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Hearing loss (HL) affects more than 5% of the global population, with projections indicating an impact of up to 50% on young individuals in the next years. HL treatments remain limited due to the inner ear\'s hermeticism. HL often involves inflammatory processes, underscoring the need for enhanced delivery of antiinflammatory agents to the inner ear. Our research focuses on the development of a directed therapy based on magnetic nanoparticles (MNPs). We previously synthesized biocompatible folic acid-coated iron oxide-core nanoparticles (MNPs@FA) as potential carriers for the anti-inflammatory Diclofenac (Dfc). This study aims to incorporate Dfc onto MNPs@FA to facilitate targeted drug delivery to the inner ear. Through optimizing the loading procedure, we achieved optimal loading capacity. Dfc release was studied in the simulated target fluid and the administration vehicle. Complete characterization is also shown. In vitro biocompatibility testing ensured the biosafety of the resulting formulation. Subsequent ex vivo targeting assays on murine cochleae validated the nanosystems\' ability to penetrate the round window membrane, one of the main HL therapy barriers. These findings serve as validation before continuing to more complex in vivo studies. Together, the data here presented represent an advancement in addressing unmet medical needs in HL therapy.

Increasing carbon dioxide levels associated with climate change will likely have a devastating effect on aquatic ecosystems. Aquatic environments sequester carbon dioxide, resulting in acidic conditions that can negatively affect fish development. Increasing climate change impacts in the coming decades will have an outsized effect on younger generations. Therefore, our research had two interconnected goals: 1) understand how aquatic acidification affects the development of zebrafish, and 2) support a high school scientist\'s ability to address environmental questions of increasing importance to her generation. Working with teachers and other mentors, the first author designed and conducted the research, first in her high school, then in a university research laboratory. Zebrafish embryos were reared in varying pH conditions (6.7-8.2) for up to 7 days. We assessed fish length and development of the inner ear, including the otoliths; structures that depend on calcium carbonate for proper development. Although pH did not affect fish length, fish reared in pH 7.75 had smaller anterior otoliths, showing that pH can impact zebrafish ear development. Furthermore, we demonstrate how zebrafish may be used for high school students to pursue open-ended questions using different levels of available resources.

The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.

Bevezetés: A Ménière-betegség gyógyíthatatlan, de menedzselhető betegség. Alapja az endolympha terének „kitágulása”, az endolympha hydrops. Lehet egy- vagy kétoldali. A tünetek megjelenése alapján metakrón vagy szinkrón megjelenésről beszélhetünk. Hasonló tünetekkel jelentkezhet az autoimmun belsőfül-betegség. Célkitűzés: Kétoldali Ménière-betegséggel diagnosztizált betegek (7 beteg: 2 férfi és 5 nő) belső fülének feltérképezése, immunológiai statusuk felderítése, továbbá az egyéb kórképektől, főleg az autoimmun belsőfül-betegségtől való differenciálás, tapasztalatok alapján egy kivizsgálási protokoll felállítása. Módszer: Kétoldali Ménière-betegeknél rohammentes állapotban a fül-orr-gégészeti, otoneurológiai és immunológiai status, valamint az anamnézis felvétele, továbbá az angularis vestibuloocularis reflex (aVOR) nagy és kis frekvenciájú működésének felmérése. Az előbbit videofejimpulzus-teszt (vHIT), míg az utóbbit kalorizációs teszt során vizsgáltuk. Tisztahang-küszöbaudiogramot végeztünk. Mágneses rezonanciás képalkotó segítségével koponyafelvétel készült. Az immunológiai laborvizsgálat vérszérumból történt. Eredmények: A betegeknél szisztémás autoimmun betegség nem igazolódott. Minden esetben kétoldali, a mély frekvenciákat is érintő pancochlearis sensorineuralis halláscsökkenés volt látható. vHIT során két esetben a magas frekvenciájú aVOR érintettsége is igazolható volt, melyet a betegség előrehaladottságának véleményeztünk. A többi esetben ép működésű, magas frekvenciájú aVOR-t találtunk. A kalorizációs teszt során minden esetben kétoldali ívjáratparesis volt látható. Megbeszélés: A szakirodalomban számos tanulmány foglalkozik az általunk megfigyelt, a vHIT és a kalorizációs teszt közötti diszkrepanciával. Ez az aVOR receptorának, a crista ampullarisnak az anatómiájából következhet: míg a magas frekvenciájú aVOR-t a centrálisan elhelyezkedő I-es típusú szőrsejtek érzékelik, addig az alacsony frekvenciájú aVOR-t a perifériásan elhelyezkedő II-es típusú szőrsejtek. Az utóbbiak szelektív károsodását figyelték meg Ménière-betegségben és autoimmun belsőfül-betegségben is. Ugyanakkor segített a differenciálásban a betegek rendezett immunológiai statusa, az intravénás kortikoszteroidra adott gyenge válaszuk, egy esetben pedig a saccotomiát követő állapotjavulás. Következtetés: A tapasztalatok alapján egy kivizsgálási protokollt kíséreltünk meg felállítani olyan betegek esetében, akik kétoldali fültünetekkel, rohamokban jelentkező, forgó jellegű szédüléssel jelentkeznek. Javasoljuk többek között a vHIT, a kalorizációs teszt és az immunológiai kivizsgálás elvégzését is. Megfontolandónak tartjuk egy multicentrikus vizsgálat elvégzését is mindkét kórképpel kapcsolatban. Orv Hetil. 2024; 165(30): 1176–1183.

