3% women) with complete data on all variables of interest were included in the current analysis.P from 0.001 to 0.01). Those with poor hearing also had higher scores of GDS-15 and prevalence of depressive symptoms (both P < 0.001) . Mediation analysis showed that the proportion of the association mediated through social isolation was 13%  and the results remained after adjusting for potential confounders  (Table not shown).Table Sensitivity analyses using GDS-15 score of 8 or more as the cut-off point to define the presence of depressive symptoms showed similar results. Poor hearing was significantly associated with higher odds of depressive symptoms  . Fourth, our participants might not be fully representative to the general population due to the oversampling of women. Nevertheless, we adjusted for sex in the regression models as well as tested the interaction between hearing loss and sex, and we found no evidence that the associations varied by sex. Thus the unbalanced sex ratio might not be a major concern. Fifth, as our data were collected by interview, those with hearing difficulty might not be able to answer the questions correctly due to their poor hearing. However, as the interviews were conducted one-on-one and face-to-face by well-trained nurses using a computer-assisted questionnaire, the impact of hearing difficulty on hearing and answering the questions correctly was minimized.Strengthens of our study included the large number of participants and a quantitative mediation analysis on social isolation. However, our study also had some limitations. First, causal inference could not be confirmed in the current study using cross-sectional analysis. Second, hearing status was classified by self-report. Further studies with hearing status measured by pure-tone audiometry are warranted , 57. ThiIn conclusion, our study showed that poor hearing was associated with a higher risk of depressive symptoms, and the association could not be fully explained by social isolation. Further investigation to shed light on the exact mechanisms behind this phenomenon is warranted. Health professionals and clinical practitioners are recommended to increase their awareness and understanding of depressive symptoms related to hearing status.Additional file 1: Supplementary Table 1. The four types of social isolation question and thescoring criteria for the composite social isolation score. Supplementary Table2. The Chinese version of four types of social isolation question and thescoring criteria for the composite social isolation score. Supplementary Table3. Associationof hearing loss with depressive symptoms (GDS-15 score ≥8). Supplementary Table4. Association of hearingloss with depressive symptoms after excluding participants with hearing aids (n=20).


International studies also show the high prevalence of hearing loss in the elderly.According to recent investigations, as the number of elderly people increase, the prevalence of presbycusis interfering in the life quality of this population also increases. Even among health care professionals, there is a huge lack of knowledge about the advantages and gains a specific hearing reeducation can bring about for the elderly with hearing impairment.the papers hereby analyzed showed that the public health care centers with physicians and speech and hearing therapists, should establish the guidelines for the development of diagnostic programs, purchase of hearing aids and, most specially, hearing reeducation for the elderly with presbycusis, so that they may enjoy their social relations, and thus enhance their life quality. However, in Brazil, studies and research in this area only beginning. Brazil today boasts an important growth in its elderly population. In the year of 2020, we expect to have a total of 32 million people over 60 years of age. Without any shadow of doubt, this fact puts us within the group of countries in the world with growing longevity, which extends itself to never before considered limitsAging-related hearing loss is a highly prevalent phenomenon in the elderly population,Epidemiological studies are being largely carried out in developed countriesIn general, there is a consensus, not only concerning a drop in auditory function associated with natural human aging, but also in relation to a greater hearing loss in men when compared to womenThere is a great difference in the definition of criteria used to determine tonal averages; the different degrees of hearing loss; the reference between the better and the worse ear, and the different age ranges of the elderly population, consequently affecting its prevalence in the elderly population seen in different epidemiological studies. Thus, there is an effort in order to standardize these criteriaDefined as an aging-related hearing loss, some authorsPeripheral hearing reduction in this population brings about loss to the entire auditory function. The quality of central auditory process also drops, directly impacting the elderly social relations. Hearing as a whole involves not only “hearing”, but also the understanding of what is “heard”, which is compromised and requires special attention from the professionals involved in audiology and aging?This study aims at revising the literature about hearing loss and its implications for the elderly population, under an updated perspective.In Brazil, presbycusis has been blamed as the most frequent cause of hearing impairment in the elderly, causing understanding difficulties during verbal communication.Both the physiological and natural aspects of presbycusis have been approached by many authors in the national