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Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Patients or Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results (odds ratio [OR], 5.475; 95% confidence interval [CI], 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively). No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Early intervention to manage high blood pressure (BP) in young adulthood is a promising approach for the prevention of future cardiovascular diseases. We aimed to examine the ability of childhood health information to predict the incidence of young adults with high BP. This cohort study included baseline clinical data of Japanese individuals aged 12-13 years. A total of 1129 participants were followed up for an average of 8.6 years. We examined the association of childhood variables consisting of body weight, body mass index, systolic BP, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet count, uric acid, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the development of high BP defined as ≥120/80 mmHg at 18-22 years old. At follow-up, the prevalence of high BP was 42.2% in men and 7.7% in women. Young men with high BP had childhood baseline characteristics that included higher body weight, body mass index, systolic BP, red blood cell count, hemoglobin, hematocrit, and uric acid than normotensive men. Young women with high BP had higher body weight, systolic BP, and uric acid at baseline. Multivariable logistic regression analysis revealed that a model including body weight, systolic BP, hematocrit, and uric acid had the highest predictive power (AUC 0.65 [95% CI, 0.62-0.69]) for men, and a model including body weight, systolic BP, and uric acid had the highest predictive power (AUC 0.70 [95% CI, 0.58-0.81]) for women. Comprehensive childhood health information contributes to the prediction of high BP in young adults.

This study presents methods to develop a three-dimensional numerical foot model and to identify the loading condition that is used to design a stable sole for running shoes. In a previous study, the authors proposed a method to optimize the shape of the sole to increase stability while maintaining the cushioning property. In the problem formulation, the loading condition was given as a boundary force distributed on the top surface of the sole. The aim of this study is to replace the loading condition with the force and moment at the origin of the ankle joint coordinate (AJC) system by modeling a foot with a finite element model. A finite element model of a foot is constructed using X-ray CT image data, and consists of bony structures, soft tissue, and plantar fascia. The plantar fascia is set at the bottom of the bony structures. The force and moment used in the finite element analysis are identified by inverse dynamic analysis using an experimental measurement in the practical operation of the ground reaction force (GRF) when the GRF in the direction of the foot length becomes minimum. In the finite element analysis, the finite deformation containing the contact condition between the bottom surface of the foot and the ground representing a sole made of resin is considered. For an index of the shoe stability, we define a heel eversion angle (HEA) by the rotational angle of the heel with respect to an axis in the foot length direction and evaluate it by finite element analysis. The validity of the finite element foot model as well as the force and moment obtained in this study are confirmed based on the agreement in the HEA results between the experiment and finite element analysis.

Background Coronary artery fistulas are rare and most commonly asymptomatic; however, they can become enlarged and rupture in some cases. Case summary We report a case of a 51-year-old woman who was brought to our hospital unconscious in an ambulance. Cardiac tamponade caused by the rupture of an aneurismal coronary-pulmonary artery fistula (CPAF) was detected by contrast-enhanced computed tomography and confirmed by invasive coronary angiography. Due to prompt diagnosis and subsequent surgical intervention, the patient’s condition was rapidly improved, and she was discharged from the hospital. Discussion Coronary-pulmonary artery fistula aneurysm rupture requires rapid diagnosis and treatment, and thus, in cases with cardiac tamponade and coronary aneurysm, CPAF aneurysm rupture should be considered.

Hypertension is the most common non-communicable disease among adults and is the most important modifiable risk factor for premature cardiovascular disease. The increasing worldwide burden of hypertension is a major global health issue. Early prevention with lifestyle modification or pharmaceutical treatment reduces the incidence of hypertension and the risk of subsequent cardiovascular disease. Therefore, identification of young persons at risk for hypertension has the obvious benefit of providing a chance for early intervention. Previous studies have demonstrated the positive association of elevated childhood blood pressure with hypertension in adulthood. Accumulated evidence also indicates the possibility that elevated pediatric blood pressure is associated with increased risk of future cardiovascular disease. In this article, we review the tracking of blood pressure from childhood to adulthood and emphasize the importance of pediatric blood pressure monitoring and control for predicting and preventing adult hypertension and cardiovascular disease.

