Hearing impairment, or hearing loss, can be caused by several factors and the implications vary according to the type, degree, cause and age of occurrence. Hearing screening should be a common procedure, allowing the pre-clinical identification and necessary referrals, avoiding the consequences of auditory deprivation. Mobile apps have shown to be a good alternative for hearing assessment.The objective was to develop an app and assess its performance in identifying hearing loss by comparing it with another validated screening tool.Ouviu, was created using audiological knowledge and tools available on the iOS platform. We evaluated 185 people, aged between 6 and 96 years, distributed into 5 age groups, performing audiometry and hearing screening using two tools: HearCheck and the application.The application, called The results showed that the sensitivity of the application in identifying hearing loss was approximately 97%, while that of HearCheck was 79%. The positive predictive value of the application showed that the probability of a person being identified with this tool and actually having a hearing loss was 94%, while for HearCheck it was 96%. False negatives, which failed hearing loss identification, were fewer in the app (3%) than in HearCheck (21%).Consequently, the developed application was shown to be effective as a hearing screening tool, surpassing HearCheck in identifying mild hearing loss. In addition to being portable, easy to apply, low cost and rapidly performed, the application has the advantage of assessing environmental noise to perform the exam, as well as the fact that it is not necessary to attach any hardware to the mobile device. Hearing is an extremely complex function, being essential for the processing of acoustic events and for the emission and understanding of speech signals. Hearing loss can be caused by several factors and, among them, the prenatal etiologies such as genetic inheritance, inner ear malformations, congenital infections by the rubella virus, cytomegalovirus, herpes, toxoplasmosis and syphilis; perinatal causes, such as anoxia, prematurity, hyperbilirubinemia, head trauma and sound trauma; and postnatal problems, including metabolic causes such as hypothyroidism and diabetes, viral infections such as rubella, chickenpox, influenza, mumps, cytomegalovirus, bacterial meningitis, encephalitis and chronic otitis media.The consequences of hearing loss vary according to the type, degree, cause and age of its occurrence. Linguistic, educational and psychosocial impairments can be observed in children and adolescents.Hearing loss diagnosis and rehabilitation should be attained early, both in children and in individuals at other stages of life. However, hearing loss occurs gradually, with a slow progression in many situations and it is often not perceived or denied by the individual.Currently, screening can be performed using standardized questionnairesCartilha Idosa), the use of the Whispered Voice Test was proposed as an integral part of the measurements that should be performed in the elderly. However, Bauer et al. (2017)Hearing screening is an already established concern, and several alternatives have been suggested for this purpose. This concern is no different with the elderly population. We know that access to hearing tests is not a reality for this population. Displacement, referrals, qualified professionals and places for exams are some of the barriers faced by this age group. Therefore, in the Elderly Booklet  are available for download on iOS and Android platforms, and many of them are free of charge. Some have already been tested with positive results, while others.lack careful study.12Despite the existence of some applications, we saw that some issues made them difficult to use on a larger scale. The main one was the use of headphones, since the need to have hardware like this makes it difficult to use, due to the impositions of cleaning after use, of having good-quality headphones, of having a more invasive contact with the assessed individual and greater expense. We also did not find national apps validated for the Brazilian population that were free of charge. Moreover, most existing applications seek to replicate audiometry, screening all frequencies. As our intention was to screen, we wanted something more concise that could be used by other professionals who do not necessarily have audiological knowledge and that would take into account the environmental noise at the testing site.Observing the need for a differentiated screening instrument that would assist in the screening of hearing acuity, we considered developing an application, believing that this would prove to be a simple, inexpensive, effective, safe and quick way to identify possible losses. Therefore, the present study main objective was to develop and evaluate the performance of a hearing screening application in different age groups .Instituto de Geriatria e Gerontologia da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) and the Research Ethics Committee of PUCRS, CAAE 57742016.8.0000.5336, was a cross-sectional, observational, descriptive, and comparative one. The sample consisted of individuals aged from 6 years old onward who underwent hearing assessment, by their own initiative or by referral from health professionals, with the collection period comprising one year (August 2016 to August 2017).The study, approved by the Scientific Committee of The entire collection was carried out at Universidade Federal do Rio Grande do Sul (UFRGS), using the equipment of the Audiology Clinic of that institution.The individuals were divided into groups with at least 38 research subjects in each – as per the sample calculation, according to Hajian-Tilaki (2014)Subjects who had obstructive cerumen in the external auditory canal, uni- or bilaterally, were excluded. The individuals, after signing the Free Consent form, answered a personal data sheet with relevant information for the research and, subsequently, they were submitted to the evaluations. Meatoscopy exam, hearing screening with the Hearchek Screener equipment (Siemens), auditory screening with the developed application and pure tone audiometry were performed.Meatoscopy aimed to verify the absence of obstructive cerumen in the participants’ auditory canal, and it was the first examination performed. Hearing screening with the HearCheck equipment was performed according to the manufacturer's standards and for the analysis of the results, the criteria proposed by Cardoso et al. (2014) was employed.Ouviu”, was developed on the iOS platform to perform auditory screening. This evaluation instrument was developed in partnership with Escola Politécnica of PUCRS. It consists of the following procedures: Environmental noise analyzer , test  and results . We chose to present the sounds in a free field, and not through headphones. To evaluate the results of the application, tests were considered negative when the participants heard the frequencies of 1000, 2000 and 4000 Hz at 20 dB and at the frequencies of 500 and 8000 Hz at 40 dB, whereas they were considered positive when the participants did not hear in at least one of the mentioned frequencies and intensities. This criterion was built based on the hearing thresholds within the normal range obtained at the audiometry of the first 10 participants of each age group.The application, called “The audiometry was performed and analyzed according to the World Health Organization (WHO) standards.After performing the tests, the data were entered into a database created in Microsoft Excel. The analyses were performed using the EPIINFO software, with the aim of analyzing the association between the assessed variables.https://developer.apple.com/av-foundation/) was used. The used concept was the amplitude . Frequency and intensity tests of the waves generated by the speaker built into the fourth generation iPod Touch device were performed. Two test batteries were performed, one to understand the physical limitations of the device in generating the frequencies  and the second for the desired intensities (20–40–60 dB). The amplitude was controlled through an application that allowed changing it according to the power measured in the decibel meter. The decibel meter used was provided by LABELO  in a test room with sound insulation. Thus, it was possible to adjust the application to work on the iOS platform with the following adjustments: at the maximum output intensity of the equipment (iPod Touch), at the frequencies of 1000, 2000, 4000 and 8000 producing pure tones at the intensities 40 dBHL and 60 dBHL, and the frequency of 500 Hz producing 40 dBHL (60 dB production was not supported by the equipment). These intensity values were measured for the moment they reached the subject and not when they left the equipment. Intensities below 40 dBHL could not be measured, due to the wave characteristics and their dispersion in the environment. But they were programmed to be produced from visual and auditory adjustments of the waves produced by the equipment and the perceptions of the involved professionals.The application was developed on the Xcode development platform, version 9.4.1, using the Swift programming language, version 3.3. The AVFoundation's native video and audio manipulation framework , “Moderate” (40 dBHL) and “Strong” (60 dBHL). It should be noted that it was decided not to use headphones and simultaneous testing between the ears, since the use of headphones would imply costs and the need for sanitation between the participants’ use (which would make it difficult to use in the primary or home care). The absence of headphones made it difficult for the intensity generated by the source  to be the same as the one that reached the subject, causing the need for adjustments so that the intensity generated was sufficient to reach, for instance, 40 dB in the ears. This problem meant that we could not state that intensities below 40 dB would be measured, since the environmental noise is mistaken by the produced sound. For this purpose, we chose to adjust the output with algorithms that were visually and audibly less than 40 dBHL. HearCheck, for example, emits a 1000 Hz pure tone at 35 dBHL as a minimum value.After some versions and measurements in a specific laboratory, and also due to the precise specifications of the iPod hardware, the frequencies and intensities were distributed as follows: the frequencies of 1000, 2000 and 4000 Hz present the moderate and strong intensities confirmed at 40 and 60 dB, respectively, and weak ; the frequency of 8000 Hz with all confirmed intensities; and the frequency of 500 Hz with the assessed moderate intensity, the weak intensity without confirmation, and the strong intensity (60 dB) was not supported by the equipment (not being produced).As for the application results, tests were considered negative when the participants heard the frequencies of 1000, 2000 and 4000 Hz at moderate and weak intensities, and the frequencies of 500 and 8000 Hz at moderate intensity. And they were considered positive when the participants did not hear at least one of the frequencies and the intensity was