literatureAccording to Portmann and PortmannFew studies carried out in Brazil were identified, so far, that tried to estimate the prevalence of presbycusis and even these did not use populational based samples. This fact is leaving a large gap, considering the current longevity and life expectancy of the elderlyThe Hearing Impairment Among Adults - HIAStudies presented at the HIA showed an increase in presbycusis prevalence with age. It is considered a natural hearing impairment that grows significantly as people age, and this brings adverse effects in social activities and participation, impacting their life quality. This group of researchers concluded that although there are different types of presbycusis, the evidence gathered do not suggest different prevalence rates among the different countries for people of the same age and gender.713,854 million people with some permanent hearing disability. This classification encompasses a total of 5.7 million people with hearing disability; however it does not inform the type and level of hearing loss, nor the age of these individuals, thus precluding a better understanding of this population. This classification includes school age children, adults and the elderly, in other words, everyone with some kind of hearing impairment.In Brazil, data from the Demographic CensusHearing assessment in the elderly must encompass not only objective and subjective tests that aim at defining the individual's audiologic thresholds, but it also has a more general task, which is to evaluate the peripheral hearing quality coming from the central information processing; and also consider the patient's own perception of his/her hearing loss, at a functional level in his/her daily family and social activitiesTherefore, in the audiologic evaluation of the elderly, the audiologist must not lose sight of the need to use the tools necessary to evaluate both the peripheral and the central auditory apparatus. According to RönnbergFrequency-specific sensibility must be evaluated by subjective and objective tests, according to the need of each patient. Some tests will inform about outer and middle ear functioning, which is fundamental for a proper amplification and conduction of sound waves to the inner ear. Other tests complete this information, by evaluating the inner ear, where sound waves are transformed into sound impulses, broken down into frequency, time and intensity elements, which are then transmitted to the auditory cortex, by means of the auditory pathways.Therefore, peripheral activities are responsible for sound sensation, while central activities are in charge of decoding the message received and, concurrently, by its recoding, in a new format required by the nervous system.Primary auditory cortex discriminates sound frequencies and intensities; it bears a temporal pattern and is involved in sound source location. The association areas are functional areas which are directly related to speech sound recognition. Thus, the auditory central nervous system is intimately related to language processing and other cognitive and emotional functionsConsidering auditory functionality, capacities to detect, locate, discriminate, recognize and understand the sound message are all evokedDuring tonal audiometry, it is possible to notice the quality of peripheral hearing central information processing, both in terms of the speech recognition index and in relation to understanding and performing the orders given by the examiner. All such factors should be considered by the audiologist during hearing assessment of an elderly person, taking them as basic parameters used in other investigations related to the central auditory system.We still have to investigate possible difficulties related to hearing functional use. Self-assessment questionnaires have been broadly recommended by National and International authors.It is not always that tonal audiometry results correspond to the findings from the functional use of hearing by the elderlyAll this information will be fundamental in order to consider patient's education after audiologic evaluation in the elderly. The prescription of a hearing aid and the hearing reeducation process are directly related to these factors.The hearing apparatus is one of the most important factors related to the development of oral communication. A failure in this system can start a chain reaction, that is, a hearing impairment causes great communication difficulties that in its turn bring about deterioration in life quality.Early diagnosis and intervention in aging-related hearing loss are paramount in order to provide the elderly with a good life quality. Studies and research in this area point toward a functional change based on brain plasticity, even in the adult populationEarly prescription, fitting and using of a hearing aid, that is, immediately after the diagnosis of a mild and/or moderate hearing loss, may contribute to preventing an increase in the hearing loss level and other related alterations such as psychosocial issues for the affected individual.Some constant studies and research on the work of Musiek and RintelmannHowever, the referral of these patients to acquire a hearing aid is only the starting point, because without hearing reeducation, often times these patients abandon the deviceAccording to Couto-Lenzi44, when an elderly, used to normal hearing, loses his/her hearing, or has it reduced, the discomfort is immediate. The difficulties start when they try to communicate with family members, close friends and workmates, later on, in stores, grocery stores, and other social activities. Other social implications