The current Research Topic tries to highlight some of the most relevant recent advances regarding sensorineural hearing loss (SNHL). The etiology of SNHL primarily involves hereditary factors, ototoxic drugs, noise, and aging, all of which trigger two main mechanisms: damage to the organ of Corti, namely mechanosensory hair cells (HCs) and non-sensory supporting cells (SCs), and/or loss of spiral ganglion neurons (SGNs) that subsequently form the auditory nerve and hence connect the inner ear to the brain.Nicolson reviews peripheral forms of hereditary hearing loss and strategies to study underlying molecular mechanisms using animal models and cell lines. Hereditary hearing loss affects different sites within the inner ear, including the stria vascularis, organ of Corti, and SGNs, all with complementary animal models for studying specific genetic defects. In humans with hearing loss, diagnostic genetic testing leads to novel variants that may have clinical implications. In their article “A Novel Variant in the TBC1D24 Lipid-Binding Pocket Causes Autosomal Dominant Hearing Loss: Evidence for a Genotype-Phenotype Correlation,” Parzefall et al. describe a novel variant of TBC1D24 that causes autosomal dominant hearing loss. This genotype-phenotype correlation study hypothesizes that specific residues affected in TBC1D24 regulate synaptic vesicle trafficking that may be involved in molecular mechanism of disease. These variants can be studied in the future in an animal model or in vitro to further dissect molecular mechanisms.Hereditary hearing loss accounts for one in 500 new births  inhibitor Y-27632 regenerated SGN axons and synapses between inner HCs and the auditory nerve. In a similar in vitro model, Gao et al. show in the article “Insulin-Like Growth Factor 1 on the Maintenance of Ribbon Synapses in Mouse Cochlear Explant Cultures” that insulin-like growth factor 1 (IGF-1) is crucial to maintain such synapses, which is corroborated by the fact that its deficiency is a cause of human hearing loss  linked to bone-binding bisphosphonates also promotes synaptogenesis in vitro. These studies further open the possibility to preserve ribbon synapses and auditory neurons even in the absence of healthy HCs, thus increasing the panel of potential novel co-treatments to be used during cochlear implantation . This investigation presents evidence for initial spike generators that are located just beneath the inner HCs. Moreover, the authors illustrate the feasibility of obtaining high quality human inner ear tissue during select procedures, demonstrating the potential of collaborative work between surgeons and scientists to advance the auditory field.The above-mentioned synapses represent the connections between (inner) HCs and SGNs. As discovered in recent years, they represent one of the most vulnerable parts of the auditory periphery with cochlear synaptopathy interrupting the communication between these two cell types, resulting in SNHL. Several strategies to prevent or mitigate this condition are presented in the current Research Topic. In their paper “Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea,”  Lenarz, . In the Varela-Nieto et al. review the scarce data available on the role of small molecules, nitrones, with the property of being radical oxygen and nitrogen species scavengers in the article “Use of Radical Oxygen Species Scavenger Nitrones to Treat Oxidative Stress-Mediated Hearing Loss: State of the Art and Challenges.” Further, dealing with the potential of antioxidants and vasodilators to treat the consequences of noise exposure, “Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?” by Alvarado et al. discusses the pros and cons of these therapies, as well as their potential to be translated to clinical practice.Among the intracellular events that have been repeatedly described as a cause of injury and death in the cochlea we find oxidative stress, either associated to aging or noxious stimuli, such as noise or ototoxic drugs. This Research Topic includes several articles exploring these mechanisms. Nacher-Soler et al. describe an alternative method in “Local Cisplatin Delivery in Mouse Reliably Models Sensorineural Ototoxicity Without Systemic Adverse Effects,” where they apply a cisplatin solution into the murine middle ear, the so-called otic bulla. This model reliably resulted in the desired hearing loss and HC damage without any distress or morbidity, hence allowing the study of ototoxic effects without having to continuously worry about animal safety.One of the above-mentioned ototoxic drugs is the commonly used chemotherapeutic cisplatin. In human patients and animal experiments, it is usually delivered systemically. Yet, this triggers substantial morbidity in rodents, even leading to premature death. 1-Methylnicotinamide Against High-Fat Diet- and Age-Induced Hearing Loss via Moderate Overexpression of Sirtuin 1 Protein,” Miwa showed that mice fed a high-fat diet exhibited ARHL and decreased SIRT1 and SIRT3 expression levels in the cochlea. He also showed that N1-methylnicotinamide (MNAM) supplementation increased SIRT1 and SIRT3 expression levels in the cochlea and suppressed ARHL. Furthermore, Altschuler et al. showed in their study, “Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice,” that adding rapamycin to the diets of mice at 14 months of age delayed ARHL. These findings all indicate potential treatment strategies for SNHL.Age-related hearing loss (ARHL) is the most common form of SNHL. In the study “Protective Effects of NIyer and Groves summarize the current state of targeted reprogramming of SCs to HCs. Specifically, they emphasize that the single transcription factor, ATOH1, is insufficient alone in adult inner ears for reprogramming. The field is coalescing on the idea that a combination of reprogramming factors will unlock the regenerative capacity of cochlear SCs in adult mouse cochleae. This presents an exciting and novel frontier in driving HC regeneration in adult mammals, a feat previously thought to be herculean.As the inner ear is a non-regenerative organ in adult mammals, many groups try to establish the replacement of HCs as a potential therapeutic option for SNHL. A variety of strategies have been described in the literature to achieve this, with a focus on species that are able to regenerate their sensory epithelium like birds or fish, or neonatal mammalian tissues that appear more plastic. In their review, “Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells,” Warchol et al. used larval zebrafish to assess the response of macrophages to neomycin ototoxicity in “Macrophages Respond Rapidly to Ototoxic Injury of Lateral Line Hair Cells but Are Not Required for Hair Cell Regeneration.” The early inflammatory response was triggered by “local” macrophages and the migration of these cells was significantly lower when Src-family kinases were inhibited. Furthermore, macrophages appear not to be essential for HC regeneration in this model. Similar to zebrafish, neonatal mammalian cochlear SCs and avian basilar papilla SCs have the capacity for HC regeneration. In their article “Initiation of Supporting Cell Activation for Hair Cell Regeneration in the Avian Auditory Epithelium: An Explant Culture Model,” Matsunaga et al. focused on the avian auditory epithelium as a tool for investigating HC regeneration, establishing an explant culture model in chick basilar papillae. This model can be used to explore the molecular mechanisms of SC activation leading to HC regeneration in chick basilar papillae and the development of therapeutics for HC regeneration in the mammalian cochlea. Another regenerative strategy that has been at the forefront of hearing research for years focuses on stem/progenitor cells. In the article “Successful Treatment of Noise-Induced Hearing Loss by Mesenchymal Stromal Cells: An RNAseq Analysis of Protective/Repair Pathways,” Warnecke et al. carried out elaborate RNAseq experiments and demonstrated that mesenchymal stromal cells (MSCs) could mitigate damage sustained during severe sound trauma. Following noise exposure, mice received intracochlear injections to deliver these multipotent cells derived from human umbilical cord Wharton's jelly into perilymph and the effects on various molecular pathways were analyzed. Such studies of transplanted cells of different lineages while enticing, remain in their infancy.As mentioned, the HCs of fish lateral line neuromasts are very similar to those in the inner ear, but regenerate as opposed to their mammalian counterparts. In summary, this Research Topic includes a plethora of promising approaches that will hopefully result in translational clinical studies and transformative therapies benefitting patients suffering from SNHL.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.TJ was supported by the NIH/NIDCD (K08DC019683). IV-N was supported by PID2020-115274RB-I00 from the Spanish MCIN/AEI/10.13039/501100011033 and FEDER.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.


