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DOI： 10.1136/bcr-2023-259348

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PURPOSE: Removal of the current calcium alginate packing materials to the middle meatus in endoscopic sinus surgery (ESS) is usually accompanied by discomfort or pain owing to the hard and brittle nature of these materials. Plus moist HS-W® is a new calcium alginate packing material released in 2022 developed to overcome this issue by changing the uronic acid component. We aimed to compare the discomfort/pain during the removal of Plus moist HS-W® with Kaltostat®, as well as their suitability as packing materials in ESS. METHODS: Kaltostat® and Plus moist HS-W® were used as packing materials in 22 and 21 patients who underwent ESS in 2021 and 2022, respectively. Patients were asked to rate the pain during the packing removal 10 days after ESS using the Numerical Rating Scale (NRS). The ratio of residual packing materials, number of suctions (insertions/extractions of the suction cannula), and time required to remove packing materials were measured. Postoperative complications such as hemorrhage, local infection, lateralization of the middle turbinate, and synechia of the middle meatus were also evaluated. RESULTS: The Plus moist HS-W® group exhibited significantly lower NRS pain scores, a lower ratio of residual packing materials, a reduced number of suctions, and a shorter time required to remove the packing. No obvious postoperative complications occurred in both groups except for one suspicious case of a slight infection in the Kaltostat® group. CONCLUSION: Compared with Kaltostat®, Plus moist HS-W®, characterized by better gelatinization than Kaltostat®, benefits patients by minimizing discomfort/pain during removal. LEVEL OF EVIDENCE: Level 3.

DOI： 10.1007/s00405-023-08437-4

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BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

DOI： 10.1007/s10147-023-02423-w

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Ectopic parathyroid lesions can be difficult to detect. In the present study, we used near-infrared autofluorescence imaging (NIFI) in three cases of ectopic parathyroid lesions. Our results suggest that NIFI may be a confirmation tool for parathyroid pathology and an intraoperative navigation tool in vivo and ex vivo. Laryngoscope, 134:496-500, 2024.

DOI： 10.1002/lary.30728

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Language：Japanese   Publisher：新潟県医師会  

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DOI： 10.1007/s10147-024-02545-9

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The sarcopenia index (SI), calculated as [(serum creatinine/serum cystatin C) × 100], maybe a simpler alternative for measuring muscle mass than computed tomography (CT) and bioelectrical impedance analysis (BIA). We enrolled 112 patients with head and neck cancers (HNC). The correlation of the SI with muscle surface area measured by CT (CTMSA, n = 82) and muscle mass by BIA (BIA-MM, n = 41) was tested. Cutoff values were set for SI, CTMSA, and BIA-MM. Overall survival (OS) was compared between the high- and low-SI/CTMSA/BIA-MM groups. The SI was correlated with CTMSA (r = 0.43) and BIA-MM (r = 0.52). The optimal cutoff values of SI, CTMSA, and BIA-MM were 76.1 (area under the curve [AUC] = 0.67), 129.2 (AUC = 0.59), and 46.1 (AUC = 0.62), respectively. OS was significantly lower in the low-SI group (78% at 1 year and 69% at 2 years) than in the high-SI group (94% at 1 year and 86% at 2 years; p = 0.006). There was no significant difference in OS between the low-and high-CTMSA and -BIA-MM groups. The SI, which only requires a blood sample, is a useful marker of muscle mass that correlates with short-term prognosis in patients with HNC.

DOI： 10.1080/01635581.2023.2290299

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.oor.2023.100107

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INTRODUCTION: Immune-related adverse events (irAEs) are prognostic factors for patients on nivolumab. However, predictors of irAEs have not yet been identified. We aimed to investigate the predictors of irAEs occurrence and nivolumab discontinuation due to irAEs. METHODS: Sixty-two patients with recurrent/metastatic head and neck squamous cell carcinoma received nivolumab therapy between June 2017 and December 2020. Treatment outcome was compared between the groups with or without irAEs. The irAE (+) group was further divided by nivolumab discontinuation. Progression-free survival (PFS) and overall survival (OS) were compared between the groups. Predictors of irAE occurrence were analyzed. RESULTS: Twenty-one patients (33.9%) developed irAEs, and six (28.6%) discontinued nivolumab due to severe irAEs. The irAE (+) group had significantly longer PFS and OS than the irAE (-) group (median PFS, 12.7 vs. 1.9 months; median OS, 33.1 vs. 12.8 months). The treatment outcomes in the discontinuation group were comparable to those in the non-discontinuation group. The maximum absolute eosinophil count (AEC) during nivolumab therapy was significantly higher in the irAE (+) group than in the irAE (-) group (548.8 vs. 182) and higher in the discontinuation group than in the non-discontinuation group (729.3 vs. 368.6). The receiver operating characteristic curve showed that the maximum AEC had a moderate-to-high accuracy for predicting irAE occurrence (area under the curve [AUC], 0.757) and nivolumab discontinuation (AUC, 0.893). DISCUSSION: Monitoring AEC during nivolumab therapy may be useful in predicting irAE occurrence, nivolumab discontinuation, and disease prognosis.

DOI： 10.1002/cam4.6648

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DOI： 10.1016/j.oraloncology.2023.106501

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NRF2 is a transcription factor responsible for antioxidant stress responses that is usually regulated in a redox-dependent manner. p62 bodies formed by liquid-liquid phase separation contain Ser349-phosphorylated p62, which participates in the redox-independent activation of NRF2. However, the regulatory mechanism and physiological significance of p62 phosphorylation remain unclear. Here, we identify ULK1 as a kinase responsible for the phosphorylation of p62. ULK1 colocalizes with p62 bodies, directly interacting with p62. ULK1-dependent phosphorylation of p62 allows KEAP1 to be retained within p62 bodies, thus activating NRF2. p62S351E/+ mice are phosphomimetic knock-in mice in which Ser351, corresponding to human Ser349, is replaced by Glu. These mice, but not their phosphodefective p62S351A/S351A counterparts, exhibit NRF2 hyperactivation and growth retardation. This retardation is caused by malnutrition and dehydration due to obstruction of the esophagus and forestomach secondary to hyperkeratosis, a phenotype also observed in systemic Keap1-knockout mice. Our results expand our understanding of the physiological importance of the redox-independent NRF2 activation pathway and provide new insights into the role of phase separation in this process.

DOI： 10.15252/embj.2022113349

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BACKGROUND: During oral and head and neck surgery, oral vestibular incisions may require a transverse incision on the upper lip mucosa, resulting in possible sensory disturbances in the area innervated by infraorbital nerve (ION) branches. Although sensory disturbances are attributed to nerve injuries, anatomy textbooks have not showed the precise distribution patterns of the ION branches in the upper lip. Furthermore, no detailed study has been available on this issue. This study aimed to reveal the precise distribution patterns of ION branches in the upper lip by dissecting the detached upper lip and cheek area using a stereomicroscope. METHODS: During a gross anatomy course at Niigata University (2021-2022), nine human cadavers were examined with special focus on the relationship between ION branches in the upper lip and the layered structure of facial muscles. RESULTS: The ION branched to the inferior palpebral (IP), external and internal nasal, and superior labial (lateral and medial) nerves. The ION branches in the upper lip did not run in a horizontal pattern from outside to inside but showed a predominantly vertical pattern. Considering their course, incising the upper lip mucosa transversely may cause paresthesia of the ION branches. The internal nasal (IN) and medial superior labial (SLm) branches tended to penetrate the orbicularis oris and descend between this muscle and labial glands, whereas the lateral superior labial (SLl) branches tended to innervate the skin. CONCLUSIONS: These findings suggest that a lateral mucosal incision is recommended for oral vestibular incisions of the upper lip and that deeper incisions to the labial glands should be avoided when incising the medial side to preserve the ION during surgery from an anatomical point of view.

