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Background Activated factor X (FXa), which contributes to chronic inflammation via protease-activated receptor 2 (PAR2), might play an important role in atrial fibrillation (AF) arrhythmogenesis. This study aimed to assess whether PAR2 signaling contributes to AF arrhythmogenesis and whether rivaroxaban ameliorates atrial inflammation and prevents AF.Methods and Results:In Study 1, PAR2 deficient (PAR2-/-) and wild-type mice were infused with angiotensin II (Ang II) or a vehicle via an osmotic minipump for 2 weeks. In Study 2, spontaneously hypertensive rats (SHRs) were treated with rivaroxaban, warfarin, or vehicle for 2 weeks after 8 h of right atrial rapid pacing. The AF inducibility and atrial remodeling in both studies were examined. Ang II-treated PAR2-/- mice had a lower incidence of AF and less mRNA expression of collagen1 and collagen3 in the atrium compared to wild-type mice treated with Ang II. Rivaroxaban significantly reduced AF inducibility compared with warfarin or vehicle. In SHRs treated with a vehicle, rapid atrial pacing promoted gene expression of inflammatory and fibrosis-related biomarkers in the atrium. Rivaroxaban, but not warfarin, significantly reduced expression levels of these genes. Conclusions The FXa-PAR2 signaling pathway might contribute to AF arrhythmogenesis associated with atrial inflammation. A direct FXa inhibitor, rivaroxaban, could prevent atrial inflammation and reduce AF inducibility, probably by inhibiting the pro-inflammatory activation.

Background: The coagulation system is closely linked with vascular inflammation, although the underlying mechanisms are still obscure. Recent studies show that protease-activated receptor (PAR)-2, a major receptor of activated factor X, is expressed in both vascular cells and leukocytes, suggesting that PAR-2 may contribute to the pathogenesis of inflammatory diseases. Here we investigated the role of PAR-2 in vascular inflammation and atherogenesis. Methods: We generated apolipoprotein E-deficient ( ApoE -/- ) mice lacking systemic PAR-2 expression ( PAR-2 -/- ApoE -/- ). ApoE -/- mice, which lack or express PAR-2 only in bone marrow (BM) cells, were also generated by BM transplantation. Atherosclerotic lesions were investigated after 20 weeks on a Western-type diet by histological analyses, quantitative reverse transcription polymerase chain reaction, and Western blotting. In vitro experiments using BM-derived macrophages were performed to confirm the proinflammatory roles of PAR-2. The association between plasma activated factor X level and the severity of coronary atherosclerosis was also examined in humans who underwent coronary intervention. Results: PAR-2 -/- ApoE -/- mice showed reduced atherosclerotic lesions in the aortic arch ( P P P P P ApoE -/- mice. Systemic PAR2 deletion in ApoE -/- mice significantly decreased the expression of inflammatory molecules in the aorta. The results of BM transplantation experiments demonstrated that PAR-2 in hematopoietic cells contributed to atherogenesis in ApoE -/- mice. PAR-2 deletion did not alter metabolic parameters. In vitro experiments demonstrated that activated factor X or a specific peptide agonist of PAR-2 significantly increased the expression of inflammatory molecules and lipid uptake in BM-derived macrophages from wild-type mice compared with those from PAR-2–deficient mice. Activation of nuclear factor-κB signaling was involved in PAR-2–associated vascular inflammation and macrophage activation. In humans who underwent coronary intervention, plasma activated factor X level independently correlated with the severity of coronary atherosclerosis as determined by Gensini score ( P P Conclusions: PAR-2 signaling activates macrophages and promotes vascular inflammation, increasing atherosclerosis in ApoE -/- mice. This signaling pathway may also participate in atherogenesis in humans.

