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4. DNA Damage Induced by Radiation Exposure from Cardiac Catheterization

Author

Yuichiro Jin, Daiki Yaegashi, Lin Shi, Mari Ishida, Chiemi Sakai, Tetsuro Yokokawa, Yu Abe, Akira Sakai, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Naoko Hijioka, Kazuo Awai, Satoshi Tashiro, Yasuchika Takeishi, and Takafumi Ishida

Subjects
General Medicine, Cardiology and Cardiovascular Medicine
Published
2022

8. Prognostic Value of the Pattern of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) Bleeding Risk Score for Long-Term Mortality After Percutaneous Coronary Intervention

Author

Joh, Akama, Takeshi, Shimizu, Takuya, Ando, Fumiya, Anzai, Yuuki, Muto, Yusuke, Kimishima, Takatoyo, Kiko, Akiomi, Yoshihisa, Takayoshi, Yamaki, Hiroyuki, Kunii, Kazuhiko, Nakazato, Takafumi, Ishida, and Yasuchika, Takeishi

Subjects
Aged, 80 and over, Heart Failure, Male, Hemorrhage, Coronary Artery Disease, Kaplan-Meier Estimate, General Medicine, Middle Aged, Prognosis, Medication Adherence, Cohort Studies, Hospitalization, Survival Rate, Percutaneous Coronary Intervention, Postoperative Complications, Predictive Value of Tests, Risk Factors, Humans, Female, Stents, Cardiology and Cardiovascular Medicine, Platelet Aggregation Inhibitors, Aged, Proportional Hazards Models
Abstract

The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score has been proposed to predict the risk of bleeding events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS bleeding risk score for long term all-cause mortality, cardiac mortality and hospitalization due to heart failure has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS bleeding risk score for all-cause and cardiac mortalities and hospitalization due to heart failure after PCI. Consecutive 1061 patients who had undergone PCI were divided into 3 groups based on the PARIS bleeding risk score; low (n = 112), intermediate (n = 419) and high-risk groups (n = 530). We prospectively followed up the 3 groups for all-cause and cardiac mortalities and hospitalization due to heart failure. Kaplan-Meier analysis revealed that all of the outcomes were highest in the high-risk group among the 3 groups (P0.001, P0.001 and P0.001 respectively). Multivariable Cox proportional hazard analysis, adjusted for confounding factors, revealed that all-cause mortality of the intermediate or high-risk groups was higher than those of the low-risk group (adjusted hazard ratio 6.06 and 12.50, P = 0.013 and P0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.

Published
2022

9. Static Hydrophobic Cuprous Oxide Surface Fabricated via One-Step Laser-Induced Oxidation of a Copper Substrate

Author

Xi Yu, Yoshiki Tanaka, Tomoki Kakiuchi, Takafumi Ishida, Koh Saitoh, Fumihiro Itoigawa, Makoto Kuwahara, and Shingo Ono

Subjects
Control and Systems Engineering, Mechanical Engineering, Electrical and Electronic Engineering, femtosecond laser processing, surface modification, hydrophobic surface
Abstract

In this study, we developed a one-step method for fabricating hydrophobic surfaces on copper (Cu) substrates. Cuprous oxide (Cu2O) with low free energy was successfully formed after low-fluence laser direct irradiation. The formation of Cu2O enhanced the hydrophobicity of the Cu substrate surface, and the contact angle linearly increased with the proportion of Cu2O. The Cu2O fabricated by low-fluence laser treatment showed the same crystal plane orientation as the pristine Cu substrate, implying an epitaxial growth of Cu2O on a Cu substrate.

Published
2023
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10. Cigarette smoke induces mitochondrial DNA damage and activates cGAS-STING pathway -Application to a biomarker for atherosclerosis

Author

Keitaro Ueda, Chiemi Sakai, Takafumi Ishida, Kosuke Morita, Yusuke Kobayashi, Yasunori Horikoshi, Akiko Baba, Yuma Okazaki, Masao Yoshizumi, Satoshi Tashiro, and Mari Ishida

Subjects
General Medicine
Abstract

Cigarette smoking is a major risk factor for atherosclerosis. We previously reported that DNA damage was accumulated in atherosclerotic plaque, and was increased in human mononuclear cells by smoking. As vascular endothelial cells are known to modulate inflammation, we investigated the mechanism by which smoking activates innate immunity in endothelial cells focusing on DNA damage. Furthermore, we sought to characterize the plasma level of cell-free DNA (cfDNA), a result of mitochondrial and/or genomic DNA damage, as a biomarker for atherosclerosis. Cigarette smoke extract (CSE) increased DNA damage in the nucleus and mitochondria in human endothelial cells. Mitochondrial damage induced minority mitochondrial outer membrane permeabilization, which was insufficient for cell death but instead led to nuclear DNA damage. DNA fragments, derived from the nucleus and mitochondria, were accumulated in the cytosol, and caused a persistent increase in IL-6 mRNA expression via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. cfDNA, quantified with quantitative PCR in culture medium was increased by CSE. Consistent with in vitro results, plasma mitochondrial cfDNA (mt-cfDNA) and nuclear cfDNA (n-cfDNA) were increased in young healthy smokers compared with age-matched nonsmokers. Additionally, both mt-cfDNA and n-cfDNA were significantly increased in patients with atherosclerosis compared with the normal controls. Our multivariate analysis revealed that only mt-cfDNA predicted the risk of atherosclerosis. In conclusion, accumulated cytosolic DNA caused by cigarette smoke and the resultant activation of the cGAS-STING pathway may be a mechanism of atherosclerosis development. The plasma level of mt-cfDNA, possibly as a result of DNA damage, may be a useful biomarker for atherosclerosis.

Published
2023

11. Role of DNA damage in the pathogenesis of atherosclerosis

Author

Mari Ishida, Chiemi Sakai, and Takafumi Ishida

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Atherosclerosis is a cause of coronary artery disease, abdominal aortic aneurysm, and stroke. The pathogenesis underlying atherosclerosis is complex but it is clear that inflammation plays a pivotal role. Inflammation in atherosclerosis is triggered by the recognition of intracellular contents released from damaged cells by pattern recognition receptors, and is therefore sterile and chronic. Because the DNA of these cells is damaged, cellular senescence is also involved in this inflammation. Here, we will discuss the emerging evidence of a relationship between DNA damage and inflammation in the pathogenesis of atherosclerosis, with a focus on intracellular events and cell fates that arise following DNA damage. Recent evidence will lead us to potential therapeutic targets and allow us to explore potential preventative and therapeutic strategies.

Published
2022

12. Identification of Torquetenovirus Species in Patients with Kawasaki Disease Using a Newly Developed Species-Specific PCR Method

Author

Pietro Giorgio Spezia, Fabio Filippini, Yoshiro Nagao, Tetsuya Sano, Takafumi Ishida, and Fabrizio Maggi

Subjects
Inorganic Chemistry, Organic Chemistry, anellovirus, quantitative PCR, next-generation sequencing, primer set, quality score, General Medicine, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Catalysis, Computer Science Applications
Abstract

A next-generation sequencing (NGS) study identified a very high viral load of Torquetenovirus (TTV) in KD patients. We aimed to evaluate the feasibility of a newly developed quantitative species-specific TTV-PCR (ssTTV-PCR) method to identify the etiology of KD. We applied ssTTV-PCR to samples collected from 11 KD patients and 22 matched control subjects who participated in our previous prospective study. We used the NGS dataset from the previous study to validate ssTTV-PCR. The TTV loads in whole blood and nasopharyngeal aspirates correlated highly (Spearman’s R = 0.8931, p < 0.0001, n = 33), supporting the validity of ssTTV-PCR. The ssTTV-PCR and NGS results were largely consistent. However, inconsistencies occurred when ssTTV-PCR was more sensitive than NGS, when the PCR primer sequences mismatched the viral sequences in the participants, and when the NGS quality score was low. Interpretation of NGS requires complex procedures. ssTTV-PCR is more sensitive than NGS but may fail to detect a fast-evolving TTV species. It would be prudent to update primer sets using NGS data. With this precaution, ssTTV-PCR can be used reliably in a future large-scale etiological study for KD.