DOI： 10.1016/j.aanat.2023.152118

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On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography-mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 μL of whole blood from dosed rats within ∼10 min. This approach with the 'reusable' sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

DOI： 10.1016/j.heliyon.2023.e15963

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J07551&link_issn=&doc_id=20230201440008&doc_link_id=%2Fdz0tokei%2F2023%2F012601%2F009%2F0038-0045%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0tokei%2F2023%2F012601%2F009%2F0038-0045%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a functional chronic vestibular syndrome with symptom exacerbation by upright posture, motion, and complex visual stimuli. Among these exacerbating factors, visual exacerbation is the most specific characteristic of PPPD requiring further investigation. We hypothesized that stimulus-induced changes occur in the functional connectivity (FC) rather than simple neural activation that is involved in visual stimulation. The present study aimed to identify the neural basis of PPPD by investigating FC before and after visual stimulation. METHODS: Eleven patients with PPPD and 11 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI (rs-fMRI) before and after task-based fMRI with visual stimuli. RESULTS: At pre-stimulus, FC between the vestibular cortex and visual areas was low, while that between the somatosensory and visual areas was high in PPPD compared with that in HCs. FC between the visuospatial (parahippocampal gyrus) and spatial cognitive areas (inferior parietal lobule) was elevated in PPPD even in the pre-stimulus condition, which no longer increased at post-stimulus as observed in HCs. In the post-stimulus condition, FC between the visual and spatial cognitive areas and that between the visual and prefrontal areas increased compared with that in the pre-stimulus condition in PPPD. Task-based fMRI demonstrated that no brain regions showed different activities between the HC and PPPD groups during visual stimulation. DISCUSSION: In PPPD, vestibular inputs may not be fully utilized in the vestibulo-visuo-somatosensory network. Given that the FC between visuospatial and spatial cognitive areas increased even in HCs after visual stimuli, elevated status of this FC in combination with the high FC between the somatosensory and visual areas would be involved in the visual exacerbation in PPPD. An increase in FC from the visual areas to spatial cognitive and prefrontal areas after visual stimuli may account for the prolonged symptoms after visual exacerbation and anxious status in PPPD.

DOI： 10.3389/fneur.2023.1215004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Tinnitus therapies have been combined with the use of varieties of sound/noise. For masking external sounds, location of the masker in space is important; however, effects of the spatial location of the masker on tinnitus are less understood. We aimed to test whether a masking sound location would affect the perception level of simulated tinnitus. The 4 kHz simulated tinnitus was induced in the right ear of healthy volunteers through an open-type earphone. White noise was presented to the right ear using a single-sided headphone or a speaker positioned on the right side at a distance of 1.8 m for masking the simulated tinnitus. In other sessions, monaurally recorded noise localized within the head (inside-head noise) or binaurally recorded noise localized outside the head (outside-head noise) was separately presented from a dual-sided headphone. The noise presented from a distant speaker and the outside-head noise masked the simulated tinnitus in 71.1% and 77.1% of measurements at a lower intensity compared to the noise beside the ear and the inside-head noise, respectively. In conclusion, spatial information regarding the masking noise may play a role in reducing the perception level of simulated tinnitus. Binaurally recorded sounds may be beneficial for an acoustic therapy of tinnitus.

DOI： 10.1038/s41598-022-05535-x

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Other Link： https://www.nature.com/articles/s41598-022-05535-x

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PURPOSE: Persistent hypoparathyroidism (hypoPT) is a major complication of total thyroidectomy. Nonetheless, previous reports may have underestimated the prevalence of hypoPT due to patient selection bias. We aimed to estimate the actual prevalence of persistent hypoPT after total thyroidectomy and to find predictive factors for postoperative hypoPT. METHODS: This study retrospectively reviewed data from a health insurance claims-based database provided by the Japan Medical Data Center Co., Ltd. From 2009 to 2019, 2388 patients who underwent total thyroidectomy were identified using the medical procedure codes. Persistent hypoPT was defined as the prescription of active vitamin D supplements for >1 year postoperatively and the assignment of hypoPT codes. The prevalence of persistent hypoPT was estimated at two different levels: minimum and maximum estimations with or without postoperative osteoporosis and/or renal failure codes. Correlates for persistent hypoPT were investigated among several demographic and clinical variables. RESULTS: Of the 2388 patients, 1752 (73.4%) were women with a mean age of 45 years. The types of diseases were: benign thyroid disease (n = 235), malignant thyroid tumors (n = 1570), Graves ' disease (n = 558), and malignancy combined with Graves' disease (n = 25). The minimum and the maximum estimation of the prevalence of persistent hypoPT were 15.0 and 20.3%, respectively. Multivariate logistic regression analysis showed that the malignant tumor (odds ratio, 1.8) independently correlated with persistent hypoPT. CONCLUSIONS: The prevalence of persistent hypoPT after total thyroidectomy estimated by the claims-based database was higher than previously recognized. Comprehensive attempts to preserve parathyroid function, especially in malignant diseases, are essential.

DOI： 10.1007/s12020-022-03153-1

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Posture and gait are maintained by sensory inputs from the vestibular, visual, and somatosensory systems and motor outputs. Upon vestibular damage, the visual and/or somatosensory systems functionally substitute by cortical mechanisms called "sensory reweighting". We investigated the cerebrocortical mechanisms underlying sensory reweighting after unilateral labyrinthectomy (UL) in mice. Arc-dVenus transgenic mice, in which the gene encoding the fluorescent protein dVenus is transcribed under the control of the promoter of the immediate early gene Arc, were used in combination with whole-brain three-dimensional (3D) imaging. Performance on the rotarod was measured as a behavioral correlate of sensory reweighting. Following left UL, all mice showed the head roll-tilt until UL10, indicating the vestibular periphery damage. The rotarod performance worsened in the UL mice from UL1 to UL3, which rapidly recovered. Whole-brain 3D imaging revealed that the number of activated neurons in S1, but not in V1, in UL7 was higher than that in sham-treated mice. At UL7, medial prefrontal cortex (mPFC) and agranular insular cortex (AIC) activation was also observed. Therefore, sensory reweighting to the somatosensory system could compensate for vestibular dysfunction following UL; further, mPFC and AIC contribute to the integration of sensory and motor functions to restore balance.

DOI： 10.1038/s41598-022-19678-4

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DOI： 10.1016/S1473-3099(22)00316-4

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OBJECTIVE: The management for malodour of malignant fungating wounds (MFWs) in head and neck cancer (HNC) is unestablished. We evaluated the effects of a novel odour transferrer on malodour generated by MFWs in patients with HNC. METHODS: A spray-type odour transferrer approved by the Japanese government for safe use in humans produces a good scent by binding to bad odour. The odour of MFWs in 13 patients with HNC was scored by 37 medical staff and the patients' families using an odour scale ranging from 0 to 4 before and 1 week after application of the odour transferrer. RESULTS: The odour score marked by all investigators (n=37), nurses (n=21) and doctors (n=11) decreased significantly (p<0.01). The odour score decreased by more than 2 points for 73% of all investigators after odour transferrer application. CONCLUSION: This novel odour transferrer functions as an effective deodorant for MFWs in patients with HNC. It can be used by non-medical staff and may benefit patients with bad odours arising from MFWs as well as their families and medical staff.