Background It is well known that warfarin inhibits the synthesis of vitamin K-dependent anticoagulants, including thrombin, protein C and S, and factor Xa, leading, paradoxically, to an initial hypercoagulable state. Edoxaban, a direct inhibitor of activated factor X is widely used for the treatment of acute venous thromboembolism (VTE). However, the effect of edoxaban on circulating coagulation factors, in patients with acute VTE, remains unknown. Methods and results We enrolled 57 patients with acute VTE with/without pulmonary embolism treated with edoxaban (n = 37) or warfarin (n = 20) in a clinical setting. Before treatment and 2 weeks after treatment, we evaluated thrombotic burden using ultrasound or computed tomography angiography. We also evaluated thrombin generation, represented by prothrombin fragment F1 + 2; thrombus degradation, represented by D-dimer; and levels of anticoagulants, including protein C, protein S, and antithrombin III. Both edoxaban and warfarin treatment improved thrombotic burden and decreased prothrombin fragment F1 + 2, and D-dimer. Edoxaban treatment preserved protein C and protein S levels. In contrast, warfarin decreased protein C and protein S levels. Neither treatment affected antithrombin III. Conclusions Edoxaban improves VTE while preserving protein C and protein S levels, thereby indicating that edoxaban improves thrombotic burden while maintaining levels of anticoagulants.

Effects of GaAs/indium tin oxide (ITO)/Si junctions on III-V-on-Si multijunction solar cells are examined by fabricating and characterizing InGaP/GaAs/ITO/Si triple-junction (3J) solar cells. The 3J cells are fabricated by evaporating $\approx$ 100-nm-thick ITO films on the surfaces of Si bottom cells and bonding the InGaP/GaAs double-junction (2J) subcells and the ITO films using surface-activated bonding technologies at room temperature. The current–voltage characteristics of 3J cells with $p^{+}$ -GaAs/ITO/ $n^{+}$ -Si and $n^{+}$ -GaAs/ITO/ $n^{+}$ -Si junctions are compared with those of an InGaP/GaAs/Si 3J cell. The parasitic resistance of the respective 3J cells is estimated by analyzing their characteristics in the dark. We find that the 3J cell with an $n^{+}$ -GaAs/ITO/ $n^{+}$ -Si junction shows the lowest parasitic resistance, which is the origin of its lowest differential resistance at the open-circuit voltage and highest fill factor. This means that $n^{+}$ -GaAs/ITO/ $n^{+}$ -Si junctions are promising for improving the performances of III-V-on-Si hybrid multijunction cells. The spectral response characteristics of these cells indicate that the thickness of the ITO films must be optimized.

Renin is the rate‐limiting enzyme of the renin–angiotensin system cascade, which drives the pathophysiological progression of heart failure. Species differences in the amino acid sequence of the catalytic domain of renin limit evaluations of the potency and efficacy of human renin inhibitors in animal models, and a high dose of inhibitors is usually needed to show its organ‐protective effects in rodents. In the present study, we developed a novel murine heart failure model (triple‐tg) to enable us to evaluate the cardioprotective effect of renin inhibitors at more relevant doses for humans, by cross‐breeding calsequestrin transgenic (CSQ‐tg) mice with human renin and human angiotensinogen double‐transgenic mice. The triple‐tg mice exhibited increased plasma renin activity, worsened cardiac hypertrophy, and higher mortality compared to CSQ‐tg mice. Triple‐tg mice treated with 10 mg·kg−1 of TAK‐272 (imarikiren/SCO‐272), an orally active direct renin inhibitor, exhibited improvements in heart failure phenotypes, such as cardiac hypertrophy and survival rate; however, a dose of 300 mg·kg−1 was required to improve symptoms in CSQ‐tg mice. Our results suggest that this newly generated triple‐tg heart failure model is useful to evaluate the cardioprotective effects of human renin inhibitors at clinically relevant doses, thereby minimizing the concerns of off‐target effects related to much higher drug exposure than that achieved in clinical study., A high dose of human renin inhibitors is required to show efficacy in rodent models due to species differences between renin. We developed a novel murine heart failure model (triple‐tg) by cross‐breeding calsequestrin transgenic mice with human renin and human angiotensinogen double‐transgenic mice and investigated the cardioprotective effect of imarikiren at clinically relevant doses.

