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Mumps virus infections primarily involve the parotid glands and most frequently affect school-aged children. We present three unusual adult cases of mumps with dyspnea secondary to severe swelling of the salivary glands and review previously reported cases in the literature. Dyspnea developed progressively after the onset of salivary gland swelling. Laryngoscopy revealed an advanced edematous change in the supraglottis obstructing the airway. In two cases, tracheotomy was needed because of rapid worsening of the supraglottic edema. Questioning regarding breathing problems and laryngoscopic examination is therefore recommended when one encounters a mumps case with combined parotid and salivary gland swelling. [ABSTRACT FROM AUTHOR]

Abstract Introduction A chondrosarcoma originating from the hyoid bone is very rare. Here, we describe a case of low-grade chondrosarcoma of hyoid origin and discuss its preoperative imaging features, including those on positron emission tomography-computed tomography, and its recurrence rate. Case presentation A 42-year-old Japanese man noticed a mass in the right submandibular region of his neck. A hard 3.0 × 2.8 cm tumor was noted on the right side of his hyoid bone. The mass was immobile and moved with deglutition. Conclusion Even though radiographic studies, including positron emission tomography-computed tomography, were inconclusive, the cartilaginous tumor was surgically removed en bloc, and the tumor was diagnosed based on the results of pathological investigations. Close follow-up is recommended in such cases due to the potential for recurrences, because local recurrence occurred in 50% of the reported cases of grade one chondrosarcomas.

Background: Reduction of spontaneous nystagmus by fixation, a characteristic feature of peripheral nystagmus, is important for differentiating between peripheral and central vestibular disorders. In the emergency room, Frenzel goggles are recommended to observe spontaneous nystagmus for the differential diagnosis of acute vestibular syndrome. We developed a portable loupe with a Fresnel lens to observe nystagmus. The loupe does not require power supply and can be used under ceiling lights. The aim of this study was to quantitatively and objectively compare the abilities of the loupe and conventional Frenzel goggles to observe spontaneous nystagmus and to verify that the loupe can detect peripheral nystagmus that cannot be observed with the naked eye., Methods: Visual impact susceptibility was compared between the loupe and Frenzel goggles using the slow-phase velocity of nystagmus induced by the caloric test in 15 participants. Subsequently, under lighting, the nystagmus observations under the naked eye condition and with the use of the loupe were compared. Furthermore, the visibility of nystagmus was evaluated from recorded videographic images., Results: In observations of nystagmus induced by the caloric test, the visual impact of the loupe was not inferior to that of Frenzel goggles. The mean slow-phase velocity of nystagmus recorded with the loupe was significantly higher than that observed with the naked eye. Nystagmus weakened under bright lighting could be recovered by the loupe as fixation was blocked and the direction of the nystagmus could be defined., Conclusions: The results showed that the loupe is helpful in observing nystagmus, which is weakly observed with the naked eye under bright light. This portable, low-cost loupe, which yields superior results, can serve as an alternative to conventional Frenzel goggles in emergency medical settings where rapid assessment is required., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Research Ethics Committee of Mejiro University (Approval number: 23 medicine-006). Participants were informed regarding the purpose and methods of the study in writing, and written informed consent for participation was obtained. All methods were conducted in accordance with the relevant guidelines and regulations. Consent for publication: Written informed consent was obtained from the participants for publishing the data. Written informed consent was obtained from all participants for the publication of identifying information/images in this online open-access publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Claudin-18 splice variant 2 (CLDN18.2), a tight junction protein, is a highly cell type-specific antigen that is expressed by differentiated gastric mucosa cells. The expression of CLDN18.2 in gastric mucosa cells may be retained upon malignant transformation and is displayed on the surface of several tumors, including gastric/gastroesophageal junction adenocarcinoma. Zolbetuximab is a genetically engineered, highly purified chimeric (mouse/human IgG1) antibody directed against CLDN18.2. Nausea and vomiting were observed as adverse events of zolbetuximab. To investigate the mechanism of nausea and vomiting in humans, we evaluated emesis (retching and vomiting) and conducted histopathologic assessment in ferrets after the administration of zolbetuximab. Emesis was frequently observed in all ferrets treated with zolbetuximab in the first hour after administration. Histopathologic assessment revealed the surface of the gastric mucosa was the primary site of emesis-associated tissue damage. The effect of antiemetics (dexamethasone, ondansetron, fosaprepitant, and olanzapine) on emesis induced by zolbetuximab was investigated. Fosaprepitant showed suppressive effects on emesis, and use of dexamethasone or concomitant use of fosaprepitant with other antiemetics tended to alleviate gastric tissue damage. The onset of emesis in humans receiving zolbetuximab may be associated with damage in the gastric mucosa, and antiemetics may mitigate gastrointestinal adverse events., Competing Interests: Declaration of competing interest All authors are employees of Astellas Pharma, Inc. or its affiliates., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The subjective visual vertical (SVV) test can evaluate otolith function and spatial awareness and is performed in dedicated vertigo centers using specialized equipment; however, it is not otherwise widely used because of the specific equipment and space requirements. An SVV test smartphone app was developed to easily perform assessments in outpatient facilities., Objective: This study aimed to verify whether the SVV test smartphone app with commercially available virtual reality goggles can be used in a clinical setting., Methods: The reference range was calculated for 15 healthy participants. We included 14 adult patients with unilateral vestibular neuritis, sudden sensorineural hearing loss with vertigo, and Meniere disease and investigated the correlation between the SVV test results and vestibular evoked myogenic potential (VEMP) results., Results: The SVV reference range of healthy participants for the sitting front-facing position was small, ranging from -2.6º to 2.3º. Among the 14 patients, 6 (43%) exceeded the reference range for healthy participants. The SVV of patients with vestibular neuritis and sudden sensorineural hearing loss tended to deviate to the affected side. A total of 9 (64%) had abnormal cervical VEMP (cVEMP) values and 6 (43%) had abnormal ocular VEMP (oVEMP) values. No significant difference was found between the presence or absence of abnormal SVV values and the presence or absence of abnormal cVEMP and oVEMP values; however, the odds ratios (ORs) suggested a higher likelihood of abnormal SVV values among those with abnormal cVEMP and oVEMP responses (OR 2.40, 95% CI 0.18-32.88; P>.99; and OR 2, 95% CI 0.90-4.45; P=.46, respectively)., Conclusions: The SVV app can be used anywhere and in a short period while reducing directional bias by using virtual reality goggles, thus making it highly versatile and useful as a practical otolith dysfunction screening tool., (©Akiko Umibe, Hiroaki Fushiki, Reiko Tsunoda, Tatsuaki Kuroda, Kazuhiro Kuroda, Yasuhiro Tanaka. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.06.2024.)

