What is the prevalence of hearing loss and hearing aid use at the population level in France?In this cohort study including 186 460 French volunteers aged 18 to 75 years with audiometric data, 25% had hearing loss and 4% had disabling hearing loss. Among participants with disabling hearing loss, 37% reported using hearing aids.The findings suggest that hearing loss is prevalent among French adults and that hearing aids are underused. Although hearing loss is common in the population worldwide, the prevalence of hearing loss and hearing aid use is not known.To estimate the prevalence of hearing loss and hearing aid use in the adult French population.This cohort study used data from the CONSTANCES cohort, a representative sample of the French population. Volunteers aged 18 to 75 years were recruited at 21 preventive health centers between January 1, 2012, and December 31, 2019. The present study included participants with audiometric data.The main outcomes were prevalence of hearing loss and disabling hearing loss overall and by sex and age group and prevalence of self-reported hearing aid use among those with disabling hearing loss. Hearing loss was defined as a pure-tone average (PTA) in the better ear of 20 dB or higher, and disabling hearing loss was defined as a PTA in the better ear of 35 dB or higher.Of 200 870 participants in the CONSTANCES study, 186 460 had full audiometric data and were included in this study ; 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Of these participants, 24.8%  had hearing loss and 4.3%  had disabling hearing loss. The prevalence rates of hearing loss increased from 3.4%  at age 18 to 25 years to 73.3%  at age 71 to 75 years among men and from 4.4%  at age 18 to 25 years to 64.1%  at age 71 to 75 years among women. The prevalence of disabling hearing loss increased from 0.3%  among participants aged 18 to 25 years to 23.3%  among participants aged 71 to 75 years. Among the 8050 participants with disabling hearing loss, 36.8%  reported using hearing aids, including 56.7%  aged 18 to 25 years and 32.9%  aged 71 to 75 years.In this cohort study, hearing loss was prevalent in France, and the prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. These findings suggest that hearing loss prevention and screening in the French population are needed. This cohort study estimates the prevalence of hearing loss and hearing aid use overall and by sex and age in the adult population in France. The World Health Organization recently estimated that unaddressed hearing loss represents an annual worldwide cost of $980 billion, including health care, education, productivity loss, and societal costs.3 In addition to constraining the ability to communicate, hearing loss is associated with delayed language among children, social isolation, altered quality of life, depression, cognitive decline, and dementia.8Hearing loss affects 1.57 billion people worldwide, and projections suggest that 2.45 billion people will have hearing loss by 2050.14 Existing studies collected data mostly in the 1990s,15 and the prevalence of hearing loss has evolved in parallel with the aging of the population.18 These limitations were highlighted in the 2019 Global Burden of Disease Study1 and in several other studies.21 Although some nationally representative studies have reported audiometric data on subsamples, such as the National Health and Nutrition Examination Survey,23 representative studies of large sample sizes are lacking in the field, notably in Europe. For instance, in France, the latest estimation of hearing loss prevalence was performed in 2008 and relied on self-reported answers, with estimates of hearing loss ranging from 8.5% to 16.1% depending on the question.24 Moreover, examining patient characteristics associated with hearing loss may help identify the populations at greatest risk of hearing loss and inform preventive strategies for hearing loss.Prevalence estimates of hearing loss are scarce, derived primarily from small and nonrepresentative studies, most often based on self-reports of hearing loss instead of objective audiometric testing, and often based on age-restricted cohorts.26 an underuse of hearing aids has been suggested.27 However, estimates of hearing aid use are not nationwide and were calculated mostly in older populations.29 This study used a large, nationwide representative sample of the French adult population with full data on audiometric testing to estimate the prevalence of hearing loss and hearing aid use in the French population and to assess the characteristics associated with hearing loss and hearing aid use.Although the association of hearing aids with improvements in several health-related outcomes are increasingly recognized,31 Between January 1, 2012, and December 31, 2019, adults aged 18 to 75 years were randomly selected from the National Health Insurance Fund , which covers salaried workers who are professionally active or retired and their dependents (>85% of the French population), following a sampling scheme stratified by age, sex, socioeconomic status, and region of France to ensure a representative sample of the Caisse Nationale d’Assurance Maladie. Questionnaires on social, demographic, and health information, including personal and family history of diseases; events; and lifestyle behavior characteristics were self-administered at inclusion. A comprehensive health examination was performed at participating medical centers (21 centers across the French metropolitan territory) during which medical and clinical examinations, anthropometric measurements, and biological tests were performed. All included participants provided written informed consent. The CONSTANCES study followed the Declaration of Helsinki47 and was approved by the National Data Protection Authority and the institutional review board of the National Institute for Medical Research (INSERM). The present study was approved by the Comité d’Evaluation Ethique de l’Inserm. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.This cohort study included data from the CONSTANCES study, an ongoing nationwide study in France with a general purpose and a specific focus on occupational and social determinants of health and aging. The study design is detailed elsewhere.48 The pure-tone average (PTA) was calculated as the mean of the 0.5-, 1-, 2-, and 4-kHz frequencies for each ear. No hearing loss was defined as a PTA in the better ear of less than 20 dB, hearing loss as a PTA in the better ear of 20 dB or higher, and disabling hearing loss as a PTA in the better ear of 35 dB or higher, in accordance with recent recommendations.32Participants were offered a hearing test at study inclusion, performed in a soundproof testing room (for 74.3% of participants) or an air-ambient quiet room depending on the recruitment center’s equipment. Air-conduction thresholds were determined for 0.5, 1, 2, 4, and 8 kHz, and testing was performed from −10 dB to 85 dB in 5-dB increments. All measuring processes were performed in accordance with the ISO 8253-1 standard.27Audiometric testing was not performed for participants who used hearing aids at baseline. These participants were considered to have disabling hearing loss (PTA in the better ear of ≥35 dB) in the main analysis. This level of hearing loss generally corresponds with the threshold value for which hearing aids are advised and mostly accepted by individuals.33 Prevalent cardiovascular diseases (CVDs) were defined as a self-reported history of myocardial infarction, angina, stroke, or peripheral arterial disease. Noise exposure at work was self-reported on the basis of the following question: “Do you work (or have you worked) in an atmosphere where you needed to raise your voice to speak to someone located less than 2 meters from you?” Living alone and currently working (yes or no) were recorded. Smoking was categorized as never, former smoker, and current smoker. The degree of diploma was assessed using the 2011 International Standard Classification of Education (ISCED)49 and categorized as primary education, lower secondary education, upper secondary education, bachelor’s degree or equivalent education, and master’s or doctoral degrees . Monthly household income was recorded and categorized into quartiles of European household income34 as less than €1000, €1000 to €1500, €1500 to €2100, and more than €2100 per month . Living area was dichotomized as rural or urban.Diabetes was defined as self-reported treatment for diabetes or fasting blood glucose level of 126.1 mg/dL or higher . Hypertension was defined as self-reported treated hypertension or a measured systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher at study inclusion. Depression was defined as self-reported treated depression or a Center for Epidemiologic Studies Depression Scale score of 19 or higher, according to the validated cutoff of the French version.23 and included sex, age, body mass index (BMI), history of noise exposure at work, diabetes, hypertension, prevalent CVD, depression, smoking status, degree of diploma, household income, living alone, currently working, and type of living area . The prevalence of hearing aid use among participants with disabling hearing loss was estimated. Logistic regression modeling was used to quantify associations between covariates and hearing aid use among participants with disabling hearing loss.Prevalence rates of hearing loss and disabling hearing loss were calculated in the total population and by age group and sex, and 95% CIs were estimated. Characteristics associated with hearing loss and disabling hearing loss were examined using separate logistic regression models, and odds ratios (ORs) and 95% CIs were estimated. Candidate covariates were selected based on prior literature35 Second, analysis of characteristics associated with hearing loss was repeated using PTA as a continuous variable. Linear regression analysis was performed with a regression spline for age because of the nonlinear association between age and PTA. Third, prevalence estimates and characteristics associated with disabling hearing loss were rerun after reclassification of participants with hearing aids as presenting with any hearing loss (instead of disabling hearing loss) because hearing aids may be beneficial even for mild hearing loss .26 Fourth, multivariable regression models were rerun after imputing missing data using multiple imputation by chain equation.36 Fifth, the rates of hearing loss and hearing aid use calculated in this study were used to estimate the prevalence of hearing loss and hearing aid use in Europe, accounting for the age and sex population structure of the European population .37 All analyses were performed using R, version 3.5.1 .Several additional analyses were performed to assess the robustness of the findings. First, prevalence rates were re-estimated using weighting coefficients that were calculated in the CONSTANCES study for participants included in 2013, 2014, 2015, and 2016. The weighting coefficients took into account a nonparticipation correction factor based on the passive follow-up of a control cohort of nonparticipants, as described elsewhere.Of 200 870 participants recruited in the CONSTANCES cohort, 14 410 had missing audiometric data . After exclusions, the study