The phenomenon of Late-Onset Unilateral Auditory Deprivation was first reported in 1984. However, a high number of unilateral hearing aid fittings are still carried out in cases of bilateral hearing loss, justified by non-auditory factors such as cost, vanity, misinformation and public health policies.To carry out behavioral and electrophysiological assessment of the auditory performance of adults using unilateral amplification compared with individuals exposed to bilateral symmetric auditory stimulation.Thirty five adults, all with symmetric bilateral sensorineural hearing loss, regular users of unilateral hearing aid, bilateral hearing aids and not users of hearing aids, were assessed on behavioral and electrophysiological tests.p < 0.05). This same group also had poorer performance on the Sentence Recognition Test in Noise held in free field.Variance analysis revealed that in the unilaterally fitted group, P300 latency was significantly greater in ears with auditory deprivation compared with those fitted with the hearing aid (These results corroborate findings in the literature showing that unilateral auditory deprivation can lead to physiological and perceptual changes. The advantages of binaural hearing have been extensively communicated and documented: the possibility of functionally using both ears brings about a better understanding of speech in a noisy or reverberating environment; the capacity to locate sounds is highly dependent on the possibility of perceiving sounds with both ears at the same timeFitting a bilateral hearing aid uses the possibility of interaction between both hearing pathways and, thus, provides the hearing impaired with the possibility of using both ears with superior quality of sound in terms of clarity, redundancy, binaural summation effect, stereophonics, no head shadow effects and, even a greater effectiveness in tinnitus suppressionLong hearing deprivation periods, either partial or complete, caused by fitting an unilateral hearing aid in individuals with bilateral hearing loss, are the basis of a phenomenon which was first described in 1984st Eriksholm Workshop1” in Auditory Acclimatization and DeprivationThe relevance of these findings became more evident since the holding of the “Adults with hearing loss frequently complain of the difficulty in understanding speech in noisy environments. In order to obtain a more realistic estimate of how much communication and speech understanding are compromised, it is necessary to use assessment procedures which focus on the individual's skills to process the auditory information in situations which more closely mimic the ones he has in his daily routines. Since it is not possible to infer such difficulty based on speech tests carried out in silent environments, it is paramount to use these speech tests in the presence of noise in order to properly assess these skillsThe importance of utilizing electrophysiological tests, especially the long latency auditory evoked potentials in the investigation of the auditory system, rests not only on the possibility of confirming the behavioral findings, but they also help understand the underlying physiological mechanisms and, therefore, prove to be excellent monitors of functional changeTherefore, there is increasingly more evidence as to its use as an objective instrument, rather than an invasive one in functional diagnosis, in the monitoring of changes to the central auditory nervous system, in the investigation of the auditory function plasticity and in the assessment of the neuroelectric activity of the auditory pathways - from the auditory nerve all the way to the cerebral cortexIn assessing the cortical audiological potential, the P300 component has been used with the advantage of being regularly registered in individuals with hearing loss as long as it does not prevent the patient from perceiving the rare and frequent stimuli with the same easeDeprivation or asymmetry upon hearing stimulation seem to be responsible for generating a modification on the topographical representation of the auditory pathway corresponding to the auditory cortexThe present paper aimed at comparing the auditory performance of individuals with bilateral hearing loss acquired in adult life, broken down into unilateral hearing aid users, bilateral users and individuals not using hearing aids by means of a behavioral assessment and the P300.This study is a clinical and prospective investigation which has been approved by the Ethics in Research Committee, under protocol # 0973/07.The present study was developed in a public service of hearing health. The series was made randomly made up by a total of 35 individuals who came to our institution for hearing assessment, for the fitting of a hearing aid or follow up of those who already used hearing aids who required a reassessment of their hearing and or concerning their performance with the hearing aid.In order to enable the comparisons intended in this study, we created three groups of patients: one study group called “Unilateral Fitted Group” (UFG) made up of 15 participants users of hearing aids and two comparison groups called “Bilateral Fitted Group” (BFG) including 10 individuals using hearing aid in both ears and “Not Fitted Group (NFG), including 10 participants who had never before used a hearing aid. Thus, we had 35 participants in this study, adults and elderly  with ages ranging between 48 and 90 years.To include patients in the study, we used the following criteria: a) adult individuals older than 18 years, of both genders; b) having sensorineural hearing loss (air-bone conduction gap ≤ 10 dB in any frequency) bilateral, symmetrical, acquired at adult age; c) mean value of tonal thresholds  ≤70 dB HL. For the symmetry criterion, we used the one adopted by Silman et al.Tympanometry was done to all the participants who had normal tympanometric pressures (+50 to -100 daPa) besides a report of no past of middle ear problems, ruling out temporary or permanent damage to the middle ear, which could impact the results.in situ measures or thresholds with hearing aids.The battery of tests employed in the three groups was based on a behavioral evaluation  and electrophysiological assessment , carried out without the patients wearing the hearing aid. Thus, the analysis did not include data on the type or brand of the hearing aid, adjusts or algorithms utilized, results from The hearing behavioral assessments were carried out in a sound proof booth, according to the ANSI 3.1 standard, from 1991. We used the GSI-61 two-channel audiometer, from Grason-Stadler, with supra-aural TDH-50P phones, calibrate according to ANSI 3.6 standards from 1989 and IEC-1988 and speakers. When the test required the use of digital playing, we used the portable NS-P4113 CD player coupled to the audiometer.The threshold tonal audiometry was carried out by air conduction in the frequencies of 250 to 8000 Hz, with supra-aural phones and, by bone conduction in the frequencies of 500 to 4000 Hz, by means of a bone vibrator.most comfortable level - MCL). The material utilized for this study involved four lists with 25 monosyllable words in each, developed by Pen and Mangabeira-Albernaz,The Speech Recognition Index (SRI) test was carried out by means of monosyllable words which level of presentation was of 40 dB SL (sound level), based on the mean value of thresholds in the frequencies of 500, 1000 and 2000 Hz. Should such level of presentation cause discomfort, we chose to use the level of greatest comfort reported by the patient (The List of Phrases in Portuguese (LPP) testBiologic Systems Corp device, version 5.7, and the auditory stimuli were presented by means of ER-3A insertion phones. The electrode position followed the International Electrode System (IES) standard 10-20Tone Burst  stimuli were generated, at a presentation rate of 1.1/sec. The level of presentation for the stimuli varied between 70 and 85 dB HL, according to the hearing and comfort thresholds for pure tones without hearing aids. It was also required to compare and judge the balance of the intensity of the stimuli detected in both ears. In order to trigger the P300 wave, we used the rare-frequency paradigm of two tones of different frequencies  presented in a random fashion, with a likelihood of appearance between 20% and 80%, respectively. There was a total of 300 stimuli, presented to both ears, and only one record of the ipsilateral trace was captured, which was not replicated in orders to avoid interference by tiredness. The analysis of the P300, of its latency and amplitude, was carried out by three experienced examiners, independently and without them knowing the aim of the study.The electrophysiological assessment was carried out without the use of hearing aids, by means of the Long Latency Auditory Evoked Potential (LLAEP) - P300, recorded with the four channel The results from all the tests were recorded and plotted on a table. A descriptive and statistical analysis was carried out involving all the variables considered in the study.This case-control study is characterized by an interaural/intra-subject comparison of the same group: the Unilateral Fitted Group, in which the hearing-aid fitted ear is compared to the one without the hearing aid, a situation in which, in the same individual, the ear stimulated with a hearing aid acts as a control for the ear deprived of hearing stimulus, which one can define as a situation of combined control. The same procedure is employed in the Bilateral Fitted Group and in the Not Fitted Group: the right ear performance is compared to that of the left ear, with the goal of looking for differences in the interaural performance of the individuals in the SRI, Recognition of Phrases in Noise and P300 tests.versus BFG versus NFG) in the phrases recognition in noise test employed in free field.Besides comparing the interaural performance of the individuals in each one of the groups, there was also a comparison of the performance among the three groups  was employed in each hypothesis test.The inferential statistical analysis was carried out by means of the Variance Analysis test, with repeated measures or p = 0.029) only concerning the time of hearing loss diagnosis between the not fitted group and those with a hearing aid .The ages of the participants in this study varied between 48 and 90 years (M = 70.2 years), the three tone threshold mean value for 0.5, 1 and 2 kHz was 31.6 to 69.1 dB HL (M = 50 dB); the time of hearing loss diagnosis was between three and 20 years (M = 8.3 years). In the groups of patients using sound amplification, the time interval between the initial fitting test and the current reassessment (“time using the hearing aid”) varied between two and 15 years (M = 5.8 years); the time reported of daily use of the hearing aid (“hours of daily use”) was between eight and 18 hours/day (M = 12 hours/day). The variance analysis revealed significant differences  as in the Not Fitted Group (NFG), there were no statistically significant difference in the performance average when the right and left ears were compared in the SRI tests  in the ear with hearing deprivation, when compared to the ear with hearing aid in the UFG  there were no differences in the mean performance between the ear in deprivation and the one fitted with the hearing aid in the List of Monosyllable Words tests , in the  the UFG .This study involved 35 individuals, and although the lack of statistical power of some measures can be associated with the small sample, they do point out important clinical arguments.The lack of significant differences between the ear in deprivation and the ear fitted with the hearing aid in the UFG was not expected and came in disagreement with the literatureAnalyzing the results from the LPP test of phrases recognition in noise, carried out with phones, did not show differences in interaural performance in any of the three groups. The lack of statistical differences in performance between the ear in deprivation and the one with the aid in the UFG was not expected. Nonetheless, when the analysis was carried out in a qualitative and individual fashion, there as a great variability in the performance pattern of this group, and it was possible to notice that while a substantial number of individuals (10 in 15) had a systematically worse performance in the deprived ear when compared to the fitted one, some had an excellent individual performance, which may have improved the general mean result of the S/N ratio in this ear. Therefore, although this analysis did not prove to be statistically significant, it brought about clinically important information as to the difference in the performance between the ear which uses the aid and the one deprived of hearing in the UFG.The use of the LLAEP P300 component has not received so much attention in the monitoring of changes to the central auditory nervous system as other fields in science such as psychology and neurology or in the use of the N1-P2 component of this same potential. This limited use may be justified because of the recording of large variability in the intersubject comparison of the amplitude and latency values. Its use in this study has been justified by the likelihood of broadening the reach of its use, on the feasibility of using it in patients with hearing loss and the situation in which each individual would be his/her own control (“intrasubject” assessment). Thus, it is possible to eliminate the variable inherent to the test when comparing subjects or the different age ranges, making it so that small differences may become very consistent from the experimental view point.p = 0.007). The P300 latency is directly related to the time the individual needs to perceive, process and categorize the stimulus which is directly associated with the information processing speedThe variance analysis showed that only in the group using unilateral amplification we found significant interaural asymmetry. Although only 14 of the 15 subjects in this group were able to generate the P300 component, the latency of this component in the deprived ear proved to be statistically higher than what was registered in the ear fitted with the hearing aid  the auditory systemAlthough the relationship between observing perceptual changes and physiological changes is largely accepted, it is still unclear as to how and how much this may happen. The latency change in the auditory evoked potentials has been described as a neurophysiological correlation of neuronal plasticity, often times preceding a behavioral change which requires longer time to showp = 0.001) and the BFG (p = 0.086) shows important information which deserve to be discussed. In a more detailed analysis, the better performance of the UFG may be associated to two determining factors for a better communication behavior: degree and time of general auditory deprivation.The phrases recognition test in noise, carried out in a free field, was employed with the goal of assessing the use these individuals make of binaural hearing, and, as it happened in the other tests, it was carried out without the use of the hearing aids, in such a way that it would not be a bias factor depending on the degree of maintenance, type or brand of the hearing aid, adjustments of the algorithms utilized. This was the only test in which we carried out a comparative analysis of the performance “between groups”, contrary to the other tests which comparison was only “intra-aural/inter-subject”, within each specific group. The worst general mean performance in the S/N ratio of the NFG compared to the UFG (p = 0.029) and which concurrently, although not significantly, bear a lower degree of hearing involvement (p = 0.216) in comparison to the other two groups. Inversely, the worst performance of the BFG vis-à -vis the UFG may have been increased by the fact that this group had a long mean period of general hearing deprivation before fitting the hearing aids. Even taking into account these important variables and characteristics from each individual, within each group we can not refrain from showing the worst general performance of the NFG and the difficulties faced by these individuals in situations involving speech in noisy environments. The statistically significant finding of a worse performance in controlled tests is a strong evidence that the effects of such deprivation is large enough to compromise the communication performanceSuch favorable difference to this group, not only associated with the UFG as well as the BFG, is justified by the fact that participants of the UFG are still in the initial process of fitting hearing aids, showing that the diagnosis may have been carried out more recently and, therefore, register a shorter time of hearing loss  in silent environments or in the recognition of phrases in noise (LPP) when employed using phones.Have worse signal/noise ratio performance in the medium threshold in the test of phrases in noise (LPP) carried out in the free field when compared to those individuals with binaural hearing aids and those who do not use hearing aids.Had higher P300 potential latency in the hearing deprived ear when compared to the ear with the hearing aid.