Low birth weight (LBW) is a risk factor for chronic kidney disease (CKD) in later life and is becoming increasingly common in developed countries, including Japan. Furthermore, a serial decrease in birth weight has been associated with an increasing prevalence of CKD stage 2 in male Japanese adolescents. Sex-specific differences affect CKD susceptibility, and the association between birth weight and CKD in women, has not been elucidated. In this study, we investigated the sex-specific effect of LBW on renal function. Annual cross-sectional data of 2417 Japanese adolescents (males 1736; females 681), aged 15–16 years, were evaluated over 8 years (2007–2014). Over the study period, mean birth weights decreased significantly in males (p

Hypertension is a global public health issue and the most important preventable cause of cardiovascular diseases. Despite the clinical availability of many antihypertensive drugs, many hypertensive patients have poor medication adherence and blood pressure control due, at least partially, to the asymptomatic and chronic characteristics of hypertension. Immunotherapeutic approaches have the potential to improve medication adherence in hypertension because they induce prolonged therapeutic effects and need a low frequency of administration. The first attempts to reduce blood pressure by using vaccines targeting the renin-angiotensin system were made more than half a century ago; however, at the time, a poor understanding of immunology and the mechanisms of hypertension and a lack of optimal vaccine technologies such as suitable antigen design, proper adjuvants, and effective antigen delivery systems meant that attempts to develop antihypertensive vaccines failed. Recent advances in immunology and vaccinology have provided potential therapeutic immunologic approaches to treat not only infectious diseases but also cancers and other noncommunicable diseases. One important biotechnology that has had a major impact on modern vaccinology is virus-like particle technology, which can efficiently deliver vaccine antigens without the need for artificial adjuvants. A human clinical trial that indicated the effectiveness and safety of a virus-like particle-based antiangiotensin II vaccine marked a turning point in the field of therapeutic antihypertensive vaccines. Here, we review the history of the development of immunotherapies for the treatment of hypertension and discuss the current perspectives in the field.

The Japanese hypertension guidelines report that essential hypertension is detected in 1–3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Within the disease’s complicated pathogenic mechanism, activation of the advanced glycation end-products (AGEs)–receptor for AGEs (RAGE) axis plays a pivotal role in the development and progression of DKD. To provide a new therapeutic strategy against DKD progression, we developed a vaccine against RAGE. Three rounds of immunization of mice with the RAGE vaccine successfully induced antigen-specific serum IgG antibody titers, and elevated antibody titers were sustained for at least 38 weeks. In addition, RAGE vaccination significantly attenuated the increase in urinary albumin excretion in streptozotocin-induced diabetic mice (type 1 diabetes model) and leptin-receptor–deficient db/db mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination suppressed glomerular hypertrophy and mesangial expansion in both diabetic models and significantly reduced glomerular basement membrane thickness in streptozotocin-induced diabetic mice. Results of an in vitro study indicated that the serum IgG antibody elicited by RAGE vaccination suppressed the expression of AGE-induced vascular cell adhesion molecule 1 and intracellular adhesion molecule 1 in endothelial cells. Thus, our newly developed RAGE vaccine attenuated the progression of DKD in mice and is a promising potential therapeutic strategy for patients with DKD.

Laboratory tests of adolescents are often interpreted by using reference intervals derived from adults, even though these populations differ in their physical and physiologic characteristics and disease susceptibility. Therefore, to examine the distribution of laboratory values specific for adolescents, we analyzed hematologic and biochemical measurements obtained from 12,023 healthy Japanese adolescents (ages 15 through 18 years; male, 9165; female, 2858) during 2009 through 2018. Distributions were shown as medians with 95% (2.5th and 97.5th percentiles) of values and were compared with those from previous studies that examined similar Asian populations. There were some differences between hematologic parameters, serum creatinine and uric acid concentration, and lipid levels of Japanese adults and adolescents. In comparison with other Asian populations, the distributions of serum uric acid and high-density–lipoprotein cholesterol in the present study were slightly higher than those in the other studies. Although further research is need, the distributions of hematologic and biochemical tests in adolescents may have the potential to facilitate the early identification and management of disease in this population.