population consisted of 186 460 participants with a mean (SD) age of 47.1 (13.5) years; 100 330 (53.8%) were female, and 86 130 (46.2%) were male. Compared with included participants, excluded participants were more often living alone in urban areas, were currently working, had a higher-degree diploma, and more often had depression but were less often exposed to noise at work and less often had hypertension  presented with any hearing loss. The prevalence of hearing loss increased with age, from 3.4%  at age 18 to 25 years to 73.3%  at age 71 to 75 years among men and from 4.4%  at age 18 to 25 years to 64.1%  at age 71 to 75 years among women . PrevaleDisabling hearing loss was noted in 8050 study participants . Disabling hearing loss also increased with age, from 0.3%  among those aged 18 to 25 years to 23.3%  among participants aged 71 to 75 years . DiffereThe distribution of study participants’ characteristics according to hearing loss status is reported in These results were similar in multivariate analysis, in which age, male sex, BMI, noise exposure at work, diabetes, prevalent CVD, depression, and smoking status were associated with higher odds of any hearing loss and disabling hearing loss. Higher educational level, higher household income, current working status, living in urban areas, and living alone were associated with lower odds of hearing loss and disabling hearing loss .Among 8050 participants with disabling hearing loss, 36.8%  reported using hearing aids. Hearing aid use decreased with age from 56.7%  among participants aged 18 to 25 years to 36.0%  among participants aged 65 to 70 years and 32.9%  among participants aged 71 to 75 years .The characteristics of participants with and without hearing aids are described in Weighted and unweighted prevalence estimates of any hearing loss and disabling hearing loss were in the same range  in the present study. However, only 1 data source is available for France in the Global Burden of Disease Study,1 and it reports newborn hearing screening.In this cohort study of a nationally representative sample of the French adult population, 24.8% of participants had any hearing loss and 4.3% had disabling hearing loss; among those with disabling hearing loss, 36.8% reported using hearing aids. Prevalence estimates of hearing loss using objective testing are scarce. Worldwide estimates of hearing loss provided by the 2019 Global Burden of Disease Study relied on 113 data sources from 54 countries and considered all ages from birth to 100 years,38 Among 28 339 participants aged 19 to 100 years recruited in the last wave of the HUNT study (HUNT4), the prevalence of hearing loss was 2.7% at ages 20 to 44 years and 15.4% at ages 45 to 64 years compared with 7.2% at ages 20 to 44 years and 32.8% at ages 45 to 64 years in the present study. Similar discrepancies were observed for disabling hearing loss. These between-cohort disagreements may reflect different background population characteristics, but data on comorbidities are not yet available for HUNT4. Other community-based studies provided prevalence estimates of hearing loss in subsamples23 or in studies with incomplete audiometric testing40 or included selected age groups.12 Outside Europe, a South Korean study found that hearing loss was present in 13.4% of 18 650 participants aged 12 years or older.41 Data on comorbidities and hearing aid use were not reported in that study, however.To our knowledge, the Nord-Trøndelag Health Study (HUNT) study from Norway is the sole nationwide representative study in Europe with prevalence estimates of hearing loss using objective measures.26 Orji et al27 estimated that 83% of individuals  worldwide and 77% of individuals in Europe with disabling hearing loss did not use hearing aids in an analysis derived from the 2019 Global Burden of Disease Study. A total of 63.2% of participants with disabling hearing loss in the present study did not use hearing aids. Of note, we observed a decrease in use of hearing aids associated with increasing age despite the prevalence of hearing loss increasing with age. Younger adults may have more social and professional interactions than older adults, which may be associated with greater use of hearing aids among younger adults than among older adults. Moreover, lower educational level and lower income were associated with underuse of hearing aids; thus, clinicians should pay attention to these populations. The underuse of hearing aids may be reconsidered as even greater than current estimates because indications for hearing aid use may expand beyond disabling hearing loss. Research suggests an association of hearing aids with improvement in mild hearing loss .26 Only 7% of individuals in the larger population of participants in the CONSTANCES cohort with any hearing loss were using hearing aids. Those findings are of particular importance in France, where full reimbursement for hearing aids was established after completion of this study.42 Thus, future estimates of hearing aid use in this cohort study may reveal the potential association of this public health policy with hearing aid adoption.Hearing aids remain underused despite their association with improved outcomes, such as increased quality of life or reduced cognitive decline, compared with hearing loss without use of hearing aids.44 policy makers may contemplate the implementation of screening programs based on the following considerations: (1) the heavy burden of hearing loss, particularly at 60 years or older, when more than half of the population experiences hearing loss; (2) the negative consequences of untreated hearing loss 4; (3) the benefits associated with hearing rehabilitation26; and (4) the absence of adverse effects of screening for hearing loss.43 The third implication relies on implementation of strategies to improve hearing aid adoption among individuals with hearing loss. These programs should include strategies aimed at increasing awareness of and access to hearing aids, such as the strategies initiated in the US with the Over the Counter Hearing Aid Act in 201745 or in France with better reimbursement for hearing aids since 2020.42Because of the association of hearing loss with health, the burden of hearing loss may have important public health implications. The first implication relies on the implementation of preventive strategies for hearing loss. Beyond early diagnosis and management of ear diseases, the current study identifies several factors associated with hearing loss that are modifiable or preventable, such as cardiometabolic risk factors  and lifestyle risk factors (BMI and smoking status). Noise exposure at work was also associated with hearing loss; thus, noise prevention strategies at work may be beneficial. Socioeconomic inequalities among individuals with hearing loss are a challenge to address. The second implication relies on the screening and treatment of hearing loss. Although formal evidence is lacking regarding benefits associated with screening and treatment of hearing loss, as recently revealed by the US Preventive Task Force,46This study has limitations. First, participants with hearing aids at baseline did not have audiometric data. However, those participants were alternatively considered as presenting with disabling hearing loss or with any hearing loss and results remained similar. Second, bone conduction testing was not available, precluding assessment of the type of hearing loss . Moreover, causes of hearing loss were unavailable, precluding estimations of the proportion of avoidable hearing loss cases due to ear diseases. Third, older individuals experience the highest prevalence of hearing loss, but the upper age limit in the current study was 75 years, which precluded the estimation of prevalence rates beyond this age. Fourth, as in all cohort studies including volunteers, a healthy participant bias cannot be ruled out; thus, the current prevalence rates may be underestimates. Fifth, the prevalence of hearing loss and hearing aid use in Europe estimated in the present study should be interpreted with caution because they represent estimates derived from a single country, whereas variation in the prevalence of hearing impairment across Europe has been reported.In this cohort study, hearing loss was prevalent in France, and prevalence of hearing loss increased with age among both men and women. Hearing aids were underused, particularly among older individuals. Hearing loss is a field with unique opportunities because diagnosis and rehabilitation are accessible and mostly noninvasive.


Mucormycosis is an intrusive contagious disease caused by the Mucorales fungus. The infection spreads mostly by spore inhalation, skin wounds, catheters and needles, and contaminated food. Immunocompromised people in developed countries, such as those with hematological malignancies, organ transplants, and neutropenia, are at risk. Diabetics and those who have endured significant trauma are the most vulnerable to mucormycosis infection in impoverished nations .It has the ability to migrate hematogenous from the site of infection to other body locations and generate thrombosis and tissue infarction, which is a feature of mucormycosis infection. In the battle against infection, phagocytes are an important host defense mechanism . The priMucormycosis has a significant morbidity and death incidence in those who have undergone hematopoietic stem-cell transplantation (HSCT). According to recent studies, the incidence of Mucormycosis in HSCT patients is predicted to be around 5% . It is tNotably, there are no biomarkers available to detect mucormycosis infection in HSCT patients. The galactomannan and -D-glucan assays for Aspergillus cannot identify antigen components of the Mucorales cell wall. To identify mucormycosis from more prevalent and antifungal-sensitive molds like Aspergillus, a direct investigation of fluids and cultures taken from sterile regions is essential . The finMore than half of HSCT patients having mucormycosis exhibit lung infection, 10%–15% have central nervous system involvement, and 0%–40% have sinus involvement. The disseminated illness affects at least 10% of HSCT patients with mucormycosis ,10. InvaEnhanced immunological and metabolic aspects, such as the use of tapered dosages of steroids and immunosuppressive drugs when possible, and hyperglycemia control, should be regularly monitored in the therapy of mucormycosis in SOT and HSCT patients . Given tThree critical techniques for addressing mucormycosis in hematological patients are (1) prompt initiation of effective antifungal medication, (2) substantial “early” surgical dissection of necrotic lesions, and (3) speedy control of underlying disease, when feasible . Only twThe present study includes printed and published information; therefore, formal ethical clearance was not applicable for this study.NA.NA.NA.All authors meet the inclusion criteria, and all authors read and approved the final version of the manuscript.Name of the registry: NA.Unique Identifying number or registration ID: NA.Hyperlink to your specific registration (must be publicly accessible and will be checked): NA.mehedi.bmb.mbstu@gmail.com.Mohammad Mehedi HasanDepartment of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh. Email: NA.


