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73 results on '"Chang, Yen"'

1. Predictive value of motor-evoked potentials for motor recovery in patients with hemiparesis secondary to acute ischemic stroke

Author

Cheng-Chang Yen, Hsin-Hung Chen, Chao-Hsien Lee, and Ching-Huang Lin

Subjects
Stroke, motor evoked potential, paretic limb, motor recovery, Medicine
Abstract

AbstractBackground Motor recovery following a stroke is related to the initial stroke severity and corticospinal tract integrity. One of the outcomes representing corticospinal tract integrity is the motor evoked potential (MEP). This study aimed to investigate the predictive value of MEP for motor recovery in patients with acute ischemic stroke.Patients and Methods Patients with hemiparesis secondary to initial acute ischemic stroke were enrolled. MEPs of the upper limb were assessed as preserved (MEP+) or absent (MEP-) response ≤10 days post-stroke. Fugl-Meyer assessment (FMA) was performed at baseline and post-stroke at 30 and 90 days. A modified Rankin scale (mRS) was conducted at 90 days post-stroke. Patients were divided into two groups according to the highest FMA score of MEP- patients. Generalized estimating equations and logistic regression were used for our study analysis.Results Sixty-one participants were included in this study. The highest FMA score of MEP- patients ≤10 days after stroke was 38. Among patients with an initial FMA score ≤38, FMA scores at 30 and 90 days post-stroke were significantly higher in MEP + patients than in MEP- patients. Proportional recovery at 30 and 90 days post-stroke was significantly higher in MEP + patients than in MEP- patients. MEP + patients had a higher percentage of good functional outcomes than MEP- patients, without statistical difference. Among patients with initial FMA score >38, FMA scores were 60.4 ± 4.8 and 63.9 ± 2.9 and proportional recovery was 65.2 ± 27.0% and 83.7 ± 24.6% at 30 and 90 days post-stroke, respectively.Conclusions Among patients with moderate-to-severe ischemic stroke, MEP + patients had better motor recoveries (approximately 70%) than MEP– patients at 90 days post-stroke. MEP + patients had better functional outcomes than MEP- patients.

Published
2023
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2. Integrating Citizen Scientist Data into the Surveillance System for Avian Influenza Virus, Taiwan

Author

Hong-Dar Isaac Wu, Ruey-Shing Lin, Wen-Han Hwang, Mei-Liang Huang, Bo-Jia Chen, Tseng-Chang Yen, and Day-Yu Chao

Subjects
avian influenza, citizen science, surveillance, risk map, spatial analysis, wild birds, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

The continuing circulation and reassortment with low-pathogenicity avian influenza Gs/Gd (goose/Guangdong/1996)-like avian influenza viruses (AIVs) has caused huge economic losses and raised public health concerns over the zoonotic potential. Virologic surveillance of wild birds has been suggested as part of a global AIV surveillance system. However, underreporting and biased selection of sampling sites has rendered gaining information about the transmission and evolution of highly pathogenic AIV problematic. We explored the use of the Citizen Scientist eBird database to elucidate the dynamic distribution of wild birds in Taiwan and their potential for AIV exchange with domestic poultry. Through the 2-stage analytical framework, we associated nonignorable risk with 10 species of wild birds with >100 significant positive results. We generated a risk map, which served as the guide for highly pathogenic AIV surveillance. Our methodologic blueprint has the potential to be incorporated into the global AIV surveillance system of wild birds.

Published
2023
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3. Automatic recognition of murmurs of ventricular septal defect using convolutional recurrent neural networks with temporal attentive pooling

Author

Jou-Kou Wang, Yun-Fan Chang, Kun-Hsi Tsai, Wei-Chien Wang, Chang-Yen Tsai, Chui-Hsuan Cheng, and Yu Tsao

Subjects
Medicine, Science
Abstract

Abstract Recognizing specific heart sound patterns is important for the diagnosis of structural heart diseases. However, the correct recognition of heart murmur depends largely on clinical experience. Accurately identifying abnormal heart sound patterns is challenging for young and inexperienced clinicians. This study is aimed at the development of a novel algorithm that can automatically recognize systolic murmurs in patients with ventricular septal defects (VSDs). Heart sounds from 51 subjects with VSDs and 25 subjects without a significant heart malformation were obtained in this study. Subsequently, the soundtracks were divided into different training and testing sets to establish the recognition system and evaluate the performance. The automatic murmur recognition system was based on a novel temporal attentive pooling-convolutional recurrent neural network (TAP-CRNN) model. On analyzing the performance using the test data that comprised 178 VSD heart sounds and 60 normal heart sounds, a sensitivity rate of 96.0% was obtained along with a specificity of 96.7%. When analyzing the heart sounds recorded in the second aortic and tricuspid areas, both the sensitivity and specificity were 100%. We demonstrated that the proposed TAP-CRNN system can accurately recognize the systolic murmurs of VSD patients, showing promising potential for the development of software for classifying the heart murmurs of several other structural heart diseases.

Published
2020
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4. Study of Asian indexes by a newly derived dynamic model

Author

Tsung-Jui Chiang-Lin, Yong-Shiuan Lee, Tzong-Hann Shieh, Chien-Chang Yen, and Shang-Yueh Tsai

Subjects
Medicine, Science
Abstract

We take the stock prices as a dynamic system and characterize its movements by a newly derived dynamic model, called the new Price Reversion Model (nPRM), for which the solution is derived and carefully analyzed under different circumstances. We also develop a procedure of applying the nPRM to real daily closing prices of a stock index. This proposed procedure brings a different perspective to the study of stock prices based on thermodynamics, and the time varying coefficients in the nPRM offer economic meanings of the stock movements. More specifically, the average of smoothed historical data A in the nPRM, analogous to the environment temperature in the Newton’s law of cooling, represent an implied equilibrium price. The heat transfer coefficient κ is adapted to be either negative or positive, which illustrates the speed of convergence or divergence of stock prices, respectively. The empirical study of ten Asian stock indexes shows that the nPRM accurately characterizes and forecasts the market values.

Published
2022

5. Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant.

Author

Yung-Chang Yen, Pei-Huan Chu, Po-Liang Lu, Yung-Cheng Lin, Yong-Ying Shi, Li-Chiu Chou, Chu-Feng Wang, Yi-Ying Lin, Hui-Ju Su, Chien-Ching Lin, Jing-Yun Zeng, Yu-Chang Tyan, Guan-Ming Ke, and Pei-Yu Chu

Subjects
Medicine, Science
Abstract

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

Published
2016
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6. Automatic recognition of murmurs of ventricular septal defect using convolutional recurrent neural networks with temporal attentive pooling

Author

Yun-Fan Chang, Jou-Kou Wang, Chui-Hsuan Cheng, Wei-Chien Wang, Yu Tsao, Chang-Yen Tsai, and Kun-Hsi Tsai

Subjects
Adult, Heart Defects, Congenital, Male, congenital, hereditary, and neonatal diseases and abnormalities, Systolic Murmurs, medicine.medical_specialty, Adolescent, Heart malformation, Science, Cardiology, Diseases, Heart Auscultation, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Internal medicine, Diagnosis, Humans, Medicine, cardiovascular diseases, Child, Sound (medical instrument), Multidisciplinary, Heart Murmurs, Artificial neural network, business.industry, Models, Cardiovascular, Health care, Signal Processing, Computer-Assisted, Cardiovascular diseases, Recurrent neural network, Child, Preschool, Heart sounds, Heart murmur, Female, Neural Networks, Computer, medicine.symptom, business, Software
Abstract

Recognizing specific heart sound patterns is important for the diagnosis of structural heart diseases. However, the correct recognition of heart murmur depends largely on clinical experience. Accurately identifying abnormal heart sound patterns is challenging for young and inexperienced clinicians. This study is aimed at the development of a novel algorithm that can automatically recognize systolic murmurs in patients with ventricular septal defects (VSDs). Heart sounds from 51 subjects with VSDs and 25 subjects without a significant heart malformation were obtained in this study. Subsequently, the soundtracks were divided into different training and testing sets to establish the recognition system and evaluate the performance. The automatic murmur recognition system was based on a novel temporal attentive pooling-convolutional recurrent neural network (TAP-CRNN) model. On analyzing the performance using the test data that comprised 178 VSD heart sounds and 60 normal heart sounds, a sensitivity rate of 96.0% was obtained along with a specificity of 96.7%. When analyzing the heart sounds recorded in the second aortic and tricuspid areas, both the sensitivity and specificity were 100%. We demonstrated that the proposed TAP-CRNN system can accurately recognize the systolic murmurs of VSD patients, showing promising potential for the development of software for classifying the heart murmurs of several other structural heart diseases.

Published
2020

7. Incidence of Severe Lead Poisoning in Children in Trinidad Resulting from Battery Recycling Operations

Author

I. Chang-Yen, A. Hosein-Rahaman, and C. Emrit

Subjects
business.industry, Battery recycling, Environmental health, Incidence (epidemiology), Medicine, Environmental pollution, Lead smelting, Chelation therapy, business, Lead–acid battery, medicine.disease, Elevated blood, Lead poisoning
Abstract

Lead poisoning in children has become a very topical issue, largely due to the realization that blood lead levels previously thought safe, could result in adverse long-term effects. In the Caribbean, cases of lead poisoning have been reported in Jamaica, involving children playing with discarded lead battery plates. Likewise, lead smelting and battery repair operations have resulted in elevated blood lead levels of children involved in, or living close to, these activities. This chapter is an example of severe environmental pollution that resulted from lead battery recycling operations, and subsequent toxicity to an entire extended family in Trinidad. Blood lead levels of the others showed that four other children suffered class V poisoning, requiring immediate medical and environmental management. Chelation therapy was administered to most of them, resulting in significant reduction in their blood lead levels.

Published
2020

8. Novel Mutations in the TMPRSS3 Gene may Contribute to Taiwanese Patients with Nonsyndromic Hearing Loss

Author

Swee-Hee Wong, Jiann-Jou Yang, Yung-Chang Yen, and Shuan-Yow Li

Subjects
Adult, Silent mutation, Adolescent, Xenopus, medicine.medical_treatment, Mutation, Missense, Taiwan, Deafness, medicine.disease_cause, Article, Catalysis, lcsh:Chemistry, Inorganic Chemistry, Serine, Young Adult, xenopus oocyte, medicine, otorhinolaryngologic diseases, Animals, Humans, Point Mutation, Missense mutation, Physical and Theoretical Chemistry, Child, lcsh:QH301-705.5, Molecular Biology, Gene, Spectroscopy, TMPRSS3, hearing loss, Serine protease, Genetics, Mutation, Protease, sGASP, biology, Serine Endopeptidases, Organic Chemistry, Intron, Membrane Proteins, General Medicine, Introns, Neoplasm Proteins, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, biology.protein, mutation
Abstract

A previous study indicated that mutations in the transmembrane protease serine 3 (TMPRSS3) gene, which encodes a transmembrane serine protease, cause nonsyndromic hearing loss (NSHL). This was the first description of a serine protease involved in hearing loss (HL). In Taiwan, however, data on the TMPRSS3 gene&rsquo, s association with NSHL is still insufficient. In this study, we described 10 mutations of TMPRSS3 genes found in 14 patients after screening 230 children with NSHL. The prevalence of the TMPRSS3 mutation appeared to be 6.09% (14/230). Of the 10 mutations, three were missense mutations: c.239G&gt, A (p.R80H), c.551T&gt, C (p.L184S), and 1253C&gt, T (p.A418V), three were silent mutations, and four were mutations in introns. To determine the functional importance of TMPRSS3 mutations, we constructed plasmids carrying TMPRSS3 mutations of p.R80H, p.L184S, and p.A418V. TMPRSS3 function can be examined by secretory genetic assay for site-specific proteolysis (sGASP) and Xenopus oocyte expression system. Our results showed that p.R80H, p.L184S, and p.A418V TMPRSS3 mutations gave ratios of 19.4%, 13.2%, and 27.6%, respectively, via the sGASP system. Moreover, these three TMPRSS3 mutations failed to activate the epithelial sodium channel (ENaC) in the Xenopus oocyte expression system. These results indicate that the p.R80H, p.L184S, and p.A418V missense mutations of TMPRSS3 resulted in greatly diminishing the proteolytic activity of TMPRSS3. Our study provides information for understanding the importance of TMPRSS3 in the NSHL of Taiwanese children and provides a novel molecular explanation for the role of TMPRSS3 in HL.

Published
2020
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9. Renal function is associated with 1-month and 1-year mortality in patients with ischemic stroke

Author

I-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Sheng-Feng Sung, Pai-Hao Huang, Jie-Yuan Li, Yu Sun, Cheng-Yu Wei, Li-Ming Lien, I-Ju Tsai, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyu, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Chih-Hao Chen, Hsin-Hsi Tsai, Han-Jung Chen, Kan Lu, Shih-Pin Hsu, Hung-Chang Kuo, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Meng-Tsang Hsieh, Po-Chao Liliang, Cheng-Loong Liang, Hao-Kuang Wang, Yu-Tun Tsai, Kuo-Wei Wang, Jui-Sheng Chen, Po-Yuan Chen, Yi-Ching Wang, Chih-Hung Chen, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Ruey-Tay Lin, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Huey-Juan Lin, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, An-Chih Chen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Wei-Lun Chang, Pai-Yi Chiu, Min-Hsien Hsu, Po-Chi Chan, Chau-Hsiung Pan, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Wei-Chieh Chang, Ta-Chang Lai, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Siu-Pak Lee, Ming-Hui Sun, Li-Ying Ke, Po-Lin Chen, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiunn-Tay Lee, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu- Hua Lai, Chun-I. Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Tsuey-Ru Chiang, Pin-Wen Liao, Mei-Ching Lee, Jen-Tse Chen, Sian-King Lie, Mu-Chien Sun, Pi-Ju Hsiao, Wei-Liang Chen, Ta-Cheng Chen, Chen-Shu Chang, Chien-Hsu Lai, Chieh-Sen Chuang, Yen-Yu Chen, Shinn-Kuang Lin, Yu-Chin Su, Jen-Lun Shiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Guei-Chiuan Chen, Po-Jen Hsu, Chun-Yuan Chang, I.-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I. Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau-Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Chao-Hsien Hung, Chia Fang Lee, Sheng-Kung Yang, Chih-Lin Chen, Wei Lin, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Lung Chan, Nai-Fang Chi, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E. Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Cheng-Yang Hsieh, Wei-Fen Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Kun-Chang Tsai, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Adult, Male, Stroke registry, medicine.medical_specialty, Time Factors, Adolescent, Taiwan, Renal function, 030204 cardiovascular system & hematology, Kidney, Risk Assessment, Brain Ischemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, In patient, Registries, Risk factor, Stroke, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Middle Aged, Prognosis, medicine.disease, Ischemic stroke, Cardiology, Female, Kidney Diseases, Cardiology and Cardiovascular Medicine, business, 1 year mortality, 030217 neurology & neurosurgery, Glomerular Filtration Rate
Abstract

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Published
2018

10. Screening of peptide libraries against protective antigen of Bacillus anthracis in a disposable microfluidic cartridge.