Accumulation of DNA double-strand breaks (DSBs) is linked to aging and age-related diseases. We recently reported the possible association of DNA DSBs with altered DNA methylation in murine models of kidney disease. However, DSBs and DNA methylation in human kidneys was not adequately investigated. This study was a cross-sectional observational study to evaluate the glomerular DNA DSB marker γH2AX and phosphorylated Ataxia Telangiectasia Mutated (pATM), and the DNA methylation marker 5-methyl cytosine (5mC) by immunostaining, and investigated the association with pathological features and clinical parameters in 29 patients with IgA nephropathy. To evaluate podocyte DSBs, quantitative long-distance PCR of the nephrin gene using laser-microdissected glomerular samples and immunofluorescent double-staining with WT1 and γH2AX were performed. Glomerular γH2AX level was associated with glomerular DNA methylation level in IgA nephropathy. Podocytopathic features were associated with increased number of WT1(+)γH2AX(+) cells and reduced amount of PCR product of the nephrin gene, which indicate podocyte DNA DSBs. Glomerular γH2AX and 5mC levels were significantly associated with the slope of eGFR decline over one year in IgA nephropathy patients using multiple regression analysis adjusted for age, baseline eGFR, amount of proteinuria at biopsy and immunosuppressive therapy after biopsy. Glomerular γH2AX level was associated with DNA methylation level, both of which may be a good predictor of renal outcome in IgA nephropathy.

Background and aims: Low birth weight is associated not only with poor birth outcome but also chronic health conditions such as hypertension in later life. B-type natriuretic peptide (BNP) is a prognostic factor of cardiovascular events in the general population. However, the association between birth weight and BNP remains unclear. Here, we examined the relationships among birth weight and risk factors for atherosclerosis, including BNP, in Japanese workers. Methods: A total of 1109 (517 male, 592 female; age 40–70 years) participants in an annual medical checkup were enrolled. Subjects were divided into three groups according to birth weight, and the associations between their birth weight and risk factors for atherosclerosis were examined by statistical analysis. Results: Jonckheere–Terpstra trend test according to birth weight category revealed that although birth weight was not correlated with BNP level, it was inversely associated with HbA1c in men and with diastolic blood pressure in women. Correlation coefficient tests for both categorical and continuous birth weight data confirmed the trend test findings. Multiple regression analysis indicated that birth weight was an explanatory factor for HbA1c in men and for diastolic blood pressure in women. Conclusions: Although no significant association was observed between birth weight and BNP, inverse associations between birth weight and HbA1c in men and diastolic blood pressure in women were found. These findings suggest that birth weight may partially predict future risk of cardiovascular events.

Clinical availability of anti-obesity drugs is limited, and their inadequate effectiveness and safety concerns sometimes discourage widespread use. A therapeutic vaccine has the potential to be an attractive tool for preventing and treating obesity, because of the possibility of prolonged therapeutic effect and low frequency of administration. Experimental investigations have shown that vaccines targeting endogenous molecules that promote obesity could be a viable alternative. Recent novelties in drug-delivery systems and biotechnology will support further progress in vaccine development. This chapter provides an overview of recent advances in the area.

Plant-based vaccines (PbVs), developed with novel plant genetic engineering technologies, offer a new strategy for the production, storage, and delivery of vaccines. PbVs can overcome practical and economic concerns surrounding injectable vaccines, including the need for medical staff to perform the injections and the costs of production and refrigeration. The development of unrefrigerated, needle-free vaccines will support the prevention of infectious diseases in developing countries. Although no PbV has yet been licensed for human clinical use, some are now in clinical trials. Antigen-encoding genes introduced into potatoes, lettuce, spinach, corn, tobacco, soybeans, and rice can produce vaccines against mucosal and systemic infectious diseases, including enterotoxigenic Escherichia coli, Vibrio cholerae, norovirus, influenza virus, hepatitis B virus, and rabies virus. This chapter introduces the plant genetic engineering technologies used and clinical trials of PbVs.