Oryza sativa) is the most important food crop all over the world, while white-backed planthopper (WBPH), Sogatella furcifera (Horváth) (Hemiptera: Delphacidae) is an important pest causing rice yield reduction. The purpose of this study is to evaluate the sublethal effects of strain BEdy1 Beauveria bassiana  Vuill.  on S. furcifera using the two-sex life table analytical method, compare the life tables of the F0 and F1 generations of WBPHs which were treated with sublethal concentrations  of B. bassiana BEdy1 with a control group. The results showed that the duration of the egg, 4th-instar and 5th-instar nymph, pre-adult, total pre-oviposition (TPOP) and mean generation time (T) for the LC25 treatment were significantly longer than those of the control and LC10 treatment. However, the duration of the adult, the longevity of male and female adults and the oviposition days of female adults for the LC25 treatment were significantly shortened. The fecundity of female adults, intrinsic rate of increase (r), net reproductive rate (R0) and finite rate of increase (λ) for the LC25 treatment were significantly decreased compared with those of other treatments. The duration of the egg and pre-adult stage for the LC10 treatment were longer than those of the control group, but the population parameters showed no significant difference. Therefore, the LC25 of B. bassiana BEdy1 can inhibit the population growth of S. furcifera.Rice ( Oryza sativa), one of the most important cereal crops and the main food source for more than a third of the global population, is cultivated in over 100 countries currently, and Asian nations account for 90% of rice production in the world [Sogatella furcifera Horváth (Homoptera: Delphacidae), is a typical r-strategy pest, one of the destructive long-distance migratory pests of rice in Asia, its permanent breeding areas are in the tropics, and it commonly migrates from the subtropic to temperate areas [Rice  Vuill. , a cosmopolitan and soil-borne fungus, is commercialized as a biological insecticide worldwide and it has exhibited great potential in controlling many pests [B. bassiana when applied in the field. Infection efficiency depends on the number of conidia, relative humidity, temperature and ultraviolet radiation, and exposure to fungistatic compounds on the phylloplane can reduce the efficacy of entomogenous fungi [B. bassiana on pests.ny pests , includiny pests ,18,19. Hus fungi ,21,22; aS. furcifera [B. bassiana on S. furcifera are still unknown.Sublethal effects contain physiological and behavioral effects, including effects on neurophysiology, development, adult longevity, immunology, fecundity, sex ratio, feeding behavior, oviposition behavior and learning performance . To dateurcifera ,26,27,28Beauveria bassiana BEdy1, isolated from Ergania doriae yunnanus Heller (Coleoptera: Curculionidae), has great potential for development and application in the future [10 and LC25 doses of B. bassiana BEdy1 on the biological traits of S. furcifera in various stages under the F0 and F1 generations [e future . In thiserations ,31. The Sogatella furcifera was collected from a rice field in Hongyanba , Xuyong County, Luzhou City, Sichuan Province, China, in 2020 and reared on rice (TN1) seedlings (about 15 cm high) without exposure to any pesticides for more than 15 generations in the intelligent artificial climate chamber  under 26 ± 1 °C, 70% ± 10% relative humidity and a photoperiod of 14 h:10 h (L:D).All experiments were performed in the Agricultural Pest Laboratory at the College of Agronomy, Sichuan Agricultural University.Beauveria bassiana strain BEdy1 used in the test was provided by Shang Jing’s research group, Phytopathology Laboratory, College of Agronomy, Sichuan Agricultural University. The GenBank accession number of this fungus on the NCBI database is MK345993. The test strain was cultured on PPDA  in plastic petri dishes (90 mm diameter), wrapped with Parafilm and placed in darkness at 26 ± 1 °C. After 10–12 days, B. bassiana was harvested using a sterile blade, followed by the conidial suspension being placed inside a reagent bottle containing 0.05% Tween-80 Sterile water for later experiments.The B. bassiana strain BEdy1 at five concentrations , with 0.05% Tween-80 Sterile water treatment served as a control. Firstly, we observed the molting of nymphs under the microscope every day and collected thirty healthy and uniform 3rd-instar nymphs with a suction trap as one group. For each group, 3 mL of the spore suspension was sprayed on the body wall of 30 3rd-instar nymphs with a hand-held spray. After spraying, they were transferred to a plastic cup (500 mL) containing 15 rice seedlings with 4–5 leaf stage leaves that were washed with ddH2O. At last, the death number was recorded after 96 h, and the individual nymphs were gently touched with a small brush, and the nymphs that were weak and unable to crawl normally served as the death record. There were three replicates for each treatment; toxicity data of the LC10 and LC25 values, confidence intervals at the 95% level and chi-square values were calculated using POLO Plus 2.0 statistical software .Using the spray method, treatment of WBPH 3rd-instar nymphs with B. bassiana on the life table parameters of S. furcifera were followed by Xiang’s and Ali’s approach with some modifications [0 individuals. Based on the bioassay result, the sensitive populations of 3rd-instar nymphs were treated with LC10 and LC25 of B. bassiana (the treatment group) and 0.05% Tween-80 (the control group). After 96 h of treatment according to the method in The sublethal effects of ications ,25. Firs0 treated with B. bassiana BEdy1 and the control treatment were collected as the F1 generation. In the first step, 150 1st-instar nymphs were randomly selected from the F0 offspring as the experimental population. The first 100 nymphs were numbered and used for the formal test, and the last 50 nymphs were numbered and used for replacement. They were fed separately in a test tube containing a rice seedling to observe the stage and condition of WBPHs. When these nymphs became adults, they were paired up as described above. The rice seedlings in test tubes were replaced every day. We checked the number of eggs in the replaced rice seedlings until all the adults died. Eventually, biological parameters were recorded, including the development duration, longevity and fecundity.The offspring of Fxjs), female age-specific fecundity (xjf), population age-specific survival rate (xl), population age-specific fecundity (xm), age-life expectancy (xje), age-stage-specific reproductive value (xjv), intrinsic rate of increase (r), finite rate (λ), net reproductive rate (R0) and mean generation time (T) were calculated [Analysis of the raw life table data was conducted using the age-stage two-sex life table theory ,33. The lculated ,35.xjs, xf, xl, xm, xje, xmxl and xjv were plotted using Sigmaplot 14.0 . The mean and standard error values  of the life table parameters were accurately estimated using the bootstrapping technique [echnique . The sigechnique .10 and LC25 of B. bassiana to the 3rd-instar nymphs of the WBPH at 96 h were 8.29 × 103 spores/mL and 1.65 × 106 spores/mL, respectively.The results  showed tB. bassiana BEdy1, there was no significant difference in the lifespan of the F0 generation adults compared with the control group. The average number of eggs laid by the females of the F0 generation treated with LC25 was significantly lower than that of the control and LC10 treatment groups (p < 0.05).The result  showed t1 generation of WBPH treated with LC10 and LC25 of B. bassiana was able to complete its development (10 and LC25 treatment groups (6.51 days and 6.86 days) were significantly longer than those of the control (5.66 days), and the development times of the 1st-instar nymph showed no significant differences between all three treatments. The development times of the 2nd-instar nymph (2.20 days) and 3rd-instar nymph (2.66 days) of the LC10 treatment were significantly shortened (p < 0.05), when compared with the control group. The development times of 4th-instar nymph (2.95 days), 5th-instar nymph (3.97 days) and pre-adult (21.11 days) of the LC25 treatment were significantly longer than those of the control group (p < 0.05). The development times of adult (13.87 days) and the survival time of male and female adults  of the LC25 treatment group were the shortest of the three treatments, but the total pre-oviposition (TPOP) (24.76 days) of LC25 was significantly longer than the control and LC10 treatment groups (p < 0.05). There was no significant difference in the adult pre-oviposition (APOP) of adults in the B. bassiana treatment group compared with the control group (p > 0.05). Days of spawning were 9.33 days for the LC25 treatment group, significantly lower (p < 0.05) when compared with the other two treatments. The average number of eggs laid by females was the lowest in the LC25 treatment group, with an average of only 133.02 eggs per female (p < 0.05). In addition, the male-to-female ratios of the offspring after the control and spray, LC10 and LC25, treatments were 1.16:1, 1.04:1 and 1:1, respectively.The results showed that the Felopment . The devr) (0.143), the finite rate of increase (λ) (1.154) and the net reproductive rate (R0) (61.69) of the LC25 treatment group were significantly lower than those of the LC10 treatment and the control groups (p < 0.05) , the average generation period T (28.73 days) of the LC25 treatment group was significantly prolonged (p < 0.05), indicating that the time required for the population to reach a stable growth rate to the R0 became longer; there was no significant difference in various population parameters between the control and LC10 treatment groups (p < 0.05).The