Background: Falls in older adults are a significant public health concern, and age-related macular degeneration (AMD) and glaucoma have been identified as potential visual risk factors. This study was designed to assess equilibrium function, fall risk, and fall-related self-efficacy (an individual's belief in their capacity to act in ways necessary to reach specific goals) in patients with AMD and glaucoma., Methods: This observational study was performed at the Otorhinolaryngology Department of Shinseikai Toyama Hospital. The cohort comprised 60 participants (AMD; n = 30; median age, 76.0 years; and glaucoma; n = 30; median age, 64.5 years). Visual acuity and visual fields were assessed using the decimal best-corrected visual acuity and Humphrey visual field tests, respectively. The evaluation metrics included pathological eye movement analysis, bedside head impulse test, single-leg upright test, eye-tracking test, optokinetic nystagmus, and posturography. Furthermore, we administered questionnaires for fall risk determinants including the Dizziness Handicap Inventory, Activities-Specific Balance Confidence Scale, Falls Efficacy Scale-International, and Hospital Anxiety and Depression Scale. The collected data were analyzed using descriptive statistics, and Spearman's correlation analysis was employed to examine the interrelations among the equilibrium function, fall risk, and other pertinent variables., Results: Most participants exhibited standard outcomes in equilibrium function evaluations. Visual acuity and field deficits had a minimal impact on subjective dizziness manifestations, degree of disability, and fall-related self-efficacy. Both groups predominantly showed high self-efficacy. No significant correlation was observed between visual acuity or field deficits and body equilibrium function or fall risk. However, greater peripheral visual field impairment was associated with a tendency for sensory reweighting from visual to somatosensory., Conclusion: Self-efficacy was higher and fall risk was relatively lower among patients with mild-to-moderate visual impairment, with a tendency for sensory reweighting from visual to somatosensory in those with greater peripheral visual field impairment. Further studies are required to validate these findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tokunaga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Artificial intelligence models can learn from medical literature and clinical cases and generate answers that rival human experts. However, challenges remain in the analysis of complex data containing images and diagrams., Objective: This study aims to assess the answering capabilities and accuracy of ChatGPT-4 Vision (GPT-4V) for a set of 100 questions, including image-based questions, from the 2023 otolaryngology board certification examination., Methods: Answers to 100 questions from the 2023 otolaryngology board certification examination, including image-based questions, were generated using GPT-4V. The accuracy rate was evaluated using different prompts, and the presence of images, clinical area of the questions, and variations in the answer content were examined., Results: The accuracy rate for text-only input was, on average, 24.7% but improved to 47.3% with the addition of English translation and prompts (P<.001). The average nonresponse rate for text-only input was 46.3%; this decreased to 2.7% with the addition of English translation and prompts (P<.001). The accuracy rate was lower for image-based questions than for text-only questions across all types of input, with a relatively high nonresponse rate. General questions and questions from the fields of head and neck allergies and nasal allergies had relatively high accuracy rates, which increased with the addition of translation and prompts. In terms of content, questions related to anatomy had the highest accuracy rate. For all content types, the addition of translation and prompts increased the accuracy rate. As for the performance based on image-based questions, the average of correct answer rate with text-only input was 30.4%, and that with text-plus-image input was 41.3% (P=.02)., Conclusions: Examination of artificial intelligence's answering capabilities for the otolaryngology board certification examination improves our understanding of its potential and limitations in this field. Although the improvement was noted with the addition of translation and prompts, the accuracy rate for image-based questions was lower than that for text-based questions, suggesting room for improvement in GPT-4V at this stage. Furthermore, text-plus-image input answers a higher rate in image-based questions. Our findings imply the usefulness and potential of GPT-4V in medicine; however, future consideration of safe use methods is needed., (©Masao Noda, Takayoshi Ueno, Ryota Koshu, Yuji Takaso, Mari Dias Shimada, Chizu Saito, Hisashi Sugimoto, Hiroaki Fushiki, Makoto Ito, Akihiro Nomura, Tomokazu Yoshizaki. Originally published in JMIR Medical Education (https://mededu.jmir.org), 28.03.2024.)

