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BACKGROUND: Previous studies have reported altered neural activity in the motor cortex after short-term cast immobilization, even in healthy participants. However, the effects of short-term movement restriction on tissue structure are not well understood. OBJECTIVE: To investigate the effects of short-term lower limb immobilization on muscle tissue hardness. METHODS: Seventeen healthy participants were enrolled in the study. Each participant’s non-dominant lower limb was fixed with a soft bandage and medical splint for 10 h. Gastrocnemius muscle tissue hardness was measured using a tissue hardness meter before cast application and immediately after cast removal. Measurements were performed five times for each lower limb, and the three values with the lowest coefficient of variance were adopted as the value of muscle tissue hardness. RESULTS: Gastrocnemius muscle tissue hardness in the immobilized limb was lower after cast removal than that before cast application (from 53.6 to 51.8; p< 0.01), whereas the non-fixed limb showed an increase in muscle tissue hardness at the end of the experiment (from 52.9 to 54.3; p= 0.03). CONCLUSION: The findings indicate that 10 h movement restriction induced a reduction in muscle tissue hardness, suggesting acute adverse effects of cast immobilization for orthopedic treatment.

Background: Mitochondrial DNA (mtDNA)-induced myocardial inflammation is intimately involved in cardiac remodeling. ZBP1 (Z-DNA binding protein 1) is a pattern recognition receptor positively regulating inflammation in response to mtDNA in inflammatory cells, fibroblasts, and endothelial cells. However, the role of ZBP1 in myocardial inflammation and cardiac remodeling remains unclear. The aim of this study was to elucidate the role of ZBP1 in mtDNA-induced inflammation in cardiomyocytes and failing hearts. Methods: mtDNA was administrated into isolated cardiomyocytes. Myocardial infarctionwas conducted in wild type and ZBP1 knockout mice. Results: We here found that, unlike in macrophages, ZBP1 knockdown unexpectedly exacerbated mtDNA-induced inflammation such as increases in IL (interleukin)-1β and IL-6, accompanied by increases in RIPK3 (receptor interacting protein kinase 3), phosphorylated NF-κB (nuclear factor-κB), and NLRP3 (nucleotide-binding domain and leucine-rich-repeat family pyrin domain containing 3) in cardiomyocytes. RIPK3 knockdown canceled further increases in phosphorylated NF-κB, NLRP3, IL-1β, and IL-6 by ZBP1 knockdown in cardiomyocytes in response to mtDNA. Furthermore, NF-κB knockdown suppressed such increases in NLRP3, IL-1β, and IL-6 by ZBP1 knockdown in response to mtDNA. CpG-oligodeoxynucleotide, a Toll-like receptor 9 stimulator, increased RIPK3, IL-1β, and IL-6 and ZBP1 knockdown exacerbated them. Dloop, a component of mtDNA, but not Tert and B2m , components of nuclear DNA, was increased in cytosolic fraction from noninfarcted region of mouse hearts after myocardial infarction compared with control hearts. Consistent with this change, ZBP1, RIPK3, phosphorylated NF-κB, NLRP3, IL-1β, and IL-6 were increased in failing hearts. ZBP1 knockout mice exacerbated left ventricular dilatation and dysfunction after myocardial infarction, accompanied by further increases in RIPK3, phosphorylated NF-κB, NLRP3, IL-1β, and IL-6. In histological analysis, ZBP1 knockout increased interstitial fibrosis and myocardial apoptosis in failing hearts. Conclusions: Our study reveals unexpected protective roles of ZBP1 against cardiac remodeling as an endogenous suppressor of mtDNA-induced myocardial inflammation.

Reports of mortality-associated risk factors in patients with coronavirus disease (COVID-19) are limited.We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (N=158) and those who were alive at discharge (N=2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study.Patients who died were older (71.1 years versus 51.6 years, P0.001), had higher median D-dimer values on admission (1.7 μg/mL versus 0.8 μg/mL, P0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% versus 63%, moderate: 47% versus 31%, and severe: 37% versus 6.2%, P0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs. 1.5%, P0.001; major bleeding: 12.7% vs. 1.4%, P0.001). Multivariable logistic regression analysis revealed that age70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk.This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

The patient was a 70-year-old man who underwent transurethral resection of a bladder tumor. The pathological diagnosis was urothelial carcinoma (UC) with sarcomatoid variant, ≧pT2. After neoadjuvant chemotherapy using gemcitabine and cisplatin (GC), radical cystectomy was performed. The histopathological diagnosis was no tumor remnant (ypT0ypN0). Seven months later, the patient underwent an emergency partial ileectomy for ileal occlusion, after sudden complaints of vomiting and abdominal pain and fullness. Postoperatively, two cycles of adjuvant GC chemotherapy were administered. Approximately 10 months after ileal metastasis, a mesenteric tumor appeared. After seven cycles of methotrexate/epirubicin/nedaplatin and 32 cycles of pembrolizumab therapy, the mesentery was resected. The pathological diagnosis was UC with sarcomatoid variant. No recurrence was noted for 2 years after resection of the mesentery.