Background Fluoine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a useful modality of inflammatory disease. Epicardial adipose tissue (EAT) contains abundant ganglionated plexi, therefore EAT inflammation may cause atrial arrhythmia, such as atrial premature contraction (APC) and atrial fibrillation (AF). Previous studies have shown that inflammatory activity of EAT has relation to the presence of AF. However, it is unknown whether EAT inflammation contributes to the occurrence of AF. Methods Out of 20720 examinees who underwent FDG-PET/CT for screening of cancer in the years 2012–2018, 151 (aged 65.6±12.0 years old, 62 females) had ambulatory electrocardiographic monitoring (Holter ECG) within a year and non-detection of AF. Standardized uptake value (SUV) was measured in fat adjacent to roof of left atrium (ROOF), atrioventricular groove (AV), left main coronary artery (LMT), and right ventricular blood pool (RV). In order to correct for blood pool activity, SUV of ROOF, AV, and LMT were divided by SUV of RV respectively, yielding target-to-background ratio (TBR). As regards to arterial inflammation, measurements were performed with SUV in ascending aorta (A-Ao) and in superior vena cava (SVC) as blood pool. In the same way, SUV of A-Ao was divided by SUV of SVC, yielding TBR. Results According to Holter ECG, APC≥100 beats per day was seen in 60 patients (Group A), but not in the other 91 (Group B). In Group A, TBR of ROOF, AV, and LMT were all significantly higher than Group B (p Conclusions Although EAT inflammation evaluated by SUV is related to frequent APCs, only in fat adjacent to roof of left atrium is associated with and predicts future occurrence of AF. Arterial inflammation measured by SUV has no relation to atrial arrhythmia.

FPGAs can be a promising accelerator used for MEC (Multi-access Edge Computing) which provides timing critical services for a number of terminals at the base stations near from edges. Although a high-end FPGA can support a fixed latency computation with a relatively small power consumption, they are expensive and the available acceleration circuits are limited into a size of single FPGA. FiC (Flow-in-Cloud) has been developed for building a virtual large FPGA from a number of middle-range economical FPGAs connected with high speed serial links. Although the current target of FiC is cloud computing, it is more suitable for the future MEC, because huge hardware resource can be supported with small cost. One of the problem to use such multi-FPGA systems for timing critical computation is network uncertainty. With a common packet switching, the computation speed is influenced with the network traffic. That is, the fixed latency computation which could be supported by a single FPGA is hard to be supported with multi-FPGA systems using common packet switching networks. In order to address this problem, we introduced STDM (Static Time Division Multiplexing) switch in the FiC system. Since the STDM always supports a constant communication latency, transfer time can be estimated beforehand. Through the implementation of the STDM switch on the FPGA board for FiC, it appeared that the utilization ratio of the LUTs for the STDM switch is smaller than 14%. The required number of slots is less than 16 even for a system with 256 nodes. We implemented the Conjugate Gradient method, which includes all-to-all communication, on 4x2 FiC system. It achieved 17.9 times performance improvement of Intel E5-2667 2.90GHz CPU with 6 cores.

FiC (Flow-in-Cloud) is a multi-FPGA system to realize a monolithic large FPGA image with multiple cost-efficient mid-range FPGAs connected with flexible and high bandwidth interconnection network. The FPGA is used as both for computational resource and the network circuit switch, and separating FPGA regions by partial reconfiguration (PR) design technique. In this paper, we will introduce the FPGA design methodology with the PR technique for the FiC system. Evaluation result shows that the proposed design methodology reduces design and configuration time, and it enables to replace the region for computation without stopping the network running on the same FPGA.

Obesity prevalence continues to increase in both adults and children worldwide and greatly contributes to increased morbidity and mortality. Although there are some anti-obesity drugs globally available for clinical use, their inadequate effectiveness coupled with safety concerns sometimes discourage the widespread use of anti-obesity medication. Because of its prolonged therapeutic effect and low frequency of administration, a therapeutic vaccine may be an attractive strategy for the prevention and treatment of obesity. Over the last two decades, several attempts have been made to develop vaccines for the control of obesity. Animal studies have shown that vaccines targeting ghrelin, glucose-dependent insulinotropic polypeptide, adipocytes, somatostatin, and adenovirus 36 successfully led to a reduction in weight gain without serious adverse effects. This chapter provides an overview of recent progress toward a therapeutic vaccine against obesity.

We developed a power converter for small hydroelectric generation. It is an AC/DC/AC conversion system with an inverter for permanent magnetic generator control and an inverter for system interconnection contained in one package. Sensorless PM rotating machine speed control with MPPT was applied to generator control. For MPPT, A similar generator control system for solar power generation was applied and stability control was added while accounting for the fact that hydroelectric generation is subject to higher fluctuation in the power generation amount than solar power generation. In addition, a protective function was added to prevent the mechanical system from entering a critical speed range such as overspeed or mechanical resonance speed.