Published
2023

14. DNA Damage Induced by Radiation Exposure from Cardiac Catheterization

Author

Yuichiro, Jin, Daiki, Yaegashi, Lin, Shi, Mari, Ishida, Chiemi, Sakai, Tetsuro, Yokokawa, Yu, Abe, Akira, Sakai, Takayoshi, Yamaki, Hiroyuki, Kunii, Kazuhiko, Nakazato, Naoko, Hijioka, Kazuo, Awai, Satoshi, Tashiro, Yasuchika, Takeishi, and Takafumi, Ishida

Subjects
Cardiac Catheterization, Cytokines, Humans, RNA, Messenger, Radiation Exposure, In Situ Hybridization, Fluorescence, DNA Damage
Abstract

Almost 40% of medical radiation exposure is related to cardiac imaging or intervention. However, the biological effects of low-dose radiation from medical imaging remain largely unknown. This study aimed to evaluate the effects of ionized radiation from cardiac catheterization on genomic DNA integrity and inflammatory cytokines in patients and operators.Peripheral mononuclear cells (MNCs) were isolated from patients (n = 51) and operators (n = 35) before and after coronary angiography and/or percutaneous coronary intervention. The expression of γH2AX, a marker for DNA double-strand breaks, was measured by immunofluorescence. Dicentric chromosomes (DICs), a form of chromosome aberrations, were assayed using a fluorescent in situ hybridization technique.In the patient MNCs, the numbers of γH2AX foci and DICs increased after cardiac catheterization by 4.5 ± 9.4-fold and 71 ± 122%, respectively (P0.05 for both). The mRNA expressions of interleukin (IL)-1α, IL-1β, leukemia inhibitory factor, and caspase-1 were significantly increased by radiation exposure from cardiac catheterization. The increase in IL-1β was significantly correlated with that of γH2AX, but not with the dose area product. In the operators, neither γH2AX foci nor the DIC level was changed, but IL-1β mRNA was significantly increased. The protein expression of IκBα was significantly decreased in both groups.DNA damage was increased in the MNCs of patients, but not of operators, who underwent cardiac catheterization. Inflammatory cytokines were increased in both the patients and operators, presumably through NF-κB activation. Further efforts to reduce radiation exposure from cardiac catheterization are necessary for both patients and operators.

Published
2022

15. Crucial role of hematopoietic JAK2 V617F in the development of aortic aneurysms

Author

Kento Wada, Norio Komatsu, Kazuhiko Ikeda, Tetsuro Yokokawa, Koichi Sugimoto, Tomofumi Misaka, Soji Morishita, Yasuchika Takeishi, Yusuke Kimishima, Keiji Minakawa, and Takafumi Ishida

Subjects
0303 health sciences, Pathology, medicine.medical_specialty, Apolipoprotein B, biology, business.industry, Transgene, medicine.medical_treatment, Abdominal aorta, Hematology, Hematopoietic stem cell transplantation, 030204 cardiovascular system & hematology, MMP9, Angiotensin II, 03 medical and health sciences, Haematopoiesis, surgical procedures, operative, 0302 clinical medicine, medicine.artery, biology.protein, Medicine, business, STAT3, 030304 developmental biology
Abstract

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.

Published
2021

16. Cancer therapeutics-related cardiovascular dysfunction: Basic mechanisms and clinical manifestation

Author

Masayoshi Oikawa, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Although recent advances in cancer treatment improve cancer prognosis, cancer therapeutics-related cardiovascular dysfunction (CTRCD) significantly contributes to the global burden of cardiovascular disease. CTRCD causes two crucial issues: first, premature treatment interruption or discontinuation of chemotherapy; second, the development of congestive heart failure during and after cancer treatment. Thus, early detection and prompt treatment of CTRCD may improve the prognosis in cancer patients. This review covers representative anticancer drugs, including anthracyclines, human epidermal growth factor 2 inhibitors, tyrosine kinase inhibitors, proteasome inhibitors, and immune checkpoint inhibitors. We focus on the molecular mechanisms of CTRCD and various approaches to diagnosis, prevention, monitoring, and treatment.

Published
2022

17. The clinical implication of new‐onset in‐hospital atrial fibrillation in patients with acute decompensated heart failure

Author

Takashi Kaneshiro, Kazuhiko Nakazato, Tomofumi Misaka, Minoru Nodera, Tetsuro Yokokawa, Masashi Kamioka, Yasuchika Takeishi, Takafumi Ishida, and Akiomi Yoshihisa

Subjects
lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, Acute decompensated heart failure, business.industry, Post discharge, acute heart failure, Incidence (epidemiology), cerebrovascular event, atrial fibrillation after discharge, Atrial fibrillation, Original Articles, medicine.disease, New onset, lcsh:RC666-701, Internal medicine, new‐onset in‐hospital atrial fibrillation, medicine, Cardiology, In patient, Original Article, Risk factor, Cardiology and Cardiovascular Medicine, business, Cardiac deaths, cardiac death
Abstract

Background To investigate the clinical implication of the temporal difference in atrial fibrillation (AF)‐onset in acute decompensated heart failure (ADHF) and its impact on post‐discharge prognosis. Methods 336 new‐onset ADHF patients without any history of AF before admission were enrolled (201 males, 63 ± 16 year‐old) and classified into two groups based on their history of AF: the Control group (No AF was detected during hospitalization, n = 278), and the In‐hos‐AF group (AF occurred during hospitalization, n = 58). Post discharge prognosis including rehospitalization due to worsening HF, cardiac death, all‐cause death and cerebrovascular event were compared. Results Kaplan‐Meier analysis demonstrated that the incidence of rehospitalization due to HF, cardiac death, all‐cause death and cerebrovascular event in the In‐hos‐AF group was not significantly different from that in the Control group (P > 0.05 respectively). However, when AF recurred in the In‐hos‐AF group patients (n = 24, 41%) after discharge, the incidence of rehospitalization due to HF and cardiac deaths were higher than those without AF recurrence (P = 0.018 and P = 0.027 respectively). Cox proportional analysis revealed that AF developing after discharge was proven to be an independent risk factor for rehospitalization due to HF (HR 1.845, P = 0.043), cardiac death (HR 3.562, P = 0.013) and all‐cause deaths (HR 2.138, P = 0.020). Conclusion Clinical outcomes of new‐onset in‐hospital AF patients were as good as those without AF history until AF recurrence. However, AF recurrence led to worse prognosis. Therefore, treatment for new‐onset in‐hospital AF in ADHF patients might be postponed until AF recurrence., Clinical outcome in the new‐onset in‐hospital AF in patients with ADHFD, compared with those who had no history of AF.

Published
2020

18. Genetic Polymorphism of Glutathione S-transferase and Cervical Cancer Susceptibility in Northeastern Thailand

Author

Mayuree Wongpratate, Sophida Phuthong, Takafumi Ishida, Wannapa Settheetham-Ishida, and Sitakan Natphopsuk

Subjects
Cervical cancer, biology, business.industry, Wild type, Physiology, Building and Construction, medicine.disease, GSTP1, Glutathione S-transferase, Genotype, Genetic predisposition, biology.protein, Medicine, Gene polymorphism, Electrical and Electronic Engineering, business, Carcinogen
Abstract

Background: Exposure to certain carcinogens together with host genetic predisposition likely has an influence on cervical carcinogenesis. Objective: Our aim was to evaluate synergistic effects of glutathione S-transferase (GST) polymorphisms and risk behaviors (i.e., smoking and contraceptive use) on squamous cell cervical cancer (SCCA) development in northeastern Thailand. Methods: Subjects were 198 (SCCA) patients and 198 age-matched healthy controls. Multiplex PCR and PCR-RFLP were used to determine GSTT1 and GSTA1 gene polymorphism, respectively. Results: Interaction between the four polymorphic loci of GSTs (GSTM1, GSTT1, GSTP1 and GSTA1) and increased risk for cervical cancer was not observed. The three genotypes of GSTM1 consistently showed significant risks of smoking with a lower OR for the Null individuals (1.741) at around one -fourth of wild type homozygous individuals (8.000). The effects of GST polymorphisms on cervical cancer risk under the use of hormonal contraceptives apparently did not occur. Conclusions: The predisposition of smoking risk is related to the GST genotype. It is suggested that knowing one’s own genotype data will contribute to the prevention of SCCA by controlling risk habits.

Published
2020

19. Biological Effects of Low-Dose Chest CT on Chromosomal DNA

Author

Satoshi Tashiro, Wataru Fukumoto, Yoshihiro Miyata, Chiemi Sakai, Morihito Okada, Tomoyuki Akita, Kazuo Awai, Takafumi Ishida, Hiroaki Sakane, Lin Shi, and Mari Ishida

Subjects
Male, Radiography, medicine.medical_treatment, Radiation Dosage, Chromosomes, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, DNA Breaks, Double-Stranded, Radiology, Nuclear Medicine and imaging, Prospective Studies, Lung cancer, Prospective cohort study, Aged, Aged, 80 and over, Chemotherapy, medicine.diagnostic_test, business.industry, medicine.disease, Radiation therapy, 030220 oncology & carcinogenesis, Female, Radiography, Thoracic, National Lung Screening Trial, Tomography, Tomography, X-Ray Computed, business, Nuclear medicine, Fluorescence in situ hybridization
Abstract

Background Although the National Lung Screening Trial reported a significant reduction in lung cancer mortality when low-dose (LD) CT chest examinations are used for a diagnosis, their biologic effects from radiation exposure remain unclear. Purpose To compare LD CT and standard-dose (SD) CT for DNA double-strand breaks and chromosome aberrations (CAs) in peripheral blood lymphocytes. Materials and Methods Between March 2016 and June 2018, 209 participants who were referred to a respiratory surgery department for chest CT studies were prospectively enrolled in this study. Individuals were excluded if they had undergone radiography examinations within the last 3 days or had undergone chemotherapy or radiation therapy. Peripheral blood samples were obtained before and 15 minutes after CT. The number of γ-H2AX foci and unstable CAs in lymphocytes was quantified by immunofluorescent staining of γ-H2AX and by fluorescence in situ hybridization by using peptide nucleic acid probes for centromeres and telomeres, respectively. The Wilcoxon signed rank test was used for statistical analysis. Bonferroni correction was applied for multiple comparisons. Results Of the 209 participants (105 women, 104 men; mean age, 67.0 years ± 11.3 [standard deviation]), 107 underwent chest LD CT and 102 underwent chest SD CT. Sex distribution, age, and body size metrics were similar between the two groups. The median effective dose of LD CT and SD CT was 1.5 and 5.0 mSv, respectively. The number of double-strand breaks and CAs increased after a SD CT examination (γ-H2AX, P < .001; CAs, P = .003); the number of double-strand breaks and CAs before and after LD CT was not different (γ-H2AX, P = .45; CAs, P = .69). Conclusion No effect of low-dose CT on human DNA was detected. In the same setting, DNA double-strand breaks and chromosome aberrations increased after standard-dose CT. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Brenner in this issue.