Author

Joshua M Kogot, Yanting Zhang, Stephen J Moore, Paul Pagano, Dimitra N Stratis-Cullum, David Chang-Yen, Marek Turewicz, Paul M Pellegrino, Andre de Fusco, H Tom Soh, and Nancy E Stagliano

Subjects
Medicine, Science
Abstract

Bacterial surface peptide display has gained popularity as a method of affinity reagent generation for a wide variety of applications ranging from drug discovery to pathogen detection. In order to isolate the bacterial clones that express peptides with high affinities to the target molecule, multiple rounds of manual magnetic activated cell sorting (MACS) followed by multiple rounds of fluorescence activated cell sorting (FACS) are conventionally used. Although such manual methods are effective, alternative means of library screening which improve the reproducibility, reduce the cost, reduce cross contamination, and minimize exposure to hazardous target materials are highly desired for practical application. Toward this end, we report the first semi-automated system demonstrating the potential for screening bacterially displayed peptides using disposable microfluidic cartridges. The Micro-Magnetic Separation platform (MMS) is capable of screening a bacterial library containing 3 × 10¹⁰ members in 15 minutes and requires minimal operator training. Using this system, we report the isolation of twenty-four distinct peptide ligands that bind to the protective antigen (PA) of Bacilus anthracis in three rounds of selection. A consensus motif WXCFTC was found using the MMS and was also found in one of the PA binders isolated by the conventional MACS/FACS approach. We compared MMS and MACS rare cell recovery over cell populations ranging from 0.1% to 0.0000001% and found that both magnetic sorting methods could recover cells down to 0.0000001% initial cell population, with the MMS having overall lower standard deviation of cell recovery. We believe the MMS system offers a compelling approach towards highly efficient, semi-automated screening of molecular libraries that is at least equal to manual magnetic sorting methods and produced, for the first time, 15-mer peptide binders to PA protein that exhibit better affinity and specificity than peptides isolated using conventional MACS/FACS.

Published
2011
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11. Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients

Author

I.-Kuan Wang, Chung-Hsiang Liu, Tzung-Hai Yen, Jiann-Shing Jeng, Shih-Pin Hsu, Chih-Hung Chen, Li-Ming Lien, Ruey-Tay Lin, An-Chih Chen, Huey-Juan Lin, Hsin-Yi Chi, Ta-Chang Lai, Yu Sun, Siu-Pak Lee, Sheng-Feng Sung, Po-Lin Chen, Jiunn-Tay Lee, Tsuey-Ru Chiang, Shinn-Kuang Lin, Chih-Hsin Muo, Henry Ma, Chi-Pang Wen, Fung-Chang Sung, Chung Y. Hsu, Chon-Haw Tsai, Wei-Shih Huang, Chung-Ta Lu, Tzung-Chang Tsai, Chun-Hung Tseng, Kang-Hsu Lin, Woei-Cherng Shyn, Yu-Wan Yang, Yen-Liang Liu, Der-Yang Cho, Chun-Chung Chen, Sung-Chun Tang, Li-Kai Tsai, Shin-Joe Yeh, Han-Jung Chen, Cheng-Sen Chang, Hung-Chang Kuo, Lian-Hui Lee, Huan-Wen Tsui, Jung-Chi Tsou, Yan-Tang Wang, Yi-Cheng Tai, Kun-Chang Tsai, Yen-Wen Chen, Kan Lu, Po-Chao Liliang, Yu-Tun Tsai, Cheng-Loong Liang, Kuo-Wei Wang, Hao-Kuang Wang, Jui-Sheng Chen, Po-Yuan Chen, Cien-Leong Chye, Wei-Jie Tzeng, Pei-Hua Wu, Pi-Shan Sung, Han-Chieh Hsieh, Hui-Chen Su, Hou-Chang Chiu, Wei-Hung Chen, Chyi-Huey Bai, Tzu-Hsuan Huang, Chi-Ieong Lau, Ya-Ying Wu, Hsu-Ling Yeh, Anna Chang, Ching-Huang Lin, Cheng-Chang Yen, Chun-Hung Chen, Gim-Thean Khor, A-Ching Chao, Hsiu-Fen Lin, Poyin Huang, Der-Shin Ke, Chia-Yu Chang, Poh-Shiow Yeh, Kao-Chang Lin, Tain-Junn Cheng, Chih-Ho Chou, Chun-Ming Yang, Hsiu-Chu Shen, Shih-Jei Tsai, Tsong-Ming Lu, Sheng-Ling Kung, Mei-Ju Lee, Hsi-Hsien Chou, Chou-Hsiung Pan, Po-Chi Chan, Min-Hsien Hsu, Wei-Lun Chang, Zhi-Zang Huang, Hai-Ming Shoung, Yi-Chen Lo, Fu-Hwa Wang, Jiu-Haw Yin, Chung-Jen Wang, Kai-Chen Wang, Li-Mei Chen, Jong-Chyou Denq, Chien-Jung Lu, Cheng-Huai Lin, Chieh-Cheng Huang, Chang-Hsiu Liu, Hoi-Fong Chan, Ming-Hui Sun, Li-Ying Ke, Yu-Shan Lee, Cheung-Ter Ong, Chi-Shun Wu, Yung-Chu Hsu, Yu-Hsiang Su, Ling-Chien Hung, Jiann-Chyun Lin, Yaw-Don Hsu, Giia-Sheun Peng, Chang-Hung Hsu, Chun-Chieh Lin, Che-Hung Yen, Chun-An Cheng, Yueh-Feng Sung, Yuan-Liang Chen, Ming-Tung Lien, Chung-Hsing Chou, Chia-Chen Liu, Fu-Chi Yang, Yi-Chung Wu, An-Chen Tso, Yu-Hua Lai, Chun-I Chiang, Chia-Kuang Tsai, Meng-Ta Liu, Ying-Che Lin, Yu-Chuan Hsu, Mei-Ching Lee, Pai-Hao Huang, Sian-King Lie, Pin-Wen Liao, Jen-Tse Chen, Mu-Chien Sun, Tien-Pao Lai, Wei-Liang Chen, Yen-Chun Chen, Ta-Cheng Chen, Wen-Fu Wang, Kwo-Whei Lee, Chen-Shu Chang, Chien-Hsu Lai, Siao-Ya Shih, Chieh-Sen Chuang, Yen-Yu Chen, Chien-Min Chen, Yu-Chin Su, Cheng-Lun Hsiao, Fu-Yi Yang, Chih-Yang Liu, Han-Lin Chiang, Chun-Yuan Chang, I-sheng Lin, Chung-Hsien Chien, Yang-Chuang Chang, Ping-Kun Chen, Pai-Yi Chiu, Yu-Jen Hsiao, Chen-Wen Fang, Yu-Wei Chen, Kuo-Ying Lee, Yun-Yu Lin, Chen-Hua Li, Hui-Fen Tsai, Chuan-Fa Hsieh, Chih-Dong Yang, Shiumn-Jen Liaw, How-Chin Liao, Shoou-Jeng Yeh, Ling-Li Wu, Liang-Po Hsieh, Yong-Hui Lee, Chung-Wen Chen, Chih-Shan Hsu, Ye-Jian Jhih, Hao-Yu Zhuang, Yan-Hong Pan, Shin-An Shih, Chin-I Chen, Jia-Ying Sung, Hsing-Yu Weng, Hao-Wen Teng, Jing-Er Lee, Chih-Shan Huang, Shu-Ping Chao, Rey-Yue Yuan, Jau- Jiuan Sheu, Jia-Ming Yu, Chun-Sum Ho, Ting-Chun Lin, Shih-Chieh Yu, Jiunn-Rong Chen, Song-Yen Tsai, Cheng-Yu Wei, Chao-Nan Yang, Chao-Hsien Hung, Ian Shih, Hung-Pin Tseng, Chin-Hsiung Liu, Chun-Liang Lin, Hung-Chih Lin, Pi-Tzu Chen, Chaur-Jong Hu, Nai-Fang Chi, Lung Chan, Chang-Ming Chern, Chun-Jen Lin, Shuu-Jiun Wang, Li-Chi Hsu, Wen-Jang Wong, I-Hui Lee, Der-Jen Yen, Ching-Piao Tsai, Shang-Yeong Kwan, Bing-Wen Soong, Shih-Pin Chen, Kwong-Kum Liao, Kung-Ping Lin, Chien Chen, Din-E Shan, Jong-Ling Fuh, Pei-Ning Wang, Yi-Chung Lee, Yu-Hsiang Yu, Hui-Chi Huang, Jui-Yao Tsai, Ming-Hsiu Wu, Shi-Cheng Chen, Szu-Yi Chiang, Chiung-Yao Wang, Ming-Chin Hsu, Chien-Chung Chen, Po-Yen Yeh, Yu-Tai Tsai, Ko-Yi Wang, Tsang-Shan Chen, Ping-Keung Yip, Vinchi Wang, Kaw-Chen Wang, Chung-Fen Tsai, Chao-Ching Chen, Chih-Hao Chen, Yi-Chien Liu, Shao-Yuan Chen, Zi-Hao Zhao, Zhi-Peng Wei, Shey-Lin Wu, Ching-Kuan Liu, Ryh-Huei Lin, Ching-Hua Chu, Sui-Hing Yan, Yi-Chun Lin, Pei-Yun Chen, Sheng-Huang Hsiao, Bak-Sau Yip, Pei-Chun Tsai, Ping-Chen Chou, Tsam-Ming Kuo, Yi-Chen Lee, Yi-Pin Chiu, Yi-Sheng Liao, Ming-Jun Tsai, and Hsin-Yi Kao

Subjects
Male, Stroke registry, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Taiwan, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Dialysis patients, Brain Ischemia, 03 medical and health sciences, chemistry.chemical_compound, Patient Admission, 0302 clinical medicine, Renal Dialysis, Risk Factors, Internal medicine, medicine, Humans, Registries, Serum cholesterol, Dialysis, Aged, Proportional Hazards Models, Aged, 80 and over, Cholesterol, business.industry, Mortality rate, Rehabilitation, Middle Aged, Prognosis, Stroke, chemistry, 30 day mortality, Ischemic stroke, Cardiology, Kidney Failure, Chronic, Female, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Published
2017

12. An Application of NGS for WDR36 Gene in Taiwanese Patients with Juvenile-Onset Open-Angle Glaucoma

Author

Hsuan-An Su, Yung-Chang Yen, Jiann-Jou Yang, and Shuan-Yow Li

Subjects
medicine.medical_specialty, education.field_of_study, Open angle glaucoma, business.industry, Population, Glaucoma, General Medicine, Disease, medicine.disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Juvenile onset, Polymorphism (computer science), Ophthalmology, 030221 ophthalmology & optometry, medicine, education, business, Gene
Abstract

Primary open-angle glaucoma (POAG) is one of the most important disease in ophthalmology with high prevalence and risk of irreversible blindness. If diagnosed before the age of 35, it is usually categorized as juvenile open-angle glaucoma (JOAG). The WDR36 gene is reckoned as one of the major causative genes of POAG, and had been studied to be related to the pathogenesis of POAG in the literature. We have selected 61 JOAG patients and 61 JOAG-free individuals, and by next-generation sequencing method, the WDR36 gene of the subjects were analyzed. We identified 26 variations exclusively in JOAG group. Among these 26 variations, there were 3 noteworthy variations. First, a novel variation c.460-650A>G was found in our study which might cause premature termination of splicing of the conserved domain in WDR36; second, c.1494+1111G>T (rs13178997) had significantly different frequency in our JOAG patients compared to the reference frequency on NCBI; third, a variation c.710+30C>T (rs10038177) was found in our study, which had already been reported to be related to high-pressure glaucoma. We offer the profile of WDR36 in JOAG in Taiwan population, and we suggest that WDR36 gene is involved in the pathogenesis of JOAG as a subordinate modifier gene.

Published
2017

13. Ferulic acid-mediated protection against neomycin-induced hair cell loss in transgenic zebrafish

Author

Shuan-Yow Li, Tsai-Ching Hsu, Yung-Chang Yen, Ju Chang-Chien, and Jiann-Jou Yang

Subjects
0301 basic medicine, Transgene, Medicine (miscellaneous), Biology, Green fluorescent protein, 03 medical and health sciences, 0302 clinical medicine, Ototoxicity, medicine, Inner ear, TX341-641, Nutrition and Dietetics, Nutrition. Foods and food supply, Neomycin, Anatomy, Ferulic acid, medicine.disease, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Sensorineural hearing loss, Hair cell, 030217 neurology & neurosurgery, Intracellular, Transgenic zebrafish, Food Science, medicine.drug
Abstract

Ferulic acid (FA) derivatives have applied in American clinical trials for preventing and treating auditory dysfunctions. However, the effects of FA on neomycin-mediated sensorineural hearing loss are still unknown. We developed a transgenic zebrafish ( pvalb3b:TagGFP ) expressing green-colored hair cells in the inner ear and lateral line neuromasts by Tol2 system. Then, we determined the effects of FA on neomycin-induced ototoxicity in 4 dpf transgenic larvae. FA conferred significant protection against hair cell loss across a wide range of neomycin concentrations. In addition, FA significantly decreased intracellular ROS production and TUNAL reactions in larvae pretreated with FA prior to neomycin exposure. These findings suggest that FA has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. The green hair cells of transgenic zebrafish lateral line may provide a useful basis on which to investigate the cellular pathways related to the hair cell death and survival imparted by FA.