Introduction: Head impulse, nystagmus, and test of skew (HINTS) is more accurate for the early diagnosis of occipital fossa stroke than magnetic resonance imaging. However, the head impulse test (HIT) is relatively challenging to perform, as it is subjective. Herein, we developed a prototype video HIT (vHIT) system using an iPhone (Apple, Cupertino, CA, USA) that is compact, easy to operate, and analyzable by our iPhone application., Methods: The iPhone-vHIT and a vHIT using EyeSeeCam (Interacoustics, Eden Prairie, NM, USA) were performed on a healthy man in his 30s and on a patient with vestibular neuritis who visited the Mejiro University Ear Institute Clinic. For the iPhone-vHIT, eye movements were detected by analyzing high-speed videos captured using an iPhone camera, and head movements were followed using an iPhone gyro sensor. An iPhone fixation brace was used to capture the video without any blurring., Results: The iPhone-vHIT system obtained vHIT waveforms similar to those of the EyeSeeCam-vHIT system in the healthy man and the patient with vestibular neuritis. The iPhone-vHIT system effectively detected the reduced vestibulo-ocular reflex gain in patients with vestibular neuritis. The iPhone-vHIT system at 120 frames per second was less sensitive to catch-up saccades than the EyeSeeCam., Conclusion: vHIT systems using a smartphone have been reported but are currently unavailable. At present, the iPhone-vHIT application in this study is the only available smartphone-based vHIT system for screening of peripheral vestibular dysfunction. We believe that the prototype iPhone-vHIT with a high-speed camera will be clinically used to perform the vHIT, even though it only examines the lateral semicircular canal., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Objectives: To investigate the effect of early vestibular rehabilitation on physical function and dizziness in patients with acute vestibular disorders., Databases Reviewed: The electronic databases examined included PubMed (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (via Dialog), and PEDro., Methods: The inclusion criteria in terms of the study participants were patients 20 years and older with an acute unilateral peripheral vestibular disorder. We included individual randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and crossover trials. The outcomes were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function. Early vestibular rehabilitation was defined as rehabilitation within 14 days of vestibular disorder onset or surgery. Main outcome measures were gait, balance (eyes open, eyes close), activities of daily living, dizziness, and vestibular function., Results: Twelve trials involving 542 participants were included. Early vestibular rehabilitation improved the Dizziness Handicap Inventory by -7.18 (95% confidence interval [CI], -10.48 to -3.88), balance during eyes close by -1.40 (95% CI, -2.42 to -0.39), and dizziness by -1.47 (95% CI, -2.74 to -0.21) compared with no intervention or placebo., Conclusion: The present study demonstrated that early vestibular rehabilitation improved the Dizziness Handicap Inventory, balance (eyes close), and subjective dizziness in a patient with acute vestibular disorders. This result indicates that early vestibular rehabilitation can promote vestibular compensation., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Background: Dizziness and vertigo can be caused by various factors, such as peripheral vestibular and central disorders. Although consultations with specialists are advisable when necessary, patients with severe vertigo symptoms may have limited mobility, which may interfere with hospital visits. The spread of COVID-19 has further limited the number of hospital visits for patients with dizziness; therefore, a method of medical care that enables more accurate treatment under time and geographical constraints is needed. Telemedicine has become widespread, owing to the popularity of smartphone and tablet devices in recent years, and the use of devices and systems has made it possible to provide efficient medical care. However, no previous scoping review has mapped existing studies on telemedicine for vertigo and dizziness, and no recommendations have been made regarding which devices and systems should be used for specific diseases., Objective: The aim of this review was to map and assess previous studies on the use of information communications technology, smartphones, and apps for treating patients with vertigo and discuss the added value of introducing telemedicine to improve the quality of medical care and create an environment that builds security and trust among patients., Methods: A scoping review was conducted with the methodological framework of Arksey and O'Malley and in accordance with the of the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews) guidelines. The PubMed, MEDLINE, and Cochrane Library databases were searched to retrieve previous reports on smartphone-assisted telemedicine treatment for vertigo published between January 2000 and May 2023. Two authors independently assessed eligibility and extracted data., Results: This review included 20 papers that reported devices or systems for telemedicine for vestibular dysfunction. Among studies that reported the use of a device or app, 2 were related to anamnesis and subjective symptoms, 12 were related to objective examination, 7 were related to remote diagnosis, and 7 were related to treatment and rehabilitation., Conclusions: With the advancement of technology, the use of telemedicine in patients with dizziness may be feasible. In the future, it will be necessary to consider how telemedicine can be used in dizziness treatment and develop an effective treatment system combining in-person medical care and the effective use of devices for the management of severe vertigo and related diseases. The smooth introduction of telemedicine in vertigo treatment is expected to improve the quality of treatment, increase opportunities for patients to receive medical care, and reduce time and travel costs, leading to a sense of security and trust among patients., (©Masao Noda, Tatsuaki Kuroda, Akihiro Nomura, Makoto Ito, Tomokazu Yoshizaki, Hiroaki Fushiki. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 11.09.2023.)