at least moderate. This criterion was built from the hearing thresholds within the normal range obtained in audiometry. Participants with normal hearing were the beacons of negative results in the application, and those with HL of different degrees were the positive result for the same device.The test application time – relevant data, since the demand in primary and home care is high – was measured in some applications, with an average time of 30 s, which may be shorter if the patient responds quickly, and up to 45 s, if the patient does not answer to any intensity (maximum time). For comparison purposes, the time used in HearCheck was also measured. The test is performed within a pre-defined time by the device, with 40 s for each ear. Still thinking about primary care, the application shows advantages over the free tests available on the internet since it was validated, checks environmental noise and does not need a computer to be applied.The sample  consisteOuviu and HearCheck applications. The positive predictive value and the negative predictive value are related to Hearing Loss. For the analyses, the result of audiometry  was used as a fixed variable. The following were considered: True Negative, for those who had a negative result for Hearing Loss  both in the screening (at the application or HearCheck) and in the audiometry; True Positive, for those who had Hearing Loss detected in both screening and audiometry; False Positive, for those who had a positive screening and normal hearing; and False Negative, for those who had a negative screening and, however, had hearing loss. The degree of loss was used for analysis of responses to screening (positive or negative) and presence or absence of HL for the other analyses.The results achieved are related to the sensitivity and specificity of the Both screenings were mostly sensitive to identify HL, with HearCheck sensitivity being 79% and the application's, 97%. Similarly, specificity also showed high values, 98% and 96% for HearCheck and app, respectively, with both instruments being able to assess participants with hearing levels within normal standards.HearCheck's positive predictive value showed that the likelihood of a person being identified with this instrument and actually having HL was 96%. The application's rate was 94%. On the contrary, the negative predictive values of 89% and 98% showed the probability that the person who had a negative screening in fact did not have HL.The true positives, screenings with positive results for HL and with HL, were 54 (79%) in HearCheck and 66 (97%) in the application. In contrast, the true negatives, negative screenings and absence of HL were 98% (115) with HearCheck, and 97% (113) with the app. The false positives, a positive screening for HL and absence of HL were 2 and 4 for HearCheck and app, respectively. The false negatives, which failed to identify HL, were 20.59% (14) for HearCheck, and 3% (2) for the app.Finally, the accuracy of the screening in discriminating between HL and normal hearing in the entire sample was 91% for HearCheck and 97% for the application.When developing the application, the first concern we had was with environmental noise. Fearing that it would interfere with the test results, we placed a noise analyzer on the home screen. The analyzer aims at allowing the start of the test only when it detects ambient noise limits <60 dB. The concern with environmental noise at the place where the screening was applied was raised as being an important factor for the quality of the tests in other studies.The pure tones of the frequencies of 500, 1000, 2000 and 4000 Hz, and the intensities  were chosen considering those established by the WHO. The weak intensity, presented as lower than 40 dB, refers to the minimum intensity required within the normal range; moderate (at 40 dB) is an analogy to moderate hearing loss; and the strong one refers to deeper degrees of loss.19The normality standards were established and considered the results of the audiometry. To have a negative test in the application, the subject should hear the moderate and weak intensities at the frequencies of 1000, 2000 and 4000 Hz, and at least the moderate intensity of 500 and 8000 Hz, thus suggesting normal hearing. Not hearing the moderate intensities was seen as indicating some degree of hearing impairment. The cutoff point of our study was similar to that proposed by Abu-Ghanem et al. (2016),The time of the test application, considered important for a screening tool, was 30 s, on average, and could be shorter if the patient responds quickly, and up to 45 s, if the patient did not respond to any intensity (maximum time). For comparison purposes, the time used in HearCheck was also measured. The test is performed in a pre-defined time by the device, being 40 s in each ear. The testing times for both tools are similar to those found in another validation study that measured time less than one minute (49 s) in children, and slightly longer than one minute (74 s) in adults.We evaluated 185 people aged 6–96 years within a one-year period. The findings were analyzed for the total number of participants and by age group. Only the long-lived elderly group did not reach the desired number of participants (38), despite the long collection time (12 months). As our objective was to evaluate patients who came to the Audiology Clinic, without interfering with the demand, we chose not to call any external participants.In all age groups, women were the majority of the assessed individuals. Women were also the majority in the validation study of another application and comprised 71% of the sample.With the results obtained in audiometry, we found that most of the hearing results were within the normal range, followed by mild, moderate and severe HL. This percentage of HL observed in the study was higher than the global estimate of 5.3%;Regarding the age distribution, the group aged 6 to 19 years (children and adolescents) was the second age group with the smallest hearing loss, since the age group with the smallest loss was that of young adults. In the other age groups, the frequency of hearing loss increased with age, being present in all long-lived elderly individuals. Again, in our sample, among children, adolescents, adults and the elderly, we had a higher frequency of HL than that reported worldwide and nationally. As expected, there was an increase in the frequency of HL among the elderly and long-lived elderly individuals, which corroborates world and national data.In general, HearCheck and the app performed similarly in all age groups. The first one was better at identifying normal hearing, and the second at identifying HL. HearCheck failed to identify mild HL but was effective in the higher degrees of HL. The application, in turn, was sensitive in all degrees of HL. In the joint analysis, with all age groups, where the majority showed hearing degrees within the normal standards, the performance of the tests was satisfactory. Both screenings were mostly sensitive to identify HL, with HearCheck sensitivity being lower than that of the application. Likewise, specificity also showed high values for both tests, being able to identify participants with hearing within normal standards. HearCheck overall sensitivity was lower than the instrument validation test, and the specificity was similar.Ouviu application. The accuracy of the screenings showed that they were vigorous in discriminating between HL and normal hearing in the entire assessed sample.As for the application, in a study with participants aged between 3 and 97 years old, quite different age groups such as in our sample, the sensitivity found was lower (81.7%) than that of our application, as well as the specificity (83.1%).Ouviu normal hearing criteria were included in the analyses. New evaluations of the application can confirm the obtained results.Our limitations regarding the platform on which it was developed comprise the access restrictions of mobile devices other than the iPods where the tests were performed. These limitations are also our future suggestions for improving the application for wider use on other platforms. Another limitation was the fact that the 50 participants whose audiometry results were used to establish the The development, which comprised from determining the frequencies and intensities that would be presented, through the form of display and adjustments to the layout and recording of the results, was designed to cover the “flaws” observed in other available applications. When we chose not to use headphones, we had problems with the calibration of the intensities, the reason why we were unable to state at what intensity it was working with the “weak” intensity. However, we did not have to worry about headphones hygiene, standardization and the costs they would bring.Regarding the establishment of normality standards, considering the results of audiometry, we proposed that: listening to moderate and weak intensities at the frequencies of 1000, 2000 and 4000 Hz, and at least the moderate intensity of 500 and 8000 Hz is suggestive of normal hearing. On the other hand, not hearing the moderate intensities already indicates some degree of hearing impairment, and the subject must be referred to audiometry exams.The application performance was satisfactory in all assessed age groups, as well as the HearCheck. Although both instruments were effective, the application showed a better accuracy than HearCheck and was more precise to identify HL of all degrees (including the mild degree). In addition to the previously described benefits, the application also shows advantages in terms of cost, speed, access to testing and applicability. Moreover, there are no portable devices available on the market that can generate calibrated sounds at the proposed frequencies and intensities.Ouviu app and in the results obtained with it, is due to the competence of the team involved in its development. Specific knowledge of computer science and audiology was shared and joined with efforts to create a tool that would be both viable and meet the clinical needs. The authors would like to thank Henrique Valcanaia and Marcos Vinícius Kuquert for the development of the application, which allowed the collection of data to be analyzed for this research. The participants who volunteered to take the exams, the students of the Speech Therapy course at Universidade Federal do Rio Grande do Sul who helped with data collection. This work was supported by Coordenação de Aperfeiçoamento de Pessoal Nível Superior – Brasil (CAPES), funding code 001.We believe that the success, both in the development of the We developed an application that met our needs, capable of performing a quick HL screening with an effective performance in different groups, which included children as well as the long-lived elderly.The final layout, proposed with the completion of data collection, analysis and result rationale, will be completed and made available on Apple Store.Study supported by Coordenação de Aperfeiçoamento de Pessoal Nível Superior – Brasil (CAPES) – funding code 001.The authors declare no conflicts of interest.