The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion. J. Med. Invest. 66 : 185-187, February, 2019.

Background: Despite improvements in outcome for patients treated with triplet and quadruplet based regimens, multiple myeloma is still a relapsing and ultimately fatal disease. We previously reported that targeting an investigational attenuated form of IFNα, or Attenukine™, to multiple myeloma (MM) tumor cells via direct fusion to an anti-CD38 antibody (TAK-573) has direct anti-proliferative activity on MM cancer cells in vitro and induces robust and durable responses in MM xenograft tumor models, alone and in combination with standard-of-care (SOC) agents. Here, we further elucidate the broad immunomodulatory impact and antitumor activity of a murine reactive version of TAK-573, anti-mouse CD38-attenuated murine IFNα (mCD38-mATT), alone and in combination with SOC agents in immunocompetent murine tumor models of MM. Methods: Murine CD38 receptor expression and direct sensitivity to murine IFNα (mIFNα) of 2 murine MM cell lines were characterized. Murine MM cell line-derived tumor models were established in immunocompetent mice and antitumor activity of mCD38-mATT treatment was evaluated alone and in combination with approved SOC agents for MM. Pharmacodynamic changes in the tumor immune microenvironment post-treatment were determined using multicolor flow cytometry. Results: Both MM murine tumor cell lines were insensitive to direct mIFNα treatment, indicating a reliance on immune-mediated antitumor activity when tested in vivo. Immunoprofiling analyses post-administration with single-agent mCD38-mATT indicated increased prevalence and activation of NK cells in peripheral blood and increased intratumoral CD8+ T: Treg and CD8+ T: CD4+ T cell ratios, compared to anti-mCD38 antibody or murine IFNα alone. Follow-on experiments evaluating single-agent mCD38-mATT indicated modest activity on tumor growth in vivo. Combination administration of mCD38-mATT with SOC agents had increased anti-tumor activity compared to either single-agent administration alone. Conclusion: Administration of mCD38-mATT induced broad immunomodulation and antitumor responses, alone and in combination with SOC agents in immunocompetent mouse models, highlighting the impact of this agent on CD38+ cells, both tumor and immune. These results support further investigation of combination therapies in the ongoing clinical evaluation of TAK-573 in a Phase 1 trial in patients with relapsed refractory MM. Citation Format: Tomoya Hara, Christina Wong, Jie Yu, Sabrina Collins, Haiqing Wang, Hiroshi Sugimoto, Hong Zhang, Pia Bjorck, Michael D. Curley. A murine reactive version of TAK-573 (anti-CD38 attenuated IFNα fusion protein) shows immunomodulatory and antitumor activity, alone and in combination with standard-of-care agents, in IFNa-insensitive, immunocompetent murine multiple myeloma tumor models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5546.

By using the sacrificial layer (SL) etching, GaAs substrates are separated from III–V epi substrate//Si substrate junctions that are made by surface activated bonding (SAB) technologies. The post-bonding low-temperature (300- ∘ C) annealing plays an essential role in achieving a promising ( ∼ 90%) bonding yield. The effects of the post-bonding annealing are investigated by hard X-ray photoemission spectroscopy and current–voltage measurements of GaAs//Si bonding interfaces. It is found that the concentration of oxygen atoms at interfaces is reduced and the resistance decreases to 1.6–2.1 m Ω cm 2 by the low-temperature annealing. Aluminum fluoride complexes are not observed by X-ray photoelectron spectroscopy on the exposed surfaces of separated GaAs substrates. The roughness average of the surfaces is ≈ 0.25–0.30 nm. The characteristics of double junction cells fabricated on the GaAs//Si junctions prepared by the SL etching are almost the same as those of cells fabricated by dissolving GaAs substrates after bonding. These results indicate that multijunction cells could be fabricated in a process sequence compatible with reuse of GaAs substrates by combining the SL etching and SAB.