Proteinuria is a central component of chronic kidney disease and an independent risk factor for cardiovascular disease. Kidney podocytes have an essential role as a filtration barrier against proteinuria. Kruppel-like Factor 4 (KLF4) is expressed in podocytes and decreased in glomerular diseases leading to methylation of the nephrin promoter, decreased nephrin expression and proteinuria. Treatment with an angiotensin receptor blocker (ARB) reduced methylation of the nephrin promoter in murine glomeruli of an adriamycin nephropathy model with recovery of KLF4 expression and a decrease in albuminuria. In podocyte-specific KLF4 knockout mice, the effect of ARB on albuminuria and the nephrin promoter methylation was attenuated. In cultured human podocytes, angiotensin II reduced KLF4 expression and caused methylation of the nephrin promoter with decreased nephrin expression. In patients, nephrin promoter methylation was increased in proteinuric kidney diseases with decreased KLF4 and nephrin expression. KLF4 expression in ARB-treated patients was higher in patients with than without ARB treatment. Thus, angiotensin II can modulate epigenetic regulation in podocytes and ARB inhibits these actions in part via KLF4 in proteinuric kidney diseases. This study provides a new concept that renin-angiotensin system blockade can exert therapeutic effects through epigenetic modulation of the kidney gene expression.

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To combat global increases in the prevalence of lifestyle-related diseases and concomitant infectious diseases, we aimed to develop an innovative intranasal vaccine that simultaneously targets both hypertension and pneumonia, is not given by invasive injection, and offers prolonged therapeutic effect and reduced frequency of administration.Angiotensin II type 1 receptor-pneumococcal surface protein A (AT1R-PspA) vaccine, consisting of a cationic nanometer-sized hydrogel incorporating AT1R partial peptide conjugated with PspA and cyclic diguanylate monophosphate adjuvant, was created and given intranasally to spontaneously hypertensive rats (SHRs). Antigen-specific antibodies and blood pressure were examined to evaluate immune responses and the antihypertensive effect of the vaccine. To examine the protective effect of antibodies induced by vaccination on pneumococcal infection, sera obtained from immunized SHRs were incubated with a lethal dose of Streptococcus pneumoniae and then administered to mice.Five doses of AT1R-PspA nasal-vaccine-induced AT1R-specific serum IgG antibody production and attenuated the development of hypertension in SHRs in the long term. Both in-vitro and in-vivo studies revealed that responses to angiotensin II were suppressed in vaccinated rats. Mice passively immunized with sera obtained from AT1R-PspA-vaccinated SHRs were protected from lethal pneumococcal infection.Intranasal immunization with AT1R-PspA vaccine has the potential to simultaneously attenuate the development of hypertension and protect from lethal pneumococcal infection.

Because the mucosa is the major entry route for most pathogens, the development of mucosal vaccines is a rational approach for protecting against these undesired agents. Mucosal administration of vaccine antigen is useful for non-infectious chronic diseases as well, because of its advantages over injection routes, including comparable efficacy in the induction of systemic immune responses, less pain, and no risk of adverse events at the injection site. However, because it is difficult to effectively induce and regulate antigen-specific mucosal and systemic immune responses when antigen alone is mucosally administered, an appropriate form of mucosal delivery vehicle must be used. Antigen delivery systems involving nanogels, which act as artificial chaperones and mucosal adhesives, are a promising approach to overcoming this problem. Here, we introduce current perspectives regarding the development of nanogel-based nasal vaccines for both infectious and lifestyle-related diseases.

Sensor nodes used in Internet of Things (IoT) are required to work an extremely long time without replacing the battery. Natural renewable energy such as a solar battery is a hopeful candidate for such nodes. Here, a power model for operating an Silicon on Insulator (SOI) device with a solar battery including a large inner resistance is proposed, and applied to a micro-controller V850E-star and an accelerator CMA-SOTB2. Unlike the ideal case, the maximum operational frequency was achieved with reverse biasing by suppressing the leakage current which decreases the supply voltage. Under the room light with a large inner resistance, the strong reverse bias is effective, while a relatively weak reverse bias is advantageous under the bright light. The proposed model is appeared to be useful to estimate the appropriate body bias voltage both for V850E-star and CMA-SOTB2. In the V850E-star, the estimated operational frequencies were different from the real chip, while they were relatively matched when CMA-SOTB2 was used under the low illuminance.

The present paper describes a solution to a non-parametric shape optimization problem of a brake model to suppress squeal noise. The brake model consists of a rotor and a pad, between which Coulomb friction occurs. The main problem is defined as a complex eigenvalue problem of the brake model obtained from the equation of motion. As an objective cost function, we use the positive real part of the complex eigenvalue generating the brake squeal. The volume of the pad is used as a constraint cost function. The Frechet derivative of the objective cost function with respect to the domain variation, which we refer to as the shape derivative of the objective cost function, is evaluated using the solution of the main problem and the adjoint problem. A scheme by which to solve the shape optimization problem using an iterative algorithm based on the H 1 gradient method (the traction method) for reshaping is presented. Numerical results obtained using a simple rotor-pad model reveal that the real part of the target complex eigenvalue decreases monotonically, thus satisfying the volume constraint.

Macro-reentrant ventricular tachycardias (VT) utilizing the bundle branches and Purkinje fibers have been reported as verapamil sensitive VT (idiopathic left VT), bundle branch reentrant VT (BBRT) and inter-fascicular reentrant tachycardia (inter-fascicular VT). However, diagnostic confusion exists with these VTs due to the difficulty in differentiating between them with conventional electrophysiological (EP) studies. The aim of this study was to clarify the EP and anatomical entity of inter-fascicular VT, and provide successful methods for the radio frequency catheter ablation (RFCA) of inter-fascicular VT. A total of nine patients were included in this study. All patients were diagnosed with idiopathic left VT in the first session, and underwent a second session after a failed RFCA. Detailed EP studies guided by a three-dimensional (3D) mapping system were performed to further analyze the VTs. All VTs were finally diagnosed as inter-fascicular VT. They were successfully cured with RFCA targeting the left anterior or posterior fascicle, which was regarded as a requisite part of the reentrant circuit of the inter-fascicular VT, using 3D and fluoroscopic images combined with a detailed EP investigation instead of the conventional RFCA method targeting Purkinje potentials for the RFCA of idiopathic left VT. Inter-fascicular VT could be misdiagnosed as idiopathic left VT due to the limitations of the conventional EP study. Failed RFCA in presumptive idiopathic left VT cases has to be carefully investigated by further analysis, and a tailored RFCA strategy targeting the requisite portions of the left fascicles in the inter-fascicular VT reentrant circuit will be required for the successful elimination of the inter-fascicular VT.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Obesity is associated with multiple comorbidities such as cardiovascular diseases and has a huge economic impact on the health-care system. However, the treatment of obesity remains insufficient in terms of efficacy, tolerability, and safety. Here we created a nasal vaccine against obesity for the first time. To avoid the injectable administration-caused pain and skin-related adverse event, we focused on the intranasal route of antigen delivery. We developed a vaccine antigen (ghrelin-PspA (pneumococcal surface protein A)), which is a recombinant fusion protein incorporating ghrelin, a hormone that stimulates food intake and decreases energy expenditure, and PspA, a candidate of pneumococcal vaccine as a carrier protein. Ghrelin-PspA antigen was mixed with cyclic di-GMP adjuvant to enhance the immunogenicity and incorporated within a nanometer-sized hydrogel for the effective antigen delivery. Intranasal immunization with ghrelin-PspA vaccine elicited serum immunoglobulin G antibodies against ghrelin and attenuated body weight gain in diet-induced obesity mice. This obesity-attenuating effect was caused by a decrease in fat accumulation and an increase in energy expenditure that was partially due to an increase in the expression of mitochondrial uncoupling protein 1 in brown adipose tissue. The development of this nasal vaccine provides a new strategy for the prevention and treatment of obesity.