Background: Dizziness is a common complaint of patients treated by primary care physicians. It is predominantly caused by peripheral vestibular disorders; however, central nervous system disorders should be excluded. Examination of the eye movements and nystagmus can help differentiate the disorders of the central nervous system from the peripheral vestibular disorders; however, it is often not performed appropriately. In medical education practice, nystagmus observation may facilitate an understanding of vestibular function and nystagmus characteristics. Thus, we proposed a medical education practice to master nystagmus observation using a recently developed portable Fresnel magnifying loupe that could be shielded by one eye., Methods: Thirty-three students from the Department of Physical Therapy and the Department of Speech, Language, and Hearing Therapy of the Mejiro University participated in this study. Postrotatory nystagmus was measured and compared using the new loupe and control methods, namely the naked eye and Frenzel goggles; we rated the ease of visibility using a five-point scale., Results: The number of detected cases of nystagmus was significantly higher with the new loupe than with the naked eye (p = 0.001). In addition, there were no significant differences in the nystagmus counts between the observations using the new loupe and Frenzel goggles (p = 0.087). No significant difference was observed in the visibility of eye movements between the loupe and naked eye (p = 1.00). The Frenzel goggles provided better visibility compared to that by the loupe (p = 0.034); however, none of the participants reported poor visibility using any of these methods., Conclusions: Our newly developed Fresnel loupe allows for the observation of nystagmus counts a level of reduction in fixation suppression similar to that of Frenzel goggles in an educational practice setting. Furthermore, it enables the detection of significantly more nystagmus counts compared to that by the naked eye. It offers several advantages over Frenzel goggles, including its lightweight, thin, durable, and portable design. Additionally, the loupe does not rely on a power source and can be used under normal room lighting conditions., Trial Registration: This study was approved by the Medical Research Ethics Committee of Mejiro University (approval number: 21medicine-021)., (© 2023. The Author(s).)

Purpose: Fatty acid oxidation (FAO) is a key parameter for evaluating cardiovascular, oncologic, neurologic, and other metabolic diseases. Several single-photon emission computed tomography and positron emission tomography (PET) tracers have been developed to measure FAO. Among these, 18-[ 18 F]fluoro-4-thia-oleate ([ 18 F]FTO), first developed by DeGrado et al., is well characterized. Here, we synthesized several analogs of [ 18 F]FTO to improve the metabolic stability of the C- 18 F bond, and preliminarily evaluated their performance in monkey PET studies., Procedures: Several secondary 18 F-fluorinated analogs, 17-[ 18 F]fluoro-4-thia-oleate (17-[ 18 F]FTO), 15-[ 18 F]fluoro-4-thia-oleate (15-[ 18 F]FTO), 12-[ 18 F]fluoro-4-thia-oleate (12-[ 18 F]FTO), 7-[ 18 F]fluoro-4-thia-oleate, (7-[ 18 F]FTO, [ 18 F]AS3504073-00), and 6-[ 18 F]fluoro-4-thia-oleate (6-[ 18 F]FTO), were synthesized from tosylate or bromide precursors using similar procedures. Nucleophilic 18 F fluorination on each precursor was performed using [ 18 F]tetrabutylammonium fluoride/tetrabutylammonium hydrocarbonate, followed by hydrolysis of methylester. All synthesized 18 F-labeled compounds were administered to cynomolgus monkeys, and PET measurements were performed. From the monkey PET studies, 7-[ 18 F]FTO was selected as the best tracer and used to perform preliminary evaluations in mice., Results: All five compounds had sufficient quality and stability for animal experiments. In monkey PET studies, 12-, 7-, and 6-[ 18 F]FTO showed greater accumulation in the heart than [ 18 F]FTO, but not 17- and 15-[ 18 F]FTO. Only 7-[ 18 F]FTO did not show significant accumulation in the bone. The standardized uptake values (SUVs) for 12-[ 18 F]FTO, 7-[ 18 F]FTO, and 6-[ 18 F]FTO were 9.77, 9.26, and 7.25 in the heart, and 3.17, n.d., and 1.96 in the bone 1 h after administration, respectively. In mouse distribution studies, SUVs 1 h after administration of 7-[ 18 F]FTO and [ 18 F]FTO were 10.4 and 10.0 in the heart, and 0.37 and 3.48 in the femur, respectively. Administration of etomoxir, a carnitine palmitoyltransferase inhibitor, reduced SUVs of 7-[ 18 F]FTO and [ 18 F]FTO in the heart by 91% and 87%, respectively., Conclusions: We developed a novel PET tracer 7-[ 18 F]FTO/[ 18 F]AS3504073-00 for FAO imaging. 7-[ 18 F]FTO had an excellent PET tracer profile, suggesting it may be a useful tracer for FAO imaging. Further evaluations of the tracer are ongoing., (© 2022. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Persistent postural-perceptual dizziness (PPPD) is a relatively new disease entity, with diagnostic criteria published by the Bárány Society. PPPD is often preceded by a peripheral or central vestibular disorder. It is not clear how coexisting deficits due to preceding vestibular disorders affect PPPD symptoms., Objective: This study aimed to characterize the clinical features of PPPD with or without isolated otolith dysfunction using vestibular function tests., Methods: The study included 43 patients (12 males and 31 females) who were diagnosed with PPPD and completed oculomotor-vestibular function tests. The Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), Niigata PPPD Questionnaire (NPQ), and Romberg test for stabilometry were examined. The 43 patients with PPPD were classified into four categories based on vestibular evoked myogenic potential (VEMP) and video head impulse test (vHIT) results: normal function for both semicircular canals and otoliths (normal), isolated otolith dysfunction (iOtoDys), isolated semicircular canal dysfunction (iCanalDys), and dysfunction of both otoliths and semicircular canals (OtoCanalDys)., Results: Among the 43 patients with PPPD, the iOtoDys group was the largest (44.2%), followed by the normal group (37.2%), iCanalDys group (9.3%), and OtoCanalDys group (9.3%). Eight of the 19 iOtoDys patients showed both abnormal cVEMP and oVEMP responses unilaterally or bilaterally (both sacculus and utriculus damage type), whereas 11 showed either an abnormal cVEMP or an abnormal oVEMP response (either sacculus or utriculus damage type). In a three-group comparison of the both sacculus and utriculus damage type, the either sacculus or utriculus damage type, and the normal group, the mean total, functional, and emotional DHI scores were significantly higher for the both sacculus and utriculus damage type than for the either sacculus or utriculus damage type. The Romberg ratio, a measure of stabilometry, was significantly higher for the normal group than for the both sacculus and utriculus damage type and the sacculus or utriculus damage type in the iOtoDys group., Conclusions: The coexistence of sacculus and utriculus damage may exacerbate dizziness symptoms in patients with PPPD. Determining the presence and extent of otolith damage in PPPD may provide useful information on the pathophysiology and treatment strategies of PPPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Azami, Fushiki, Tsunoda, Kamo, Ogihara, Tanaka and Kato.)

