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Sample records for cardiovascular phenotypes based

  1. A rule-based electronic phenotyping algorithm for detecting clinically relevant cardiovascular disease cases.

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    Esteban, Santiago; Rodríguez Tablado, Manuel; Ricci, Ricardo Ignacio; Terrasa, Sergio; Kopitowski, Karin

    2017-07-14

    The implementation of electronic medical records (EMR) is becoming increasingly common. Error and data loss reduction, patient-care efficiency increase, decision-making assistance and facilitation of event surveillance, are some of the many processes that EMRs help improve. In addition, they show a lot of promise in terms of data collection to facilitate observational epidemiological studies and their use for this purpose has increased significantly over the recent years. Even though the quantity and availability of the data are clearly improved thanks to EMRs, still, the problem of the quality of the data remains. This is especially important when attempting to determine if an event has actually occurred or not. We sought to assess the sensitivity, specificity, and agreement level of a codes-based algorithm for the detection of clinically relevant cardiovascular (CaVD) and cerebrovascular (CeVD) disease cases, using data from EMRs. Three family physicians from the research group selected clinically relevant CaVD and CeVD terms from the international classification of primary care, Second Edition (ICPC-2), the ICD 10 version 2015 and SNOMED-CT 2015 Edition. These terms included both signs, symptoms, diagnoses and procedures associated with CaVD and CeVD. Terms not related to symptoms, signs, diagnoses or procedures of CaVD or CeVD and also those describing incidental findings without clinical relevance were excluded. The algorithm yielded a positive result if the patient had at least one of the selected terms in their medical records, as long as it was not recorded as an error. Else, if no terms were found, the patient was classified as negative. This algorithm was applied to a randomly selected sample of the active patients within the hospital's HMO by 1/1/2005 that were 40-79 years old, had at least one year of seniority in the HMO and at least one clinical encounter. Thus, patients were classified into four groups: (1) Negative patients (2) Patients with Ca

  2. Investigating Risk Factors for Cardiovascular Disease Based on Polycystic Ovary Syndrome phenotypes in the 18-14 year Old High School Girls in Shiraz 2009

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    MH Dabbaghmaneh

    2012-05-01

    Full Text Available Introduction: In patients with polycystic ovary syndrome hyperinsulinaemia, insulin resistance, dyslipidemia and hyperglycemia may represent an increased risk for coronary cardiovascular disease .This study aimed to investigate risk factors for cardiovascular disease based on polycystic ovary syndrome phenotypes in Shiraz. Methods: This Cross-sectional study was performed on 3200 students aged 18-14. Demographic survey, clinical signs of androgen excess (acne, hirsutism, alopecia, Ultrasound were applied in order to find the cyst. Tests included prolactin, dehydroepiandrodion sulfate, and oral glucose tolerance test, fasting blood glucose, blood sugar two hours later, triglycerides, cholesterol, high density lipoprotein. Data were submitted to SPSS software, version 11.5 and then analyzed by chi-square tests. Results: The serum cholesterol mean in four phenotypes had a statistically significant relationship with non-PCOS patients(p<0.05. Mean of serum cholesterol in oligomenorrhea, Hyperandrogenism and polycystic ovary phenotype (195.09±30.28 was higher than the other phenotypes. Mean of serum cholesterol and low density lipoprotein(LDL-C were significantly higher in patients with Hyperandrogenism and polycystic ovarian phenotype(130.046±26.27 and oligomenorrhea, Hyperandrogenism and polycystic ovary syndrome phenotype(138.58±28.34 compared with non-infected individuals. Serum glucose mean in all phenotype was higher than non-infected after two hours and it showed a significant relation in oligomenorrhea and also polycystic ovarian phenotype(98.03 ± 20.98 versus 87.5±12.97 with non-infected individuals. Conclusion: Biochemical factors that lead to increased risk of cardiovascular diseases is increased in patients with polycystic ovary syndrome. Therefore, it should be attended in prevention programs

  3. Cell Phenotype Transitions in Cardiovascular Calcification

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    Luis Hortells

    2018-03-01

    Full Text Available Cardiovascular calcification was originally considered a passive, degenerative process, however with the advance of cellular and molecular biology techniques it is now appreciated that ectopic calcification is an active biological process. Vascular calcification is the most common form of ectopic calcification, and aging as well as specific disease states such as atherosclerosis, diabetes, and genetic mutations, exhibit this pathology. In the vessels and valves, endothelial cells, smooth muscle cells, and fibroblast-like cells contribute to the formation of extracellular calcified nodules. Research suggests that these vascular cells undergo a phenotypic switch whereby they acquire osteoblast-like characteristics, however the mechanisms driving the early aspects of these cell transitions are not fully understood. Osteoblasts are true bone-forming cells and differentiate from their pluripotent precursor, the mesenchymal stem cell (MSC; vascular cells that acquire the ability to calcify share aspects of the transcriptional programs exhibited by MSCs differentiating into osteoblasts. What is unknown is whether a fully-differentiated vascular cell directly acquires the ability to calcify by the upregulation of osteogenic genes or, whether these vascular cells first de-differentiate into an MSC-like state before obtaining a “second hit” that induces them to re-differentiate down an osteogenic lineage. Addressing these questions will enable progress in preventative and regenerative medicine strategies to combat vascular calcification pathologies. In this review, we will summarize what is known about the phenotypic switching of vascular endothelial, smooth muscle, and valvular cells.