Published
2017

14. A Randomized Controlled Trial Comparing the Efficacy of P6 Acupuncture Plus Ondansetron versus Ondansetron or P6 Acupuncture in the Prevention of Nausea and Vomiting after Bupivacaine-Morphine Spinal Anesthesia

Author

Lídia Raquel de Carvalho, Paulo do Nascimento Junior, Wei Tzon Hackan Chang Colares, Marilia P. Modolo, José Reinaldo Cerqueira Braz, Norma Sueli Pinheiro Módolo, and Chang Yen Yin

Subjects
Bupivacaine, medicine.medical_specialty, Nausea, business.industry, Surgery, law.invention, Ondansetron, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, 030220 oncology & carcinogenesis, Anesthesia, Vomiting, medicine, Post-anesthesia care unit, Acupuncture, medicine.symptom, business, Postoperative nausea and vomiting, medicine.drug
Abstract

Objective: To compare P6 acupuncture plus ondansetron with either ondansetron or P6 acupuncture in the prevention of postoperative nausea and vomiting (PONV) in patients submitted to spinal anesthesia. Methods: A randomized controlled trial was performed with 90 patients undergoing orthopedic surgery under spinal anesthesia with bupivacaine, 15 to 17.5 mg, and morphine, 100 μg. They were assigned to one of the three groups: Group Ondansetron (n = 30), patients were given ondansetron, 8 mg intravenously, before spinal block was performed; Group P6 acupuncture (n = 30), patients were subjected to bilateral electrical stimulation of P6 acupoint for 30 minutes before anesthesia; and Group P6 acupuncture plus ondansetron (n = 30), the exact combination of the groups Ondansetron and P6 acupuncture. Results: In the post anesthesia care unit, the incidence of nausea and vomiting ranged from 13.3% to 26.7% and from 6.7% to 13.3%, respectively, with no significant differences among groups (p > 0.05). Ondansetron group had the highest incidence of nausea (73.3%) (p < 0.001) and vomiting (43.3%) (p < 0.001) at the ward from 0 to 24 hours, followed by P6 acupuncture (33.3% and 26.7%) and P6 acupuncture plus ondansetron groups (16.0% and 0%). Conclusion: Preoperative stimulation of P6 acupoint in combination with ondansetron has higher efficacy than either P6 acupoint stimulation or the administration of ondansetron on the prevention of PONV in patients submitted to bupivacaine-morphine spinal anesthesia.

Published
2017

15. Mobile community learning programme's effectiveness in case management for psychiatric nurses: A preliminary randomised controlled trial

Author

Chien Hung Liu, Chang Yen Liao, Pei Ru Chao, Kuo Chung Chu, and Wen-I Liu

Subjects
Adult, medicine.medical_specialty, Taiwan, Psychiatric Nursing, Education, law.invention, Teaching hospital, Education, Distance, 03 medical and health sciences, 0302 clinical medicine, Education, Nursing, Continuing, Randomized controlled trial, Mobile community, law, Surveys and Questionnaires, medicine, Global health, Humans, 030212 general & internal medicine, Psychiatry, Competence (human resources), General Nursing, 030504 nursing, Continuing education, Middle Aged, Case management, Female, 0305 other medical science, Psychology, Case Management, Experience sharing
Abstract

The global health care system has applied case management (CM) as a care delivery service provided by nurses. Nurses require continuing education in CM to enhance their professional knowledge and competence. Mobile communities have been used to promote continuing education for medical professionals. However, limited studies have examined the effectiveness of such learning programmes in CM for psychiatric nurses.To evaluate the effectiveness of a mobile community learning (MCL) programme in CM for psychiatric nurses.This study used an experimental two-group pre- and post-test design.Psychiatric nurses employed in a psychiatric teaching hospital situated in northern Taiwan were recruited.Nurses were randomly allocated to the experimental or comparison group. The former participated in the learning intervention in CM. The CM knowledge index and a competence scale were used to determine outcomes. Pre-tests and 2-month post-tests were conducted. The MCL programme comprised five simulated learning modules, self-assessment questions, learning cases, learning resources and experience sharing. A two-way repeated-measures analysis of variance was performed to evaluate the effect of the intervention on target outcomes.The questionnaires were completed by 48 participants. The two groups possessed high homogeneity with regard to characteristics and pre-test outcomes. Differences between the two groups regarding CM knowledge (F = 22.99, p .01) and competence (F = 6.33, p = .015) were significant. The programme had a positive benefit on the learning experience in the experimental group; the mean satisfaction score for the programme reached 4.27 (range, 1-5).MCL programmes for psychiatric nurses can effectively enhance CM knowledge and competence. However, these methods cannot completely replace the continuing education approach for achieving CM competence.

Published
2019

16. An Ultra-sensitive Electrochemical Sensor for the Detection of Oxidative Stress Biomarker 3-Nitro-l-tyrosine in Human Blood Serum and Saliva Samples Based on Reduced Graphene Oxide Entrapped Zirconium (IV) Oxide

Author

Tse-Wei Chen, Bih-Show Lou, Elayappan Tamilalagan, Selvarasu Maheshwaran, Shen-Ming Chen, Chang Yen Tzu, and Muthumariappan Akilarasan

Subjects
Saliva, Zirconium, Chromatography, Renewable Energy, Sustainability and the Environment, Graphene, Chemistry, Oxide, chemistry.chemical_element, Condensed Matter Physics, medicine.disease_cause, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Electrochemical gas sensor, law.invention, chemistry.chemical_compound, Biomarker, law, Materials Chemistry, Electrochemistry, medicine, Oxidative stress, Ultra sensitive
Published
2020

17. Metabolic risk factors are associated with non-hepatitis B non-hepatitis C hepatocellular carcinoma in Taiwan, an endemic area of chronic hepatitis B

Author

Cheng-Chung Tsai, Chih-Chen Hong, Yung-Ming Jeng, Shiu-Feng Huang, Il-Chi Chang, Cheng-Chung Wu, Hock-Liew Eng, Chao-Long Chen, Ming-Chih Ho, John Wang, Chi-Ling Chen, Hui-Hwa Tseng, Ying-Ying Shen, Tseng-Chang Yen, Yun-Fan Liaw, Hsien-Chung Yu, Chau-Ting Yeh, Wei-Chen Lee, and Pei-Jer Chen

Subjects
medicine.medical_specialty, Cirrhosis, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, neoplasms, Hepatitis B virus, Hepatology, business.industry, Fatty liver, virus diseases, Hepatitis C, Original Articles, Hepatitis B, medicine.disease, digestive system diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Original Article, business, Liver cancer
Abstract

Metabolic risk factors, such as obesity, fatty liver, high lipidemia, and diabetes mellitus are associated with increased risk for nonviral hepatocellular carcinoma (HCC); however, few nonviral HCC studies have stratified patients according to underlying etiologies. From 2005 to 2011, 3,843 patients with HCC were recruited into the Taiwan Liver Cancer Network. Of these patients, 411 (10.69%) who were negative for hepatitis B virus (HBV), surface antigen, HBV DNA, and anti-hepatitis C virus (HCV) antibody were classified as non-HBV non-HCV (NBNC)-HCC. Detailed clinical analyses of these patients were compared with age- and sex-matched patients with HBV-HCC or HCV-HCC for the associated metabolic risk factors. For this comparison, 420 patients with HBV-HCC and 420 patients with HCV-HCC were selected from the 3,843 patients with HCC. Multivariate analyses showed fatty liver (by echography), high triglyceride levels (>160 mg/dL), and diabetes mellitus history to be significantly associated only with NBNC-HCC and not with the matched patients with HBV- or HCV-HCC. When the patients with HCC were further divided into four groups based on history of alcoholism and cirrhotic status, the group without alcoholism and without cirrhosis exhibited the strongest association with the metabolic risk factors. Based on trend analyses, patients with NBNC-HCC with or without alcoholism were significantly different from the matched patients with HBV- or HCV-HCC, except for patients with alcoholism and cirrhosis, in having more than two of the above three risk factors. Conclusion: Metabolic risk factors are significantly associated with nonviral HCC, especially for patients without alcoholism in Taiwan. Because the prevalence of viral HCC is decreasing due to the success of universal vaccination and antiviral therapy, strategies for cancer prevention, prediction, and surveillance for HCC will require modification. (Hepatology Communications 2018;2:747-759).

Published
2018

18. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author

Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johannes, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inês, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Markus, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, McKenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr. , W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang H, Knowles J, Hlatky M, Fortmann S, Assimes TL, Quertermous T, Go A, Iribarren C, Absher D, Risch N, Meyers R, Sidney S, Ziegler A, Schillert A, Bickel C, Sinning C, Rupprecht HJ, Lackner K, Wild P, Schnabel R, Blankenberg S, Zeller T, Münzel T, Perret C, Cambien F, Tiret L, Nicaud V, Proust C, Dehghan A, Hofman A, Uitterlinden A, van Duijn C, Levy D, Whitteman J, Cupples LA, Demissie-Banjaw S, Ramachandran V, Smith A, Gudnason V, Boerwinkle E, Folsom A, Morrison A, Psaty BM, Chen IY, Rotter JI, Bis J, Volcik K, Rice K, Taylor KD, Marciante K, Smith N, Glazer N, Heckbert S, Harris T, Lumley T, Kong A, Thorleifsson G, Thorgeirsson G, Holm H, Gulcher JR, Stefansson K, Andersen K, Gretarsdottir S, Thorsteinsdottir U, Preuss M, Schreiber S, Meitinger T, König IR, Lieb W, Hengstenberg C, Schunkert H, Erdmann J, Fisher M, Grosshennig A, Medack A, Stark K, Linsel-Nitschke P, Bruse P, Aherrahrou Z, Peters A, Loley C, Willenborg C, Nahrstedt J, Freyer J, Gulde S, Doering A, Meisinger C, Wichmann HE, Klopp N, Illig T, Meinitzer A, Tomaschitz A, Halperin E, Dobnig H, Scharnagl H, Kleber M, Laaksonen R, Pilz S, Grammer TB, Stojakovic T, Renner W, März W, Böhm BO, Winkelmann BR, Winkler K, Hoffmann M, O'Donnell CJ, Voight BF, Altshuler D, Siscovick DS, Musunuru K, Peltonen L, Barbalic M, Melander O, Elosua R, Kathiresan S, Schwartz SM, Salomaa V, Guiducci C, Burtt N, Gabriel SB, Stewart AF, Wells GA, Chen L, Jarinova O, Roberts R, McPherson R, Dandona S, Pichard AD, Rader DJ, Devaney J, Lindsay JM, Kent KM, Qu L, Satler L, Burnett MS, Li M, Reilly MP, Wilensky R, Waksman R, Epstein S, Mattha W, Knouf CW, Waterworth DM, Hakonarson HH, Walker M, Mooser V, Hall AS, Balmforth AJ, Wright BJ, Nelson C, Thompson JR, Samani NJ, Braund PS, Ball SG, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, Stricker B, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Uitterlinden AG, Willerson JT, van Duijn CM, Witteman JC, Vasan RS, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Parsa A, Gao X, Yang Q, Smith AV, O'Connell JR, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson A, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria, Francesco, Metter J, de Boer J, Siscovick D, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turne ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Vasan R, Felix SB, Watzinger N, Larson MG, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Stricker BH, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Arnett D, Blettner M, Friedrich N, Benjamin EJ, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic T, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Abecasis GR, Lightstone L, Scott J, Navis G, Elliot P, Kooner JS., AII - Amsterdam institute for Infection and Immunity, Nephrology, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Epidemiology, Medical Microbiology & Infectious Diseases, Radiology & Nuclear Medicine, Cardiology, Internal Medicine, Clinical Genetics, Erasmus MC other, Obstetrics & Gynecology, International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Clinical Pharmacology and The Genome Centre, Queen Mary University of London (QMUL), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Program in Medical and Population Genetics, Harvard University-Massachusetts Institute of Technology (MIT), Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'An, Arora, Pankaj, Dehghan, Abba, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, Mcardle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthia, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johanne, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inê, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Marku, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margu, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Mckenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thoma, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, Jame, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr., W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Ander, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcu, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Pano, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Jano, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charle, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Mari, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang, H, Knowles, J, Hlatky, M, Fortmann, S, Assimes, Tl, Quertermous, T, Go, A, Iribarren, C, Absher, D, Risch, N, Meyers, R, Sidney, S, Ziegler, A, Schillert, A, Bickel, C, Sinning, C, Rupprecht, Hj, Lackner, K, Wild, P, Schnabel, R, Blankenberg, S, Zeller, T, Münzel, T, Perret, C, Cambien, F, Tiret, L, Nicaud, V, Proust, C, Dehghan, A, Hofman, A, Uitterlinden, A, van Duijn, C, Levy, D, Whitteman, J, Cupples, La, Demissie-Banjaw, S, Ramachandran, V, Smith, A, Gudnason, V, Boerwinkle, E, Folsom, A, Morrison, A, Psaty, Bm, Chen, Iy, Rotter, Ji, Bis, J, Volcik, K, Rice, K, Taylor, Kd, Marciante, K, Smith, N, Glazer, N, Heckbert, S, Harris, T, Lumley, T, Kong, A, Thorleifsson, G, Thorgeirsson, G, Holm, H, Gulcher, Jr, Stefansson, K, Andersen, K, Gretarsdottir, S, Thorsteinsdottir, U, Preuss, M, Schreiber, S, Meitinger, T, König, Ir, Lieb, W, Hengstenberg, C, Schunkert, H, Erdmann, J, Fisher, M, Grosshennig, A, Medack, A, Stark, K, Linsel-Nitschke, P, Bruse, P, Aherrahrou, Z, Peters, A, Loley, C, Willenborg, C, Nahrstedt, J, Freyer, J, Gulde, S, Doering, A, Meisinger, C, Wichmann, He, Klopp, N, Illig, T, Meinitzer, A, Tomaschitz, A, Halperin, E, Dobnig, H, Scharnagl, H, Kleber, M, Laaksonen, R, Pilz, S, Grammer, Tb, Stojakovic, T, Renner, W, März, W, Böhm, Bo, Winkelmann, Br, Winkler, K, Hoffmann, M, O'Donnell, Cj, Voight, Bf, Altshuler, D, Siscovick, D, Musunuru, K, Peltonen, L, Barbalic, M, Melander, O, Elosua, R, Kathiresan, S, Schwartz, Sm, Salomaa, V, Guiducci, C, Burtt, N, Gabriel, Sb, Stewart, Af, Wells, Ga, Chen, L, Jarinova, O, Roberts, R, Mcpherson, R, Dandona, S, Pichard, Ad, Rader, Dj, Devaney, J, Lindsay, Jm, Kent, Km, Qu, L, 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H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliot, P, and Kooner, Js.