Published
2020

20. Significance of Pulmonary Vascular Resistance and Diastolic Pressure Gradient on the New Definition of Combined Post-Capillary Pulmonary Hypertension

Author

Tetsuro Yokokawa, Yasuchika Takeishi, Hiroyuki Kunii, Atsushi Kobayashi, Kazuhiko Nakazato, Koichi Sugimoto, Akiomi Yoshihisa, Tomofumi Misaka, Takayoshi Yamaki, Takafumi Ishida, and Masayoshi Oikawa

Subjects
Adult, Male, medicine.medical_specialty, Heart disease, Hypertension, Pulmonary, Heart Valve Diseases, Myocardial Ischemia, Hemodynamics, Blood Pressure, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Group B, 03 medical and health sciences, 0302 clinical medicine, Diastole, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Proportional Hazards Models, Heart Failure, business.industry, Proportional hazards model, General Medicine, Middle Aged, Prognosis, medicine.disease, Pulmonary hypertension, Death, Survival Rate, Blood pressure, medicine.anatomical_structure, Vascular resistance, Cardiology, Female, Vascular Resistance, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business, Ischemic heart
Abstract

Pulmonary hypertension (PH) caused by left-sided heart disease (LHD-PH) is classified into 2 types: isolated post-capillary PH (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH). However, the impact of pulmonary vascular resistance (PVR) or diastolic pressure gradient (DPG) on the prognosis of LHD-PH has varied among previous studies. Thus, we verified the significance of PVR or DPG on the prognosis of LHD-PH in our series.We analyzed 243 consecutive LHD-PH patients. The patients were divided into 3 groups: Group A, patients with PVR ≤ 3 Wood unit (WU) and DPG7 mmHg; Group B, patients with either PVR3 WU or DPG ≥ 7 mmHg; and Group C, patients with PVR3 WU and DPG ≥ 7 mmHg.The Kaplan-Meier curve demonstrated that Group B had lower cardiac death-free survival compared with Group A, whereas no significant differences were observed when compared with Group C. In the Cox hazard model, DPG was not associated with cardiac death in the LHD-PH patients. However, only in the ischemic heart disease group, patients with DPG ≥ 7 mmHg had worse prognosis compared with those with normal DPG.The cardiac death-free rate of patients with either increased PVR or DPG was close to that of patients with both increased PVR and DPG. It seems reasonable to define Cpc-PH only by PVR in the new criteria. However, the significance of DPG in LHD-PH might be dependent on the underlying cause of LHD-PH.

Published
2020

21. Residual Gensini Score Is Associated With Long-Term Cardiac Mortality in Patients With Heart Failure After Percutaneous Coronary Intervention

Author

Tetsuro Yokokawa, Yasuchika Takeishi, Kazuhiko Nakazato, Takafumi Ishida, Takeshi Shimizu, Tomofumi Misaka, Takayoshi Yamaki, Takatoyo Kiko, Akiomi Yoshihisa, and Hiroyuki Kunii

Subjects
Heart Failure, medicine.medical_specialty, Ejection fraction, business.industry, Anemia, medicine.medical_treatment, Original article, Percutaneous coronary intervention, General Medicine, Prognosis, Revascularization, medicine.disease, Coronary artery disease, Heart failure, Internal medicine, Conventional PCI, Residual Gensini score, medicine, Cardiology, business, Dyslipidemia
Abstract

Background: Coronary revascularization is important in heart failure (HF) with ischemic etiology. Coronary scoring systems are useful to evaluate coronary artery disease, but said systems for residual stenosis after revascularization are still poorly understood. Therefore, the aim of the current study was to clarify the prognostic impact of residual stenosis using a coronary scoring system, Gensini score, in HF patients after percutaneous coronary intervention (PCI). Methods and Results: We analyzed consecutive hospitalized ischemic HF patients (n=199) who underwent PCI. We calculated residual Gensini score after PCI, and divided the patients into 2 groups based on median residual Gensini score. The patients with high scores (≥10, n=101) had a higher prevalence of anemia, lower prevalence of dyslipidemia, and lower left ventricular ejection fraction, compared with those with low scores (

Published
2020

22. Prognostic significance of premature ventricular complex burden on hospitalized patients with heart failure

Author

Atsushi Kobayashi, Takashi Kaneshiro, Takafumi Ishida, Shinya Yamada, Masayoshi Oikawa, Takamasa Sato, Akiomi Yoshihisa, Yasuchika Takeishi, and Masashi Kamioka

Subjects
medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, heart failure, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Medicine, Clinical significance, 030212 general & internal medicine, cardiac death, Ejection fraction, business.industry, Proportional hazards model, readmission, Hazard ratio, Area under the curve, Original Articles, medicine.disease, Confidence interval, Holter monitoring, lcsh:RC666-701, Heart failure, Cardiology, Original Article, premature ventricular complex, Cardiology and Cardiovascular Medicine, business
Abstract

Background The clinical significance of premature ventricular complexes (PVCs) in heart failure (HF) remains unclear. We aimed to clarify the associations of PVC burden with re‐hospitalization and cardiac death in HF patients. Methods We studied 435 HF patients (271 men, mean age 65 years). All patients were hospitalized for worsening HF. After optimal medications, echocardiography, 24 hours Holter monitoring and cardiopulmonary exercise testing were performed before discharge. The clinical characteristics and outcomes of the HF patients were investigated. Results During a median follow‐up period of 2.3 years, there were 125 (28.7%) cardiac events (re‐hospitalization due to worsening HF, fatal arrhythmias, or cardiac death). The patients with cardiac events had higher PVC burden compared to those without (median 0.374%/d [interquartile range 0.013‐1.510] vs median 0.026%/d [interquartile range 0.000‐0.534], P 0.145%/d) to be a predictive factor of cardiac events (area under the curve: 0.64). Kaplan‐Meier analysis demonstrated that cardiac events were more frequent in patients with high‐PVC burden (>0.145%/d, n = 194) compared to those with low‐PVC burden (≤0.145%/d, n = 241). Furthermore, the high‐PVC burden patients had left ventricular (LV) and atrial dilatation, reduced LV ejection fraction, and impaired exercise capacity, compared to the low‐PVC burden patients. In Cox proportional hazards analysis, high‐PVC burden was significantly associated with cardiac events with a hazard ratio of 2.028 (95% confidence interval: 1.418‐2.901, P, The frequency of premature ventricular complex after optimal medication was significantly associated appropriate implantable cardioverter defibrillator therapy, readmission due to worsening heart failure or cardiac death in hospitalized patients with heart failure, even if the frequency was low (>0.145%/d).

Published
2020

23. Pulmonary Hypertension and Hereditary Hemorrhagic Telangiectasia Related to an ACVRL1 Mutation

Author

Tetsuro Yokokawa, Yasuchika Takeishi, Akiomi Yoshihisa, Kazuhiko Nakazato, Takafumi Ishida, Hiroko Morisaki, Koichi Sugimoto, Yusuke Kimishima, Osamu Yamada, and Tomofumi Misaka

Subjects
medicine.medical_specialty, Mutation, medicine.diagnostic_test, business.industry, ACVRL1, General Medicine, Receptor type, medicine.disease_cause, medicine.disease, Gastroenterology, Pulmonary hypertension, Internal medicine, medicine.artery, Pulmonary artery, Internal Medicine, medicine, LUNG HEMORRHAGE, medicine.symptom, business, Telangiectasia, Genetic testing
Abstract

Pulmonary hypertension and hereditary hemorrhagic telangiectasia (HHT) have an association mediated by activin A receptor type II-like 1 (ACVRL1) gene pathogenic variants. A 30-year-old woman was previously admitted to a hospital due to lung hemorrhage, and was diagnosed with pulmonary hypertension, but stopped follow-up visits. At 48 years of age, she was admitted to our hospital and was diagnosed with HHT. Genetic testing revealed an ACVRL1 pathogenic variant. After the initiation of pulmonary vasodilator treatment, the patient's mean pulmonary artery pressure started to decrease from 43 mmHg, declining to 37 mmHg when she was 58 years of age. This is the first report describing the 28-year follow-up of an HHT and pulmonary hypertension patient with an ACVRL1 mutation.