DOI： 10.1136/spcare-2022-003824

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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OBJECTIVE: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. MATERIALS AND METHODS: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. RESULTS: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). CONCLUSION: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

DOI： 10.3389/fsurg.2022.1049116

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BACKGROUND: Head and neck mucosal melanoma (HNMM) is a rare and aggressive subtype of melanoma. HNMM often develops as a recurrent or metastatic disease, and its prognosis is worse than that of cutaneous melanoma. Recent large-scale clinical studies have reported favorable outcomes with immune checkpoint inhibitors (ICIs) for melanoma. However, these clinical trials included only a small number of HNMM cases. This study aimed to estimate treatment outcomes and prognostic predictors of ICIs for advanced HNMM. METHODS: Cases of advanced HNMM, defined as unresectable or metastatic HNMM at the initial diagnosis (five patients) or development of recurrent/metastatic HNMM after initial treatment (27 patients), were included in this study. Survival analysis and a search for prognostic factors were performed for these 32 patients. Furthermore, the detailed clinical course of patients who received ICI treatment was investigated. RESULTS: The median overall survival (OS) of 32 patients with advanced HNMM was 25.3 months. The estimated 1-, 3-, and 5-year OS rates were 68.4%, 42.8%, and 34.3%, respectively. Fourteen patients (43.7%) received ICIs, whereas 18 (56.3%) did not. Univariate analysis showed that ICI treatment was the only factor associated with a better 1-year OS. Patients who received ICI treatment had significantly longer OS (median OS: not reached, 1-year OS: 85.7%) than those who did not (median OS: 11.3 months, 1-year OS: 54.5%). The overall response and disease control rates of patients who received ICI treatment were 50% and 64.3%, respectively. Patients who achieved complete response (CR) or partial response (PR) to ICI treatment survived significantly longer (1-year OS: 100%) than those who did not (1-year OS: 71.4%). Among the five patients who discontinued ICI treatment due to severe immune-related adverse events (irAEs), four did not receive salvage treatments but showed durable treatment effects and survived for 9.8-54.2 months at the end of the follow-up period. CONCLUSIONS: ICI treatment achieved a favorable OS for advanced HNMM. CR/PR to ICI treatment and discontinuation owing to severe irAEs were favorable predictors of OS.

DOI： 10.3389/fsurg.2022.1032626

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OBJECTIVE: The global standard for chemoradiation therapy (CCRT) for head and neck squamous cell carcinoma is cisplatin 100 mg/m2 administered once every three weeks, although cisplatin 80 mg/m2 is also widely used as an alternative treatment to reduce adverse events in Japan. We aimed to assess the long-term survival outcomes and late adverse events associated with CCRT with a 3-weekly cisplatin dose of 80 mg/m2. METHODS: A phase 2 study on CCRT with a 3-weekly cisplatin dose of 80 mg/m2 was performed in 47 patients between April 2015 and December 2016 at four centers in Japan. Survival outcomes and late adverse events at 5 years after this phase 2 trial were investigated. RESULTS: The median follow-up period was 61 months. The 5-year progression-free survival/overall survival of all 47 patients was 66.0%/76.6%, while that of patients with stage III, IV disease (UICC) was 65.6%/71.9%. Seventeen patients (36%) experienced dysphagia as a late adverse event. Univariate and multivariate analyses revealed a significant association between acute mucositis/low body mass index (BMI) during CCRT and late dysphagia. CONCLUSION: The survival outcomes of CCRT with a 3-weekly cisplatin dose of 80 mg/m2 may be comparable to the previously reported dose of 100 mg/m2. Acute mucositis and low BMI at CCRT were risk factors for late dysphagia, indicating the importance of managing these conditions during CCRT to prevent late adverse events. Caution and care for acute mucositis and swallowing training in patients with low BMI may be important for preventing late-stage dysphagia.

DOI： 10.3389/fsurg.2022.1035349

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INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a chronic vestibular syndrome lasting more than 3 months. The core vestibular symptoms are dizziness, unsteadiness, and non-spinning vertigo, which are exacerbated by upright posture or walking, active or passive motion, and exposure to moving or complex visual stimuli. Among these, visual exacerbation is a key feature of PPPD for which the neural mechanisms are unknown. We hypothesized that vestibular symptoms may be exacerbated by visual stimuli through gaze behavioral change after exposure to moving or complex visual stimuli. The study aimed to examine gaze stability after exposure to moving visual stimuli in patients with PPPD. METHODS: Fourteen healthy controls (HCs), 27 patients with PPPD, and 12 patients with unilateral vestibular hypofunction (UVH), showing chronic vestibular symptoms for >3 months, were enrolled in the study. The participants were instructed to fixate on the gazing point at the center of a screen for 30 s before and after 90 s of exposure to moving visual stimuli. Gaze stability, best represented by the bivariate contour ellipse area (BCEA), was compared among three groups, both before and after exposure to the moving visual stimuli. Comparisons between pre- and post-moving visual stimuli in BCEA were also conducted. Correlation between the post/pre ratio of BCEA and vestibular tests, several clinical symptom scales including the Dizziness Handicap Inventory, Niigata PPPD Questionnaire, and Hospital Anxiety and Depression Scale, and the exacerbation of dizziness by exposure to moving visual stimuli was examined in the PPPD group. RESULTS: BCEA, both before and after exposure to moving visual stimuli in the PPPD group, was not different from that in HC and UVH groups. In the PPPD group, BCEA increased significantly after exposure to moving visual stimuli. The post/pre ratio of BCEA correlated with the occurrence of exacerbation of the dizziness sensation by exposure to moving visual stimuli; however, it did not correlate with vestibular tests or clinical symptom scales. CONCLUSION: Patients with PPPD were more likely to exhibit gaze instability after exposure to moving visual stimuli, which potentially exacerbated vestibular symptoms. This phenomenon may help elucidate the neural mechanisms of visual exacerbation in patients with PPPD.

DOI： 10.3389/fnhum.2022.1056556

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OBJECTIVE: To examine the validity of head roll-tilt subjective visual vertical (HT-SVV) in diagnosing persistent postural-perceptual dizziness (PPPD). STUDY DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Sixty-one patients with PPPD, 10 with unilateral vestibular hypofunction (UVH), and 11 with psychogenic dizziness (PD), showing chronic vestibular symptoms for >3 months. INTERVENTIONS: Head-tilt perception gain (HTPG, i.e., mean perceptual gain [perceived/actual tilt angle]) during right or left head tilt of approximately 30° (HT-SVV) and conventional head-upright SVV (UP-SVV) were measured. Bithermal caloric testing, cervical and ocular vestibular-evoked myogenic potentials (cVEMP and oVEMP), and posturography were conducted. MAIN OUTCOME MEASURES: Multiple comparisons were performed for the HT-SVV and other vestibular tests among the disease groups. A receiver operating characteristic curve was created to predict PPPD using HTPG. RESULTS: HTPG was significantly greater in the PPPD group than in the UVH and PD groups. There were no significant differences in UP-SVV, cVEMP, oVEMP, and posturography (foam ratio and Romberg ratio on foam) among the disease groups, while the UVH group had the highest canal paresis compared to the other two groups. The area under the curve of the receiver operating characteristic curve for predicting PPPD was 0.764, and the HTPG value of 1.202 had a specificity of 95.2% for diagnosing PPPD. CONCLUSIONS: While conventional vestibular tests including UP-SVV, VEMPs, and posturography did not show abnormalities in PPPD, high HTPG in the HT-SVV test, an excessive perception of head tilt, can be a specific marker for discriminating PPPD from other chronic vestibular diseases.