Bone morphogenetic proteins may hold broad potential for use in the reconstruction of bone defects resulting from tumor resection or trauma and in assisting bone healing thanks to methods enabling the synthesis of recombinant human bone morphogenetic protein-2 (rhBMP-2).rhBMP-2 was implanted with atelopeptide type I collagen as a carrier into the calf muscles of 3-, 8-, and 48-wk-old Wistar/ST male rats. After 21 d, the formation of ectopic neoplastic bone was examined in soft x-ray imaging, and the bone mineral content, bone area, and bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry. In addition, hematoxylin-eosin and von Kossa staining and proliferation cell nuclear antigen immunostaining were performed.BMD values determined by dual-energy x-ray absorptiometry were 29.40 (standard deviation ±5.47), 24.15 (±2.33), and 19.01 (±2.02) mg/cm(2) in the 3-, 8-, and 48-wk-old rats, respectively, demonstrating that BMD significantly decreased with aging (P 0.05). The von Kossa stain-positive area decreased significantly with aging (P 0.01). The number of proliferation cell nuclear antigen-positive cells also decreased significantly with aging (P 0.01).The capacity of rhBMP-2 to induce ectopic bone formation decreases with aging. These findings will be of considerable benefit in the development of clinical treatments for the regeneration of cranio-maxillofacial bone in elderly patients.

The renin-angiotensin system (RAS), which plays an important role in the progression of heart failure, is efficiently blocked by the inhibition of renin, the rate-limiting enzyme in the RAS cascade. In the present study, we investigated the cardioprotective effects of TAK-272 (SCO-272, imarikiren), a novel, orally effective direct renin inhibitor (DRI), and compared its efficacy with that of aliskiren, a DRI that is already available in the market. TAK-272 was administered to calsequestrin transgenic (CSQ-tg) heart failure mouse model that show severe symptoms and high mortality. The CSQ-tg mice treated with 300 mg/kg, the highest dose tested, of TAK-272 showed significantly reduced plasma renin activity (PRA), cardiac hypertrophy, and lung congestion. Further, TAK-272 reduced cardiomyocyte injury accompanied by an attenuation of the increase in NADPH oxidase 4 and nitric oxide synthase 3 expressions. TAK-272 also prolonged the survival of CSQ-tg mice in a dose-dependent manner (30 mg/kg: P = 0.42, 100 mg/kg: P = 0.12, 300 mg/kg: P < 0.01). Additionally, when compared at the same dose level (300 mg/kg), TAK-272 showed strong and sustained PRA inhibition and reduced the heart weight and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, a heart failure biomarker, while aliskiren showed a significant weaker PRA inhibition and failed to demonstrate any cardioprotective effects. Our results showed that TAK-272 is an orally active and persistent renin inhibitor, which reduced the mortality of CSQ-tg mice and conferred protection against cardiac hypertrophy and injury. Thus, TAK-272 treatment could provide a new therapeutic approach for heart failure.

Using surface-activated bonding technologies we fabricate InGaP/GaAs/ITO/Si hybrid triple-junction (3J) cells with p+-GaAs/ITO and those with n+-GaAs/ITO bonding interfaces. ITO films deposited on the emitter of Si bottom cells work as intermediate layers between III-V and Si sub cells. The samples are not heated during the bonding process. The photovoltaic characteristics of the fabricated 3J cells are compared with characteristics of conventional 3J cells without intermediate layers. The InGaP/GaAs/ITO/Si 3J cells with $n$ + -GaAs/ITO bonding interfaces reveal the highest conversion efficiency and the lowest differential resistance among the investigated 3J cells, which implies the potential of ITO-based intermediate layers for achieving more excellent performances of hybrid multi-junction cells.