Subjects
novel loci, Kidney Disease, Polymorphism, Single Nucleotide/*genetics, [SDV]Life Sciences [q-bio], left ventricular wall thickness, LOCI, Genome-wide association study, Blood Pressure, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, RELEVANCE, Africa/ethnology, Cardiovascular Disease, genetics, Kidney Diseases/genetics, Stroke, genome wide association study, POPULATION, ta118, Blood pressure, hypertension, stroke, coronary artery disease, ddc:616, 0303 health sciences, education.field_of_study, Asia/ethnology, Multidisciplinary, Coronary Artery Disease/genetics, COMMON VARIANTS, Genetic Predisposition to Disease/*genetics, 3. Good health, Europe, Cardiovascular Diseases, Hypertension, Cardiology, Kidney Diseases, HEALTH, Human, medicine.medical_specialty, Asia, Population, Renal function, Polymorphism, Single Nucleotide, Europe/ethnology, Article, CLONING, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Stroke/genetics, Internal medicine, medicine, Humans, Cardiovascular Diseases/*genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, METAANALYSIS, 030304 developmental biology, RECEPTOR, genes, blood pressure, cardiovascular disease risk, medicine.disease, Africa, Blood Pressure/*genetics/physiology, Hypertension/genetics, Kidney disease, Genome-Wide Association Study
Abstract

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published

Published
2011

20. Effect of metformin on the incidence of head and neck cancer in diabetics

Author

Charlene Lin, Shih Wei Lin, Shih-Feng Weng, Yung Chang Yen, and Yong-Song Lin

Subjects
Oncology, medicine.medical_specialty, business.industry, Head and neck cancer, Hazard ratio, Cancer, medicine.disease, Lower risk, Metformin, Otorhinolaryngology, Nasopharyngeal carcinoma, Internal medicine, Diabetes mellitus, Cohort, medicine, business, medicine.drug
Abstract

Background The purpose of this study was to examine the effect of metformin on head and neck cancer in patients with diabetes. Methods We compared 66,600 patients, all with diabetes and all newly diagnosed with head and neck cancer in 2002. Half were being treated with metformin for diabetes (Met+) and half were not (Met−: controls). All were matched for comorbidities (obesity, coronary artery disease, hyperlipidemia, and hypertension), sex, and age. The risk of head and neck cancer at the end of 2011 was determined. Results The incidence of head and neck cancer was 34% lower in the Met+ cohort than in the Met− cohort (adjusted hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.55–0.79). The risks for oropharyngeal cancer (adjusted HR = 0.66; 95% CI = 0.17–0.74) and nasopharyngeal carcinoma (NPC; adjusted HR = 0.50; 95% CI = 0.31–0.80) were significantly lower in the Met+ cohort than in the Met− cohort. Conclusion Metformin is associated with a lower risk of developing head and neck cancer in patients with diabetes. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1268–1273, 2015

Published
2014

21. AB032. S7-3. Introduction of Taiwan Liver Cancer Network

Author

Pei-Jer Chen, Tseng-Chang Yen, Chi-Ling Chen, Shiu-Feng Huang, Il-Chi Chang, and Yun-Fan Liaw

Subjects
Oncology, medicine.medical_specialty, Speaker Abstracts, business.industry, Internal medicine, Medicine, business, Liver cancer, medicine.disease, Biobank
Abstract

Liver cancers and lung cancer are the 2 leading cancer deaths in Taiwan. Thus, these 2 cancers are the most important cancers in Taiwan, and both have been chosen as the main target diseases by National Research Program for Genomic Medicine. For Liver cancers, only the early stage patients (10. Since TLCN has become NHRI Biobank, which is supported by Government fund and has been approved by the Ministry of Health and Welfare, it can accept the application not only from the scientists, but also the industries directly. The final goal of this project is to improve the treatment and survival of liver cancer patients in Taiwan through successful researches in the liver carcinogenetic mechanism, prevention, screening, early detection and therapies.

Published
2019

22. The role of autonomic nervous system function in hypothermia-mediated sepsis protection

Author

Chih-Hsiang Kao, Yun-Te Chang, Hong-Tai Chang, Jung-Shun Tsai, Po-Tsang Lee, Mu-Shun Huang, Neng-Chyan Huang, Cheng-Chang Yen, and Shue-Ren Wann

Subjects
Male, Cyclophosphamide, Post injection, Autonomic Nervous System, medicine.disease_cause, Severity of Illness Index, Rats, Sprague-Dawley, Sepsis, Electrocardiography, Random Allocation, Heart Rate, Hypothermia, Induced, medicine, Animals, Heart rate variability, High severity, business.industry, General Medicine, Staphylococcal Infections, Hypothermia, medicine.disease, Rats, Disease Models, Animal, Autonomic nervous system, Logistic Models, Staphylococcus aureus, Anesthesia, Multivariate Analysis, Emergency Medicine, medicine.symptom, business, medicine.drug
Abstract

Objective The objective of this study is to determine whether hypothermia will lessen decreases in heart rate variability and improve outcome in a rat model of sepsis. Methods Thirty-six male Sprague-Dawley rats were randomized into 3 groups: control, low sepsis, and high sepsis groups. These groups were each subdivided into a normothermia (37°C) (n = 6) and a hypothermia group (34°C) (n = 6). Cyclophosphamide (100 mg/kg) was administered 5 days before Staphylococcus aureus injection to produce conditions in which sepsis could be induced reliably. Hypothermic rats received temperature reduction for 1 hour post injection. Electrocardiogram was recorded before, after, and 1 day after staphylococcal injection, and the low frequency, high frequency (HF), and LF/HF ratio measurements of heart rate variability and the frequencies of arrhythmia were recorded. The effects of time, sepsis severity, and hypothermia on these variables were analyzed using a multivariate generalized estimation equation mode. Results Four deaths occurred in the normothermic group, and none, in the hypothermic group. Sepsis of both low and high severity increased low frequency and HF 1 day after sepsis induction. Hypothermia significantly decreased HF in low, but not high sepsis severity. Conclusions Hypothermia decreased mortality in septic rats. The influence of hypothermia on HF depended on the severity of the sepsis.

Published
2013

23. Myofascial Pain Syndrome: Correlation between the Irritability of Trigger Points and the Prevalence of Local Twitch Responses during Trigger Point Injection

Author

Shu Min Chen, Jo Tong Chen, Wei Chang Yen, Ta Shen Kuan, Chien Tsung Tsai, Chang-Zern Hong, and Chi Yen Feng

Subjects
Myofascial trigger point, Trigger point injection, Pressure pain, business.industry, Myofascial pain syndrome, medicine.disease, Irritability, Correlation, Rheumatology, Anesthesia, medicine, Nociceptor, medicine.symptom, business, Trapezius muscle
Abstract

ObjectiveTo assess the correlation between the trigger point [TrP] irritability in the myofascial pain syndrome [MPS] and the prevalence of one or more local twitch responses [LTRs] during TrP injection.MethodsPatients with MPS, active TrPs in the trapezius muscle, and a pain intensity greater than 5 [numerical pain scale, 0 = no pain; 10 = worst pain in life] were recruited for this study. Pain intensity and pressure pain threshold [PPT] were measured before and immediately after TrP injection.ResultsA total of 72 MPS patients [30 males, 42 females] participated in this study. It was found that the pain intensity was significantly reduced [P

Published
2012

24. Mechanism of Two Novel Human GJC3 Missense Mutations in Causing Non-Syndromic Hearing Loss

Author

Wei-Guang Liang, Yung-Chang Yen, Shuan-Yow Li, Jiann-Jou Yang, Ching-Chyuan Su, and Jhih-Hao Nian

Subjects
Databases, Factual, Hearing loss, Molecular Sequence Data, Mutant, Cell, Mutation, Missense, Biophysics, Nerve Tissue Proteins, Biology, medicine.disease_cause, Biochemistry, Connexins, Mutant protein, medicine, Humans, Missense mutation, Amino Acid Sequence, Cloning, Molecular, Hearing Loss, Gene, Mutation, Computational Biology, Cell Biology, General Medicine, Molecular biology, Protein Structure, Tertiary, medicine.anatomical_structure, medicine.symptom, Sequence Alignment, Intracellular, HeLa Cells
Abstract

Connexins (CXs), as a component of gap junction channel, are homologous four transmembrane-domain proteins, with numerous studies confirming their auditory functions. Among a cohort of patients having incurred non-syndromic hearing loss, we identified two novel missense mutations, p.R15G and p.L23H, in the GJC3 gene encoding CX30.2/CX31.3, as causally related to hearing loss in previous study. However, the functional alteration of CX30.2/CX31.3 caused by the mutant GJC3 gene remains unknown. In this study, we compared the intracellular distribution of mutant CX30.2/CX31.3 (p.R15G and p.L23H) with the wild-type (WT) protein in HeLa cells and the effect of the mutant protein had on those cells. Analytical results indicated that p.R15G and p.L23H mutant exhibited continuous staining along apposed cell membranes in the fluorescent localization assay, which is the same with the WT. Moreover, ATP release (hemichannel function) is less in HeLa cells carrying mutant GJC3 genes than those of WT expressing cells. We believe that although p.R15G and p.L23H mutants do not decrease the trafficking of CX proteins, mutations in GJC3 genes result in a loss of hemichannel function of CX30.2/CX31.3 protein, possibly causing hearing loss. Results of this study provide a novel molecular explanation for the role of GJC3 in hearing loss.

Published
2012

25. Relapse and Long-Acting Injectable Risperidone: A 1-Year Mirror Image Study with a National Claims Database in Taiwan

Author

Kuan-Pin Su, Hui Chih Chang, Chao Hsiun Tang, Feng Chang Yen, and Shih-Jen Tsai

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Databases, Factual, National Health Programs, Cost-Benefit Analysis, Taiwan, MEDLINE, Injections, Intramuscular, Young Adult, Statistical significance, Outcome Assessment, Health Care, Secondary Prevention, Humans, Medicine, National Health Insurance, Young adult, Psychiatry, Aged, relapse, Risperidone, business.industry, Health Policy, Public Health, Environmental and Occupational Health, Length of Stay, Middle Aged, medicine.disease, National health insurance, Schizophrenia, Cohort, risperidone long-acting injection, Female, business, Antipsychotic Agents, Follow-Up Studies, Diagnosis of schizophrenia, medicine.drug
Abstract

Objectives: The development of long-acting, injectable atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The study was designed to assess whether a risperidone long-acting injection (RLAI) is associated with reduced relapses and service utilization in the real world. Methods: The Psychiatric Inpatients Medical Claims dataset was used for the analysis. It is a longitudinal dataset that includes the National Health Insurance claims of service uses by a cohort of mentally ill patients. The inclusion criteria for this analysis were patients who: 1) had available information for at least 12 months after the first dose of RLAI; 2) had a primary diagnosis of schizophrenia; and 3) were regularly treated with RLAI for at least 1 year. Patients who accumulatively received at least 75-mg RLAI per 3-month period were considered to be undergoing regular treatment. Wilcoxon signed rank tests were performed to compare differences in numbers of acute admissions, hospital days, emergency room visits, and relapses between the pre- and post-RLAI periods in this 1-year mirror-image study. Results: In total, 108 patients were eligible for analysis. Significant reductions in the total annual numbers of acute hospital admissions by 55% (80 vs. 36, P = 0.0003), hospital days by 48% (4106 vs. 2126, P = 0.0021), and relapses by 54% (115 vs. 53, P = 0.0005) were observed. A reduction of emergency room visits was also observed, but did not reach statistical significance (55 vs. 25, P = 0.1255). Conclusions: This 1-year mirror-image analysis with claims-based data demonstrated that RLAI treatment was associated with reductions in relapses and hospital service utilization.

Published
2009

26. Haplotype analysis of single nucleotide polymorphisms in the vascular endothelial growth factor (VEGFA) gene and antidepressant treatment response in major depressive disorder

Author

Tai-Jui Chen, Shih-Jen Tsai, Chen-Jee Hong, Ying-Jay Liou, Feng-Chang Yen, Younger W.-Y. Yu, Mao-Liang Chen, and Sheue-Jane Hou

Subjects
Adult, Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Time Factors, Genotype, Serotonin reuptake inhibitor, Citalopram, Pharmacology, Polymorphism, Single Nucleotide, Young Adult, chemistry.chemical_compound, Gene Frequency, Fluoxetine, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Biological Psychiatry, Depressive Disorder, Major, Middle Aged, medicine.disease, Antidepressive Agents, Vascular endothelial growth factor, Psychiatry and Mental health, Vascular endothelial growth factor A, Endocrinology, chemistry, Pharmacogenetics, Major depressive disorder, Antidepressant, Female, Psychology, medicine.drug
Abstract

Vascular endothelial growth factor (VEGF) has been implicated in neurotrophy and neurogenesis, which play a pivotal role in brain development and may be involved in antidepressant therapeutic mechanisms. Recent animal studies demonstrate that VEGF levels are increased by several antidepressants, including selective serotonin reuptake inhibitors, and that VEGF signalling is required for antidepressant-induced behavioural response. We hypothesized that common genetic variants in the VEGF gene (official gene name: VEGFA) may be associated with the therapeutic response to antidepressants in major depressive disorders (MDD). Seven VEGFA polymorphisms were genotyped in 351 patients with MDD who were treated with selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressants and who were were studied in a therapeutic evaluation for at least 4 weeks. Of the 351 patients, 158 completed an 8-week therapeutic evaluation. No significant association with either 4-week or 8-week antidepressant therapeutic effect was shown in the alleles and genotypes of single loci, or haplotypes from two blocks constructed from these polymorphisms. Our findings suggested that VEGFA genetic variants do not play a major role in the response to selective serotonin reuptake inhibitors.

