Intra-population variability of the saccular, utricular and lagenar otoliths of the garfish Belone belone (Linnaeus, 1760) from South-Western Ionian Sea (Central Mediterranean Sea).

The garfish Belone belone represents the only valid endemic Belone species for the Mediterranean Sea and the eastern Atlantic Ocean. It shows a wide global distribution range, with a high commercial value and ecological relevance in the pelagic domain. Despite this, there needs to be more knowledge regarding the otoliths of this species, with the total absence of descriptions regarding asterisci and lapilli from Mediterranean populations and a lack of studies on the reliability of shape analysis on its sagittae. The present paper aims to provide the first main contours description of the three otoliths pairs from a Mediterranean population, providing an accurate investigation of morphology, morphometry, and intra-specific variability of sagittae, lapilli, and asterisci. Results showed (i) the absence of directional bilateral asymmetry and sexual asymmetry for the three otoliths pairs, (ii) a different morphology and morphometry of sagittae, lapilli and asterisci than those described in the literature, and (iii) an enhanced variability between sagittae morphometry and shape between the three investigated size classes. All these data confirmed the reliability of the studied species of shape analysis, showing a geographical and size-related variability of otoliths features probably related to genetics, environmental conditions, and life habits variations.

Nestin-expressing cells are mitotically active in the mammalian inner ear.

Nestin expression is associated with pluripotency. Growing evidence suggests nestin is involved in hair cell development. The objective of this study was to investigate the morphology and role of nestin-expressing cells residing in the early postnatal murine inner ear. A lineage-tracing nestin reporter mouse line was used to further characterize these cells. Their cochleae and vestibular organs were immunostained and whole-mounted for cell counting. We found Nestin-expressing cells present in low numbers throughout the inner ear. Three morphotypes were observed: bipolar, unipolar, and globular. Mitotic activity was noted in nestin-expressing cells in the cochlea, utricle, saccule, and crista. Nestin-expressing cell characteristics were then observed after hair cell ablation in two mouse models. First, a reporter model demonstrated nestin expression in a significantly higher proportion of hair cells after hair cell ablation than in control cochleae. However, in a lineage tracing nestin reporter mouse, none of the new hair cells which repopulated the organ of Corti after hair cell ablation expressed nestin, nor did the nestin-expressing cells change in morphotype. In conclusion, Nestin-expressing cells were identified in the cochlea and vestibular organs. After hair cell ablation, nestin-expressing cells did not react to the insult. However, a small number of nestin-expressing cells in all inner ear tissues exhibited mitotic activity, supporting progenitor cell potential, though perhaps not involved in hair cell regeneration.

Insights into enlarged prostatic utricles and Müllerian duct system remnants associated with posterior hypospadias.

INTRODUCTION: The prostatic utricle (PU) consists of the caudal remnant of the Müllerian duct and the urogenital sinus. The term "vagina masculina" is used if other Müllerian structures are associated with the PU. This work aims to investigate the incidence, management, and follow up of enlarged PUs and Müllerian remnants in males with posterior hypospadias. PATIENTS AND METHODS: This study presents a retrospective review of cases presented with posterior hypospadias over a 5-year period. Prior to hypospadias repair, retrograde urethrograms were used to investigate enlarged PU. Subsequently, they were classified according to the Ikoma score and further assessed by karyotyping and cystoscope. Surgical excision was indicated in cases with symptomatic utricles or vagina masculina. RESULTS: Thirty patients were included in the study in the period between 2015 and 2020 (Table). All cases were asymptomatic initially. Twelve patients were diagnosed with enlarged PU; three of them had vagina masculina. One case with perineal hypospadias had a separate perineal opening for PU. Following hypospadias repair, three of the eight cases treated conservatively turned symptomatic. DISCUSSION: The incidence of enlarged PU and Müllerian remnants varied among different studies. However, it increased as the severity of hypospadias increased. Preoperative urethrogram was helpful in the diagnosis and classification of PU, but it had its limitations. Cystoscope was more advantageous in diagnosing vagina masculina. Although most cases were asymptomatic, some turned symptomatic after hypospadias repair. Some cases with perineal hypospadias had PU with a separate perineal opening. CONCLUSION: The incidence of enlarged PUs or Müllerian remnants was 40%. Although cases were asymptomatic before hypospadias surgery, some cases turned into symptomatic after hypospadias repair. In some cases, the PU or Müllerian remnants had a separate perineal opening. They can be classified as a particular form of Ikoma grade III necessitating surgical intervention.