Osseous atresia and chronic otitis media are diseases benefit with middle ear implants. Surgery for atresia is technically complicated, has significant number of complications and functional results are often poor. The osseointegrated hearing aids are an alternative. They provide a very good functional gain, but have many problems with the skin and osseointegration. In chronic otitis media, the ossiculoplasty solved partially the hearing problem. Unfortunately in some cases of otitis media and in open cavities fitted with conventional hearing aids the gain is unsatisfactory.To determine the usefulness of an active middle ear implant.Longitudinal Study. Vibrant-Soundbrigde was implanted in 8 patients with severe mixed hearing loss. 4 patients had chronic otitis media and 4 had unilateral atresia. The placement of the stimulator (FMT or Floating Mass Transducer) was in 5 patients on round window, 2 in stapes and one in the oval window.Functional gain was 35 dB, 40 dB, 48.7 dB and 50 dB for the frequencies 500, 1000, 2000 and 4000 Hz, respectively.Vibrant-Soundbrigde is an excellent option in hearing recovery in severe and profound mixed hearing loss. It also provides an excellent functional gain in diseases difficult to treat with conventional hearing aids. With the advent of middle ear implants (MEI) many diseases have been benefited from these devices. Osseous atresia and the wide chapter of chronic otitis media are the principal groups of diseases benefit from this type of hearing aid. Every day the indications are increasing and with it the experience of hearing restoration in different pathologies. Although that in the external atresia we have a wide array of treatment options, they have not always been satisfactory especially in terms of functional outcomes. Thus we have that the surgery for atresia is technically complicated, it also has a significant rate of complications and functional results finally are often poor. The osteointegrated hearing aids (BAHA and Ponto) are an alternative to conventional surgery.These devices provide a very good functional gain and are easy to install, but has a high rate of skin problems and difficulties with osteointegration. Finally, many patients rejected this kind of devices for aesthetic reasons.On the other hand, in chronic otitis media, exist and have been described numerous techniques and prostheses to restore hearing. The ossiculoplasty with many variants of prosthesis  and different materials  have only partially solved the problem. While we have established and standardized techniques, functional failure often leads the patient to disappointment as the only alternative being the conventional hearing aid. Unfortunately in some of these otitis media, especially those who are sequelae at tympanic membrane (perforations or tympanosclerosis) or large open cavities, the use of conventional hearing aids is difficult and often unsatisfactory.For all these reasons is that they have appeared and developed a group of middle ear implantable hearing aids. The common characteristic is that the amplification mechanism must be housed in the middle ear. This prosthesis uses different mechanisms such as mechanical, electromagnetic, and piezoelectric stimulation. In this paper we have used the device Vibrant-Soundbrigde (VSB) which uses vibratory energy to stimulate the inner ear and allows a high possibility of implantation sites at the middle ear. The Floating Mass Transducer (FMT) could be placed in ossicular chain, in round or oval window or joint to any middle ear prosthesis. The study aims to determine the utility through the functional gain in patients implanted with VSB with severe mixed hearing loss, where conventional hearing aids cannot be used or do not provide adequate results.We use Vibrant-Soundbrigde device, manufactured by Med-el, Austria. This device is an implantable hearing aid consists of two main parts. An external processor with the battery, the electronic and the microphone, called AP 404 or Amadé, and an implantable part which consists of two key components the VORP (Vibrating Ossicular Replacement Prosthesis) and FMT (Floating Mass Transducer).The VORP is connected to a cable at the distal end with the floating mass transducer (FMT). This is the electromagnetic coil can be placed on any mobile portion of the middle ear, ie the ossicles or windows, or you can join the FMT to any ossicular replacement prosthesis available.Initial results are presented in 8 patients implanted with the VSB with severe mixed hearing loss. The age of the patients was from 12 to 57, with an average of 41.3 years. We have operated five men and three women. Four of these patients had chronic otitis media with cholesteatoma, while the other four suffered from unilateral atresia of external auditory canal.All patients suffering from chronic otitis media have been previously conventional hearing aid users with poor results as well as active (wet) cavities during use. In these cases the VSB was putting after removed of cholesteatoma in a second stage. The main reason is the necessity of dry cavities to avoid explantations. Finally, in the open cavities is essential to make a bony groove to place the cable, and then cover it with bone pate a cartilage.Patients with unilateral atresia had not used any type of device to improve hearing.The placement of the stimulator (FMT) was in 5 patients in the round window, 2 in stapes and the remaining in the oval window.The technique in patients with the floating mass transducer (FMT) in the round window consists of some very important steps. The most important step, is the exposure of the round window membrane generously, because one end of the FMT should be fully contacted on the surface of membrane to conduct properly the energy to the inner ear. The other step is to protect the membrane with a piece of temporalis fascia to prevent damage. In this manner it has great physical link with very good sound conduction.In the technique on the stapes, we put the FMT directly attached by titanium clip to some crura or on the capitel of the stapes. It is necessary to note that this alternative is common when there is no ossicular chain, usual in radical mastoid surgery.Finally in one patient we had to place the prosthesis on the footplate (not a visible round window). We carry out a total stapedectomy and covered with fascia the oval window, on which we place the FMT.Audiometric thresholds were measured pre-and post-implant in the frequencies 500, 1000, 2000 and 4000 Hz. Postoperative measurements were performed at 30, 60 and 90 days, settling for this work measurements of the third month.With regard to pre-surgical measurements should be mentioned that in only one patient had an extra hearing loss of 10 dB in 2000 Hz and 15 dB at 4000 Hz attributable to the surgical maneuver and corresponded to a patient with FMT on stapes placement. The remaining patients remained unchanged from their pre-surgical thresholds. These preoperatively thresholds were on average in 8 patients of 67.5 dB, 68.1 dB,73.1 dB and 80 dB respectively. In the postoperative measurements average threshold were 32.5 dB at 500 Hz, 28.1 dB at 1000 Hz, 24.3 dB at 2000 Hz and 30 dB in 4000 Hz. . So funcWith regard to surgery in atresia, there is a long way, unfortunately not always successful. SiegertIn a review conducted at Oklahoma University, only 50% of patients reaches threshold near 30 dBYellow et al published results in atresioplasty surgery with pure tone average thresholds and bone-air gap of 37.5 and 29.4 dB, respectivelyRegarding to osseointegrated hearing aids, should be mentioned that there are reports claiming that the closure of the gap has reached 85.1% of patients with external atresiaAs seen on functional outcome is good, but this surgery has an important number of major complications. Hobson et al.Finally, it should be mentioned that the support (Abutment) is percutaneous and many patients reject the idea for aesthetic reasons and maintenance. With respect to the use of VSB in atresia in adults and adolescents, Kiefer described 14 patients with post-implant audiometric thresholds below 30dB.Chronic otitis media is generally associated with some degree of hearing loss. Da CostaAlaani et al.Streitberger et al.VSB device is a very important option in hearing recovery in severe and profound mixed hearing loss. It also provides an excellent functional gain in diseases difficult to treat with conventional equipment such as wet radical cavities impossible to equip with molds (in cavities without inflammatory activity) or in the case of external atresia without the possibility of using hearing aids for air.