A 70-year-old woman with dyspnea on exertion was admitted to our hospital. She had a history of apical hypertrophic cardiomyopathy (HCM) and repeated hospitalization for heart failure. Results of physical examination were normal except for leg edema. Echocardiography showed apical HCM with preserved LV systolic function (LVEF=70%). Although dyspnea on exertion and leg edema improved rapidly with the use of diuretics, her symptoms soon worsened when daily activity was started again. In order to examine the effect of preload on hemodynamics, we performed a lower limb positive pressure test by compressing both legs using a household air leg massager. Echocardiography showed increases in mitral E velocity, E/A ratio and pulmonary venous D flow as well as decrease in stroke volume during the lower limb positive pressure test. Simultaneously-recorded pressure study also showed elevated LVEDP and increased v wave of pulmonary capillary wedge pressure. These results suggested that even a small increase in preload led to elevation of LVEDP and symptomatic worsening due to severe diastolic heart failure in the present case. The lower limb positive pressure test may be useful for assessing the effect of preload on hemodynamics in patients with diastolic heart failure.

The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.

Platelet rich plasma (PRP) contains a high concentration of thrombocytes and the a granules of platelets contain platelet released growth factors. The usefulness of PRP for regeneration of bone and soft tissues has been reported previously. We firstly reported the efficacy of PRP prepared using the Magellan Autologous Platelet Separator System for intractable skin ulcers such as diabetic and venous ulcers. The system consists of a microprocessor controlled centrifuge, syringe pumps, and necessary single use processing components. No complications occurred in any patients and the wounds achieved complete epithelialization. Our results have shown the efficiency of platelet rich plasma for the treatment of intractable skin ulcers.

Background The hospitalization rate for acute coronary syndrome (ACS) for people aged ≤50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged ≤50 years. Methods and results We retrospectively reviewed 102 (male/ female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged ≤50 compared to patients aged 51–74 and ≥75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and triglyceride levels, independently correlated with early ACS onset. Conversely, low-density and high-density lipoproteins, glycated hemoglobin, and hypertension did not correlate with early ACS onset. Subgroup analyses of male patients revealed that decreased ratios of EPA/AA and DHA/AA independently correlated with early ACS onset. Conclusion Decreased EPA/AA and DHA/AA ratios may be risk factors for early onset of ACS, suggesting that reduced EPA/AA and DHA/AA may represent targets for preventing ACS in Japanese young people. Electronic supplementary material The online version of this article (doi:10.1186/s12937-015-0102-4) contains supplementary material, which is available to authorized users.

Introduction Chronic skin ulcers, such as diabetic ulcers, venous leg ulcers and pressure ulcers, are intractable and increasing in prevalence, representing a costly problem in healthcare. We developed a combination therapy with a gelatin sheet, capable of providing sustained release of platelet-rich plasma (PRP). The objective of this study is to investigate the safety and efficacy of autologous PRP covered with a hydrocolloid dressing and PRP covered with a gelatin sheet in the treatment of chronic skin ulcers. Methods and analysis Thirty patients with chronic skin ulcers who have not healed with conventional therapy for at least 1 month are being recruited. The patients will receive PRP after debridement, and the wounds will be covered with a hydrocolloid dressing or gelatin sheet. The efficacy will be evaluated according to the time from the beginning of PRP application to secondary healing or the day on which wound closure is achieved with a relatively simple surgical procedure, such as skin grafting or suturing. All patients will be followed up until 6 weeks after application to observe adverse events related to the application of PRP and the dressings. This study was designed to address and compare the safety and efficacy of PRP covered with a hydrocolloid dressing versus a gelatin sheet. If successful, this combination therapy may be an alternative to bioengineered skin substitutes containing living cells and lead to substantial progress in the management of chronic skin ulcers. Ethics and dissemination The study protocol was approved by the Institutional Review Board of Kansai Medical University (KMU Number 0649-1, 4 August 2014: V.1.0). The findings of this trial will be disseminated through peer-reviewed journals, and national and international scientific meetings as well as to the patients. Trial registration number UMIN000015689.