Purpose: Iatrogenic ureteral injury (IUI) can complicate minimally invasive and open abdominopelvic surgery. The incidence of IUI is low and dependent on the type of surgery (< 10 %), but it is associated with high morbidity. Therefore, intraoperative visualization of the ureter is critical to reduce the incidence of IUI, and some methodologies for ureter visualization have been developed. Amongst these, near-infrared fluorescence (NIRF) visualization is thought to bring an advantage with real-time retroperitoneal visualization through the retroperitoneum. We investigated an indocyanine green (ICG) derivative, ASP5354, which emits NIRF at 820 nm when exposed to near-infrared light at a wavelength of 780 nm, in a rodent and porcine model., Procedures: Wistar rats and Göttingen minipigs under anesthesia were laparotomized and then administered ASP5354 chloride intravenously at dose of 0.03 and 0.3 mg/kg for rats and 0.001 and 0.01 mg/kg for minipigs, respectively. Videos of the abdominal cavity in minipigs were taken using a near-infrared fluorescent camera (pde-neo) and assessed visually by three independent clinicians. Toxicological evaluation was demonstrated with cynomolgus monkeys., Results: The proportion of animals whose ureters were visible up to 3 h after administration of ASP5354 chloride were 33 % at 0.001 mg/kg and 100 % at 0.01 mg/kg, respectively. In a toxicological study in cynomolgus monkeys, ASP5354 chloride demonstrated no significant toxicity, suggesting that 0.01 mg/kg provides an optimal dose when used clinically and could allow for ureter visualization during routine surgical procedures., Conclusions: The dose of 0.01 mg/kg provided an optimal dose for ureter visualization up to 3 h after administration. ASP5354 shows promise for ureter visualization during abdominopelvic surgery, which may potentially lower the risk of IUI., (© 2021. World Molecular Imaging Society.)

Objectives: This study investigated the effects of a supervised home-based vestibular rehabilitation program using a booklet on gait function and dizziness in patients with chronic peripheral vestibular hypofunction., Methods: This was a non-blinded, randomized, controlled trial. Patients (n=42) with chronic peripheral vestibular hypofunction were randomly divided into the vestibular rehabilitation group (VR group; n=20) or the control group (n=22). Patients in the VR group received a supervised home-based vestibular rehabilitation program using a booklet in addition to physician care for 4 weeks. The physical therapist checked the home program when the VR group visited the outpatient clinic once a week. Patients in the control group received physician care only during the trial period. The primary outcome was functional gait assessment (FGA). The secondary outcomes were the dynamic gait index (DGI) and the dizziness handicap inventory (DHI)., Results: Two-way repeated measures analysis of variance showed a significant interaction for FGA, DGI, DHI total, and DHI emotional scores (P<0.05) with the VR group improving more than the control group. No significant interactions were found for DHI physical and DHI functional scores (P≥0.05)., Conclusions: The home-based vestibular rehabilitation program in this study was effective in improving gait function and dizziness in patients with chronic peripheral vestibular hypofunction. Regular supervision may have improved adherence to home exercise and contributed to the effectiveness of vestibular rehabilitation., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflicts of interest., (2023 The Japanese Association of Rehabilitation Medicine.)

Nerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with clinical chronic pain conditions, anti-NGF IgGs are associated with safety concerns such as effects on fetal and postnatal development and the risk of rapidly progressive osteoarthritis. To overcome these drawbacks, we generated a novel anti-NGF PEGylated Fab' antibody. The anti-NGF PEGylated Fab' showed specific binding to and biological inhibitory activity against NGF, and analgesic effects in adjuvant-induced arthritis model mice in a similar manner to an anti-NGF IgG. In collagen-induced arthritis model mice, the anti-NGF PEGylated Fab' showed higher accumulation in inflamed foot pads than the anti-NGF IgG. In pregnant rats and non-human primates, the anti-NGF PEGylated Fab' was undetectable in fetuses, while the anti-NGF IgG was detected and caused abnormal postnatal development. The PEGylated Fab' and IgG also differed in their ability to form immune complexes in vitro. Additionally, while both PEGylated Fab' and IgG showed analgesic effects in sodium monoiodoacetate-induced arthritic model rats, their effects on edema were surprisingly quite different. While the anti-NGF IgG promoted edema over time, the anti-NGF PEGylated Fab' did not. The anti-NGF PEGylated Fab' (ASP6294) may thus be a potential therapeutic candidate with lower risk of adverse effects for various diseases in which NGF is involved such as OA and chronic back pain.

Objective: Previous studies have reported that developmental, environmental, medical, psychological, visual, and other sensory-related factors can influence the outcome of vestibular rehabilitation. However, only a few studies have used patient's daily lives as the main outcome. In addition, in some studies, rehabilitation was not supervised by a physical therapist. This study aimed to determine the factors associated with the outcome of physical-therapist-supervised vestibular rehabilitation in patients with peripheral vestibular disorders, with the impact of dizziness on quality of life as the main outcome., Methods: This retrospective cohort study included 47 patients with peripheral vestibular disorders. A physical therapist provided 40 min of vestibular rehabilitation once a week for 4 weeks. Age, sex, disease duration, Dizziness Handicap Inventory (DHI), Timed Up-and-Go test (TUG), Dynamic Gait Index (DGI), Functional Gait Assessment (FGA), Activity-Specific Balance Confidence Scale (ABC scale), and Hospital Anxiety and Depression Scale (HADS) were investigated. Multiple regression analysis was performed, with the DHI rate of change before and after the intervention as the objective variable., Results: Vestibular rehabilitation improved all outcomes. In the multiple regression analysis, the ABC scale was identified as a factor that significantly influenced the DHI rate of change (β = -0.428, p < 0.01)., Conclusion: A higher ABC scale score was associated with a lower DHI rate of change (i.e., better improvement). Therefore, it may be important to assess psychological aspects, especially confidence in balance, when implementing vestibular rehabilitation in patients with peripheral vestibular disorders., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objective: This study aimed to investigate the prevalence of sarcopenia and factors associated with sarcopenia in patients with dizziness., Study Design: This is a cross-sectional study., Patients: A total of 162 patients 65 years or older with the chief complaint of dizziness or vertigo (dizziness group) and 132 community-dwelling elderly (control group) were recruited during their visit to the otolaryngology clinic between May 2020 and October 2021., Results: Of the 162 patients with dizziness (dizziness group), 53 (32.7%) were classified as sarcopenia according to the 2019 criteria of the Asian Working Group for Sarcopenia. There were significant differences in the prevalence of sarcopenia between the dizziness group and the control group ( p < 0.01). The factors that significantly affected the sarcopenia, in order of greater odds ratio, were HADS&#95;A, age, and DHI&#95;Total (odds ratio = 1.223, 1.130, and 1.022, respectively)., Conclusions: The present study shows that (i) the prevalence of sarcopenia in patients with dizziness is higher than a community-dwelling elderly; (ii) patients with dizziness and sarcopenia have higher DHI&#95;functional, DHI&#95;emotional, DHI&#95;total, and HADS&#95;A compared with patients with dizziness but without sarcopenia; and (iii) age, HADS&#95;A, and DHI were associated with sarcopenia in patients with dizziness., (Copyright © 2022, Otology & Neurotology, Inc.)

Objective: To investigate the utilization and demographic characteristics of in-hospital rehabilitation for patients with acute vestibular neuritis using the Japan Medical Data Center (JMDC) database., Methods: We gathered information on patients that were at least 20 years of age who were admitted with a diagnosis of VN (ICD-10 code: H81.2). We defined in-hospital rehabilitation service use as payment of insurance claims for at least one session of rehabilitation during admission., Results: We identified 809 patients that were eligible for this study; among these, 59 patients (7.3%) received rehabilitation while 750 patients did not. The median total time spent and the median time per day in inpatient rehabilitation were 140 min and 11.7 min, respectively. Factors that significantly affected the rehabilitation service use, in order of greater odds, were primary care, internal medicine, and age in multivariate logistic regression analysis (odds ratio = 4.42, 2.17, 1.33, respectively)., Conclusions: This study showed that (1) utilization of rehabilitation services by acute patients with VN was low; and (2) age, admission to internal medicine, and admission to primary care were associated with the use of rehabilitation services., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022. Published by Elsevier B.V.)

