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In the maritime industry and university, the education and training of a ship handling is carried out by a ship bridge simulator. The education using the simulator is popular worldwide because we are able to train emergency situations, and a lot of trainees can go through the same scenario. The evaluation of simulator training is subjectively. The master and professor evaluate their performance and ship’s track subjectively. That evaluation depends on their experiences. In this paper, we propose a real time evaluation support system using a physiological index. The system evaluates mental workload in the real time, and the system supports instructors to monitor cadet’s mental workload during their simulator training. The instructors can understand not only their performance but also their mental workload to evaluate their training.

We have been developed the salivary NO 3 − measurement device which gives quantitative values of human mental workload from only one-drop saliva. We think this device help people in maritime societies, especially navigators, to reduce their mental workload on duties. In this paper, we introduce 2 systems: the physiological response system using salivary NO 3 − as a helpful physiological index, and the recomposed sensor system which improves the sensor part of a conventional salivary NO 3 − measurement device. In addition, we introduce one example of experimental results in a ship-simulator where we use the improved salivary NO 3 − measurement device. We acknowledge that the evaluation of mental workload by the conventional salivary NO 3 − measurement device is effect through on-board experiments and ship-simulator experiments. As a result, this conventional device is the good physiological index, however, it has a problem. The sensor of the salivary NO 3 − measurement device is the ion-sensitive field-effect transistors, which have the drift characteristic giving a noise to the measured values. So far, we have solved the drift problem by calibrations before every measurement. This time we fundamentally solve this drift problem to re-compose a new sensor on the salivary NO 3 − measurement device. Through ship-simulator experiments, we validate the effectiveness of the new salivary NO 3 − measurement device with the new sensor.

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 Conclusions These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78-84.

Background Clinical hypertension is associated with renal inflammation and elevated circulating levels of proinflammatory cytokines. IL-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines and plays a crucial role in inflammation. Inhibition of IL-1 may contribute to modulation of the Angiotensin II (AngII)-induced hypertension response. This study aimed to elucidate the effects of IL-1Ra and anti-IL-1beta antibody (01BSUR) on AngII-induced hypertension and renal inflammation. Methods and results To determine the contribution of IL-1Ra to AngII-induced renal inflammation, male wild-type (WT) and IL-1Ra-deficient (IL-1Ra−/−) mice were infused with AngII (1000ng/kg/min) using subcutaneous osmotic pumps for 14 days. We checked blood pressure, histological change, and several mRNA expressions 14 days after infusion. Fourteen days after infusion, systolic blood pressure (197±5 vs 169±9 mmHg, p Conclusions Inhibition of interleukin-1 by both endogenous IL-1Ra and exogenous 01BSUR decreased AngII-induced hypertension and renal damage in mice, suggesting suppression of IL-1 may provide an additional strategy to protect against renal damage in hypertensive patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI

From our preceding studies, we disclosed the characteristics of the under-development device, called salivary NO 3 − Ion-Sensitive Field-Effect Transistors (NO 3 −-ISFETs). These transistors have evaluated the navigators’ mental workload in maneuvering a ship through the ship simulator experiments which can arrange the uniform experimental circumstances at the different simulator’s scenario. The NO 3 −-ISFETs give the quantitative evaluation of the mental workload, using NO 3 − in onedrop saliva. The NO 3 −-ISFETs are supposed to be used for the navigators working anywhere in a ship around the clock. Therefore, our goal is to complete the NO 3 −-ISFETs, which have the durability for mucin in saliva when they measure the salivary NO 3 − long time for the purpose of the prevention of navigator’s human factors in their duties. This time, we tried to carry out another ship-simulator experiment with new NO 3 −-ISFETs changed the polymer which is used at the device’s sensor part. We can confirm the instrumental difference between conventional NO 3 −-ISFETs and new ones, while we evaluate the variability of navigators’ mental workload.