Published
2020

24. Genetic Polymorphisms of Vitamin D Receptor Gene are Associated with Cervical Cancer Risk in Northeastern Thailand

Author

Sitakan Natphopsuk, Sophida Phuthong, Wannapa Settheetham-Ishida, and Takafumi Ishida

Subjects
medicine.medical_specialty, Genotype, cervical cancer, Uterine Cervical Neoplasms, Calcitriol receptor, Gastroenterology, chemistry.chemical_compound, Risk Factors, Internal medicine, Molecular marker, Biomarkers, Tumor, Medicine, Humans, Allele, Cervical cancer, Genetic polymorphism, Polymorphism, Genetic, business.industry, Haplotype, General Medicine, medicine.disease, Prognosis, Thailand, Increased risk, chemistry, Vitamin D receptor, Case-Control Studies, Carcinoma, Squamous Cell, Receptors, Calcitriol, Female, business, Vitamin d receptor gene, Research Article, Follow-Up Studies
Abstract

Objective This study aimed to explore whether VDR polymorphisms (Fok1, Apa1 and Taq1) are associated to the cervical cancer in Thai population. Materials and methods Subjects of 204 cervical cancer patient and 204 age-matched healthy control were enrolled in the case-control study. VDR polymorphisms were detected by using real-time PCR. Haplotype analysis of three loci was applied to the obtained genotypes. Results Significantly increased risk for cervical cancer was observed in carriers of TT genotype (p = 0.0388) and T allele (p = 0.0357) of Fok1 and TC genotype (p = 0.0001), CC genotype (p = 0.0160) and the C allele of Taq1 (p = 0.0001). Haplotype analyses revealed a significant correlation between C-T-C, T-G-C and T-T-C haplotypes and elevated risk for cervical cancer (OR = 2.06; 95%CI = 1.06-4.00; p = 0.0313, OR = 2.15; 95%CI = 1.22-3.80; p = 0.0078 and OR = 2.81; 95%CI = 1.53-5.16; p = 0.0006, respectively). Furthermore, haplotype carrying C allele of Taq1 (C-G-C + C-T-C + T-G-C + T-T-C) significantly increased cervical cancer risk with OR of 1.92 (95%CI = 1.32-2.79, p = 0.0006). Conclusion Our finding revealed an association between VDR polymorphisms and cervical cancer risk. Taq1 C allele might be a molecular marker for cervical cancer development. .

Published
2020

25. Cardiac Troponin I Predicts Elevated B-type Natriuretic Peptide in Patients Treated with Anthracycline-Containing Chemotherapy

Author

Tetsuro Yokokawa, Takafumi Ishida, Yasuchika Takeishi, Akiomi Yoshihisa, Daiki Yaegashi, Makiko Miyata, Tomofumi Misaka, Masayoshi Oikawa, and Kazuhiko Nakazato

Subjects
Male, Cancer Research, medicine.medical_specialty, Anthracycline, medicine.drug_class, medicine.medical_treatment, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Natriuretic Peptide, Brain, Troponin I, Natriuretic peptide, medicine, Humans, Anthracyclines, In patient, 030212 general & internal medicine, Cardiotoxicity, Chemotherapy, business.industry, Cancer, General Medicine, Middle Aged, musculoskeletal system, medicine.disease, Oncology, Echocardiography, 030220 oncology & carcinogenesis, cardiovascular system, Cardiology, Female, business, Blood sampling
Abstract

Background: Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis. Objectives: The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy. Methods: 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months. Results: The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels. Conclusion: Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.

Published
2020

26. Genetic Polymorphisms of the Human Cytochrome P450 1A1 (CYP1A1) and Cervical Cancer Susceptibility among Northeast Thai Women

Author

Sitakan Natphopsuk, Sophida Phuthong, Takafumi Ishida, Wannapa Ishida, and Mayuree Wongpratate

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Genotype, cervical cancer, CYP1A1, Uterine Cervical Neoplasms, Genetic polymorphisms, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Biomarkers, Tumor, Cytochrome P-450 CYP1A1, polycyclic compounds, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, heterocyclic compounds, Carcinogen, Aged, risk, Aged, 80 and over, Cervical cancer, biology, business.industry, Haplotype, Cytochrome P450, General Medicine, Middle Aged, respiratory system, Prognosis, medicine.disease, 030104 developmental biology, Case-Control Studies, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, biology.protein, Female, Thai women, business, Follow-Up Studies, Research Article, Human cytochrome
Abstract

Background: CYP1A1 is an enzyme in phase I of the cytochrome P450 (CYP) superfamily, and plays a key role in detoxification of carcinogens. Host genetic predisposition in the CYP1A1 may be associated with an increased susceptibility to cervical cancer.The study aimed to evaluate four common polymorphisms of the CYP1A1 and cervical cancer susceptibility among Northeast Thai women. Methods: A case-control study was conducted involving 204 patients with squamous cell cervical cancer (SCCA) and 204 age-matched healthy controls. DNA was extracted from peripheral blood leucocytes. CYP1A1 m1, m3, and m4 genotypes were detected using PCR-RFLP, whereas the CYP1A1 m2 genotype was investigated using real-time PCR. Haplotype analysis was performed using PHASE algorithm version 2.1.1. Results: CYP1A1 m3 was monomorphic. Association between the common CYP1A1 polymorphisms, m1 and m2, and cervical cancer risk was not observed (p>0.05), nor was any association found between the m1–m2–m4 haplotype and cervical cancer risk (p>0.05). Interestingly, the CA genotype of CYP1A1 m4 was observed in 30.88% of the cervical cancer patients but was absent in healthy controls. Conclusion: Our results demonstrated a possible involvement of the CYP1A1 m4 polymorphism but no other common polymorphisms (viz., m1, m2, and m3) in the risk for cervical cancer.This finding may be useful when screening for risk of cervical cancer among Northeast Thai women.

Published
2020

31. Abstract 9546: Cancer Therapeutics-Related Cardiac Dysfunction is Associated With High Risk of Cancer-Related Mortality in Patients Treated With Anthracycline-Containing Chemotherapy

Author

Masayoshi Oikawa, Daiki Yaegashi, Sayoko Yokokawa, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Takashi Kaneshiro, ATSUSHI KOBAYASHI, Akiomi Yoshihisa, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a concerning problem in anthracycline-containing chemotherapy. However, the impact of CTRCD on cancer-related mortality is remained to be elucidated. Methods: Consecutive 174 patients planned for anthracycline-containing chemotherapy were enrolled. Echocardiography and blood test were performed at baseline, 3 months, 6 months, 12 months after starting chemotherapy, and after that every 3 months until cardiotoxic chemotherapy was completed. Results: Of 174 patients, CTRCD was developed in 16 patients (CTRCD group, median onset was 8 months), and the other patients (no-CTRCD group) showed normal left ventricular ejection fraction (LVEF). CTRCD group showed higher levels of peak troponin I (0.05 [0.04-0.16] ng/ml vs. 0.02 [0.02-0.04] ng/ml, P Conclusion: The development of CTRCD was associated with high risk of cancer death, but not with cardiac death. Cardioprotective treatment and careful cancer monitoring are required to the patients with CTRCD.

Published
2021

32. Abstract 9577: Resting Energy Expenditure is Important Factor to Predict Cardiac Mortality in Chronic Heart Failure

Author

Takamasa Sato, Akiomi Yoshihisa, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: Parameters derived from cardiopulmonary exercise testing (CPX) including peak oxygen consumption (VO 2 ) are important prognostic factors in patients with chronic heart failure (CHF). However, all patients with CHF cannot undergo CPX because of such as exercise intolerance. On the other hands, resting parameters derived from respiratory gas analyzer including resting energy expenditure (REE) could be easily measured and clinical significance of these parameters had not been fully elucidated in patients with CHF. We aimed to determine the prognostic impact of REE in patients with CHF. Methods: A total of 1185 consecutive CHF patients underwent CPX were enrolled. The subjects of this study were divided into two groups according to median REE and we compered the clinical characteristics between two groups. Also, we examined the value of REE (Weir’ formula: 3.941resting VO 2 +1.106resting VCO 2 ) to predict cardiac mortality in CHF patients. Results: In all subjects, 966 were males, median age was 63 years. Median resting VO 2 was 236 ml/min, median resting VCO 2 was 222 ml/min and median REE was 1178 kcal/day. Patients with low REE (2 and lower resting VCO 2 and lower peak VO 2 than those with high REE ( > 1178 kcal/day). But left ventricular ejection fraction was similar between two groups. Patients with low REE had significantly higher rates of cardiac death, all cause death and composite cardiac events (cardiac death and re-hospitalization due to worsening heart failure) than those with high REE. Furthermore, REE was the independent predictor of cardiac death, all-cause death and composite cardiac events in the Cox proportional hazard analysis after adjusting for cofounding variables including peak VO 2 . Conclusions: REE as well as peak VO 2 is important predictor of cardiac mortality in patients with CHF.