However, the B and K2 vitamin biosynthesis by the whole gastrointestinal microbiome and their abundances in different dietary strategies are largely unknown. Here, we reanalyzed our previous large-scale metagenomic data on the gastrointestinal microbiome of seven ruminant species and recruited 17,425 nonredundant microbial genomes from published datasets to gain a comprehensive understanding of the microbe-mediated B and K2 vitamin biosynthesis in ruminants.B and K2 vitamin biosynthesis. Our results indicated that the total abundances of B and K2 vitamin biosynthesis were dominant in the stomach microbiome, while the biosynthesis of thiamine, niacin, and pyridoxine was more abundant in the large intestine. By examining 17,425 nonredundant genomes, we identified 2366 high-quality genomes that were predicted to de novo biosynthesize at least one vitamin. Genomic analysis suggested that only 2.7% of these genomes can synthesize five or more vitamins, and nearly half of genomes can synthesize only one vitamin. Moreover, we found that most genomes possessed cobalamin transporters or cobalamin-dependent enzymes to consume cobalamin directly, and only a few microbial genomes possessed a complete cobalamin biosynthesis pathway. Based on these genomic data, we examined the effect of the high-grain (HG) diet on the vitamin biosynthesis of the rumen microbiome of dairy cattle. We revealed that most vitamin biosynthesis was enhanced in the HG group, while only cobalamin synthesis was inhibited in the HG group, indicating that dietary fiber is vital for cobalamin biosynthesis.We identified 1,135,807 genes and 167 enzymes involved in B and K2 vitamin biosynthesis in ruminants. Our findings demonstrated the regional heterogeneity and dietary effect of vitamin biosynthetic potential in the ruminant gastrointestinal microbiome and interpreted the biosynthesis mechanisms of these microbes and their physiological adaptability. This study expands our understanding of microbe-mediated vitamin biosynthesis in ruminants and may provide novel targets for manipulation to improve the production of these essential vitamins.We primarily provided a gene catalog and 2366 microbial genomes involved in B and KVideo abstract.The online version contains supplementary material available at 10.1186/s40168-022-01298-9. For exaoduction . In addiformance –9, such formance  and anorformance . TherefobioW for pimelate and bioZ, bioG, bioH, and bioK for malonyl-ACP) from malonyl-ACP or pimelate. Specially, cobalamin has the most complex biosynthesis pathway among B vitamins, which can only be de novo biosynthesized by prokaryotes through two routes: aerobic or anaerobic pathway, according to the time of cobalt insertion and the oxygen requirement [cbiK in the anaerobic pathway, while via cobNST in the aerobic pathway. Studies based on microbial cultivation have pointed out that some specific rumen microbes can synthesize B vitamins, such as Corynebacterium vitaeruminis DSM 20294T [Fibrobacter succinogenes [Selenomonas ruminantium [Prevotella, Bacteroides, and Ruminococcus 1) and B vitamin abundance based on 16S rRNA sequencings are also reported [Vitamin biosynthesis from microorganisms has been found in the human gut and rumen , 13, 14.uirement . In detaM 20294T , Fibrobainogenes , and Selinantium . In addireported , 20.2 vitamin biosynthesis from microbiome are widespread in the GIT and how the non-rumen regions contributed to the vitamin pool is needed to further explore. In addition, understanding the complex biosynthesis process of B and K2 vitamins throughout the GIT is key to informing strategies for the subsequent targeted regulation of gastrointestinal microbiota to improve vitamin production and utilization in ruminants. Furthermore, evidence has been identified that changing the ratio of forage to concentrate in the dietary regime can alter the vitamin concentrations in the rumen of calves, sheep, and steers [Unlike humans, ruminants have evolved a compartmentalized stomach and their complete GIT contains 10 distinct physical compartments . These spatially specialized regions were uncovered to harbor a dissimilar microbial community, resulting from transformations in physiology substrate availabilities, retention time of digesta, and pH levels –24. Prevd steers . However2 vitamin biosynthesis from our previous study [2 vitamin biosynthesis in ruminants. In addition, our genomic analysis provided deep insights into cobalamin synthesis system present in the GIT microbiome, and a comprehensive understanding of microbe-mediated vitamin biosynthesis in response to a high-grain diet perturbation. The findings may provide novel solutions for developing effective strategies to enhance microbial B and K2 vitamin biosynthesis in ruminant GIT.Here, we identified 1,135,807 genes and 2366 high-quality genomes involved in B and Kus study  and publus study –36. Usin2 (menaquinone) de novo biosynthesis pathways  involved in eight B vitamins  and KthiH was prevalent in the GIT microbiome  or the futalosine pathway. The classical pathway was more enriched in the ruminant GIT microbiome , followed by Firmicutes (33.24%) and Proteobacteria  [Bacteroidetes, while members of the phylum Euryarchaeota were crucial executors of vitamin biosynthesis in the small intestine. In addition, the biosynthetic genes related to riboflavin, niacin, folate, and menaquinone were mainly derived from Bacteroidetes, accounting for more than 50%, especially menaquinone (up to 76.37%). For cobalamin, 12.08% of biosynthetic genes were classified into the phylum Euryarchaeota, whose proportion was much higher than other vitamins  . Notably2 vitamin biosynthetic genes were Prevotella, Bacteroides, Clostridium, Ruminococcus, Methanobrevibacter, Fibrobacter, and Alistipes  and Bacteroides spp. (21.53%) were the most important indicators in the varied GIT vitamin biosynthesis , and the abundance of la spp. 2.33% and cobI and finally chelated with cobalt via cobNST. By contrast, precorrin 2 was chelated with cobalt to produce cobalt-sirohydrochlorin in the second step of anaerobic pathway. The aerobic and anaerobic pathways converged into cob(II)yrinate a,c diamide, which was finally converted into a cobamide coenzyme . Here, the abundance of cobG and cobF was low (TPM < 10) in the aerobic pathway, indicating that this pathway is rarely present in the anaerobic environment of the ruminant GIT  with low abundance in the anaerobic pathway also indicate that the de novo biosynthesis of cobalamin is likely restricted in the ruminant GIT microbiome  were mainly classified into the phyla Bacteroidetes and Firmicutes, while cobIKHL and cbiHFG enriched in the small intestine were classified into the phyla Firmicutes and Euryarchaeota  [2 vitamin  and Firmicutes (38.3%), respectively, followed by 114 genomes for Actinobacteria (4.8%), 106 genomes for Proteobacteria (4.5%), and 58 genomes for Euryarchaeota (2.5%)  , we obtaFirmicutes  and another two genomes assigned to Proteobacteria (lack of riboflavin biosynthesis)  and 371 niacin-producing genomes were mainly classified into the phylum Bacteroidetes (63.6%) , and cobalamin was mainly synthesized by Firmicutes-affiliated genomes (86.8%). Interestingly, we found that Bacteroidetes-affiliated genomes could not synthesize folate and cobalamin in these 2366 genomes  with other non-producing genomes (NPGs) at the taxonomic and functional levels. We observed that several phyla contained more annotated genomes to synthesize vitamins, including Bacteroidetes, Proteobacteria, Actinobacteria, Elusimicrobia, Fibrobacteres, Campylobacterota, Verrucomicrobia, and Desulfobacterota  in the aerobic pathway, which were involved in corrin ring synthesis (convert precorrin 2 to precorrin 6A) and cobalt chelation  lost five indispensable genes  in the anaerobic pathway; Bacteroides-affiliated genomes lacked cysG, cbiT, and cbiE genes; Methanobrevibacter- and Clostridium-affiliated genomes lacked cysG, cbiH, cbiT, and cbiE genes; and Ruminococcus-affiliated genomes lacked cysG, cbiH, and cbiE genes. We also found that all Methanobrevibacter-affiliated genomes lacked MMAB and cobP in the post-cobyrinate a,c diamide pathway. The key genes of these PCGs had appropriate complementarity, suggesting that they were expected to synthesize cobalamin collaboratively [The cobalamin de novo biosynthesis pathway was mainly contributed by the members of the genera cus Fig. d. Howevecus Fig. . Thus, tratively .Fig. 4GePrevotella- and Bacteroides-affiliated genomes  were commonly present in the genomes classified into the class Negativicutes and the genera Clostridium and Ruminococcus , methylmalonyl-CoA mutase (MCM), and ribonucleotide reductase (nrdJ). These results indicate that the capability of using cobalamin is widespread in ruminant GIT microbiomes, but only a few microbes have a complete cobalamin de novo biosynthesis pathway.We additionally analyzed cobalamin utilization by predicting the presence or absence of genes related to cobalamin transporters and cobalamin-dependent enzymes in the two genomic datasets , and the biosynthesis pathway abundance of three vitamins, including riboflavin (9.87%), niacin (9.24%), and thiamine (7.07%), were the most significant variables during the diet shifts . Among the genomes, 1849 (73.4%) were enriched in the CON group, and 671 (26.6%) were enriched in the HG group , while the CON-enriched genomes were mainly classified into the phylum Bacteroidetes . At the functional level, the starch-degrading enzymes  were significantly predominant in the HG-enriched genomes, which were mainly affiliated with the genera Sharpea, Agathobacter, Lachnospira, and Lachnobacterium   and Kyoto Encyclopedia of Genes and Genomes  [http://bio-bwa.sourceforge.net) [2 vitamin biosynthesis was calculated as the summation of the abundance of KOs in this pathway. Alpha (richness and Shannon index) and beta (Bray-Curtis distance) diversity were calculated using the R vegan package [We recruited a nonredundant ruminant GIT microbial gene catalog (RGMGC) with 154,335,274 genes from our previous study . Taxonomp/kegg/)  databaserge.net)  with maxrge.net) . The rel package  (v.2.5-6https://github.com/Ecogenomics/CheckM/wiki) was used to evaluate the completeness and contamination of all 17,425 genomes based on lineage_wf workflow, and 5318 high-quality (completeness > 90% and contamination < 5%) genomes were retained for the downstream analysis. Genome size was corrected using genomic completeness and contamination according to a previous study [We collected 10,373 MAGs from our previous study  and 7052us study .https://gtdb.ecogenomic.org/), and functional annotations were performed using DIAMOND [2 vitamins de novo. Based on the indispensable functional roles (102), we identified 2366 genomes that were predicted to synthesize B and K2 vitamins de novo. Phylogenetic trees were generated based on the concatenated protein sequences using PhyloPhlAn [2 vitamins in each genome. KOs present in more than 90% of individuals in each genomic dataset were identified as core functions among VPGs or NPGs.Prodigal  (v.2.6.3 DIAMOND  (v.0.9.2 DIAMOND  databaseyloPhlAn  (v.1.0) yloPhlAn  (v.3) anyloPhlAn   and cobalamin-dependent enzymes   and beta (Bray-Curtis distance) diversity were calculated using the R vegan package [2 vitamin biosynthesis between the CON and HG groups, and AMOVA was calculated using mothur [P < 0.05). We obtained 2520 differentially enriched genomes in the HG and CON groups. Protein sequences encoded by each genome were aligned to the CAZy database [We reanalyzed the metagenomic data from Mu et al.  regardin package  (v.2.5-6g mothur  (v.1.44.g mothur . The abudatabase  (v.7) usdatabase  (v.3.2.1https://www.r-project.org) [P value < 0.05. The PCoA was compared using AMOVA in mothur [P value < 0.05. Convergent cross-mapping was used to detect causal interactions using the R multispatialCCM package (v.1.0) [P value < 0.05.The abundance of vitamin biosynthesis pathways, VPGs, and the diversity of vitamin biosynthesis-related taxa were compared using Wilcoxon-rank sum test in R (ect.org)  with a sn mothur  (v.1.44. (v.1.0) . Random  (v.1.0) . Varianc (v.1.0) . Linear Additional file 1: Fig. S1. The biosynthesis pathway of thiamine. Fig. S2. The biosynthesis pathway of riboflavin. Fig. S3. The biosynthesis pathway of niacin. Fig. S4. The biosynthesis pathway of pantothenate. Fig. S5. The biosynthesis pathway of pyridoxine. Fig. S6. The biosynthesis pathway of biotin. Fig. S7. The biosynthesis pathway of folate. Fig. S8. The biosynthesis pathway of cobalamin. Fig. S9. The biosynthesis pathway of menaquinone. Fig. S10. Variability in differences of vitamin biosynthesis explained by regions and species. Fig. S11. Chord plot of the distribution of vitamin biosynthetic genes among different phyla. Fig. S12. Phylogenetic distribution of vitamin biosynthetic genes at the genus level throughout the GIT regions. Fig. S13. The important indicators for regional heterogeneity identified by Random Forest model. Fig. S14. The detection of causal interactions between structure of GIT microbiota and vitamin biosynthesis pathway. Fig. S15. Vitamin synthesis capabilities of 31 genomes assigned to the genera Salmonella and Escherichia. Fig. S16. Variability in differences of vitamin biosynthesis explained by diets. Fig. S17. The detection of causal interactions between Bacteroides and Fibrobacter and cobalamin biosynthesis. Fig. S18. The important indicators for dietary shifts identified by Random Forest model.Additional file 2: Table S1. Detailed information for B and K2 vitamin biosynthesis. Table S2. Relative abundance of 123 functional roles in the B and K2 vitamin biosynthesis pathways. Table S3. Distribution of vitamin biosynthesis among different phyla.Additional file 3: Table S4. Combination of indispensable functional roles for B and K2 vitamin de novo biosynthesis. Table S5. Collection of 17,425 ruminant microbial genomes. Table S6. Taxonomic classification of 5318 high-quality genomes. Table S7. Genomic statistics and vitamin synthesis capabilities of 2366 VPGs. Table S8. Comparison of KOs between VPGs and other NPGs.Additional file 4: Table S9. Detailed information for cobalamin biosynthesis and utilization of the 675 genomes in Fig. Table S10. KOs assigned to cobalamin transporters and cobalamin-dependent enzymes.Additional file 5: Table S11. Taxonomic classification and GH family counts of the 2520 differentially enriched genomes in the CON and HG groups. Table S12. Differentially enriched GH families in the CON and HG groups.