population parameters of the intrinsic growth rate ( < 0.05) , indicatxjs) of the offspring of WBPHs treated with LC10 and LC25 of B. bassiana and the control group. The results showed that the xjs curves of the F1 generation of the control and B. bassiana-treated groups had some overlap. The curves of pre-adult developmental stages had similar fluctuations among the three treatments, and the age-specific survival rate curves of adults all ended with male adults. The overall survival rate of nymphs and the age-stage survival rates of male and female adults in the LC25 treatment group were lower than those in the LC10 treatment and control groups, but the difference in survival rates between male and female adults was smaller.xl) curves in the figure began to decline from the 29th to the 31st days, and the xl curve of LC25 decreased more rapidly, from 88% to 32% within 7 days. The female age-specific fecundity (xf7) curve refers to the number of eggs laid by females per day at age x and stage 7. The graph showed that the control group reached a peak of 25.04 eggs on the 27th day. In contrast, the age-specific fecundity curves of LC10- and LC25-treated females reached the maximum on the 26th day (21.82 eggs) and 29th day (20.45 eggs), respectively. Age-specific fecundity of the total population (xm) refers to the average number of eggs laid by the entire population at age x, and the xm of the LC25 treatment group was lower than that of the control and LC10 treatment groups. In addition, the age-specific maternity (xmxl) was the product of the population age-specific survival rate (xl) and the age-specific fecundity of the total population (xm), and the LC25-treated group in the figure had the lowest xmxl, i.e., the total single female egg production was lower than other groups.xje) refers to the time that individuals at age x and stage j can remain alive. The age-stage life expectancy (xje) of the three treatments in the figure decreased with increasing age and stage. After being treated with B. bassiana at LC25 concentration, the life expectancy of newborn eggs was 33.8 days, which was lower than that of the control treatment (35.45 days). In addition, the age-stage life expectancy of male adults in the three treatments was higher than that of female adults.xjv) indicated the contribution of an individual at age x stage j to population growth. The results  and control treatment (96.25 eggs/day) > LC25 treatment (73.52 eggs/day). In addition, the reproductive value curve of the 5th-instar nymphs in the LC25 treatment group appeared with two peaks, and the second peak was higher than the previous one.The age-stage reproductive value  used in production. For these reasons, B. bassiana BEdy1 has great prospects for application in the large-scale production and management of S. furcifera. However, when evaluating the control ability of entomogenous fungi against pests, the application potential of fungi is usually underestimated when only using the index of the lethal effect; actually, sublethal concentrations in fields occur when the concentration of insecticides gradually decreases after a preliminary application for a few days or weeks, and the host is very likely to be exposed to sublethal doses at that time [B. bassiana is used to control WBPHs, it will produce a wide range of sublethal effects. Our goal is to explore the sublethal effect of B. bassiana on WBPHs by using the TWOSEX-MSChart Software [B. bassiana on S. furcifera for the sustainability of agricultural production.s adults . Our prehat time ,37. TherSoftware ; it is iB. bassiana, which had adverse effects on the growth, development and reproduction of the parent and offspring, consistent with previous research results [Nilaparvata lugens (Stål) (Homoptera: Delphacidae) parental females sublethal treated with B. bassiana NJBb2101 did not change the longevity significantly compared with the control, but the fecundity of F0 females decreased. The development duration of the offspring nymphs of WBPH treated with B. bassiana BEdy1 LC25 was significantly prolonged, and the average fecundity of F1 females was significantly lower than that of the control; similarly, the effect of entomopathogenic fungus on N. lugens, Aedes albopictus (Skuse) (Diptera: Culicidae), Brevicoryne brassicae (L.) (Hemiptera: Aphididae), Bactrocera zonata (Saunders) (Diptera: Tephritidae) and Bactrocera dorsalisi (Hendel) (Diptera: Tephritidae) was found to be that the nymphal stage was prolonged and fecundity was reduced compared with those of the control [Metarhizium anisopliae (Metschn.) Sorokīn  nor B. bassiana had significant sublethal effects on the larval growth and oviposition of Cyclocephala lurida (Bland) (Coleoptera: Scarabaeidae) [Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) treated with B. bassiana was significantly decreased as compared to the control [B. bassiana strains and host species. In addition, some studies have shown that entomogenous fungi can deter pests from feeding, resisting immune defense and using host nutrients [S. furcifera.According to our results, when WBPH nymphs were treated with a sublethal dose of  results , the lon control ,39,40,41baeidae) . Contrar control , some poutrients ,45,46, tr, λ, R0 and T of the F1 generation changed significantly, and the r, λ and R0 of the LC25 treatment group were significantly shorter than those of the control group. Similarly, the r, λ and R0 were shorter than the control but T was not changed significantly after Bactericera cockerelli (Sulc) (Hemiptera: Triozidae) were treated with sub-lethal doses of B. bassiana [T of the LC25 treatment was significantly longer than that of the control; similarly, B. bassiana had this effect on Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) and Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) [B. bassiana LC25 may have a long-term influence on S. furcifera physiology and an inhibitory effect on the population growth of WBPH.The assessment of life table parameters is essential for determining the overall sublethal effects of entomogenous fungi on insect survival, developmental time, and reproduction. Through data analysis of life table parameters, the bassiana . Our resripidae) ,49. Our xjs and xl) can reflect the population growth of insects after fungal treatment, which is an important reference for judging the adaptability of insect populations to pathogenic fungi [B. bassiana, which showed that the age-stage survival rate (xjs) of each age stage was lower than that of the control, and the age-specific survival rate (xl) of the population showed a linear downward trend [xjs of male adults of the LC25 treatment group was always higher than the xjs of female adults, which was unfavorable to the development of the population, and the xl of the treatment group also decreased faster than the control, indicating that the population development of the offspring was inhibited. According to xjv and xje, the reproductive values of female adults in the B. bassiana treatment group decreased, and the life expectancy was lower than that of the control, which was consistent with the results of A. albopictus and F. occidentalis [S. furcifera had poor adaptability to B. bassiana at LC25 concentration.In addition, the survival rate (ic fungi . The poprd trend . Additiodentalis ,49, whicB. bassiana BEdy1 on S. furcifera and this study has shown that sublethal dose B. bassiana BEdy1 can affect the host growth, development and reproduction, as well as inhibiting the population growth, of WBPHs, and the results justified the significance of assessing the sublethal effects of B. bassiana on S. furcifera populations in the field. These observations also have important implications for the long-term management of S. furcifera. However, a limitation exists in our study: as with other studies on the sublethal effects of the WBPH [B. bassiana on insects is the result of multiple factors, such as mechanical damage resulting from tissue destruction, depletion of nutrient resources and toxicosis [B. bassiana and S. furcifera; an in-depth study of these possible theories will be of some help in improving the IPM of rice.The purpose of the current study was to determine the sublethal effects of the WBPH ,26,27,28the WBPH ,53,54. Ioxicosis , and fur


Purpose: Etomidate is widely used in general anesthesia and sedation, and significant individual differences are observed during anesthesia induction. This study aimed to explore the molecular mechanisms of different etomidate susceptibility at the genetic level.Methods: 128 patients were enrolled in the study. The bispectral index (BIS), mean arterial pressure (MAP) and heart rate (HR) were recorded when the patients entered the operating room for 5 min, before the administration of etomidate, 30 s, 60 s, 90 s, 120 s and 150 s after the administration of etomidate, and the corresponding single nucleotide polymorphisms (SNPs) were analyzed.Results: Significant individual differences were observed in etomidate anesthesia. The results of two-way ANOVA showed that CYP2C9 rs1559, GABRB2 rs2561, GABRA2 rs279858, GABRA2 rs279863 were associated with the BIS value during etomidate anesthesia; UGT1A9 rs11692021 was associated with the Extended Observer’s Assessment of Alertness and Sedation (EOAA/S) score during etomidate anesthesia; GABRB2 rs2561 was associated with MAP. Multiple linear stepwise regression model results showed that CYP2C9 rs1559, GABRA2 rs279858 and GABRB2 rs2561 were associated with the BIS value and UGT1A9 rs11692021 was associated with the EOAA/S score; GABRB2 rs2561 was associated with MAP.Conclusion: GABRA2 rs279858, GABRB2 rs2561, CYP2C9 rs1559 and UGT1A9 rs11692021 are the SNPs with individual differences during etomidate anesthesia. This is the first to study the SNPs of