Police officers are exposed to impact noise coming from firearms, which may cause irreversible injuries to the hearing system.To evaluate the noise exposure in shooting stands during gunfire exercises, to analyze the acoustic impact of the noise produced by the firearms and to associate it with tonal audiometry results.Cross-sectional.To measure noise intensity we used a digital sound level meter, and the acoustic analysis was carried out by means of the oscillations and cochlear response curves provided by the Praat software. 30 police officers were selected .The peak level measured was 113.1 dB(C) from a .40 pistol and 116.8 dB(C) for a .38 revolver. The values obtained for oscillation and Praat was 17.9±0.3 Barks, corresponding to the rate of 4,120 and 4,580 Hz. Audiometry indicated greater hearing loss at 4,000Hz in 86.7% of the cases.With the acoustic analysis it was possible to show cause and effect between the main areas of energy excitation of the cochlea (Praat cochlear response curve) and the frequencies of low hearing acuity. It is acoustically made up of numerous sound waves with anarchically distributed amplitude and phase ratios, causing an unpleasant sensationNoise, in Portuguese, is a word derived from Latin's Impact noises are usually produced by quick gas expansion, such as that produced by firearms or bomb explosions. These types of sound can reach intensities of 140 dB SPL (sound pressure level) in frequencies around 2 and 3 kHz and, for this reason, they are harmful for human hearingWhen the human ear is exposed to impact noise, at a sound intensity of 120 dB or higher, there is a risk for acoustic trauma. This noise intensity can cause important and abrupt lesions to the cochlea, such as base membrane rupture, tissue and hair cell disarray. Clinically, one of the consequences of impact noise is an immediate and permanent unilateral or bilateral hearing loss, with tinnitus. In some cases, the hearing loss may improve after a few daysNIHL is a sensorineural hearing loss, which initially involves the frequency range between 3 and 6 kHz, where the 8 kHz has to be better than the worst threshold The Occupational Hygiene StandardOne of the industries which expose its workers to high noise levels is the military, especially when practicing with firearms. The firearm explosion noises are among the number one causes of noise-induced hearing loss in the United StatesAuditory profile studies with military personnel in Brazil have shown high rates of hearing loss in this population, and such fact is associated with the excessive exposure to impact noise without individual protection equipmentIn a study about the auditory profile of military personnel from the Brazilian Army, carried out by means of an interview, otoscopy and audiometric exam, we observed audiometric changes which were supposedly induced by noise in 38.1%, with a predominance of unilateral hearing loss. We also noticed that 64.5 % of the military people examined did not use proper hearing protectionOther authors measured the level of noise at the workplace of the police force of Paraná, and found sound intensities higher than 100 dB SPLIn the Singapore Armed Forces, they studied the effects of basic military training on hearing. The researchers studied the audiometries of 85 military personnel before and after training, and found a prevalence of 9.4% of hearing loss, which was kept the same after one year. The study allowed us to conclude that the hearing protection program of the Singapore armed forces is efficient and preserves the auditory health of its officersA recent study involved the audiological profile of five police officers from the Montes Claros Police Force - MG, Brazil. In checking sound pressure levels, the mean level found at the shooting stand was 97.4 dB and of the five police officers studied, two had audiometric curves with a notch, one unilateral and the other was bilateral, and one showed mild sensorineural hearing loss in the high frequencies with a drop-shaped audiometric curveThe international literature suggests the need for a hearing preserving program for police officers and military personnel because of the high sound intensities to which this population is exposed to in their work environmentThere is a great need to implement a hearing preservation program (HPP) to prevent noise-induced hearing loss, when the noise in the work environment exceeds 85 dB (A) during an 8-hour working shift, for continuous or intermittent noise, or 120 dB (C), for impact noise. Within this program, the first factors to be considered are: environment recognition and noise exposure quantificationAll the previously described papers quantified the intensity levels or sound pressure (SIL ou SPL) from the firearm noise, to which these people are exposed during practice and the relationship of this exposure to the audiometric changes found among the officers examined; however, without a study of the physical characteristics of this type of noise and its influences on the types of hearing loss studied.The literature has only a handful of studies associated with the acoustic analysis of non-verbal sounds. There are studies which analyze the temporal and spectral representation of the sound stimulusRecently in the USA, a study was carried out to estimate the auditory risk of shooting civil firearms. Different types of weapons were analyzed: rifle, shotgun, .38 revolver and 9mm pistol. The maximum peaks obtained in the study were 141 a 164 dB (SPL). Considering the revolver and the pistol, in the analysis of the acoustic spectrum, the peaks of greatest energy were concentrated in the low and medium frequencies, with decreases in the high frequenciesThe influence of the noise spectrum in the prevalence of NIHL among workers was carried out in plants with noise levels above 85 dB. The authors did not find associations between the frequency bands with intense noise levels and the hearing damage injury•Transitional attack: corresponds to the passage of silence to sound and in most musical instruments it lasts between some milliseconds and some hundredths of a second; it is very important for timbre recognition, and if cut, the instrument becomes non-classifiable in most of the cases;•Period of stability: time between the previous and the following; usually corresponding to the period of a few tenths of a second to some seconds; it is extremely important for certain sound characteristics such as volume and intensity;•Extinction transitory (drop): period in which the sound is extinguished; it is very important for recognizing timbre, and if cut, the instrument becomes non-classifiable in most of the cases.As far as the sounds of musical instruments are concerned, the acoustic measures of duration, intensity and frequency of resonances are the ones most often used in the acoustic analysis of these stimuliDuring the gunshot noise study period, the stability is more important than the other parameters because of duration, intensity and volume in which the soldier will be exposed to this type of sound.Considered fundamental to associate the exposure of military personnel to firearm noise, the goal of the present study was to assess noise exposure at the shooting stand of the police force, to analyze the acoustic spectrum of the noise produced by the firearms, transforming these values into the Bark scale, in order to compare these data with the audiometric results.We analyzed noise levels from the firearms during gun shooting practice in the Police Academy of the State of São Paulo, analysis from the noise of the firearms used during the shooting practice, and measures of tonal audiometry from a sample of the population of military personnel of this squad. We chose the two weapons which are most frequently used by these officers: .38 revolver and .40 pistol; usually called 38 revolver and .40 pistol, respectively.This study was submitted to the Ethics Committee in Research, having been duly approved (protocol CEP # 2762/2007), and the procedures realized are in compliance with Resolution 196/1996, from the National Health Council.Noise measurement was done by means of a digital decibelimeter from MINIPA, model MSL - 1350, programmed in the fast response circuit (fast), “C” weighted, according to NR-15, in its Attachment #II, and measure range between 65 and 130 dB. The guns used were the .38 revolver and the .40 pistol, both from Taurus Co.During training in the shooting booth, the number of participating police officers varied between 12 and 15, and each individual shot the gun 50 times. Thus, multiplying the number of shots by the number of individuals, we calculate from 600 to 750 impact pulses per period of training.The police officers are duly equipped with Individual Protection Equipment (IPE.), according to NR 620, from Ordinance 3214/78Kay Elemetrics and analyzed through the PraatIn order to analyze the acoustic spectrum we used a portable DAT recorder coupled to a stereo microphone. The recordings were digitalized in a sampling rate of 44,000 Hz with the use of CSL from Since the goal of research work was to relate the military exposure with the level of noise submitted to during the training period we adopted the following procedures:Praat graph, we plotted the temporal graph of the sound intensity level (dB)   and we efon scale) in the two gunshot sequences  from each shooting sequence in order to establish in which regions of the cochlear base membrane there was a higher degree of deflection generated by the noise intensity. Since each region corresponds to a resonance frequency range, such as the Critical Band, it is supposed that the regions are subjected to a higher likelihood of damaging the hair cells because of the high gunshot intensity . The Criequences .Praat application. We employed the t-student statistical test in order to assess the relationship between the two groups of independent samples with a 5% significance level (a = 0.05) for the null hypothesis (Ho). Knowing these instances of greater excitation, we can raise the Barks band in which this excitation happens and, with that, we establish its frequency range.With that, it was possible to compare the peak instants obtained from the temporal graphs (wave form and sound intensity level) and the time instants in which there is greater base membrane excitation from the cochleograms . If the instants are statistically similar, we can assume that instant as the one with the greatest base membrane excitation. These values were established through the data matrix of the graphs available at the Thus, it was possible to also identify the spectral shape curve of the gunshot sound from the two types of firearms in order to analyze and discuss the transitional period of the attack, stability and extinction transitional. This curve is relevant in order to determine the mean energy density in function of frequency .Figure 2Grason - StadlerThe auditory threshold measures were carried out in an acoustic booth, with a GSI 61 McNemar test starting from the threshold ratios. We used the non-parametric test for two ratios, which assesses the level of disagreement of a variable between two paired samples. The unilateral alteration (left or right ear) is what we call disagreeing pairs. The significance level used was 1% (a = 0.01) for the null hypothesis (H0).We have also assessed the asymmetry of the audiological values between the tonal audiometry thresholds of the right and left ears using the The background noise on the measurement days was 75.3 dB (C), in average, and the maximum peaks