Clinical Application of Ureteroscope-Assisted Laparoscopic Surgery for Prostatic Utricle in Children.

Purpose: To investigate the use of ureteroscope-assisted laparoscopic surgery (UALS) in treating symptomatic prostatic utricle (PU) in children. Materials and Methods: Data on surgically treated cases of PU at the Department of Urology in Hunan Children's Hospital between September 2014 and September 2022 were retrospectively collected and analyzed. The diagnosis was confirmed by cystourethroscopy followed by ureteroscopy, and PU was excised by ureteroscope-assisted laparoscopy. Results: A total of 21 patients with PU were enrolled in this study. The median age of the patients at surgery was 8.1 (4.6-11.5) years. Karyotyping was available for 15 children: 13 (86.7%) were 46XY, 1 (6.7%) was 45X/46XY, and 1 (6.7%) was 45X/46XY/47XYY. The median length of the PU was 5.0 (4.1-7.1) cm. Nineteen patients underwent only ureteroscope-assisted laparoscopic excision, whereas 2 also had a perineal incision. All excisions were successfully performed. The median intraoperative blood loss was 25.0 (20.0-37.5) mL. The median hospital stay and follow-up durations were 18.0 (14.5-25.0) days and 24.0 (13.5-49.0) months, respectively. The patients reported no postoperative clinical symptoms. Conclusion: UALS allows for accurate patient positioning and thorough exposure of the anatomical structures, and it is a safe, effective, and minimally invasive treatment for PU in children.

Transmembrane Channel-Like (Tmc) Subunits Contribute to Frequency Sensitivity in the Zebrafish Utricle.

Information about dynamic head motion is conveyed by a central "striolar" zone of vestibular hair cells and afferent neurons in the inner ear. How vestibular hair cells are tuned to transduce dynamic stimuli at the molecular level is not well understood. Here we take advantage of the differential expression pattern of tmc1, tmc2a, and tmc2b, which encode channel subunits of the mechanotransduction complex in zebrafish vestibular hair cells. To test the role of various combinations of Tmc subunits in transducing dynamic head movements, we measured reflexive eye movements induced by high-frequency stimuli in single versus double tmc mutants. We found that Tmc2a function correlates with the broadest range of frequency sensitivity, whereas Tmc2b mainly contributes to lower-frequency responses. Tmc1, which is largely excluded from the striolar zone, plays a minor role in sensing lower-frequency stimuli. Our study suggests that the Tmc subunits impart functional differences to the mechanotransduction of dynamic stimuli.Significance Statement Information about dynamic head movements is transmitted by sensory receptors, known as hair cells, in the labyrinth of the inner ear. The sensitivity of hair cells to fast or slow movements of the head differs according to cell type. Whether the mechanotransduction complex that converts mechanical stimuli into electrical signals in hair cells participates in conveying frequency information is not clear. Here we find that the transmembrane channel-like 1/2 genes, which encode a central component of the complex, are differentially expressed in the utricle and contribute to frequency sensitivity in zebrafish.

Comparison of the saccules and lagenae in six macrourid fishes from different deep-sea habitatsa).

There are substantial interspecific differences in the morphology of the ears of the more than 34 000 living fish species. However, almost nothing is known about the functional significance of these differences. One reason is that most comparative studies have been conducted on shallow-water species with far less focus on the numerous species that inhabit the depths of the oceans. Thus, to get a better sense of ear diversity in fishes and its potential role in hearing, this study focuses on the saccule and lagena, the primary auditory end organs, in six species of the family Macrouridae (rattails), a large group of fishes that typically inhabit depths from 1000 to 4000 m. The inner ears and, particularly, the saccules and lagenae in these species are large with the saccule resembling that of other Gadiformes. The lagenae of all macrourids studied here have serrated edge otoliths and highly diverse hair cell ciliary bundle shapes. The differences found in the inner ear anatomy of macrourids likely reflect the sensory advantages in different habitats that are related to the benefits and constraints at different depths, the fish's particular lifestyle, and the trade-off among different sensory systems.