of the hearing loss in the elderly involve his/her daily routines, such as listening to the radio and watching TV; speaking on the phone; shopping; talking; playing musical instruments; listening to music and singing; working out; doing Yoga and exercises in the water; participating in courses, seminars, classes and talks.Precursor of the “Perdoncini” method for Hearing and Language challenged population in Brazil; Couto-Lenzi adapted this work in order to be used in the auditory reeducation for the elderly, of which the main goal is to facilitate communications based on the thorough use of residual hearing.A reduction in information processing speed, commonly seen in the elderly, may significantly affect speech perception performance when added to a specific frequency sensibility deficit, and this worsens the communication difficulties of this population.Linguistic implications are directly related to the degree of hearing loss, which may vary from mild to profound46. Loss goes from a difficulty in understanding spoken messages, especially in noise environments, up to significant communication alterations, which impairs the person's capacity to actively participate in daily conversations, and there are also voice alterations because of the incapacity to have voice feedback and thus control it.Some aspects pointed out in studies and research has contributed to the development of a proper hearing reeducation work for the elderly. For instance, one has to consider the fact that in noisy environments, words in a context are more intelligible that isolated words or those without the benefit of a phase context and the very situations peculiar to language communication. Moreover, the phrase context imposes a reduction in possible alternatives, and speech intelligibility increases as the number of possible alternatives reduces.According to the aforementioned authors, word predictability has a direct impact on the intelligibility of what will be heard. And when a phrase is presented to a listener at a given context which is established by prior expressions and the very situations in which the expressions are presented, phrase understanding is better when compared to a neutral context, or even an unknown context for the listener in that specific situation.All these information allow the creation of auditory reeducation strategies that will allow the development of the auditory function in a proper way, improving the person's well being in his/her social and family settings, since it enhances this person's hearing skills.Awareness about hearing difficulties, associated to frequency-specific sensibility, must be clarified and informed to the elderly and the people who live with them. The interruption in this hearing reeducation work must be partial and progressive. Return to it must happen whenever necessary. The family must receive specific guidelines aiming at reintegrating the elderly with hearing loss to their social and family settings.According to Jerger et al.Gates et al.All the authors and studies hereby analyzed showed a high aging-related hearing loss prevalence, even when one considers the different criteria used in order to define hearing loss. According to Rosenhall48, as the number of elderly people increase in the general population, also increases the prevalence of presbycusis, which interferes in the life quality of this population. International scientific literatureThe etiology of aging-related hearing loss has brought about some important discussions. To try to discriminate among the effects of natural aging process on the hearing system and the pathological/environmental effects has posed as a great challenge for researchers in this field. The International Organization for Standardization - ISO 7029On the other hand, according to the same authors aforementioned, the tracing of such individuals may lead us towards a non-representative elderly population, that almost always is exposed to the factors mentioned by ISO 702950 and, thus, exclude most elderly from current research.The literature review has shown that there is a current consensus, in which presbycusis has been considered an outcome of multifactorial etiology: sociocusis, exogenous and endogenous factors such as non-occupational noise and inadequate diet; nosocusis, factors related to pathologies that impact the otoacoustic system such as ototoxic drugs, inflammation and systemic diseases; and the natural and physiologic degeneration that happens with aging. All of these factors represent the multifactorial aspect of hearing loss in the elderly.As far as the audiologic evaluation is concerned, studies and research in general, establish that specific physiological aspects be considered in this population, since both central structures and peripheral mechanisms are affected by aging. Peripheral hearing assessment, the central processing of information and the very perception the elderly have about the social and emotional impact a hearing loss brings about to one's life must be taken into account. Therefore, the evaluation must be thorough, involving the individual as a whole.Auditory reeducation for the elderly must prioritize those activities that aim, through the reintroduction of auditory feedback by means of using a hearing aid, a change in central auditory functioning standards of this population, possible with the development of central auditory skills. Hearing aid devices prescription and fitting alone are not enough without a correct patient education as to the benefits and gains of such device for both the patient and his/her family.Without proper education and without the