FOXF2 is required for cochlear development in humans and mice.

Molecular mechanisms governing the development of the human cochlea remain largely unknown. Through genome sequencing, we identified a homozygous FOXF2 variant c.325A>T (p.I109F) in a child with profound sensorineural hearing loss (SNHL) associated with incomplete partition type I anomaly of the cochlea. This variant is not found in public databases or in over 1000 ethnicity-matched control individuals. I109 is a highly conserved residue in the forkhead box (Fox) domain of FOXF2, a member of the Fox protein family of transcription factors that regulate the expression of genes involved in embryogenic development as well as adult life. Our in vitro studies show that the half-life of mutant FOXF2 is reduced compared to that of wild type. Foxf2 is expressed in the cochlea of developing and adult mice. The mouse knockout of Foxf2 shows shortened and malformed cochleae, in addition to altered shape of hair cells with innervation and planar cell polarity defects. Expressions of Eya1 and Pax3, genes essential for cochlear development, are reduced in the cochleae of Foxf2 knockout mice. We conclude that FOXF2 plays a major role in cochlear development and its dysfunction leads to SNHL and developmental anomalies of the cochlea in humans and mice.

Perception of male otolaryngologists on gender discrimination: a comparative study.

PURPOSE: To gather information on perception of male otolaryngologists (MORLs) about gender discrimination towards female otolaryngologists (FORLs). METHODS: MORLs were invited to participate to an online survey. Minimum participation requirement was completion of at least their first year of residency. The responses were analyzed and compared vis-a-vis with the previously conducted similar survey among FORLs. RESULTS: Statistically significant responses on the Likert scale are classified in four main groups. MORLs and FORLs share the same views about financial factors, benefits and opportunities, housework as burden, establishing work-life balance and physical strength requirements. They have opposing views about FORLs being meticulous, exposed to more negative attitude of the opposite gender and men's dominance in decision-making. FORLs don't have consensus, but MORLs disagree about MORLs being favored in pursuing academic careers. On the other hand, MORLs don't have consensus, but FORLs agree about patients having more confidence in MORLs. CONCLUSION: MORLs don't usually have any confrontation with FORLs in regards to the roles of women in the society such as their motherhood role. On the other hand, MORLs show rather a contradiction on their perception towards the gender discrimination mainly in achieving career goals by FORLs such as growing in the profession and holding managing roles. When the views of the both gender group are compared, MORLs don't seem to fully acknowledge FORLs' gender discrimination experience.

Analysis of cochlear implant revision surgeries.

PURPOSE: This study aimed to evaluate the reasons for cochlear implant (CI) revision surgeries in pediatric and adult groups. METHODS: A total of 490 CIs were used for 423 patients between August 2005 and August 2019. Among these, patients who underwent a CI revision surgery were identified retrospectively. The reasons for CI revision surgeries were classified mainly as medical problems and device failure. These were also determined according to implant brands. RESULTS: Of 423 patients with a CI surgery, 27 (6.3%) underwent a CI revision surgery. The revision implant rate was 4.9% for the pediatric group and 1.4% for the adult group. Five patients underwent a CI revision surgery due to medical problems (23.8%) and 16 due to device failure (76.2%) in the pediatric group, while 3 patients (50.0%) underwent a CI revision surgery due to medical problems and 3 (50.0%) due to device failure in adults. CONCLUSIONS: A CI surgery is safe for patients with severe-to-profound sensorineural hearing loss, although a CI revision surgery has some potential. Device failure is the most common cause in children. It may be due to early implantation, frequent fall when children learn walking, or impaired vestibular function.

Irregular Contour of Inner Ear Structures and Hypomineralized Areas at Otic Capsule: Are They Other Additional Imaging Findings of Incomplete Partition-III?

PURPOSE: Incomplete partition III (IP-III) characterized by congenital mixed or sensorineural hearing loss is a rare genetic disease transmitted through X-linked inheritance. Incomplete partition III can be easily achieved based on pathognomonic computed tomography findings. The aims of this study were to investigate the otic capsule abnormalities in IP-III and to report irregular contour of membranous labyrinth and hypomineralized areas at otic capsule, which have not previously been described. MATERIALS AND METHODS: The otic capsule features of 10 subjects (8 affected patients, 1 of whom is a female; 2 carrier mothers), who were diagnosed on clinical and typical radiologic findings, were analyzed. RESULTS: All patients had typical IP-III as described in the literature. Seven of 10 patients had irregular contour. Seven of 10 patients demonstrated hypomineralized areas, which were very hypodense to normally develop otic capsule areas. One affected patients and 2 carrier mothers had a normal-looking membranous labyrinth contour and normal mineralization at otic capsule. CONCLUSIONS: We report for the first time the irregular contour of inner ear structures and hypodense otic capsule areas in patients with IP-III. We think that though speculative, abnormal development of the inner endosteal layer results in irregular contour of inner ear structures. Hypomineralized areas at otic capsule could be explained by abnormal development of middle enchondral layer due to reduced or absent vascular supply from middle ear mucosa during fetal life. These findings may be accepted as additional criteria of IP-III.

