41 research outputs found

    Left Atrial Functional Response after a Marathon

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    Background: Middle-aged marathon runners have an increased risk of developing atrial fibrillation (AF). A previous study described that repetitive marathon running was associated with left atrial (LA) dysfunction. However, whether this change is common in marathon runners and which runners are at risk of LA dysfunction remain unknown. The purpose of this study was to determine which factors could predict LA dysfunction. Methods and results: We prospectively examined 12 healthy amateur volunteers (9 males, 31±8 years old) who participated in a full marathon. All echocardiographic measurements and speckle-tracking echocardiography were performed before and after the marathon. The endpoint was defined as reduced LA reservoir strain one day after the marathon (non-responder group). Seven participants were in the non-responder group. Age (35±9 vs. 26±2 yrs., p=0.020), augmentation index (76±12 vs. 55±8, p=0.002), and diastolic blood pressures (83±11 vs. 70±7 mmHg, p=0.021) in the non-responder group were significantly higher compared with the responder group. In multivariate linear regression analysis, only the augmentation index was an independent predictor of reduced LA reservoir function after the marathon (ÎČ=-0.646, p=0.023). Conclusion: The augmentation index was a predictive marker for reduction in LA reservoir function after a marathon in healthy amateur volunteers

    Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations

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    Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients

    Demand for ecolabeled seafood in the Japanese market: A conjoint analysis of the impact of information and interaction with other labels

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    The use of seafood ecolabels is expanding in the world marketplace, but so are labels indicating other product attributes, such as country of origin and wild vs. farmed. The interactive effects of these labels and attributes in evaluating consumers' preferences for ecolabeled seafood are relatively unexplored. In this paper we investigate (1) the direct and interactive effects of seafood ecolabels with other common fish labels, and (2) how consumers' perceptions about the state of marine stocks and the valuation of ecolabels may be affected by different information. We find moderate interactive effects between ecolabels and country of origin labels, whereas the valuation for seafood ecolabels is fairly high. In terms of information, we find that consumers' perceptions about fish stock levels changed (negatively) after receiving information on declining stock levels, and more sensationalized information led to increased change. However, valuation for a seafood ecolabel increases only when the information was perceived positively (credible/interesting); whereas exaggerated information (which was also perceived less credible) had insignificant effects on WTP

    Demand for ecolabeled seafood in the Japanese market: A conjoint analysis of the impact of information and interaction with other labels

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    The use of seafood ecolabels is expanding in the world marketplace, but so are labels indicating other product attributes, such as country of origin and wild vs. farmed. The interactive effects of these labels and attributes in evaluating consumers\u27 preferences for ecolabeled seafood are relatively unexplored. In this paper we investigate (1) the direct and interactive effects of seafood ecolabels with other common fish labels, and (2) how consumers\u27 perceptions about the state of marine stocks and the valuation of ecolabels may be affected by different information. We find moderate interactive effects between ecolabels and country of origin labels, whereas the valuation for seafood ecolabels is fairly high. In terms of information, we find that consumers\u27 perceptions about fish stock levels changed (negatively) after receiving information on declining stock levels, and more sensationalized information led to increased change. However, valuation for a seafood ecolabel increases only when the information was perceived positively (credible/interesting); whereas exaggerated information (which was also perceived less credible) had insignificant effects on WTP. © 2013 Elsevier Ltd

    Photoinduced radical generation and trapping by acrylonitrile of N-Boc secondary amine and N-Boc N-methyl α-amino acid ester at α-position using two-molecule photoredox catalysts

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    The photoreaction of an N-Boc secondary amine and N-Boc N-methyl α-amino acid ester with acrylonitrile using inexpensive two-molecule photoredox catalysts results in the production of α-alkylated amine through the generation of an α-carbamy radical under mild conditions. In particular, this mothed leads to a regioselective modification of N-Boc N-methyl α-amino acid ester with the retention of α-chirality through the generation of the less stable primary α-carbamyl radical

    A novel anti-NGF PEGylated Fab’ provides analgesia with lower risk of adverse effects

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    ABSTRACTNerve growth factor (NGF) has emerged as a key driver of pain perception in several chronic pain conditions, including osteoarthritis (OA), and plays an important role in the generation and survival of neurons. Although anti-NGF antibodies improve pain control and physical function in patients with clinical chronic pain conditions, anti-NGF IgGs are associated with safety concerns such as effects on fetal and postnatal development and the risk of rapidly progressive osteoarthritis. To overcome these drawbacks, we generated a novel anti-NGF PEGylated Fab’ antibody. The anti-NGF PEGylated Fab’ showed specific binding to and biological inhibitory activity against NGF, and analgesic effects in adjuvant-induced arthritis model mice in a similar manner to an anti-NGF IgG. In collagen-induced arthritis model mice, the anti-NGF PEGylated Fab’ showed higher accumulation in inflamed foot pads than the anti-NGF IgG. In pregnant rats and non-human primates, the anti-NGF PEGylated Fab’ was undetectable in fetuses, while the anti-NGF IgG was detected and caused abnormal postnatal development. The PEGylated Fab’ and IgG also differed in their ability to form immune complexes in vitro. Additionally, while both PEGylated Fab’ and IgG showed analgesic effects in sodium monoiodoacetate-induced arthritic model rats, their effects on edema were surprisingly quite different. While the anti-NGF IgG promoted edema over time, the anti-NGF PEGylated Fab’ did not. The anti-NGF PEGylated Fab’ (ASP6294) may thus be a potential therapeutic candidate with lower risk of adverse effects for various diseases in which NGF is involved such as OA and chronic back pain

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    Objectives There is a high prevalence of left ventricular diastolic dysfunction (LVDD) in systemic sclerosis (SSc) which is associated with high mortality. Thus, early detection of LVDD could be important in management of SSc. We hypothesised that exercise echocardiography in SSc patients with normal resting haemodynamics may expose early phase LVDD, which could affect its prognosis, defined as cardiovascular death and unplanned hospitalisation for heart failure. Methods Between January 2014 and December 2018, we prospectively enrolled 140 patients with SSc who underwent 6-minute walk (6MW) stress echocardiographic studies with normal range of estimated mean pulmonary arterial pressure (mPAP) (<25 mm Hg) and mean pulmonary artery wedge pressure (mPAWP) (<15 mm Hg) at rest. We used ΔmPAP/Δcardiac output (CO) to assess pulmonary vascular reserve and ΔmPAWP/ΔCO to assess LV cardiac reserve between resting and post-6MW. Results During a median period of 3.6 years (IQR 2.0–5.1 years), 25 patients (18%) reached the composite outcome. Both ΔmPAP/ΔCO and ΔmPAWP/ΔCO in patients with events were significantly greater than in those without events (8.9±3.8 mm Hg/L/min vs 3.0±1.7 mm Hg/L/min; p=0.002, and 2.2±0.9 mm Hg/L/min vs 0.9±0.5 mm Hg/L/min; p1.4 mm Hg/L/min) and impaired pulmonary vascular reserve (ΔmPAP/ΔCO>3.0 mm Hg/L/min) had worse outcomes compared with those without these abnormalities (p<0.001). Conclusion The 6MW stress echocardiography revealed impaired LV cardiac reserve in SSc patients with normal resting haemodynamics. Furthermore, LV cardiac reserve independently associates with clinical worsening in SSc, providing incremental prognostic utility, in addition to pulmonary vascular parameters
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