DOI： 10.1097/MAO.0000000000003340

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Excitable cochlear hair cells convert the mechanical energy of sounds into the electrical signals necessary for neurotransmission. The key process is cellular depolarization via K+ entry from K+ -enriched endolymph through hair cells' mechanosensitive channels. Positive 80 mV potential in endolymph accelerates the K+ entry, thereby sensitizing hearing. This potential represents positive extracellular potential within the epithelial-like stria vascularis; the latter potential stems from K+ equilibrium potential (EK ) across the strial membrane. Extra- and intracellular [K+ ] determining EK are likely maintained by continuous unidirectional circulation of K+ through a putative K+ transport pathway containing hair cells and stria. Whether and how the non-excitable tissue stria vascularis responds to acoustic stimuli remains unclear. Therefore, we analysed a cochlear portion for the best frequency, 1 kHz, by theoretical and experimental approaches. We have previously developed a computational model that integrates ion channels and transporters in the stria and hair cells into a circuit and described a circulation current composed of K+ . Here, in this model, mimicking of hair cells' K+ flow induced by a 1 kHz sound modulated the circulation current and affected the strial ion transport mechanisms; the latter effect resulted in monotonically decreasing potential and increasing [K+ ] in the extracellular strial compartment. Similar results were obtained when the stria in acoustically stimulated animals was examined using microelectrodes detecting the potential and [K+ ]. Measured potential dynamics mirrored the EK change. Collectively, because stria vascularis is electrically coupled to hair cells by the circulation current in vivo too, the strial electrochemical properties respond to sounds. KEY POINTS: A highly positive potential of +80 mV in K+ -enriched endolymph in the mammalian cochlea accelerates sound-induced K+ entry into excitable sensory hair cells, a process that triggers hearing. This unique endolymphatic potential represents an EK -based battery for a non-excitable epithelial-like tissue, the stria vascularis. To examine whether and how the stria vascularis responds to sounds, we used our computational model, in which strial channels and transporters are serially connected to those hair cells in a closed-loop circuit, and found that mimicking hair cell excitation by acoustic stimuli resulted in increased extracellular [K+ ] and decreased the battery's potential within the stria. This observation was overall verified by electrophysiological experiments using live guinea pigs. The sensitivity of electrochemical properties of the stria to sounds indicates that this tissue is electrically coupled to hair cells by a radial ionic flow called a circulation current.

DOI： 10.1113/JP281981

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AVES  

DOI： 10.5152/iao.2021.20142

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

DOI： 10.3389/fsurg.2021.708245

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc  

DOI： 10.1002/lary.29310

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Hearing loss affects &amp;gt;5% of the global population and therefore, has a great social and clinical impact. Sensorineural hearing loss, which can be caused by different factors, such as acoustic trauma, aging, and administration of certain classes of drugs, stems primarily from a dysfunction of the cochlea in the inner ear. Few therapeutic strategies against sensorineural hearing loss are available. To develop effective treatments for this disease, it is crucial to precisely determine the behavior of ototoxic and therapeutic agents in the microenvironment of the cochlea in live animals. Since the 1980s, a number of studies have addressed this issue by different methodologies. However, there is much less information on pharmacokinetics in the cochlea than that in other organs; the delay in ontological pharmacology is likely due to technical difficulties with accessing the cochlea, a tiny organ that is encased with a bony wall and has a fine and complicated internal structure. In this review, we not only summarize the observations and insights obtained in classic and recent studies on pharmacokinetics in the cochlea but also describe relevant analytical techniques, with their strengths, limitations, and prospects.

DOI： 10.3389/fphar.2021.633505

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OBJECTIVES/HYPOTHESIS: To assess the ability of near-infrared fluorescence imaging (NIFI) to identify parathyroid glands (PGs) among histologically proven PG/non-PG specimens compared with a surgeon's visual acumen, and to determine NIFI sensitivity in detecting incidentally resected PGs from thyroidectomy specimens, compared to the surgeon's visual inspection. STUDY DESIGN: Prospective study. METHODS: With mean age of 61 years, 36 patients with various thyroid diseases were enrolled. Possible PGs (n = 28) and lymph nodes (n = 32) were identified by the experienced surgeon's visual inspection. Using NIFI, 15 PGs were further identified from thyroidectomy specimens. For these 75 specimens, the surgeon's judgments (PG vs. non-PG) were recorded. Histological evaluation was performed after examining the NIFI auto-fluorescence of each specimen. RESULTS: There were no significant differences in sensitivity, specificity, positive predictive value, and negative predictive value between the surgeon's visual inspection and NIFI in identifying PGs, with values of 100%/97.1%, 85.0%/87.5%, 85.4%/87.2%, and 100%/97.2%, respectively. The sensitivity of NIFI (82.9%) for detection of PGs from thyroidectomy specimens was significantly higher than that of the surgeon's visual inspection (61.0%). False negative specimens contained bleeding/congestion and/or encapsulation by thick tissues, whereas false positive specimens contained electrocoagulated tissues. CONCLUSIONS: NIFI showed results comparable to the experienced surgeon's visual inspection in identifying PGs. This could benefit novice surgeons. NIFI may be useful for experienced surgeons to locate incidentally resected PGs within thyroidectomy specimens for auto-transplantation. Prevention of intra-gland bleeding and congestion, careful removal of thick capsules, and bloodless surgeries without electrocoagulation are important for reducing false positive and false negative results. Laryngoscope, 131:1188-1193, 2021.

DOI： 10.1002/lary.29163

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

DOI： 10.3389/fneur.2021.652366

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01099&link_issn=&doc_id=20210226330006&doc_link_id=10.3950%2Fjibiinkoka.124.122&url=https%3A%2F%2Fdoi.org%2F10.3950%2Fjibiinkoka.124.122&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

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DOI： 10.1093/ndt/gfaa319

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BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.

DOI： 10.1093/ndt/gfaa223

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
Auditory neurophysiological responses, such as steady-state responses, event-related potential P300/P3, and phase-amplitude coupling, are promising translational biomarkers for schizophrenia, but their molecular underpinning is poorly understood. Focusing on ErbB receptor signals that are implicated in both schizophrenia and auditory processing/cognition, we explored the causal biological links between ErbB signals and these auditory traits with an experimental intervention into rats. We peripherally challenged rat pups with one of the amniotic ErbB ligands, epidermal growth factor (EGF), and characterized its consequence on the series of these auditory electrocorticographic measures. Auditory brainstem responses (ABRs) and cortical ON responses were also assessed under anesthesia to estimate the influence of higher brain regions. An auditory steady-state paradigm revealed attenuation of spectral power and phase synchrony to 40-Hz stimuli in EGF-challenged rats. We observed a reduction in duration mismatch negativity-like potentials and a delay of P3a responses, all of which are relevant to the reported auditory pathophysiological traits of patients with schizophrenia. Moreover, the perinatal EGF challenges resulted in enhanced theta-alpha/beta and theta-gamma coupling within the auditory cortex and changes in ABRs. However, the EGF challenges retained the normal ranges of cortical ON responses, potentially ruling out their fundamental auditory deficits. Perinatal exposure of an ErbB ligand to rats strikingly reproduced the whole series of aberrant auditory responses and oscillations previously reported in patients with schizophrenia. Accordingly, these findings suggest that developmental deficits in ErbB/EGF signaling might be involved in the auditory pathophysiology associated with schizophrenia.

