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This study presents an energy‐based attack detection method involving an encrypted bilateral control system using wave variables. In the considered bilateral control system, the leader and follower receive the follower's force information and the leader's velocity information, respectively, through the wave variables. The considered attack model multiplies the wave variables by an attack parameter, which is possible due to the malleability of the encryption scheme. The bilateral control system will be destabilized if the attacker chooses a relatively large parameter value. This motivates in developing a passivity observer for each leader and follower side to compute the total energy and constructing an energy‐based detection method that can be incorporated into the encrypted bilateral control system and is summarized in the presented theorem. Furthermore, this study provides a specific design for reasonable threshold parameters concerning the control system energy. The theorem and the experimental validation confirm that the developed encrypted wave‐variable‐based bilateral control system with the proposed attack detector is secure and effective as a countermeasure against malleability‐based attacks. [ABSTRACT FROM AUTHOR]

We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

Aim: To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis. Methods: Ninety‐two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty‐six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively. Results: The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size. Conclusions: Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication. [ABSTRACT FROM AUTHOR]

Whether malnutrition during the early phase of recovery from acute myocardial infarction (AMI) could be a predictor of mortality or morbidity has not been ascertained. We examined 289 AMI patients. All-cause mortality and composite endpoints (all-cause mortality, nonfatal stroke, nonfatal acute coronary syndrome, and hospitalization for acute decompensated heart failure) during the follow-up duration (median 39 months) were evaluated. There were 108 (37.8%) malnourished patients with GNRIs of less than 98 on arrival; however, malnourished patients significantly decreased to 91 (31.4%) during the convalescence period (p < 0.01). The incidence rates of mortality and primary composite endpoints were significantly higher in the malnourished group than in the well-nourished group both on arrival and during the convalescence period (All p < 0.05). Nutrition guidance significantly improved GNRI in a group of patients who were undernourished (94.7 vs. 91.0, p < 0.01). Malnourished patients on admission who received nutritional guidance showed similar all-cause mortality with well-nourished patients, whereas malnourished patients without receiving nutritional guidance demonstrated significantly worse compared to the others (p = 0.03). The assessment of GNRI during the convalescence period is a useful risk predictor for patients with AMI. Nutritional guidance may improve the prognoses of patients with poor nutritional status. [ABSTRACT FROM AUTHOR]

In this study, we investigated trainees' adaptation by conducting static balance training in a tandem standing posture. The horizontal tensile force loads in the front, back, left, and right directions were applied using pneumatic artificial muscles. We analyzed the adaptation that occurred during training by changing the direction of the horizontal tensile load on the lumbar region according to the tendency of the trainee. We conducted the experiments using the following protocol. Ten trainees participated in the experiment. In Phase 1, we applied loads in four directions the same number of times in random order to investigate the weak direction in the balance of each trainee. In Phase 2, we measured five trainees in each group: Group 1 was trained in the same way as Phase 1, and Group 2 was intensively trained in two directions in which the balance found in Phase 1 was difficult to maintain. In Phase 3, we performed the same experiment as in Phase 1. We analyzed the adaptation of the trainees using the margin of stability (MoS), a balance evaluation index. We compared the experimental results of Phases 1 and 3. In Group 1, the tendency for improvement in balance was unclear. On the other hand, the balance index in Group 2 improved in four out of five trainees in both the front-back and left-right directions. These results suggest that the training method concentrating on the weak direction could provide a clear directionality to the training effect. [ABSTRACT FROM AUTHOR]