Pathology repositories worldwide store millions of celloidin-processed human brain and temporal bone (TB) sections vital for studying central nervous system diseases and sensory organs. However, accessing these sections for modern molecular-pathological research, like immunohistochemistry, is hindered by the challenge of removing celloidin without damaging tissue. In this study, we explored the use of polyethylene glycols (PEGs), a class of non-hazardous, ethylene glycol oligomers, combined with an improved section mounting technique, to gently and effectively dissolve celloidin from sections archived for up to 40 years. Optimizing our protocol involved exploring celloidin dissolution kinetics in PEGs of varying molecular weights and terminations, as well as different temperatures. Low molecular weight PEGs, particularly PEG 200, were the most efficient celloidin solvent. Nuclear magnetic resonance (NMR) spectroscopy of celloidin-PEG 200 dissolution products revealed no chemical alterations, suggesting pure solvation without chemical modification. Because the solvation of celloidin in PEG was inhibited by proteins, we further developed a protein-free mounting protocol allowing complete celloidin removal in 30 to 60 minutes by immersing in PEG 200. In summary, our approach overcomes major methodological hurdles, rendering decades-old archival celloidin sections viable for immunohistochemical and other molecular biological techniques, while enhancing safety and workflow efficiency.

Inner ear organoids play a crucial role in hearing research. In comparison to other animal models and 2D cell culture systems, inner ear organoids offer significant advantages for studying the mechanisms of inner ear development and exploring novel approaches to disease treatment. Inner ear organoids derived from human cells are more closely resemble normal human organs in development and function. The 3D culture system of the inner ear organoid enhances cell-cell interactions and mimics the internal environment. In this review, the progress and limitations of organoid culture methods derived from tissue-specific progenitors and pluripotent stem cells (PSCs) are summarized, which may offer new insights into generating organoids that closely resemble the inner ear in terms of morphology and function.

UNASSIGNED: Meniere disease, characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure, is a common cause of vertigo in humans. The pathogenesis of Meniere disease remains unknown. The current study aimed to describe a novel pathological change discovered in the inner ears of patients with Meniere disease who underwent labyrinthectomy.
UNASSIGNED: This retrospective case-control study was conducted with 21 patients with MD who underwent labyrinthectomy. A total of 15 patients diagnosed with acoustic neuroma or glomus jugular tumor were review over the same period of time as control. The clinical information of the patients and the pathological features of the membrane are described.
UNASSIGNED: The new pathological tissue was a morbid membrane structure sealing the round window, characterized by the formation of lymphatic capillaries. Histochemical and immunofluorescent staining was positive for D2-40, LYVE-1, podoplanin, and PROX1, which are the classical markers of the lymphatic vessels. Transmission electron microscopy revealed that the lymph capillaries lacked a typical basement membrane and that their ends were blind, composed of a single layer of endothelial cells with valval connection structures between adjacent capillary epithelial cells.
UNASSIGNED: This is the first report of lymphatic vessels in the human inner ear, and this pathological structure is a completely new discovery. The lymphatic vessels may develop due to inflammation or decompensation of pressure in the inner ear, suggesting that the inner ear can reactively form lymphatic vessels in some inflammation and fluid flow-dependent pathological conditions. The current findings help in improving our understanding of the pathogenesis of Meniere disease.

Death of mechanosensory hair cells in the inner ear is a common cause of auditory and vestibular impairment in mammals, which have a limited ability to regrow these cells after damage. In contrast, non-mammalian vertebrates, including zebrafish, can robustly regenerate hair cells after severe organ damage. The zebrafish inner ear provides an understudied model system for understanding hair cell regeneration in organs that are highly conserved with their mammalian counterparts. Here, we quantitatively examine hair cell addition during growth and regeneration of the larval zebrafish inner ear. We used a genetically encoded ablation method to induce hair cell death and we observed gradual regeneration with correct spatial patterning over a 2-week period following ablation. Supporting cells, which surround and are a source of new hair cells, divide in response to hair cell ablation, expanding the possible progenitor pool. In parallel, nascent hair cells arise from direct transdifferentiation of progenitor pool cells temporally uncoupled from supporting cell division. These findings reveal a previously unrecognized mechanism of hair cell regeneration with implications for how hair cells may be encouraged to regenerate in the mammalian ear.

Following up on our previous observation that early B cell factor (EBF) sites are enriched in open chromatin of the developing sensory epithelium of the mouse cochlea, we investigated the effect of deletion of Ebf1 on inner ear development. We used a Cre driver to delete Ebf1 at the otocyst stage prior to development of the cochlea. We examined the cochlea at postnatal day (P) 1 and found that the sensory epithelium had doubled in size but the length of the cochlear duct was unaffected. We also found that deletion of Ebf1 led to ectopic sensory patches in the Kölliker\'s organ. Innervation of the developing organ of Corti was disrupted with no obvious spiral bundles. The ectopic patches were also innervated. All the extra hair cells (HCs) within the sensory epithelium and Kölliker\'s organ contained mechanoelectrical transduction channels as indicated by rapid uptake of FM1-43. The excessive numbers of HCs were still present in the adult Ebf1 conditional knockout (cKO) animal. The animals had no detectable auditory brainstem response (ABR) suggesting that this gene is essential for hearing development.