The RANS (RIKEN Accelerator driven Neutron Source), one of compact accelerator neutron sources (CANS), tries to expand its performance by installing a cold neutron which may provide new opportunities in many applications. RANS is a low power CANS with a proton beam of 7 MeV and 100 µA at maximum. A moderator system was constructed based on results of optimization design study with mesitylene. Recently, we have done performance tests aiming at showing characteristics as cold neutron source. Cryogenic mesitylene moderator was installed on a plug with a new target moderator reflector configuration of RANS. Experiment using a gas electron multiplier (GEM) detector was carried out to measure neutron spectra of the cold moderator. This paper describes performance of the cold moderator in terms of 1) Cold neutron gain of optimization design with respect to a polyethylene moderator, 2) Temperature dependency of cold neutron spectrum flux regarding scattering kernel (SK), and 3) comparison between experiment and calculation. A note is given for comparison between calculations with different SKs available. Also, two-dimensional imaging of cold and thermal neutron spectrum flux on the viewed surface is shown with a pinhole slit configuration.

Introduction: It is critical to develop accurate and universally available biomarkers for dementia diseases to appropriately deal with the dementia problems under world-wide rapid increasing of patients with dementia. In this sense, electroencephalography (EEG) has been utilized as a promising examination to screen and assist in diagnosing dementia, with advantages of sensitiveness to neural functions, inexpensiveness, and high availability. Moreover, the algorithm-based deep learning can expand EEG applicability, yielding accurate and automatic classification easily applied even in general hospitals without any research specialist. Methods: We utilized a novel deep neural network, with which high accuracy of discrimination was archived in neurological disorders in the previous study. Based on this network, we analyzed EEG data of healthy volunteers (HVs, N = 55), patients with Alzheimer’s disease (AD, N = 101), dementia with Lewy bodies (DLB, N = 75), and idiopathic normal pressure hydrocephalus (iNPH, N = 60) to evaluate the discriminative accuracy of these diseases. Results: High discriminative accuracies were archived between HV and patients with dementia, yielding 81.7% (vs. AD), 93.9% (vs. DLB), 93.1% (vs. iNPH), and 87.7% (vs. AD, DLB, and iNPH). Conclusion: This study revealed that the EEG data of patients with dementia were successfully discriminated from HVs based on a novel deep learning algorithm, which could be useful for automatic screening and assisting diagnosis of dementia diseases.

To determine the clinical characteristics of and risk factors for suspected reinfection with coronavirus 2019 (COVID-19). This was a retrospective cohort study using population-based notification records of residents in Kyoto City (1.4 M) with laboratory-confirmed COVID-19 infection between 1 March 2020 and 15 April 2022. Reinfection was defined by two or more positive COVID-19 test results ≧ 90 days apart. Demographic characteristics, the route and timing of infection and history of vaccination were analysed to identify risk factors for reinfection. Among the cohort of 107, 475 patients, reinfection was identified in 0.66% (n = 709). The age group with the highest reinfection rate was 18-39 years (1.06%), followed by 40-59 years (0.58%). Compared to the medical and nursing professionals, individuals who worked in the construction and manufacturing industry (odds ratio [OR]: 2.86; 95% confidence interval [CI]: 1.66-4.92) and hospitality industry (OR: 2.05; 95% CI: 1.28-.31) were more likely to be reinfected. Symptomatic cases at initial infection, receiving more than 2 doses of vaccination and risk factors for severe infection at initial infection were protective factors against reinfection. Of the reinfected individuals, the reinfection route was unknown in 65%. Reinfection with COVID-19 is uncommon, with suspected reinfections more likely in adults, those with high exposure and unvaccinated individuals; the reinfection route was unknown in the majority of cases. This study confirmed the need to continue with self-protection efforts and to implement vaccination programs in high-risk populations.

A prototype MgB2 bulk with a diameter of 20 mm and a thickness of 2 mm was synthesized using the MVT (Magnesium Vapor Transport) method, which can realize dense and high-purity MgB2 bulks by transporting and diffusing pure magnesium vapor into boron pellets. Owing to its superior Jc-B characteristic, the obtained bulk by the MVT method exhibited, compared to similar bulks synthesized by the conventional in-situ method, a comparable trapped magnetic field at only one-tenth the thickness. Using the measured Jc(B) data, the influence of the geometry and the size of the bulk synthesized by the MVT method on the trapped magnetic field was investigated by numerical simulation. The simulation results suggest that a bulk fabricated by the MVT method can efficiently achieve a large trapped magnetic field with a thinner thickness for a fixed diameter than a bulk fabricated by the in-situ method.