Background: Atherosclerosis is a chronic inflammatory disease responsible for most cases of heart disease and stroke in Western countries. The cytotoxic drug cyclophosphamide (CPA) can modulate immune functions, and it has therefore been used to treat patients with autoimmune diseases. Extension of survival of patients with severe atherosclerosis has been reported after CPA treatment, but the underlying mechanism is still poorly understood. Methods and results: We have investigated the effects of CPA in a murine model of atherosclerosis. Continuous oral administration of low-dose CPA (20 mg/kg/day) prevented atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice fed with a high fat diet. After 12 weeks, CPA treatment delayed progression of atherosclerosis in the mice (9.92% vs 3.32%, P

Background Left ventricular (LV) remodeling, through excessive inflammation, leads to heart failure. Exercise (Ex) training is associated with a risk reduction in heart failure through direct and indirect mechanisms by which Ex contributes an anti-inflammatory effect. During Ex, contracting muscle fibers release myokines, including interleukins (ILs), tumor necrosis factor α (TNF-α), follistatin-like protein 1 (FSTL-1), and fibroblast growth factor 21 (FGF-21), into the bloodstream. These myokines may have beneficial effects on other damaged organs, such as an infarcted myocardium, through anti-inflammatory effects. However, the exact mechanisms of the anti-inflammatory effects of voluntary Ex in myocardial infarction (MI) are poorly understood. Therefore, we investigated the effect of voluntary Ex on cardiac remodeling and inflammation, the relationship between cardiac remodeling and skeletal muscle (SKM) response, and circulating myokine levels in a mouse model of MI. Methods Twelve-week-old male C57BL/6J mice were used and divided into the following 4 groups: sham operation (Sham), MI, Sham+Ex, and MI+Ex. MI was induced by ligation of the left anterior descending coronary artery. Ex groups began voluntary wheel running for 4 weeks after the operation. An echocardiography was performed at baseline and 4 weeks after the operation. The mRNA levels in the LV infarcted area and SKM were measured with RT-PCR and western blot analysis. Plasma levels of myokines were also measured with immunoassays. Results Four weeks after MI induction, echocardiographic evaluation showed that the MI mice had a larger LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) than the Sham mice. The MI mice also showed higher mRNA levels of TNF-α, IL-1β, IL-6, and IL-10 in the LV tissue when compared to the Sham mice. These changes were significantly ameliorated in the MI+Ex mice. Interestingly, in the MI+Ex mice, mRNA levels of IL-6, IL-1β, FSTL-1, and FGF-21 in the SKM were significantly higher than in the MI mice, while there were no significant differences in TNF-α and IL-10 levels in all groups. Similarly, protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sirtuin-1, and mitochondrial transcriptional factor A of mitochondrial function markers in SKM were also significantly higher in the MI+Ex mice than in the MI mice. Furthermore, there were significant correlations between plasma levels of IL-1β, but not other myokines, and LVEDD, and LVESD. In addition, there was also a significant correlation between the SKM IL-1β level and LVESD in the Sham+Ex mice (all, P Conclusions Amelioration of cardiac remodeling and inflammation by voluntary Ex is associated with increased myokines, especially IL-1β, in a MI mouse model. These results suggest that increased myokine levels, through voluntary exercise, may play an important role in the prevention of cardiac remodeling after MI.

We have studied on the stress measurement by making use of salivary nitrate, which can be a candidate of stress markers, with ion-selective field-effect transistors (ISFETs). ISFETs are suitable for on-site single-drop analysis of salivary nitrate within 10 seconds. However, when ISFETs are used for salivary nitrate, ISFETs have a problem which is called the initial drift. The initial drift makes it difficult for determination of an accurate nitrate monitoring. Thus, the purpose of this study is to suppress an initial drift and to search for new easy polymer to possess more performance of sensor responses than conventional matrix membrane such as PVC. In this research, we investigated ISFETs using specific matrix membrane for example, KP-13, Pellethane® and P7281-PU. The initial drift was evaluated from the fluctuation of the response values generated by ISFETs which are immersed in saliva or aqueous solution. As a result, P7281-PU showed its suppression effect for the initial drift in the whole saliva and various solutions. Furthermore, the cause of drift may be H+ diffusion, and drift suppression effect of P7281-PU may be affected by urethane bond capturing H+ in ion-selective membrane. This result suggests a continuous nitrate monitoring and development of wearable sensors.

