Josephson Plasma Mode in Fields Parallel to Layers of Bi_2Sr_2CaCu_2O_{8+\delta}

Josephson plasma resonance measurements under magnetic fields parallel to the CuO_2 layers as functions of magnetic field, temperature, and microwave frequency have been performed in Bi_2Sr_2CaCu_2O_{8+\delta} single crystals with doping range being from optimal to under-doped side. The feature of the resonance is quite unique and cannot be explained by the conventional understandings of the Josephson plasma for H \parallel c, that requires a new theory including coupling effect between Josephson vortex lattice and Josephson plasma.Comment: 2 pages, 2 figure

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

Right adrenal vein identification using unenhanced magnetic resonance imaging

Purpose: Unenhanced magnetic resonance imaging (MRI) is known to be useful in characterizing adrenal adenomas through the implementation of in-phase (IPI) and opposed-phase imaging (OPI) based on chemical shift artifacts. However, whether unenhanced MRI can contribute to the identification of right adrenal vein (RAV) remains unclear. The aim of this study was to evaluate the feasibility of unenhanced MRI for the identification of RAV. Material and methods: This retrospective study reviewed 30 patients (16 men; median age 60 years; range 34-76 years) who underwent MRI and subsequent adrenal venous sampling (AVS). Chemical shift MRI was acquired using echo times of 2.3 ms (OPI) and 4.6 ms (IPI) with a slice thickness of 3 mm and a gap of 1 mm. T2-weighted imaging (T2WI) was also performed. Identification of RAVs was performed by 2 independent radiologists. Inter-observer agreement on a 3-point rating scale was evaluated using κ statistics. The identification rate of RAVs was compared between OPI, IPI, and T2WI using McNemar’s test. Results: Good inter-observer agreement was found for the OPI (κ = 0.744), whereas fair agreement was obtained for both other sequences (IPI: κ = 0.375; T2WI: 0.348). For both raters, the identification rate of RAVs was higher with OPI (36/60; 60.0%) than with other sequences (IPI: 16/60, 26.7%; T2WI: 9/60, 15.0%; p < 0.05, each). Conclusions: OPI may play a screening role in the identification of RAVs preceding AVS, which could reduce the required radiation exposure and doses of contrast agent

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

Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Fas(lpr/lpr) Mice

Objective: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. Methods: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr/J mice. We performed 3′ untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223−/−Faslpr/lpr mice and the lupus phenotypes were analyzed. Results: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr/J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3′ UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223−/−Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8− cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223−/−Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. Conclusion: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis

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

Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice

The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis