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Histamine, which is mainly produced by mast cells and basophils, participates in various allergic symptoms, and some studies have reported that macrophages also produce histamine. Moreover, recent studies have revealed that macrophages, especially alternatively activated macrophages (M2) induced by T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, participate in the pathogenesis of allergic diseases. The major source of Th2 cytokines is antigen-specific Th2 cells. To elucidate the relationship between histamine, macrophages, and Th2 cells in allergic inflammation, we established a macrophage-Th2 cell co-culture model in vitro and an antigen-specific Th2 cell transfer mouse model of rhinitis. In vitro analyses indicated that macrophages produce histamine by interacting with antigen-specific Th2 cells through the antigen. Furthermore, Th2 cells and macrophages cooperatively elicited rhinitis in the mouse model. We determined that histamine induces Th2- and macrophage-elicited sneezing responses through H1 receptor signaling, whereas it induces nasal eosinophil infiltrations through H4 receptor signaling. Collectively, these results indicate a novel histamine production mechanism by macrophages, in which Th2 cells and macrophages cooperatively induce nasal allergic inflammation through histamine signaling.

Background Migraine and dizziness often coexist, with vestibular migraine (VM) presenting with vestibular symptoms and headaches. Calcitonin gene-related peptide (CGRP) may be involved in motion-induced symptoms; however, studies on the use of anti-CGRP monoclonal antibodies (mAbs) for the treatment of VM have yielded conflicting results. This study aimed to clarify the effectiveness of anti-CGRP mAbs in VM treatment. Methods This retrospective observational cohort study, conducted between 1 January 2021 and 31 March 2023, assessed 12 Japanese patients with VM who were treated with anti-CGRP mAbs (CGRP group) for 6 months and 11 Japanese patients who received standard of care for VM and served as controls. Clinical questionnaires and equilibrium tests were administered, with primary outcomes including changes in Dizziness Handicap Inventory (DHI) scores compared with baseline values. Objective variables included the DHI score and explanatory variables included demographic data, balance test results, head-up tilt (HUT) test results, vestibular test results and questionnaire survey results. Analysis of variance was used to assess the treatment effects of anti-CGRP mAbs, and multivariate regression analysis was performed to identify mAb responders. Results After 6 months, the CGRP group showed significant improvements in DHI scores [0 versus 6 months, odds ratio (95% confidence interval): 22.01 (0.13–43.88)] and number of vertigo/dizziness attacks per month [0 versus 6 months: 10.28 (2.80–17.76)]. No significant difference was observed in the control group [DHI scores, 0 versus 6 months: 0.65 (−26.84 to 28.14); number of vertigo/dizziness attacks per month, 0 versus 6 months: − 8.07 (− 23.77 to 7.62)]. Multivariate regression analysis showed that autonomic function at baseline was associated with mAb response in patients [β estimates (95% confidence interval): 3.63 (0.21–7.06)]. Conclusions Treatment with anti-CGRP mAbs was more effective than conventional treatment in preventing migraine in patients with VM. While the identified factors associated with treatment responsiveness offer valuable insights into personalised treatment approaches, further prospective studies are warranted to validate the findings due to our study’s retrospective design and limited sample size.

Objective Histamine derived from mast cells and basophils plays important roles in inducing allergic symptoms. Although T cells also produce histamine, the involvement of the histamine produced from T cells has remained enigmatic. We sought to reveal the roles of T helper 2 (Th2) cell-derived histamine in nasal allergic disorders. Methods The histamine production from Th2 cells was measured by EIA. The mRNA expression of histidine decarboxylase (HDC) was measured by real-time PCR. To investigate the roles of Th2 cell-derived histamine in vivo, we analyzed an antigen-specific Th2 cell transfer mouse model. Results Th2 cells produced histamine by T cell receptor stimulation, and these properties were specific for Th2 cells, but not Th1 cells and naïve CD4 T cells. The histamine produced from Th2 cells was involved in the infiltrations of Th2 cells in response to antigen exposure. Conclusion These results suggest that Th2 cell-derived histamine play important roles in nasal allergic disorders.

The pathophysiology of coronavirus disease 2019 (COVID-19) remains elusive, although it has been associated with symptoms such as dizziness and vertigo. Here, we report a case of vestibular neuritis following COVID-19 in a 57-year-old man who presented with rotational vertigo and dizziness exacerbated by neck rotation. The video head impulse test (vHIT) and ocular vestibular evoked myogenic potential (oVEMP) initially indicated right superior vestibular neuritis. Over a seven-month follow-up, improvements in vHIT and oVEMP were consistent with typical vestibular neuritis recovery; however, persistent postural instability and prolonged orthostatic hypotension suggested additional autonomic nervous system dysfunction. This case highlights the potential long-term vestibular impact of COVID-19.