DOI： 10.1093/schizbullopen/sgaa070

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BACKGROUND: Early detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection. METHODS: Sixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined. RESULTS: The 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness. CONCLUSION: The treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

DOI： 10.3389/fsurg.2021.813260

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/JIBIINKOKA.124.998

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Objective: We aimed to compare the outcomes and safety of chemoradiotherapy (CRT) between elderly and non-elderly patients with head and neck squamous cell carcinoma (HNSCC). It is difficult to assess the causal effect of age because of possible differences in general conditions among individuals. Therefore, we adjusted the background factors of elderly and non-elderly patients using propensity score matching (PSM). Methods: A total of 146 patients with HNSCC who received CRT were divided into an elderly (≥70 years, n = 35) and non-elderly group (<70 years, n = 111). Pre-treatment characteristics, including the performance status, Charlson comorbidity index, body mass index, primary site, and TNM stage were adjusted by PSM. We compared the outcomes and safety of CRT with high-dose single-agent cisplatin (CDDP) as well as outcomes following recurrence between the groups, before and after PSM. Results: The total dose of CDDP administered during CRT was significantly lower in the elderly group before PSM. However, it became comparable to the non-elderly group and adverse events did not differ between the groups following PSM, resulting in a comparable CRT completion rate. Overall-, disease specific-, and progression-free survivals of elderly patients were comparable to those of non-elderly patients following PSM. In contrast, elderly patients with recurrence could receive fewer salvage treatments than their non-elderly counterparts, resulting in worse survival. Conclusions: CRT with high-dose CDDP is safe and effective for the treatment of elderly patients with HNSCC. However, salvage treatments can be rarely conducted for elderly patients with a recurrence, considering a deterioration of their general condition.

DOI： 10.3389/fsurg.2021.753049

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media S.A.  

DOI： 10.3389/fsurg.2020.601692

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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BACKGROUND: It was reported that treatment outcomes of the salvage chemotherapy (SCT) following nivolumab are fairly good compared with those of nivolumab itself. However, predictive factors of SCT for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) were not determined. METHODS: Twenty-one R/M HNSCC patients received SCT following nivolumab. The treatment outcome and predictive factors for the favorable response to SCT were investigated. RESULTS: The objective response rate (ORR) and the disease control rate of SCT were 52.4% and 81.0%, respectively. The median progression-free survival and the median overall survival time were 5.4 and 12.9 months, respectively. Patients with positive programmed death-ligand 1 (PD-L1) expression showed greater tumor shrinkage evaluated by the response evaluation criteria in solid tumors and higher ORR than those with negative PD-L1 expression. CONCLUSIONS: Treatment outcome of SCT following nivolumab in R/M HNSCC was favorable. PD-L1 expression may be a predictive factor of SCT.

DOI： 10.1002/hed.26374

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.anl.2020.02.017

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J00580&link_issn=&doc_id=20201006300003&doc_link_id=10.5631%2Fjibirin.113.615&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.113.615&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NLM (Medline)  

DOI： 10.1097/MAO.0000000000002720

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Endoscopic submucosal dissection (ESD) has gained wide acceptance as a minimally invasive and curative surgery for superficial head and neck carcinoma. However, the safety of ESD for superficial pharyngeal carcinoma after radiotherapy has not been elucidated. Superficial hypopharyngeal carcinoma of the left pyriform sinus developed in a 76-year-old man who had undergone concurrent chemoradiotherapy for T2N2bM0 pyriform sinus carcinoma on the opposite side 12 months before. He underwent ESD without complications. Because tumor invasion into the muscular layer was a concern, the muscular layer was partially resected with the tumor. Twelve days after discharge, he presented with a sore throat and difficulty in swallowing. Endoscopy and computed tomography revealed necrosis due to wound infection with abscess formation around the left carotid artery. The common carotid artery subsequently ruptured. Although the surgical intervention was performed, he passed away 46 days after ESD due to carotid blowout. ESD is a minimally invasive treatment for superficial head and neck carcinoma, but carotid blowout can occur in cases after radiation. Prior radiotherapy and deeper dissection into the muscular layer may hamper wound epithelization, resulting in infection-induced necrosis and carotid blowout. Diligent monitoring of wound healing is essential in patients who have previously undergone irradiation.

DOI： 10.1016/j.anl.2020.08.020

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PURPOSE: Sarcopenia, defined as a decrease in the skeletal muscle mass and its function, is associated with a poor clinical outcome in several malignancies. We aimed to examine whether sarcopenia can be a predictor of incompletion of concurrent chemoradiotherapy (CCRT) and survival for head and neck cancer (HNC) patients. METHODS: Forty-one male HNC patients who received CCRT were enrolled in the study. Cross-sectional muscle areas at the third lumbar vertebral level were normalized by the squared height of the patients and were termed the lumbar skeletal muscle index (LSMI, cm2/m2), a marker of sarcopenia. Patients were divided into high (30/41, 73%) and low (11/41, 27%) LSMI groups. The LSMI cut-off value was set at 39.7 cm2/m2 based on a receiver operating characteristic curve for incompletion of CCRT. The groups were compared for survival rate by the Kaplan-Meier method. Factors predicting incompletion of CCRT were investigated among several variables. RESULTS: Multivariate analysis showed that a pre-treatment low LSMI (P = 0.033) and age over 70 years (P = 0.023) were the only significant predictors for incompletion of CCRT. The 2-year disease-specific survival (DSS) rate was significantly lower in the low LSMI group (61%) than in the high LSMI group (97%, P = 0.012), whereas there were no differences in the DSS rate between the low and high body mass index groups. CONCLUSION: The prevalence of sarcopenia in HNC patients receiving CCRT was 27%. Its presence before treatment was a significant predictor of incomplete CCRT and poor DSS rate in HNC patients.

DOI： 10.1007/s00405-020-06273-4

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PURPOSE: The importance of nivolumab for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is rapidly increasing. However, prognostic factors have not been determined for predicting treatment outcome. We aimed to investigate the prognostic factors in R/M HNSCC patients treated with nivolumab. METHODS: This retrospective study included 42 patients with R/M HNSCC who received nivolumab therapy. Correlations of overall survival (OS) with various patient characteristics including age, recurrent/metastatic site, performance status (PS), programmed death-ligand 1 positivity, body mass index, neutrophil-to-lymphocyte ratio, modified Glasgow prognostic score (mGPS), previous cetuximab administration, and immune-related adverse events were investigated. RESULTS: The overall response rate and disease control rate were 16.7% and 45.2%, respectively. Estimated 1-year OS and progression-free survival (PFS) were 56.4% and 24.5%, respectively. Multivariate analysis revealed that PS = 2 (hazard ratio 0.147; 95% CI 0.041-0.527; p = 0.003) and mGPS = 2 (hazard ratio 0.188; 95% CI, 0.057-0.620; p = 0.006) were independent predictors of poor OS. Given that the PS and mGPS were independent prognostic factors, we classified patients into three groups according to PS and mGPS: Group 1, both PS and mGPS were 0 or 1 (n = 30); Group 2, either PS or mGPS was 2 (n = 9); Group 3, both PS and mGPS were 2 (n = 3). The OS curves were significantly stratified among the three groups. CONCLUSION: The combination of PS and mGPS accurately predicted OS after nivolumab therapy. Preventive intervention to maintain general condition without simultaneously exceeding level 2 of PS and mGPS might be important for improving treatment outcomes of nivolumab.