Shusuke Yagi,1 Akira Takashima,1 Minoru Mitsugi,2 Toshihiro Wada,2 Junko Hotchi,1 Ken-ichi Aihara,3 Tomoya Hara,1 Masayoshi Ishida,1 Daiju Fukuda,4 Takayuki Ise,1 Koji Yamaguchi,1 Takeshi Tobiume,1 Takashi Iwase,1 Hirotsugu Yamada,1 Takeshi Soeki,1 Tetsuzo Wakatsuki,1 Michio Shimabukuro,4 Masashi Akaike,5 Masataka Sata11Department of Cardiovascular Medicine, Graduate School of Health Biosciences, University of Tokushima, Tokushima, 2Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, 3Department of Medicine and Bioregulatory Sciences, 4Department of Cardio-Diabetes Medicine, 5Department of Medical Education, Graduate School of Health Biosciences, University of Tokushima, Tokushima, JapanBackground: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP) control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) combination tablet containing a regular dose of irbesartan (100 mg) and a high dose of amlodipine (10 mg) with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol levels, independent of the BP-lowering effect. Treatment with the combination tablet did not affect serum triglycerides, plasma glucose, glycated hemoglobin, serum potassium or creatinine levels, or the urinary albumin excretion rate.Conclusion: The combination tablet containing amlodipine 10 mg and irbesartan 100 mg had a greater BP-lowering effect than an ARB and a low-dose or regular-dose CCB. In addition, the combination tablet had more favorable effects on serum uric acid, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels in patients with hypertension.Keywords: blood pressure, combination tablet, uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol

Background Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. Methods We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. Results Pearson correlation analysis showed that EPA (R = 0.25, P

A 63-year-old man presented to a clinic because of sudden onset of severe longitudinal back pain and was transferred to the intensive care unit (ICU) of our hospital. He had been hypertensive for 30 years; however, he had never been referred to a clinic for treatment. Physical examination findings were unremarkable, except for high blood pressure (BP) (220/110mmHg) and heart rate (80 beats/min). Electrocardiography and chest radiography findings were normal. Blood examination showed leukocytosis (9700/μL) without an increased plasma fibrin degradation products level (2 μg/mL). The patient was diagnosed with acute type B aortic dissection (AD) with a thrombosed false lumen by enhanced computed tomography (Fig. 1). We administered an 8-mg/day transdermal patch of bisoprolol after titration of intravenous nicardipine (Fig. 2). Six hours later, systolic BP decreased to 112 mm Hg and heart rate decreased to 54 beats/min. Additionally, the ventricular force (dP/dt) of aortic pressure decreased over time. After intravenous nicardipine was withdrawn, 40 mg of olmesartan, 80 mg of nifedipine, and 2 mg of doxazosin in addition to the 8-mg transdermal patch of bisoprolol were administered, and systolic BP was well controlled to b120 mm Hg. He was discharged 23 days after the onset of AD without any complication. BP reduction is critical to preventing lethal complications, including enlargement of aortic aneurysm and aortic rupture in the acute phase [1]. dP/dt and stress on the aorta are risk factors, and therefore, β-blockers should be the first drug of choice because they have negative chronotropic and negative inotropic effects [2]. Maintaining systolic BP between 100 and 120 mm Hg with a heart rate b60 beats/min is an attainable temporal goal [3], which was achieved with intravenous nicardipine and transdermal bisoprolol in the present case. However, in many cases, multiple BP-lowering agents are required to achieve this goal. Intravenous agents should be chosen for controlling BP because of the need for titration of the dose, especially in patients with a

A 44-year-old woman consulted us with local swelling at the insertion site of a central venous port system. She had been undergoing chemotherapy for advanced gastric cancer via a totally implantable central venous catheter system for 9 months. Physical examination was normal except for the local swelling. Chest x-ray demonstrated disappearance of the catheter from the connection site of its subcutaneous port. An unexplained abnormal linear structure was found …

A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

A 37-year-old man presenting with fever and chest pain was admitted to our hospital. Electrocardiogram showed sinus tachycardia and complete left bundle branch block. Transthoracic echocardiogram showed infective endocarditis in the bicuspid aortic valve, complicated by multiple hyperechoic vegetations and severe aortic regurgitation. Blood cultures were negative and intravenous empiric antibiotic therapy was begun. However, fever lasted for 7 days and follow-up echocardiography revealed a newly emerged perivalvular abscess. The patient eventually underwent an urgent aortic root replacement that confirmed the echocardiographic findings. Our case report emphasizes that all patients with suspected aortic valve endocarditis should undergo early and follow-up echocardiographic studies.