Noise-induced damage in the zebrafish inner ear endorgans: evidence for higher acoustic sensitivity of saccular and lagenar hair cells.

The three otolithic endorgans of the inner ear are known to be involved in sound detection in different teleost fishes, yet their relative roles for auditory-vestibular functions within the same species remain uncertain. In zebrafish (Danio rerio), the saccule and utricle are thought to play key functions in encoding auditory and vestibular information, respectively, but the biological function of the lagena is not clear. We hypothesized that the zebrafish saccule serves as a primary auditory endorgan, making it more vulnerable to noise exposure, and that the lagena might have an auditory function given its connectivity to the saccule and the dominant vestibular function of the utricle. We compared the impact of acoustic trauma (continuous white noise at 168 dB for 24 h) between the sensory epithelia of the three otolithic endorgans. Noise treatment caused hair cell loss in both the saccule and lagena but not in the utricle. This effect was identified immediately after acoustic treatment and did not increase 24 h post-trauma. Furthermore, hair cell loss was accompanied by a reduction in presynaptic activity measured based on ribeye b presence, but mainly in the saccule, supporting its main contribution for noise-induced hearing loss. Our findings support the hypothesis that the saccule plays a major role in sound detection and that the lagena is also acoustically affected, extending the species hearing dynamic range.

Cross-species analysis and comparison of the inner ear between chickens and mice.

The inner ear of mammals includes the cochlea and vestibule, which house specialized hair cells that are responsible for hearing and balance, respectively. While cochlear hair cells fail to regenerate following damage, those of the utricle, which is part of the vestibular apparatus, show partial regeneration. In birds, the macula lagena, a unique ear structure in this clade, has the ability to regenerate hair cells similarly to the utricle. Many studies have sought to explain regeneration in terms of evolution and species differences. However, it remains unclear what the cellular and molecular basis is behind the differences in inner ear structures and between avians and mammals. In the present study, we first investigated the anatomical structures of the inner ear of both chickens and rodents. We then performed RNA sequencing (RNA-Seq) and made cross-species analyses of the expression of homologous genes obtained from the inner ear tissue from both chickens and mice. Finally, we focused on the lagena, the basilar papilla, and the utricle in chickens and identified differentially expressed genes between tissues and determined the expression patterns of genes involved in inner ear structure formation by single-cell RNA sequencing and bulk RNA-Seq. We concluded that the cellular and molecular composition of the lagena is more similar to that of the utricle than the cochlea. Taken together, our study provides a valuable resource for the study of inner ear evolution and development.

Transient connection between the vestibular aqueduct and utricle: A study using sagittal sections of human embryonic heads.

BACKGROUND: The aqeductus vestibuli (aqueduct) is believed to connect to the saccule in embryos and adults. However, in embryos, the saccule and utricle are known to communicate widely to provide a common endolymph space "atrium". METHODS: Using sagittal histological sections from five embryos (crown-rump length or CRL, 14-21 mm), nine early fetuses (CRL 24-35 mm) and 12 midterm and near-term fetuses (CRL 82-272 mm), we revisited the development and growth of the human ear aqueduct. RESULTS: The atrium took on a thick tube-like appearance as an antero-inferior continuation of the aqueduct, but soon divided into multiple gulfs. Most of the gulfs corresponded to the ampullae of semicircular ducts, while one gulf at the antero-medio-inferior corner corresponded to the future saccule. Notably, in eight of the 14 embryos and early fetuses, the aqueduct ended at the utricle near the primitive ampulla of the anterior (superior) or posterior semicircular duct. Conversely, an embryo of CRL 21 mm was the smallest specimen in which the aqueduct joined the gulf-like saccule. At midterm and near-term, the growing perilymph space separated the aqueduct from the utricle and appeared to push the aqueduct toward the saccule. A topographical change occurred between the embryonic superiorly located utricle and the inferiorly-located saccule to create the antero-posterior arrangement in adults. CONCLUSIONS: Consequently, the vestibular end of the aqueduct was most likely to migrate anteriorly from the utricle to the saccule at 6-8 weeks possibly due to differential growth of the endothelium. Previous reconstructions of the embryonic aqueduct might be biased by the adult morphology.