Preventing or reversing hearing loss is challenging in Ménière's disease. Betahistine, as a histamine agonist, has been tried in controlling vertigo in patients with Ménière's disease, but its effectiveness on hearing problems is not known.To examine the effect of betahistine on hearing function in not-previously-treated patients with Ménière's disease and to define possible contributors in this regard.A total of 200 not-previously-treated patients with definite unilateral Ménière's disease received betahistine by mouth . Changes in indicators of hearing status before and six months after treatment were documented. Hearing loss was considered as the mean hearing level >25 dB HL at five frequencies.p < 0.001). Both patients’ age and the duration of disease correlated negatively with the improvement in hearing function. Post treatment hearing loss was independently associated with age, the initial hearing level and the chronicity of disease. The corresponding optimal cut-off points for predicating a persistent hearing loss 6 months after treatment were 47 years, 38 dB HL, and 1.4 years, respectively.The mean duration of disease was 3.37 years. Six months after treatment the mean hearing level decreased by 6.35 dB compared to that at the baseline (Oral betahistine was significantly effective in preventing/reversing hearing deterioration in patients with Ménière's disease. Age, the hearing level on admission, and the disease duration were independent predictors of hearing status after treatment. Described for the first time in 1861 by Prosper Ménière, Ménière's disease or idiopathic endolymphatic hydrops is a disorder of the inner ear. Elevated pressure in the endolymph can cause four symptoms: (1) fluctuating sensorineural hearing loss, (2) occasional episodic vertigo, (3) tinnitus, and (4) aural fullness.The audiometric pattern of hearing loss in Ménière's disease fluctuates by time. While the hearing loss is limited to low frequencies in the early stages, medium and high frequencies are also involved during the progression of disease. Appropriate treatments, however, may prevent, or at least defer hearing loss in Ménière's disease, particularly when they are started early after the onset of symptoms.Since the disease is a chronic condition that evolves over a rather long period of time, time series analyses are required for evaluating the effectiveness of treatment and the estimation of prognosis.Betahistine (Serc) is a histamine agonist that has been found effective in symptomatic treatment of Ménière's disease. Although the exact mechanism(s) of action is unknown, betahistine is thought to act by increasing blood flow to the cochlear stria vascularis and/or preventing the activity of the vestibular nuclei.5By now, some studies have tried to test the actual usefulness of this medication in Ménière's disease, but because the majority of them are methodologically flawed, reaching a definite conclusion has been impossible. This is why betahistine has not been approved by the US Food and Drug Administration (FDA) to be used in patients with Ménière's disease.In spite of this, Smith et al.A total of 200 not-previously-treated patients with definite Ménière's disease were consecutively recruited from a teaching clinic between 2011 and 2013. The ethics committee of a local university approved this study (no. 5/4/6629), and written informed consents were obtained from the participants.Subjects with probable/possible Ménière's disease, bilateral involvement, prior otological surgery, or underlying systemic diseases were not included.The diagnosis and grading of Ménière's disease was according to the guidelines offered by the American Academy of Otolaryngology – Head and Neck Surgery.Each patient underwent otoscopy and audiometry under quiescent state without vertiginous attack at baseline and six months post treatment.A standard audiometer  was used for the measurement of hearing thresholds. At four frequencies  the four tone average was calculated from the worst audiogram during the interval of three months before and six months after treatment.Patients received betahistine dihydrochloride  by mouth, initially 16 mg three times a day, with food, at a maintenance dose of 24–48 mg daily divided in doses to control symptoms.12General dietary recommendations such as low sodium intake were implemented, but no other medication except for betahistine was allowed during the study period.6): hearing level at baseline – hearing level 6 months after treatment.6 > 0Hearing improvement: IHLHearing loss: six-month post treatment mean hearing level >25 dB HL.Improvement in the hearing level six months after treatment /Pearson coefficient (r) was calculated to investigate correlations between variables. A stepwise descending logistic regression analysis/linear regression model was used in constructing a multivariate analysis. The receiver operator characteristics (ROC) curve was drawn in determining areas under the curve and optimal cut-off values. A significance level was set at p ≤ 0.05.The SPSS software version 19.0  was used for statistical analysis. Distribution of numeric data was tested using the Kolmogorov–Smirnov method. The numeric data were shown as the mean ± standard deviation or the mean . The contingency tables (Pearson chi-square test), McNemar test, independent samples The study variables including demographic information and general data at the time of admission are summarized in p < 0.001)  .Figure 16 was 6.35 dB , denoting a hearing improvement in 60 patients (30%) at the endpoint.The mean IHLp < 0.001).Six months after treatment a retained hearing loss was detected in 90 patients, indicating a 30.23% decrease by the treatment  in females and 5.07 dB  in males (Mann–Whitney U test p = 0.23). A significant, reverse correlation was seen between age and IHL6  , whereas a negative, significant correlation was present between IHL6 and the duration of disease  (The mean IHL = 0.03)  A, indic< 0.001) B.Figure 6 .In a linear regression model, both age and the duration of disease were independently associated with IHLp = 0.31). Patients with hearing improvement, however, were significantly younger . The mean disease duration was significantly lower in the cases with hearing improvement than in those with no change or deterioration in hearing function six months after treatment . The mean baseline hearing level was 33.75 dB HL  in patients with hearing improvement and 33.14 dB HL  in the remaining ones (Mann–Whitney U test p = 0.79).Males and females had similar hearing improvement rates after treatment  = 0.96 and p = 0.002, Exp(B) = 1.00, respectively). With areas under the ROC curves of 0.62 (p = 0.01) and 0.69 (p < 0.001), the related optimal cut-off points were 44  and 1.4 , respectively , male gender (chi-square test p = 0.05), a more chronic disease (Mann–Whitney U test p < 0.001) and a high baseline hearing level (Mann–Whitney U test p < 0.001) were significantly associated with persistent hearing loss after treatment.Variables in relation to persistent hearing loss after treatment are summarized in p = 0.11, Exp(B) = 2.41), all the remaining variables including age  = 1.06), disease chronicity  = 1.00) and baseline hearing level  = 1.10) were found as independent contributors to the post treatment hearing function.In multivariate analysis, except for sex (p = 0.01), 0.75 (p < 0.001) and 0.76 (p < 0.001), the optimal cut-off points were 47 , 1.4  and 38 , respectively.The related ROC curves of age, disease chronicity and baseline hearing level are shown in Although a large variability exists as to the symptoms appearing in the course of Ménière's disease, hearing loss is usually accounted as an inevitable consequence.A younger age and shorter duration of the disease were two independent predictors of post treatment hearing improvement in this work. Similarly, in a study on pure tone audiograms of 300 patients with Ménière's disease, Paparella et al.p < 0.001). In addition to age and the duration of disease, admitting hearing level (in multivariate study) and sex (in univariate study) were other predicting factors in this regard.Considering the effect of treatment on hearing loss (i.e. the mean hearing level of five frequencies >25 dB HL), the percentage of patients affected by this problem decreased significantly from 64.5% at the baseline to 45% at the endpoint , 38 , and 1.4 , respectively.In a study by Kotimaki et al.In normal people the rate of hearing loss by aging at various frequencies may differ between males and females. This gender-related difference may explain our finding in terms of the effect of sex on the responsiveness of hearing loss to medical treatment. More studies, however, are needed to draw a solid conclusion in this regard.In the present work we excluded patients with bilateral disease because bilaterality has been suggested as a predicting factor for poor hearing prognosis in patients with Ménière's diseaseAnother limitation of the present work was a relatively short follow-up of hearing condition after treatment (six months). Longer follow-ups may be required in this regard.Patients recruited in this study were diagnosed recently as cases with Ménière's disease. Medical records and patients’ declarations were the only documents we relied on to evaluate history and possible previous treatments. This may decrease the reliability of employed data in this work.Despite statistically significant hearing improvements detected in the current study, these changes might not be clinically advantageous. It should be acknowledged that it was not possible to verify if the patients were in an inter-crises period, when the hearing is usually better. That could have happened for the patients presenting with mild losses, and so, reaching uniform clinical outcomes could have been affected adversely.The final limitation was that only the results of a conservative, not consensually accepted medical treatment (i.e. betahistine) were considered in this study. This approach was chosen because nonpharmacologic treatments are diverse and their outcome varies significantly between studies.8Based on the findings of this study, oral betahistine is effective in preventing/correcting hearing problems in patients with Ménière's disease. Age and the duration of disease independently contributed to the effectiveness of the medication. Sex and the initial hearing level may also play a role in this regard.The authors declare no conflicts of interest.


