39 research outputs found

    Prevalence of Metabolic Syndrome and Its Components among Japanese Workers by Clustered Business Category

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    博士(医学)福島県立医科大

    Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis

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    Ascofuranone (AF), a meroterpenoid isolated from various filamentous fungi, including Acremonium egyptiacum, has been reported as a potential lead candidate for drug development against parasites and cancer. In this study, we demonstrated that AF and its derivatives are potent anthelminthic agents, particularly against Echinococcus multilocularis, which is the causative agent of alveolar echinococcosis. We measured the inhibitory activities of AF and its derivatives on the mitochondrial aerobic and anaerobic respiratory systems of E. multilocularis larvae. Several derivatives inhibited complex II (succinate:quinone reductase [SQR]; IC50 = 0.037 to 0.135 mM) and also complex I to III (NADH:cytochrome c reductase; IC50 = 0.008 to 0.401 mM), but not complex I (NADH:quinone reductase), indicating that mitochondrial complexes II and III are the targets. In particular, complex II inhibition in the anaerobic pathway was notable because E. multilocularis employs NADH:fumarate reductase (fumarate respiration), in addition to NADH oxidase (oxygen respiration), resulting in complete shutdown of ATP synthesis by oxidative phosphorylation. A structure-activity relationship study of E. multilocularis complex II revealed that the functional groups of AF are essential for inhibition. Binding mode prediction of AF derivatives to complex II indicated potential hydrophobic and hydrogen bond interactions between AF derivatives and amino acid residues within the quinone binding site. Ex vivo culture assays revealed that AF derivatives progressively reduced the viability of protoscoleces under both aerobic and anaerobic conditions. These findings confirm that AF and its derivatives are the first dual inhibitors of fumarate and oxygen respiration in E. multilocularis and are potential lead compounds in the development of anti-echinococcal drugs

    Visualizing the decline of public interest in the Great East Japan Earthquake and Fukushima Daiichi nuclear power plant accident by analyzing letters to the editor in Japanese newspapers

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    This study aimed to delineate the decline in public interest toward the March 2011 Great East Japan Earthquake (GEJE) and the Fukushima Daiichi nuclear power plant (FNPP) accident in Japan over a ten-year period. In this longitudinal descriptive study, we searched for publications within a ten-year period in Letters to the Editor that mentioned the GEJE, the FNPP accident, or the January 1995 Great Hanshin-Awaji Earthquake (GHAE) that occurred in Japan, using the official databases of the three largest Japanese newspapers. The GEJE- and GHAE-related publications (4,809 and 2,092, respectively) are depicted as scatter plots. The results show a gradual decrease in the publications mentioning GEJE or GHAE. The impact of GEJE and FNPP on Japanese society was enormous, but the public interest waned over time. Communication strategies that maintain a high public interest in previous disasters may be necessary

    Association between subjective economic status and refusal of life-prolonging treatment: a cross-sectional study using content analysis with stratified random sampling

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    Introduction: Older adults tend to refuse life-prolonging treatment for various reasons, and it is important to respect their choice of treatment at the end-of-life stage. The present study examines the associations of subjective economic status and gender with reasons for refusal of life-prolonging treatment in older adults in general population. Methods: In this cross-sectional study, using stratified random sampling, 1,595 older adults living in Koriyama City, Japan, as of 2016, completed self-administered questionnaires on subjective economic status and preference for life-prolonging treatment, with free-description regarding reasons for refusal. We analyzed the associations between the combination of subjective economic status and gender with frequently mentioned terms and their clusters regarding such reasons, using χ2 test, content analysis, text mining and hierarchical cluster analysis. Results: The combinations of subjective economic status and gender were significantly associated with clustered reasons for refusal of life-prolonging treatment (p < 0.01). The reasons frequently mentioned were: 'avoidance of unnecessary medical care' and 'dignity' in well-off females; and 'financial burden on family' in poor males. Conclusions: Our findings suggest that older adults who at first glance appear to be freely refusing life-prolonging treatment, may have their decision making restricted through economic constraints

    Association between participation in sports club activities and decision-making preferences in end-of-life treatment among Japanese elderly people:a cross-sectional study

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    Introduction: Decision-making regarding treatment at the end-of-life stage is an important issue for the elderly and their families. Such decision-making may be influenced by activities that promote communication and physical health. The purpose of this study was to examine the association between participation in sports club activities and decision-making regarding life-prolonging treatment among the general community-dwelling Japanese elderly. Methods: In this cross-sectional study, which used stratified random sampling, 1,603 elderly people aged 65 years or older as of January 2016, living in Fukushima prefecture, Japan were enrolled. Data was collected by a self-completed questionnaire (effective response rate: 53.4%). The association of sports club activity participation with a preference for accepting or declining life-prolonging treatment was analyzed by multinomial logistic regression analysis. Results: Of those participating in sports club activities, the results revealed an odds ratios of 1.812 for participants declining life-prolonging treatment (95% CI=1.325 to 2.477) and 1.948 for those who preferred life-prolonging treatment (95% CI=1.160 to 3.271). Conclusions: The present study suggests that participation in sports club activities is associated with articulating decisions about life-prolonging treatment in end-of-life care. Consideration of patient involvement in daily activities in non-medical settings may enhance decision-making for end-of-life care planning

    Diagnostic Criteria of FMD and NID

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    Background - Diagnostic criteria of flow-mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin-induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function. Methods and Results - We investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no-risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow-Mediated Dilation Japan study and the Flow-Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver-operator characteristic curve analysis of FMD to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no-risk group was 7.1%. Receiver-operator characteristic curve analysis of NID to discriminate subjects in the no-risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no-risk group was 15.6%. Conclusions - We propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects

    Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

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    BackgroundThe usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.Methods and ResultsWe measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.ConclusionsIn patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

    FMD, PWV, and Cardiovascular Events

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    Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification
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