[Vestibular evoked myogenic potentials in patients with recurrent benign paroxysmal positional vertigo]. / Vestibulyarnye vyzvannye miogennye potentsialy u patsientov s retsidiviruyushchim dobrokachestvennym paroksizmal'nym pozitsionnym golovokruzheniem.

Registration of ocular and cervical vestibular evoked myogenic potentials (oVEMPs and cVEMPs) reflects the function of otolith receptors: sacculus and utriculus. Benign paroxysmal positional vertigo (BPPV) is a disease of the inner ear as a result of the utriculus disfunction and migration of otoliths into semicircular channels. OBJECTIVE: To study the function of otolith receptors (sacculus and utriculus) with using VEMPs registration in patients with first-time and recurrent posterior semicircular canal BPPV before and after repositional maneuvers. MATERIAL AND METHODS: Registration and comparison of the results of oVEMPs and cVEMPs were performed in 50 patients with first-time posterior semicircular canal idiopathic BPPV and 26 patients with recurrent posterior semicircular canal BPPV before and after repositional treatment. RESULTS AND DISCUSSION: Clinically significant asymmetry of the amplitude of oVEMPs before treatment was recorded in 14 (38%) of patients with first-time BPPV and in 15 (57.7%) of patients with recurrent BPPV; cVEMPs - in 6 (12%) of patients with first-time BPPV and in 6 (23.1%) of patients with recurrent BPPV. Successful repositional treatment did not affect the amplitude of cVEMPs in any of the groups of patients, but led to a significant increase in the amplitude of oVEMPs on the affected side in patients with first-time BPPV. In patients with recurrent BPPV, despite the absence of symptoms of otolithiasis, the asymmetry of the amplitude of oVEMPs persisted during remission (p<0.05), which can be considered as a prognostically unfavorable factor of disease recurrence.

First evidence of the link between internal and external structure of the human inner ear otolith system using 3D morphometric modeling.

Our sense of balance is among the most central of our sensory systems, particularly in the evolution of human positional behavior. The peripheral vestibular system (PVS) comprises the organs responsible for this sense; the semicircular canals (detecting angular acceleration) and otolith organs (utricle and saccule; detecting linear acceleration, vibration, and head tilt). Reconstructing vestibular evolution in the human lineage, however, is problematic. In contrast to considerable study of the canals, relationships between external bone and internal membranous otolith organs (otolith system) remain largely unexplored. This limits our understanding of vestibular functional morphology. This study combines spherical harmonic modeling and landmark-based shape analyses to model the configuration of the human otolith system. Our approach serves two aims: (1) test the hypothesis that bony form covaries with internal membranous anatomy; and (2) create a 3D morphometric model visualizing bony and membranous structure. Results demonstrate significant associations between bony and membranous tissues of the otolith system. These data provide the first evidence that external structure of the human otolith system is directly related to internal anatomy, suggesting a basic biological relationship. Our results visualize this structural relationship, offering new avenues into vestibular biomechanical modeling and assessing the evolution of the human balance system.

A low-frequency acceleration sensor inspired by saccule in human vestibule.

A human vestibular system is a group of devices in the inner ear that govern the balancing movement of the head, in which the saccule is responsible for sensing gravity accelerations. Imitating the sensing principle and structure of the Sensory Hair (SH) cell in the saccule, a Bionic Sensory Hair (BSH) was developed, and 9 BSH arrays were arranged in the bionic macular at the bottom of the spherical shell to prepare a Bionic Saccule (BS). Based on the piezoelectric equation, the electromechanical theoretical models of the BSH cantilever and BS were deduced. They were subjected to impact oscillations using an exciter, and their output charges were analyzed to check their sensing ability. The results showed that BSH could sense its bending deflection, and the BS could sense its position change in the sagittal plane and in space. They exhibited a sensitivity of 1.6104 Pc s2/m and a fast response and similar sensing principles and low resonance frequency to those of the human saccule. The BS is expected to be used in the field of robotics and clinical disease diagnosis as a part of the artificial vestibular system in the future.