measured were 113.1 dB(C) for the .40 pistol and 116.8 dB(C) for the .38 caliber revolver. The noise level mean values were 114.8 dB(C) and 111.9 dB(C), respectively, for the revolver and the pistol.t-student test employed between the two groups of analyses resulted in p=0.29 (p>a=0.05) for the 1st shot and p=0.17 (p>a=0.05) for the 2nd shot, confirming the null hypothesis (Ho), in other words, there were no significant differences in the results comparison between the times of the two samples .The time instants in which we had the highest noise intensity in the temporal scale and the greatest excitation in the spectral analysis by means of the cochleograms for the two shooting sequences are depicted on st and 2nd shot, respectively. For the .40 pistol, the Bark scale was 17.8 and 17.6 in average for the 1st and 2nd shots, respectively. Therefore, we can consider that in average, for the two types of weapons, the value was around 17.9±0.3 Barks, corresponding, by linear interpolation, to a cochlear stimulation area between 4120 and 4580 Hz.Thus, the statistical test guaranteed the use of the excitation peak time values from the cochleograph  as a refThe spectral form  has a dep value = 0.22 (p>a=0.01), statistically confirming the symmetry of the hearing alteration in this sample.The data obtained in the tonal audiometry test of this sample of police officers, depicted on During practice with firearms, we identified at least 600 sound impacts caused by firing the weapons. Since the Norma Técnica FundacentroOther authors also found high levels of sound intensity in the occupational environment of police officersThe data hereby presented is in agreement with those in the national and international literature, concerning the identification of an unhealthy occupational environment and point to the need to create a hearing protection program for these law enforcement professionalsThe temporal  and speca priori, the regions in which there was a higher degree of cochlear basal membrane excitation with this type of noise, enabling the establishment of corresponding frequency ranges. In the Praat cochleograph analysis it was possible to notice an intense concentration of energy within 17.9±0.3 Barks, in other words, in the sensitivity region of the high cochlear frequencies: 4120 and 4580 Hz.The acoustic and psychoacoustic analyses of the gun shooting sounds pointed to some relevant aspects on the cause-and-effect analyses concerning the hearing loss detected in this sample of police officers. It established, Audiometric findings corroborated what was presented in the Praat cochleograph, since the frequency with the worst auditory thresholds was the 4,000 Hz . TherefoThe data presented in the acoustic and audiometric analyses confirm that the permanent exposure to noise damage the outer hair cells, especially those on the cochlear basal turn, very likely because this is the part of the organ which is most commonly stimulatedAlthough the statistical results on the hearing loss asymmetry between the ears (right and left) lead us to accept the null hypothesis (Ho), we have noticed that the proportion of hearing loss is slightly higher on the left ear for all frequencies, except 8,000 Hz - in which the proportion is the same . This faThe measures and analyses carried out enabled the recognition of the environment and the quantification of the noise exposureConcerning the acoustic analysis, the present study found results which were similar to those reported from the United States: the highest energy peaks were concentrated in the low and medium frequencies, with a drop in the high frequenciesAnother study reports on the relationship between the noise acoustic spectrum and NIHL; however, the authors did not do a psychoacoustic analysis to prove their resultsThe present study identified sound pressure levels which were higher than the ones recommended by the Fundacentro NHO 01 standard, which establishes that the maximum limit for the population studied should not go above 109 dB(C).Praat's cochleograph) on the high frequencies, and the audiometric findings show the cause and effect relation between the firearm shots and the hearing loss.Based on the acoustic and psychoacoustic analyses of the gun shots, it was possible to show that there is a coincidence between the main areas of energy concentration (Thus, we conclude for the need of developing a hearing protection program for the police officers in order to prevent the onset, as well as the worsening, of hearing loss in this population.


Triclosan (TCS) is a widely used chemical whose effects on human health remains elusive. TCS may play a role in a variety of health issues, including endocrine dysfunction, irregular embryonic development, and immune suppression. It is possible that TCS’s penetrative abilities across all body barriers, including the blood–brain barrier, may make bioaccumulation the primary driver of these issues. In addition, chronic overuse of this chemical in everyday life may further contribute to the already increasing problem of antibiotic resistance. TCS research has steadily increased since its transition from medical to commercial use over the last 50 years. However, there are some clear gaps in the depth of this research as the safety of this agent is not fully agreed upon. The Food and Drug Administration recently issued regulatory rules regarding TCS in some commercial products; however, it is still found in a variety of goods marketed as “antimicrobial” or “antibacterial”. The purpose of this bibliometric study is to analyze research trends in this field and determine the amount of global attention TCS has received as to its relevancy in human health. Documenting and determining research concentration trends related to this field may outline where additional research is most necessary, as well as demonstrate the most valuable research produced and its relation to the advancement of our understanding of TCS. We found there to be a shift in research from TCS and its role in medical environments, to research based on the indirect effects of TCS through environmental contaminations, such as the propagation of antibiotic resistance. This shift was coupled with an increase in global research related to this field and identified China as a significant contributor. Although TCS has received notice, the simple fact of its continued use in so many common products, as well as the unclear understanding of its direct health impacts, reinforces the need for additional and more conclusive research before it has possible irreversible effects on our environment and health. Triclosan (TCS), or 5-chloro-2- phenol, is an antimicrobial agent, registered pesticide, and known toxicant, which is a frequent and common ingredient in household products, such as deodorant, liquid soaps, cosmetics, and furniture . TCS wasTCS targets the phospholipid membrane through its detergent-like property that affects the stability of lipid structures . Some baResearch on the effectiveness of TCS remains inconclusive. TCS has been reported to be especially useful in the prevention of the spread of disease in healthcare settings, effectively performing as an antimicrobial agent. Most notably, the use of TCS-coated sutures proves especially efficient in the prevention of surgical site infections post closure, when used in decontaminated surgical environments . HoweverAntibiotic and antimicrobial overuse seeps into every form of our daily life and continually puts us at higher risk of bacteria that we do not have the ability to fight when resistance emerges . AlthougTCS was also detected in neonatal cord blood. A study in New York City showed that 100% of urine samples from 181 expectant mothers and 51% of cord blood samples from their infants contained TCS ,20. PeriIn the 2016 ruling on the safety of TCS, the FDA determined that although TCS has been shown to cause significant endocrine disruption in rat models, because of the physiological differences between humans and rats, TCS should pose no risk to human health . They thAltogether, TCS is a potential risk to human health in development, neuropsychology, immunity, the emergence of AR, and others; however, it remains prevalent throughout our everyday use of common commercial products. The status and trends of research on the effect of TCS on human health have not been systematically analyzed in recent years. Therefore, the purpose of this bibliometric study is to analyze research trends in this field and determine the amount of global attention it has received regarding its effects, thus identifying a potential gap in global research trends for the suggestion of future research endeavors.®, which broadly encompasses research from multiple scientific fields. A search of the data was performed on 8 November 2021. All data were imported into Microsoft Excel and VOSviewer for analysis [The workflow demonstrates the data collection process used in this analysis . All datanalysis . The sea® Excel. This includes growth trends, citations per year, main researchers, and most prominent journals that published TCS research. Further visual analysis was then carried out in VOSviewer 1.6.17. VOSviewer is a software tool for constructing visuals related to bibliographic information [This study involves the analysis of research related to the TCS and its effect on human health in a broad range of concentrations. TCS dates back to its original patent in 1966 filed by the company Ciba-Geigy and was then introduced into medical settings in 1973 [ormation . This inA total of 3278 documents that fit the search criteria were analyzed. Research growth was analyzed between the dates of 1 January 1973, and 11 February 2021. Although TCS was patented in 1966 for use in medical procedures and environments, research related to TCS on human health did not emerge until 1973 . In addiAnalyzing the subject and concentration of TCS-related research in three main phases can outline a more detailed research trend and make clear what areas may need more focus . These pA total of 3278 publications related to TCS and health led to a total of 123,534 citations . The treScience of the Total Environment and Chemosphere lead in publication number by almost two-fold in comparison to other journals of this type  was eliminated from hand soaps in 2016 by the FDA but remains in a variety of everyday items, yet the effect on human health remain elusive. So, we have attempted to identify the research trends of TCS to determine whether research resources have been adequately spent to resolve the issue of uncertainty. TCS research has substantially increased over the last 50 years, but we determined that there are definitive gaps that remain in certain areas of focus. Although a large number of publications and citations have been produced, the vast majority are in relation only to the environmental impacts of TCS or its use in specific products, such as dentifrices and surgical devices. We found a significant lack of research in relation directly to TCS and human health in comparison with that related to its environmental impact. This, in conjunction with the FDA’s acknowledgment of a lack of definitive understanding of the role TCS could play in dermal carcinogenicity, endocrine dysfunction, and antibiotic resistance, proves the need for additional research in these fields. Since the current study is based on bibliometric analysis, it is focused on identifying overall trends, so we plan to provide a fuller picture of the collective understanding of TCS research in review paper format.