etomidate, which can provide certain evidence for the future use of etomidate anesthesia and theoretical basis for precision anesthesia. Etomidate is widely used in general anesthesia and sedation, especially in patients with cardiovascular disease, because it does not inhibit sympathetic tone or myocardial function  and has It is found that different patients have different sensitivity to etomidate. Keita et al. found that factors such as age could change the sensitivity of patients to etomidate . Howeverin vivo mediated by α2B receptors (Gamma-aminobutyric acid type A (GABAA) receptors have been confirmed to be the target of etomidate . Etomidaeceptors ; They aleceptors . In addieceptors , but it This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology . All patients signed informed consent. A total of 128 participants undergoing elective ear nose and throat (ENT) surgery with general anesthesia were recruited from december 2019 to november 2020 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. All participants denied blood ties. The inclusion criteria were as follows: 1) patients undergoing elective ENT with general anesthesia; 2) age between 20-55 years old; 3) no history of surgery; 4) no history of drug use and addiction, such as opioids, opium, heroin, marijuana, Meth, ecstasy and K powder, etc; 5) no hypertension, coronary heart disease, diabetes and other medical history; 6) ASA I or II. Exclusion criteria: 1) History of allergy or drug dependence; 2) Pregnancy or breastfeeding; 3) Abnormal liver and kidney function; 4) History of hypertension, diabetes, coronary heart disease and other cardiovascular diseases; 5) Patients with any neurological or psychological disease; 6) Other diseases that may affect the test results, for example, patients with adrenal insufficiency. The preoperative visits were all conducted by the same anesthesiologist.The patients were not given premedication before surgery. After the patients entered the operating room, the non-invasive blood pressure, electrocardiogram, bispectral index (BIS) and blood oxygen saturation of the patient were routinely monitored, and the Extended Observer’s Assessment of Alertness and Sedation (EOAA/S), mean arterial pressure (MAP), heart rate (HR) and BIS values were recorded for 5 min after the patient entered the room (T1), before the administration of etomidate (T2), 30 s (T3), 60 s (T4), 90 s (T5), 120 s (T6) and 150 s (T7) after the etomidate administration. The regular dose of etomidate takes 15–20 s to take effect, the effect reaches its peak in about 1 min, and the duration of action is about 2–3 min . In addiFour milliliter venous blood was collected from each patient 10 min prior to induction of anesthesia. Samples were stored at -80°C and subsequently extracted using the TIANamp Genomic DNA kit. The Snap shot technology system was used to determine genotypes based on detection by MALDI-TOF MS .p < 0.05 was considered as deviation from equilibrium. To further evaluate the independent influence of these clinical factors , multiple stepwise linear regression analysis was applied, with p < 0.05 indicating statistical significance. Two-tailed p < 0.05 was used in the statistical analysis.All statistical analyses were performed by SPSS 27.0 software . Categorical variables were described with percentages, and continuous variables were presented with mean ± standard deviation (SD). Patients were divided into two groups, homozygous for the major allele, heterozygous for the major allele and homozygous for the minor allele . Differen = 20); 2) severe muscle fibrillation led to trial termination (n = 1); 3) HR was too fast after etomidate administration (n = 1); 4) propofol was added to patients who developed irritability after etomidate administration (n = 2); 5) endotracheal intubation was performed immediately after the upper airway was obstructed (n = 1); 6) HR was less than 50 bpm after the etomidate administration, then atropine was given to increase the HR (n = 1). Finally, a total of 102 patients  were collected and genotyped. The age (years) and BMI (kg/m2) of the participants were 37.60 ± 8.62 and 23.88 ± 3.30 respectively. The experimental flow chart was shown in Ultimately, 128 patients were enrolled in the study. 26 patients were excluded due to the following reasons: 1) blood samples or clinical data were not completely recorded , 4.7% ± 13.4% (p = 0.0005), 2.1% ± 12.9% and 0.9% ± 11%, respectively; MAP was 91.84 ± 11.28 mmHg when the patients were quiet for 5 min after entering the operating room, and MAP was 75.87 ± 13.72 mmHg before etomidate anesthesia. MAP at 30 s, 60 s, 90 s, 120 s and 150s were 92.25 ± 11.40 mmHg, 91.70 ± 11.88 mmHg, 91.03 ± 11.65 mmHg, 91.96 ± 11.88 mmHg, and 92.80 ± 11.74 mmHg, respectively. Compared with the basal MAP, the MAP change rate at 30 s, 60 s, 90 s, 120 s, and 150 s were 0.5% ± 2.9%, -0.1% ± 5.0%, -0.8% ± 5.9%, 0.3% ± 7.2% and 1.2% ± 7.1%, respectively . The remaining 40 SNPs had genetic variation in patients and were in compliance with the HWE equilibrium .The sedation depth induced by etomidate was assessed using the BIS and EOAA/S scores. According to the SNP genotyping results, the patients were divided into two groups: 1) homozygous for major allele; 2) heterozygote for major allele and homozygous for minor allele. For BIS, 4 SNPs  showed significant differences at different time points; for EOAA/S score, only one SNP (UGT1A9 rs11692021) had a statistically significant difference .In order to study the effects of multiple factors  and corresponding SNPs on BIS, a multiple linear stepwise regression model was used to perform regression analysis on these factors. The results showed that CYP2C9 rs1559 and GABRA2 rs279858 had statistical significance at T5 (120 s) after intravenous etomidate; GABRB2 rs2561 had statistical significance at T6 (120 s); GABRB2 rs2561 had statistical significance at T7 (150 s). However, there was no significant difference in age, gender and BMI at any time pointe .In order to study the effects of multiple factors  and the corresponding SNPs on EOAA/S scores, a multiple linear stepwise regression model was used to perform regression analysis on these factors. The results showed that gender differences were statistically significant at T3 (30 s); The UGT1A9 rs11692021 was statistically significant at T4 (60 s); Gender and BMI were statistically significant at T5 (90 s); BMI was statistically significant at T6 (120 s) and T7 (150 s) .MAP was used as one of the hemodynamic indexes. According to the SNP genotyping results, the patients were divided into two groups: 1) homozygous for major allele; 2) heterozygote for major allele and homozygous for minor allele. Only one SNP (GABRB2 rs2561) was significantly different in MAP .In order to study the effects of multiple factors  and the corresponding SNPs on MAP, a multiple linear stepwise regression model was used to perform regression analysis on these factors. The results showed that age and GABRB2 rs2561 were statistically significant at T3 (30s), T4 (60s) and T5 (90s); Age, GABRB2 rs2561 and BMI were statistically significant at T6 (120s) and T7 (150s) .In the present study, we found that there were obvious individual differences during the etomidate anesthesia. According to the target of etomidate and its metabolic mechanisms, 48 possible SNPs were screened in this experiment. Among them, CYP2C9 rs1559, GABRA2 rs279858 and GABRB2 rs2561 were associated with BIS values during etomidate anesthesia; UGT1A9 rs11692021 was associated with MOAA/S score; In addition, GABRB2 rs2561 were associated with MAP.Previous studies have confirmed that etomidate mainly acts on GABAA receptors . A type To date, there is no literature on the correlation between etomidate sensitivity and SNPs. However, some studies have reported the relationship between propofol and SNPs, while propofol and etomidate have similar mechanisms of action. Zeng et al. found that GABRB2 rs3816596 and GABRA1 rs4263535 polymorphisms were associated with susceptibility to propofol sedation. ABRA1 rs1157122 and GABRB2 rs76774144 polymorphisms were associated with the degree of blood pressure drop after propofol infusion . A previCYP2C9 and UGT1A9 are the major metabolic genes for many drugs, including anesthetics. Propofol is primarily metabolized by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 are involved in the later steps of propofol metabolism . A previThe sample size of this study is relatively small. We will further expand the sample size in the follow-up study to enhance the statistical power of the relevant SNP to verify the results of this study. Besides, the genes we selected are only based on the currently known polymorphisms, and many genes that have not yet been discovered due to genetic polymorphisms may have an effect on the effect of etomidate. Moreover, in this study, two-way ANOVA and multiple linear regression models were used to jointly verify the differential SNPs. However, results presented were not adjusted for multiple comparisons. When we adjusted for multiple comparisons, these associations were no longer statistically significant. The reason for this result may be related to the size of the sample. Therefore, we will increase the sample size for further verification in subsequent experiments. However, the current findings still have great inspiration, prompting us to carry out further research.In summary, our study suggested that significant individual differences were observed in etomidate induced anesthesia. GABRA2 rs279858, GABRB2 rs2561, CYP2C9 rs1559 and UGT1A9 rs11692021 are the SNPs with individual differences during etomidate anesthesia. This is the first to study the SNPs of etomidate, which can provide certain evidence for the future use of etomidate anesthesia.