  4. Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype.

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    Sanin, Veronika; Pfetsch, Vanessa; Koenig, Wolfgang

    2017-07-01

    This study aimed to present the current information on the genetic background of dyslipidemias and provide insights into the complex pathophysiological role of several plasma lipids/lipoproteins in the pathogenesis of atherosclerotic cardiovascular disease. Furthermore, we aim to summarize established therapies and describe the scientific rationale for the development of novel therapeutic strategies. Evidence from genetic studies suggests that besides lowering low-density lipoprotein cholesterol, pharmacological reduction of triglyceride-rich lipoproteins, or lipoprotein(a) will reduce risk for coronary heart disease. Dyslipidemia, in particular hypercholesterolemia, is a common clinical condition and represents an important determinant of atherosclerotic vascular disease. Treatment decisions are currently guided by the causative lipid phenotype and the presence of other risk factors suggesting a very high cardiovascular risk. Therefore, the identification of lipid disorders and the optimal combination of therapeutic strategies provide an outstanding opportunity for reducing the onset and burden of cardiovascular disease.

  5. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

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    Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens; Wissing, Marie-Louise M; Naver, Klara V; Mikkelsen, Anne-Lis; Nilas, Lisbeth; Skouby, Sven O

    2015-10-01

    Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  6. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

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    Kashyap, Sonu; Warner, Gina; Hu, Zeng; Gao, Feng; Osman, Mazen; Al Saiegh, Yousif; Lien, Karen R; Nath, Karl; Grande, Joseph P

    2017-01-01

    Renovascular hypertension (RVH) has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK) from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129 genetic background) by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  7. Sex differences in correlates of intermediate phenotypes and prevalent cardiovascular disease in the general population

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    Renate B. Schnabel

    2015-04-01

    Full Text Available Background-There are marked sex differences in cardiovascular disease [CVD] manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences.Methods and Results-In 5000 individuals of the population-based Gutenberg Health Study, mean age 55±11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD (coronary artery disease, heart failure, stroke, myocardial infarction, lower extremity artery disease [LEAD] N=561.We observed differential distributions of CVD risk factors with a higher risk factor burden in men. Manifest coronary artery disease, stroke, myocardial infarction and LEAD were more frequent in men; the proportion of heart failure was higher in women. Intermediate phenotypes showed clear sex differences with more beneficial values in women. Fairly linear changes towards less beneficial values with age were observed in both sexes. In multivariable-adjusted regression analyses age, systolic blood pressure and body mass index were consistently associated with intermediate phenotypes in both sexes with different ranking according to random forests, maximum model R² 0.43. Risk factor-adjusted associations with prevalent CVD showed some differences by sex. No interactions by menopausal status were observed. Conclusions-In a population-based cohort we observed sex differences in risk factors and a broad range of intermediate phenotypes of noninvasive cardiovascular structure and function. Their relation to prevalent CVD differed markedly. Our results indicate the need of future investigations to understand sex differences in CVD manifestation.

  8. Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.

    Directory of Open Access Journals (Sweden)

    Sonu Kashyap

    Full Text Available Renovascular hypertension (RVH has deleterious effects on both the kidney and the heart. TGF-β signaling through Smad3 directs tissue fibrosis in chronic injury models. In the 2-kidney 1-clip (2K1C model of RVH, employing mice on the 129 genetic background, Smad3 deficiency (KO protects the stenotic kidney (STK from development of interstitial fibrosis. However, these mice have an increased incidence of sudden cardiac death following 2K1C surgery. The purpose of this study was to characterize the cardiovascular phenotype of these mice. Renal artery stenosis (RAS was established in Wild-type (WT and Smad3 KO mice (129 genetic background by placement of a polytetrafluoroethylene cuff on the right renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice, 1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice studied at 3 days following surgery showed extensive myocyte necrosis in KO but not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2 expression, macrophage influx, and increased MMP-9 activity. At later time points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or dissections were observed at any time point. Smad3 KO mice were backcrossed to the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days following surgery in 62.5% of mice; necropsy revealed aortic dissections as the cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the C57BL/6J background did not develop significant chronic renal damage. We conclude that the cardiovascular manifestations of Smad3 deficient mice are strain-specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice. Future studies will define mechanisms underlying this strain-specific effect on the cardiovascular system.

  9. Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.

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    Nishiwaki, Masato; Ikewaki, Katsunori; Ayaori, Makoto; Mizuno, Kyoichi; Ohashi, Yasuo; Ohsuzu, Fumitaka; Ishikawa, Toshitsugu; Nakamura, Haruo

    2013-03-01

    The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  10. The continuum of monocyte phenotypes: Experimental evidence and prognostic utility in assessing cardiovascular risk.

