慢性期末梢前庭障害に対する前庭リハビリテーションの身体活動量と主観的なめまい感に対する効果：6カ月間のランダム化比較試験

Introduction: The present study aimed to determine whether supervised vestibular rehabilitation therapy (VRT) by physical therapists (PTs) affects subjective dizziness in patients with chronic vestibular disorders, and whether supervised VRT-induced changes in subjective dizziness are related to the changes in physical activity levels in daily life. Methods: Patients (n = 47) with chronic peripheral vestibular disorders were randomly divided into the VRT group (n = 25) and control group (n = 22). Patients in the VRT group received weekly supervised visits from PTs for a period of 6 months. Every other month, both groups were advised by neuro-otologists to increase the amount of activity in their daily life. All patients wore an accelerometer device, which recorded their physical activity for seven successive days before the end of the intervention. Patients also completed the dizziness and unsteadiness questionnaires before and after the intervention. Results: Subjective dizziness decreased significantly regardless of whether supervised VRT was administered; however, dizziness evoked by social activity and head and body movements improved more significantly in the VRT group than in the control group. In the VRT group, there was a significant negative correlation between the increase in sedentary behavior and improvement in subjective dizziness, and a significant positive correlation between the increase in light physical activity and improvement in subjective dizziness at the second month of intervention. The VRT group showed a significantly higher rate of increase in light physical activity than the control group, after 6 months of intervention. Conclusion: Supervised VRT could be highly effective in treating subjective dizziness in patients with chronic peripheral vestibular disorders. We believe frequent (weekly) and medium-term (6 months) PT-guided interventions may be highly effective in enhancing physical activity in daily life, and may subsequently improve subjective dizziness in these patients. Trial registration: This clinical study was registered with University hospital Medical Information Network (identification number: 000028832). https://www.umin.ac.jp/博士（医学）・甲第878号・令和5年3月15

Development of Safety Measures of Bicycle Trafflc by Observation wffh Deep-Leamlng, Drive Recorder Data, Probe Blcycle wlth LIDAR, and Connected Simulators

This research outlines the development of evaluating safety measures for bicycle traffic using state-of-the-art technology, which was started since 2020 as a four-year project. The project is funded by the Commission on Advanced Road Technology in the Ministry of Land, Infrastructure, Transport and Tourism(MLIT). While Japan has a high bicycle modal share of 12% (2010), bicycle-related fatalities are relatively high among other countries in the IRTAD database (2019). Under these circumstances, since 2007, various measures for bicycle traffic measures have been implemented to improve the safe bicycle traffic environment, including the revision of the Road Traffic Act and the formulation of a national plan to promote bicycle use. However, serious accidents involving bicycles are remained in some specific cases. According to the government's traffic accident analysis results (2019), right-hook crash at signalized intersections are one of the most serious types of collision involving bicycles, along with accidents at unsignalized intersections involving vehicles turning left, rear-end collisions, and single vehicle accidents due to off-road deviation. In particular, proactive safety measures are required at signalized intersections along arterial roads, where electric personal mobility vehicles traveling at speeds of up to 20 km/h are expected to share with bicycles in the future. In order to evaluate safety measures for bicycle-vehicle crashes, this project set the following goals. 1) Identify factors influencing near-miss incidents and collisions through analysis of drive recorder data and accident statistical data. 2) Detailed analysis of traffic conditions from the cyclist's perspective using a probe bicycle equipped with a LiDAR sensor. 3) Development of an experimental environment using a connected simulator for evaluation of cooperative driving behavior. 4) Clarification of experimental conditions to evaluate different scenarios and conditions with and without intervention. 5) Proposal of effective interventions to improve crash cases based on experiments

難治性の良性発作性頭位めまい症はヘッドアップした姿勢で就寝することにより治り得る：6ヶ月間のランダム化比較試験

Objectives: The aim of the present study was to assess head-position management for intractable idiopathic benign paroxysmal positional vertigo (BPPV) when lying down. We hypothesized that head-up sleep (HUS) could prevent free-floating otoliths from entering the semicircular canals. Study design: A prospective two-arm multicenter randomized controlled trial. Methods: BPPV was diagnosed in 611 patients (611/1,520; 40.2%) according to the 2015 diagnostic guidelines issued by the International Classification of Vestibular Disorders. Among them, 201 patients were intractable (201/611; 32.9%), 88 of whom were idiopathic and subsequently enrolled in the study. Patients randomly received intervention with HUS at greater than 45° (n = 44) or head-down sleep (HDS; n = 44) when lying down. Before treatment, they completed several examinations, including subjective visual vertical (SVV). The specific diagnoses for the 88 patients with BPPV included horizontal type cupula (n = 40), horizontal type canal (n = 13), posterior type (n = 26), and probable and/or atypical BPPV (n = 9). Results: Patient backgrounds did not differ significantly between the HUS and HDS groups. Visual analog scale (VAS) scores of vertiginous sensation were significantly lower in the HUS group than in the HDS group at both the third month and sixth month post-treatment. Positional/positioning nystagmus observed just before treatment disappeared significantly more often in the HUS group than in the HDS group until the sixth post-treatment month. Further, especially in HUS group, VAS scores in SVV- group (n = 24) were significantly lower than those in the SVV+ group (n = 20) sixth month post-treatment. Conclusions: Controlling free-floating otoliths is not easy due to aging of the otolith organs. Repeatedly returning the endless free-floating debris from the canals to the utricle through physical means is not a good strategy. Therefore, HUS when lying down at home could be recommended as an initial treatment for patients with intractable idiopathic BPPV. Level of evidence: 1b.博士（医学）・甲第764号・令和3年3月15日© 2019 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals, Inc. on behalf of The Triological Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made