小型月探査機の役割は、中・大型月探査機ではリスクが高く、探査が困難な狭い場所や急斜面を探査することである。月面のレゴリスや急斜面は、小型の月探査機にとって課題となっている。そこで、本研究では、スクリュユニットを用いた探査機に着目した。登坂性能を向上させるための新しいスクリュ形状として、スクリュの入口径と出口径が異なる「テーパ型スクリュ」を提案した。スクリュのテーパ形状と羽根の枚数を比較し、登坂性能と消費電力がどのように変化するかを検証した。また、3Dスキャナを用いて各スクリュの砂の充填量を解析し、搬送量から走行性能を評価した。その結果、テーパー形状にすることで軽量化が期待できることが明らかになった。さらに、羽根の枚数を増やすことで、登坂性能が向上した。, Regolith and steep slopes on the lunar surface are challenges for small lunar rovers. Therefore, this study focused on a probe using a screw unit. We propose a "tapered screw" with different screw radius inlet and outlet diameters as a new screw geometry to improve the hill climbing performance of Screw. We compared the taper shape of the screw and the number of blades to verify how hill climbing performance and power consumption change. In addition, the sand filling rate of each screw thread was analyzed using a 3D scanner, and running performance was evaluated based on the amount of sand transported. As a result, it is clear that a tapered shape is expected to reduce weight. Furthermore, increasing the number of blades improved hill climbing performance.

AIMS: Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large-scale Japanese AHF registry. METHODS AND RESULTS: The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all-cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72-86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction

The preset study evaluated the outcome of living-donor segmental lung transplantation for pediatric patients.Between August 2009 and May 2021, we performed living-donor segmental lung transplantation in 6 critically ill pediatric patients, including 1 patient on a ventilator alone and another patient on a ventilator and extracorporeal membrane oxygenation (ECMO). There were 4 male and 2 female patients, with a median age of 7 years (range, 4-15 years) and a median height of 112.7 cm (range, 95-125.2 cm). The diagnoses included complications of allogeneic hematopoietic stem cell transplantation (n = 4) and pulmonary fibrosis (n = 2). All patients received bilateral lung transplantation under cardiopulmonary bypass. A basal segment and a lower lobe were implanted in 3 patients, and a basal segment and an S6 segment were implanted in the other 3 patients. In 2 patients, the right S6 segmental graft was horizontally rotated 180° and implanted as the left lung.Among the 9 segmental grafts implanted, 7 functioned well after reperfusion. Two rotated S6 segmental grafts became congestive, with 1 requiring graft extraction and the other venous repair, which was successful. There was 1 hospital death (14 days) due to sepsis and 1 late death (9 years) due to leukoencephalopathy. The remaining 4 patients are currently alive at 9 months, 10 months, 1.3 years, and 1.9 years.Living-donor segmental lung transplantation was a technically difficult but feasible procedure with acceptable outcomes for small pediatric patients with chest cavities that were too small for adult lower lobe implantation.

Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch.Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS).A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112.UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents.ClinicalTrials.gov identifier, NCT03661138.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Com o aumento da longevidade e expectativa da população mundial, há o crescimento também de patologias e comorbidades, acarretando na prática desenfreada da polimedicação ou polifarmácia. Realizar uma revisão integrativa da literatura sobre a atenção farmacêutica na polimedicação da população idosa no Brasil. Estudo de revisão integrativa, de cunho exploratório, qualitativo, transversal e descritivo, investigados nas bases de dados científicas: Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências das Saúde (LILACS) e National Library os Medicine (MEDLINE), partindo dos descritores em Ciências da saúde (DeCS): “Polimedicação”, “Atenção farmacêutica” e “idosos”, no recorte temporal de 2017 a 2022. Foram selecionados artigos que retrataram que a prática da polimedicação é comum na população idosa, a atenção farmacêutica atua para minimizar os problemas relacionados ao medicamento. Assim, a atuação do farmacêutico é importante para a promoção de saúde e uso racional de medicamentos para a população idosa no Brasil.

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.

To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE.We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models.The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT-S and 0.88 [p = 0.001] for CAVE-S at the testing data).Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2022.

In a digital twin, a humanoid robot can be the counterpart of a simulated agent in the real world. In addition, a human, virtual avatar, and avatar robot might constitute digital triplets. We propose an inflatable cybernetic avatar (CA) with a humanoid upper body using an inflatable structure that can represent gestures. This inflatable CA is much lighter, safer, and cheaper than conventional humanoid robots and can be folded when deflated. These properties are ideal for physical human–robot interaction (pHRI) and allow real-time collection of human behavior through interaction. In the experiment, basic movements such as nodding and raising arms were measured using motion capture systems. This paper demonstrates the proposed inflatable CA in a hybrid event. We also conducted an experiment to measure the touch interactions using tactile sensors attached to the fabric of the inflatable part. A psychologically secure inflatable humanoid CA is a promising platform for physical interaction experiments.