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    Cignarella, Andrea; Tedesco, Serena; Cappellari, Roberta; Fadini, Gian Paolo

    2018-03-30

    The monocyte-macrophage cell lineage represents a major player in innate immunity, and is involved in many physiologic and pathologic conditions. Particularly, monocyte-macrophages play a very important role in atherosclerosis and cardiovascular disease. Monocyte heterogeneity is well recognized but the biologic and clinical meaning of the various monocyte subtypes is not entirely understood. Traditionally, monocytes can be divided in classical, intermediate, and nonclassical based on expression of the surface antigens CD14 and CD16. While macrophage diversity is now well recognized to organize as a continuum, monocyte subsets have long been considered as separated entities. However, mounting evidence obtained by tracking the ontology of human monocytes help clarifying that monocytes mature from classical to nonclassical ones, through an intermediate phenotype. This concept is therefore best depicted as a continuum, whereas the subdivision into discrete CD14/CD16 subsets appears an oversimplification. In this review, we discuss the evidence supporting the existence of a monocyte continuum along with the technical challenges of monocyte characterization. In particular, we describe the advantage of considering monocytes along a continuous distribution for the evaluation of cardiovascular risk. We make the point that small transition along the monocyte continuum better reflects cardiovascular risk than a simplified analysis of discrete monocyte subsets. Recognizing the monocyte continuum can be helpful to model other pathophysiologic conditions where these cells are involved. ©2018 Society for Leukocyte Biology.

  11. Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

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    Joseph Loscalzo

    2013-01-01

    Full Text Available Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease.

  12. Polycystic ovary syndrome: Cardiovascular risk factors according to specific phenotypes

    DEFF Research Database (Denmark)

    Aziz, Mubeena; Sidelmann, Johannes Jakobsen; Faber, Jens

    2015-01-01

    INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk...... of cardiovascular disease in women with PCOS. MATERIAL AND METHODS: 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS...

  13. Association of heme oxygenase-1 GT-repeat polymorphism with blood pressure phenotypes and its relevance to future cardiovascular mortality risk: an observation based on arsenic-exposed individuals.

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    Wu, Meei-Maan; Chiou, Hung-Yi; Chen, Chi-Ling; Hsu, Ling-I; Lien, Li-Ming; Wang, Chih-Hao; Hsieh, Yi-Chen; Wang, Yuan-Hung; Hsueh, Yu-Mei; Lee, Te-Chang; Cheng, Wen-Fang; Chen, Chien-Jen

    2011-12-01

    Heme oxygenase (HO)-1 is up-regulated as a cellular defense responding to stressful stimuli in experimental studies. A GT-repeat length polymorphism in the HO-1 gene promoter was inversely correlated to HO-1 induction. Here, we reported the association of GT-repeat polymorphism with blood pressure (BP) phenotypes, and their interaction on cardiovascular (CV) mortality risk in arsenic-exposed cohorts. Associations of GT-repeat polymorphism with BP phenotypes were investigated at baseline in a cross-sectional design. Effect of GT-repeat polymorphism on CV mortality was investigated in a longitudinal design stratified by hypertension. GT-repeat variants were grouped by S (accounting for CV covariates. Totally, 894 participants were recruited and analyzed. At baseline, carriers with HO-1 S alleles had lower diastolic BP (L/S genotypes, P = 0.014) and a lower possibility of being hypertensive (L/S genotypes, P = 0.048). After follow-up, HO-1 S allele was significantly associated with a reduced CV risk in hypertensive participants [relative mortality ratio (RMR) 0.27 (CI 0.11, 0.69), P = 0.007] but not in normotensive. Hypertensive participants without carrying the S allele had a 5.23-fold increased risk [RMR 5.23 (CI 1.99, 13.69), P = 0.0008] of CV mortality compared with normotensive carrying the S alleles. HO-1 short GT-repeat polymorphism may play a protective role in BP regulation and CV mortality risk in hypertensive individuals against environmental stressors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Characteristic cardiac phenotypes are detected by cardiovascular magnetic resonance in patients with different clinical phenotypes and genotypes of mitochondrial myopathy.