All patients were randomly divided into three subgroups depending on the scheme of steroid administration: (1) the first subgroup with only intravenously administered dexamethasone (0.1 mg per kg body weight twice a day for three days), (2) the second subgroup with a combination of methods of administration of steroids  and after this time the dose of prednisone was reduced)) and (3) the third subgroup without steroid therapy (control group). The results were measured by pure tone audiometry (PTA) in three periods: (1) before implantation, (2) during activation of the processor (one month after implantation), and (3) 12 months after activation. Patients’ hearing thresholds before implantation were on average 82 dB HL, 77 dB HL, and 88 dB HL, respectively. (3) Results: The majority of the patients from the first subgroup had hearing preserved partially (77.8%). A similar result was observed in the second study group  . The opposite was true in the control group; a plurality of control patients (38.5%) had no measurable hearing 12 months after the activation of the processor. (4) Conclusions: Pharmacological treatment consisting of the administration of steroids in patients who had undergone cochlear implantation with the Advanced Bionics HiRes Ultra 3D cochlear implant system may be beneficial for preserving residual hearing in patients. Around 466 million people globally live with disabling hearing loss resulting from a range of causes. This number is projected to rise . In rece®, Advanced Bionics® and Oticon Medical®). The aim of this study was to evaluate the clinical effectiveness of two different steroid schemes of administration and two methods of administration  on the preservation of residual hearing in adult patients who underwent cochlear implantation with an Advanced Bionics cochlear system (HiRes Ultra 3D cochlear implant system with Slim J electrode) in comparison with the patients without steroid therapy. Patients who met the inclusion criteria were randomly divided into one of the three subgroups with different pharmacological treatments: (1) dexamethasone , (2) dexamethasone  and prednisone , (3) no steroid therapy. This research is a part of a bigger project with the purpose of optimizing the effectiveness of steroids in the preservation of residual hearing during the cochlear implantation procedure with different cochlear implantation systems  after implantation in comparison with the preoperative period. The assumption was that the results after surgery will be higher than before surgery. The average hearing threshold was measured at 11 frequencies . The secondary endpoint was to calculate the HP rate (hearing preservation rate) by comparing the hearing thresholds in the two different periods: (1) preoperatively and (2) postoperatively.Consent has been given (number: IFPS: KB/06/2016) by the Bioethics Committee of the Institute of Physiology and Pathology of Hearing. The inclusion criteria of this study consisted of: (1) age above 18 years, (2) qualification for cochlear implantation and severe or profound hearing loss : (1) PDT EAS or (2) PDT ES ), (3) heThe 35 patients who were enrolled to the study were randomly divided into three subgroups. The first group consisted of 9 patients (4 women and 5 men). The age range in the first subgroup was between 34 and 71 years old (51.3 ± 11.9). The second subgroup of 13 patients (9 women and 4 men) were aged between 28 and 84 (61.4 ± 13.4). The third subgroup consisted of 13 patients (8 women and 5 men), with the age range being between 20 and 76 (59.6 ± 14.7) . Table 1Each subgroup underwent a different steroid scheme of administration. In the first subgroup, dexamethasone was administered intravenously (0.1 mg per kg of body weight) 30 min before the cochlear implant surgery and for three consecutive days every 12 h . In the The methods of this study follow those described in Skarzynska et al. (2018) and Skarżyńska et al. (2021), which also form part of our project on steroid therapy in patients undergoing cochlear implantation. The primary endpoint was measured as an average hearing threshold across all 11 frequencies (0.125–8 kHz) using both octaves and half-octaves according to the International Organization for Standardization ISO 8253-1:2010. All measurements were conducted in the same soundproof cabin by an experienced technician using the same diagnostic audiometer, the Madsen Itera II  with calibrated earphones (TDH-39P) . The secondary outcome measure was hearing preservation (HP), which was calculated by comparing hearing thresholds 1-year post-operation with the preoperative hearing thresholds according to the HP formula .HP = (1Equation (1). Hearing Preservation (HP) equation. ) .Then, the results were divided into minimal hearing preservation  0–25%; partial hearing preservation  26–75%; and complete hearing preservation (complete HP) > 75%. The assumption of normality was checked with the Shapiro–Wilk test. This assumption was not fully met, and groups were unequally sized, so non-parametric tests were used for further analysis. The Kruskal–Wallis test was performed to compare hearing thresholds from the three groups in the preoperative period and at the 12-month follow-up separately. Differences between hearing thresholds in the preoperative and 12-months post-operation were assessed separately in each group through the Wilcoxon signed-rank test. The chi-square test was used to assess the differences between the three groups in terms of hearing preservation. The analysis was conducted using IBM SPSS Statistics (v. 24).Hearing thresholds, as a primary outcome, were averaged across all frequencies (0.125–8 kHz). Preoperative outcomes were compared with those obtained 12 months after CI activation. Hearing thresholds at CI activation are shown additionally. Averaged hearing thresholds for all patients according to treatment type are shown in p = 0.061). In the activation period, hearing thresholds differed significantly . A difference was found between the oral + i.v. and the control group . Hearing thresholds before implantation in the patients in all three groups were similar . Additional comparisons revealed slight differences between the intravenous and the control group  and between the oral + i.v. and the control group . Twelve months after activation, the outcomes again differed significantly  worsened by about 9 dB  between the pre-operative and post-operative periods, with the difference being statistically significant . In the oral + i.v. group, the mean difference between pre-op  and 12-month outcomes  was about 16 dB, and again the difference was statistically significant . In the control group, the deterioration was about 14 dB  and was statistically significant .Hearing thresholds pre-operation and 12 months after CI activation within each group were compared. In the intravenous group, the mean result  were similar to the 12-month outcomes  . In the oral + i.v. group, the mean pre-op hearing threshold in the non-operated ears was M = 63.30 (SD = 24.35), the 12-month hearing threshold was M = 65.24 (SD = 24.46), and again the change was not statistically significant . In the control group, there was a slight  deterioration from pre-op M = 64.48 (SD = 9.45) to 12-month post-op M = 66.40 (SD = 24.42) score . The mean change in the non-operated ears was 1.93 dB HL.Hearing thresholds were also observed in patients’ non-operated ears. Generally, the hearing thresholds were stable over 12 months in the non-operated ears. In the intravenous group, the preoperative outcomes in the non-operated ears  are shown in 2 = 9.60; p = 0.143).The majority of the patients in the intravenous group had hearing preserved partially (77.8%). A similar result was observed in the oral + i.v. group . The opposite was true in the control group. A plurality of control patients (38.5%) had no measurable hearing 12 months after activation. However, the difference between the three groups was not statistically significant  electric stimulation and (2) pharmacotherapy (in the perioperative period). The aim of developing better atraumatic implant electrodes and improving the surgical technique is very important but depends on many different factors such as surgery skills, type of electrode in the cochlear implant, the patient’s preoperative condition , and pharmacotherapy. At the same time, there is still an urgent need for pharmacologically effective and clinically approved drugs to protect hair cells in the cochlea ,16. As fM = 91.06 (SD = 9.92), which was statistically significant. In the oral + i.v. group (the second subgroup), the mean difference between pre-op and 12-month outcomes was about 16 dB, and again the difference was statistically significant. In the control group, the deterioration was also about 14 dB and was statistically significant. As far as the results of this study are concerned, the hearing thresholds before implantation in the patients in the three groups were similar. In the activation period, hearing the thresholds differed significantly. A difference was found between the oral + i.v. and the control group. Twelve months after activation, the outcomes again differed. Additional comparisons revealed slight differences between the intravenous and the control group and between the oral + i.v. and the control group. Hearing thresholds pre-operation and 12 months after CI activation within each group were compared. In the intravenous group, the mean preoperative outcomes worsened by about 9 dB to The secondary endpoint in this study was hearing preservation. The majority of the patients in the intravenous group had hearing preserved partially (77.8%). Similar results were observed in the oral + i.v. group . The opposite was true in the control group, as a plurality (38.5%) showed no measurable hearing 12 months after activation. Thus, the subgroups with pharmacotherapy (steroids) gained better hearing preservation results than the non-steroid group (the control group). However, the difference between the three groups was not statistically significant. The explanation for the fact that there was no difference in hearing preservation between the residual hearing of the first and the second group may lay in the pharmacology and pharmacokinetics of dexamethasone and prednisone. Both substances are examples of the same pharmacological group (glucocorticoids), but the strength of their anti-inflammatory activities is different. Dexamethasone has the highest activity . Prednisone is a prodrug, and consequently it has to be metabolized into the active substance prednisolone in the liver. When a patient has liver functional problems , prednisone may be inefficiently converted into the active metabolite by cytochrome P450, and as a result he or she does not experience the pharmacological anti-inflammatory activity ,20. Secop < 0.05), but the average change was equal to 2 dB and it was lower than the audiometer resolution. The audiometer resolution is equal to 5 dB (the step size was 5 dB). As a result, this size was on the one hand statistically significant but on the other it was not clinically important or significant. Consequently, and in general, in the non-operated ears of patients who were enrolled in this study in the preoperative period and 12 months post-operation on average changes in hearing thresholds were not observed. According to the results of implanted ears in comparison with non-implanted ears, in the first and the second group (the steroids groups) in the two periods (preoperatively and 12 months post-operation) the hearing thresholds were stable. In the control group, according to the results of the non-operated ears, the change was statistically significant ). However, at the same time, due to the limited number of patients enrolled in the study and the unequal number of patients in each subgroup, non-parametric statistical analysis was used to gain reliable results. This manuscript is part of a bigger project that aims to assess the clinical effectiveness of anti-inflammatory pharmacotherapy (steroids) in protecting residual hearing in different groups of patients and with different cochlear implant systems. As a result, the possibility of enrolling equal numbers of patients in this study was limited, but in comparison with other sites in other countries in Europe, we still managed to enroll a high number of implanted patients in this study on Advanced Bionics cochlear systems.According to the literature, this study is the first to compare the effectiveness of steroid (dexamethasone and prednisone) therapy in the preoperative and postoperative period under two different pharmacotherapy schemes in patients who had undergone cochlear implantation with the Advanced Bionics cochlear implant system. The hearing preservation rate was better in the two treatment groups (77.8% and 61.5%) in comparison with the control group (38.5%). However, steroid therapy may not play the most important role in the preservation of residual hearing in patients implanted with the Advanced Bionics HiRes Ultra 3D cochlear implant system.