concern of providing a customized and adequate prescription for each patient, many elderly will end up not using the device. According to LichtensteinAccording to Rosenhall53, in a study that tried to describe the psychosocial consequences of presbycusis, although the elderly population is concerned with hearing deterioration, only 8% requested a hearing aid device after audiologic evaluation. Lack of knowledge about the benefits of the device and of hearing reeducation, as well as the prejudice about hearing aids have also contributed to not using one.Even among health care professionals, the lack of knowledge regarding the advantages and gains a specific hearing reeducation program may bring about to the elderly is still large.Access to a hearing aid is still another relevant aspect that must be brought out43. Law #1.948/96, from July 03, 1996; which regulates law # 8.842, from January 04, 1994, concerning the National Policy for the Elderly, makes the Ministry of Health responsible for providing orthesis and prosthesis necessary for the recovery and rehabilitation of health in the elderly.Nonetheless, when referred to a public health care facility, the elderly with hearing loss and a prescription for a hearing aid can not get the benefit. Public health care facilities today prioritize children with hearing loss over the elderly in order to provide a hearing aid free of charge for the patient. On the other hand, the cost of each one of these devices is around 4 to 5 minimum wages, and usually two of them are prescribed - doubling that cost.Thus, the elderly are put aside of a truly participative and cooperative social life. In general, our society still lacks information about the hearing impairment in this population, and the consequences it brings to their lives. Espmark16 sees a need to educate people about the possibility of rehabilitation in cases of presbycusis. According to him, the hearing aid is important not only for communication and spatial orientation, but also because hearing reinstates our existence as human beings.World scenario for aging-related hearing loss has received significant contributions from studies and research that are being carried out in the field of audiology and aging, especially in Scandinavia, the United Kingdom, the United States, Australia and Japan.In Brazil, studies and research are only starting. The Federal University of São Paulo, the Paulista School of Medicine and the Catholic University of São Paulo have pioneered studies in this field.27,28 A few other isolated studies may be found in Santa CatarinaAccording to Decree # 1.948/96, aforementioned, the Ministry of Health, by means of the Health Care Secretariat, together with the State Secretaries of Health Care in the states, the Federal District and the municipalities, among other actions, is responsible for supporting epidemiological studies and research aiming at expanding the knowledge we have on the elderly, and to subsidize prevention, treatment and rehabilitation efforts.This emergent increase in the elderly population around the world opens a new field of research for all of us, professionals engaged in a better life quality to the population - audiology of aging.Therefore, it is necessary to include in health services agenda, this view within audiology, so that the elderly may benefit from the results of prospective studies and public health care services that involve physicians and speech and hearing specialists engaged with this issue.In the current demographic setting, it is urgent to establish guidelines in order to develop diagnostic programs, hearing aid supply and, mainly, a specific program of auditory reeducation for the elderly with hearing loss, so that they may enjoy and participate fully in their social relations and thus have a better life quality.


Noise-induced hearing loss has been studied for many years and today many experts also investigate the synergic action of chemical products, since they can be potentially ototoxic.to investigate the audiological findings in workers exposed to occupational noise and pesticide and to compare it to data from noise-exposed workers.Clinical retrospective.individuals that had been exposed to pesticide and noise (group I), and individuals that had been exposed to noise only (group II).The classification of the audiometric findings showed in that group I: 35% had normal hearing thresholds, 53.75% had degree 1 hearing loss and 11.25% had degree 2 hearing loss; and group II had 57.5% of normal hearing, 40% had degree 1 hearing loss and only 2.5% had degree 2 hearing loss. The analysis of the audiometric findings also showed a significant worsening after comparing groups I and II thresholds, in the frequency of 3 kHz on the left ear and 4 kHz on both ears.The analysis showed that group I had worse audiometric thresholds compared to group II. Thanks to technological development, the most spread type of pollution is sound pollution, and everyone is subject to being exposed to noise levels which are harmful for human health.Noise, by itself, is harmful to health when the sound level is higher than 85 dB, depending on the duration and the systematic exposure to it. For this reason, based on this sound intensity, audiometries are periodically carried out in industrial plantsNoise induced hearing loss (NIHL) happens because of the systemic and prolonged exposure to intense noise, it is a chronic and irreversible disease, since it involves the hair cells of the organ of Corti. This disorder is also recognized by numerous authors as the most prevalent occupational-related disorderNIHL initially affects the