Published
2009

27. The Myofascial Trigger Point Region

Author

Shu Min Chen, Yueh-Ling Hsieh, Jo Tong Chen, Wei Chang Yen, Ta Shen Kuan, and Chang-Zern Hong

Subjects
Adult, Male, Pain Threshold, Upper trapezius, medicine.medical_specialty, Pressure pain, Physical Therapy, Sports Therapy and Rehabilitation, Electromyography, Irritability, Motor Endplate, Correlation, Physical medicine and rehabilitation, Threshold of pain, medicine, Humans, Muscle, Skeletal, Myofascial Pain Syndromes, Myofascial trigger point, medicine.diagnostic_test, business.industry, Rehabilitation, Middle Aged, medicine.disease, Upper trapezius muscle, Female, medicine.symptom, business
Abstract

Kuan T-S, Hsieh Y-L, Chen S-M, Chen J-T, Yen W-C, Hong C-Z: The myofascial trigger point region: correlation between the degree of irritability and the prevalence of endplate noise. Am J Phys Med Rehabil 2007;86:183‐189. Objective: This study was designed to investigate the correlation between the irritability of the myofascial trigger point (MTrP) and the prevalence of endplate noise (EPN) in the MTrP region of human skeletal muscle. Design: Twenty normal subjects with latent MTrPs and 12 patients with active MTrPs in the upper trapezius muscles were recruited for this study. The patients reported the subjective pain intensity of the active MTrP (0‐10). The MTrP and an adjacent non-MTrP site were confirmed and marked for the measurement of pressure pain threshold (with a pressure algometer) and the prevalence of EPN (with electromyographic recordings). Results: The prevalence of EPN in the MTrP regions was significantly higher (P 0.01) in the active MTrPs than in the latent ones. However, no EPN could be found in the non-MTrP region near either the active or the latent MTrPs. The pain intensity and the pressure pain threshold were highly correlated with the prevalence of EPN in the MTrP region (r 0.742 and 0.716, respectively). Conclusions: The irritability of an MTrP is highly correlated with the prevalence of EPN in the MTrP region of the upper trapezius muscle. The assessment of EPN prevalence in an MTrP region may be applied to evaluate the irritability of that MTrP.

Published
2007

28. Effect of LED optical characteristics on temporal behavior ofo-cresol decomposition by UV/TiO2 process

Author

Chang-Yen Wu, Hua-Wei Chen, and Young Ku

Subjects
Aqueous solution, Renewable Energy, Sustainability and the Environment, Chemistry, business.industry, General Chemical Engineering, Attenuation, Organic Chemistry, Analytical chemistry, medicine.disease_cause, Pollution, Decomposition, law.invention, Inorganic Chemistry, Light intensity, Fuel Technology, Optics, law, Photocatalysis, medicine, Irradiation, business, Waste Management and Disposal, Ultraviolet, Biotechnology, Light-emitting diode
Abstract

BACKGROUND: An ultraviolet light-emitting diode (UV-LED) was used in this investigation as the light source for the photocatalytic decomposition of o-cresol in aqueous solution because of its efficiency, design flexibility, and durability. The UV light intensities of the corn-shaped LED tube designed in this investigation were relatively uniform due to the correct arrangement of LEDs. RESULTS: For experiments conducted with initial o-cresol concentrations of 9 mg L−1 and pH 3, more than 80% of o-cresols were decomposed after 8 h of irradiation. The calculated photonic efficiency (about 1·06%) for experiments conducted with continuous illumination was much lower than those (1·69–6·27%) obtained with periodic illumination. CONCLUSION: The proposed Langmuir–Hinshelwood kinetic model with modification of UV light intensity attenuation could be adequately applied to describe the temporal behavior of the o-cresol decomposition in aqueous solution by the UV-LED/TiO2 process. Copyright © 2007 Society of Chemical Industry

Published
2007

29. RISK OF RETINAL VEIN OCCLUSION IN PATIENTS WITH PSORIASIS: A Population-Based Cohort Study

Author

Shih-Feng Weng, Yung Chang Yen, Yong-Song Lin, and Feng Jie Lai

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Databases, Factual, National Health Programs, Population, Taiwan, Risk Factors, Psoriasis, Internal medicine, Retinal Vein Occlusion, medicine, Humans, Risk factor, education, Child, Aged, Proportional Hazards Models, Retrospective Studies, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Age Factors, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Confidence interval, Surgery, Ophthalmology, Child, Preschool, Female, business, Cohort study
Abstract

Purpose To investigate the risk of developing retinal vein occlusion (RVO) in patients with psoriasis. Methods In this retrospective population-based cohort study, 30,198 patients with psoriasis (Psoriasis((+)) group) and 30,198 controls without psoriasis (Psoriasis((−)) group) between 2001 and 2006 from the Taiwan National Health Insurance Research Database were selected. Results The incidence of RVO was 1.46 times higher in the Psoriasis((+)) group than in the Psoriasis((−)) group (3.61 vs. 2.47/10,000 person-years) (adjusted hazard ratio = 1.50; 95% confidence interval = 1.07-2.10) calculated using Cox proportional hazard regression. Age was an independent risk factor for RVO (adjusted hazard ratio: 11.9 for patients 65 years or older vs. 1.00 for those 0-49 years old). In the 65 years or older Psoriasis((+)) group, the incidence of developing RVO was 1.97 times higher (95% confidence interval = 1.19-3.26) than in the 65 years or older Psoriasis((−)) group. In Psoriasis((+)) women, the incidence of developing RVO was 1.82 times higher (95% = 1.05-3.14) than in Psoriasis((−)) women. For the subgroup with comorbid hypertension, the incidence of developing RVO was 2.07 times higher (95% confidence interval = 1.22-3.50) in the Psoriasis((+)) group than in the Psoriasis((−)) group. Conclusion Psoriasis was significantly associated with a higher risk of developing RVO.

Published
2015

30. Higher risk of developing sudden sensorineural hearing loss in patients with chronic otitis media

Author

Yung-Song Lin, Shih-Feng Weng, Yung-Chang Yen, and Charlene Lin

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Hearing loss, Hearing Loss, Sensorineural, Taiwan, Rate ratio, Risk Factors, Internal medicine, medicine, Humans, Child, Aged, Retrospective Studies, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Case-control study, Infant, Retrospective cohort study, Hearing Loss, Sudden, Middle Aged, medicine.disease, Surgery, Otitis Media, Otorhinolaryngology, Case-Control Studies, Child, Preschool, Cohort, Chronic Disease, Sensorineural hearing loss, Female, medicine.symptom, business
Abstract

Importance Several sources have suggested an association between chronic sensory hearing impairment and chronic otitis media (COM). However, to our knowledge, no studies have evaluated the risk of sudden sensorineural hearing loss (SSNHL) in patients with COM (COM-positive). Objective To examine the risk of developing SSNHL in COM-positive patients. Design, Setting, and Participants This was a retrospective cohort study; we compared 10 248 patients with newly diagnosed COM from January 1, 2001, through December 31, 2008, with 30 744 age- and sex-matched controls using data from Taiwan’s National Health Insurance Research Database. Methods We followed each patient and evaluated the incidence of SSNHL. Main Outcomes and Measures The incidence of SSNHL at the end of 2011. Results The incidence of SSNHL was 3 times higher in the COM-positive cohort than in the COM-negative cohort (14.47 vs 4.83 per 10 000 person-years). Cox proportional hazard regressions showed that the adjusted hazard ratio (AHR) was 3.02 (95% CI, 2.30-3.98). A stratified analysis showed that the highest risk of developing SSNHL was in the first follow-up year (incidence rate ratio [IRR], 3.87; 95% CI, 1.93-7.79). Thereafter, the risk declined during years 1 to 5 and then peaked (IRR, 3.01; 95% CI, 1.89-4.79). Patients who needed surgery had a higher incidence of SSNHL (AHR, 2.69; 95% CI, 1.62-4.48) compared with patients who needed only medication and observation. Conclusions and Relevance Chronic otitis media was significantly associated with a higher risk of developing SSNHL.

Published
2015

31. Risk of sudden sensorineural hearing loss in patients with psoriasis: a retrospective cohort study

Author

Feng Jie Lai, Yung Chang Yen, Yong-Song Lin, and Shih-Feng Weng

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Hearing loss, Hearing Loss, Sensorineural, Population, Taiwan, Dermatology, Disease, Comorbidity, Audiology, Young Adult, Psoriasis, medicine, Humans, education, Child, Aged, Retrospective Studies, Autoimmune disease, education.field_of_study, business.industry, Incidence, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Child, Preschool, Sensorineural hearing loss, Female, medicine.symptom, business
Abstract

Psoriasis, a common immune-mediated disease, affects approximately 2% of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis.We tested the hypothesis that psoriasis is a risk factor for developing SSNHL.Using Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n=28,817) with gender-, age-, and comorbidities-matched controls (n=28,817). We followed each patient until the end of 2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis.The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95% confidence interval [CI] 1.18-1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95% CI 1.05-2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different.Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.

Published
2015

32. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Khaw, Kay-Tee, Kim, Eric, Grammer, Tanja B, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J F, Mach, François, McArdle, Wendy L, Gräßler, Jürgen, Meisinger, Christa, Mitchell, Braxton D, Muller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Grönberg, Henrik, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Ridker, Paul M, Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Fall, Tove, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Gusto, Gaëlle, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Haessler, Jeffrey, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Hall, Per, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B, Haller, Toomas, Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Hingorani, Aroon, Hallmans, Goran, Hofman, Albert, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hunt, Steven C, Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Hartman, Catharina A, Kähönen, Mika, Kaprio, Jaakko, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S, Koudstaal, Peter J, Krauss, Ronald M, Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O, Hassinen, Maija, Laakso, Markku, Lakka, Timo A, Lind, Lars, Lindgren, Cecilia M, Martin, Nicholas G, März, Winfried, McCarthy, Mark I, McKenzie, Colin A, Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D, Munroe, Patricia B, Njølstad, Inger, Pedersen, Nancy L, Power, Chris, Pramstaller, Peter P, Price, Jackie F, Psaty, Bruce M, Quertermous, Thomas, Heard-Costa, Nancy L, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K, Saramies, Jouko, Schwarz, Peter E H, Sheu, Wayne H-H, Shuldiner, Alan R, Siegbahn, Agneta, Spector, Tim D, Helmer, Quinta, Stefansson, Kari, Strachan, David P, Tayo, Bamidele O, Tremoli, Elena, Uusitupa, Matti, van Duijn, Cornelia M, Vollenweider, Peter, Wallentin, Lars, Wareham, 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EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Eriksson, J., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Peacock, M., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., van Meurs JB., Weedon, MN., Wichmann, H., Young, L., Bierut, LJ., Boyd, HA., Econs, MJ., Van T'Hooft, Ferdinand M., Njølstad, Inger, Abecasis, Gonçalo R., Barroso, Inɥ, The MIGEN Consortium, Investigator, Casari, GIORGIO NEVIO, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life 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Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, 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Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes

Subjects
Male, LOCI, Genome-wide association study, Continental Population Groups/genetics, VARIANTS, Body Mass Index, Insulin Secretion, Insulin, Age Factor, Adiposity, ddc:616, Adipogenesis, Genetic Predisposition to Disease/genetics, Synapse, 3. Good health, Continental Population Group, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE, ddc:500, Adipogenesis/genetics, Single Nucleotide/genetics, Age Factors, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Glutamic Acid, Humans, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses, Genome-Wide Association Study, Multidisciplinary, genetics [Adiposity], Human, Socio-culturale, genetics [Energy Metabolism], ta3111, genetic, body mass index, obesity, SDG 3 - Good Health and Well-being, GLYCEMIC TRAITS, genetics [Continental Population Groups], Genetic variability, Polymorphism, GENOME-WIDE ASSOCIATION, genetics [Adipogenesis], METAANALYSIS, Genetic association, Adipogenesi, genetics [Quantitative Trait Loci], ta1184, metabolism [Glutamic Acid], ta1182, PATHWAYS, metabolism [Synapses], ta3121, medicine.disease, metabolism [Insulin], Adiposity/genetics, Clinical Medicine, Quantitative Trait Loci/genetics, Body mass index, HUMAN HEIGHT, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Synapses/metabolism, Medizin, Obesity/genetics, Bioinformatics, genetic basis, Obesity/metabolism, genetics [Obesity], body mass index (BMI), genetics [Genetic Predisposition to Disease], ethnology [Europe], 2. Zero hunger, Genetics, ARCHITECTURE, Genetics of obesity, Medicine (all), Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Insulin/metabolism/secretion, Glutamic Acid/metabolism, genetics [Polymorphism, Single Nucleotide], EXPRESSION, Insulin/metabolism, PROVIDES INSIGHTS, genetics [Racial Groups], Biology, Obesity/genetics/metabolism, Europe/ethnology, metabolism [Obesity], Mendelian randomization, medicine, Energy Metabolism/genetics, body mass, genetic analysis, obesity, Klinisk medicin
Abstract

Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Published
2015

33. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, 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Kolcic, Ivana, Lahti, Jari, Lai, Sandra, Laisk, Triin, Laven, Joop S E, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Marongiu, Mara, Blangero, John, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Newman, Anne B, Paré, Guillaume, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Pop, Victor J M, Räikkönen, Katri, Sala, Cinzia, Salumets, Andres, Smith, Jennifer A, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Styrkarsdottir, Unnur, Tenesa, Albert, Scherag, André, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Voorhuis, Marlies, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Claudi-Boehm, Simone, Zgaga, Lina, Zygmunt, Marek, Arnold, Alice M, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Hu, Frank B, Hunter, David J, Launer, Lenore J, Crawford, Dana C, 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Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Space Sciences Laboratory [Berkeley] (SSL), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, King‘s College London, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Universität Leipzig [Leipzig], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of California [Irvine] (UCI), German Research Center for Environmental Health, University of Bonn, Czech Academy of Sciences [Prague] (ASCR), Yale University School of Medicine, University of Oxford [Oxford], German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Laval University, Laval University [Québec], Turku University Hospital, Lausanne university hospital, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej Bedrac, S, Nguyen, T, Nogues, X, Patel, M, Prezelj, J, Scollen, S, Siggeirsdottir, K, Svensson, O, Trummer, O, van Schoor, N, Woo, J, Zhu, K, Balcells, S, Brandi, M, Cheng, S, Christiansen, C, Cooper, C, Frost, M, Goltzman, D, González Macías, J, Karlsson, M, Khusnutdinova, E, Koh, J, Kollia, P, Langdahl, B, Leslie, W, Lips, P, Ljunggren, Ö, Lorenc, R, Marc, J, Mellström, D, Obermayer Pietsch, B, Olmos, J, Pettersson Kymmer, U, Reid, D, Riancho, J, Rousseau, F, Tang, N, Urreizti, R, Van Hul, W, Zarrabeitia, M, Castano Betancourt, M, Herrera, L, Ingvarsson, T, Johannsdottir, H, Kwan, T, Li, R, Luben, R, Medina Gómez, C, Palsson, S, Reppe, S, Sigurdsson, G, van Meurs, J, Verlaan, D, Williams, F, Zhou, Y, Gautvik, K, Raychaudhuri, S, Cauley, J, Clark, G, Cummings, S, Danoy, P, Dennison, E, Eastell, R, Eisman, J, Jackson, R, Jones, G, Khaw, K, Mccloskey, E, Nandakumar, K, Peacock, M, Pols, H, Prince, R, Reid, I, Robbins, J, Sambrook, P, Sham, P, Tylavsky, F, Econs, M, Kung, A, Reeve, J, Streeten, E, Karasik, D, Ralston, S, Ioannidis, J, Kiel, D, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Mäkinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkilä, O, Hietala, K, Kytö, J, Lahermo, P, Lehto, M, Österholm, A, Parkkonen, M, Pitkäniemi, J, Rosengård Bärlund, M, Saraheimo, M, Sarti, C, Söderlund, J, Soro Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Wadén, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Tregouet, D, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Möllsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Fraser, R, Freitag, D, Gurdasani, D, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Van den Herik, E, Volcik, K, Asiki, G, Been, L, Bolton, J, Bonnycastle, L, Burnett, M, Cesana, G, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Kastelein, J, Kim, E, Komulainen, P, Lin, S, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Stančáková, A, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Willemsen, G, Young, E, Bennett, F, Boomsma, D, Bovet, P, Chen, Y, Feranil, A, Freimer, N, Hsiung, C, Järvelin, M, Kesäniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Martin, N, Meneton, P, Moilanen, L, Njølstad, I, Price, J, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sõber, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjögren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Grässler, J, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Stanèáková, A, Raffel, L, Yao, J, Schwartz, S, Ikram, M, Longstreth W., J, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Morken, M, Laitinen, J, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Würtz, P, Ong, R, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Dominiczak, A, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Anderson, C, Gordon, S, Guo, Q, Henders, A, Lambert, A, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Alizadeh, B, de Boer, R, Boezen, H, van der Klauw, M, Ormel, J, Postma, D, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Lecoeur, C, Johnson, P, Hottenga, J, Salo, P, Bielak, L, Zhao, W, Horikoshi, M, Navarro, P, Chen, H, Rybin, D, Song, K, An, P, Marullo, L, Jansen, H, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Toenjes, A, Peyser, P, Körner, A, Cucca, F, Balkau, B, Bouatia Naji, N, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Hedman, Å, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Higashio, J, Williams, R, Nato, A, Ambite, J, Manolio, T, Hindorff, L, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown Gentry, K, Thornton Wells, T, Dumitrescu, L, Jeff, J, Bush, W, Mitchell, S, Goodloe, R, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Zheng, W, Spencer, K, Pendergrass, S, Wilkens, L, Park, L, Tiirikainen, M, Kolonel, L, Lim, U, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Schumacher, F, Anderson, G, Carlson, C, Prentice, R, Wu, C, Carty, C, Gong, J, Rosse, S, Young, A, Haessler, J, Kocarnik, J, Lin, Y, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chanock, S, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hall, P, Hankinson, S, Hass, M, Heath, A, Janssens, A, Keyzer, J, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Medland, S, Melzer, D, Newman, A, Paré, G, Peeters, P, Pop, V, Räikkönen, K, Salumets, A, Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes

Subjects
Adipose Tissue/metabolism, Male, genetic association, subcutaneous fat, Transcription, Genetic, Adipocytes, Adipogenesis, Adipose Tissue, Age Factors, Body Mass Index, Continental Population Groups, Epigenesis, Genetic, Europe, Female, Genome, Human, Humans, Insulin, Insulin Resistance, Models, Biological, Neovascularization, Physiologic, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Characteristics, Waist-Hip Ratio, Body Fat Distribution, Genome-Wide Association Study, Multidisciplinary, Insulin Resistance/genetics, Genome-wide association study, Continental Population Groups/genetics, genetic analysis, heritability, gene cluster, Science::Biological sciences::Human anatomy and physiology [DRNTU], 0302 clinical medicine, high density lipoprotein cholesterol, Models, genetics [Insulin Resistance], histone modification, Age Factor, insulin receptor, 0303 health sciences, Adipocyte, Human/genetics, CARDIOGRAMplusC4D Consortium, ADIPOGENIC DIFFERENTIATION, genetic correlation, body fat, Continental Population Group, priority journal, 5 trisphosphate 3 phosphatase, GEFOS Consortium, meta analysis (topic), Science & Technology - Other Topics, ddc:500, transcription regulation, Adipogenesis/genetics, Single Nucleotide/genetics, Human, medicine.medical_specialty, Waist, phosphatidylinositol 3, European, ta3111, genetic regulation, Article, developmental biology, 03 medical and health sciences, MAGIC Investigators, transcription initiation site, SDG 3 - Good Health and Well-being, Genetic, genomics, GLYCEMIC TRAITS, genetics [Continental Population Groups], Polymorphism, GENOME-WIDE ASSOCIATION, Physiologic, genetics [Adipogenesis], Adipocytes/metabolism, Europe/ethnology, Genome, Human/genetics, Insulin/metabolism, Neovascularization, Physiologic/genetics, Obesity/genetics, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Transcription, Genetic/genetics, Genetic/genetics, Adipogenesi, Science & Technology, adiponectin, [ SDV ] Life Sciences [q-bio], vasculotropin, genetics [Quantitative Trait Loci], ta1184, Racial Groups, ta1182, gene mapping, ta3121, triacylglycerol blood level, medicine.disease, Biological, major clinical study, amino acid sequence, metabolism [Insulin], Endocrinology, metabolism [Adipocytes], genetic loci, insulin, body fat, GLGC, International Endogene Consortium, metabolism [Adipose Tissue], Body mass index, HUMAN HEIGHT, Epigenesis, LifeLines Cohort Study, ReproGen Consortium, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, tissue level, Physiologic/genetics, [SDV]Life Sciences [q-bio], Medizin, Adipose tissue, low density lipoprotein cholesterol, PAGE Consortium, COMMON SNPS, angiogenesis, Waist–hip ratio, genetics [Obesity], MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, single nucleotide polymorphism, fat, genetic variability, molecular biology, body mass index (BMI), ethnology [Europe], peroxisome proliferator activated receptor, 2. Zero hunger, Genetics, Genome, Single Nucleotide, waist circumference, insulin, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, triacylglycerol, vasculotropin, developmental biology, gene expression, genome, numerical model, adipocyte, adipose tissue, body fat distribution, body mass, female, gene locus, gene structure, hip circumference, human, insulin resistance, lipoprotein blood level, male, obesity, protein protein interaction, sex difference, waist hip ratio, Multidisciplinary Sciences, genetics [Transcription, Genetic], genetics [Polymorphism, Single Nucleotide], ADIPOGen Consortium, genetics [Neovascularization, Physiologic], Transcription, SUSCEPTIBILITY LOCI, General Science & Technology, ICBP, 030209 endocrinology & metabolism, Biology, adipocyte, MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio, MESENCHYMAL STEM-CELLS, GENIE Consortium, SEXUAL-DIMORPHISM, Insulin resistance, Internal medicine, medicine, genetics [Genome, Human], ABDOMINAL ADIPOSITY, Neovascularization, 030304 developmental biology, FALSE DISCOVERY, CKDGen Consortium, Sex Characteristic, MuTHER Consortium, numerical model
Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P

Published
2015

34. Blood lead levels in primary school children in Trinidad and Tobago

Author

Jay Manohar, Avril Siung-Chang, Rohit Doon, Ivan Chang-Yen, Michele A. Monteil, and Wayne Simon Rajkumar

Subjects
Male, medicine.medical_specialty, Environmental Engineering, education, Risk Assessment, Biological fluid, Environmental protection, Environmental health, Epidemiology, Humans, Environmental Chemistry, Medicine, Child, Waste Management and Disposal, West indies, medicine.diagnostic_test, business.industry, Public health, Baseline survey, Pollution, Trinidad and Tobago, Lead, El Niño, Child, Preschool, Environmental Pollutants, Female, Blood lead level, business, Risk assessment, Environmental Monitoring
Abstract

This study is the first national baseline survey of blood lead levels (BLLs) conducted on primary school children (ages 5-7 years) in Trinidad and Tobago. A total of 1,761 students from 61 schools participated in the study over a 3-month period. Measurements of capillary BLLs were assessed as well as responses to a risk assessment questionnaire. BLLs ranged from1 microg/dL to 28.6 microg/dL with a geometric mean of 2.8 microg/dL, which compared favourably with results from the U.S. 1991-94 National Health and Nutrition Examination Survey. Fifteen (0.9%) children had a BLLor=10 microg/dL (10.8-28.6 microg/dL) of which three (0.2%) met the U.S. criteria for lead poisoning (BLLor=20 microg/dL). Further environmental investigations are required to identify source(s) of lead exposure in cases with high BLL.

Published
2006

35. Electrostatic self-assembly of a ruthenium-based oxygen sensitive dye using polyion–dye interpolyelectrolyte formation

Author

Bruce K. Gale, Yuri Lvov, David A. Chang-Yen, and Michael J. McShane

Subjects
Materials science, medicine.diagnostic_test, Scanning electron microscope, Inorganic chemistry, Layer by layer, Metals and Alloys, chemistry.chemical_element, Quartz crystal microbalance, Condensed Matter Physics, Fluorescence spectroscopy, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Ruthenium, Absorbance, Adsorption, chemistry, Spectrophotometry, Materials Chemistry, medicine, Electrical and Electronic Engineering, Instrumentation
Abstract

The dye tris(2,2′-bipyridyl dichlororuthenium) hexahydrate has been successfully applied to glass and silica surfaces using the technique of layer by layer self-assembly. Solutions of both admixed polyion–dye and pure dye were used to attempt adsorption of the dye onto the substrates. Characterization of the constructed dye layers was performed using quartz crystal microbalance (QCM), UV-Vis absorbance spectrophotometry, fluorescence spectroscopy, and scanning electron microscopy (SEM) methods. Successive, controlled addition of multiple dye layers has been demonstrated, and exposure to different levels of dissolved oxygen shows that the films containing entrapped dye molecules retain sensing properties.

Published
2002

36. The connexin 30.3 of zebrafish homologue of human connexin 26 may play similar role in the inner ear

Author

Ju Chang-Chien, Shaun-Yow Li, Jiann-Jou Yang, Kuo-Hsuan Chien, Yung-Chang Yen, and Tsai-Ching Hsu

Subjects
Cytoplasm, animal structures, Time Factors, Genotype, Connexin, In situ hybridization, Biology, Transfection, Connexins, Morpholinos, otorhinolaryngologic diseases, medicine, Animals, Humans, Inner ear, RNA, Messenger, Zebrafish, Phylogeny, fungi, Embryogenesis, Cell Membrane, Gene Expression Regulation, Developmental, Zebrafish Proteins, biology.organism_classification, Phenotype, Molecular biology, Sensory Systems, Reverse transcription polymerase chain reaction, Connexin 26, medicine.anatomical_structure, Ear, Inner, Gene Knockdown Techniques, embryonic structures, Models, Animal, HeLa Cells
Abstract

The intercellular gap junction channels formed by connexins (CXs) are important for recycling potassium ions in the inner ear. CXs are encoded by a family of the CX gene, such as GJB2 , and the mechanism leading to mutant connexin-associated diseases, including hearing loss, remains to be elucidated. In this study, using bioinformatics, we found that two zebrafish cx genes, cx27.5 and cx30.3 , are likely homologous to human and mouse GJB2 . During embryogenesis, zebrafish cx27.5 was rarely expressed at 1.5–3 h post-fertilization (hpf), but a relatively high level of cx27.5 expression was detected from 6 to 96 hpf. However, zebrafish cx30.3 transcripts were hardly detected until 9 hpf. The temporal experiment was conducted in whole larvae. Both cx27.5 and cx30.3 transcripts were revealed significantly in the inner ear by reverse transcription polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization (WISH). In the HeLa cell model, we found that zebrafish Cx27.5 was distributed intracellularly in the cytoplasm, whereas Cx30.3 was localized in the plasma membrane of HeLa cells stably expressing Cx proteins. The expression pattern of zebrafish Cx30.3 in HeLa cells was more similar to that of cells expressing human CX26 than Cx27.5. In addition, we found that Cx30.3 was localized in the cell membrane of hair cells within the inner ear by immunohistochemistry (IHC), suggesting that zebrafish cx30.3 might play an essential role in the development of the inner ear, in the same manner as human GJB2 . We then performed morpholino knockdown studies in zebrafish embryos to elucidate the physiological functions of Cx30.3. The zebrafish cx30.3 morphants exhibited wild-type-like and heart edema phenotypes with smaller inner ears at 72 hpf. Based on these results, we suggest that the zebrafish Cx30.3 and mammalian CX26 may play alike roles in the inner ear. Thus, zebrafish can potentially serve as a model for studying hearing loss disorders that result from human CX26 mutations.