Optimal CVD risk was defined as nondiabetic, nonsmoking, systolic blood pressure (SBP) < 120 and diastolic (D)BP < 80 mm Hg, and total cholesterol < 180 mg/dL. Major CVD risk factors were diabetes, smoking, hypertension, and total cholesterol ≥ 240 mg/dL or statin use. We identified 6332 patients ; 64.0% had hearing loss. Sex-stratified logistic regression adjusted for age, noise exposure, hearing aid use, and body mass index examined associations between hearing loss and CVD risk. For males, diabetes, hypertension, smoking, and ≥ 2 major CVD risk factors were associated with hearing loss. For females, diabetes, smoking, and ≥ 2 major CVD risk factors were significant risk factors. Compared to those with no CVD risk factors, there is a higher likelihood of hearing loss in patients with ≥ 2 major CVD risk factors. Future research to better understand sex dependence in the hearing loss-hypertension relationship is indicated.Hearing loss has been associated with individual cardiovascular disease (CVD) risk factors and, to a lesser extent, CVD risk metrics. However, these relationships are understudied in clinical populations. We conducted a retrospective study of electronic health records to evaluate the relationship between hearing loss and CVD risk burden. Hearing loss was defined as puretone average (PTA In older adults, hearing loss is a prevalent health condition6 and often presents comorbidly with other chronic conditions7. Once sensorineural hearing loss related to aging or systemic disease such as cardiovascular disease (CVD) begins, it cannot be reversed, making identification and treatment of modifiable risk factors critical for prevention and reduction of morbidity risk. To that end, numerous epidemiological studies have sought to identify modifiable risk factors for hearing loss with increased attention being paid to CVD risk factors (e.g. diabetes and smoking).Hearing loss is estimated to affect 27.7 million adults in the USA10. In mice, exposure to cigarette smoke leads to loss of spiral ganglion neurons, likely due to increase in cochlear oxidative stress11. Physiological studies in the spontaneously hypertensive rat demonstrated that the stria vascularis is the primary auditory site of lesion in hypertension12 and further suggest that hypertension accelerates age-related hearing loss13. Chinchillas fed a high-cholesterol diet have increased serum cholesterol levels, cochlear lysosomes, and accumulation of extracellular glycogen14. It is thought these morphological changes reflect strial and organ of Corti damage.Various mechanisms might underlie associations between CVD risk factors and auditory dysfunction. Histological examinations have identified strial atrophy, loss of spiral ganglion neurons and outer hair cells, and basilar membrane thickening as primary pathologic findings in diabetes15, diabetes18, hypertension20, and hyperlipidemia21. Examination of relationships with overall CVD risk have also been performed. These reports have explored associations between hearing loss and metabolic syndrome26, the American Heart Association’s Life’s Simple 727, and Framingham Risk Score28. Results of these studies are inconclusive as some have shown that aggregate CVD risk is associated with hearing loss28, though others, including a longitudinal study of metabolic syndrome and incident hearing loss24, have not25. Further, most published research on this topic has utilized epidemiological datasets . Published clinical reports have limited generalizability having been primarily conducted in Asian22 or Iranian26 populations. Understanding these relationships in the American clinical population is of interest because providers routinely treat patients with CVD risk factors. Using NHANES 1999–2010 data, Saydah et al.29 found that ~ 70% of U.S. adults ≥ 18 years have at least one CVD risk factor with multiple comorbidities being common.In human studies, reports suggest independent associations between hearing loss and tobacco smoking30. Male sex has been associated with hearing loss in humans31 and reduced cochlear integrity in rhesus monkeys32. There is a higher risk of incident hearing loss among men, even for low-risk men 33. Some studies relating hearing loss to CVD risk factors suggest sex-specific associations. A significant relationship between self-reported myocardial infarction and cochlear impairment was observed in the Epidemiology of Hearing Loss Study, but only in women34. A study of Medicare beneficiaries in the Health, Aging, and Body Composition study found that high blood pressure (BP) was associated with hearing loss, but only in white men35. An investigation of persons > 80 years old found the association between CVD risk factors and hearing loss to be stronger in men, a finding partly explained by cardioprotective effects of estrogen36. Together this evidence suggests that there may be sex-based differences in hearing status related to CVD-risk factors although significant gaps in our understanding remain.Sex differences factor into both hearing and cardiovascular health. For example, evidence suggests that women with certain CVD risk factors  are at higher risk of CVD events (e.g. stroke) than menThe aim of the present retrospective chart review was to investigate the relationship between hearing loss and CVD risk factor burden in a clinical sample. Our assessment of CVD risk was based on risk factors commonly managed in the primary care setting; namely, hypertension, hyperlipidemia, tobacco smoking, and diabetes. Adjusting for potential confounders, we compared hearing in patients with major CVD risk factors to hearing in patients with optimal CVD risk status (i.e. no major risk factors). A secondary aim was to evaluate sex differences in these relationships. We hypothesized that increasing CVD risk load would be associated with greater odds of hearing loss. In doing so, we sought to advance understanding of the relationship between CVD risk and hearing loss, which may illuminate pathways for improved prevention and intervention.We conducted a retrospective review of clinical data from patients seen at UCHealth, a large Colorado academic medical center, between 1-Jan 2011 and 31-Jul 2019. Patients aged ≥ 18 years who underwent audiological and general health evaluations (including BP measurement and glucose and lipid panels) were identified via query of Health Data Compass Data Warehouse electronic health records (EHRs).We manually extracted audiological data from the records of 7069 patients, which were entered into a deidentified database. We directly exported all other data including patient demographics and CVD risk factor status from EHRs. Identifiable personal health information was not included in the database. Ethical approval and informed consent statements were exempted (#19-1400) by the Colorado Multiple Institutional Review Board. All methods were carried out in accordance with relevant guidelines and regulations.From the core group of patients, we excluded individuals with bilateral abnormal tympanograms (i.e. static acoustic admittance < 0.3 or > 1.8 mmohs or peak pressure < − 150 daPa), suspected or diagnosed conductive pathology (primarily identified by measurement of an air–bone gap > 10 dB at one or more frequencies between 250 and 4000 Hz), sudden sensorineural hearing loss, history of otologic surgery, acoustic neuroma, cochlear implants, ototoxic medication use, and missing CVD risk factor or audiometric data resulting in a final sample of 6332 patients , [c] 180–199 mg/dL , and [d] < 180 mg/dL . Diabetes, current smoking, cholesterol group (a), and BP group (a) were classified as major risk factors.Diabetes, tobacco smoking, hyperlipemia, hypertension served as independent variables. We classified tobacco smoking status (Never/Current/Former) based on self-report. We defined diabetes as use of antihyperglycemics, fasting plasma glucose ≥ 126 mg/dL, random serum/plasma glucose ≥ 200 mg/dL [or 11.1 mmol/L]), and/or physician diagnosis indicated by International Classification of Disease codes (versions 9 and 10). We categorized BP into four strata based on systolic (S) and diastolic (D) BP levels: [a] SBP ≥ 160 mmHg or DBP ≥ 100 mmHg, or use of antihypertensives, [b] SBP 140–159 or DBP 90–99 mmHg (elevated), [c] SBP 120–139 or DBP 80–89 mmHg , and [d] SBP < 120 and DBP < 80 mmHg 37 we created five mutually exclusive risk categories: [a] optimal levels of all four CVD risk factors, [b] ≥ 1 CVD risk factors non-optimal, [c] ≥ 1 CVD risk factors elevated, [d] exactly 1 major CVD risk factor, and [e] ≥ 2 major CVD risk factors. Second, we computed Framingham Risk Scores per D’Agostino et al.’s algorithm38. This score represents 10-year absolute CVD risk and risk of individual events .Based on the four CVD risk factors, we defined CVD risk burden categorically and continuously. First, per Bogle et al.Audiological data consisted of information obtained during audiological examination . Audiologic evaluations were completed by a licensed audiologist based on our institution’s standard of care. We captured portions of the assessment, including case history, and air- and bone-conduction puretone audiometry . If necessary, masking was performed, and masked thresholds were used in place of unmasked thresholds in statistical models. For all frequencies, in the case of nonresponse, thresholds were defined as 130 dB HL. Finally, noise exposure history  was determined via case history. For statistical analysis, noise history was collapsed into one binary variable (Yes/No).0.5,1,2,4]) > 20 dB HL in the poorer ear. We also evaluated hearing thresholds continuously at discrete audiometric frequencies.Our primary outcome variable was hearing loss, which we defined as average threshold at 0.5, 1, 2, and 4 kHz . We used linear regression to compare thresholds at individual audiometric frequencies between the five CVD risk strata using the optimal group as reference. We also used linear regression to examine the relationship between PTA0.5,1,2,4 and Framingham Risk Score. Fully adjusted models included age, sex (unless stratified), noise exposure, hearing aid use (yes/no), and body mass index (BMI) as covariates. Models for individual risk factors (e.g. diabetes) were adjusted for the other three CVD risk factors. We fit models separately for men and women. Additional models were constructed for prediabetes and former tobacco smoking although these factors were not considered for aggregate CVD risk classification. P-values < 0.05 were considered statistically significant. Analysis was done using the glm function in R (R Core Team (2019) v. 3.6.1).We report continuous measures as mean (SEM) and categorical measures as number (percent). We compared categorical variables using the Chi-square test and continuous variables with two-tailed Portions of this work were presented at the Association of Diabetes Care and Education Specialists conference in August of 2020 and at the American Academy of Audiology conference in April of 2021.p < 0.001). The hearing loss group contained more males than the normal hearing group . For both groups, most individuals were non-Hispanic white. High cholesterol, hypertension, and diabetes were more common in patients with hearing loss; the prevalence of current smoking was similar between groups.We present patient characteristics in Table 0.5,1,2,4) by hearing loss status. Noise exposure, particularly military-related, was more common in persons with hearing loss than those without. For those with hearing loss, most (84.35%) had bilateral loss and on average, hearing loss was mild . Supplementary Table Table Supplementary Table Associations between hearing loss and CVD risk factors are shown in Table Next, because sex-specific relationships were identified upon audiometric analysis Fig. , we repo0.5,1,2,4 is reflected by the R value of 0.419 shown in Supplementary Fig. Finally, the strength of the relationship between Framingham Risk Score and PTAThis study evaluated the relationship between CVD risk factors and hearing loss in 6332 patients. We used CVD risk metrics commonly employed in primary care and hypothesized that there would be a positive relationship between increasing CVD risk factor load and likelihood of hearing loss. First, our results demonstrated that diabetics and current smokers had increased odds of hearing loss. Having ≥ 2 major CVD risk factors was associated with 92% increased odds