Utility of Inter-Frequency Amplitude Ratio of Vestibular-Evoked Myogenic Potentials in Identifying Meniere's Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: A recently devised parameter of vestibular-evoked myogenic potential (VEMP) based on the principles of frequency tuning is the inter-frequency amplitude ratio (IFAR). It refers to the ratio of the amplitude of 1000 Hz tone burst evoked VEMP to 500 Hz evoked tone burst. A pathology like Meniere's disease changes the frequency response and alters the frequency tuning of the otolith organs. Because IFAR is based on the principle of frequency tuning of VEMP, it is likely to help identify Meniere's disease. Few studies in the last decade have investigated the utility of IFAR in identifying Meniere's disease. However, a systematic review and a meta-analysis on IFAR in Meniere's disease are lacking. The present study investigates whether the IFAR of VEMP helps identify Meniere's disease and differentiates it from healthy ears and other vestibular pathologies. DESIGN: The present study is a systematic review and a meta-analysis. The studies investigating the IFAR of cervical and ocular VEMPs in Meniere's disease, healthy controls, and other vestibular pathologies were searched across research databases such as PubMed, Science Direct, and Scopus. The search strategy was developed using the PICO (population, intervention, comparison, and outcomes) format, and Medical Subject Headings (MeSH) terms and Boolean operators were employed. The systematic review was performed using the Rayyan software, whereas the Review Manager software was used to carry out the meta-analysis. A total of 16,605 articles were retrieved from the databases. After the duplicate removal, 2472 articles remained. These were eliminated using title screening, abstract screening, and full-length inspections. A total of nine articles were found eligible for quality assessment and meta-analysis, and the New Castle-Ottawa Scale was used for quality assessment. After the data extraction, 24 six articles were found to have the desired data format for the meta-analysis. RESULTS: The results showed significantly higher IFAR in the affected ears of individuals in the Meniere's disease group than in the control group's unaffected ears. There was no significant difference between the unaffected ears of individuals in the Meniere's disease group and the ears of the control group. The only study on Meniere's disease and benign paroxysmal positional vertigo found significantly larger ocular VEMP IFAR in ears with Meniere's disease than in benign paroxysmal positional vertigo. CONCLUSIONS: This systematic review and meta-analysis found IFAR efficient in differentiating Meniere's disease from healthy controls. We also found an enhanced IFAR as a potential marker for Meniere's disease. However, more investigations are needed to confirm the utility of an enhanced IFAR value in the exclusive identification of Meniere's disease.

Differential Expression of Na/K-ATPase in the Human Saccule of Patients With and Without Otologic Disease.

HYPOTHESIS: Na + , K + -ATPase (Na/K-ATPase) α1 subunit expression in the saccule of patients diagnosed with otologic disease is different compared with normal controls. BACKGROUND: We have recently characterized changes in the expression of Na/K-ATPase α1 subunit in the normal and pathological cochlea; however, no studies have determined the distribution Na/K-ATPase α1 subunit in the human saccule. The present study uses archival temporal bones to study the expression Na/K-ATPase α1 subunit in the human saccule. METHODS: Archival celloidin formalin fixed 20-micron thick sections of the vestibule from patients diagnosed with Menière's disease (n = 5), otosclerosis (n = 5), sensorineural hearing loss, and normal hearing and balance (n = 5) were analyzed. Sections containing the saccular macula were immunoreacted with mouse monoclonal antibodies against Na/K-ATPase α1 subunit. Micrographs were acquired using a high-resolution digital camera coupled to a light inverted microscope. RESULTS: In the normal human saccule vestibular sensory epithelium, Na/K-ATPase α1 immunoreactivity (IR) was present in nerve fibers and calyces that surround type I vestibular hair cells and nerve terminals. The transition epithelium cells were also Na/K-ATPase α1 immunoreactive. Comparison between normal and pathological specimens showed that there was a significant reduction of Na/K-ATPase α1 IR in the saccule vestibular sensory epithelium from patients with Menière's disease, otosclerosis, and sensorineural hearing loss. CONCLUSIONS: The decrease of Na/K-ATPase-IR α1 in the saccule vestibular sensory epithelium from patients with otopathologies suggests its critical role in inner ear homeostasis and pathology.

Enlarged prostatic utricle and vagina masculinus in boys with disorders of sex development.