DOI： 10.1007/s00405-020-05945-5

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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OBJECTIVE: To test whether the threshold of nerve integrity monitor (NIM) responses during facial nerve decompression surgery can predict the postoperative outcome. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Twenty peripheral facial palsy patients who underwent transmastoid decompression surgery. INTERVENTION: During decompression surgery, thresholds of NIM responses were measured via direct facial nerve stimulation at three sites: the geniculate ganglion (GG), the second genu (2 G), and the stylomastoid foramen. MAIN OUTCOME MEASURES: Facial nerve function was evaluated before and 6 months after surgery using the Yanagihara grading score (maximum score = 40 points). Complete recovery was defined as an improvement of the grading score to ≥ 36 points without synkinesis. Variables including age, sex, disease (Bell's palsy or Ramsay Hunt syndrome), time after onset, Yanagihara grading score, and electroneurography before surgery, and the thresholds of NIM responses during surgery were compared in the complete and incomplete recovery groups. NIM responders were defined as those exhibiting a NIM response of < 1.5 mA at any site. Postoperative Yanagihara grading scores in NIM responders and NIM nonresponders were compared. RESULTS: No variables differed significantly in the complete and incomplete recovery groups before surgery. NIM response thresholds in the complete recovery group at the GG and the 2nd G were significantly lower than the corresponding thresholds in the incomplete recovery group. The postoperative Yanagihara grading scores of NIM responders were significantly better than those of NIM nonresponders. CONCLUSION: NIM responses to intraoperative direct facial nerve stimulation were useful for predicting outcomes after decompression surgery.

DOI： 10.1097/MAO.0000000000002594

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DOI： 10.1097/MAO.0000000000002663

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MAO.0000000000002663

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Language：Japanese   Publisher：(一社)日本内分泌外科学会  

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Identifying the specific functional regulator of integrin family molecules in cancer cells is critical because they are directly involved in tumor invasion and metastasis. Here we report high expression of PLOD2 in oropharyngeal squamous cell carcinomas (SCCs) and its critical role as a stabilizer of integrin β1, enabling integrin β1 to initiate tumor invasion/metastasis. Integrin β1 stabilized by PLOD2-mediated hydroxylation was recruited to the plasma membrane, its functional site, and accelerated tumor cell motility, leading to tumor metastasis in vivo, whereas loss of PLOD2 expression abrogated it. In accordance with molecular analysis, examination of oropharyngeal SCC tissues from patients corroborated PLOD2 expression associated with integrin β1 at the invasive front of tumor nests. PLOD2 is thus implicated as the key regulator of integrin β1 that prominently regulates tumor invasion and metastasis, and it provides important clues engendering novel therapeutics for these intractable cancers.

DOI： 10.1016/j.isci.2020.100850

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.113.615

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Equilibrium Research  

DOI： 10.3757/jser.79.62

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OBJECTIVE: To examine the association between hearing impairment and cognitive decline and to identify possible risk factors for presbycusis. STUDY DESIGN: Cross-sectional survey in prospective cohort study. SETTING: University hospital. PATIENTS: A total of 322 participants aged >60 years, for whom all the below data were available, were enrolled in the study. There were 168 females and 154 males with a median age of 71 years (range: 60-89 yrs). INTERVENTIONS: PROST (Project in Sado for Total Health), a medical database in Sado island Japan, was analyzed. MAIN OUTCOME MEASURES: Data on pure-tone audiometry, mini-mental state examination (MMSE), polymorphism of apolipoprotein E4 (ApoE4), diabetes mellitus, hypertension, smoking, and alcohol consumption were extracted. Hearing impairment was defined as an average frequency between 0.25 and 8 kHz that exceeded 30 dB. Multivariate analysis was used to identify which of the above factors could predict the hearing impairment. Hearing threshold of each Hz was compared between the ApoE4 (+/+), (+/-), and (-/-) groups. RESULTS: Among various factors, only low MMSE scores (<24) showed significant association with hearing impairment. There were no differences in the hearing threshold of all frequencies between ApoE status groups. CONCLUSIONS: Hearing impairment was associated with low MMSE sores, regardless of the ApoE4 status. If ApoE4 status would be a common upstream predictor for both the hearing and cognitive impairment, hearing threshold would be related to ApoE4 status. However, these results may suggest that hearing impairment may be causally related to the cognitive dysfunction, perhaps via the cognitive load mechanisms.

DOI： 10.1097/MAO.0000000000002415

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04210&link_issn=&doc_id=20191115330005&doc_link_id=10.5106%2Fjjshns.29.123&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.29.123&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Lippincott Williams and Wilkins  

DOI： 10.1097/MAO.0000000000002325

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.anl.2019.01.012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd  

DOI： 10.1080/00016489.2019.1612531

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J04210&link_issn=&doc_id=20190312410012&doc_link_id=10.5106%2Fjjshns.28.313&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.28.313&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

DOI： 10.1007/s00405-019-05385-w

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DOI： 10.1016/j.anl.2018.11.007

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DOI： 10.1016/j.anl.2018.10.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.anl.2018.02.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.anl.2018.02.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.anl.2017.12.004

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：日本内分泌外科学会・日本甲状腺外科学会  

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OBJECTIVE: The presence of endolymphatic hydrops in the inner ear, which can be detected with gadolinium-enhanced magnetic resonance imaging (Gd-MRI), is widely recognized as the main pathological cause of Ménière's disease (MD). However, the precise mechanisms underlying the development of endolymphatic hydrops remains unclear. One hypothesis proposes a relationship between the presence of a high jugular bulb (HJB) and MD, which disrupts the vestibular aqueduct leading to the development of endolymphatic hydrops. This study sought to identify anatomical features in MD patients using computed tomography (CT) images of the temporal bone. METHODS: Fifty-nine MD patients meeting the AAO-HNS diagnostic criteria and exhibiting endolymphatic hydrops in Gd-MRI were enrolled between July 2009 and December 2015. We only included MD patients who showed unilateral endolymphatic hydrops in Gd-MRI. Sixty-six patients with otosclerosis or facial palsy were also enrolled as control participants. In both groups, patients with other pathologies (e.g., chronic otitis media or cholesteatoma) and patients <16years old were excluded. HJB was defined as a JB that was observable in the axial CT image at the level where the round window could be visualized. JB surface area was measured on the axial image at the level where the foramen spinosum could be visualized. Finally, to investigate the relationship between the pneumatization of perivestibular aqueductal air cells and the existence of endolymphatic hydrops, the development of the air cells was rated using a three-grade evaluation system and the distance between the posterior semicircular canal (PSCC) and the posterior fossa dura was measured. RESULTS: The presence of HJB was observed in 22 of 59 affected sides of MD patients and in 17 healthy sides. The likelihood that HJB was detected on an affected side (22/39) was not significantly above chance (50%). The HJB detection rate did not significantly differ between the three groups (MD affected side, MD healthy side, and control patients). Furthermore, there were no significant group differences in JB surface area, distance between the PSCC and posterior fossa dura, or the development of perivestibular aqueductal air cells. CONCLUSION: We did not find any relationship between the anatomy of the temporal bones and the existence of endolymphatic hydrops. Moreover, we found no evidence suggesting that HJB or poor development of perivestibular aqueductal air cells were the cause of endolymphatic hydrops in MD patients.