Aims: Evidence on the association between ambient temperature and the onset of acute heart failure (AHF) is scarce and mixed. We sought to investigate the incidence of AHF admissions based on ambient temperature change, with particular interest in detecting the difference between AHF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). Methods and results: Individualized AHF admission data from January 2015 to December 2016 were obtained from a multicentre registry (Tokyo CCU Network Database). The primary event was the daily number of admissions. A linear regression model, using the lowest ambient temperature as the explanatory variable, was selected for the best‐estimate model. We also applied the cubic spline model using five knots according to the percentiles of the distribution of the lowest ambient temperature. We divided the entire population into HFpEF + HFmrEF and HFrEF for comparison. In addition, the in‐hospital treatment and mortality rates were obtained according to the interquartile ranges (IQRs) of the lowest ambient temperature (IQR1 <5.5°C; IQR25.5–13.3°C; IQR3 13.3–19.7°C; and IQR4 >19.7°C). The number of admissions for HFpEF, HFmrEF and HFrEF were 2736 (36%), 1539 (20%), and 3354 (44%), respectively. The lowest ambient temperature on the admission day was inversely correlated with the admission frequency for both HFpEF + HFmrEF and HFrEF patients, with a stronger correlation in patients with HFpEF + HFmrEF (R2 = 0.25 vs. 0.05, P < 0.001). In the sensitivity analysis, the decrease in the ambient temperature was associated with the greatest incremental increases in HFpEF, followed by HFmrEF and HFrEF patients (3.5% vs. 2.8% vs. 1.5% per −1°C, P < 0.001), with marked increase in admissions of hypertensive patients (systolic blood pressure >140 mmHg vs. 140–100 mmHg vs. <100 mmHg, 3.0% vs. 2.0% vs. 0.8% per −1°C, P for interaction <0.001). A mediator analysis indicated the presence of the mediator effect of systolic blood pressure. The in‐hospital mortality rate (7.5%) did not significantly change according to ambient temperature (P = 0.62). Conclusions: Lower ambient temperature was associated with higher frequency of AHF admissions, and the effect was more pronounced in HFpEF and HFmrEF patients than in those with HFrEF. [ABSTRACT FROM AUTHOR]

We experienced a case of primary percutaneous coronary intervention for ST‐elevation myocardial infarction (STEMI) with coronavirus disease 2019 (COVID‐19) using appropriate infection prevention protocol. However, recanalization was difficult due to severe coagulopathy. Further researches are needed to clarify optimal treatment for STEMI in patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Background and aims Methods Results Conclusions Successful left atrial posterior wall isolation (LAPWI) using only the cryoballoon (CB) is technically challenging for the treatment of atrial fibrillation (AF). This study aimed to evaluate the efficacy of the cross‐over technique, wherein an overlapped ablation is performed by placing the CB from both directions in contact with the LAPW.This was a single‐center, retrospective, observational study of 194 consecutive patients with persistent atrial fibrillation (PerAF) who underwent a first‐time procedure of pulmonary vein isolation (PVI) + PWI (108 patients) or PVI‐only (86 patients) using the CB. The cross‐over technique was applied in all LAPWI.For ablation of the LA roof and bottom, respectively, a mean of 8.6 ± 1.0 (right to left [R→L] 4.3 ± 1.1 and left to right [L→R] 4.3 ± 1.1) and 9.1 ± 1.2 (R→L 4.6 ± 1.6 and L→R 4.5 ± 1.2) CB applications were delivered. LAPW was successfully isolated solely using the CB in 99.1% of patients. Although the PVI + PWI group had significantly longer procedure time, no severe adverse events were observed in either group. During a median follow‐up of 19 months, freedom from recurrence of all atrial tachyarrhythmias was achieved in 93.5% of the PVI + PWI group and 72.9% of the PVI‐only group (p = .011).LAPWI performed solely with the CB using the cross‐over technique is feasibly, safe, and was independently associated with a significantly higher freedom from recurrence of atrial tachyarrhythmias compared with PVI alone in patients with PerAF. [ABSTRACT FROM AUTHOR]

Abstract Background Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. Methods Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. Results Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). Conclusions These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.