Association Between Incomplete Partition Type III and Abnormal Hypothalamic Morphology: Further Imaging Evidence.

PURPOSE: Incomplete partition III (IP-III), characterized by congenital mixed or sensorineural hearing loss, is a rare genetic disease transmitted through X-linked mode of inheritance. Inner ear findings of IP-III have been well described and allow an immediate diagnosis to be made. Recently, an association between IP-III and distinct hypothalamic malformations has been reported in some of the patients with IP-III. The purpose of this study was to investigate the morphologic abnormalities of the hypothalamus in IP-III. MATERIALS AND METHODS: Magnetic resonance imaging studies of 8 subjects, including 1 set of brothers, who were diagnosed with IP-III based on their clinical and inner ear imaging findings, were analyzed. RESULTS: Of the 8 subjects, 7 demonstrated some degree of morphologic abnormality of the hypothalamus. Of these, 2 showed asymmetrical thickening, 1 showed symmetrical thickening, and 4 showed mass-like enlargement of the hypothalamus. Six of 7 subjects with hypothalamic abnormalities showed asymmetry in caudal extension of the abnormalities, which was more discernible on coronal oblique T2-weighted images. Clinically, none of the subjects had endocrinologic or neurologic symptoms. CONCLUSIONS: This retrospective analysis presents further magnetic resonance imaging evidence on the association between the rare IP-III malformations and the presence of hypothalamic morphologic abnormalities.

Women in otolaryngology in Turkey: Insight of gender equality, career development and work-life balance.

OBJECTIVE: The aim of this study is to collect information about the demographics, academic ambitions, job satisfactions, career development and work-life balance of female otorhinolaryngologists (FORL) in Turkey and to determine their experiences with, and attitudes towards gender discrimination throughout their academic careers. STUDY DESIGN AND SETTING: A prospective survey study. SUBJECTS AND METHODS: The study was aimed to include all FORL who completed their residency program. An online survey was used to collect their responses. RESULTS: Out of 208 invitations, 156 FORL participated to the survey. The mean age of the participants was 39.7 ±â€¯6.1 (29-75) years. 16.6% of the FORL used to occupy or still occupying administrative positions in their respective medical centers; 15.4% of them used to be assigned or still being assigned to a duty in otorhinolaryngology associations. Gender discrimination was 2.5 fold higher (p = 0.006 OR: 2.55 (95% CI 1.31, 4.99) in departments where there were no female faculty members. 53.2% of the female surgeons were both physically and psychologically harassed for their gender during their residency programs to deter from completing their program in otolaryngology. This finding is 4.1 fold higher than those who stated that they had not been exposed to any such gender discrimination (p = 0.001 OR: 4.094 (95% CI 2.22, 7.57). CONCLUSION: Healthcare policy-makers and institutions should consider taking all the necessary actions to prevent gender discrimination in order to increase job satisfaction and achievements of female specialists in the field of otorhinolaryngology.

MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss.

While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with sensorineural hearing loss.

Comprehensive analysis via exome sequencing uncovers genetic etiology in autosomal recessive nonsyndromic deafness in a large multiethnic cohort.

PURPOSE: Autosomal recessive nonsyndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity, with reported mutations in 58 different genes. This study was designed to detect deafness-causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). METHODS: After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador, and Puerto Rico to screen for mutations in all known ARNSD genes. RESULTS: We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%), and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes, suggesting founder effects. CONCLUSION: We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.Genet Med 18 4, 364-371.

Novel domain-specific POU3F4 mutations are associated with X-linked deafness: examples from different populations.

BACKGROUND: Mutations in the POU3F4 gene cause X-linked deafness type 3 (DFN3), which is characterized by inner ear anomalies. METHODS: Three Turkish, one Ecuadorian, and one Nigerian families were included based on either inner ear anomalies detected in probands or X-linked family histories. Exome sequencing and/or Sanger sequencing were performed in order to identify the causative DNA variants in these families. RESULTS: Four novel, c.707A>C (p.(Glu236Ala)), c.772delG (p.(Glu258ArgfsX30)), c.902C>T (p.(Pro301Leu)), c.987T>C (p.(Ile308Thr)), and one previously reported mutation c.346delG (p.(Ala116ProfsX26)) in POU3F4, were identified. All mutations identified are predicted to affect the POU-specific or POU homeo domains of the protein and co-segregated with deafness in all families. CONCLUSIONS: Expanding the spectrum of POU3F4 mutations in different populations along with their associated phenotypes provides better understanding of their clinical importance and will be helpful in clinical evaluation and counseling of the affected individuals.