Overall, 466 million people worldwide are estimated to be living with hearing loss. Most sensorineural hearing loss is caused by degeneration and loss of hair cells in the cochlea of the inner ear. Hair cells are specialized mechanoreceptors which transduce mechanical forces transmitted by sound to electrical activities  If hearing capacity of an individual has been deprived entirely since birth, how will this affect cognitive function? (2) If hearing is only partially deprived, will this still affect cognitive ability? (3) Will restoring hearing by wearing hearing aids or cochlear implants (CIs) also improve cognitive capacity? And (4) What is the neural basis underlying cognitive deficits caused by hearing impairment? In this Research Topic, 17 studies were accepted to address the questions above, at least partially. Thus, this Research Topic could provide new insights of the link between hearing loss and cognitive disorders and offer new evidence that supports the hypothesis that reduced sound input leads to impaired cognitive ability.Gao Q. et al. reviewed the literature on the developmental factors affecting speech perception of Mandarin-speaking children with CIs. The paper suggests that, compared with continuous improvements in speech perception in bilateral CI recipients, the outcome of speech perception in children with unilateral CIs is still not clear and requires more attention on their cognitive development. In this Research Topic, the study has investigated the mechanisms underlying visual-induced auditory interaction in pre-lingually deaf children . Mirror mechanism can be considered as an activation of the mirror neuron which refers to a combined process of perception and execution. Their study examined the reliability of the visual-auditory interaction in pre-lingually deaf children with CIs and demonstrated that the CI-induced activation of mirror neurons could explain deficiencies in the classical cross-modal interaction.CIs are one of the most exciting auditory technological advancements which has brought great benefits to people with profound hearing loss. It remains unclear whether a CI can bring a significant change in cognition after hearing restoration. Several papers in this section focused on CI and cognition. Wang Y. et al. shows that the cortical responses elicited by vocal emotional stimulation on the left pre-motor and supplementary motor area, the right middle temporal gyrus, and the right superior temporal gyrus are significantly different between preoperative and postoperative tests. Tian et al. reported that altered neural processing was associated with vocal emotional stimulation after CIs in a different study. Functional near-infrared spectroscopy imaging was used to investigate the cerebral representation of different sound sources. This study shows that the oxyhemoglobin response displays a different pattern of neural activities between the lateral and front sources in the auditory cortex and dorsolateral prefrontal cortex. Although CIs can restore and improve audibility in deaf children, it is not clear if children with CIs have impaired auditory sensory gating. Chen et al. carried out an investigation and showed that auditory sensory gating can develop during the early phase in children with CIs, however, long-term auditory deprivation may have a negative effect on sensory gating and attentional performance. Wang Q. et al. conducted a prospective cohort study on normal-hearing young adults who experienced measurable high-intensity noise exposure during a 1-day outdoor music festival. They show that the wave I amplitude of the auditory brainstem response decreases significantly after noise exposure. Their study provides evidence that cochlear synaptopathy may impair speech perception under a noise background.Functional near-infrared spectroscopy imaging was used to assess the changes in neural activity in different brain regions after a CI. The study conducted by Fu et al. conducted a study on the relationship between hearing loss and cognitive impairment in the elderly Chinese population. The study indicates that untreated age-related hearing loss (ARHL) can influence participants' performance during cognitive assessments. Xu et al. assessed the association of hearing acuity and cognitive function among a low-income elderly population in rural China. A total of 737 residents aged over 60 years were enrolled in this cross-sectional study. The study showed that hearing is associated with cognitive decline among older individuals. Another study by Diao et al. reported the correlation between hearing loss and cognitive decline in the elderly population. Gao J. et al. examined if middle ear surgery can affect cognitive ability and quality of life in patients with ARHL and chronic otitis media (COM). Interestingly, both the cognitive capacity and quality of life are improved after middle ear surgery. Guo P. et al. performed an functional MRI (fMRI) study on 45 children with congenital sensorineural hearing loss (CSNHL) to study the alteration of regional homogeneity. They found that children with CSNHL display regional homogeneity (ReHo) alterations in the auditory, visual, motor, and other related brain regions, suggesting a strong relationship between ReHo values and age involved in informatic integration and processing.Liu et al. investigated how binaural cues of the primary auditory cortex are developed and affected by early reversible unilateral conductive hearing loss. They show that (1) the monaural response type, the binaural interaction type, and the distributions of the best interaural level differences (ILDs) in the auditory cortex display adult-like patterns shortly after hearing onset; (2) the developmental refinement of binaural processing can be disrupted by unilateral conductive hearing loss even in adulthood. These findings reveal the neuronal mechanism of the developmental refinements and plasticity in the perception of sound spatial location. To investigate the mechanism underlying ARHL and cognitive dysfunction, Deng et al. used the hippocampal transcriptome to study the correlations between impaired glutamatergic synapse pathway and ARHL. Their study shows that an impaired hippocampal glutamatergic synapse pathway is correlated with ARHL and cognitive dysfunction, and glutamine synthetase can serve as a crucial regulator in this process.Animal models are a crucial tool to examine the mechanisms underlying cognitive disorders caused by hearing loss. This Research Topic also includes a number of papers that explored the connection of hearing loss with cognitive disorders using animal models. Li et al. examined time-dependent dynamic alterations in microglial activation and hippocampal neurogenesis after C57BL/6J mice were exposed to a single dose of broadband noise at 123 dB SPL. They show that the stress response and hearing loss may contribute to the alterations of microglia and hippocampal neurogenesis. In a different study, Guo R. et al. examined social memory in mice after complete elimination of peripheral auditory input before onset of hearing. They used a mouse model with complete hearing deprivation by deleting Otof . Their study reported a significant impaired social memory in the Otof knockout mice, suggesting that hearing is required for the formation of social memory. The illustration below shows the work of their study .The serotonin transporter (SERT) greatly affects the activity of serotonergic neurons in the central nervous system. In this Research Topic, a et al.  performevia hearing aids and CIs could improve cognitive ability. In addition, we would also like to see more exciting basic science studies to elucidate the neuronal circuits that are responsible for cognitive disorders.In summary, the 17 studies published in this Research Topic provide evidence on the connection between hearing loss and cognitive disorders. We are looking forward to seeing more evidence from prospective large-sample clinical trials on this topic, especially on the studies to test if hearing restoration KL and WS contributed to the literature review and manuscript drafting. DH contributed to writing and revising the manuscript. XZ, SB, and SG wrote sections of the manuscript. All the authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China , as well as the NIH grant R01 DC016807 from the NIDCD.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Enlarged Vestibular Aqueduct Syndrome is characterized by a widening of the vestibular aqueduct, associated with sensorineural hearing loss, or sometimes with mixed hearing loss, which may be congenital or acquired during childhood. The sensorineural hearing loss may be classified into mild, moderate and severe, associated with sudden periods of improvement or aggravation. The enlargement of the vestibular aqueduct is the most common inner ear anomaly. This syndrome is admitted as a result of a genetic abnormality of the vestibular aqueduct development, previous to the fifth week of gestation. The incidence of this syndrome ranges from 1% to 1.3%, with the possibility of getting up to 7%, depending on the examined population. The aim of this study was to analyze three cases of LVAS seen at the Otorhinolaryngology and Radiology Department of Sao Camilo Hospital - Sao Paulo. Two of these three cases were of brothers, from the same mother but from different fathers. Two were male and one was female and the ages ranged from 9 to 30 years old. The diagnostic method of election was CT - Computerized Tomography of the temporal bones. The recommended management of the cases was conservative, except for those of cranial trauma, barotrauma and, if necessary, the use of hearing aids. Large Vestibular Aqueduct (LVA) is known as the most common form of inner ear anomaly and it may be radiologically diagnosed using temporal bone computed tomography (CT scan) and inner ear Magnetic Resonance Imaging (MRI). Non-syndromic sensorineural hearing loss (NSSHL) associated with LVA has been a source of interest because it is associated with future clinical characteristics, including hearing fluctuation, many cases of progressive sensorineural hearing loss, sometimes mixed loss, which normally starts in childhood and may also be associated with vestibular symptoms. Large Vestibular Aqueduct Syndrome (LVAS) was described for the first time by Valvassori and ClemisIn children, differential diagnosis of sensorineural loss should be made with congenital infectious diseases  or acquired diseases . Differential diagnosis should also be made with HIV infection because it is a neurotrophic virus. Moreover, other causes should be investigated, such as ototoxicity, autoimmune diseases, traumatic, vascular and hereditary diseases. Even after investigating such factors, the etiology may remain unknown. Bento et al.T.R.M.P, female, 30 years of age, born and living in Osasco–SP, with history of intermittent rotation dizziness and tinnitus for 6 months. She was medicated with Gingko Biloba (80 mg BID) and ordered vectoelectronystagmography with diagnosis of Irritative Peripheral Vestibular Syndrome. She presented tinnitus, disabling dizziness and retromastoid pain on the left. She also reported progressive hearing loss of fluctuating characteristics since childhood , of undefined cause, using a hearing aid on the left since the age of 8 years. In her clinical history she presented fetal distress at birth and language development delay in childhood. ENT examination revealed at otoscopy tympanic membrane opacity and no other findings. We ordered temporal bone CT scan, pure tone audiometry and vocal discrimination, immittanciometry, ABR, head self-rotation, complete blood test, fast glucose, serological tests for syphilis, toxoplasmosis, cytomegalovirus, rubella and measles; autoimmune disease factors .Pure tone audiometry and vocal discrimination showed moderate to severe mixed loss in speech frequencies and profound loss in high frequencies on the right and mild sensorineural loss in speech frequencies and severe loss in high frequencies on the left . BrainstR.R.R.S.G, male, 9 years, born and living in Sao Paulo, with history of progressive and fluctuating bilateral hearing loss since the age of 2 years, especially on the right, without apparent cause. According to the mother, the child spoke too loud and needed the TV volume always up. He did not report otalgia or otorrhea. The patient reported episodes of constant tinnitus, such as a whistle, especially on the left. Did not report dizziness. Uses bilateral hearing aids since the age of 7 years. He presented history of deafness in the family . He is the only child of the mother's second marriage. Gestation and delivery were uneventful. The physical examination presented normal otoscopy and oroscopy, and rhinoscopy showed pale and hypertrophic lower conchae. Audiometry showed moderate to severe mixed loss on the right and moderate loss on the left . TemporaB.R.G, female, 16 years, born and living in Sao Paulo. The mother reported that 10 years before she detected hearing loss on the left when she realized the daughter did not respond to sounds coming from sources on the left side. She looked for an ENT doctor, who asked for audiometry and confirmed severe hearing loss on the left without any apparent defined cause. For the past 4 years she has had constant mild rotation dizziness, with no other associated symptoms. She has not worn hearing aids. History of deafness in the family . Uneventful gestation and birth. As to common childhood diseases, she reported varicella at the age of 2 years. ENT examination was normal. Pure tone audiometry presented severe mixed hearing loss on the left . TemporaThe main symptoms of the patient are summed up in Vestibular aqueduct (VA) is a bony canal that communicates the posterior-medial portion of the epidural space vestibule with the medium posterior fossa Whereas the other portions of the ear have been developed since birth, vestibular aqueduct and endolymphatic sac are immature and small. As the posterior cranial fossa is expanded, VA and endolymphatic sac quickly increase in size and reach maturity at about the age of 4 yearsUsing graphic reconstruction techniques, Kodama and SandoVA is considered normal when it does not exceed the diameter of the adjacent semicircular canal or when it is inferior to 1.5mm.LVAS is characterized by enlargement associated with, which may also be mixed, with no defined cause. One of the many hypotheses considered are affection to homeostasis in endolymphatic circulation as a result of ductal enlargement, with consequent damage to cochlear neuroepithelium-GRADE I: lumen of the aqueduct is only visualized in the temporal bone cortex.-GRADE II: lumen of the aqueduct is visible close to common crura.-GRADE III: lumen of the aqueduct is larger than the common crura, but it is not visible in the topography of the vestibule output.-GRADE IV: the internal portion of the aqueduct is visible and its diameter in the output topography is smaller or equal to the common crura.-GRADE V: the internal portion of the aqueduct is visible and the diameter of the output topography is larger than the diameter of the common crura.Antonelli classified VA enlargement into 5 grades. This measure is made from the intermediate point between the external opening and the common crura region.Initially we thought that the hearing loss would remain unaltered during the whole life. Later, it was noticed that the hearing loss could fluctuate or deteriorate progressivelyChildren with LVAS may have moderate or severe hearing loss in childhood, but residual hearing allows the child to get adapted to some situations, such as for example, to go to school and to develop spoken language with the use of conventional hearing aidsRecently, much attention has been given to the hereditary nature of this syndrome. Griffth et al.A reported possibility is that the gene of sensorineural hearing loss is located at the same gene of Pendred syndrome. The most widely accepted hypothesis is that a gene mutation would cause NSSHL in patients with LVAS, which makes us believe that different mutations to the Pendred gene would cause different phenotypes and also non-syndromic sensorineural hearing loss associated with LVA and Pendred syndrome. According to Urman and TalbotClinical picture of LVAS is variable, normally its onset is at childhood and there is moderate to severe fluctuating or progressive loss; sometimes, it may also be sudden. Vertigo may be present and it is more common than it is believed.There is no audiometric curve that characterizes or indicates the hypothesis of LVAS, reason why we should be attentive in cases of mixed loss and NSSHL in childhood. Abe et al.Current studies In our case reports, patients 2 and 3 were brothers by mother, with respective ages of 9 and 16 years with hearing loss since childhood, and they also presented family history of deafness . In cases 1 and 2, patients presented mixed or sensorineural loss since childhood, and tinnitus in the affected ears since childhood, which spoke in favor of LVAS and CT scan showing large vestibular aqueduct . In the As to LVA management, many treatment options have been described. Jackler and De La CruzIn the reported cases, treatment has been conservative: to prevent head trauma, barotrauma and radical sports to try to reduce the risk of hearing loss by trauma. Patients 1 and 2 had used hearing aids respectively for 22 and 2 years with hearing improvement. Patient 3 did not use hearing aid because he reported he could hear well and did not need hearing aids. Patient 1 is not taking anti-vertigo medication, because he has been following a diet after the detection of hypoglycemia, which may be a possible cause of dizziness. Relatives of cases 2 and 3 are currently being studied because there were hearing losses to be defined.As to cochlear implant, recent studies have confirmed that it serves to maintain sufficient hearing to integrate the children in regular schoolsHowever, there are no comparative studies showing hearing gain in LVAS implanted patients after the age of 9 years, which made us maintain our conservative management approach with these patients.LVAS is a clinical entity that should be part of the differential diagnosis of sensorineural hearing loss, progressive mixed loss genetic syndromes in children. Early diagnosis is essential because it allows more favorable rehabilitation treatment such as cochlear implant, which has shown favorable results when the diagnosis of LVAS is made at an early age.