DOI： 10.1016/j.anl.2017.09.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41598-018-28034-4

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Other Link： http://www.nature.com/articles/s41598-018-28034-4

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

DOI： 10.1007/s12565-016-0383-5

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/23772484.2018.1477508

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Lippincott Williams and Wilkins  

DOI： 10.1097/MAO.0000000000001587

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Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerular disease, in which the mucosal immune response elicited particularly in the tonsils or intestine has been estimated to be involved in the development of the disease. To explore the relationship between IgAN and bacterial flora in the tonsils, we conducted a comprehensive microbiome analysis. Methods: We enrolled 48 IgAN patients, 21 recurrent tonsillitis (RT) patients without urine abnormalities and 30 children with tonsillar hyperplasia (TH) who had undergone tonsillectomy previously. Genomic DNA from tonsillar crypts of each patient was extracted, and V4 regions of the 16S ribosomal RNA gene were amplified and analysed using a high-throughput multiplexed sequencing approach. Differences in genus composition among the three study groups were statistically analysed by permutational multivariate analysis of variance and visualized by principal component analysis (PCA). Results: Substantial diversity in bacterial composition was detected in each sample. Prevotella spp., Fusobacterium spp., Sphingomonas spp. and Treponema spp. were predominant in IgAN patients. The percentage of abundance of Prevotella spp., Haemophilus spp., Porphyromonas spp. and Treponema spp. in IgAN patients was significantly different from that in TH patients. However, there was no significant difference in the percentage of abundance of any bacterial genus between IgAN and RT patients. PCA did not distinguish IgAN from RT, although it discriminated TH. No significant differences in microbiome composition among the groups of IgAN patients according to clinicopathological parameters were observed. Conclusions: Similar patterns of bacteria are present in tonsillar crypts of both IgAN and RT patients, suggesting that the host response to these bacteria might be important in the development of IgAN.

DOI： 10.1093/ndt/gfw343

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Lippincott Williams and Wilkins  

DOI： 10.1097/MAO.0000000000001566

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DOI： 10.1007/s00405-017-4739-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc.  

DOI： 10.1002/lary.26579

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Language：Japanese   Publisher：(一社)日本鼻科学会  

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DOI： 10.1177/0003489417705395

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DOI： 10.18103/mra.v5i6

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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DOI： 10.1080/00016489.2016.1227478

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As a canalith repositioning procedure effectively treats H-BPPV with TGPN, but not PGPN, the differentiation between patients with PGPN and with TGPN is essential. The purpose of this study is to determine the observation period enough to distinguish TGPN from PGPN.

DOI： 10.1080/00016489.2016.1227478

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DOI： 10.1097/MAO.0000000000001223

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DOI： 10.3233/VES-170622

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DOI： 10.2220/biomedres.38.239

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DOI： 10.3233/VES-170521

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DOI： 10.1159/000479387

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DOI： 10.1080/23772484.2017.1303605

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DOI： 10.1177/0194599816660072

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DOI： 10.1038/srep34421

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Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

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DOI： 10.5981/jjhnc.42.70

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J01099&link_issn=&doc_id=20160204510005&doc_link_id=%2Fdz0jibik%2F2016%2F011901%2F005%2F0029-0036%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2016%2F011901%2F005%2F0029-0036%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.119.941

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DOI： 10.3233/VES-160582

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DOI： 10.1159/000449238

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.119.118

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DOI： 10.3109/00016489.2015.1104723

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DOI： 10.1080/23772484.2016.1256214

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.109.83

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.118.1150

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

DOI： 10.3950/jibiinkoka.118.1150

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.118.770

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DOI： 10.1007/s10157-014-0968-z

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DOI： 10.1136/bmjopen-2014-006607

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DOI： 10.3109/00016489.2015.1040172

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DOI： 10.3109/00016489.2015.1043143

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Equilibrium Research  

DOI： 10.3757/jser.74.66

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DOI： 10.1097/MAO.0000000000000469

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DOI： 10.3109/00016489.2014.923114

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DOI： 10.1002/lary.24614

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Language：Japanese   Publisher：(NPO)日本気管食道科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J01054&link_issn=&doc_id=20140821390004&doc_link_id=%2Fea4broes%2F2014%2F006504%2F004%2F0322-0329%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2014%2F006504%2F004%2F0322-0329%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Abstract Conclusion: The finding of deteriorated hearing loss at the initial visit at middle to high frequencies is a factor of poor hearing prognosis in M?ni?re&#039;s disease. Early intervention with instructions for lifestyle changes may lead to good outcomes in hearing. Objective: An attempt was made to examine long-term changes in hearing loss in unilateral M?ni?re&#039;s disease and factors associated with prognosis of hearing loss retrospectively. Methods: Based on their last hearing level of the affected ear, 36 patients were subdivided into two groups: the poor prognosis of hearing (PPH) group and the good prognosis of hearing (GPH) group. Results: In the PPH group, the hearing levels at the initial visit at middle and high frequencies were significantly worse than those in the GPH group. Moreover, the hearing loss progressed during the first 2 years of the disease, and stayed flat to approximately 50 dB at the later stage. Conversely, the hearing loss at the onset in the GPH group showed no further progression over the first 2 years, and remained constant to approximately 35 dB at the later stage. In addition, the mean intervals from the onset to the initial visit in the PPH group were significantly longer than those in the GPH group.

DOI： 10.3109/00016489.2014.923114

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MAO.0000000000000306

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DOI： 10.1097/MAO.0000000000000306

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DOI： 10.1016/j.brainres.2014.02.016

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J00038&link_issn=&doc_id=20140228020006&doc_link_id=%2Fee6mehei%2F2014%2F007301%2F006%2F0037-0043%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fee6mehei%2F2014%2F007301%2F006%2F0037-0043%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0081636

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DOI： 10.3109/00016489.2013.831480

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DOI： 10.1016/j.anl.2012.11.008

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Language：Japanese   Publisher：(一社)日本めまい平衡医学会  

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Language：Japanese   Publisher：(一社)日本耳科学会  

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DOI： 10.3109/00016489.2013.795290

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DOI： 10.1016/j.neulet.2013.07.019

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J01099&link_issn=&doc_id=20130823310005&doc_link_id=10031194947&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10031194947&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3109/00016489.2012.763180

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DOI： 10.3109/00016489.2012.759274

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In the patient with true anterior canalolithiasis, the direction of positional nystagmus during reverse Epley maneuver was constant and its axis was perpendicular to the plane of the right ASCC three-dimensionally. In contrast, in the patient with pseudo-anterior canalolithiasis, the first positional nystagmus of which the axis was perpendicular to the plane of the left ASCC became a second positional nystagmus of which the axis was perpendicular to the plane of the right PSCC during the reverse Epley maneuver.