Abstract Background The association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear. We assessed lipid profiles, plasma CET activity, and in-stent intimal hyperplasia after fenofibrate treatment in patients who underwent elective coronary stenting. Methods Forty-three consecutive patients who underwent elective coronary stenting were randomized to the fenofibrate group (300 mg/day for 25 weeks, n = 22) or the control group (n = 21). At baseline and follow up, CET activity and lipoprotein profiles were measured, and quantitative coronary angiography was performed. Results In the fenofibrate group, the levels of large very low-density lipoprotein cholesterol, and small low-density lipoprotein (LDL) cholesterol decreased and those of small high-density lipoprotein (HDL) cholesterol increased. Besides, CET activity decreased independent of the effect of fenofibrate on total and LDL cholesterol. The reduction of CET activity significantly correlated with the increase in LDL particle size (r = 0.47, P = 0.03) and the decrease of triglycerides in large HDL subclasses (r = 0.48, P = 0.03). Although there were no significant differences in restenosis parameters between the two groups, low CET activity significantly correlated with the inhibition of neointimal hyperplasia (r = 0.56, P = 0.01). Conclusions Fenofibrate inhibited CET activity and thereby improved atherogenic lipoprotein profiles, and reduced intimal hyperplasia after coronary stenting.

Background: Peak oxygen uptake (peak VO2) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO2 and HRR on long‐term prognosis after off‐pump coronary artery bypass grafting (OP‐CABG) remains unclear. Hypothesis: To determine the prognostic impact of peak VO2 and HRR in patients after OP‐CABG. Results: We enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP‐CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow‐up period of 103 months. The non‐survivor had significantly lower levels of peak VO2 (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p <.01) and HRR (24.2 ± 1.8 vs. 32.7 ± 0.8 beats/min, p <.01) than the survivor. In both groups, peak VO2 significantly correlated with HRR (p <.01). Moreover, patients were divided into four groups according to the peak VO2 and HRR levels for predicting total mortality. The low‐peak VO2/low‐HRR group had a significantly higher mortality risk than the other groups (hazards ratio, 5.61; 95% confidence interval, 2.59–12.16; p <.01). After adjusted the confounding factors, peak VO2 and HRR were independently associated with total mortality (both p <.05). Conclusions: HRR is a simple parameter of CPET and an important prognostic marker for the risk stratification of total mortality even in patients with low‐peak VO2 after OP‐CABG. [ABSTRACT FROM AUTHOR]

Abstract Background Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice. Results Elevated levels of VLCSFA were confirmed in macrophages from ALDP-deficient mice. The levels of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), intracellular reactive oxygen species (ROS), and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interluekin-6 (IL-6), and interleukin-12p70 (IL-12p70), were significantly higher in macrophages from ALDP-deficient mice than in those from wild-type mice. The inducible NO synthase (iNOS) mRNA expression also showed an increase in macrophages from ALDP-deficient mice. Conclusion These results suggested that VLCSFA accumulation in macrophages may contribute to the pathogenesis of inflammatory diseases through the enhancement of inflammatory and oxidative responses.

Aim: We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. Methods: We used 6‐, 12‐ and 24‐month (6 M, 12 M and 24 M)‐old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real‐time polymerase chain reaction, immunoblotting and histological analyses. Results: The muscle weight and myocyte cross‐sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4‐hydroxy‐2‐nonenal and 3‐nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator‐activated receptor gamma coactivator 1 (PGC)‐α, peroxisome proliferator‐activated receptor gamma coactivator‐1β, sirtuin‐1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin–proteasome pathway genes muscle ring finger‐1 and atrogin‐1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated‐Akt and ‐p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). Conclusions: These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78–84. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Heart failure with preserved ejection fraction (HFpEF) is now recognized as a geriatric syndrome with multifactorial pathophysiology and clinical heterogeneity rather than a solely left ventricular diastolic dysfunction. Because the pathophysiology of HFpEF is suggested to differ by age, this study compared the clinical characteristics and prognostic factors between HFpEF patients aged 65 to 84 years and those aged 85 years or older. DESIGN: Retrospective cohort study. SETTING: The Tokyo CCU Network including 73 hospitals in Tokyo, Japan. PARTICIPANTS: Individuals aged 65 years or older with HFpEF (N = 4305). MEASUREMENTS: Very old patients were defined as those aged 85 years or older. Potential risk factors for in‐hospital mortality were selected by univariate analyses, and those with a P value <.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. RESULTS: Prevalence of hypertension was significantly higher in very old patients, whereas prevalence of coronary artery disease, diabetes mellitus, hyperlipidemia, and smoking was significantly higher in patients aged 65 to 84 years. In very old patients, low systolic blood pressure (hazard ratio [HR] =.988), high serum creatinine level (HR = 1.34), and coexisting chronic obstructive pulmonary disease (COPD; HR = 2.01) were identified as independent risk factors for in‐hospital mortality. In contrast, low systolic blood pressure (HR =.987) and low body mass index (HR =.935) were identified as independent risk factors in patients aged 65 to 84 years. CONCLUSION: Significant differences were observed in the clinical characteristics and prognostic factors for in‐hospital mortality between HFpEF patients aged 65 to 84 and those 85 years and older. Of note, coexisting COPD was associated with significantly lower survival rate only in patients aged 85 years and older, suggesting the prognostic impact of concomitant pulmonary disease in HFpEF may increase with age. These results have implications for future research and management of older HFpEF patients. J Am Geriatr Soc 00:1–6, 2019. J Am Geriatr Soc 67:2123–2128, 2019 [ABSTRACT FROM AUTHOR]