Computed tomographic findings of X-linked deafness: a spectrum from child to mother, from young to old, from boy to girl, from mixed to sudden hearing loss.

PURPOSE: Congenital mixed hearing loss associated with fixed stapes footplate is a rare disorder transmitted through X-linked inheritance. The purpose of this study was to report the radiologic findings of X-linked deafness with middle ear anomalies in affected children and young patients and in carrier women. MATERIALS AND METHODS: The computed tomographic and audiometric findings of 7 subjects (4 affected children and young patients, 1 of whom is a girl; 2 carrier mothers; and a man who presented with sudden hearing loss) from different families were analyzed. RESULTS: Computed tomography showed bulbous dilatation of the fundi of the internal auditory canals, incomplete bony separation between the basal turn of the cochleas and the lateral ends of the internal auditory canal, deficiency of the modiolus, enlarged first part of the facial nerve, and dilatation of the superior and the inferior vestibular nerve canal and the singular canal. Besides these characteristic findings, dilatation of the vestibular aqueduct was seen except in the man. Middle ear anomalies including oval and/or round window and/or stapes abnormalities were also detected in three affected patients. The carrier mothers had milder forms of some characteristic findings. CONCLUSIONS: Because of the risks of stapes surgery in X-linked deafness, recognition of the characteristic imaging features of these disorders is important. Especially in young patients with mixed hearing loss, temporal bone computed tomography should be performed before stapes surgery to avoid the complication of stapes gusher. Middle ear anomalies might be highly associated with X-linked deafness.

The round window diameter in congenital aural atresia and comparison with sensorineural hearing loss and control group.

OBJECTIVE: The aim of this study was to measure round window (RW) diameters in patients with congenital aural atresia (CAA) or sensorineural hearing loss (SNHL) and a normal control group and to analyze whether differences exist between these groups. METHODS: Temporal bone computed tomographic scans of 12 patients with CAA (5 males, 7 females) aged 1 to 50 years (median age, 6 years), 12 patients with SNHL (8 males, 4 females) aged 2 to 32 years (median age, 5 years), and 11 patients (3 males, 7 females) aged 2 months to 53 years (median age, 8 years) randomly selected from a pool of patients with unilateral chronic otitis media or cholesteatoma were reviewed. We measured RW diameter on oblique reconstruction planes. To prevent possible individual differences, skull width was measured. RESULTS: There were no statistically significant differences between all groups for skull width. Both RW diameter and RW membrane width were found smaller in the CAA group than both SNHL group and control group with statistical significance, whereas there were no statistically significant differences between the SNHL group and the control group. CONCLUSIONS: We found that both the RW diameter and RW membrane width in CAA were smaller than those in the control group. If this finding is supported in future studies, the production of floating mass transducer with different sizes may be useful. We suggest that RW diameter should be measured in each patient before operation and thus a floating mass transducer with the appropriate caliber should be chosen.

Evaluation of the efficacy of curcumin in experimentally induced acute otitis media in rats.

OBJECTIVES: We investigated the effect of curcumin (CMN) in the treatment of experimentally induced acute otitis media (AOM) in rats. METHOD: Thirty-two Sprague-Dawley female rats were used, yielding 64 temporal bones. Group 1 was the control group. For groups 2 to 4, AOM was induced experimentally, and saline, antibiotics (sulbactam-ampicillin), or CMN were administered for 14 days to groups 2, 3, and 4, respectively. During the histological examination, thickening of the tympanic membrane, damage to the epithelium, inflammation, and sclerosis were evaluated. RESULTS: The AOM+antibiotic and AOM+CMN groups exhibited reduced histological damage compared with the AOM+saline group. No significant differences in thickening of the tympanic membrane or damage to the epithelium or inflammation were observed between the AOM+antibiotic and the AOM+CMN groups. However, the sclerosis values of the AOM+CMN group were significantly lower than those of the AOM+antibiotic group. CONCLUSION: CMN treatment resulted in similar effects on the experimentally induced AOM model as did the antibiotic treatment. The efficacy of this treatment may be related to its effects on the production of various inflammatory cytokines. In light of the worldwide increase in antibiotic resistance and the mild side effects of CMN, we suggest that CMN therapy may be a promising option in AOM treatment.