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    Florian, Anca; Ludwig, Anna; Stubbe-Dräger, Bianca; Boentert, Matthias; Young, Peter; Waltenberger, Johannes; Rösch, Sabine; Sechtem, Udo; Yilmaz, Ali

    2015-05-22

    Mitochondrial myopathies (MM) are a heterogeneous group of inherited conditions resulting from a primary defect in the mitochondrial respiratory chain with consecutively impaired cellular energy metabolism. Small sized studies using mainly electrocardiography (ECG) and echocardiography have revealed cardiac abnormalities ranging from conduction abnormalities and arrhythmias to hypertrophic or dilated cardiomyopathy in these patients. Recently, characteristic patterns of cardiac involvement were documented by cardiovascular magnetic resonance (CMR) in patients with chronic progressive external ophthalmoplegia (CPEO)/Kearns-Sayre syndrome (KSS) and with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The present study aimed to characterize the prevalence and pattern of cardiac abnormalities and to test the additional diagnostic value of CMR in this patient population. The hypothesis that different neuromuscular MM syndromes present with different cardiac disease phenotypes was evaluated. Sixty-four MM patients (50 ± 15 years, 44% male) and 25 matched controls (52 ± 14 years, 36% male) prospectively underwent cardiac evaluations including CMR (comprising cine- and late-gadolinium-enhancement (LGE) imaging). Based on the neuromuscular phenotype and genotype, the patients were grouped: (a) CPEO/KSS (N = 33); (b) MELAS/-like (N = 11); c) myoclonic epilepsy with ragged-red fibers (MERRF) (N = 3) and d) other non-specific MM forms (N = 17). Among the 64 MM patients, 34 (53%) had at least one abnormal CMR finding: 18 (28%) demonstrated an impaired left ventricular ejection-fraction (LV-EF patients showed significantly higher maximal wall thickness (10 ± 3 vs. 8 ± 2 mm, p = 0.005) and concentricity (LV mass to end-diastolic volume: 0.84 ± 0.27 vs. 0.67 ± 0.11, p patients showed the highest frequency of cardiac disease (in 10/11 (91%)), a mostly concentric LV hypertrophy (6/9; 67%) with or

  15. Nontraditional risk factors for cardiovascular disease and visceral adiposity index among different body size phenotypes.

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    Du, T; Zhang, J; Yuan, G; Zhang, M; Zhou, X; Liu, Z; Sun, X; Yu, X

    2015-01-01

    Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities). We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01). Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Plant-based diets and cardiovascular health.

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    Satija, Ambika; Hu, Frank B

    2018-02-13

    Plant-based diets, defined in terms of low frequency of animal food consumption, have been increasingly recommended for their health benefits. Numerous studies have found plant-based diets, especially when rich in high quality plant foods such as whole grains, fruits, vegetables, and nuts, to be associated with lower risk of cardiovascular outcomes and intermediate risk factors. This review summarizes the current evidence base examining the associations of plant-based diets with cardiovascular endpoints, and discusses the potential biological mechanisms underlying their health effects, practical recommendations and applications of this research, and directions for future research. Healthful plant-based diets should be recommended as an environmentally sustainable dietary option for improved cardiovascular health. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Binge eating disorder and obesity: preliminary evidence for distinct cardiovascular and psychological phenotypes.

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    Klatzkin, Rebecca R; Gaffney, Sierra; Cyrus, Kathryn; Bigus, Elizabeth; Brownley, Kimberly A

    2015-04-01

    This study investigated cardiovascular functioning, mood, and eating-related psychological factors at rest and in response to mental stress in three groups of women: 1) Obese women with binge eating disorder (BED; n=9); 2) obese non-BED women (n=15); and 3) normal weight (NW) non-BED women (n=15). Compared to both obese and NW non-BED women, obese women with BED showed heightened overall blood pressure and reported greater depression symptoms, perceived stress, and eating-related psychopathology. Additionally, obese women with BED reported greater overall negative affect and state anxiety compared to obese non-BED women. The heart rate response to stress was blunted in the obese BED group compared to the other groups, but this effect was no longer significant after controlling for baseline differences in depression. Correlational analyses revealed a positive association between stress-induced changes in hunger and cardiovascular measures only in obese women with BED. Longitudinal studies are needed to determine if stress dysregulation and stress-induced increases in hunger contribute to the onset and/or maintenance of BED. In particular, studies utilizing an additional NW BED control group are warranted in order to further examine the impact of BED above and beyond the impact of obesity on psychophysiological functioning and to inform the growing literature regarding stress-related factors that distinguish the BED and obesity phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Register-based studies of cardiovascular disease

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    Abildstrøm, Steen Z; Torp-Pedersen, Christian; Madsen, Mette

    2011-01-01

    Introduction: The use of the unique personal identification number in the Nordic database systems enables the researchers to link the registers at the individual level. The registers can be used for both defining specific patient populations and to identify later events during follow-up. This rev...... the hospitalisation rate and treatment of cardiovascular disease. The risk of unmeasured factors affecting the results calls for cautious interpretation of the results.......-up. This review gives three examples within cardiovascular epidemiology to illustrate the use of the national administrative registers available to all researchers upon request. Research topics: The hospitalisation rate of acute myocardial infarction (AMI) was expected to be increased and case-fatality rate......-based treatment increased significantly over time and adherence to treatment was high. Finally, use of specific nonsteroidal antiinflammatory drugs by healthy subjects was associated with a dose-dependent increase in cardiovascular risk. CONCLUSION: The nationwide registers have proven very useful in monitoring...