Power assistive devices have been developed in recent years. To detect the wearer's motion, conventional devices require users to wear sensors. However, wearing many sensors increases the wearing time, and usability of the device will become worse. We developed a soft gait assistive suit actuated by pneumatic artificial rubber muscles (PARMs) and proposed its control method. The proposed suit is easy to wear because the attachment unit does not have any electrical sensors that need to be attached to the trainee's body. A target application is forward walking exercise on a treadmill. The control unit detects the pre-swing phase in the gait cycle using the pressure information in the calf back PARMs. After the detection, the suit assists the trainee's leg motion. The assist force is generated by the controlled PARM pressure, and the pressure input time is changed appropriately considering the gait cycle time. We conducted walking experiments; (1) verifies the proposed control method works correctly, and (2) verifies whether the gait assistive suit is effective for decreasing muscular activity. Finally, we confirmed that the accurate phase detection can be achieved by using the proposed control method, and the suit can reduce muscular activity of the trainee's leg. [ABSTRACT FROM AUTHOR]

A cylindrical soft actuator is suitable for applications in which pneumatic or hydraulic cylinders are conventionally used. In this report, we discuss the force output model of a spring-reinforced-type cylindrical soft actuator. This type of actuator outputs a larger force than the air pressure multiplied by the pressure-receiving area. We construct a quasi-static model to explore the reason for this phenomenon, based on the strength of materials. A thick-walled cylinder model with three boundary conditions was defined and analyzed. The model indicates that the rubber cylinder itself transmits pneumatic pressure and contributes to the output force. We also modeled the relationship between the pressure and the elongation of the soft actuator. Experiments were conducted to evaluate the proposed models. [ABSTRACT FROM AUTHOR]

Objectives: Follistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI). Methods and results: A consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P < 0.01). After excluding patients with creatinine clearance < 60 mL/min and hsCRP ≥ 0.2 mg/dL, the remaining 214 were followed for a median of 5.1 years. Twenty (9.3%) patients experienced MACCE. Receiver operating characteristics curve analysis estimated an FSTL1 cutoff of 41.1 ng/mL to predict MACCE occurrence. Kaplan–Meier analysis found a higher MACCE rate in patients with high (≥ 41.1 ng/mL) than with low (< 41.1 ng/mL) FSTL1 (P < 0.01). Multivariate Cox hazard analysis found that high FSTL1 was an independent predictor of MACCE (hazard ratio 4.54, 95% confidence interval: 1.45–20.07, P < 0.01). Conclusion: High plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP. [ABSTRACT FROM AUTHOR]