Evaluation of the Impact of Cochlear Implantation on Patients' Working Life: A Cross-Sectional Study.

Hearing loss that arises from various causes at different stages of life has a direct impact on individuals' physical and mental well-being. This paper aimed to evaluate the employment, workplace adaptation, productivity, and professional success of individuals who have hearing loss and whose hearing loss is corrected with a cochlear implant. In this cross-sectional study, data were collected between November 2022 and March 2023 with the participation of individuals with cochlear implants living in several settlements in all regions of Türkiye. A total of 142 participants with severe hearing loss who were corrected with a cochlear implant were included in this study. The survey method was used to collect data for the study. The questionnaire consisted of 32 questions and was distributed to the participants online. In the first part of the questionnaire (questions 1-10), the general characteristics of implant patients were investigated. In the second part (questions 11-32), the positive or negative effects of implantation on the work lives of the participants were evaluated. Almost half of the research group (49.3%, n = 70) consisted of women, and the mean age of the participants was determined to be 35.8 ± 14.8 years. There was no significant difference between gender, educational status, implanted side, working time, working style (physical, desk), and factors affecting work life (p > 0.05). Professional satisfaction and success at work increased significantly more in those with acquired hearing loss (p = 0.010). Post-implantation workplace compliance, success, and productivity were found to be higher in those with acquired hearing loss (p = 0.013). Hearing loss had a significantly less negative impact on work performance in those implanted in childhood than in those implanted in adulthood (p = 0.043). It was observed that hearing loss had a greater negative impact on the work life of married people (p = 0.006). Cochlear implantation greatly enhances workplace satisfaction, increases self-confidence, and has a positive impact on the future of profoundly deaf individuals.

Evaluation of nasal airway alterations associated with septorhinoplasty by both objective and subjective methods.

The aim of functional septorhinoplasty is to create an esthetically elegant nose and harmony in the face by preserving nasal function as well as maintaining or restoring adequate airway. Since nasal complaints are usually subjective, it may be difficult to evaluate the functions objectively. In the present study, we aimed to investigate the alterations in nasal function associated with septorhinoplasty by using both objective and subjective methods. The study population consisted of 40 patients who underwent septorhinoplasty and 40 healthy controls. Before and after the operation, visual analog scale, acoustic rhinometry, rhinomanometry, and Odiosoft-Rhino test were applied to all patients and controls. There were significant differences in all parameters both before and after the operation. While a significant difference was obtained between the patient and control groups in terms of preoperative values, no significant difference was found between postoperative values of these groups. Both objective and subjective methods are important in evaluations.

Investigation of the presence of biofilms in chronic suppurative otitis media, nonsuppurative otitis media, and chronic otitis media with cholesteatoma by scanning electron microscopy.

OBJECTIVE: Biofilms have been shown to play a major role in the pathogenesis of otolaryngologic infections. However, very limited studies have been undertaken to demonstrate the presence of biofilms in tissues from patients with chronic otitis media (COM) with or without cholesteatoma. Our objective is to study the presence of biofilms in humans with chronic suppurative and nonsuppurative otitis media and cholesteatoma. Study Design. In all, 102 tissue specimens (middle ear, mastoid tissue, and ossicle samples) were collected during surgery from 34 patients. METHODS: The samples were processed for the investigation of biofilms by scanning electron microscopy (SEM). RESULTS: Our research supports the hypothesis in which biofilms are involved in chronic suppurative otitis media, cholesteatoma, and, to a lesser degree, chronic nonsuppurative otitis media. There were higher rates in hypertrophic and granulated tissue samples than in normal mucosa. In addition, the presence of biofilms was significantly higher in the middle ear mucosa compared with the mastoid and ossicle samples. CONCLUSION: In the clinic, the careful use of topical or systemic antimicrobials is essential, and, during surgery, hypertrophic tissue must be carefully removed from normal tissue.

Effects of Unilateral Audio-Vestibular Insufficiency on Spatial Hearing.