[Purpose] This study aimed to compare the effects of different intervention frequencies on walking ability and balance in patients with chronic unilateral vestibular hypofunction. [Participants and Methods] Participants included in this case-control study were assigned to one of two groups: the multiple-intervention (once a week) and single-intervention groups. Results for the Timed Up and Go test, Dynamic Gait Index, Functional Gait Assessment, and Activities-specific Balance Confidence scale were determined at baseline and four weeks after initiating the vestibular rehabilitation program. Thereafter, intra- and inter-group differences in the rates of change of these parameters were determined. [Results] The Timed Up and Go test values, Dynamic Gait Index, and Functional Gait Assessment scores improved significantly after four weeks in the multiple-intervention group. The improvement rate in the Timed Up and Go test differed significantly between the two groups. The Activities-specific Balance Confidence scale scores did not significantly change in either group after four weeks. [Conclusion] Compared to a single intervention, multiple interventions by a physical therapist produced significantly greater benefits in a relatively shorter period of time in patients with chronic unilateral vestibular hypofunction., (2022©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Objective: A few studies have analyzed the physical activity in patients with dizziness. Levels of physical activity using 3-axial accelerometer were reported to be lower in patients with chronic dizziness compared to healthy adults. However, the sample size was small and confounding factors were not adjusted in the study. As the age, balance, anxiety, and depression likely contribute to dizziness, the contribution of physical activity to dizziness should be evaluated after adjusting for these potential confounders. We investigated the relationship between physical activity, postural stability, anxiety, and handicap in patients with dizziness using multivariate analysis., Methods: This cross-sectional study included 59 patients with dizziness. The physical activity was measured using a 3-axial accelerometer. We also assessed the Dizziness Handicap Inventory (DHI), Hospital and Anxiety and Depression Scale (HADS), and the total center of pressure path length eyes open and eyes closed (COP&#95;EO, COP&#95;EC). To be eligible for analysis, the participants were required to wear the accelerometer for at least four days, with at least 10 h/day of wear time each day., Results: There were significant differences in the light physical activity (LPA) and moderate to vigorous intensity physical activity (MVPA) between the mild (DHI ≦30) and severe (DHI > 60) groups. Factors that significantly affected the DHI&#95;T score, in order of greater β, were LPA, COP&#95;EC, female, and HADS&#95;A (β = -0.546, 0.459, 0.437, 0.239, respectively)., Conclusions: The present study demonstrated that the patients in the severe group had shorter LPA and MVPA times than that of the patients in the mild group. Additionally, LPA was associated with DHI&#95;T in patients with dizziness. Therefore, physical activity, especially LPA (e.g., activities of daily living), may need to be assessed in patients with dizziness., (Copyright © 2021. Published by Elsevier B.V.)

Background: Although dizziness is one of the most common symptoms of menopause, the underlying mechanism is not precisely known. Therefore, this study aimed to investigate the prevalence of, and the factors associated with, dizziness in peri- and postmenopausal women., Methods: We conducted a cross-sectional study in which we analyzed the first-visit records of 471 Japanese women aged 40 to 65 years who enrolled in a health and nutrition education program at a menopause clinic. The prevalence of dizziness was estimated according to the participants' responses to the Menopausal Health-Related Quality of Life Questionnaire. The background characteristics of age, menopause status, body composition, cardiovascular parameters, basal metabolism, and physical fitness; other menopausal symptoms, including vasomotor, insomnia, depression, and anxiety symptoms; and lifestyle characteristics were assessed for their associations with dizziness., Results: The percentage of women who suffered from dizziness once a week or more frequently was 35.7%. Compared to the women without dizziness, those with the symptom were younger; had a higher body weight, body mass index, body fat percentage, muscle mass, and waist-to-hip ratio; had higher systolic pressure; were slower in reaction time; had higher physical and psychological symptom scores of menopause; exercised less regularly; and consumed less alcohol. A multivariate logistic regression analysis revealed that the anxiety symptom, which was evaluated by the Hospital Anxiety and Depression Scale, was the sole factor that was independently associated with dizziness (adjusted odds ratio 1.14; 95% confidence interval 1.08-1.20)., Conclusions: Dizziness is highly prevalent in Japanese peri- and postmenopausal women and it is associated with anxiety. The treatment of anxiety in this population might improve the symptom., Competing Interests: Prior to beginning the study, the research protocol was approved by the Tokyo Medical and Dental University’s Review Board, and written informed consent was obtained from all participants. All study procedures were performed in accordance with the Declaration of Helsinki.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: We examined plastic changes in the vestibulo-ocular reflex (VOR) during low-frequency vertical head rotation, a condition under which otolith inputs from the vestibular system are essential for VOR generation., Methods: For adaptive conditioning of the vertical VOR, 0.02Hz sinusoidal pitch rotation for one hour about the earth's horizontal axis was synchronized with out-of-phase vertical visual stimulation from a random dot pattern., Results: A vertical VOR was well evoked when the upright animal rotated around the earth-horizontal axis (EHA) at low frequency due to the changing gravity stimulus and dynamic stimulation of the otoliths. After adaptive conditioning, the amplitude of the vertical VOR increased by an average of 32.1%., Conclusion: Our observations showing plasticity in the otolithic contribution to the VOR may provide a new strategy for visual-vestibular mismatch training in patients with otolithic disorders. This low-frequency vertical head rotation protocol also provides a model for investigating the mechanisms underlying the adaptation of VORs mediated by otolith activation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Nectin-4 is selectively overexpressed in a variety of cancers and is currently under clinical investigation as a therapeutic target. A monoclonal antibody against nectin-4 (AGS-22M6) was evaluated as an Immuno-positron emission tomography (ImmunoPET) reagent. Its ability to assay nectin-4 expression as well as detect nectin-4 positive tumors in the liver and bone was evaluated using mouse models., Procedures: The biodistribution of [(89)Zr]AGS-22M6 was evaluated in mice bearing tumors with varying levels of nectin-4 expression. An isogenic breast cancer tumor line was used to model metastatic liver and bone disease in mice. The biodistribution of [(18)F]AGS-22M6 in cynomolgus monkeys was evaluated., Results: A positive correlation was demonstrated between tumor nectin-4 expression and [(89)Zr]AGS-22M6 uptake. Tumors in the liver and bone were detected and differentiated based on nectin-4 expression. [(18)F]AGS-22M6 showed limited uptake in cynomolgus monkey tissues., Conclusions: [(89)Zr]AGS-22M6 is a promising ImmunoPET reagent that can assay nectin-4 expression in both primary and metastatic lesions.