Severe and profound idiopathic sudden sensorineural hearing loss (ISSNHL) generally leads to unfavorable prognosis, and has a considerable impact on patient quality of life. However, related prognostic factors remain controversial.To elaborate the relationship between vestibular function impairment and the prognosis of patients with severe and profound ISSNHL, and investigated the relevant factors affecting prognosis.Forty-nine patients with severe and profound ISSNHL were divided into good outcome group  and poor outcome group  according to hearing outcomes. The clinical characteristics and the proportion of abnormal vestibular function tests in these two groups were analyzed by univariate analysis, and multivariable logistic regression analysis was performed for parameters with significant differences.Forty-six patients had abnormal vestibular function test results . The number of vestibular organ injuries was 1.82 ± 1.29 in all patients, with higher mean numbers in PO group (2.22 ± 1.37) than in GO group (1.32 ± 0.99). Univariate analysis revealed no statistical differences between the GO and PO groups in terms of gender, age, side of the affected ear, vestibular symptoms, delayed treatment, instantaneous gain value of horizontal semicircular canal, regression gain value of vertical semicircular canal, abnormal rates of oVEMP, cVEMP, caloric test and vHIT in anterior and horizontal semicircular canal, however, significant differences were found in the initial hearing loss and abnormal vHIT of posterior semicircular canal (PSC). Multivariable analysis revealed that only PSC injury was an independent risk factor for predicting the prognosis of patients with severe and profound ISSNHL. Patients with abnormal PSC function had worse initial hearing impairment and prognosis than patients with normal PSC function. The sensitivity of abnormal PSC function in predicting poor prognosis in patients with severe and profound ISSNHL was 66.67%, specificity was 95.45%, and positive and negative likelihood ratios were 14.65 and 0.35, respectively.Abnormal PSC function is an independent risk factor for poor prognosis in patients with severe and profound ISSNHL. Ischemia in the branches of the internal auditory artery supplying the cochlea and PSC may be the underlying mechanism. Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined as an otologic emergency in which three or more consecutive frequency hearing thresholds rise suddenly by 30 dB or more within 72 h, accompanied by tinnitus and concurrent or delayed vestibular symptoms in some patients . PreviouThere is no consensus on the prognostic factors of ISSNHL and various factors have been identified including the degree of initial hearing loss, age at onset, presence of vestibular symptoms, classification of hearing loss, and time of intervention –9. RecenA retrospective study was performed on patients with ISSNHL who were hospitalized at the Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between September 2020 and September 2022. This study was approved by the Institutional Ethics Committee of Xinhua Hospital, Shanghai Jiao Tong University (NM: XHEC-D-2022-259), and all patients provided consent for their data to be used for this research.The following inclusion criteria applied: patients with unilateral ISSNHL, PTA  ≥ 65 dB in the affected ear, and normal hearing in the opposite ear; intact tympanic and Type A tympanogram in both ears; complete patient medical record data and records of pure tone audiometry (performed on the first day of admission and the day before discharge), ocular vestibular-evoked myogenic potential test (oVEMP), cervical vestibular-evoked myogenic potential test (cVEMP), caloric test, and video head impulse test (vHIT). Exclusion criteria were as follows: a history of genetic disorders associated with familial deafness; sensorineural hearing loss secondary to noise exposure or ototoxic drugs; space-occupying lesions of the internal auditory canal, central organic pathology, and external and middle ear disease; a malignant tumor; inability to complete the course of treatment or audiology-vestibular function test due to liver or kidney disease or other reasons.A total of 49 patients were included in this study. All enrolled patients underwent an audiology-vestibular function test on the first day of admission, and hearing was retested the day before discharge after one course of treatment. The treatment protocol was as follows: (i) daily intravenous dexamethasone 10 mg, (ii) daily intratympanic injection of dexamethasone (5 mg), and (iii) daily hyperbaric oxygen therapy. The completion of 10 days of treatment was considered completion of the course of treatment.Pure tone audiometry was performed using the MADSEN Astera clinical diagnostic audiometry system . The binaural PTA was taken as the mean of the four frequencies of 500, 1,000, 2,000, and 4,000 Hz. Severe hearing loss was defined as a pretreatment hearing level between 65 and 80 dB HL, and profound hearing loss was defined as a pretreatment hearing level ≥ 80 dB HL, according to the latest standards of the World Health Organization .An EyeSeeCam head tosser (Interacoustics Company) was used for the testing. The patient wore an eye patch containing a head velocity monitoring sensor and was placed in the sitting position with the head held still and the eyes focused on a fixed point (target point) 1.5 m in front of them. The examiner stood behind the patient and calibrated the target point before examining the horizontal and vertical semicircular canals in the conjugate plane of each of the three pairs of semicircular canals following the standard vHIT technique. The EyeSeeCamTM software objectively recorded the 60 ms instantaneous gain value of the horizontal semicircular canal, regression gain value of the vertical semicircular canal, asymmetry ratio of the three pairs of conjugate semicircular canals, and refixation saccades from the beginning to the end of the head impulse. Any one of the following conditions was considered abnormal: (i) an instantaneous gain value of the horizontal semicircular canal <0.8 and a regression gain value of the vertical semicircular canal <0.7; and (ii) 10 or more refixation saccades with a peak angular velocity >100°/s in 20 head impulses .The patient was placed in the supine position, with the head in forward flexion at 30° to ensure that the horizontal semicircular canal was perpendicular to the floor. Cold air (24°C) and hot air (50°C) were instilled into the patient's ears separately for 60 s each time. The patient's electronystagmogram was recorded for 1 min after instillation, with the interval between instillations being 5 min after the disappearance of the previous nystagmus. The average slow-phase velocity (SPV) during the strongest period of temperature-induced nystagmus was recorded, and canal paresis (CP) was calculated using the Jongkees formula, which reflects the asymmetry of the horizontal semicircular canal bilaterally. A CP value >25% was considered abnormal and indicated a relative reduction in ipsilateral horizontal semicircular canal function. The dominant preponderance ratio (DP) was calculated to determine the lateral preponderance of nystagmus, and a DP value >30% was considered abnormal.The Biologic Navigator Pro Auditory Evoked Potential  was used to perform the test. The reference electrode was placed between the clavicular joints, the ground electrode was placed between the two eyebrows of the forehead, and the left and right test electrodes were placed in the middle of the sternocleidomastoid muscle on the left and right sides, respectively, with an electrode impedance of ≤ 5 kΩ. The stimulation signal was 500 Hz, with 90 dB nHL short tone bursts, 1 ms rise/fall time, 2 ms duration at peak, 5 Hz stimulation rate, and 50 superimposed times. The stimulation sound was delivered using air conduction insert earphones to elicit a VEMP response. The patient was instructed to lift the head off the pillow after hearing the unilateral stimulation sound and to elevate the head 30° in the supine position to keep the sternocleidomastoid muscle tense until the stimulation sound stopped, before returning to the original lying position.The equipment and relevant parameters used for the testing were the same as those described above. The reference electrode was placed on the lower jaw, ground electrode was placed between the two eyebrows on the forehead, and test electrode was placed 1 cm below the central part of the contralateral eyelid. The patient was instructed to gaze upward after hearing the unilateral stimulation sound, keeping the eye position at 25–30° and blinking as little as possible to maintain the lower oblique muscle tone until the stimulation sound stopped.The interwave amplitude of P1-N1 was recorded as the vertical distance between the apex of the N1 and P1 waves. The amplitude asymmetry ratio (AR) was calculated as the ratio of the absolute value of the difference between the amplitudes of the two sides to the sum of the wave amplitudes of the two sides. Abnormal VEMP was defined as a waveform not elicited or an AR of >29% .According to the Chinese Medical Association of Otolaryngology criteria, the return of the hearing threshold of the damaged frequencies to normal, healthy ear, or pre-disease levels was considered complete recovery; partial recovery was defined as hearing improvement > 30 dB HL; slight recovery was defined as hearing improvement between 15 and 30 dB HL, and no recovery was defined as hearing improvement of <15 dB HL  and the poor outcome group .t-test was used for data that was normally distributed, and the rank sum test was used for data that was not normally distributed. The differences between groups were analyzed using univariable logistic regression analysis, and those parameters with significant differences were analyzed using multivariable logistic regression analysis. Differences were considered statistically significant at P < 0.05.SPSS software (version 26.0) was used to analyze the data. Measurement data were expressed as mean ± standard deviation (M ± SD), and count data were expressed as percentages. The Shapiro-Wilks test was performed to test the normal distribution of the measurement data, the independent This study enrolled 49 patients  were enrolled in this study, with 17 right ears and 32 left ears. Twenty-six patients had vestibular symptoms at the time of the consultation . The mean timeframe between the onset of symptoms and treatment was 5.94 ± 4.64 (1–21 days). Severe hearing loss was observed in 14 ears and profound hearing loss was observed in 35 ears. The mean hearing threshold of the affected ear was 92.09 ± 18.05 dB HL before treatment and 66.76 ± 33.32 dB HL after treatment. Of the 46 patients who underwent abnormal vestibular function tests , 29 had abnormal oVEMP , 28 had abnormal cVEMP , 25 had abnormal caloric tests , and 23 had abnormal vHIT tests , including 19  with abnormal posterior semicircular canal (PSC) function, 12  with abnormal horizontal semicircular canal function, and one  with abnormal anterior semicircular canal function .There were 22 patients  in the GO group, including 16 left ears and six right ears, of which nine had vestibular symptoms at the time of the consultation. The mean hearing threshold of the affected ear was 85.00 ± 17.47 dB HL before treatment, and 38.18 ± 19.17 dB HL after treatment.There were 27 patients  in PO group, including 16 left ears and 11 right ears, in which 17 patients had vestibular symptoms at the time of the consultation. The mean hearing threshold of the affected ear was 97.87 ± 16.67 dB HL before treatment, and 90.05 ± 22.32 dB HL after treatment. A comparison of clinical data between the two groups is shown in In the vestibular function test results in the GO group, the abnormality rate of oVEMP was the highest , followed by cVEMP , caloric test , horizontal semicircular canal , and PSC . No anterior semicircular canal dysfunction was observed.In the vestibular function examination results in the PO group, the abnormality rate of cVEMP  and PSC  was the highest, followed by the oVEMP , caloric test , horizontal semicircular canal , and anterior semicircular canal . The differences in the vestibular function tests between the two groups are shown in R2 = 0.8597; the linear equation was y = −0.1025x + 0.4925). The specific modes of vestibular organs injuries between GO group and PO group were shown in The number of vestibular organ injuries was 1.82 ± 1.29 in all patients, with higher mean numbers in the PO group (2.22 ± 1.37) than in the GO group (1.32 ± 0.99). The difference in the number of vestibular organ injuries between the two groups is shown in P = 0.016) and abnormal vHIT result in PSC (P = 0.001) between the GO and PO groups; there was no significant difference in gender, age, side of the affected ear, vestibular symptoms, delayed treatment, instantaneous gain value of the horizontal semicircular canal, regression gain value of the vertical semicircular canal, abnormal rates of oVEMP, cVEMP, caloric test, and vHIT in the anterior and horizontal semicircular canals between these two groups. Multivariable logistic regression analysis of the parameters with significant differences showed that the significance of initial hearing loss disappeared, and only PSC injury was an independent risk factor for prognosis . These are listed in Univariable logistic regression analysis of clinical characteristics and vestibular function test revealed that there were significant differences in the initial hearing threshold . The patients/participants provided their written informed consent to participate in this study.JC, MD, and JY contributed to the study design. XM, JS, and QinZ preformed VEMPs, caloric test, and vHIT. YY and DG contributed to statistical analysis and manuscript draft. All authors helped to perform the analysis and to revise the manuscript with constructive discussions. All authors contributed to the article and approved the submitted version.