Globally, around 34 million children are affected by disabling hearing loss. Among Western newborns hearing loss shows a prevalence of about 2 per thousand, with about 4 times higher rates in other parts of the world such as Sub-Saharan Africa or South Asia. The scene of childhood hearing loss diagnosis and intervention has rapidly changed within the past two decades. Newborn hearing screening, followed by timely diagnosis and fitting with hearing technology, combined with early access to family-centered early intervention programs has shown significant effects on child language and psycho-social development and on family quality of life. Childhood hearing loss has thus proved to be a condition with highly malleable outcomes. The effectiveness of early intervention is largely determined by the quality of national and regional multidisciplinary networks and the active involvement of families.An overarching model of early intervention is presented by our group . QualityZee and Dirks  demonstrTwo studies refer to the early identification of hearing loss. Elliot et al.  investigThe retrospective chart analysis by Minami et al.  examinesIdentification of the genetic cause of hearing loss has become common in Western countries. Notini et al.  present Three contributions relate to developmental assessments required for tailored early intervention. In accordance with the key role of parent-child interaction for child and family outcomes, Curtin et al.  present A number of contributions to this special issue relate directly to the practice and outcomes of family-centered early intervention. Dirks and Szarkowski , underliFinally, our Linz group  presentsThe international contributions to this special issue bring together the evidence that support the effectiveness of well-integrated multidisciplinary networks, including family-centeredness in early identification and parent counselling, developmental surveillance, implementation of early intervention and upcoming research. There is still a tremendous need to increase global contributions to the field of early intervention in pediatric hearing loss.


Aim: to analyze the clinical and hearing information from individuals with AS, more specifically the correlation between renal disorder and hearing loss (HL). Study design: clinical prospective with cross-sectional cohort. Materials and Methods: 37 individuals underwent otorhinolaryngological evaluation and were submitted to audiologic tests. For HL statistical analysis we considered only the results from the pure tone audiometries. Results: of the 28 individuals with clinical alterations, we found 46.4% of DLX and 53.6% of AD. HL happened to 46.1% of the individuals evaluated. 12 patients presented HL in the audiometric test: 11.5% mild and 34.6% moderate. Comparing the normal relatives with those with renal disorder; all that had HL also had renal disorder. In 30.8% the curve shape was mild descending in the high frequencies and in 11.5% it was flat. Conclusions: The inheritance pattern distribution does not match literature descriptions. HL is a frequent extra-renal finding. There is an association between renal involvement and HL (p= 0.009). The most frequent curve shapes: mild descending in the high frequencies and flat. There was no association between HL and age. There is no correlation between the HL and gender in this group.Alport Syndrome (AS) is a hereditary disease, characterized by nephropathy, often times with sensorineural hearing loss and ocular defects.  Alport Syndrome (AS) is a hereditary disorder characterized by hematuria, which usually leads to renal failure. It can be followed by extra-renal manifestations. Therefore, often times, kidney disease is associated with sensorineural hearing loss (SNHL) and ocular effects.The goal is to analyze clinical and hearing data from individuals with Alport Syndrome, with emphasis in the correlation between renal alteration and hearing loss.This study and the Free Consent Form were approved by the Institution”s Ethics in Research Committee (Project # 118/05). This is a cross-sectional cohort clinical prospective study.We assessed eight families and drew the respective genetic map, with information of at least one more generation. Clinical and audiologic data of the index cases  referred were collected, and the family members who agreed to participate were evaluated. All the families matched at least two strict diagnostic criteria.Thirty-seven individuals from these families agreed to take part in the study and carried out an assessment made of: detailed clinical and family history, complete otorhinolaryngological physical exam, assessing prior lab exam results . Families 2, 5, 6 and 8 had individuals who underwent renal biopsy with histological alterations matching those found in individuals with Alport Syndrome. Patients did not have prior history of noise exposure nor of using ototoxic agents. Families 1, 4 and 5 had individuals with ocular alterations. We did not see any patient with anterior lens cone.Audiological tests were carried out following the same standardization in index cases and in other family members who agreed to take part in the project. Children below three years of age who did not respond properly to the tests or could not be conditioned, for statistical purposes, were considered as not having gone through audiometric tests.Results were classified, considering the mean value at 500, 1.000, 2.000 and 4.000 Hz, in the worst ear in: mild (21 - 40 dB HL); moderate (41 - 60 dB HL); moderately severe (61 - 80 dB HL); severe (81 - 100 dB HL); profound (> 100 dB HL) and not tested.A 15 dB difference between the ears in at least two frequencies or a 10 dB difference in four frequencies defines an asymmetrical hearing loss, and the symmetrical hearing loss has the same configuration and difference < 15 dB in the same frequencies between the ears.Audiometric curves were classified according to what was described on The genetic maps of the eight families were crafted from the data collected and with the results from the audiologic tests, separating the ones who took part in the study (in red) from those who only provide information.Using the EpiInfo software, version 3.2, the following statistical tests were applied: chi-squared (c2) and Fisher Exact Test. We considered a 95% confidence interval in our statistical comparisons.1 -Genetic maps2 -Statistical analysis of the clinical and hearing dataUsing standard symbols, the information obtained about the family history of the probands evaluated were graphically shown in the following genetic maps .2 -StatiThirty-seven members from the eight families went through the evaluation approved by the Ethics in Research Committee of the Institution (Project # 118/05). The nine normal individuals were taken off the study.Females prevailed in this group , and males were less commonly found .Adults prevailed in this group of patients ; pre-school and school aged children and teenagers together represent 50.0% (14/28).Inheritance patterns were obtained after we created and analyzed the inheritance patterns. In this sample we found 46.4% of DLX and 53.6% of DA.Twelve patients had hearing alterations in their audiometric tests: 11.5% (3/26) with mild alteration and 34.6% (9/26) with moderate alteration. Infants (below two years of age) who could not undergo the pure tone audiometry were taken off the analysis. In relation to the patients with mild hearing alterations age range (3/26): one was of school age (11 years) and two were adults. Of the patients with moderate alteration (9/26) the age distribution is the following: one school aged child (eight years), two teenagers (14 and 17 years) and six adults. Hearing loss happened in 46.1% (12/26) of the individuals evaluated. Five patients were referred to hearing aid fitting during our study.We analyzed family members without clinical problems and we compared them with those that had renal disorder. All of those who had hearing problems also had renal involvement. There is an association between renal involvement and hearing impairment (p= 0.009). RD%: 20.36 -61.45. 52% (13/25) of the patients in any stage of the renal disease did not have alterations in their audiologic tests. 48% (12/25) of the patients at any stage of the renal disease manifested mild or moderate hearing disorder. From this analysis we excluded those infants (2/37) who did not undergo pure tone audiometry and one individual (1/37) who had not undergone urine tests during the study.13 patients had normal audiometric curves (50.0%) and 30.8% have a mildly descending curve in the high frequencies (8/26). A flat curve happened in 11.5% (3/26). The less frequent configurations were: sudden drop in high frequencies and U type. Two infants were taken off the study.In the group studied, although we observed 30.8% (8/26) with symmetrical hearing loss when both ears are compared, 19.2% (5/26) had asymmetrical hearing loss. Two infants were taken off the study.We observed hearing alterations in the school-aged children, in the adolescents and in adults. We did not detect hearing changes in pre-school aged children. We took off the study those two infants who did not undergo pure tone audiometry. There was no statistically significant correlation between the hearing alteration and age among the patients studied.In this group we observed 60.0% (6/10) of men with hearing disorder and 37.5% (6/16) of women with hearing disorder. There were 10/16 (62.5%) women without hearing disorder and 4/10 (40.0%) of men with the same problem. Two did not undergo audiometry because their ages were not suitable for the test. Literature reports that hearing loss happens, more frequently, in men when compared to women.In this study we had more women (57.1%) being evaluated than men (42.9%). In family 2 we noticed four males who died and in family 8 there were three members who died. This could also contribute to a lower participation of men in the study .Table 2IPre-school aged, school aged and adolescents make up 50.0% (14/28) of the cases analyzed . In the The creation of inheritance patterns and discussing them with the genetic team has contributed to the analysis of the families . We obseProving that hearing disorder helps diagnose AS in the patients who had not undergone renal biopsy, making up a strict diagnostic criteria. Renal biopsy may be dubious in children and in women or, still, risky in cases of severe renal involvement.In this sample we found 46.4% of DLX and 53.6% DA . The intWe analyzed family members without clinical involvement and compared them to those who had renal alteration . All of Hearing alteration happens before the stage of renal failure, showing that it is not determined by uremia. It happens because of alterations in the basal membranes in the organs potentially affected by AS, according to the literature.12HL is never seen without kidney symptoms.Hearing disorder progression suggests poor renal diagnosis, thus stressing the close tie between hearing alterations and renal failure in men and women.14Among the patients assessed in this sample, twelve had hearing disorders in their audiometric test: 11.5% 3/26) had mild disorder and 34.6% (9/26) had moderate hearing disorder . As far  had mild17There was no statistically significant correlation between the hearing disorder and the age of the patients studied . NotwithStill in this study group, 50.0% (13/26) of the patients had normal audiometric curves and 30.8% (8/26) had a mild descending curve in the high frequencies . 11.5% (Three audiometric curve types were seen in the 51 ears with hearing loss: cup shape (47.1%), descending (41.2%) and flat (11.7%).In the group assessed, we noticed 30.8% 8/26) of symmetrical losses and 19.2% had asymmetrical hearing loss (5/26) when comparing the two ears . The lit of symmeIn this study we noticed 60.0% (6/10) of men with hearing alterations and 37.5% (6/16) of women. 62.5% (10/16) of women without hearing loss and 40.0% (4/10) of men in the same situation . LiteratPrognosis has changed with the development of renal transplant, increasing the longevity of patients with AS and renal failure. Making HL development investigation and its rehabilitation relevant for the life quality of these individuals. There is a broad research field to be developed, with genetically modified animals or animal models, in order to understand the disease mechanisms involved in the hearing disorder and normal hearing. These same models can be employed in the study of new treatment modalities.Not only the pathophysiological mechanisms of SNHL in AS still require additional studies, but also the clinical symptoms, hearing alterations and genotype-phenotype relation. The work of multidisciplinary groups from multiple centers shall bring about more information about the disease and its clinical course, diagnostic methods and treatment modalities. HL in AS is still a very exciting area for research by geneticists and otolaryngologists.-The inheritance patterns observed were AD and DLX. The distribution of inheritance patterns, in the present investigation, does not coincide with what is described in the literature.-Hearing loss is frequently found in AS.-All of those with hearing alterations also had renal involvement. There is a clear association between renal involvement and hearing alteration (p= 0.009).-Audiometric curve types more commonly found in this sample were: mild drop in high frequencies and flat curves. The less frequently found curve types were: sudden drop and U-shaped type.-There was no association between hearing alteration and age, found in the present study.-We did not find correlations between these hearing alteration and gender in this study.