  19. Cardiovascular and metabolic profiles amongst different polycystic ovary syndrome phenotypes: who is really at risk?

    Science.gov (United States)

    Daan, Nadine M P; Louwers, Yvonne V; Koster, Maria P H; Eijkemans, Marinus J C; de Rijke, Yolanda B; Lentjes, Eef W G; Fauser, Bart C J M; Laven, Joop S E

    2014-11-01

    To study the cardiometabolic profile characteristics and compare the prevalence of cardiovascular (CV) risk factors between women with different polycystic ovary syndrome (PCOS) phenotypes. A cross-sectional multicenter study analyzing 2,288 well phenotyped women with PCOS. Specialized reproductive outpatient clinic. Women of reproductive age (18-45 years) diagnosed with PCOS. Women suspected of oligo- or anovulation underwent a standardized screening consisting of a systematic medical and reproductive history taking, anthropometric measurements, and transvaginal ultrasonography followed by an extensive endocrinologic/metabolic evaluation. Differences in cardiometabolic profile characteristics and CV risk factor prevalence between women with different PCOS phenotypes, i.e., obesity/overweight, hypertension, insulin resistance, dyslipidemia, and metabolic syndrome. Women with hyperandrogenic PCOS (n=1,219; 53.3% of total) presented with a worse cardiometabolic profile and a higher prevalence of CV risk factors, such as obesity and overweight, insulin resistance, and metabolic syndrome, compared with women with nonhyperandrogenic PCOS. In women with nonhyperandrogenic PCOS overweight/obesity (28.5%) and dyslipidemia (low-density lipoprotein cholesterol≥3.0 mmol/L; 52.2%) were highly prevalent. Women with hyperandrogenic PCOS have a worse cardiometabolic profile and higher prevalence of CV risk factors compared with women with nonhyperandrogenic PCOS. However, all women with PCOS should be screened for the presence of CV risk factors, since the frequently found derangements at a young age imply an elevated risk for the development of CV disease later in life. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    AlShahrani, Mona; Hoehndorf, Robert

    2018-01-01

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease's (or patient's) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  1. Semantic Disease Gene Embeddings (SmuDGE): phenotype-based disease gene prioritization without phenotypes

    KAUST Repository

    Alshahrani, Mona

    2018-04-30

    In the past years, several methods have been developed to incorporate information about phenotypes into computational disease gene prioritization methods. These methods commonly compute the similarity between a disease\\'s (or patient\\'s) phenotypes and a database of gene-to-phenotype associations to find the phenotypically most similar match. A key limitation of these methods is their reliance on knowledge about phenotypes associated with particular genes which is highly incomplete in humans as well as in many model organisms such as the mouse. Results: We developed SmuDGE, a method that uses feature learning to generate vector-based representations of phenotypes associated with an entity. SmuDGE can be used as a trainable semantic similarity measure to compare two sets of phenotypes (such as between a disease and gene, or a disease and patient). More importantly, SmuDGE can generate phenotype representations for entities that are only indirectly associated with phenotypes through an interaction network; for this purpose, SmuDGE exploits background knowledge in interaction networks comprising of multiple types of interactions. We demonstrate that SmuDGE can match or outperform semantic similarity in phenotype-based disease gene prioritization, and furthermore significantly extends the coverage of phenotype-based methods to all genes in a connected interaction network.

  2. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-27

    Phenotypes are the observable characteristics of an organism, and they are widely recorded in biology and medicine. To facilitate data integration, ontologies that formally describe phenotypes are being developed in several domains. I will describe a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology of phenotypes is now applied in biomedical research.

  3. Body Mass Index below Obesity Threshold Implies Similar Cardiovascular Risk among Various Polycystic Ovary Syndrome Phenotypes.

    Science.gov (United States)

    Bagir, Gulay Simsek; Bakiner, Okan S; Bozkirli, Emre; Cavlak, Gulhan; Serinsoz, Hulya; Ertorer, M Eda

    2016-01-01

    The aim of this study was to determine the cardiometabolic risk factors in different polycystic ovary syndrome (PCOS) phenotypes. This cross-sectional study was performed between 2010 and 2011. Eighty-nine patients with PCOS and 25 age- and weight-matched healthy controls were included in the study. Patients were grouped using the Rotterdam 2003 criteria as: group 1, oligomenorrhea and/or anovulation (ANOV) and hyperandrogenemia (HA) and/or hyperandrogenism (n = 23); group 2, ANOV and polycystic ovaries (PCO; n = 22); group 3, HA and PCO (n = 22); group 4, ANOV, HA and PCO (n = 22); group 5, controls (n = 25). Laboratory blood tests for diagnosis and cardiometabolic risk assessments were performed. Insulin resistance (IR) was calculated in all patients with the homeostasis model assessment of IR (HOMA-IR) formula. An euglycemic hyperinsulinemic clamp test was performed on 5 randomly selected cases in each subgroup, making 25 cases in total, and indicated as the 'M' value (mg/kg/min), which is the total body glucose disposal rate. The mean BMl values of the groups were: group 1, 26.1 ± 5.3; group 2, 27.9 ± 5.2; group 3, 24.3 ± 4.2; group 4, 27.9 ± 7.5; group 5, 24.7 ± 5.2 (p > 0.05). There were no differences in the lipid profile, plasma glucose, HOMA-IR, insulin and M values between the groups (p > 0.05). Phenotypes with oligomenorrhea/anovulation (groups 1, 2 and 4) were more obese than group 3 (p = 0.039). The cardiometabolic risk profile was similar among the PCOS subgroups. This finding could be attributed to the mean BMl values, which, being below 30, were not within the obesity range. Obesity appeared to be an important determinant of high cardiovascular risk in PCOS. © 2015 S. Karger AG, Basel.