Published
2021

33. Abstract 10926: Importance of Mitochondrial DNA Damage in Cigarette Smoke Extract-Induced Activation of Innate Immune System

Author

Keitaro Ueda, Mari Ishida, CHIEMI SAKAI, Yusuke Kobayashi, Masao Yoshizumi, and Takafumi Ishida

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Objective: Smoking is a well-known risk factor for atherosclerosis, yet the mechanism by which smoking causes atherosclerosis remains unclear. It has been reported that inflammation and DNA damage are involved in the formation and development of atherosclerosis. We have previously reported that nuclear DNA damage was increased in peripheral mononuclear cells of smokers compared to those of non-smokers, and that DNA damage was accumulated in atherosclerotic lesions. In this study, to clarify the mechanism by which smoking induces inflammation in vascular endothelial cells, we investigated the effect of cigarette smoke extract (CSE) on both nuclear and mitochondrial DNA damage and the subsequent cellular response in human umbilical vein endothelial cells (HUVEC). Methods and Results: CSE increased double-strand breaks in HUVEC. Notably, this increase was detected relatively late (after 3 days of CSE exposure) compared to other genotoxic agents. CSE also increased oxidative DNA damage both in the nucleus and mitochondria and induced mitochondrial dysfunction. Mitochondrial dysfunction decreased cytosolic protein levels of ICAD, an inhibitor of caspase-activated DNase (CAD), which causes nuclear DNA fragmentation, and increased CAD in the nucleus, suggesting that this is one of the mechanisms of nuclear DNA double-strand breaks. In addition, continuous stimulation by CSE induced the accumulation of cytosolic DNA. Interestingly, real-time PCR analysis revealed that the accumulated DNA in the cytosol was derived not only from the nucleus but also from mitochondria. We further examined whether DNA accumulated in the cytosol activated cytosolic DNA-sensing pathways. The production of cGAMP, a second messenger in cGAS (a DNA-sensing receptor) signaling, was increased by CSE. We also found that the mRNA expression of IL-6 was increased by CSE, and that the increase was suppressed by si-cGAS. Conclusions: This study showed that continuous exposure to CSE induces not only nuclear but also mitochondrial DNA damage, which leads to cytosolic DNA accumulation, and evokes chronic inflammation via the cGAS-STING pathway.

Published
2021

34. Abstract 11069: Nutritional Risk Index is a Predictive Factor of Anthracycline-Induced Cancer Therapeutics-Related Cardiac Dysfunction

Author

Daiki Yaegashi, Masayoshi Oikawa, Tetsuro Yokokawa, Tomofumi Misaka, ATSUSHI KOBAYASHI, Akiomi Yoshihisa, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: It has been reported that nutritional risk index (NRI) is one of prognostic factors in cardiovascular diseases, but little is known about its relation to the onset of cancer therapeutics-related cardiac dysfunction (CTRCD). Methods and Results: Consecutive 202 cancer patients planed for anthracycline treatment were enrolled and followed up for 12 months in our hospital from February 2017 to June 2019. The patients were divided into 2 groups based on NRI value at 100 before chemotherapy (high NRI group, n=141, 110.5 [104.7-115.6]; low NRI group, n=61, 93.7 [89.6-97.6]). Baseline left ventricular end systolic volume index and left ventricular ejection fraction (LVEF) before chemotherapy were similar between two groups. After chemotherapy, the occurrence of CTRCD was higher in low NRI group than in high NRI group (14.8% vs. 3.5%, P=0.012). Furthermore, there was a correlation between the severity of NRI categories and the development of CTRCD. When we set the cut-off value of baseline NRI from ROC analysis at 100.8, sensitivity, specificity, and area under the curve to predict the occurrence of CTRCD were 71.4%, 70.7%, and 0.698, respectively. Multivariable logistic regression analysis revealed that baseline NRI value was an independent predictor of the development of CTRCD (odds ratio 0.935, 95% CI [0.881-0.992], P=0.026). The value of net reclassification index and integrated discrimination improvement for detecting CTRCD reached statistical significance when baseline NRI value was added to the regression model including known risk factors such as age, female gender, the presence of hypertension, chronic kidney disease, cumulative anthracycline dose, the usage of HER2 inhibitor, and radiation therapy; 0.872 (95% CI [0.421-1.323], P Conclusion: Baseline NRI is a novel parameter to predict anthracycline-induced CTRCD.

Published
2021

35. Abstract 9738: Impact of Bleeding Event for New Cancer Diagnosis in Patients with Coronary Artery Disease Who Underwent Percutaneous Coronary Intervention

Author

Yuya Sakuma, Takeshi Shimizu, Yuta Kurosawa, Himika Ohara, Yukiko Sugawara, Koichiro Watanabe, Yuki Muto, Yusuke Kimishima, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: Patients with coronary artery disease who underwent percutaneous coronary intervention (PCI) are at high risk of bleeding due to antithrombotic therapy. However, the impact of bleeding event for new cancer diagnosis in patients after PCI remains unclear. Methods and Results: Consecutive 1623 patients with coronary artery disease who underwent PCI (mean age, 69.3 years; male gender, 78.5%) were enrolled. We examined a relationship between bleeding events and new cancer diagnosis. During a mean follow-up period of 48 months, 139 (8.6%) experienced bleeding events of Bleeding Academic Research Consortium (BARC) type-2/3/5, including 48 (3.0%) with BARC type-2 bleeding. Patients with bleeding event of BARC type-2/3/5 were older (72.4 vs. 68.9 years, P = 0.001), and higher prevalence of being at Academic Research Consortium criteria for high bleeding risk (72.3% vs. 46.4%, P < 0.001) than those without bleeding event. Among 1623 patients, 133 (8.2%) were diagnosed as having new cancer. The cumulative incidence of new cancer diagnosis was higher in patients with bleeding event of BARC type-2/3/5 than in those without bleeding event (P = 0.002, left figure). In addition, the cumulative incidence of new cancer diagnosis was higher in patients with bleeding event of BARC type-2 than in those without bleeding (P = 0.016, right figure). In the multivariate Cox proportional hazard analysis after adjusting for confounding factors, bleeding events of BARC type-2/3/5 and type-2 were independent predictors of new cancer diagnosis (hazard ratio 2.00, P = 0.007 and hazard ratio 2.25, P = 0.039, respectively). Conclusion: In patients with coronary artery disease after PCI, both major and minor bleeding events were associated with new cancer diagnosis. Even a minor bleeding event should be taken care as the first manifestation of underlying cancer after PCI.

Published
2021

36. Abstract 10103: The Prognostic Impact of D-dimer on Long-Term Mortality in Patients with Coronary Artery Disease After Percutaneous Coronary Intervention

Author

Yuta Kurosawa, Takeshi Shimizu, Yuki Muto, Yusuke Kimishima, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Background: D-dimer is one of common measurable coagulation markers, that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. Here we investigated the association between D-dimer and long-term mortality in CAD patients. Methods and Results: Consecutive 1440 patients with CAD who underwent percutaneous coronary intervention and survived to discharge were enrolled. We divided these patients into three groups based on plasma D-dimer levels at admission: first (D-dimer < 0.7 μg/ml, n = 455), second (0.7 ≤ D-dimer < 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532) tertiles. We compared clinical characteristics among three groups, and prospectively followed all-cause, cardiac, non-cardiac and cancer mortalities. Clinical characteristics for three groups were as follows; mean age (first tertile, second tertile, third tertile; 61.3 ± 11.3, 69.0 ± 10.8, 72.4 ± 10.8 years, P < 0.001), prevalence of chronic kidney disease (31.6%, 36.0%, 61.3%, P < 0.001), anemia (25.1%, 39.7%, 64.5%, P < 0.001), atrial fibrillation (10.8%, 14.1%, 19.7%, P < 0.001), peripheral artery disease (4.8%, 12.4%, 18.8%, P < 0.001) and heart failure (27.0%, 33.1%, 51.9%, P < 0.001). In the Kaplan-Meier analysis (mean follow-up periods 1572 days), all-cause, cardiac, non-cardiac and cancer mortalities were significantly higher in third tertile than others (P < 0.01, P < 0.01, P < 0.01 and P < 0.01, respectively). In the multivariable Cox proportional hazard analyses after adjusting for confounding factors, the high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.62, P < 0.01; HR 3.50, P < 0.01; HR 3.69, P < 0.01; and HR 3.17, P = 0.02). Conclusion: D-dimer is associated with long-term cause-specific mortality in CAD patients.