Age-related hearing loss (ARHL) is linked to dementia, with mitochondrial dysfunction playing a key role in its progression. Deficient mitochondrial tRNA modifications impair protein synthesis and energy metabolism, accelerating ARHL. Mitochonic acid 5 (MA-5) has shown promise as a therapeutic candidate by improving mitochondrial function, reducing oxidative stress, and stabilizing membrane potential. In this study, we investigated the effects of MA-5 on ARHL in cyclin-dependent kinase 5 regulatory subunit-associated protein 1 ( ) knockout (KO) mice, which exhibit early-onset ARHL due to abnormalities in mitochondrial transfer RNA (mt-tRNA) modifications. MA-5 treatment effectively attenuated ARHL progression in -KO mice by improving auditory brainstem response thresholds and distortion product otoacoustic emissions. It also reduced spiral ganglion and outer hair cell loss, while preserving the cochlear structural integrity by preventing mitochondrial degeneration in spiral ligament fibrocytes. Mechanistically, MA-5 upregulated the expression of silent information regulator sirtuin 1 and promoted the nuclear translocation of yes-associated protein, both of which are involved in regulating mitochondrial function and cellular senescence. Metabolomics analysis further demonstrated that MA-5 restored mitochondrial metabolism, reduced lactate accumulation, and maintained mitochondrial integrity. These findings suggest that MA-5 is a viable treatment option for ARHL and other age-related disorders associated with mitochondrial dysfunction.

Facial nerve abnormalities and congenital middle ear malformations originate in similar developmental stages and are often concomitant. Preoperative recognition of such a condition is desirable to prevent any damage, but it is often difficult. Here, we report two cases of middle ear malformations associated with facial nerve abnormalities, describe the computed tomography (CT) appearance, and discuss its preoperative detectability. Case 1 was a 40-year-old female with a facial nerve abnormality associated with stapes ankylosis. She underwent stapes surgery. The facial nerve was hanging over the footplate of the stapes. Case 2 was a 32-year-old female with a facial nerve abnormality associated with stapes ankylosis. She underwent an exploratory tympanotomy. The facial nerve was branched. The branches emerged from the incudo-malleolar joint, ran between the chorda tympani nerve and the incus, and ran into the temporal bone inside the canaliculus chorda tympani. For both cases, the facial nerve branches were detectable with high-resolution CT (HRCT) in the mastoid segment and were confirmed during surgery. For Case 2, the facial nerve was also visible with HRCT as soft tissue shadows in the tympanic portion on the lateral side of the stapes. These two cases highlighted the critical role of preoperative CT imaging in detecting subtle features of facial nerve anomalies, such as nerve branching in the mastoid segment or soft tissue shadows around ossicles.

Malignant tumors arising from the lacrimal sac are rare and present with diverse clinical symptoms. Many primary malignant tumors of the lacrimal sac exhibit lacrimation and are easily misdiagnosed as chronic dacryocystitis, delaying diagnosis and treatment. In this report, we describe a case of a sarcoma that was thought to have originated in the lacrimal sac.

Congenital cholesteatoma is typically an expanding cystic mass of keratinizing squamous epithelium located medial to the intact tympanic membrane in patients with no prior history of perforation, otorrhea and ear. It is generally thought to be a progressive disease and is usually surgically removed upon detection as the first-choice treatment. As such, it is rare to be observed for a long term without progression. Here we report a rare case of congenital cholesteatoma that remained in an undetectable size and did not deteriorate mild hearing loss for 12 years. A seven years old boy was referred to us with right hearing impairment. Pure-tone audiometry found conductive hearing loss with an air-bone gap of 25 dB and a high-resolution computed tomography (CT) scan found the eroded long process of incus but did not detect any soft tissue density indicating congenital cholesteatoma. He initially did not wish to undergo surgery. His hearing level and image finding remained virtually unchanged during the next 12 years of the follow-up period. Twelve years later, endoscopic ear surgery was performed, which revealed a very small cholesteatoma mass, an eroded long process of the incus and ossicular chain discontinuities. We suspect that the cholesteatoma was originally larger, partially eroded the incus, then regressed to a very small size, and remained small for at least 12 years under our observation.

The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.

Objective In this article, we aimed to describe the Foulage test (FT) and investigate the test-retest reliability of parameters recorded during stepping execution in healthy adults. Materials and methods This was a single-center prospective cohort study conducted at an outpatient clinic. It included five healthy male participants [mean age ± standard deviation (SD): 27 ± 5.4 years]. The FT was performed first with the participants' eyes open and again with their eyes closed. If the heel height was not within 2-6 cm, the participant was asked to restart. The FT value and variance of steps were automatically calculated. To verify the influence of heel height, measurements were taken at different heel heights. We also evaluated the Romberg ratio (calculated from the parameters with eyes open and closed) and defined it as the dynamic Romberg ratio. Correlations between parameters were also assessed. Results The parameters' FT value (front-back width of the band of locus shape) and variance of steps plateaued under stable conditions within a heel height of 2-6 cm. FT values and variance of steps were strongly correlated. The dynamic Romberg ratios by FT value and by the variance of steps were also strongly correlated. Conclusions The FT is a dynamic and reproducible equilibrium function test that can quantify agitation with the eyes open or closed in general outpatient clinics, and it may be employed as a clinically useful method for the observation of clinical courses in patients with vestibular disorders.