  4. Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent

    Directory of Open Access Journals (Sweden)

    Erdman Robert

    2010-09-01

    Full Text Available Abstract Background The INSIG2 gene has been implicated in cholesterol metabolism and a single nucleotide polymorphism (SNP near INSIG2 has been shown to be associated with obesity. We sought to determine the relationship of the INSIG2 SNP to cardiovascular disease (CVD related phenotypes. Methods and Results Nine hundred forty six patients undergoing percutaneous coronary intervention (PCI in wave 5 of the multicenter NHLBI Dynamic Registry were genotyped using RT-PCR/TaqMan/allelic discrimination for the rs7566605 SNP near the INSIG2 gene. Clinical variables analyzed include demographics, medical history, and procedural details. The prevalence of peripheral vascular disease (PVD was significantly higher in older men (≥65 years who were either homozygous or carriers of the obesity/lipid risk allele ("C" compared to non-carriers (odds ratio 3.4, p = 0.013 using a logistic regression model incorporating history of hypercholesterolemia, history of hypertension, cerebrovascular disease, history of diabetes, and BMI. A similar relationship with cerebrovascular disease was found in older (>65 women (odds ratio 3.4, p = 0.013. The INSIG2 SNP was not associated with BMI, nor with other clinical variables. Conclusion Age and gender may influence the association of the INSIG2 obesity SNP with PVD and cerebrovascular disease in patients with pre-existing CVD.

  5. Knowledge-based analysis of phenotypes

    KAUST Repository

    Hoendorf, Robert

    2016-01-01

    a formal framework to describe phenotypes. A formalized theory of phenotypes is not only useful for domain analysis, but can also be applied to assist in the diagnosis of rare genetic diseases, and I will show how our results on the ontology

  6. Ontology-based validation and identification of regulatory phenotypes

    KAUST Repository

    Kulmanov, Maxat

    2018-01-31

    Motivation: Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations Results: We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. Our method can also be applied to the rule-based prediction of phenotypes from functions. We show that the predicted phenotypes can be utilized for identification of protein-protein interactions and gene-disease associations. Based on experimental functional annotations, we predict phenotypes for 1,986 genes in mouse and 7,301 genes in human for which no experimental phenotypes have yet been determined.

  7. Ontology-based validation and identification of regulatory phenotypes

    KAUST Repository

    Kulmanov, Maxat; Schofield, Paul N; Gkoutos, Georgios V; Hoehndorf, Robert

    2018-01-01

    Motivation: Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations Results: We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. Our method can also be applied to the rule-based prediction of phenotypes from functions. We show that the predicted phenotypes can be utilized for identification of protein-protein interactions and gene-disease associations. Based on experimental functional annotations, we predict phenotypes for 1,986 genes in mouse and 7,301 genes in human for which no experimental phenotypes have yet been determined.

  8. Machine learning based analysis of cardiovascular images

    NARCIS (Netherlands)

    Wolterink, JM

    2017-01-01

    Cardiovascular diseases (CVDs), including coronary artery disease (CAD) and congenital heart disease (CHD) are the global leading cause of death. Computed tomography (CT) and magnetic resonance imaging (MRI) allow non-invasive imaging of cardiovascular structures. This thesis presents machine

  9. Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome.

    Directory of Open Access Journals (Sweden)

    Victoria Campuzano

    2012-02-01

    Full Text Available A hallmark feature of Williams-Beuren Syndrome (WBS is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX-mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII, oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII-mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.

  10. SQL based cardiovascular ultrasound image classification.

    Science.gov (United States)

    Nandagopalan, S; Suryanarayana, Adiga B; Sudarshan, T S B; Chandrashekar, Dhanalakshmi; Manjunath, C N

    2013-01-01

    This paper proposes a novel method to analyze and classify the cardiovascular ultrasound echocardiographic images using Naïve-Bayesian model via database OLAP-SQL. Efficient data mining algorithms based on tightly-coupled model is used to extract features. Three algorithms are proposed for classification namely Naïve-Bayesian Classifier for Discrete variables (NBCD) with SQL, NBCD with OLAP-SQL, and Naïve-Bayesian Classifier for Continuous variables (NBCC) using OLAP-SQL. The proposed model is trained with 207 patient images containing normal and abnormal categories. Out of the three proposed algorithms, a high classification accuracy of 96.59% was achieved from NBCC which is better than the earlier methods.