Published
2021

37. Abstract 10917: Dna Damage Promotes Atherosclerosis by Enhancing Inflammatory Responses via the DNA Sensing Cgas-Sting Pathway

Author

CHIEMI SAKAI, Mari Ishida, Keitaro Ueda, Yusuke Kobayashi, Masao Yoshizumi, and Takafumi Ishida

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

DNA damage is likely a key contributor to atherosclerosis. However, causative links between DNA damage and atherosclerosis are yet to be established. We investigated the role of DNA damage accumulation in atherosclerosis using the DNA repair protein Ku80-deficient apolipoprotein E knockout mice ( Ku80 +/- ApoE -/- ). Ku80 +/- ApoE -/- mice and ApoE -/- mice were fed on high-fat diet for 4 weeks. Oil red O staining showed that plaque area was significantly increased in Ku80 +/- ApoE -/- aortas. Immunohistochemical analysis of lesions from Ku80 +/- ApoE -/- mice revealed enhanced accumulation of DNA double-strand breaks (DSBs). Similar results were obtained from Ku80 +/- ApoE -/- mice fed on high-fat diet for 2 weeks which was considered as the early stages of atherosclerosis. mRNA levels of inflammatory cytokines such as IL-6, MCP-1 and IFN-β in the aorta were significantly elevated in Ku80 +/- ApoE -/- mice than those of ApoE -/- control mice. To further investigate links between DSB accumulation and enhanced proinflammatory responses, vascular smooth muscle cells were isolated from Ku80 WT (WT) and Ku80 +/- mice. mRNA levels of IL-6, MCP-1 and IFN-β were significantly elevated in Ku80 +/- cells compared to those of WT cells. Immunofluorescent analysis revealed DSB accumulation and persistent activation of the DNA repair kinase ATM in Ku80 +/- cells. In addition, senescent markers such as p16 INK4A and senescence-associated β-gal activity were also upregulated in Ku80 +/- cells. Interestingly, the level of cytosolic DNA was elevated in Ku80 +/- cells. Furthermore, phosphorylation of TANK-binding kinase 1 was significantly increased in Ku80 +/- cells, indicating the activation of the cGAS-STING DNA sensing pathway. Thus, we performed cGAS or STING silencing in Ku80 +/- cells using siRNA to test whether cGAS-STING pathway was associated with enhanced proinflammatory responses. cGAS or STING silencing attenuated mRNA level of IL-6 and protein level of IκBα, the NFκB inhibitory protein. Taken together, these results suggested that the accumulation of DSBs promoted atherosclerosis partly through enhanced inflammatory responses via the cGAS-STING activation. Therefore, cGAS-STING may be a promising target for therapeutic intervention of atherosclerosis.

Published
2021

38. Abstract 9707: Validation of Japanese High Bleeding Risk Criteria in Patients Undergoing Percutaneous Coronary Intervention and Comparisons With Contemporary Bleeding Risk Scores

Author

Takeshi Shimizu, Yusuke Kimishima, Tomofumi Misaka, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Introduction: The Japanese version of high bleeding risk (J-HBR) criteria have been established by modifying the Academic Research Consortium criteria for high bleeding risk (ARC-HBR), since East-Asian people have several distinct risk factors that were not included in ARC-HBR. We aimed to validate the J-HBR criteria for bleeding outcomes and compare with contemporary risk scores. Methods: Consecutive 1643 patients with coronary artery disease who underwent percutaneous coronary intervention were enrolled. We followed-up bleeding events of Bleeding Academic Research Consortium (BARC) 3 or 5. Results: Among 1643 patients, 1143 (69.6%) who met J-HBR criteria had a higher accumulated bleeding rate than those who did not (P < 0.001, left figure). BARC 3 or 5 bleeding event rates at 1 year were 4.8% in patients who met J-HBR criteria and 0.6% in those who did not (P < 0.01). The J-HBR criteria had higher sensitivity than ARC-HBR, PRECISE-DAPT and PARIS bleeding risk score (94.8%, 81.0%, 75.9% and 87.9%, respectively) and lower specificity than those (31.4%, 52.6%, 54.1% and 51.0%, respectively). J-HBR score was calculated by adding 1 point for major criterion and 0.5 point for minor criterion in J-HBR criteria. The bleeding event rate increased with advancing J-HBR score (right figure). The c-statistics of J-HBR score for predicting BARC 3 or 5 bleeding at 1 year was 0.74 (95% CI, 0.67 - 0.80) that was comparable to ARC-HBR score, PRECISE-DAPT score and PARIS bleeding risk score (0.73, 0.73 and 0.72, respectively). In the multivariate analysis, chronic kidney disease, anemia and heart failure were associated with BARC 3 or 5 bleeding (HR 6.39, P < 0.01; HR 3.38, P < 0.01; and HR 2.95, P < 0.01; respectively) among factors included in J-HBR criteria. Conclusions: The J-HBR criteria successfully identified patients at high bleeding risk, with high sensitivity and low specificity. The bleeding risk was closely related to J-HBR score and its individual component.

Published
2021

39. Procedural characteristics of pulmonary vein isolation with high-power short-duration setting compared to conventional setting

Author

Naoko Hijioka, Takashi Kaneshiro, Takeshi Nehashi, Kazuaki Amami, Minoru Nodera, Shinya Yamada, Masashi Kamioka, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Male, Time Factors, Middle Aged, First pass isolation, Atrial fibrillation, Pulmonary vein isolation, Dormant conduction, Electrocardiography, Treatment Outcome, Heart Conduction System, Heart Rate, Pulmonary Veins, Recurrence, RC666-701, Catheter Ablation, Diseases of the circulatory (Cardiovascular) system, Humans, Female, Cardiology and Cardiovascular Medicine, Follow-Up Studies, Retrospective Studies, Research Article, High-power short-duration ablation
Abstract

Purpose The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF). Methods We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20–35 W) in 73 patients (Conventional group) and using the HP-SD setting (45–50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups. Results The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P P Conclusion The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV.

Published
2021

40. D-Dimer Is a Predictive Factor of Cancer Therapeutics-Related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy

Author

Takafumi Ishida, Takashi Kaneshiro, Kazuhiko Nakazato, Tomofumi Misaka, Akiomi Yoshihisa, Masayoshi Oikawa, Atsushi Kobayashi, Takamasa Sato, Tetsuro Yokokawa, Yasuchika Takeishi, and Daiki Yaegashi

Subjects
Oncology, Chemotherapy, medicine.medical_specialty, cardio-oncology, business.industry, medicine.medical_treatment, Cancer, heart failure, Cardiovascular Medicine, medicine.disease, Predictive factor, Cardiac dysfunction, cancer therapeutics-related cardiac dysfunction, Internal medicine, RC666-701, D-dimer, medicine, troponin I, Diseases of the circulatory (Cardiovascular) system, In patient, business, Cardiology and Cardiovascular Medicine, Original Research
Abstract

BackgroundD-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsConsecutive 169 patients planned for cardiotoxic chemotherapy were enrolled and followed up for 12 months. All patients underwent echocardiography and blood test at baseline and at 3-, 6-, and 12 months.ResultsThe patients were divided into two groups based on the level of D-dimer (>1.65 μg/ml or ≦ 1.65 μg/ml) at baseline before chemotherapy: high D-dimer group (n = 37) and low D-dimer group (n = 132). Left ventricular ejection fraction (LVEF) decreased at 3- and 6 months after chemotherapy in high D-dimer group [baseline, 65.2% (62.8–71.4%); 3 months, 62.9% (59.0–67.7%); 6 months, 63.1% (60.0–67.1%); 12 months, 63.3% (58.8–66.0%), p = 0.03], but no change was observed in low D-dimer group. The occurrence of CTRCD within the 12-month follow-up period was higher in the high D-dimer group than in the low D-dimer group (16.2 vs. 4.5%, p = 0.0146). Multivariable logistic regression analysis revealed that high D-dimer level at baseline was an independent predictor of the development of CTRCD [odds ratio 3.93, 95% CI (1.00–15.82), p = 0.047].ConclusionWe should pay more attention to elevated D-dimer levels not only as a sign of cancer-associated thrombosis but also the future occurrence of CTRCD.