Previous studies have shown that renin-angiotensin (Ang) system vaccines may be effective for the treatment of hypertension, but their efficacy for the prevention of renal disease is unclear. The aim of this study was to compare the effects of an Ang II type 1 (AT1) receptor vaccine with an Ang II receptor blocker (ARB) and a vasodilator on blood pressure (BP) and renal injury in the L-NAME nephropathy model. Male spontaneously hypertensive rats (SHRs) were divided into six groups and treated transiently with three injections of vehicle or AT1 receptor vaccine (0.1 mg) at age 4, 6 and 8 weeks, or continuously with candesartan cilexetil (0.1 mg kg(-1) per day) or hydralazine hydrochloride (5 mg kg(-1) per day), then administered NG-nitro-L-arginine methyl ester (L-NAME) from age 18 to 21 weeks to induce renal injury. Vaccination against the AT1 receptor caused a significant increase in AT1 receptor titers, and a sustained decrease in BP. L-NAME treatment resulted in a marked increase in proteinuria in the control groups, which was completely suppressed in the AT1 vaccine-treated group, and glomerular injury scores were also significantly decreased. Real-time RT-PCR and immunofluorescence studies revealed increased renin mRNA, and increased glomerular expression of nephrin. Comparable results were seen in rats treated continuously with the ARB candesartan, but not with hydralazine. These results suggest that transient AT1 vaccination is as effective as continuous treatment with ARB, not only for the attenuation of hypertension, but also for the prevention of L-NAME-induced nephropathy in SHR.

Background Acute aortic dissection (AAD) is often missed on initial assessment. Purpose The aim of our study was to identify features associated with misdiagnosis of AAD. Methods and results We examined a total of 109 emergency room (ER) patients who were ultimately diagnosed with AAD. Misdiagnosis of AAD was defined as failure to diagnose AAD at the end of the initial assessment in the ER, and occurred in 17 patients (16%). The alternate diagnosis consisted of acute coronary syndrome (n = 10), other cardiovascular disease (n = 3), abdominal disease (n = 3), and cerebral infarction (n = 1). In the misdiagnosed patients, walk-in mode of admission to the ER (29% vs. 10%, p = 0.042) and anterior chest pain (71% vs. 41%, p = 0.025) were more frequent, and widened mediastinum (25% vs. 55%, p = 0.023) was less frequent than in diagnosed patients. The number of imaging studies performed per patient was also fewer in misdiagnosed patients than in diagnosed patients (0.82 ± 0.81 vs. 1.53 ± 0.52, p

We performed a systematic review of randomised controlled trials in order to identify the best available evidence to compare the outcome between cemented and uncemented hemiarthroplasty for treatment of intracapsular hip fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, MEDLINE and the National Research Register (UK) to retrieve all of the published randomised controlled trials designed to address these issues, in order to perform a meta-analysis. Eight studies involving 1169 patients were determined to be appropriate for meta-analysis. The following statistically significant differences were found between the cemented and uncemented prostheses: (1) longer operative time for cemented prosthesis; (2) lower reduction in mobility score for those treated with cemented prosthesis; (3) fewer patients with residual pain in the hip and lower pain score (signifying less pain) for those treated with a cemented prosthesis. Our meta-analysis has shown that there is good evidence that the use of cement during hemiarthroplasty will reduce the amount of residual hip pain and also allow better restoration of function. There is no evidence of significant adverse effects of cement on mortality or other complications encountered. These observations apply to older designs, and there is a need for randomised trials comparing hydroxyapatite-coated modern stems with cemented prostheses.

This paper presents a numerical solution to a non-parametric shape optimization problem for design of suspension arm in which strength of suspension arm is evaluated by reaction force to plastic buckling load due to compulsory displacement. To deal with buckling phenomena, the geometrical non-linearity and material non-linearity are considered. Hyper-elastic theory is applied to calculate the deformation of suspension arm, under assumption of monotonous loading. Mass and the reaction force integral to the buckling phenomena are chosen as an objective function and a constraint function, respectively. The shape derivatives of these functions are evaluated by the shape optimization theory. A numerical scheme based on a sequential quadratic approximation method is applied to reshape by using the shape gradients. In this scheme, the traction method is used to find the decent directions of the cost functions. The scheme is implemented by using a commercial shape optimization program. In this program, the shape gradients are calculated by a user sub-program which is developed by using the result of non-linear FEM analysis of a commercial solver. The numerical example for a suspension arm model shows 12% of mass reduction while keeping the reaction force integral constant.