frequencies of 6, 4 or 3 kHz; and with the progression of the loss, it can reach the regions of 8, 2, 1 kHz, 500 and 250 Hz. Moreover, the individual can have tinnitus and discomfort related to intense sounds, and once the noise exposure ends, there is no more hearing loss progression. Exposure duration and individual susceptibility are also factors which can impact disease onsetWhen considering hearing loss in the lives of workers, it is very important to know other agents which can cause and/or worsen it - chemical products among them.The first authors to discuss the interaction between noise and chemical products reported that the sensorineural hearing loss in workers exposed to solvents was more pronounced than expected in the case of noise exposure onlyOne study assessed the audiological profile of workers exposed to noise and chemical products in an alcohol and sugar plant. The authors classified the audiological findingsIn a comparative study of audiometric exams from metallurgical workers exposed to noise (group I) and noise associated with chemical products (group II), we noticed that group II individuals had a higher prevalence of hearing loss when compared to those individuals in Group IA recently held study with farmers exposed to organophosphates for five years concluded that such exposure increases the risk of the person developing hearing lossOther authors have also shown central auditory dysfunction in workers using these types of insecticides in campaigns to fight vectors in endemiesA study carried out with workers exposed to noise and pyrethroids and organophosphates insecticides found that chronic exposure to these insecticides affect the peripheral and central auditory system, regardless of a concurrent exposure to noiseAnother study analyzed audiometries from “insect busters” who worked regularly with pesticides in 2001/02, and in this latest year the company studied had 600 of these insect fighters. The study reported that 33 of these audiometric exams had NIHL-related alterations. Nonetheless, the authors argue that the study involved 37% of the workers; therefore, this figure can be three times greater. The study also challenged the hypothesis that these agents may have a synergic effectAn evaluation of the peripheral auditory alteration in a group of workers exposed to organophosphates and pyrethroid insecticides, used in control campaigns, showed that of the workers exposed to the insecticides, 63.8% had hearing loss. For the group with concurrent exposure to insecticides and noise, the hearing loss was of 66.7%. The average time taken to develop hearing alterations in the high mean frequencies, for combined exposures to insecticides and noise was 3.4 years, and for exposure to insecticides alone was 7.3 years. Hearing loss arising from concurrent exposure to both factors was higher in these frequencies than when the person was exposed to insecticides onlyThe investigation of the rural work process in nine towns in MinasGerais showed that about 50% of the workers interviewed were at least moderately affected by organophosphates and carbamates. This study shows the need for better controlling the exposure to these chemical agentsIn a study held with farmers from Rio Grande do Sul, among the chemicals they were being exposed to there were pyrethroids and organophosphates, the authors found hearing loss in 60% of the individuals exposed to pesticides and noise, on the other hand, only 7% of the control group (without exposure to noxious elements) presented altered thresholdsWhen poisoning ensues, pesticides are classified as pyrethroids and act on the central and peripheral nervous system, and the high concentration cause permanent damage or long exposure damage the peripheral nerve. While those classified as organophosphates build up in tissues and when in excess they alter the central nervous systemToday it is rare to find corporate hearing protection programs which consider chemicals as possible culprits of auditory disorders, as well as its simultaneous exposure to noise. In 1999, in a very optimistic way, the Social Security Department , listed benzene and aliphatic or aromatic hydrocarbonates as possible culprits of ototoxic hearing loss; nonetheless, this decree is limited to some solvents onlyAs to what was exposed above, some studies suggest that the exposure to two agents is really harmful to health, since they may have a synergic effect. Nonetheless, these studies are scarce and show a need for paying more attention to this matter, since there is a large number of Brazilians exposed to this hazard.The goal of the present paper was to study the audiological findings in workers exposed to occupational noise and pesticides and compare them with data obtained from workers exposed to noise only.This study was carried out in the clinical audiology department of a public institution. It is a retrospective study in which we analyzed the charts from individuals exposed to a pesticide  and noise (group I), and individuals who were exposed to noise only (group II), in the year of 2007.Each group was made up of 40 individuals, all male adults. These individuals were between 31 and 45 years, thus ruling out different diagnostic hypothesis, which happen after 45 years of life. And, in both groups noise exposure time was of 5 to 30 years.The equivalent noise level that the workers were exposed to was 98.5 dB (A)9 and the exposure time was of 3 to 4 hours per day. The employees are previously fit with Personal Protection Equipment (P.P.E), according to Standard NR 620, of Ordinance 3214/781, being relevant for our study to stress the use of proper respiratory masks and ear plugs, both certified and approved by the Ministry of Employment and Labor.The present study was approved by the Ethics in Research Committee (protocol # 2606/2007).