Mammalian Lgl Forms a Protein Complex with PAR-6 and aPKC Independently of PAR-3 to Regulate Epithelial Cell Polarity

AbstractBackground: Epithelial cells have apicobasal polarity and an asymmetric junctional complex that provides the bases for development and tissue maintenance. In both vertebrates and invertebrates, the evolutionarily conserved protein complex, PAR-6/aPKC/PAR-3, localizes to the subapical region and plays critical roles in the establishment of a junctional complex and cell polarity. In Drosophila, another set of proteins called tumor suppressors, such as Lgl, which localize separately to the basolateral membrane domain but genetically interact with the subapical proteins, also contribute to the establishment of cell polarity. However, how physically separated proteins interact remains to be clarified.Results: We show that mammalian Lgl competes for PAR-3 in forming an independent complex with PAR-6/aPKC. During cell polarization, mLgl initially colocalizes with PAR-6/aPKC at the cell-cell contact region and is phosphorylated by aPKC, followed by segregation from apical PAR-6/aPKC to the basolateral membrane after cells are polarized. Overexpression studies establish that increased amounts of the mLgl/PAR-6/aPKC complex suppress the formation of epithelial junctions; this contrasts with the previous observation that the complex containing PAR-3 promotes it.Conclusions: These results indicate that PAR-6/aPKC selectively interacts with either mLgl or PAR-3 under the control of aPKC activity to regulate epithelial cell polarity

Endolymphatic Hydrops After Sac Surgery

Meniere’s disease is a common disease, that presents with recurrent vertigo and cochlear symptoms. The pathology of Meniere’s disease was first reported to involve endolymphatic hydrops in 1938. The endolymphatic sac is thought to have a role to keep the hydrostatic pressure and endolymph homeostasis for the inner ear. As a surgery for intractable Meniere’s disease, endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids is performed to control the endolymphatic hydrops and preserve or improve inner ear function. In the present study, to observe the effect of this surgery, we calculated the endolymphatic space size using 3-Teslamagnetic resonance imaging (MRI) 4 h after intravenous injection of gadolinium enhancement at two time points: just before surgery and 2 years after. To reveal the condition of the endolymphatic space, we constructed three-dimensional MR images semi-automatically and fused the three-dimensional images of the total fluid space of inner ear and the endolymphatic space. After fusing the images, we calculated the volume of the total fluid space and endolymphatic space. Two years after surgery, 16 of 20 patients (80.0%) showed relief from vertigo/dizziness and reductions in the ratio of the volume of the endolymphatic size to the total fluid space of inner ear. Endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids could control vertigo/dizziness and decrease the endolymphatic hydrops. These results indicate that endolymphatic sac drainage is a good treatment option for patients with intractable Meniere’s disease. In addition, volumetric measurement of inner ear volume could be useful for confirming the effect of treatments on Meniere’s disease

Early Spectroscopy of the 2010 Outburst of U Scorpii

We present early spectroscopy of the recurrent nova U~Sco during the outburst in 2010. We successfully obtained time-series spectra at $t_{\rm d}=$0.37--0.44~d, where $t_{\rm d}$ denotes the time from the discovery of the present outburst. This is the first time-resolved spectroscopy on the first night of U Sco outbursts. At $t_{\rm d}\sim 0.4$~d the H$\alpha$ line consists of a blue-shifted ($-5000$ km s$^{-1}$) narrow absorption component and a wide emission component having triple peaks, a blue ($\sim -3000$ km s$^{-1}$), a central ($\sim 0$ km s$^{-1}$) and a red ($\sim +3000$ km s$^{-1}$) ones. The blue and red peaks developed more rapidly than the central one during the first night. This rapid variation would be caused by the growth of aspherical wind produced during the earliest stage of the outburst. At $t_{\rm d}=1.4$~d the H$\alpha$ line has a nearly flat-topped profile with weak blue and red peaks at $\sim \pm 3000$ km s$^{-1}$. This profile can be attributed to a nearly spherical shell, while the asphericity growing on the first night still remains. The wind asphericity is less significant after $t_{\rm d}=9$ d.Comment: 5 pages, 3 figures, Accepted for publication of PASJ Letter

Large-Scale RNA Interference Screening in Mammalian Cells Identifies Novel Regulators of Mutant Huntingtin Aggregation

In polyglutamine (polyQ) diseases including Huntington's disease (HD), mutant proteins containing expanded polyQ stretch form aggregates in neurons. Genetic or RNAi screenings in yeast, C. elegans or Drosophila have identified multiple genes modifying polyQ aggregation, a few of which are confirmed effective in mammals. However, the overall molecular mechanism underlying polyQ protein aggregation in mammalian cells still remains obscure. We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. Classification of the shRNA-targets suggests that genes with various cellular functions such as gene transcription and protein phosphorylation are involved in modifying the aggregation. Subsequent analysis suggests that, in addition to the aggregation-modifiers sensitive to proteasome inhibition, some of them, such as a transcription factor Tcf20, and kinases Csnk1d and Pik3c2a, are insensitive to it. As for Tcf20, which contains polyQ stretches at N-terminus, its binding to mutant huntingtin aggregates is observed in neuro2a cells and in HD model mouse neurons. Notably, except Pik3c2a, the rest of the modifiers identified here are novel. Thus, our first large-scale RNAi screening in mammalian system identifies previously undescribed genetic players that regulate mutant huntingtin aggregation by several, possibly mammalian-specific mechanisms

Expression of enhancer of zeste homolog 2 correlates with survival outcome in patients with metastatic breast cancer: exploratory study using primary and paired metastatic lesions

Evaluation of immunostaining of EZH2 and Ki67. (DOC 52 kb