Background: IκBNS, a nuclear IκB protein, regulates a subset of Toll-like receptor (TLR) dependent genes. A cholate-containing high-fat diet (HFD(CA(+))) induces TLR4 mediated early inflammatory response. The present study aims to clarify that the lack of IκBNS promotes atherogenesis in low-density lipoprotein receptor-deficient (LDLr−/−) mice fed HFD(CA(+)) compared with those fed a cholate-free HFD (HFD(CA(−))). Methods and results: Mice that lacked IκBNS (IκBNS−/−) were crossed with LDLr−/− mice and formation of atherosclerotic lesions was analyzed after 6-week consumption of HFD(CA(+)) or HFD(CA(−)). IκBNS−/−/LDLr−/− mice fed HFD(CA(+)) (IκBNS−/−/LDLr−/−(CA(+))) showed a 3.5-fold increase of atherosclerotic lesion size in the aorta compared with LDLr−/−(CA(+)) mice (p

Acute coronary syndrome (ACS) is an important cause of mortality and morbidity in the general population. Recent advances in percutaneous coronary intervention (PCI) and optimal medical treatment have helped to improve the prognosis of patients with ACS. The previous reports indicated that women with ACS have a higher risk of adverse outcomes. However, sex differences in clinical outcomes with contemporary coronary revascularization and medical therapy for ACS have not been elucidated. We analyzed data from 676 consecutive patients with ACS (female, n = 166; male, n = 510) who were treated by emergency PCI between 2011 and 2014 at Juntendo Shizuoka Hospital. The patients were grouped according to sex. We defined major adverse cardiovascular events as a composite of all-cause death and ACS recurrence at 1 year and compared rates of major adverse cardiac events (MACE) between the groups. Women were older (75.4 ± 11.0 vs. 66.2 ± 12.2 years) and had a higher rate of multi-vessel disease, chronic kidney disease, and Killip IV at presentation. The cumulative rate of MACE at 1 year was significantly higher among women than men (17.5 vs. 10.2 %, p = 0.02, log-rank test). However, the association between women and a higher risk of MACE was attenuated after adjusting for age (HR 1.25, 95 % CI 0.77-2.00, p = 0.36) and other variables (HR 0.93, 95 % CI 0.36-2.44, p = 0.88). Adjustment for age and other risk factors attenuated sex differences in mid-term clinical outcomes among patients with ACS after emergency PCI.

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

We challenge an evaluation of a ship bridge teammate’s mental workload. If we are able to evaluate using a quantitative index for a veteran navigator, it means we get more essential skill for practical education, for example, the educators show students the detail suggestion of skill of ship maneuvering for simulator-based and real ship handling. We think that the both of performance and mental workload are important to evaluate the skill of ship maneuvering; however, the mental workload doesn’t use yet. Regarding the index of mental workload, the heart rate variability (HRV) is popular for a lot of research fields. We usual use HRV, nasal temperature, and try saliva. The saliva is possible to evaluate the mental workload on the spot for ship maneuvering. We hope simple measurement and clear result for the index, and it is practical method in a classroom. The spot measurement is one of research target.In this study, we aim salivary NO3− concentration for simulator-based experiment. We show the res...

Background Angiotensin II (Ang II) activates components of the inflammatory cascade, which promotes hypertension and development of abdominal aortic aneurysm (AAA). This study aimed to elucidate the effects of an IL-1 receptor antagonist (IL-1Ra) and an anti-IL-1β antibody (01BSUR) on Ang II-induced AAA. Methods and results Male wild-type (WT) and IL-1Ra-deficient (IL-1Ra − / − ) mice were infused with Ang II (1000 ng/kg/min) using subcutaneous osmotic pumps for 28 days. Fourteen days post-infusion, both systolic blood pressure (SBP) (Ang II-treated IL-1Ra − / − :149 ± 2 vs. Ang II-treated WT:126 ± 3 mm Hg, p − / − mice than in WT mice. Because 28-day infusion with Ang II in IL-1Ra −/− mice significantly increased the occurrence of fatal aortic rupture (89% vs. 6%, p − / − mice than in WT mice (p − / − and WT mice (117 ± 4 vs. 115 ± 3 mm Hg, p = 0.71 (after cessation of Ang II infusion)). Histological analyses showed numerous inflammatory cells around the abdominal aorta in IL-1Ra − / − mice, but not in WT mice. Finally, compared with IgG2a treatment, treatment with 01BSUR decreased Ang II-induced AAA in IL-1Ra − / − mice. Conclusions The present study demonstrates that inhibition of IL-1β significantly suppresses AAA formation after Ang II infusion, suggesting that suppression of IL-1β may provide an additional strategy to protect against AAA in hypertensive patients.