•audiological interview, in which we surveyed identification data and the auditory health history;•threshold tonal audiometry, in which we assessed tonal thresholds of the subjects (air and bone conduction) •immittance measures, in which we analyzed data concerning tympanometry, with the aim of studying the functional integrity of the tympanic-ossicular chain in the auditory systemWe studied information concerning the following procedures:The audiometry tests were done in a sound-treated booth, using the GSI 61 Grason - Stadler audiometer. For acoustic immittance measures we used the GSI 38 Grason - Stadler immittance metering device.Audiometric findings were analyzed and classified according to the occupational profileIn order to study the level of significance between the age of the individual and the time they had been working in that position we used the Student t-test. While the statistical analysis of the comparison of the audiologic results between groups I and II was carried out by the Anova test. In both cases the level of significance was 5% (p < 0.05) and the confidence interval was established at 95% of statistical confidenceThe results from the interview showed that the main complaints from the individuals in Group I were: tinnitus (n = 25 / 52.08%); allergies (n = 13 / 27.08%) and recruitment (n = 10 / 20.83%). In Group II, the main ones were: tinnitus (n = 21 / 58.33%); recruitment (n = 9 / 25 %) and autophonia (n = 6 / 16.66 %).Among the data obtained from the anamneses, we plotted the age and duration of exposure to noise, which can be seen on In assessing the functional integrity of the tympanic-ossicular chain, specifically in the tympanometry, we noticed that in Group I, both in the right ear and in the left ear, 35 (87.5%) individuals had type A curves and 5 (12.5%) had type Ad. While in Group II, 36 (90%) had type A tympanometric curve and 4 (10%) had type Ad, also bilaterally.The results from the threshold tonal audiometries were analyzed from the frequencies of 500 Hz up to 8 kHz. In each frequency we analyzed the right and left ears of Group I compared to the right and left ears of Group II, in order to check whether or not the Anova statistical test would show significant differences between the groups. The data is presented on The results obtained from the threshold tonal audiometry, depicted on When this value is compared between the groups, we can see a worsening in the auditory thresholds in the large majority of frequencies between 3 and 8 kHz, for group I. This worsening in the hearing loss was significant in the frequencies of 3 kHz (left ear) and 4 kHz , as per depicted on And finally, we did the analyses and classified the audiometries6. Thus, we noticed that in the right ear of Group I, 16 (40%) individuals were classified as normal, 20 (50%) had level 1 hearing loss and 4 (10%) had level 2 loss. While in the left ear of this same Group 12 (30%) were considered normal, 23 (57.5%) had level 1 loss, and 5 (12.5%) had level 2 loss. In Group II, we noticed that 23 (57.5%) individuals had normal hearing, 16 (40%) had level 1 loss and only 1 (2.5%) individual had level 2 hearing loss. These values were the same for the right and the left ears.In the present study, the most frequent complaints from Group I were tinnitus, allergy and recruitment; and for Group II they were: tinnitus, recruitment and autophonia. In both groups, we have the two complaints most frequently reported by the National Committee of Noise and Auditory PreservationThe analysis of the immittance measures showed a predominance of type A curves, which matched the sensorineural profile of the noise induced hearing loss,,In the present study, we see that in both groups the audiometries showed a hearing loss in the high frequencies, with peaks at 4 and 6 kHz, as it is commonly seen in audiometries from patients with NIHLIn a quantitative analysis of the tonal threshold audiometry, a statistically significant difference was seen between the groups, with a worsening of the thresholds for group I, in the frequency of 3 kHz, in the left ear and in the frequency of 4 kHz, bilaterally.,,,,,,In classifying the audiometries, we noticed that in Group I, more than 60% of the individuals have NIHL, while in Group II, this figure drops to 42.5%, in other words, the group with concurrent exposure to noise and pesticide presented a higher incidence of hearing loss, according to this classificationAfter analyzing the audiological findings and comparing Groups I and II, we conclude that the workers exposed to occupational noise and pesticide are under a higher risk of developing hearing loss when compared to those workers exposed to noise only. Thus, it is important that Hearing Protection Programs also consider these factors so as to better prevent the damages caused by these noxious elements.