Mucormycosis or black fungus is one of the most lethal, progressing, and rapid form of deep fungal infections in humans which is caused by group of molds called mucormycetes. It is called black fungus infection due to black nasal discharges and black patches around nose found in the initial stage. The most common variety is rhino-orbito-cerebral-maxillary, although there are also pulmonary, gastrointestinal, cutaneous, and disseminated variations. In recent years, mucormycosis has become increasingly prevalent in immunocompromised individuals, with coronavirus disease 2019 (COVID-19) infection and associated consequences as the primary source of the cause. Rhino-orbito-cerebral-maxillary variety usually involves the nose, paranasal sinuses, brain, and maxilla but the involvement of mandibular bone is exceedingly rare. In this case report, we present a case of a 59-year-old male affected with mandibular mucormycosis in post-COVID scenario which is quite rare situation. Mucormycosis is a deep fungal infection caused by a saprophytic fungus that is a member of the Phycomycetes phylum and is characterized by deep, fulminant, and acute fungal infection. Although Baker first used the name in 1957, Paltauf initially reported mucormycosis, also known as zygomycosis/Phycomycosis, in 1885 . This enDuring the second coronavirus disease 2019 (COVID-19) wave in India, this crippling illness received a lot of media attention. Numerous cases of post-COVID mucormycosis have been reported, primarily as a result of (a) uncontrolled diabetes with diabetic ketoacidosis; (b) using immunosuppressive medications such as tocilizumab, baricitinib, and tofacitinib; (c) cytokine storm; (d) increased free serum iron level ; (e) increased host endothelium glucose regulator protein (GRP78) activity and its association with CotH3 (spore coat protein-ligand); and (f) endothelial damage and free radical injury lymphocytopenia . Thus, tThe dramatic increase in mucormycosis cases in the Indian subcontinent following the second wave of SARS-CoV-2 infection has drawn attention to this potentially fatal condition. Due to the black color of diseased and necrotic tissue, the name "black fungus" is frequently used to characterize this illness. During the most recent wave of the pandemic, several cases of maxillary involvement in rhino-orbito-cerebral mucormycosis have been described, but relatively few cases have included the mandible. We now describe a mandibular instance of post-COVID mucormycosis. The case was first treated for mucormycosis of the maxillary sinus but after 2.5 to three months, the jaw became involved.We describe a 59-year-old man who visited the Department of Dentistry at All India Institute of Medical Sciences (AIIMS), Patna, with the primary complaint of gum swelling and teeth mobility on lower right side of mouth for 15-20 days. A COVID-19 infection had already occurred. A diagnosis of rhino-orbito-cerebral mucormycosis and the discovery of diabetes three months later led to endoscopic surgical debridement of devitalized tissue in the turbinates, maxillary sinus, and anterior and posterior ethmoid. The patient was asymptomatic and underwent routine follow-up at the Department of ENT, AIIMS, Patna, for the following 2.5 months. However, during that time, he experienced gingival swelling and tooth mobility on the lower right side of the oral cavity, and he was subsequently referred to the department of dentistry. Gingival swelling was discovered during a clinical examination in the 43-46 area  and posaconazole (300 mg delayed-release tablets twice a day for one day followed by 300 mg daily), and an open surgical debridement of the mandible was scheduled. An intraoral vestibular approach was used to perform a marginal mandibulectomy under rigorous aseptic procedure on the right side of the afflicted mandible Figures . After dMucormycosis, one of the most deadly and fulminating fungal infections in humans, starts typically in the nose and paranasal sinuses. The fungus enters the blood vessels through angioinvasion of the descending palatine artery and internal maxillary artery. In blood arteries, mucor hyphae create thrombi that reduce tissue vascularity and result in necrosis. Furthermore, because of the elevated level of angiotensin II, thrombosis is more likely in COVID-19 patients. Due to its direct atherosclerotic effects on the vascular wall, angiotensin II is shown to be prothrombotic. These effects include increased inflammation, endothelial dysfunction, oxidative stress, endothelial cell and vascular smooth muscle cell migration, growth, and proliferation . Figure The cytokine storm, an auto-amplifying syndrome of proinflammatory cytokines, is also brought on by SARS-CoV-2. Endothelial cell vascular damage is brought on by an increase in a number of proinflammatory cytokines, such as tumor necrosis factor-alpha  and interleukin (IL)-2R, IL-6, IL-8, and IL-10. Numerous of these cytokines exhibit prothrombotic properties. The lungs, spleen, brain, stomach, and peripheral vasculature experience microvascular and macrovascular thromboembolic events as a result [Patients with rhinocerebral mucormycosis may complain of face discomfort and/or coloring, swelling, nasal or oral pus discharge, the appearance of a reddish-black nasal septum and turbinate, paresthesia, proptosis, toothache, and mobility of teeth -8.As the illness worsened, sinus tracts and tissue sloughing might emerge, and necrosis could spread to the paranasal sinuses and orbital cavities. As a result of the infection in the nasal cavity or paranasal sinuses via palatal vessels, the oral cavity involvement usually begins as palatal ulceration or necrosis and subsequently as perforation of the palate. Clinically, phycomycosis affecting the maxillary sinus might manifest as a tumor in the maxilla that resembles antrum cancer. Once the orbit is implicated, it could exhibit orbital cellulitis -8.The differential diagnoses include bacterial necrotizing infections, aspergillosis and other fungi diseases, cancer, rhinoscleroma, TB, syphilis, and other granulomatous disorders. Finding the invasive saprophytic fungus in the afflicted tissue is necessary for a definitive diagnosis as it dwells in the nose and mouth ,9.Amphotericin B, posaconazole, or isavuconazole are used as antifungal medications in primary care, combined with surgical debridement of necrotic tissue. The patient's underlying predisposing disease process, the amphotericin B injection, and early aggressive surgical debridement proved to be the three most important determinants affecting survival. Survival improved to 78% in patients who underwent broad surgical debridement as opposed to 57.5% in those who did not. Arterial thrombosis prevents amphotericin B from getting to the fungus because it thrives in necrotic tissue. Consequently, surgical debridement eliminates an infection source that is resistant to systemic therapy. Polyene antifungal drug's (L-AMB) liposomal formulation has less nephrotoxicity and is prescribed during the initial course of mucormycosis treatment. L-AMB was recommended for our patient as well ,10. In dAlthough rare and often misdiagnosed, mandibular mucormycosis might be reported to maxillofacial surgeons. This case report aimed to shed light on mandibular mucormycosis, its hypothesized etiopathogenesis, and the recommended course of therapy. This lethal disease can be prevented or reduced in frequency with early intervention and competent medical and surgical treatment with full debridement.