Single treatment of rats with the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 induces neuronal cell degeneration and death in the retrosplenial/posterior cingulate cortex (RS/PC) region, along with local cerebral glucose utilization. However, the relationship between this neuronal cell degeneration and death and glucose utilization remains unclear. To investigate the mechanism of MK-801-induced neurotoxicity and its relation to glucose utilization, changes in endogenous metabolites in the RS/PC region of MK-801 treated rats were assessed using metabolomics. Inverse correlation between citrulline and arginine levels suggested increased nitric oxide (NO) production. In addition, decreased levels of purine metabolites suggested enhanced xanthine oxidase activity accompanied with reactive oxygen species (ROS) production. Histopathological analysis confirmed that the production of ROS in the RS/PC region was increased by MK-801 and that the nonspecific NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) prevented MK-801-induced neuronal cell death. These results suggest that NO increases oxidative stress-related cell death. Increased levels of metabolites of glucose metabolism suggested enhanced energy production via glycolysis. To confirm the relationship between NO and glucose utilization, positron emission tomography (PET) imaging with [(18)F] fluoro-2-deoxy-d-glucose ([(18)F] FDG) was conducted. [(18)F] FDG-PET imaging accompanied by co-treatment of L-NAME with MK-801 demonstrated that L-NAME ameliorated MK-801-induced glucose utilization.In conclusion, MK-801 induces NO and ROS production in the RS/PC region, which might subsequently induce oxidative stress and in turn neuronal cell death. In addition, MK-801-induced NO production increased glucose utilization and affected glucose metabolism, the imbalance of which might generate additional oxidative stress related to neuronal cell death., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A novel class of phosphodiesterase 10A inhibitors with potent PDE10A inhibitory activity and reduced CYP3A4 inhibition was designed and synthesized starting from 2-[4-({[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (1). Replacement of pyridine ring of 1 with N-methyl pyridone ring drastically improved CYP3A4 inhibition, and further optimization of these quinoline analogues identified 1-methyl-5-(1-methyl-3-{[4-(quinolin-2-yl)phenoxy]methyl}-1H-pyrazol-4-yl)pyridin-2(1H)-one (42b), which showed potent PDE10A inhibitory activity and a good CYP3A4 inhibition profile. A PET study with (11)C-labeled 42b indicated that 42b exhibited good brain penetration and specifically accumulated in the rodent striatum. Further, oral administration of 42b dose-dependently attenuated phencyclidine-induced hyperlocomotion in mice with an ED50 value of 2.0mg/kg and improved visual-recognition memory impairment at 0.1 and 0.3mg/kg in mice novel object recognition test., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Receptor tyrosine kinases play a critical role in cell growth, survival, and proliferation, and are considered potential molecular targets for the treatment of cancer. Although several tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, have demonstrated clinical efficacy via the inhibition of the epidermal growth factor receptor (EGFR), most TKIs are only effective in a small proportion of patients. Positron emission tomography (PET) imaging is a methodology of molecular imaging based on nuclear imaging. PET imaging in combination with radiolabeled TKIs improves accuracy of quantitative imaging strategies and the probability of successful drug development, and may facilitate the stratification of patients. Here, we describe a protocol for PET imaging using radiolabeled TKI in preclinical trials.

Activation of anaplastic lymphoma receptor tyrosine kinase (ALK) is involved in the pathogenesis of several carcinomas, including non-small cell lung cancer (NSCLC). Echinoderm microtubule-associated protein like 4 (EML4)-ALK, which is derived from the rearrangement of ALK and EML4 genes, has been validated as a therapeutic target in a subset of patients with NSCLC. Here, we investigated the effects of ASP3026, a novel small-molecule ALK inhibitor, against ALK-driven NSCLC. ASP3026 inhibited ALK activity in an ATP-competitive manner and had an inhibitory spectrum that differed from that of crizotinib, a dual ALK/MET inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, orally administered ASP3026 was well absorbed in tumor tissues, reaching concentrations >10-fold higher than those in plasma, and induced tumor regression with a wide therapeutic margin between efficacious and toxic doses. In the same mouse model, ASP3026 enhanced the antitumor activities of paclitaxel and pemetrexed without affecting body weight. ASP3026 also showed potent antitumor activities, including tumor shrinkage to a nondetectable level, in hEML4-ALK transgenic mice and prolonged survival in mice with intrapleural NCI-H2228 xenografts. In an intrahepatic xenograft model using NCI-H2228 cells, ASP3026 induced continuous tumor regression, whereas mice treated with crizotinib showed tumor relapse after an initial response. Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance. Taken together, these findings indicate that ASP3026 has potential efficacy for NSCLC and is expected to improve the therapeutic outcomes of patients with cancer with ALK abnormality.