Published
2021

41. Health and well-being in small island communities: a cross-sectional study in the Solomon Islands

Author

Takahiro Tsukahara, Takafumi Ishida, Akira Sai, Spencer Gabriel, Freda Pitakaka, and Takuro Furusawa

Subjects
Adult, medicine.medical_specialty, Cross-sectional study, Climate Change, Atoll, Pacific Islands, Body Mass Index, Environmental health, Epidemiology, Medicine, Humans, Socioeconomic status, geography, geography.geographical_feature_category, international health services, business.industry, Public health, General Medicine, Livelihood, medicine.disease, Obesity, other metabolic, internal medicine, Cross-Sectional Studies, tropical medicine, epidemiology, Public Health, Melanesia, business, Body mass index
Abstract

ObjectivesThis study explored the health problems of inhabitants of small South Pacific Islands under the influence of climate change, focusing on three communities in the Solomon Islands.DesignCross-sectional study of the Solomon Islands’ populations.SettingA field survey was conducted in Taro Island, a small, urbanised island with a whole-community relocation plan; Manuopo community of Reef Islands, a small remote island on an atoll environment and Sasamungga, an intermediately urbanised community on a larger island. The Sasamungga community was used for comparison.ParticipantsEach community’s participants were recruited through local health authorities, and 113, 155 and 116 adults (aged 18+ years) from Taro, Manuopo and Sasamungga, respectively, participated voluntarily.MethodsEach participant’s body height, weight and body mass index were measured. A drop of blood was sampled for malaria testing; glycated haemoglobin and C reactive protein levels, measured from another drop of blood, were markers for diabetes and inflammation, respectively. The Primary Care Screening Questionnaire for Depression measured depressive mental states.Primary and secondary outcome measuresRegarding health status, the dependent variables—communicable diseases, non-communicable diseases and mental state—and independent variables—differences in communities and socioeconomic status—were measured through health check-ups and interviews of individual participants.ResultsTaro Island inhabitants had a higher risk of obesity (OR 1.13, 95% CI 1.02 to 1.27, p=0.0189), and Manuopo inhabitants had a higher risk of depression (1.25, 95% CI 1.08 to 1.44, p=0.0026) than Sasamungga inhabitants. Manuopo inhabitants recognised more serious problems of food security, livelihood, place to live and other aspects of daily living than other communities’ inhabitants.ConclusionsThe three small island communities’ observation identified different health problems: the urbanised community and remote community had a high risk of non-communicable diseases and mental disorders, respectively. These health problems should be monitored continuously during future climate-related changes.

Published
2021

42. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author

Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. 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Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing Liu , J Jaime Miranda , Olfa Saidi , Sylvain Sebert , Maroje Sorić , Gregor Starc , Edward W Gregg , Leandra Abarca-Gómez , Ziad A Abdeen , Shynar Abdrakhmanova , Suhaila Abdul Ghaffar , Hanan F Abdul Rahim , Niveen M Abu-Rmeileh , Jamila Abubakar Garba , Benjamin Acosta-Cazares , Robert J Adams , Wichai Aekplakorn , Kaosar Afsana , Shoaib Afzal , Imelda A Agdeppa , Javad Aghazadeh-Attari , Carlos A Aguilar-Salinas , Charles Agyemang , Mohamad Hasnan Ahmad , Noor Ani Ahmad , Ali Ahmadi , Naser Ahmadi , Soheir H Ahmed , Wolfgang Ahrens , Gulmira Aitmurzaeva , Kamel Ajlouni , Hazzaa M Al-Hazzaa , Badreya Al-Lahou , Rajaa Al-Raddadi , Monira Alarouj , Fadia AlBuhairan , Shahla AlDhukair , Mohamed M Ali , Abdullah Alkandari , Ala'a Alkerwi , Kristine Allin , Mar Alvarez-Pedrerol , Eman Aly , Deepak N Amarapurkar , Parisa Amiri , Norbert Amougou , Philippe Amouyel , Lars Bo Andersen , Sigmund A Anderssen , Lars Ängquist , Ranjit Mohan Anjana , Alireza Ansari-Moghaddam , Hajer Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M 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Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng 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Lundqvist, Robert, Lunet, Nuno, Lunogelo, Charle, Lustigová, Michala, Łuszczki, Edyta, Ma, Guansheng, Ma, Jun, Ma, Xu, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Macieira, Luisa M, Madar, Ahmed A, Maggi, Stefania, Magliano, Dianna J, Magnacca, Sara, Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Mäki, Päivi, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia K, Maniego, Lynell V, Manios, Yanni, Mann, Jim I, Mansour-Ghanaei, Fariborz, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Ioannidou, Eliza Markidou, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martin-Prevel, Yve, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Maruszczak, Katharina, Marventano, Stefano, Mascarenhas, Luis P, Masoodi, Shariq R, Mathiesen, Ellisiv B, Mathur, Prashant, Matijasevich, Alicia, Matsha, Tandi E, Mavrogianni, Christina, Mazur, Artur, Mbanya, Jean Claude N, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisfjord, Jørgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Menzano, Maria Teresa, Mereke, Alibek, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C, Minderico, Cláudia S, Mini, GK, Miquel, Juan Francisco, Mirjalili, Mohammad Reza, Mirkopoulou, Daphne, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K, Mohamed, Shukri F, Mohammad, Kazem, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Molbo, Drude, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monroy-Valle, Michele, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Morin, Suzanne N, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota-Pinto, Anabela, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muc, Magdalena, Mugoša, Boban, Muiesan, Maria L, Mukhtorova, Parvina, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Ei K Nang, Ei, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioanni, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)

Subjects
Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed

Published
2021

43. Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils

Author

Kazuhiko Ikeda, Atsushi Iwama, Kazuya Shimoda, Kazuhiko Nakazato, Motohiko Oshima, Kento Wada, Koki Ueda, Tetsuro Yokokawa, Keiji Minakawa, Yasuchika Takeishi, Takafumi Ishida, Yusuke Kimishima, Koichi Sugimoto, Kotaro Shide, Shuhei Koide, and Tomofumi Misaka

Subjects
Chemokine, Neutrophils, Activin Receptors, Type II, General Physics and Astronomy, Smad Proteins, Immunoproliferative disorders, Mice, hemic and lymphatic diseases, Prevalence, Medicine, Phosphorylation, Hypoxia, Lung, Cardiopulmonary disease, Multidisciplinary, biology, food and beverages, Up-Regulation, medicine.anatomical_structure, Cardiovascular diseases, Neutrophil Infiltration, Clonal Hematopoiesis, Signal Transduction, STAT3 Transcription Factor, Science, Hypertension, Pulmonary, Bone Marrow Cells, Mice, Transgenic, Vascular Remodeling, General Biochemistry, Genetics and Molecular Biology, Article, Downregulation and upregulation, Cell Line, Tumor, Animals, Humans, Progenitor cell, Respiratory tract diseases, Myeloproliferative Disorders, business.industry, ACVRL1, General Chemistry, Janus Kinase 2, medicine.disease, Pulmonary hypertension, Immunology, Mutation, biology.protein, Bone marrow, business
Abstract

Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2V617F) mice, as well as recipient mice transplanted with JAK2V617F bone marrow cells. JAK2V617F progressively upregulates Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells peripherally into mature neutrophils of pulmonary arterial regions. JAK2V617F-mediated STAT3 phosphorylation upregulates ALK1-Smad1/5/8 signaling. ALK1/2 inhibition completely prevents the development of PH in JAK2V617F mice. Finally, our prospective clinical study identified JAK2V617F-positive clonal hematopoiesis is more common in PH patients than in healthy subjects. These findings indicate that clonal hematopoiesis with JAK2V617F causally leads to PH development associated with ALK1 upregulation., Pulmonary hypertension is characterized by increased pulmonary arterial pressure, driven in part by inflammatory infiltrates. Here, the authors show that in mice, transgenic expression of mutant JAK2 leads to clonal hematopoiesis and lung accumulation of elastase- and cytokine-expressing neutrophils, and that the phenotype can be reversed by ALK1 inhibition.

Published
2021

44. Admixture with indigenous people helps local adaptation: admixture-enabled selection in Polynesians

Author

Taro Yamauchi, Izumi Naka, Ryutaro Ohtsuka, Minato Nakazawa, Kazumi Natsuhara, Takuro Furusawa, Yasuhiro Matsumura, Nao Nishida, Jun Ohashi, Takafumi Ishida, Tsukasa Inaoka, Ryosuke Kimura, and Mariko Isshiki

Subjects
Native Hawaiian or Other Pacific Islander, Evolution, common, Genetic genealogy, Oceania, Genetic ancestry, Admixture, Biology, Polynesia, Population genomics, Polynesians, parasitic diseases, QH359-425, Humans, Indigenous Peoples, QH540-549.5, Local adaptation, Ecology, Bayes Theorem, General Medicine, Rapid adaptation, Adaptation, Physiological, Positive selection, Human evolution, Homo sapiens, Evolutionary biology, common.group, Admixture-enabled selection, ATP-Binding Cassette Transporters, Approximate Bayesian computation, Near Oceania, Research Article
Abstract

Background Homo sapiens have experienced admixture many times in the last few thousand years. To examine how admixture affects local adaptation, we investigated genomes of modern Polynesians, who are shaped through admixture between Austronesian-speaking people from Southeast Asia (Asian-related ancestors) and indigenous people in Near Oceania (Papuan-related ancestors). Methods In this study local ancestry was estimated across the genome in Polynesians (23 Tongan subjects) to find the candidate regions of admixture-enabled selection contributed by Papuan-related ancestors. Results The mean proportion of Papuan-related ancestry across the Polynesian genome was estimated as 24.6% (SD = 8.63%), and two genomic regions, the extended major histocompatibility complex (xMHC) region on chromosome 6 and the ATP-binding cassette transporter sub-family C member 11 (ABCC11) gene on chromosome 16, showed proportions of Papuan-related ancestry more than 5 SD greater than the mean (> 67.8%). The coalescent simulation under the assumption of selective neutrality suggested that such signals of Papuan-related ancestry enrichment were caused by positive selection after admixture (false discovery rate = 0.045). The ABCC11 harbors a nonsynonymous SNP, rs17822931, which affects apocrine secretory cell function. The approximate Bayesian computation indicated that, in Polynesian ancestors, a strong positive selection (s = 0.0217) acted on the ancestral allele of rs17822931 derived from Papuan-related ancestors. Conclusions Our results suggest that admixture with Papuan-related ancestors contributed to the rapid local adaptation of Polynesian ancestors. Considering frequent admixture events in human evolution history, the acceleration of local adaptation through admixture should be a common event in humans.