Vanishing white matter (VWM) is a leukodystrophy that leads to neurological dysfunction and early death. Astrocytes are indicated as therapeutic target, because of their central role in VWM pathology. Previous cell replacement therapy using primary mouse glial precursors phenotypically improved VWM mice.The aim of this study was to determine the translational potential of human stem cell‐derived glial cell replacement therapy for VWM. We generated various glial cell types from human pluripotent stem cells in order to identify a human cell population that successfully ameliorates disease hallmarks of a VWM mouse model. The effects of cell grafts on motor skills and VWM brain pathology were assessed.Transplantation of human glial precursor populations improved the VWM phenotype. The intrinsic properties of these cells were partially reflected by cell fate post‐transplantation, but were also affected by the host microenvironment. Strikingly, the spread of transplanted cells into the white matter versus the gray matter was different when grafted into the VWM brain as compared to a healthy brain.Transplantation of human glial cell populations can have therapeutic effects for VWM. For further translation to the clinic, the microenvironment in the VWM patient brain should be considered as an important moderator of cell replacement therapy. Intracranial transplantation of human stem cell‐derived glial progenitor populations improves the leukodystrophy phenotype of Vanishing white matter (VWM) mice. In the VWM brain, transplanted cells show altered migration and cell fate as compared to cells transplanted into a healthy brain. Translation to the clinic should consider the microenvironment in the VWM brain as an important moderator of cell replacement therapy. Eif2b5 homozygous mice develop VWM, whereas heterozygous littermates do not and were used as healthy controls.2.2Human ESCs (hESC line H01) were differentiated into glial (precursor) cells as described in Nadadhur et al.,2.3Eif2b5R191HRag2null mouse neonates were injected in the brain as previously described.2.4+GFAP+ cells in the corpus callosum, and Plp+ cells in the white matter of the corpus callosum and cerebellum. While cognitive signs have been noted in VWM patients, especially in late‐onset cases,Animals were weighed from 4 months of age until culling. The researchers were blinded to the treatment conditions during all assessments of animals for VWM pathology as described previously in Dooves et al.2.5+ astrocytes in the corpus callosum, and in Plp+ cells in the brain white matter, cell counts were performed as described previously.RT‐PCR, immunocytochemistry, immunohistochemistry, and in situ hybridization procedures were used to determine VWM brain pathology Tables . A Leica+ cells counted in these images were used to calculate the ratio of HN+ cells in the white matter and the gray matter. No HN+ WM/GM ratios were calculated for two animals in the Pop5 group (1 control and 1 VWM) that had received a mislocalized injection, as this confounded cell localization results. No other data points of individual assays were excluded. To assess the cell fate of transplanted cells, the numbers of OLIG2+HN+ or SOX9+HN+ were divided by the total number of HN+ cells in the genu and splenium.An image was taken of the genu portion of the corpus callosum, of a portion of cortex adjacent dorsally, and of the most superficial area of the cortex dorsal to that. The splenium portion of the corpus callosum was also imaged. For each animal, 3 to 4 brain sections were imaged. The sections analyzed were as similar as possible between animals with regard to medial‐lateral location. The numbers of HN2.6+GFAP+ astrocytes in the corpus callosum, and Plp+ cells in the cerebellar white matter and the corpus callosum) and motor skill assays . The variance inflation factor (VIF) of each predictor variable was below 5, indicative of no multicollinearity among variables. To ensure this assumption was met, the variance proportions were also inspected, which showed no values of >0.9 were present.Data were analyzed with SPSS software (IBM SPSS Statistics 26.0). A binary logistic regression model was used to study the overall phenotype of VWM mutant animals that received cell transplantations Table . The modEif2b5R191H genotypes on within‐subject variables when appropriate. Welch tests with Games–Howell post hoc tests were used in case of unequal variances as indicated by a Levene's test. Non‐parametric alternatives used were Mann–Whitney U‐test or Kruskal–Wallis tests.All data were tested for normality using Shapiro–Wilks tests. To compare groups, independent t‐tests or one‐way ANOVAs with Tukey's post hoc tests were performed when appropriate. A two‐way repeated‐measures ANOVA was used to compare 3A proof‐of‐principle study on cell replacement therapy for VWM showed success by transplanting primary mouse glia progenitor cells into a VWM mouse model.3.1+ cells had migrated throughout the brain, including to the olfactory bulb, the corpus callosum, cortex, hypothalamus, hippocampus, midbrain, cerebellum, and brainstem  whereas Pop3 (vs. control post hoc p = 0.040) and Pop4 (vs. control post hoc p < 0.001) performed comparably to VWM saline‐treated animals  in the cerebellum. BG translocation is a disease marker of VWM and is sensitive to therapeutic intervention.F = 8.717, p = 0.001; males non‐significant; Figure F = 8.232, p = 0.001; Figure H (2) = 29.087, p < 0.001; Figure F = 14.753, p < 0.001; Figure + astrocytes in the corpus callosum  of the variance in pathology outcome, which was statistically significant (Chi‐squared χ2 (6) = 44.361, p < 0.001). A Hosmer & Lemeshor test was not significant, indicating good fit of the model. The model was used to determine a classification of the performance of cell‐injected VWM animals as either “saline‐injected VWM” or “saline‐injected healthy control.” Healthy controls injected with cells were excluded from analysis. A cut‐off score of <0.25 was used for the probability of being assigned as a saline‐injected VWM animal. The model classified 46.1% (6 out of 13) of VWM animals transplanted with Pop1 or Pop5 cells as performing similarly as healthy controls, indicating human glial transplants can improve the phenotype in a VWM mouse model. Table To judge in more detail whether the VWM phenotype had improved after transplantation with Pop1 or Pop5 cells, various phenotypic assays were used as validated by Dooves et al.3.3NESTIN, BLBP, GLAST, and OLIG2, in combination with the less strongly expressed GFAP and AQP4 genes, indicating that the astrocytes (progenitors) in this culture are relatively immature  = 11.25, p = 0.010) remained intact in 8‐month‐old control animals (post hoc p = 0.030) and VWM animals alike, albeit non‐significant for the latter group  and VWM animals (post hoc p = 0.019). At the same time, there was a significantly lower amount of OLIG2+HN+ cells in VWM animals compared with controls . That improvement of VWM phenotype was not a discriminatory factor in cell fate is in agreement with finding improved animals in both the Pop1 and Pop5 groups. Interestingly, mouse genotype did have an effect on the cell fate of Pop5 transplants, as indicated by a decreased OLIG23.5+ Pop1 cells was higher in VWM animals in the corpus callosum than in the cortex, and also when compared to either the cortex or the corpus callosum of heterozygous control animals  = −2,77, p = 0.039; Figure + cells showed a preferential localization to the corpus callosum in VWM animals specifically. Although an ANOVA comparing both genotypes in both cell populations was not significant, the same effect was seen in transplanted Pop5 cells, for which the ratio of HN+ cells in the white over the gray matter was also higher in VWM animals as compared to controls  showed therapeutic benefits that may result from their increased plasticity, aiding their adaptation to the new microenvironment post‐transplantation. Our results thus indicate that immature cells show better survival in the host environment than do mature cells; the mechanism of graft‐induced phenotypic improvement is most likely primarily dictated by progenitor status in vitro. At the same time, Pop3 cells were matured for a shorter period in vitro than Pop1, Pop2, or Pop5, but did not result in phenotypic improvement. Among the glial progenitor populations treated with retinoic acid during in vitro preparation, a developmental window seemed to determine success. More in‐depth expression analysis of the retinoic acid‐induced cell populations might help to determine the identity of these successful populations as well as their developmental and molecular profile. Testing additional time points in vitro might identify more efficient graft populations. However, for therapeutic benefits in patients, species differences between the human and mouse microenvironment should be considered.+ vs. residential HN− OPCs, we performed IHC‐based analysis of HN, OLIG2, and the mature oligodendrocytic marker myelin basic protein (data not shown). However, quantification proved unreliable and more in‐depth analysis of cell replacement therapy on local neural cell populations would need follow‐up in, for example, lineage‐tracking experiments. Together, our findings underscore a significant effect of the VWM brain microenvironment, in line with an earlier study suggesting that an as of yet unidentified secreted astrocytic factor is likely to contribute to VWM pathology.The transplanted cells interacted with the microenvironment in which they were transplanted. Between VWM and control animals, differences in the cell fate and spread of transplanted cells were observed. The degree of oligodendrocytic, astrocytic, or alternative cell fates did not only differ between transplanted cells, but also between VWM and control animals. In addition, a higher number of grafted cells in the white versus gray matter was observed in VWM animals as compared to healthy controls. This could suggest that affected VWM brain areas diminish the migratory capability of healthy transplanted cells. Alternatively, the diseased white matter may contain more chemo‐attractants that actively recruit transplanted cells. Similarly, it is difficult to determine to what extent the primarily oligodendrocytic cell fate signals a need of the VWM brain for myelin generation, or whether it reflects an intrinsic property of the transplanted cells. Potential alterations in endogenous oligodendrocyte precursor cell (OPC) differentiation following cell replacement therapy would be of interest. To study the maturation state of grafted HNSince the brain microenvironment of VWM mice was found to affect cell spread and cell fate post‐transplantation, future studies should also consider the human brain microenvironment in particular. Indeed, a role of the ECM has been shown in VWM with respect to the accumulation of hyaluronic acid (HA) in both patient white matterIn conclusion, we show that human stem cell‐derived glial cell transplants can have regenerative effects for VWM. Of various cell populations tested, transplantation of mixed glial cell populations showed therapeutic benefits. The VWM genotype affected cell fate and the spread of these cells, indicating an interaction effect with the microenvironment. Taking this into consideration, finding the appropriate conditions for cell replacement therapy in VWM patients might fall in the realm of personalized medicine, requiring a Goldilocks graft that is “just right.”A.E.J.H., P.S.L., N.B.B., S.D., and T.B. conducted experiments and gathered data. A.E.J.H., P.S.L., N.B.B., S.D., and T.B. analyzed the data. A.E.J.H. wrote the manuscript. V.M.H. and M.v.d.K. contributed to study design, provided supervision, materials and resources, and revised the manuscript. A.E.J, P.S.L., S.D., and N.B.B. revised the manuscript.The authors have no financial support or relationships that pose conflicts of interest to disclose.Figure S1Click here for additional data file.Figure S2Click here for additional data file.Figure S3Click here for additional data file.Appendix S1Click here for additional data file.Appendix S2Click here for additional data file.