of hearing loss compared to the optimal CVD risk stratum. Second, hypertension was associated with hearing loss, but only in males. Other relationships were similar between the sexes.15, Korean NHANES39, and the UK Biobank Resource40, which utilized a speech-in-noise test. Prospective research has also linked smoking to hearing loss41. In our study, former smoking was not associated with hearing loss, which has been shown previously40. Former smokers may adopt other positive lifestyle changes , which could be protective for auditory health. Smoking cessation may mitigate the excess risk of hearing loss associated with smoking, although further research is needed to corroborate this possibility.Of the CVD risk factors, the strongest relationship we observed was that with current smoking, which was associated with hearing loss in both sexes (MVOR = 1.85 [95% CI: 1.40–2.46]). Our findings are consistent with cross-sectional reports from the Epidemiology of Hearing Loss Study42. In a meta-analysis, Akinpelu et al.16 reported a slightly more robust association with diabetes than we found. Based on six studies, they calculated an average OR for hearing loss of 1.91 (95% CI 1.47–2.49). The studies they evaluated defined hearing loss using a cut point of 25 dB HL whereas we used 20 dB HL. Other factors such as diabetic control, disease duration, and participant demographics could also account for variable strength of the reported associations.Diabetics were at 43% higher odds of hearing loss than non-diabetics. The strength of this association was similar between the sexes. The link we observed with diabetes is consistent with past reports45. We did not find evidence to support an association between high cholesterol and hearing loss. There was widespread use of statins in our sample. In patients with hearing loss, 43% were on statins. Moreover, 18% of individuals with normal hearing were on treatment. A cross-sectional analysis of Blue Mountain Hearing Study participants aged ≥ 50 years found cholesterol-lowering medication to be negatively associated with hearing loss21. One contested possibility is that treatment positively influences auditory status, which may obscure any negative influence of hyperlipidemia itself. However, a randomized trial of the effect of atorvastatin on hearing loss progression did not find evidence to support this hypothesis46.Previous studies on the relationship between hearing loss and hyperlipemia are inconclusive and report contradictory resultsdata not shown). Cross-sectional reports including those from the NHANES31, Busselton Healthy Ageing Study28, and Hispanic Community Health Study/Study of Latinos47 have identified significant relationships between hypertension and hearing loss. Sex differences have also been reported. For example, a study of 3315 participants (aged 52–99 years) from the Rotterdam Study reported a significant relationship between low-frequency hearing loss and systolic BP in men, but not women48. An association between hypertension and high-frequency hearing loss was reported in men, but not women, from the Framingham cohort49. Wattamwar et al.36 observed a stronger relationship between CVD risk factors and hearing loss in elderly males than females. The underpinning(s) of these sex differences is unknown but may relate to the otoprotective effects of estrogen, which has been proposed for age-related and noise-induced hearing loss50.The one sex-specific relationship we observed was that between hearing loss and hypertension, which was limited to males. The prevalence of hypertension was 42% overall  had ≥ 1 major risk factors while only 45% of individuals with normal hearing had ≥ 1 major risk factors Table .28 identified a graded association between Framingham Risk Score and hearing loss in the Busselton Healthy Ageing Study. Sun et al.23 found a higher number of metabolic syndrome components to be related to hearing loss in the NHANES and a separate NHANES study determined diabetes and smoking to be a particularly harmful combination51.We observed dose-dependent relationships between odds of hearing loss and BP and total cholesterol levels, but these associations were not significant in the overall sample. Our findings indicate that increasing risk factor load is associated with greater likelihood of hearing loss. However, this seems to be the case only for major CVD risk factors as non-optimal risk factor status (e.g. prediabetes) was not significantly related to hearing loss. Our approach to defining CVD risk differs somewhat from prior reports. Nonetheless, comparisons to past research can be made. With an average participant age similar to ours, Tan et al.The clinical implications of this work are relevant to medical practitioners across specialties. Early identification of auditory dysfunction in persons with modifiable risk factors such as smoking is critical to reducing the disease burden of hearing loss. Knowledge that certain risk factors and high-risk factor load are associated with hearing loss may guide recommendations for hearing evaluations and intervention for at-risk patients. With increased attention to personalized medicine and patient-centered care, these findings support holistic medical care. In the future, clinical implications will be better understood once prospective studies can address how baseline CVD risk status influences long term auditory function.This retrospective study has important limitations. The cross-sectional design hampers determinations regarding causality and progression of hearing loss. In some instances, we were unable to capture CVD comorbidity status on the day of audiological evaluation as visits for hearing and other health concerns did not always coincide. We used CVD risk factor and BMI data from the date of the closest clinical encounter and cannot account for potential day-to-day variability in these measures. We did not adjust for medication use as the definition of CVD risk stratification included treatment. Our audiometric analysis did not adjust for multiple hypothesis tests. Data from primarily white cohorts were used to develop the Framingham Risk Score algorithm. It may not provide precise CVD risk estimates for all racial/ethnic groups. Data used to develop the original algorithm were from subjects aged 30–74 years whereas patients in our dataset ranged from 18–97 years. Last, we were only able to calculate risk scores for 5452 patients as calculation requires information that was not available for all individuals .In conclusion, this study provides data on hearing status as it relates to adverse cardiovascular health. Diabetes, smoking, and the presence of ≥ 2 major CVD risk factors significantly increased the odds of hearing loss. In males, hypertension was also a significant predictor. Improved glucose control, smoking cessation, and early BP management  may promote healthy hearing although such strategies would need to be borne out by longitudinal studies.Supplementary Figure S1.Supplementary Tables.


The signal processing strategy is a parameter that may influence the auditory performance of cochlear implant and is important to optimize this parameter to provide better speech perception, especially in difficult listening situations.To evaluate the individual's auditory performance using two different signal processing strategy.Methods: Prospective study with 11 prelingually deafened children with open-set speech recognition. A within-subjects design was used to compare performance with standard HiRes and HiRes 120 in three different moments. During test sessions, subject's performance was evaluated by warble-tone sound-field thresholds, speech perception evaluation, in quiet and in noise.In the silence, children S1, S4, S5, S7 showed better performance with the HiRes 120 strategy and children S2, S9, S11 showed better performance with the HiRes strategy. In the noise was also observed that some children performed better using the HiRes 120 strategy and other with HiRes.Not all children presented the same pattern of response to the different strategies used in this study, which reinforces the need to look at optimizing cochlear implant clinical programming. The multichannel cochlear implant (CI) is the most important advance in the treatment of people with severe and/or profound bilateral hearing loss, who do not benefit from using hearing aids (HA).However, speech perception results with the CI are closely related to factors such as age at surgery, duration of sensory deprivation, duration of device use, hearing loss etiology and optimization of programming parameters.One of the important parameters established at the time of device programming is the signal processing strategy, which defines how the CI will transform the acoustic information into electrical stimuli to be transmitted to the auditory nerve. The aim is to provide a high-fidelity electrical representation of the acoustic information captured by the speech processor microphone in order to make speech recognition possible for the CI user, especially in difficult listening situations, such as in the presence of competitive noise.In Brazil, among the brands of CIs approved for use by the National Agency for Sanitary Surveillance (ANVISA), there is the Advanced Bionics. The first CI device with this brand was implanted in March 1991 for research purposes: the Clarion 1.0, which was approved for commercial distribution in the United States by the Food and Drug Administration (FDA) in March of 1996 for adults, and in June 1997, for children - a device called Clarion 1.2. These devices provide three different signal processing strategies: the Continuous Interleaved Sampling (CIS), the Simultaneous Analog Stimulation (SAS) and the Multiple Pulsatile Sampler (MPS).A big step for the Advanced Bionics devices was the development of the HiRes speech processing, launched in 2002, which provided more temporal information than the signal processing strategies described above. The high rates of stimulation associated with the extraction of temporal fine structure cues provided by this strategy, result in the transmission of the acoustic signal to the CI user in high resolution mode. According to studies carried out by various international CI centers, HiRes strategy for optimizing the speech perception of CI users of Advanced Bionics is really noteworthyAnd in 2006, the company launched the HiRes 120 signal processing strategy, based on the technique of virtual spectral channels in order to provide a more detailed acoustic signal spectral representation, along with the other resources provided by the HiRes strategy.In the HiRes strategy, the incoming sound is filtered in 16 spectral bands and the energy of each band is extracted and passed on with high rates of stimulation, to a single corresponding electrode. In the HiRes 120 signal processing, the input signal is analyzed in a spectral range of 120 bands, so that subsequently, the energy is simultaneously retransmitted to two adjacent electrodes varying the current level ratio. This allows users of this signal strategy to take advantage of residual hearing in relation to the ability of auditory discrimination, getting spectral information with higher resolution, compared to the HiRes strategy. The increased spectral information, together with fine time resolution - already implemented in HiRes strategy, provides better speech perception results in noise, and music appreciation.Since its launch, the HiRes 120 has been recommended by the Advanced Bionics as a signal processing strategy used in programming the speech processor for children and adults. In general, the different CI manufacturers instruct speech and hearing experts from the CI team about the signal processing strategy recommended for each device model. However, it is extremely important to have a clinical evaluation of results after CI, in the different signal processing strategies, since sometimes the strategy recommended by the company does not benefit all CI users alike.In this context, the aim of this study was to analyze and compare the individual results vis-à-vis the performance of speech perception in children using CI, using two different signal processing strategies from the Advanced Bionics HiResolution system.This study was approved by the Ethics in Human Research (Protocol # 68/2011).The sample was composed of children with pre-lingual hearing loss, unilaterally