Aim: The Kihon Checklist is a useful screening tool for assessing frailty in older individuals. However, the clinical significance of the Kihon Checklist in cardiac rehabilitation patients remains unclear. The present study aimed to evaluate the relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation. Methods: We enrolled 845 consecutive patients (584 men, mean age 71 years) who participated in cardiac rehabilitation at Juntendo University Hospital, Tokyo, Japan, between November 2015 and October 2017. The patients were divided into non‐frailty (n = 287), pre‐frailty (n = 270) and frailty (n = 288) groups according to their Kihon Checklist scores. Cardiopulmonary exercise testing was carried out in 302 patients. Results: The frailty group was older and had a higher prevalence of history of heart failure than the non‐frailty group, although left ventricular ejection fraction did not differ significantly between groups. Nutritional index, trunk and limb muscle mass, lean body weight, and grip strength were significantly lower in the frailty and pre‐frailty groups than those in the non‐frailty group. In the cardiopulmonary exercise test, a stepwise significant decrease in peak oxygen uptake was observed across the three groups (non‐frailty 17.2 ± 3.6, pre‐frailty 16.0 ± 3.4, frailty 14.4 ± 3.5 mL/kg/min, P < 0.01). Multivariate regression analyses showed that the Kihon Checklist score was significantly and independently associated with peak oxygen uptake (r = −0.34, P < 0.0001). Conclusions: The Kihon Checklist, which was associated with frailty and exercise tolerance, could be used as a clinical assessment method for patients who participated in cardiac rehabilitation. Geriatr Gerontol Int 2019; 19: 287–292. [ABSTRACT FROM AUTHOR]

In pneumatic positioning and force-control systems, spool-type servo valves are widely used for obtaining quick responses and precise control. However, air leakage from these valves results in increased energy consumption. To address this problem, we developed a three-port poppet-type servo valve to reduce air leakage. The developed valve consists of a camshaft, two orifices, two metal balls, and a housing with two flow channels. The metal ball is pushed by fluid, and spring force closes the orifice. The port opens when the cam rotates and pushes the ball. The cam shape and orifice size were designed to provide the desired flow rate. The specifications of the DC motor for rotating the camshaft were determined considering the fluid force on the ball. Static and dynamic characteristics of the valve were measured. We experimentally confirmed that air leakage was 0.1 L/min or less. The ratio of air leakage to maximum flow rate was only 0.37%. Dynamic characteristic measurements showed that the valve had a bandwidth of 30 Hz. The effectiveness of the valve was demonstrated through experiments involving pressure and position control. [ABSTRACT FROM AUTHOR]

Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance. Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used. At baseline, there were no differences in physical characteristics between the WT and KO mice. Saline (vehicle, V) or AII was infused via osmotic minipumps for 4 weeks, after which, the WT + AII mice showed significant increases in Nox activity and NOX4 protein compared with the WT + V mice, as well as decreases in body weight, gastrocnemius muscle weight, and myocyte cross-sectional area. These changes were significantly attenuated in the KO + AII mice (27 ± 1 vs. 31 ± 1 g, 385 ± 3 vs. 438 ± 13mg, and 1,330 ± 30 vs. 2281 ± 150 μm2, respectively, all P < 0.05). The expression levels of phospho-Akt decreased, whereas those of muscle RING Finger-1 (MuRF-1) and MAFbx/atrogin-1 significantly increased in the WT + AII mice compared with the WT + V mice. Furthermore, nuclear factor erythroid-derived 2-like 2 (Nrf2) and the expression levels of Nrf2-regulated genes significantly decreased in the WT + AII mice compared with the WT + V mice. These changes were significantly attenuated in the KO + AII mice (P < 0.05). Conclusion: Nox4 deficiency attenuated AII-induced muscle wasting, partially through the regulation of Nrf2. The Nox4-Nrf2 axis may play an important role in the development of AII-induced muscle wasting. [ABSTRACT FROM AUTHOR]

Key Clinical Message Polycythemia vera ( PV) is a chronic myeloproliferative disease that is often complicated with thromboembolism. However, aortic stenosis ( AS) could be a manifestation of the cardiovascular complications of PV possibly through shear stress and atherosclerosis. We report a rare case of rapidly progressed AS in a patient with PV. [ABSTRACT FROM AUTHOR]