DOI： 10.3109/00016489.2012.763180

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DOI： 10.3109/00016489.2012.740163

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DOI： 10.3109/00016489.2012.709322

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

DOI： 10.3950/jibiinkoka.116.960

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DOI： 10.2152/jmi.60.236

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DOI： 10.1016/j.anl.2011.10.007

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Three kind of nystagmus, namely P-BPPV, AH-BPPV and GH-BPPV can be explained by the otoconial debris hypothesis of the same ear. Finally, the recently reported geotropic nystagmus with a long time constant may be explained by a reversible lesion such as the denatured cupula or utricular imbalance of the same ear.

DOI： 10.1016/j.anl.2011.10.007

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DOI： 10.1016/j.anl.2011.06.005

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DOI： 10.1016/j.anl.2011.03.005

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Since the cerebellar vermis is known to plays an inhibitory role on the central vertical vestibule-ocular reflex (VOR), the present results suggest that the spontaneous UBN in darkness observed in this patient was induced by an imbalance of central vertical VOR tone.

DOI： 10.1016/j.anl.2011.03.005

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DOI： 10.1016/j.neures.2011.11.007

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DOI： 10.1016/j.brainres.2011.11.047

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We previously reported that motion sickness was prevented in rats with amygdala lesion and that provocative motion stimuli increased the number of Fos-positive neurons in the amygdala, suggesting that the amygdala is one of the neural substrates involved in the development of motion sickness. NK-1 receptors in the brain stem and amygdala are thought to play an important role in emesis and affective disorders, respectively. In the present study, to elucidate a role of substance P neuronal system and NK-1 receptors in the brain stem and amygdala in the development of motion sickness, we measured changes in gene expression of NK-1 receptors and preprotachykinin, a precursor of substance P, using quantitative real-time PCR methods in solitary tract nucleus and amygdala in rats after provocative motion stimuli induced by 2G hypergravity load. Effects of systemic administration of CP-99,994, an antagonist for NK-1 receptors, on hypergravity-induced motion sickness were also examined using pica behavior, eating non-nutritive substances such as kaolin, as an index of motion sickness in rats. Hypergravity-induced motion sickness was inhibited by CP-99,994 with a dose-dependent and enantioselective manner. Preprotachykinin mRNA expression was increased in basolateral nucleus of amygdala and solitary tract nucleus after hypergravity load for 3h, whereas NK-1 receptor mRNA expression was not changed by hypergravity in amygdala and solitary tract nucleus. Present results suggest that 2G hypergravity load activated the substance P neuronal system in amygdala as well as in the brain stem and this activation would be related to the development of motion sickness.

DOI： 10.1016/j.brainres.2011.11.047

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DOI： 10.3109/00016489.2011.611535

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DOI： 10.3109/00016489.2011.580004

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DOI： 10.1097/MAO.0b013e31822558de

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DOI： 10.3109/00016489.2011.566580

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DOI： 10.3109/00016489.2010.548403

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DOI： 10.1016/j.anl.2010.08.002

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DOI： 10.1159/000324611

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DOI： 10.1016/j.anl.2010.04.004

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We report a case showing apogeotropic nystagmus with the lesion of the brain stem, and discuss a possible mechanism of central apogeotropic nystagmus. The case was a 73-year-old male. We analyzed his nystagmus three-dimensionally. He showed apogeotropic nystagmus. Axis angles of slow phase eye velocity of his apogeotropic nystagmus were not in line with the axes perpendicular to the plane of horizontal semicircular canals, but with the patient&amp;apos;s vertical axis. We then found that his nystagmus including the apogeotropic nystagmus was positioning, but not positional and that the direction of his positioning nystagmus was the same direction of postrotatory nystagmus after his head movement. His MRI scans showed an infarction around the prepositus hypoglossi nucleus of the brain. His apogeotropic nystagmus seemed to consist of a combination of prolonged postrotatory nystagmus after his head rotation to the left and right lateral position because the axis of postrotatory nystamus was in line with the axis of the head rotation. Therefore, it is suggested that a possible mechanism of central apogeotropic nystagmus is a prolonged postrotatory nystagmus after his head movement in the supine position due to the brain lesion involving the velocity storage mechanisms.

DOI： 10.1016/j.anl.2010.04.004

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DOI： 10.3757/jser.69.96

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DOI： 10.1016/j.bbrc.2010.01.120

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DOI： 10.1016/j.neuroscience.2009.11.048

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DOI： 10.1097/MAO.0b013e3181cabd77

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DOI： 10.3109/00016480902897715

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DOI： 10.1097/MAO.0b013e3181b11db5

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CONCLUSIONS: We conclude that neck imaging should be carried out for patients with persistent paroxysmal positional vertigo following diagnostic and/or therapeutic maneuvers. OBJECTIVE: It is sometimes complicated to diagnose patients with vertigo that is transiently induced by head and neck positioning. Neck-vestibular diseases also induce vertiginous sensation with head and neck movement and need to be ruled out for the diagnosis of benign paroxysmal positional vertigo (BPPV). PATIENTS AND METHODS: Two elderly female patients visited our hospital with complaints of transient vertigo induced by Dix-Hallpike positioning, suggesting posterior canal BPPV. We carried out gadolinium-enhanced neck MRI in both these cases. RESULTS: The positional nystagmus was not clearly observed or vertiginous sensation did not show any decay during repeated vestibular examination in either case. These cases were finally diagnosed as spinal cord intradural extramedullary tumor (C3-C4) by means of neck MRI.

DOI： 10.1080/00016480902915673

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DOI： 10.1016/j.anl.2008.04.010

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The study findings suggest that histamine was released from the axon terminals in the hypothalamus and brainstem and the released histamine activated post-synaptic H1 receptors there, resulting in the development of motion sickness. We first examined which subtype of post-synaptic histaminergic receptor was responsible for the development of motion sickness. We then examined whether H1 receptors were up-regulated in various areas of the rat brain after 2 G hypergravity load, because the stimulation of H1 receptor was reported to up-regulate the level of H1 receptor protein expression through augmentation of H1 receptor mRNA expression. For this purpose, we used an animal model of motion sickness, using pica (eating non-nutritive substances such as kaolin), as a behavioral index in rats. After 2 G hypergravity load, rats ate a significant amount of kaolin, indicating that they suffered from motion sickness. The hypergravity-induced kaolin intake was suppressed by mepyramine, but not by terfinadine or zolantizine. This finding indicates that cerebral post-synaptic H1 but not H2 or peripheral H1 receptors play an important role in the development of motion sickness. The expression of H1 receptor mRNA was up-regulated in the hypothalamus and brainstem, but not in the cerebral cortex after 2 G hypergravity load in rats.

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Oto-Rhino-Laryngological Society of Japan Inc.  

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Language：Japanese   Publishing type：Book review, literature introduction, etc.   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/jibiinkoka.123.1337

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Language：Japanese   Publisher：日本認知療法・認知行動療法学会  

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01099&link_issn=&doc_id=20200930440012&doc_link_id=%2Fdz0jibik%2F2020%2F012309%2F012%2F1214-1215%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz0jibik%2F2020%2F012309%2F012%2F1214-1215%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publishing type：Book review, literature introduction, etc.   Publisher：Society of Oto-Rhino-Laryngology Tokyo  

DOI： 10.3950/jibiinkoka.123.1214

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Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

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DOI： 10.4295/audiology.61.65

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Language：Japanese   Publisher：耳鼻咽喉科展望会  

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DOI： 10.4295/audiology.59.553

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DOI： 10.4295/audiology.59.369

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