implanted with the HiRes 90K devices from Advanced Bionics, aged between 5 and 10 years, from both genders, who had word-recognition-in-the-open auditory skills, according to the hearing categories proposed in 1994Considering such characteristics, the sample totaled 15 participants. However, four were excluded from the study due to problems with scheduling and return to the CI center where the study was carried out.Thus, our sample consisted of 11 participants, all users of the HiRes 90K internal component and platinum speech processor. The CI was fitted to the left ear in eight participants, and in the right ear in three. In none of the cases studied there was a history of disorders involving the internal component and all had 16 active intracochlear electrodes.Regarding the onset of hearing loss, all participants were carriers of congenital hearing impairment, they all had hearing aids prior to the CI and the CI surgery was performed before 3 years of age. With regard to etiology, four subjects were identified with genetic hearing loss and the other seven cases had an idiopathic etiology.All children who participated in this study were frequent users of CI. Regarding the use of hearing aids in the ear contralateral to the CI, six participants were using this device and five did not use the contralateral HA. All were placed in a hearing and speech treatment program in their cities of origin and were enrolled in regular schools.Such information, as well as demographic data and other information pertaining to the study were collected from the patients' medical records. The demographics of each participant are listed in the Annex A. To facilitate the identification of participants, they were numbered from 1 (S1) to 11 (S11).The participants were submitted to the procedures of this study, which included: 1) investigation of their audiometric thresholds in the free field, 2) evaluation of speech perception by means of the HINT test in silence and in noise. Both, the audiometric thresholds in free field investigation as well as the assessment of speech perception were performed with participants using only the CI, even those who used hearing aids and CI in their day-to-day.st1Evaluation (baseline): procedures performed using the HiRes 120 strategy. The HiRes 120 strategy was the baseline of the present study, since the strategy was already used by the participants of the study. After this evaluation, we changed the signal processing strategy for HiRes;nd2Evaluation: After three months of HiRes strategy use, participants were reevaluated by means of the procedures listed above. After the evaluation, we changed the processing strategy for the HiRes 120;rd3Evaluation: After three months of using the HiRes 120 strategy, the procedures listed were rerun.All procedures listed were fully applied at three different times :1stEvalBefore starting the procedures described below, was assessed the external component , through visual inspection, and the internal component was tested using telemetry impedance. The procedures were performed in order to rule out any problem with the device which could interfere in the results presented.To program the speech processor, at times when we changed the signal processing strategy, we used a portable microcomputer coupled to the programming interface and the programming software from Advanced Bionics - the SoundWave, version 2.0.After evaluating each sample point, the sound processor was programmed with maps prepared with the signal processing strategy set for each sample point (HiRes or HiRes 120), but the researcher also included in the sound processor the old map of the child, should the child not adapt to the new map. In accordance with the instructions given to the family, the child should use the new maps, adjusted after evaluation, but if the child would not adapted to the new maps, the parents could set the sound processor to the old program .First, we obtained the audiometric thresholds in free field, for each participant, in the frequencies of 500; 1,000; 2,000 and 4,000 Hz, using the warble tone.The free field audiometry was carried out in a soundproof booth of 2 x 2 meters and the audiometer used was the Midimate 622 - from Madsen Electronics, connected to an amplifier in free field and two speakers, calibrated in dB - sound pressure level (SPL). The CI user was positioned at one meter from the speaker at 0° azimuth. This procedure was performed to ensure that all participants of the study had proper audibility in the speech frequencies, not compromising the perception tests used in this study.The HINT test was developed at the House Ear Institute in 1994 to provide a reliable and efficient measurement of speech reception thresholds for sentences in silence and in noise and the Portuguese version of the test - HINT BrazilIn silence, the speech signal was presented via loudspeaker located one meter away and in front of the subject (0° azimuth) at an initial intensity of 65 dB SPL. However, this sign had a variable intensity throughout the procedure, based on the answer given by the patient. This occurred until we established the Sentence Recognition Threshold (SRT), which was achieved when 50% of the sentences were repeated correctly by the participant.In the frontal noise situation, the speech signal was presented in the presence of noise. Both signals were submitted by the same speaker, located one meter away and in front of the subject (0° azimuth). Under these conditions, the noise was calibrated and maintained at the intensity of 65 dB SPL and the intensity of the speech signal was presented initially at 50 dB SPL. The speech signal varied in intensity throughout the procedure, based on the answer given by the patient. This happened until we established the SRT, which was achieved when 50% of the sentences were repeated correctly by the participant.In the lateral noise situation, the speech signal was presented in the presence of competitive noise. The speech signal was presented in the front (0° azimuth) and one meter away from the participant, and the noise came from a speaker, positioned at 90° azimuth, ipsilateral to the CI, also one meter away from the subject. Similarly in the frontal noise situation, noise was calibrated and maintained at the intensity of 65 dB SPL and the speech signal intensity was initially presented at 50 dB SPL; however, this signal intensity was variable throughout the procedure, according to the answer given by the subject. This happened until we established the SRT, which was achieved when 50% of the sentences were repeated correctly by the participant.At the end of the test, the software automatically supplied values in dB in silence (representing the threshold), frontal noise and lateral noise  situations for each participant.It is Important to stress that the speech stimuli application sequence, in the different situations, occurred randomly in order to eliminate variables related to fatigue, participants' attention and the learning phenomenon. In order to exclude the change variable from the lists in the evaluation of speech perception in different assessment time points in this study, we chose to use the same list of sentences at different time points and in different assessment conditions for each participant.® database.The data from all stages of the study were stored in an ExcelTo analyze the performance in the three data collection points of our study in the HINT test  we used the variance analysis statistical test with repeated measures. For post-hoc comparisons we used the Tukey test.In both statistical tests used in the present study, we used the STATA computer package, version 9.0 and a significance level of 5%.All children evaluated completed the assessment proposed in the three stages of the study, except for child S10. Because the S10 child did not adapt to the signal processing strategy change performed after the first evaluation of the study and continued using the speech processor map set with the HiRes 120 strategy, she was not submitted to the proposed HiRes evaluation strategy. Thus, the results obtained by the S10 child refer only to the auditory performance using the HiRes 120 strategy.At all the time points evaluated in the study, the children had hearing thresholds with CI less than 30 dB at 500-4000 Hz frequencies. This result ensured that all children had adequate audibility in the speech frequencies, and the audibility of sounds was not a factor which influenced the auditory performance achieved by the participants.The results of each participant in the HINT test, in silence and in frontal and lateral noise can be seen in To facilitate the identification of participants, the column corresponding to the results of each participant was numbered from the participant number 1 to participant number 11.The signal processing strategy is a programming parameter directly involved in the results of speech perception after CI and, in this context, the present study aimed to analyze and compare the individual results in the speech perception performance in children using CI, using the HiRes and HiRes 120 signal processing strategies, from Advanced Bionics. According to the results obtained, we noticed that not all children had the same response pattern in the different strategies used in this study.Analyzing auditory performance in silence, some children had better hearing performance with the HiRes 120 strategy , others had better hearing performance with the HiRes strategy . When considering that few active intracochlear electrodes already provide good results in speech recognition in silent environmentsIn the assessment of speech perception in noisy situations, when the noise came from the front, children S2 and S11 had better hearing performance with the HiRes 120 strategy, and children S4, S8 and S9 had better hearing performance with the HiRes strategy. When lateral noise was introduced, children S1, S2, S8, S9 and S11 had better hearing performance with the HiRes 120 strategy and the child S6 had better hearing performance with the HiRes strategy. Considering the results of international studies designed with adult users with post-lingual hearing loss and who showed improvements in hearing performance in noise with the HiRes 120 strategyThe fact that one child (S10) have not adapted to the HiRes is also an important finding of this study, because the child claimed that the sound quality was bad and she could not understand speech when using the program set with the HiRes signal processing strategy.In order to check whether some patient characteristic influenced the response pattern obtained with different strategies; hearing performance in noise was analyzed in comparison with the characteristics of the participants (Appendix A). However, there were no demographic or hearing characteristic, such as residual hearing (pre-CI hearing thresholds), duration of sensory deprivation, age at CI surgery, age at time of evaluation or duration of CI use that has been instrumental in the response pattern presented by the participant in the study.It is worth noting in that both situations - silence and the frontal and lateral noisy, some children had a longitudinal improvement in auditory performance , represented by an SRT reduction during the evaluations, regardless of the signal processing strategy used during the evaluation. This result may be related to the improvement in listening skills. According to the inclusion and exclusion criteria of this study, only children who had hearing ability to recognize open-set words could be selected to participate in it; however, the fact that they had already reached the maximum category, proposed by GeersThus, the results presented in this study reinforce the need to do a clinical assessment when considering post-CI results in the different signal processing strategies, since sometimes the strategy recommended by the company does not benefit all CI users in the say wayTherefore, it is suggested that CI centers should develop future studies that compare the signal processing strategies of other CI devices in order to investigate the auditory performance of their hearing aid users with the recommended signal processing strategy, and others from a particular device.According to the results, we noticed that not all children presented the same response pattern vis-à-vis the different strategies used in this study, both in silence and in noise.