Published
2013

37. Risk of retinal vein occlusion in patients with systemic lupus erythematosus: a population-based cohort study

Author

Shih-Feng Weng, Yung Chang Yen, Horng An Chen, and Yong-Song Lin

Subjects
Adult, Male, medicine.medical_specialty, Retinal Vein, Adolescent, Population, Taiwan, Cohort Studies, Cellular and Molecular Neuroscience, Young Adult, Age Distribution, immune system diseases, Risk Factors, Internal medicine, Epidemiology, Occlusion, Retinal Vein Occlusion, medicine, Humans, Lupus Erythematosus, Systemic, In patient, Risk factor, Sex Distribution, skin and connective tissue diseases, education, Child, Aged, Proportional Hazards Models, Retrospective Studies, education.field_of_study, business.industry, Incidence (epidemiology), Incidence, Infant, Middle Aged, Sensory Systems, Surgery, Ophthalmology, Child, Preschool, Female, business, Cohort study
Abstract

Background/aims To investigate the risk of developing retinal vein occlusion (RVO) in patients with systemic lupus erythematosus (SLE). Methods In this retrospective population-based cohort study, 6756 patients with SLE and 40 536 controls without SLE (1:6) were selected from the Taiwan National Health Insurance Research Database claims from 2001 to 2006. Results The incidence of RVO was 3.46-times higher in the SLE group than in controls (5.61 vs 1.62 per 10 000 person-years) (adjusted HR=3.883, 95% CI 2.299 to 6.558) calculated using Cox proportional hazard regression. Age was an independent risk factor for RVO, with adjusted HRs of 4.842 for individuals aged ≥50 years compared with those 0–49 years. For each age subgroup, the risk of RVO was significantly higher only in the 0–49-year-old SLE group than in controls. In the 0–49-year-old SLE group the incidence of developing RVO was 7.92 times higher (95% CI 3.60 to 17.45) in the SLE group than in the 0–49-year-old controls. In women with SLE, the incidence of developing RVO was 3.33-times higher (95% CI 1.88 to 5.90) than in female controls. Conclusions SLE was significantly associated with an increased risk of developing RVO.

Published
2013

38. X-box binding protein 1 (XBP1) C−116G polymorphisms in bipolar disorders and age of onset

Author

Shih-Jen Tsai, Sheue-Jane Hou, Chen-Jee Hong, Chih-Ya Cheng, and Feng-Chang Yen

Subjects
Adult, Male, X-Box Binding Protein 1, Bipolar Disorder, XBP1, Genotype, Regulatory Factor X Transcription Factors, Biology, Pathogenesis, Gene Frequency, medicine, Humans, Point Mutation, Bipolar disorder, Age of Onset, Family history, Allele frequency, Genetics, Polymorphism, Genetic, General Neuroscience, Nuclear Proteins, Promoter, Middle Aged, medicine.disease, DNA-Binding Proteins, Case-Control Studies, Female, Age of onset, Transcription Factors
Abstract

X-box binding protein 1(XBP1), a critical gene in the endoplasmic reticulum stress response, is located on chromosome 22q12, which has been linked with bipolar disorders in several studies. Recently, associations have been reported between a polymorphism ( −116C → G) in the promoter region of XBP1, and bipolar disorders in both case-control study and family-based association study, however, this finding is not yet confirmed by other research using independent sample populations. To replicate this finding and determine the association between onset age of bipolar disorders and the XBP1 C−116G polymorphism, we investigated the prevalence of this polymorphism in a Chinese population (153 bipolar disorder patients and 174 controls). We were unable, however, to demonstrate a significant association between the C −116G polymorphism and bipolar disorders (P = 0.674 for genotype and P = 0.436 for allele frequency) or age at onset (P = 0.563). Further, no association was demonstrated between this polymorphism and family history in bipolar disorder patients. These negative findings suggest that the XBP1 C−116G polymorphism does not play a major role in the pathogenesis of bipolar disorders in Chinese populations. © 2004 Elsevier Ireland Ltd. All rights reserved.

Published
2004

39. Phylodynamic Characterization of an Ocular-Tropism Coxsackievirus A24 Variant

Author

Li-Chiu Chou, Chu-Feng Wang, Yu-Chang Tyan, Yong-Ying Shi, Jing-Yun Zeng, Yung-Chang Yen, Chien-Ching Lin, Po-Liang Lu, Yi-Ying Lin, Pei-Huan Chu, Guan-Ming Ke, Yung-Cheng Lin, Hui-Ju Su, and Pei-Yu Chu

Subjects
RNA viruses, 0301 basic medicine, viruses, lcsh:Medicine, Pathology and Laboratory Medicine, Enteroviruses, Geographical Locations, Medicine and Health Sciences, lcsh:Science, Phylogeny, Data Management, Genetics, education.field_of_study, Multidisciplinary, Phylogenetic tree, Acute hemorrhagic conjunctivitis, Phylogenetic Analysis, Coxsackieviruses, Phylogenetics, Medical Microbiology, Viral Pathogens, Viruses, Gene pool, Pathogens, Monte Carlo Method, Sequence Analysis, Research Article, Computer and Information Sciences, Asia, Genotype, 030106 microbiology, Population, Taiwan, Biology, Research and Analysis Methods, Microbiology, Viral Evolution, Evolution, Molecular, 03 medical and health sciences, Spatio-Temporal Analysis, Sequence Motif Analysis, Virology, medicine, Evolutionary Systematics, Molecular Biology Techniques, Sequencing Techniques, education, Molecular Biology, Microbial Pathogens, Tropism, Taxonomy, Molecular Biology Assays and Analysis Techniques, Evolutionary Biology, Base Sequence, lcsh:R, Organisms, Biology and Life Sciences, Bayes Theorem, medicine.disease, Organismal Evolution, Enterovirus C, Human, Viral Tropism, 030104 developmental biology, Viral phylodynamics, People and Places, Microbial Evolution, Tissue tropism, lcsh:Q, Capsid Proteins
Abstract

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985-2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985-1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool.

Published
2016

40. The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma

Author

Chih-Chen Hong, Shiu-Feng Huang, Hong-Dar Isaac Wu, Hock-Liew Eng, Cheng-Chung Tsai, Il-Chi Chang, Cheng-Hsiang Hsiao, Tseng-Chang Yen, Chi-Ling Chen, Yun-Fan Liaw, Chuan-Mo Lee, Gin-Ho Lo, Hui-Hwa Tseng, Pei-Jer Chen, Chao-Long Chen, John Wang, Chau-Ting Yeh, Hsien-Chung Yu, Po-Huang Lee, Miin-Fu Chen, and Cheng-Chung Wu

Subjects
Adult, Liver Cirrhosis, Male, Hepatitis B virus, medicine.medical_specialty, HBsAg, Carcinoma, Hepatocellular, Hepatitis C virus, Taiwan, Observational Study, Hepacivirus, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Aged, Hepatitis, Hepatitis B Surface Antigens, business.industry, Data Collection, Liver Neoplasms, Age Factors, virus diseases, General Medicine, Hepatitis C, Middle Aged, Hepatitis B, medicine.disease, digestive system diseases, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, DNA, Viral, Female, 030211 gastroenterology & hepatology, business, Viral hepatitis, Research Article
Abstract

Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research.

Published
2016

41. Seasonal Influence and Heavy Metal Analysis in Marine Shrimp (Penaeus spp.) Sold in Trinidad, West Indies

Author

Neela Badrie, Ivan Chang Yen, Luctchminarine Chatergoon, and Sophia Balfour

Subjects
Cadmium, biology, business.industry, fungi, chemistry.chemical_element, Aquatic animal, Seasonality, biology.organism_classification, Food safety, medicine.disease, Shrimp, Mercury (element), Fishery, chemistry, medicine, Penaeus, business, Shellfish
Abstract

Shrimp is a popular seafood in Trinidad and Tobago which is mainly caught in the coastal environs and sold mostly for domestic consumption. The objectives of the research were to determine if chemical contaminants copper, zinc, cadmium, chromium, nickel and mercury in the marine shrimp (Penaeus spp.) met international and local food safety standards and; to investigate any location by season interactions. Determination of all heavy metals was by flame atomic absorption spectroscopy except for mercury. Validation of methods was done using Certified Reference Materials namely dogfish liver and fish protein. The heavy metal findings in the marine shrimp were well below the United States Food and Drug Administration, Canada’s Food Inspection Agency and, Trinidad and Tobago’s admissible limits for human consumption. Significant differences were observed only for copper by location and season interaction and; zinc by location and season respectively.

Published
2012

42. A pneumatic neural probe structure fabricated by parylene thermal bonding technique

Author

Weileun Fang, Yu-Tao Lee, Yen-Chung Chang, and Yu-Chang Yen

Subjects
Structural material, Materials science, business.industry, Stiffness, Structural engineering, Reversible process, chemistry.chemical_compound, Buckling, Parylene, chemistry, Hardening (metallurgy), medicine, Composite material, medicine.symptom, business, Thermal bonding, Microfabrication
Abstract

This study demonstrates a novel pneumatic harden technique to enable the stiffness change of flexible neural probe structure. The probe structure is fabricated by using the parylene thermal bonding process. The merits of this pneumatic-hardening hollow-structure are as follows: (1) using the pneumatic hardening mechanism, this probe structure can easily tune its stiffness by varying the inlet air; (2) pneumatic hardening is a reversible process, and the hardening time can be arbitrarily manipulated; (3) by applying the parylene as the flexible structural material, high bio-compatibility and flexibility can both be achieved. Preliminary results show the critical buckling load can increase from 0.36gw to 0.65gw after inflating. The rat brain insertion using the air-inflated pneumatic neural probe is also demonstrated.

Published
2012

43. A study of the spatial protein organization of the postsynaptic density isolated from porcine cerebral cortex and cerebellum

Author

Chuang Chih-Fan, Yen Yun-Hong, Chang Yen-Chung, and Chang Chia-Wei

Subjects
Cerebellum, Swine, Synaptic Membranes, Nerve Tissue Proteins, Biochemistry, Analytical Chemistry, Tubulin, medicine, Animals, Actin-binding protein, Cytoskeleton, Molecular Biology, Cerebral Cortex, biology, Research, Membrane Proteins, Post-Synaptic Density, Protein subcellular localization prediction, medicine.anatomical_structure, Membrane protein, Receptors, Glutamate, Cerebral cortex, biology.protein, Excitatory postsynaptic potential, Biophysics, Postsynaptic density
Abstract

Postsynaptic density (PSD) is a protein supramolecule lying underneath the postsynaptic membrane of excitatory synapses and has been implicated to play important roles in synaptic structure and function in mammalian central nervous system. Here, PSDs were isolated from two distinct regions of porcine brain, cerebral cortex and cerebellum. SDS-PAGE and Western blotting analyses indicated that cerebral and cerebellar PSDs consisted of a similar set of proteins with noticeable differences in the abundance of various proteins between these samples. Subsequently, protein localization in these PSDs was analyzed by using the Nano-Depth-Tagging method. This method involved the use of three synthetic reagents, as agarose beads whose surface was covalently linked with a fluorescent, photoactivable, and cleavable chemical crosslinker by spacers of varied lengths. After its application was verified by using a synthetic complex consisting of four layers of different proteins, the Nano-Depth-Tagging method was used here to yield information concerning the depth distribution of various proteins in the PSD. The results indicated that in both cerebral and cerebellar PSDs, glutamate receptors, actin, and actin binding proteins resided in the peripheral regions within ∼ 10 nm deep from the surface and that scaffold proteins, tubulin subunits, microtubule-binding proteins, and membrane cytoskeleton proteins found in mammalian erythrocytes resided in the interiors deeper than 10 nm from the surface in the PSD. Finally, by using the immunoabsorption method, binding partner proteins of two proteins residing in the interiors, PSD-95 and α-tubulin, and those of two proteins residing in the peripheral regions, elongation factor-1α and calcium, calmodulin-dependent protein kinase II α subunit, of cerebral and cerebellar PSDs were identified. Overall, the results indicate a striking similarity in protein organization between the PSDs isolated from porcine cerebral cortex and cerebellum. A model of the molecular structure of the PSD has also been proposed here.

Published
2011

44. Polymorphisms in LMNA and near a SERPINA13 gene are not associated with cognitive performance in Chinese elderly males without dementia

Author

Ying Jay Liou, Heng Liang Yeh, Feng Chang Yen, Shih-Jen Tsai, Mu En Liu, Chen-Jee Hong, Sheue Jane Hou, and Albert C. Yang

Subjects
Gerontology, Male, Aging, Neuropsychological Tests, Affect (psychology), LMNA, Cognition, Asian People, medicine, Memory span, Dementia, Humans, Effects of sleep deprivation on cognitive performance, Genetic Association Studies, Serpins, Aged, Aged, 80 and over, Mini–Mental State Examination, Polymorphism, Genetic, medicine.diagnostic_test, General Neuroscience, Wechsler Adult Intelligence Scale, Middle Aged, medicine.disease, Lamin Type A, Psychology
Abstract

Aging is associated with cognitive deterioration. A recent study showed two polymorphisms (rs505058 in LMNA and rs11622883 near a SERPINA13 gene), identified in a genome-wide association study of late-onset Alzheimer's disease, to be associated with cognitive function (Mini Mental State Examination) in a UK elderly population. This study replicated these findings in Chinese elderly males without dementia. A total of 358 elderly subjects were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. Analysis of covariance was used to compare cognitive scores among genotypic groups, with age and total education years as covariates. The two polymorphisms were not associated with the global cognitive function or specific cognitive domains in the elderly without dementia. Our data argue against that these two polymorphisms may affect cognitive function in the elderly.