Transcutaneous active bone conduction hearing aids represent an alternative approach to middle ear surgery and conventional hearing aids for patients with conductive or mixed hearing loss. The aim of this study was to determine quality of life, subjective hearing experience and patients’ satisfaction after implantation of a bone conduction hearing aid.This monocentric and retrospective study included twelve adult patients who received a bone conduction hearing aid  consisting of an extracorporeal audio processor and a bone conduction implant (BCI) between 2013 and 2017. On average 40 months after implantation, the patients were asked to answer three questionnaires regarding quality of life (AqoL-8D), self-reported auditory disability (SSQ-12-B) and user’s satisfaction (APSQ) after implantation of the Bonebridge (BB). A descriptive statistical analysis of the questionnaires followed.12 patients aged 26–85 years  were recruited. The quality of life of all patients after implantation of the BB (AqoL 8D) averaged an overall utility score of 0.76 (SD ± 0.17). The mean for ‘speech hearing’ in the SSQ-12-B was + 2.43 (SD ± 2.03), + 1.94 (SD ± 1.48) for ‘spatial hearing’ and + 2.28 (SD ± 2.32) for ‘qualities of hearing’. 11 out of 12 patients reported an improvement in their overall hearing. The APSQ score for the subsection ‘wearing comfort’ was 3.50 (SD ± 0.87), ‘social life’ attained a mean of 4.17 (SD ± 1.06). The ‘device inconveniences’ reached 4.02 (SD ± 0.71) and ‘usability’ of the device was measured at 4.23 (SD ± 1.06). The average wearing time of the audio processor in the cohort was 11 h per day, with 8 of 12 patients reporting the maximum length of 12 h per day.BB implantation results in a gain in the perceived quality of life (AqoL 8D). The SSQ-12-B shows an improvement in subjective hearing. According to the APSQ, it can be assumed that the BB audio processor, although in an extracorporeal position, is rated as a useful instrument with positive impact on social life. The majority stated that they had subjectively benefited from BB implantation and that there were no significant physical or sensory limitations after implantation. Hypoacusis or hearing loss is defined as functional deficit of auditory capacity in comparison to a healthy person. It often leads to deterioration in quality of life  characteThe success of these devices depends on the audiological hearing improvement on the one hand –10 as weThe partially implantable active bone conduction hearing device Bonebridge (BB) by MedEL  consisting of an extracorporeal audio processor and the internal bone conduction implant (BCI) is indicated for patients with conductive hearing loss, mixed hearing loss and single sided deafness (SSD). The evaluation of quality of life and patient’s satisfaction as well as the self-reported auditory disability after implantation was aimed to be determined in this study.This monocentric, retrospective, observational study was approved by the local ethics committee . The user experience with the BB was reviewed by using three questionnaires.24 Patients who received the BB between January 2013 and December 2017 were assessed for eligibility. Inclusion criteria for this study was a minimum of three months experience with the BB after activation. Two patients were excluded due to chronic diseases (trisomy 21 and CHARGE syndrome) which would have significantly affected the quality-of-life outcome. Another 2 patients were excluded due to a language barrier. 20 patients were eligible, whereas 8 patients did not consent, and 12 patients finally participated in this study.On average, the patients were interviewed 40 months  after surgery. The quality of treatment was intended to be surveyed with an emphasis on the BB user’s subjective experience. Therefore, three different questionnaires were used to measure the patient related outcome (PRO) .Patients were asked to answer the Assessment of quality of life AQoL-8D) questionnaire, the Speech, spatial and qualities of hearing questionnaire SSQ-12-B) related to self-reported auditory disability and the audio processor satisfaction questionnaire (APSQ) for user satisfaction with the audio processor. No time limit was imposed on the patients to answer the questionnaires. Table 2-B relatD questioThe comparative self-reported auditory disability before and after BB was evaluated using the SSQ-12-B questionnaire (12 questions) by Noble et al.  . It inclThe APSQ by Billinger-Finke et al. (2020)  was deveThe BB by MedEl  is a partially implantable active bone conduction implant system consisting of an extracorporeal audio processor and a BCI. The audio processor Amadé or Samba of MedEl  are fixed over the implant on intact skin by a holding magnet. The BCI by itself contains a receiver coil, a demodulator, and a transducer . The BC-FMT can be surgically positioned either in the mastoid bone or retrosigmoidally, depending on the specific morphology of the patient‘s skull. For this purpose, the patients received a high-resolution temporal bone computertomography preoperatively to plan the procedure.Surgery was performed by the senior author in all cases under general anesthesia in a supine position. The mastoid and temporal bone were exposed via a retroauricular approach. The implant bed was milled out to accommodate the BC-FMT. Finally, the implant was inserted and fixed with cortical screws, followed by wound closure in layers. After completion of the primary postoperative healing process, the initial fitting of the audio processor took place 6 weeks later as an outpatient procedure.http://www.aqol.com.au/index.php/scoring-algorithms). For the SSQ-12-B questionnaire, scores for ‘speech hearing’, ‘spatial hearing’ and ‘qualities of hearing’  were calculated as mean value (± SD) over respective items. An overall score was calculated from the subscale scores. APSQ scores for the subsection ‘wearing comfort’, ‘social life’, ‘usability’, and ‘device inconveniences’ were calculated as mean value (± SD) over respective items.Baseline data collection and descriptive statistics was performed with Excel 2010 . Data were either presented at the patient level or summarized by means and standard deviations (SD) for the full cohort. AQoL-8D questionnaires were scored with the weighted utility algorithm for SPSS . Six patients received a BB implant on the right side, five on the left side. One patient was implanted bilaterally. Ten out of 12 patients had a history of tympanoplasty or stapes surgery. The etiology of hearing loss varied among our patients. Nearly two-thirds of all patients suffered from mixed hearing loss, one patient suffered from an unilateral functional deafness and the rest showed a conductive hearing loss without any inner ear deafness. 