Objectives: To determine whether temporal bone computed tomography (CT) features are linked to the presence and type of hearing loss in osteogenesis imperfecta (OI) when considering hearing-impaired OI patients and normally hearing (NH) OI ones. A secondary objective was to assess whether other factors influence CT features in a large sample: age, type of mutation, or bone mineral density (BMD). Methods: A total of 41 adults with OI underwent CTs and pure-tone audiometry in 82 ears. Hearing thresholds were normal in 64 out of 82 ears, and most had not been operated on for stapedectomy or stapedotomy. Ossicle density, footplates, oval and round windows, retrofenestral peri- and endolabyrinths, and temporal pneumatization were analyzed twice by an experienced radiologist. CT features were compared to hearing, age, collagen mutations, and bone mineral density. Results: Unexpectedly a high prevalence of footplate, ossicle, and otic capsule anomalies was observed, even in NH ears. Footplate hypodensity or thickening was mostly found in ears without conductive hearing loss. There were significantly more retrofenestral anomalies or window obstruction in ears with a sensorineural hearing loss component than in ears without. Age was significantly higher in ears with middle layer hypodensity than in ears without. Patients with mutations were expected to have reduced collagen quantity and had significantly more footplate or retrofenestral anomalies than those with qualitative mutations. BMD was significantly higher in ears without temporal hyperpneumatization. Conclusion: Temporal bone CT features in OI are present in a large proportion of patients, had they hearing loss or not, and might be determined more by collagen mutation type than by age or BMD. Osteogenesis imperfecta (OI) is a type-1 collagen genetic disease that results in abnormal bone fragility . It is mThe pathology, natural history, and treatment of hearing loss in OI resembles that of otosclerosis (OS). Computed tomography (CT) reveals fenestral, antefenestram, and otic capsule hypodensities ,7,8. HeaHowever, correlation between CT findings and hearing loss is uncertain: Swinnen et al., firstly, comparing hearing and CT scans, observed discrepancies between CT and hearing in 27.8% (17 patients) . In thisThe aims of this study were: (i) to determine whether temporal bone computed tomography (CT) features are linked to the presence and type of hearing loss in osteogenesis imperfecta (OI) when considering hearing-impaired OI patients and normally hearing (NH) OI ones; (ii) to assess whether other factors influence CT features in a large sample: age, type of mutation, or bone mineral density (BMD).This was a prospective descriptive study conducted at a tertiary referral university hospital.Participants in the present study were selected from among 64 adult OI patients recruited for a clinical trial evaluating the effect of alendronate on BMD . Only 41A typical personal history of bone fragility fractures (fractures in the absence of a car crash or major trauma) before 20 years of age, with at least three fragility fractures.At least one criterion in the following list: blue sclerae, scoliosis (the Cobb method with an angle ≥10° but ≤40°), hearing loss (defined by elevated pure-tone thresholds above 20 dB on at least two octave frequencies or a mean air-bone gap above 10 dB), abnormal laxity of ligaments defined by at least three criteria of Carter and Wilkinson, dentinogenesis imperfecta defined by at least a yellow to brown tooth, and at least one family member with OI. A low BMD of the lumbar spine or hip  measured by dual X-ray densitometry (DXA) with a T score of −2.5 or below at one site.Inclusion criteria to the clinical trial were reported in Chevrel et al. . OI was The exclusion criteria were: evidence of concomitant malignant disease, primary hyperparathyroidism, osteomalacia or other generalized bone diseases or disorders known to influence bone metabolism, renal clearance < 35 mL/mn, pregnancy or lactation, bilateral hip prosthesis, medication using glucocorticoids , anabolic steroid and/or calcitonin taken during the month prior to the study’s onset, estrogen replacement therapy, and bisphosphonates and fluoride salts during the 6 months before starting the study. None of the patients were exposed to sound trauma before the study.Ethical considerations: Informed consent was obtained from all participants. The local Ethics Committee  approved the study.Hearing tests consisted of pure-tone audiometry by air and bone conduction in standard soundproof conditions. Types of hearing loss were defined to make a possible comparison with the study by Swinnen et al. . A normaTB computed tomography was conducted less than 3 months before or after the audiometric evaluation, between 2002 and 2003. All examinations were performed on multislice CT scanners with axial volumetric acquisitions. Axial and coronal reconstructions in lateral semi-circular canal planes were performed at 0.5 to 1 mm thicknesses, with a reconstruction increment of 0.5 mm.All CT images were blindly read twice by an experienced radiologist (ALB), with a 3-month delay between readings. The patients’ hearing, and clinical and genetic features were not known by the radiologist.A middle ear assessment included temporal pneumatization, malleus, incus, and stapes density, and footplate (FP) aspect. The last was considered only in non-operated patients because of remodeling after a stapedectomy. Specific attention was given to footplate hypodensity A–E.Regarding the inner ear, round window obstruction, otic capsule layers  and premeatal  hypodensities, endolabyrinthic extension, and facial nerve canal hypodensity were also carefully evaluated F–O.Mutations of COLIA1 or COLIA2 genes were determined by J. Korkko and D. Prockop from the Tulane Center for Gene Therapy . Stop coBMD of the lumbar spine, total femurs (TOT), and femoral necks (Neck) were measured twice (R1 and R2) at baseline of the clinical trial by dual X-ray absorptiometry with a Hologic device , as mentioned in the protocol . With th2 test. Means were compared using Student’s t-test. Statistical significance was defined as a p value < 0.05.Statistical analysis was performed using IBM SPSS software . Categoric variables were compared between groups with Fisher’s exact XLabyrinthic and perilabyrinthic aspects were analyzed in 82 ears, but middle ear features were considered in only 69 non-operated ears, as their analysis was not reliable in operated ears.The first observation was the large heterogeneity of CT scan anomalies, from limited to extended ones , Table 1Regarding the middle ear, only 69 non-operated ears were considered. Both ossicles and the footplate had a normal aspect in one ear (1%), whereas ossicle hypodensities were observed in 53 ears (77%), FP thickening in 59 ears , and footplate hypodensities in 30 ears (43%), all with associated thickening.This heterogeneity was also seen for labyrinthic and perilabyrinthic bones that were completely normal in 16 out of 82 ears (20%), all non-operated. Middle layer hypodensity was observed in 58 ears (71%); 46 (56%) also had outer layer hypodensity, and 22 (27%) had inner layer hypodensity, thus, three affected layers . PremeatThere was no link between ossicular or fenestral anomalies and retrofenestral abnormality: even if 41 of the 59 ears with fenestral involvement had middle layer hypodensity, 6 ears had a normal footplate, but also had retrofenestral anomalies.p = 0.34), as shown in Hearing features of the sample are presented in No perilabyrinthic anomaly on the CT was found to be pathognomonic of an SNC. Conversely, a normal cochlear function can be observed with extensive perilabyrinthic CT anomalies.p = 0.03; 47% vs. 21%, p = 0.05; 86% vs. 37%, p = 0.001; 87% vs. 36%, p = 0.0001; and 100% vs. 40%, p = 0.003, respectively; bilateral Fisher’s exact tests). All ears with oval window obstruction presented an SNC, and most ears with round window obstruction and/or endolabyrinthic extension had an SNC, except two ears (six patients). The same results were obtained when excluding ears with an SNC possibly due to another etiology .When outer or middle layer hypodensity, endolabyrinthic extension, or round and oval windows obturation were observed, there was significantly more often an SNC than when these CT-scan features were absent  A. The agp = 0.02, and of distributions, p = 0.002; Mann–Whitney test), and those with temporal hyperpneumatization had a lower right femoral neck BMD than those without   B. Other p = 0.05; 41 vs. 11%, p = 0.02; 30 vs. 6%, p = 0.04; and 75 vs. 33%, p = 0.003, respectively; Fisher’s unilateral Khi2 tests), as shown in Finally, regarding mutations, the number of footplate, inner layer, endolabyrinth, and premeatal anomalies was significantly higher in patients with a mutation expected to induce a quantitative decrease in collagen synthesis than in patients with a mutation expected to induce qualitative changes in collagen fibers . Even if some middle ear and otic capsule features were significantly more frequent in ears with hearing loss, they were also observed in many NH ears. No specificity of the stapes footplate (FP) was found in ears with conductive hearing loss, nor of otic capsule anomalies in ears with sensorineural hearing loss.No significant effect of alendronate on OI hearing was evidenced during the follow-up time of the study . HoweverAge, BMD, and mutation type seemed to influence CT features, each in a different way. The progression of CT lesions with age is difficult to determine. The middle layers’ hypodensities were more frequent than those of the outer layers, especially in older patients, and there is a tendency towards the effect of age for FP anomalies. Oval window obstruction occurred only in ears with all three layers and premeatal hypodensities. BMD was mainly linked to hyperpneurmatization. The type of collagen mutations, expected to reduce quantity or affect quality of collagen, was found to be linked to perifacial, inner layer, and premeatal density, and to endolabyrinthic extension.Few publications on the same topic are available to compare our results with. Heterogeneity of TB anomalies and lack of progression from fenestral to retrofenestral features were not reported by Veillon et al. , probablOur results are the first to introduce significant doubt about correlation between hearing and TB histopathology in OI. Probably because OI is a general bone disease, not limited to the TB, histological involvement is different from OS; therefore, it expresses itself differently on imaging. Otic capsule bone metabolism may be different in OI than in OS; maybe bone remodeling affects inner ear microvascularization or ionic endolymphatic balance, and thus, hearing . OI mighTrying to explain the audio-histological discrepancies, we searched for an effect of age on TB CT; however, that has never been studied in the literature before. This study is the first to point out that TB anomalies may be more frequent depending on the type of collagen mutations. Mutation type is not correlated neither with prevalence, nor age of onset, type, or severity of HI, even with variations within families ,21,22,23Regarding BMD, Swinnen et al. found a lower trabecular BMD in OI patients with conductive or mixed hearing loss than in those with normal hearing or pure sensorineural loss, but comparison between TB CT and BMD has never been reported before our study . In our Technical limits, such as the impossibility to analyze oval windows in operated patients and CT heterogeneous quality, may impact our results. As in Swinnen’s study, CTs were made in different centers and with various devices . HoweverOur study of TB CT in adult OI patients shows the absence of clear progression from fenestral to retrofenestral lesions, and the absence of extension from the outer to middle layer. Moreover, CT anomalies are frequent even in normally hearing patients and not linked to a type of hearing loss. The imaging differences between OI and OS may be due to their different physiopathology. Indeed, collagen mutations have a global influence on skeletal bone remodeling. Hearing in OI is affected by other factors than just otic capsule remodeling, whereas an anomaly is limited to the TB in OS.Because progression of TB CT features is highly heterogeneous in OI, CT cannot predict the risk of an SNC, which is, anyway, much higher in OI than in OS. Moreover, CT is not of interest in making a decision about stapes surgery.