A basket-shaped microsnare has various uses such as the pull through technique during coronary intervention to chronic total occlusion (CTO). A 79-year-old man underwent angioplasty for the femoral artery occlusion. We performed a controlled antegrade and retrograde tracking (CART) with dilatation of a balloon on the antegrade guidewire. The retrograde guidewire partly ran in the true lumen but could not pass through the CTO lesion because of inadequate CART. Eventually, we successfully gripped the top of the retrograde guidewire in the CTO lesion using the basket-shaped microsnare (Soutenir(®)). The microsnare may be useful for bidirectional approach in peripheral CTO lesions.

Reconstructing a 3D face model only with a single camera without attaching landmarks and pattern projecting on a face is still a challenging task in computer vision and computer graphics. FaceGen [2011] is able to reconstruct 3D shape and texture from 2D single image based on 3D morphable model. Since the users have to determine of the facial feature points manually, the method does not work automatically. Moreover, it requires a couple of minutes to generate a 3D face model. Thus, the computational cost is not enough cheap for practical usage.

3D face models have been widely applied in various fields (e.g. biometrics, movies, video games). Especially, it is one of the most popular and challenging tasks in computer vision and computer graphics to reconstruct a 3D face model only with single camera without attaching landmarks and projecting laser dots or structured light patterns on a face. For example, Maejima proposed a method, based on generic-model approach, which can quickly reconstruct a 3D face model from 2D single photograph using a deformable face model [Maejima et al. 2008]. However, since it supposes input as a frontal face image, this method cannot express the individual facial parts' geometry such as height of nose and cheek contour accurately.

A 49-year-old man presented to our hospital with episodes of left-sided abdominal pain and fever. He had a medical history of past treated polycythaemia vera and old myocardial infarction. He had been treated with oral aspirin, and no other antithrombic agent was administrated. Physical examination was normal except for tenderness at the left …

Background To overcome the absorption of traditional fat grafting, techniques for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently being adapted for practical application. The Celution®800/CRS (Cytori Therapeutics, San Diego, CA) has enabled rapid grafting of the patient’s own freshly harvested ADRCs without requiring a culturing step. However, the optimal cell concentration and the effects of ADRCs on the characteristics of grafted fat after free fat grafting remain unclear. Methods ADRCs were isolated and purified from human fat tissue using the Celution®800/CRS. Animals that received fat grafting without the addition of ADRCs were designated the control group (group A). The number of ADRCs per grafted fat volume (mL) was adjusted to 3 × 105, 1.5 × 106, and 3 × 106 cells/mL (groups B, C, and D, respectively), mixed with free fat, and transplanted as ADRC-enriched fat grafting. These mixtures were transplanted subcutaneously into BALB/C Jcl-nu/nu mice. The volume of grafted fat was determined 5 months after transplantation, and histological assessments were performed. Results ADRC-enriched fat grafting resulted in decreased fat absorption and the formation of greater numbers of new blood vessels in the grafted fat. The optimal ADRC concentration in this study was found to be 3 × 105 cells/mL (group B), with higher concentrations resulting in increased cyst and fibril formation in the grafted fat. Conclusions This study used the Celution®800/CRS for free fat grafting and demonstrated that the concentration of transplanted ADRCs affected the engraftment and quality of the grafted fat.

Background A high-calorie diet and physical inactivity, an imbalance between caloric intake and energy consumption, are major causes of metabolic syndrome (MetS), which manifests as accumulation of visceral fat and insulin resistance. However, the lifestyle-related factors associated with visceral fat mass in healthy men are not fully understood. Methods We evaluated visceral fat area (VFA), skeletal muscle mass, caloric intake, and energy expenditure in 67 healthy male participants (mean age, 36.9 ± 8.8 years; body mass index 23.4 ± 2.5 kg/m2). Results Multiple regression analysis showed that the total skeletal muscle mass (P