7 Patients have had ear surgery due to chronic epi- or mesotympanic otitis before. Recurrent inflammation  and otosclerosis both were found in two cases. One patient showed an atresia of the external auditory canal.Patients of all ages (26–85 years) were included in this study . The lowest superdimension ‘mental’ utility score in our cohort was 0.2, and the highest was 0.75. The mean of the superdimension ‘mental’ utility scores was calculated at 0.47 (SD ± 0.17).The mean of the superdimension ‘physical’ utility scores was 0.64 SD ± 0.18) with a maximum of 0.89. and a minimum of 0.34 . The mean values of all dimension and superdimension utility scores  of the AQoL-8D questionnaire are shown in Fig. 11 Out of 12 patients reported an improvement in their overall hearing experience . The highest overall score in the evaluation of the hearing situation compared to before BB was + 4.44 and the lowest was – 2.50. Similarly, the subscale scores of ‘speech hearing’, ‘spatial hearing’ and ‘qualities of hearing’ were at least + 1 in 11 of 12 cases.A negative overall score (– 2.5) was found once. The subscale ‘speech hearing’ and ‘qualities of hearing’ were rated with – 3 and – 3.75 by patient no. 2. The subscale ‘spatial hearing’ achieved a score of 0 in this case. The results of the SSQ-12-B questionnaire are shown in Fig. The mean score of the subsection ‘wearing comfort’ was 3.50 points (SD ± 0.87). The average subsection score for ‘social life’ was 4.17 (SD ± 1.06). The ‘usability’ of the device was rated with a score of 4.23 (SD ± 1.06) and the ‘device inconveniences’ subsection was 4.02 (SD ± 0.71).The maximum for ‘wearing comfort’ was 4.33, for ‘social life’ 5.00, for ‘usability’ 4.8 and for ‘device inconveniences’ 4.8. The minimum for ‘wearing comfort’, ‘social life’ and ‘usability’ was 1.0; the minimum for ‘device inconveniences’ was 2.40. Besides one patient, 11 of 12 subsection scores were calculated above a score of 3. The results of the APSQ are shown in Fig. One aim of this study was to determine the quality of life after BB implantation. Mulrow et al. were able to demonstrate a restriction of the quality of life in a study of 472 patients who were affected by hearing loss . The resMoreover, the results of the AQoL-8D reveal that our patients rated the superdimension ‘mental’ worse than the superdimension ‘physical’ on the overall average Fig. . AccordiThe analysis of the SSQ-12-B emphasized a subjective hearing improvement in our BB patients. Our cohort reported an improved hearing experience on average subscale scores  after implantation of the BB. 11 out of 12 patients reported positive values for each SSQ-12-B score  confirmed this observation concerning the ‘spatial hearing’ using audiometric testing. Patients with SSD were excluded from this measurement. A quantifiable improvement in sound localization after BB implantation could not be determined  . Incongr6 confirmMoreover the highest SSQ-12-B-overall-scores by patient can be found at lower bone conduction thresholds of the implanted side and with little difference between the thresholds of both ears , a revision surgery  was performed. The magnetic fixation of the audio processor had not been sufficient in the obese patient. Furthermore, the patient complained of recurrent pain around the implant. The BB was removed in 2020 at the patient’s request.Regarding to the bone conduction threshold of patient no. 2 there is an individual inner ear hearing loss of 30 dB HL on the implanted ear. Questioning whether a severe inner ear deafness could have harmed the patient reported outcome, it becomes clear that other patients with similar bone conduction thresholds have rated the questionnaires with better results. In summary there cannot be found a significant pattern between certain bone conduction thresholds of our patients and their ratings in the PROM.Retrospectively, patient no. 2 can be classified as a non-user (wearing time of 0 h a day). Apart from the fact that generally up to 20% of all patients with hearing aids are non-users , specialComparing our results to the recent literature one limitation is the variable time (8 to 48 months) between BB implantation and the survey. However, Table Another limitation of our study could be seen in the missing correlation of audiological testing, which has been excluded in the sense of PRO . HoweverSince the impact of the BB in audiometric testing and the effectiveness has already been proven in previous trials –46, we fIn summary, our results show an appropriate perceived hearing rehabilitation with the BB. The evaluation of quality of life, the decrease of the self-reported auditory disability and patients’ satisfaction can confirm the BB as an adequate therapy for auditory rehabilitation. Especially the improved quality of life and the outstanding results in speech hearing of the cohort after BB implantation can lead to an increase of social life satisfaction. Spatial hearing showed the least improvement with BB, which is also discussed in recent studies and seems to be served best in the case of a binaural BB implantation.