The brain is a rare site of metastasis in malignant pleural mesothelioma (MPM), and its clinical features and prognosis remain unclear. The aim of this study was to investigate the incidence, prognosis, and risk factors for brain metastases (BM) in MPM patients. Between July 1993 and October 2014, 150 patients with histologically proven MPM were included in this retrospective study. The cumulative incidence of BM was estimated with the Kaplan-Meier method, and differences between groups were analyzed by the log-rank test. Multivariate logistic regression analysis was applied to assess risk factors for BM. The median follow-up time was 11 months (range 0-154.0 months). A total of eight patients (5.3 %) developed BM during the course of their illness. Multivariate analysis identified age

Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM.One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system.An elevated LMR was significantly associated with prolonged OS. Patients with LMR2.74 had significantly poor survival compared with LMR ≥2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS.The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability.

This study proposes the quantitative evaluation of mental workload for port-coordinator using NO₃ included in saliva, which is one of physiological indices. The NO₃ is secreted into blood and also blood-borne saliva when a human body receives the mental workload. So far the authors have tried a lot of evaluations based on a ship handling simulator; however, the authors still have not do firsthand experiments on a ship and in navigational environments. This study focuses on Hakata Port which is an ideal environment for an experimental scale. The authors were carried out an experiment for port-coordinators of Hakata Port Radio. The authors report the results of experiments.

IκBNS is a nuclear IκB protein which negatively regulates nuclear factor-κB activity. We demonstrated that IκBNS deficiency accelerates atherosclerosis in LDL receptor-deficient (LDLr−/−) mice via increased interleukin (IL)-6 production by macrophages. Previous studies showed that the increase in IL-6 might contribute to the development of atherosclerotic lesions. However, whether an anti-mouse IL-6 receptor antibody (MR16-1) can protect atherosclerotic lesions in atherogenic mice remains to be elucidated. We investigated atherosclerotic lesions in LDLr−/− and IκBNS−/−/LDLr−/− mice after 16 weeks consumption of a high-fat diet. All mice received intraperitoneal injections of MR16-1 or phosphate-buffered saline (PBS) (control) once a week during a high-fat diet consumption. Treatment of MR16-1 yielded no adverse systemic effects, and we detected no significant differences in serum cholesterol levels in either group. The atherosclerotic lesions were significantly increased in IκBNS−/−/LDLr−/− compared with LDLr−/− mice (p

The goal of our research is to quantitatively assess the mental workload of port-coordinators, who perform radio communication duties for port and harbor, by using salivary NO 3 −. We confirmed that salivary NO 3 − which is one of the physiological indices responds to mental workload, but it is not clear how it responds to various events [1]. It is necessary to examine the relationship between the response from salivary NO 3 − and various events to make how salivary NO 3 − responds to various events clear. Therefore, we utilize the duties list for port-coordinators which can classify the events to the duty items of that. The events are the points where the port-coordinators receive heavy mental workload. However, we confirmed that the existing duties list is not appropriate to examine the relationship between mental workload and various events. This research aims to construct a new duties list for port-coordinators to assess the mental workload. In this research, we measure salivary NO3− of the port-coordinators and improved the items of the duties list on the basis of heavy mental workload events and the existing duties list. We inspect the correspondence between heavy mental workload events and the items of the duties list. Through this research, we could construct a new duties list for port-coordinators which can examine the relationship between the response from salivary NO 3 − and various events. We have become able to classify various events of port-coordinators as their duty contents by using the new duties list. We will be able to clarify how salivary NO 3 − responds to various duties of port-coordinators. Therefore, we will be able to assess quantitative their mental workload.

This paper aims to acknowledge the trend of mental workload of a newly-appointed marine pilot compared with that of a veteran pilot, using the physiological index, salivary NO 3 − and LF/HF values, and confirm the effectiveness of salivary NO 3 − as a physiological index. This paper also aims to confirm that the pilots and port-coordinators' trends of mental workload respond risky situations including collision with other vessels in their duty. Pilots handle vessels for the captain in a specific port or harbor and pilots contribute the safety of the sea area. That is why to verify pilots' mental workload is essential for the purpose of preventing the risky situations. On the other hand, port-coordinators play a role of sea-safe controller at a port, and their advices by wireless radio support pilot's duty. To confirm and verify port-coordinators' mental workload is also essential. From this experiment we confirm the salivary NO 3 − and LF/HF values are useful to evaluation pilots' mental workload, and are also useful for a newly-appointed pilot's drill on board.