  11. [Hypertriglyceridemic waist phenotype: associated factors and comparison with other cardiovascular and metabolic risk indicators in the ELSA-Brasil study].

    Science.gov (United States)

    Freitas, Roberta Souza; Fonseca, Maria de Jesus Mendes da; Schmidt, Maria Inês; Molina, Maria Del Carmen Bisi; Almeida, Maria da Conceição Chagas de

    2018-03-29

    This study's objectives were to estimate the prevalence of hypertriglyceridemic waist (HTW) phenotype in participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), identify associated risk factors, and compare with other cardiovascular and metabolic risk indicators. This was a cross-sectional study with baseline data from a cohort of public employees. HTW is defined as the simultaneous presence of increased waist circumference (WC) (≥ 80cm for women, ≥ 90cm for men according to the International Diabetes Federation - IDF; and ≥ 88cm for women, ≥ 102cm for men according to the U.S. National Cholesterol Education Program - NCEP) and hypertriglyceridemia. Associations between independent variables and HTW were tested with multivariate logistic regression models. HTW was also compared to other cardiovascular and metabolic risk indicators by means of correlation tests, kappa index, sensitivity, and specificity. After exclusions, 12,811 participants were analyzed. Prevalence of HTW ranged from 24.7% (IDF) to 13.3% (NCEP). HTW was associated with age, excessive alcohol consumption, former smoking, low HDL, non-high HDL, and increased C-reactive protein, independently of gender or the criterion used to define HTW. HTW was associated with cardiovascular risk indicators, especially metabolic syndrome. The high prevalence of HTW and its association with cardiovascular risk indicators, especially metabolic syndrome, supports its use as a cardiometabolic risk screening tool in clinical practice.

  12. Excess Metabolic and Cardiovascular Risk is not Manifested in all Phenotypes of Polycystic Ovary Syndrome: Implications for Diagnosis and Treatment.

    Science.gov (United States)

    Daskalopoulos, Georgios; Karkanaki, Artemis; Piouka, Athanasia; Prapas, Nikolaos; Panidis, Dimitrios; Gkeleris, Paraschos; Athyros, Vasilios G

    2015-01-01

    To assess the potential differences in the metabolic and cardiovascular disease (CVD) risk between the distinct phenotypes of the Polycystic Ovary Syndrome (PCOS) according to the Rotterdam definition regardless of body mass index (BMI). The study included 300 women; 240 women with PCOS, according to the Rotterdam criteria and 60 controls without PCOS. All women were further subdivided, according to their BMI, into normal-weight and overweight/obese and PCOS women were furthermore subdivided to the 4 phenotypes of the syndrome. A complete hormonal and metabolic profile as well as the levels of high sensitivity C reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured. Levels of surrogate markers of subclinical atherosclerosis (hsCRP and Lp-PLA2), levels of evaluated CVD risk score using risk engines, and several correlations of CVD risk factors. hsCRP levels were higher but not significantly so in PCOS women compared with controls. In lean PCOS patients, Lp-PLA2 levels were significantly higher, compared with lean controls, mainly in the 2 classic phenotypes. Overweight/obese patients in all 4 phenotypes had significantly higher Lp-PLA2 levels compared with overweight/obese controls. Evaluated CVD risk according to 4 risk engines was not different among phenotypes and between PCOS patients and controls. There were several correlations of risk factors with metabolic syndrome and non-alcoholic fatty liver disease requiring appropriate treatment. Only 2 of 4 Rotterdam phenotypes, identical with those of the classic PCOS definition, have excess cardiometabolic risk. These need to be treated to prevent CVD events.

  13. The Role of Alcohol Consumption in the Aetiology of Different Cardiovascular Disease Phenotypes: a CALIBER Study

    Science.gov (United States)

    2013-05-28

    Chronic Stable Angina; Unstable Angina; Coronary Heart Disease Not Otherwise Specified; Acute Myocardial Infarction; Heart Failure; Ventricular Arrhythmias; Cardiac Arrest; Abdominal Aortic Aneurysm; Peripheral Arterial Disease; Ischaemic Stroke; Subarachnoid Haemorrhagic Stroke; Intracerebral Haemorrhagic Stroke; Stroke Not Otherwise Specified; Sudden Cardiac Death; Unheralded Coronary Death; Mortality; Coronary Heart Disease (CHD); Cardiovascular Disease (CVD); Fatal Cardiovascular Disease (Fatal CVD); ST Elevation Myocardial Infarction (STEMI); Non-ST Elevation Myocardial Infarction (nSTEMI); Myocardial Infarction Not Otherwise Specified (MI NOS)

  14. Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.