Published
2021

45. Kuwahara et al. Reply

Author

Makoto Kuwahara, Wataru Nagata, Kojiro Nakakura, Koh Saitoh, Nobuo Tanaka, Masato Furui, Yuya Yoshida, Toru Ujihara, and Takafumi Ishida

Subjects
General Physics and Astronomy, Electrons
Published
2021

46. Extension of focal depth by electron quasi-Bessel beam in atomic-resolution scanning transmission electron microscopy

Author

Takafumi Ishida, Takeshi Owaki, Masahiro Ohtsuka, Makoto Kuwahara, Koh Saitoh, and Tadahiro Kawasaki

Subjects
General Engineering, General Physics and Astronomy
Abstract

Extension of the focal depth of a sub-nanometer-sized electron probe in a scanning transmission electron microscope was demonstrated using an electron Bessel beam. We observed atomically-resolved annular dark-field scanning transmission electron microscope images of SrTiO3 in the [001] direction with defocus using an electron quasi-Bessel beam generated by a ring-shaped aperture in an aberration-corrected probe-forming system. The experimental results show that the defocus range over which images with a 0.2 nm spatial resolution can be acquired using the electron quasi-Bessel beam is three times longer than the corresponding defocus range for a conventional beam.

Published
2022

47. Transient electron energy-loss spectroscopy of optically stimulated gold nanoparticles using picosecond pulsed electron beam

Author

Makoto Kuwahara, Lira Mizuno, Rina Yokoi, Hideo Morishita, Takafumi Ishida, Koh Saitoh, Nobuo Tanaka, Shota Kuwahara, and Toshihide Agemura

Subjects
Physics and Astronomy (miscellaneous)
Abstract

Ultrafast phenomena in gold nanotriangles (AuNTs) were investigated using a transient electron energy-loss spectroscopy (TEELS) technique under irradiation from a 150-fs pulse laser with a wavelength of 780 nm. This investigation was conducted using a time-resolved transmission electron microscopy method that was developed to measure the dynamics of nanomaterials. Enhancement of the intensity and energy-width broadening of the energy loss were observed at the EEL peaks associated with surface and bulk plasmons on the AuNTs. The TEELS measurement revealed two decay processes of 7.8 ps and longer than 100 ps that compensate for relaxation times of excited surface plasmons using transient absorption spectroscopy. The results show that the bulk and surface plasmons have the same time evolution, i.e., that the excited electrons on the surface and in the bulk have the same relaxation processes in both electron–phonon and phonon–phonon interactions. The time evolution of electronic and lattice temperatures was also estimated based on the measured relaxation time using a two-temperature model, which revealed the volume expansion of the AuNTs and clarified the energy shifts of plasmons. Details of excited electrons in nanoparticles investigated via plasmon energy loss are expected to facilitate improvement in the performance for energy harvesting of photons in nanostructure-controlled materials.

Published
2022

48. Clinical usefulness of the pattern of non-adherence to anti-platelet regimen in stented patients (PARIS) thrombotic risk score to predict long-term all-cause mortality and heart failure hospitalization after percutaneous coronary intervention

Author

Joh Akama, Takeshi Shimizu, Takuya Ando, Fumiya Anzai, Yuuki Muto, Yusuke Kimishima, Takatoyo Kiko, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, and Yasuchika Takeishi

Subjects
Heart Failure, Hospitalization, Percutaneous Coronary Intervention, Multidisciplinary, Risk Factors, Humans, Stents, Thrombosis, Risk Assessment
Abstract

Background The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) thrombotic risk score has been proposed to estimate the risk of stent thrombotic events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS thrombotic risk score for long term all-cause and cardiac mortalities, as well as hospitalization due to heart failure, has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS thrombotic risk score for all-cause and cardiac mortalities and hospitalization due to heart failure following PCI. Methods and results Consecutive 1,061 patients who underwent PCI were divided into three groups based on PARIS thrombotic risk score; low- (n = 320), intermediate- (n = 469) and high-risk (n = 272) groups. We followed up on all three groups for all-cause mortality, cardiac mortality and hospitalization due to heart failure. Kaplan-Meier analysis showed that all outcomes were highest in the high-risk group (P < 0.001, P = 0.022 and P < 0.001, respectively). Multivariate Cox proportional hazard analysis, adjusted for confounding factors, showed that the risk of all-cause mortality and hospitalization due to heart failure of the high-risk group were higher than those of the low-risk group (hazard ratios 1.76 and 2.14, P = 0.005 and P = 0.017, respectively). Conclusion The PARIS thrombotic risk score is a significant prognostic indicator for all-cause mortality and hospitalization due to heart failure in patients after PCI.

Published
2022

49. Sporadic Cardiac Amyloidosis by Amyloidogenic Transthyretin V122I Variant

Author

Shinya Yamada, Kazuhiko Nakazato, Kazuaki Amami, Yuki Kanno, Hiroyuki Kunii, Tetsuro Yokokawa, Tomofumi Misaka, Yasuchika Takeishi, Takafumi Ishida, Masayoshi Oikawa, and Takeshi Nehashi

Subjects
Male, Tafamidis, Pathology, medicine.medical_specialty, 030204 cardiovascular system & hematology, Gene mutation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Prealbumin, 030212 general & internal medicine, Amyloid Neuropathies, Familial, Ejection fraction, biology, business.industry, Amyloidosis, nutritional and metabolic diseases, General Medicine, Middle Aged, medicine.disease, Transthyretin, Cardiac amyloidosis, chemistry, Heart failure, Mutation, biology.protein, Cardiomyopathies, Cardiology and Cardiovascular Medicine, business, Amyloid cardiomyopathy
Abstract

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.

Published
2019

50. The Fibrosis-4 Index Is Useful for Predicting Mortality in Patients with Pulmonary Hypertension due to Left Heart Disease

Author

Takuya Goto, Akiomi Yoshihisa, Kazuhiko Nakazato, Hiroyuki Kunii, Atsushi Kobayashi, Takafumi Ishida, Tomofumi Misaka, Takayoshi Yamaki, Tetsuro Yokokawa, Yasuchika Takeishi, Koichi Sugimoto, and Masayoshi Oikawa

Subjects
Adult, Male, medicine.medical_specialty, Anemia, Hypertension, Pulmonary, Renal function, Aspartate transaminase, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Severity of Illness Index, Statistics, Nonparametric, Cohort Studies, Hospitals, University, Ventricular Dysfunction, Left, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Cause of Death, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Aged, Proportional Hazards Models, Heart Failure, biology, business.industry, Proportional hazards model, General Medicine, Middle Aged, medicine.disease, Fibrosis, Survival Analysis, Pulmonary hypertension, Alanine transaminase, Heart failure, Cardiology, biology.protein, Female, Left heart disease, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Heart failure causes increased venous pressure, leading to liver dysfunction. The fibrosis-4 index is a simple index for liver fibrosis and has been reported to be useful for predicting prognosis in heart failure; however, its impact on patients with pulmonary hypertension due to left heart disease (PH-LHD) has not yet been fully elucidated.We enrolled consecutive 230 hospitalized patients who had been diagnosed as having PH-LHD. The fibrosis-4 index was calculated as follows: [aspartate transaminase (U/L) × age]/[alanine transaminase 1/2 (U/L) × platelet count (109/L) ]. We followed patients for all-cause mortality during the follow-up period (mean 1112 ± 822 days).The patients were divided into tertiles based on their fibrosis-4 index: the first tertile 0.335 to 1.381; the second tertile 1.391 to 2.311; and the third tertile 2.323 to 14.339. Compared with the first tertile, the third tertile had lower estimated glomerular filtration rates and hemoglobin levels. All-cause mortality was significantly higher in the third than in the first tertile. In a Cox proportional hazard model, the fibrosis-4 index was a predictor of all-cause mortality in PH-LHD patients (HR 1.212, 95% CI 1.099-1.337, P < 0.001).The fibrosis-4 index is associated with kidney function, anemia, and high mortality in PH-LHD patients.

Published
2019

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