PURPOSE: To determine the prevalence, radiological characteristics, and clinical symptomatology of enlarged prostatic utricles and vagina masculinus in boys with disorders of sex development. METHODS: Over 10 years (from February 2012 to March 2022), 102 boys with severe hypospadias underwent voiding cystourethrography. All patients presented with disorders of sex development and Y material in the karyotype (46,XY karyotype, 46,XY/45,X mosaic, etc.). The age of the patients at the first examination ranged from 4 days to 27 months (mean age 2.7 months). RESULTS: Voiding cystourethrography revealed the presence of a cyst posterior to the urethra in 66 patients (64.7% of cases). There were 15 cases of "vagina masculinus" and 51 of enlarged prostatic utricles. These dilations were classified according to the Ikoma classification and cyst size. In more than 2/3 of cases, the cysts were small (less than 20 mm), and in less than 8% of cases, these cysts were large. In addition, retrograde opacification revealed the presence of vesicoureteral reflux in 20% of boys with a male vagina. The most severe hypospadias with a scrotal or perineal meatus are most at risk of developing an enlarged prostatic utricle, and 80% of patients with Ikoma Grade III had a scrotal or perineal meatus. CONCLUSION: This study shows that the prevalence of enlarged prostatic utricles and vagina masculinus is high in patients with severe hypospadias. Therefore, their search should be systematic, and for clinical and therapeutic interest, the enlarged prostatic utricles should be classified according to cyst size.

Vestibular Drop Attacks and Meniere's Disease as Results of Otolithic Membrane Damage-A Numerical Model.

Meniere's disease (MD) is a condition of the inner ear with symptoms affecting both vestibular and hearing functions. Some patients with MD experience vestibular drop attacks (VDAs), which are violent falls caused by spurious vestibular signals from the utricle and/or saccule. Recent surgical work has shown that patients who experience VDAs also show disrupted utricular otolithic membranes. The objective of this study is to determine if otolithic membrane damage alone is sufficient to induce spurious vestibular signals, thus potentially eliciting VDAs and the vestibular dysfunction seen in patients with MD. We use a previously developed numerical model to describe the nonlinear dynamics of an array of active, elastically coupled hair cells. We then reduce the coupling strength of a selected region of the membrane to model the effects of tissue damage. As we reduce the coupling strength, we observe large and abrupt spikes in hair bundle position. As bundle displacements from the equilibrium position have been shown to lead to depolarization of the hair-cell soma and hence trigger neural activity, this spontaneous activity could elicit false detection of a vestibular signal. The results of this numerical model suggest that otolithic membrane damage alone may be sufficient to induce VDAs and the vestibular dysfunction seen in patients with MD. Future experimental work is needed to confirm these results in vitro.

[Clinical application progress of subjective visual vertical test].

Subjective visual vertical test is considered as an effective technique to evaluate otolith organ function and central pathway of gravity perception. This test is non-invasive, easy to operate and has little stimulation. At present, there are few such studies in China. This paper reviews the concept, measurement principle and method, influencing factors, application, advantages and disadvantages of subjective visual vertical test.

Sox2 is required in supporting cells for normal levels of vestibular hair cell regeneration in adult mice.

Sox2 is a transcription factor that is necessary in the mammalian inner ear for development of sensory hair cells and supporting cells. Sox2 is expressed in supporting cells of adult mammals, but its function in this context is poorly understood. Given its role in the developing inner ear, we hypothesized that Sox2 is required in vestibular supporting cells for regeneration of type II hair cells after damage. Using adult mice, we deleted Sox2 from Sox9-CreER-expressing supporting cells prior to diphtheria toxin-mediated hair cell destruction and used fate-mapping to assess regeneration. In utricles of control mice with normal Sox2 expression, supporting cells regenerated nearly 200 hair cells by 3 weeks post-damage, which doubled by 12 weeks. In contrast, mice with Sox2 deletion from supporting cells had approximately 20 fate-mapped hair cells at 3 weeks post-damage, and this number did not change significantly by 12 weeks, indicating regeneration was dramatically curtailed. We made similar observations for saccules and ampullae. We found no evidence that supporting cells lacking Sox2 had altered cellular density, morphology, or ultrastructure. However, some Sox2-negative supporting cell nuclei appeared to migrate apically but did not turn on hair cell markers, and type I hair cell survival was higher. Sox2 heterozygotes also had reduced regeneration in utricles, but more hair cells were replaced than mice with Sox2 deletion. Our study determined that Sox2 is required in supporting cells for normal levels of vestibular hair cell regeneration but found no other major requirements for Sox2 in adult supporting cells.