Background: Acute aortic dissection (AAD) often accompanies acute respiratory failure. The aim of this study was to clarify the relationship between the incidence of oxygenation impairment and the extent of distal type AAD. Methods and Results: A total of 49 patients with medically treated distal type AAD were retrospectively examined. AAD% was defined as the percentage of the volume of false lumen to that of aorta in the descending aorta. AAD% was measured by computed tomography. C-reactive protein (CRP) levels, white blood cell (WBC) counts, body temperature and arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio were measured serially. Oxygenation impairment was defined as a PaO2/FiO2 ratio ≤200. This occurred in 19 patients (39%). In patients with oxygenation impairment, AAD% (50.8±10.9% vs 28.0±11.9%, P

Back ground: Three-dimensional mapping systems such as the non-contact mapping system (EnSite) have been utilized for radiofrequency catheter ablation (RFCA) in cases with various kinds of arrhythmias. Methods: An EnSite system was utilized for RFCA in 12 patients with right-sided atrial tachycardia (AT). The patients were classified into two groups according to the focus of the AT in the right atrium (RA). The patients in whom the EnSite array was positioned near the focus of the AT were defined as group A, whereas those patients in whom the EnSite array was located less near the focus were defined as group B. RF energy was applied under the guidance of the mapping with the EnSite array. We investigated the relationship between the position of the EnSite array and the focus of the AT in terms of the mapping accuracy in both groups. Results: Even though the accuracy of the mapping of the breakout site and arrhythmia origin was comparable between groups A and B, the distance between the successful CA sites and the presumed AT focus according to the EnSite mapping was significantly shorter in group A than group B. Conclusions: As the location of the focus of the AT becomes closer to the proximal and distal ends of the ESB, the mapping accuracy deteriorates.

This article presents a numerical solution technique for shape optimization problems of steady-state, 3D viscous flow fields. In a previous study, the authors formulated shape optimization problems by considering the minimization of total dissipation energy in the domain of a viscous flow field, proposing a solution technique in which the traction method is applied by making use of a shape gradient. This approach was found to be effective for 2D problems for low Reynolds number flows. In the present study, the validity of the proposed solution technique is confirmed by extending its application to 3D problems.

Static design for soil nailing is based on both of the effects of tensile force developed in reinforcement (internal stability) and overall stability of reinforced zone (external stability). Authors have already obtained the result that external stability due to restraint effect is more important for the actual design of reinforced cut slope in the ordinary condition. On the other hand, usual design method takes no consideration of the stability under seismic load condition, so it is necessary to identify the behavior of the reinforced structure under seismic loading. Present study employed New-Mark method and distinct element method to investigate behavior of the reinforced slope due to seismic loading. Finally, following conclusions were obtained. If the reinforcement installed at the interval that the restraint effect sufficiently works in the ordinary condition, the deformation of the reinforced slope under the seismic loading is controllable to small value, and the stability may be guaranteed.

Background: Electrical isolation of pulmonary veins (PV) by radiofrequency (RF) ablation is often performed in patients with atrial fibrillation (AF). Current catheter technology usually requires the use of a multielectrode catheter for mapping in addition to the ablation catheter. Purpose: We evaluated the feasibility and safety of using a single, expandable electrode catheter (MESH) to map and to electrically isolate the PV. Methods and Results: Nineteen closed-chest mongrel dogs, weighing 23–35 kg, were studied under general anesthesia. Intracardiac echocardiography (ICE) was used to guide transseptal puncture and to assess PV dimensions and contact of the MESH with PV ostia. ICE and angiography of RSPV were obtained before and after ablation, and prior to sacrifice at 7–99 days. An 11.5 Fr steerable MESH was advanced and deployed at the ostium of the RSPV. Recordings were obtained via the 36 electrodes comprising the MESH. For circumferential ablation, RF current was delivered at a target temperature of 62–65°C (4 thermocouples) and maximum power of 70–100 W for 180 to 300 seconds. Each animal received 1–4 RF applications. Entrance conduction block was obtained in 13/19 treated RSPVs. Pathological examination confirmed circumferential and transmural lesions in 13 of 19 RSPV. LA mural thrombus was present in 3 animals. There was no significant PV stenosis. Conclusion: Based on this canine model, a new expandable MESH catheter may safely be used for mapping and for PV antrum isolation. This approach may decrease procedure time without compromising success rate in patients undergoing AF ablation.