This study aimed to compare spatial hearing performance between adult individuals with the unilateral sensorineural hearing loss and unilateral loss of horizontal semicircular canal function (termed canal paresis/weakness) in the same ear and adults with normal hearing thresholds and normal vestibular function and to examine associated factors (duration of hearing loss and rate of canal paresis).The study participants consisted of 20 adults (aged 48±11 years) with unilateral sensorineural hearing loss and unilateral canal paresis (unilateral weakness≥25%) in the same ear. The control group comprised 25 adults (aged 45±13 years) with normal hearing and a unilateral weakness rate below 25%. Pure tone audiometry, bithermal binaural air caloric test, Turkish Spatial Hearing Questionnaire (T-SHQ), and Standardized Mini-Mental State Exam were applied to all the individuals. When the performance of the participants in T-SHQ was examined both in terms of the subscales and the total scale, there was a statistically significant difference between the two groups in relation to the scores. A statistically significant, high, negative correlation was detected between the duration of hearing loss, the rate of canal paresis and all the subscale scores and total score of T-SHQ. According to these results, as the duration of hearing loss increased, the scores obtained from the questionnaire decreased. As the rate of canal paresis increased, vestibular involvement increased, and the T-SHQ score decreased. This study showed that adults with unilateral hearing loss and unilateral canal paresis in the same ear had lower spatial hearing performance than those with normal hearing and balance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03442-1.

Sacculocolic reflex in patients with dementia: is it possible to use it for early diagnosis?

Alzheimer disease (AD) is a progressive, irreversible entity associated with behavioral changes, memory loss and disturbance of daily life activities. Current diagnostic tools can detect neuronal degeneration in AD only after irreversible damage that already existed. Vestibular evoked myogenic potentials (VEMP) test utilizes the sacculocolic reflex arc and has been used in neuro-otology practice for many years. In this study, we aim to determine if VEMP can be used for diagnostic purposes at the earliest stages of AD. Twenty patients with AD and ten patients with mild cognitive impairment were enrolled in this study. Control group was 30 healthy volunteers with no neurological or otological diseases. Abnormal VEMP responses were found in most of the patients at different stages of AD. VEMP test may be used for early diagnosis of AD. Also, it may provide a novel advancement in understanding of pathophysiology of this disease.

[Congenital cholesteatoma frequently mistaken for temporal bone dermoid cyst: a case report]. / Siklikla temporal kemik dermoid kisti ile karisan dogustan kolesteatom: Bir olgu sunumu.

Dermoid cysts of the middle ear are very rare and can develop behind an intact tympanic membrane, just like congenital cholesteatoma. The visual and clinical symptoms of congenital cholesteatomas and dermoid cysts are difficult to distinguish from each other. Their treatments are similar, however the correct diagnosis can be obtained histopathologically after removing the lesion. In this article a case of a twenty-seven-year-old male patient, whose diagnosis was presumed to be dermoid cyst in the middle ear according to the preoperative radiologic examination but reported to be congenital cholesteatoma as a result of the postoperative histopathologic examination, was reported.

Anesthesia for a Child with Congenital Long QT Syndrome, a Case Report and Literature Review.

Long QT syndrome is an inherited disorder of the heart's electrical activity that may also be associated with malignant arrhythmia and cause sudden death. In addition to this inherited condition, several commonly used anesthetic drugs can prolong the QT interval. We present here a 17-month-old male patient who underwent general anesthesia for a cochlear implant. No cardiac arrhythmia was observed in the patient, whose muscle relaxant effect was reversed using sugammadex. The application of intravenous anesthetics was preferred to maintain anesthesia for this patient and was safely applied.

Effects of Oxygen Therapies in Experimental Acute Acoustic Trauma.

BACKGROUND: Acute acoustic trauma is defined as a sudden sensorineural hearing loss that occurs after an exposure to acoustic overstimulation. Increasing the oxygen in perilymph can be a treatment modality. Our study aims to investigate the influence of normobaric oxygen therapy on the recovery of acute acoustic trauma and to compare it with the hyperbaric oxygen therapy. METHODS: Three groups of rats (5 rats each) were exposed to white noise for 1 hour. Sensorineural hearing loss was identified using distortion product otoacoustic emission. Subsequently, the first group was treated with hyperbaric oxygen therapy, the second group was treated with normobaric oxygen therapy, and the third group did not receive any treatment and was used as a control group. RESULTS: There was a statistically significant difference within time for frequencies of 1, 1.5, and 2 kHz, but there was no statistically significant difference between groups. For frequencies of 3, 4, 5, and 6 kHz, there was a statistically significant difference within time and between groups. Between groups, recovery of distortion product otoacoustic emission values in all frequencies was better in the control group by the third, fifth, and seventh days. Comparing the values of hyperbaric oxygen therapy and normobaric oxygen therapy groups, it was observed that by the third day, the hyperbaric oxygen therapy values were better than those of the normobaric oxygen therapy values. However, by the fifth and seventh days, the normobaric oxygen therapy values were better (except at a frequency of 1 kHz). CONCLUSION: Because there is a high rate of spontaneous recovery, physicians should be more selective to treat patients with oxygen therapies.