Published
2011

45. TGF-β1 blockade of microglial chemotaxis toward Aβ aggregates involves SMAD signaling and down-regulation of CCL5

Author

Young Ji Shiao, Huey Jen Tsay, Chih Ming Pan, Fong Lee Huang, Wei Chao Huang, Yen-Jen Sung, Feng Chang Yen, Feng Shiun Shie, and Cheng Ning Yang

Subjects
Chemokine, Blotting, Western, Immunology, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Smad Proteins, SMAD, Dioxoles, lcsh:RC346-429, Cell Line, Transforming Growth Factor beta1, Cellular and Molecular Neuroscience, Cell Movement, medicine, Animals, Senile plaques, Phosphorylation, Chemokine CCL5, Neuroinflammation, lcsh:Neurology. Diseases of the nervous system, Amyloid beta-Peptides, biology, Microglia, Dose-Response Relationship, Drug, Reverse Transcriptase Polymerase Chain Reaction, General Neuroscience, Research, Chemotaxis, Molecular biology, Cell biology, Rats, medicine.anatomical_structure, Neurology, Benzamides, biology.protein, Signal transduction, Receptors, Transforming Growth Factor beta, Transforming growth factor, Signal Transduction
Abstract

BackgroundOveractivated microglia that cluster at neuritic plaques constantly release neurotoxins, which actively contribute to progressive neurodegeneration in Alzheimer's disease (AD). Therefore, attenuating microglial clustering can reduce focal neuroinflammation at neuritic plaques. Previously, we identified CCL5 and CCL2 as prominent chemokines that mediate the chemotaxis of microglia toward beta-amyloid (Aβ)aggregates. Although transforming growth factor-β1 (TGF-β1) has been shown to down-regulate the expression of chemokines in activated microglia, whether TGF-β1 can reduce the chemotaxis of microglia toward neuritic plaques in AD remains unclear.MethodsIn the present study, we investigated the effects of TGF-β1 on Aβ-induced chemotactic migration of BV-2 microglia using time-lapse recording, transwell assay, real-time PCR, ELISA, and western blotting.ResultsThe cell tracing results suggest that the morphological characteristics and migratory patterns of BV-2 microglia resemble those of microglia in slice cultures. Using this model system, we discovered that TGF-β1 reduces Aβ-induced BV-2 microglial clustering in a dose-dependent manner. Chemotactic migration of these microglial cells toward Aβ aggregates was significantly attenuated by TGF-β1. However, these microglia remained actively moving without any reduction in migration speed. Pharmacological blockade of TGF-β1 receptor I (ALK5) by SB431542 treatment reduced the inhibitory effects of TGF-β1 on Aβ-induced BV-2 microglial clustering, while preventing TGF-β1-mediated cellular events, including SMAD2 phosphorylation and CCL5 down-regulation.ConclusionsOur results suggest that TGF-β1 reduces Aβ-induced microglial chemotaxis via the SMAD2 pathway. The down-regulation of CCL5 by TGF-β1 at least partially contributes to the clustering of microglia at Aβ aggregates. The attenuating effects of SB431542 upon TGF-β1-suppressed microglial clustering may be mediated by restoration of CCL5 to normal levels. TGF-β1 may ameliorate microglia-mediated neuroinflammation in AD by preventing activated microglial clustering at neuritic plaques.

Published
2010

46. Enlargement of Abeta aggregates through chemokine-dependent microglial clustering

Author

Wei Chao Huang, Young Ji Shiao, Feng Chang Yen, Cheng Ning Yang, Huey Jen Tsay, Feng Shiun Shie, Fong Lee Huang, Yen-Jen Sung, and Jin Lieh Chan

Subjects
Chemokine, Pathology, medicine.medical_specialty, Integrins, Time Factors, Amyloid, Protein Conformation, Integrin, Apoptosis, Plaque, Amyloid, Microscopy, Atomic Force, Antibodies, Mice, Polysaccharides, mental disorders, medicine, Animals, Senile plaques, Scavenger receptor, Receptor, Cell Line, Transformed, Receptors, Scavenger, Analysis of Variance, Amyloid beta-Peptides, Microglia, biology, Dose-Response Relationship, Drug, General Neuroscience, Chemotaxis, General Medicine, Peptide Fragments, Cell biology, N-Formylmethionine Leucyl-Phenylalanine, medicine.anatomical_structure, biology.protein, Chemokines, Oligopeptides
Abstract

The number of microglia surrounding senile plaques is correlated with the size of plaques in Alzheimer's disease (AD). It is unclear whether more microglia are passively recruited toward larger senile plaques or, conversely, microglia recruited to senile plaques directly contribute to the growth of plaques. In this study, BV-2 microglia were used to delineate the role of microglia in the growth of plaques using time-lapse recording. Aggregated beta amyloid peptide (Abeta)-induced BV-2 microglia to form clusters. The recruitment of BV-2 microglia bearing membrane-adhered Abeta enlarged preexisting Abeta aggregates. The receptors involved in the microglial uptake of Abeta, including integrin, formyl peptide like receptor 1, and scavenger receptors, also mediated the microglial clustering. Neutralization antibodies against chemokines significantly attenuated Abeta-induced microglial clustering and the enlargement of Abeta aggregates. Our results reveal a novel role of microglia in directly increasing the size of Abeta aggregates and suggest the targeting of Abeta-mediated microglial chemotactic migration in developing therapeutic interventions for AD.

Published
2009

47. Tryptophan hydroxylase 2 gene is associated with major depression and antidepressant treatment response

Author

Chen-Jee Hong, Sheue-Jane Hou, Tai-Jui Chen, Younger W.-Y. Yu, Ying-Jay Liou, Shih-Jen Tsai, and Feng-Chang Yen

Subjects
Adult, Male, Genotype, Serotonin reuptake inhibitor, Taiwan, Citalopram, Pharmacology, Tryptophan Hydroxylase, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Gene Frequency, Fluoxetine, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Biological Psychiatry, Depressive Disorder, Major, TPH2, Middle Aged, medicine.disease, Antidepressive Agents, Major depressive disorder, Antidepressant, Female, Reuptake inhibitor, Psychology, Pharmacogenetics, Selective Serotonin Reuptake Inhibitors, medicine.drug
Abstract

Tryptophan hydroxylase-2 (TPH2) is the rate-limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and has been implicated in the pathogenesis of major depressive disorder (MDD) and in the mechanism of antidepressant action. This study aimed to investigate whether common genetic variation in the TPH2 gene is associated with MDD and therapeutic response to antidepressants in a Chinese population. A total of 508 MDD patients and 463 unrelated controls were recruited. Among the MDD patients, 187 accepted selective serotonin reuptake inhibitor (fluoxetine or citalopram) antidepressant treatment for 8 weeks with therapeutic evaluation before and after treatment. Five TPH2 polymorphisms were genotyped and their association with MDD or treatment response was assessed by haplotype and single-marker analysis. In single-marker-based analysis, the rs17110747-G homozygote polymorphism was found to be more frequent in the MDD patients than in the controls (P=0.002). Genotype analysis in responders (defined as those with a 50% reduction in baseline Hamilton score) and non-responders after 8 weeks of antidepressant treatment showed that the proportion of rs2171363 heterozygote carriers was higher in the responders than the non-responders (P=0.009). No significant association with MDD or antidepressant therapeutic response was discovered in haplotype analyses. Our findings show that TPH2 genetic variants may play a role in MDD susceptibility and in acute therapeutic response to selective serotonin reuptake inhibitors.

Published
2008

48. Is dysfunction of the tissue plasminogen activator (tPA)-plasmin pathway a link between major depression and cardiovascular disease?

Author

Feng-Chang Yen, Shih-Jen Tsai, and Sheue-Jane Hou

Subjects
medicine.medical_specialty, Plasmin, Inflammation, Disease, Bioinformatics, behavioral disciplines and activities, Tissue plasminogen activator, Pathogenesis, Neurotrophic factors, Internal medicine, mental disorders, medicine, Humans, Fibrinolysin, Depressive Disorder, Major, Brain, General Medicine, medicine.disease, Endocrinology, Cardiovascular Diseases, Tissue Plasminogen Activator, Major depressive disorder, medicine.symptom, Psychology, Plasminogen activator, medicine.drug
Abstract

Epidemiological, genetic and clinical studies have demonstrated an association between major depressive disorder (MDD) and cardiovascular disease (CVD). For example, MDD is a risk factor for the development of CVD, while around one fifth of patients with CVD have MDD and a significantly larger percentage have subsyndromal symptoms of depression. Furthermore, patients with CVD and depression have an increased risk of future cardiac events compared to similar cohorts without depression, independent of baseline cardiac dysfunction. Despite evidence that CVD and MDD are epidemiologically linked, the cause of this correlation is still unknown. Several risk factors including physical and psychological stress, smoking, physical inactivity and inflammation have been proposed to mediate the interaction between MDD and CVD. The tissue-type plasminogen activator (tPA)-plasminogen proteolytic cascade is widely expressed in the brain. Accumulating evidence from preclinical and clinical studies suggests that tPA and its inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. In addition, brain-derived neurotrophic factor (BDNF) is important for the pathogenesis of MDD and the tPA-plasminogen proteolytic cascade has been implicated in the cleavage of proBDNF to BDNF in the brain, by which the direction of BDNF action is controlled. Thus, it is proposed that tPA-plasmin pathway dysfunction may play a role in the link between MDD and CVD. Future study of the components in the tPA-plasminogen system in CVD patients comorbid with MDD may lead to new, potentially important insights into the link between MDD and CVD, and might also contribute to novel strategies for the management of these two common and devastating diseases.

Published
2008

49. Interleukin-1 beta (C-511T) genetic polymorphism is associated with cognitive performance in elderly males without dementia

Author

Cheng-Hsi Hsieh, Chen-Jee Hong, Ying-Jay Liou, Sheue-Jane Hou, Shih-Jen Tsai, Mu-En Liu, and Feng-Chang Yen

Subjects
Oncology, Male, medicine.medical_specialty, Aging, Apolipoprotein E4, Interleukin-1beta, Neuropsychological Tests, Polymorphism, Single Nucleotide, Statistics, Nonparametric, Cognition, Polymorphism (computer science), Reference Values, Internal medicine, Post-hoc analysis, medicine, Memory span, Dementia, Humans, Effects of sleep deprivation on cognitive performance, Cognitive decline, Aged, Genetics, Aged, 80 and over, General Neuroscience, Wechsler Adult Intelligence Scale, medicine.disease, Cross-Sectional Studies, Neurology (clinical), Geriatrics and Gerontology, Psychology, Developmental Biology
Abstract

Interleukin-1 beta (IL-1 beta), a proinflammatory cytokine, plays a significant role in age-related changes in long-term potentiation (a biological substrate for learning and/or memory) in the hippocampus of experimental animals. This study tests the hypothesis that a biallelic functional polymorphism in the promoter region (position-511) (rs16944) of the IL-1 beta gene is associated with cognitive performance in elderly males without dementia. A total of 161 elderly male subjects without major psychiatric disorders or dementia participated in this research. Cognitive functions were assessed by the Cognitive Abilities Screening Instruments (CASI) test as well as The Wechsler Digit Span Task test. A significant association was found between the IL-1 beta C-511T polymorphism and CASI score (p = 0.008), particularly in the abstraction and judgment subtest (p = 0.010), and the backward digit span test (p = 0.004). Post hoc tests indicated that the C/C genotype gained better cognitive function test results than T/T carriers, mainly in the non-apolipoprotein E allele epsilon 4 carriers. These results suggest that genetic variants of the IL-1 beta C-511T polymorphism may play a role in specific cognitive functions in normal aged males. Considering that cognitive decline in the elderly is associated with local inflammation processes, genetic variants of cytokines and their receptors should be tested to improve gene-based prediction of general cognitive function in the elderly.

Published
2008

50. Bumetanide administration attenuated traumatic brain injury through IL-1 overexpression

Author

Chi Ling Wang, Jeng Hsiung F. Peng, Chang Yen Wu, Yi Ling Yang, Kwok Tung Lu, and Hao Han Yen

Subjects
Male, medicine.medical_specialty, Time Factors, Traumatic brain injury, Interleukin-1beta, Brain Edema, Hippocampus, Sodium Potassium Chloride Symporter Inhibitors, Internal medicine, Medicine, Hippocampus (mythology), Animals, RNA, Messenger, Rats, Wistar, Bumetanide, Neurologic Examination, Neurons, Messenger RNA, Analysis of Variance, business.industry, Brain edema, Reverse Transcriptase Polymerase Chain Reaction, General Medicine, Weight drop, medicine.disease, nervous system diseases, Rats, Up-Regulation, Disease Models, Animal, Endocrinology, medicine.anatomical_structure, nervous system, Neurology, Anesthesia, Brain Injuries, Neurology (clinical), Neuron, business, Cotransporter, medicine.drug
Abstract

Objective: To examine the effects of administration of bumetanide, a specific NKCC1 inhibitor, on traumatic brain injury (TBI)-induced interleukin-1 (IL-1) expression. Methods: TBI model was induced by the calibrated weight drop device (450 g in weight, 2.0 m in height) in adult rats based on procedures previously reported. One hundred and sixty Wistar rats were divided into sham-control group and experimental group for time course works of TBI. The expression of IL-1β brain edema and neuronal damage were determined in these animals after TBI. Results: We found that both mRNA and protein of IL-1β were up-regulated in the hippocampus 3–24 hours after TBI. Animals displayed severe brain edema and neuron damage after TBI. Bumetanide (15 mg/kg), a specific Na+ −K+ −2Cl− cotransporter inhibitor, significantly attenuated the TBI-induced neuronal damage by IL-1β overexpression. The present study suggests that administration of bumetanide could significantly decreased TBI-induced inflammatory response an...

Published
2007

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