    Science.gov (United States)

    Lee, Jessica J Y; Gottlieb, Michael M; Lever, Jake; Jones, Steven J M; Blau, Nenad; van Karnebeek, Clara D M; Wasserman, Wyeth W

    2018-05-01

    Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM and their disease-characterizing phenotypes. While our efforts with IEMbase have realized benefits, taking full advantage of phenomics requires a comprehensive curation of IEM phenotypes in core phenomics projects, which is dependent upon contributions from the IEM clinical and research community. Here, we assess the inclusion of IEM biochemical phenotypes in a core phenomics project, the Human Phenotype Ontology. We then demonstrate the utility of biochemical phenotypes using a text-based phenomics method to predict gene-disease relationships, showing that the prediction of IEM genes is significantly better using biochemical rather than clinical profiles. The findings herein provide a motivating goal for the IEM community to expand the computationally accessible descriptions of biochemical phenotypes associated with IEM in phenomics resources.

  15. Functional identification of the promoter of SLC4A5, a gene associated with cardiovascular and metabolic phenotypes in the HERITAGE Family Study.

    Science.gov (United States)

    Stütz, Adrian M; Teran-Garcia, Margarita; Rao, D C; Rice, Treva; Bouchard, Claude; Rankinen, Tuomo

    2009-11-01

    The sodium bicarbonate cotransporter gene SLC4A5, associated earlier with cardiovascular phenotypes, was tested for associations in the HERITAGE Family Study, and possible mechanisms were investigated. Twelve tag-single nucleotide polymorphisms (SNPs) covering the SLC4A5 gene were analyzed in 276 Black and 503 White healthy, sedentary subjects. Associations were tested using a variance components-based (QTDT) method with data adjusted for age, sex and body size. In Whites, rs6731545 and rs7571842 were significantly associated with resting and submaximal exercise pulse pressure (PP) (0.0004 HERITAGE Family Study are likely due to neither variation in the promoter nor known coding SNPs of SLC4A5.

  16. Genetic Modifiers of Cardiovascular Phenotype Caused by Elastin Haploinsufficiency Act by Extrinsic Noncomplementation*

    Science.gov (United States)

    Kozel, Beth A.; Knutsen, Russell H.; Ye, Li; Ciliberto, Christopher H.; Broekelmann, Thomas J.; Mecham, Robert P.

    2011-01-01

    Elastin haploinsufficiency causes the cardiovascular complications associated with Williams-Beuren syndrome and isolated supravalvular aortic stenosis. Significant variability exists in the vascular pathology in these individuals. Using the Eln+/− mouse, we sought to identify the source of this variability. Following outcrossing of C57Bl/6J Eln+/−, two backgrounds were identified whose cardiovascular parameters deviated significantly from the parental strain. F1 progeny of the C57Bl/6J; Eln+/−x129X1/SvJ were more hypertensive and their arteries less compliant. In contrast, Eln+/− animals crossed to DBA/2J were protected from the pathologic changes associated with elastin insufficiency. Among the crosses, aortic elastin and collagen content did not correlate with quantitative vasculopathy traits. Quantitative trait locus analysis performed on F2 C57; Eln+/−x129 intercrosses identified highly significant peaks on chromosome 1 (LOD 9.7) for systolic blood pressure and on chromosome 9 (LOD 8.7) for aortic diameter. Additional peaks were identified that affect only Eln+/−, including a region upstream of Eln on chromosome 5 (LOD 4.5). Bioinformatic analysis of the quantitative trait locus peaks revealed several interesting candidates, including Ren1, Ncf1, and Nos1; genes whose functions are unrelated to elastic fiber assembly, but whose effects may synergize with elastin insufficiency to predispose to hypertension and stiffer blood vessels. Real time RT-PCR studies show background-specific increased expression of Ncf1 (a subunit of the NOX2 NAPDH oxidase) that parallel the presence of increased oxidative stress in Eln+/− aortas. This finding raises the possibility that polymorphisms in genes affecting the generation of reactive oxygen species alter cardiovascular function in individuals with elastin haploinsufficiency through extrinsic noncomplementation. PMID:22049077

  17. Ultra-high frequency ultrasound biomicroscopy and high throughput cardiovascular phenotyping in a large scale mouse mutagenesis screen

    Science.gov (United States)

    Liu, Xiaoqin; Francis, Richard; Tobita, Kimimasa; Kim, Andy; Leatherbury, Linda; Lo, Cecilia W.

    2013-02-01

    Ultrasound biomicroscopy (UBM) is ideally suited for phenotyping fetal mice for congenital heart disease (CHD), as imaging can be carried out noninvasively to provide both hemodynamic and structural information essential for CHD diagnosis. Using the UBM (Vevo 2100; 40Hz) in conjunction with the clinical ultrasound system (Acuson Sequioa C512; 15Hz), we developed a two-step screening protocol to scan thousands fetuses derived from ENU mutagenized pedigrees. A wide spectrum of CHD was detected by the UBM, which were subsequently confirmed with follow-up necropsy and histopathology examination with episcopic fluorescence image capture. CHD observed included outflow anomalies, left/right heart obstructive lesions, septal/valvular defects and cardiac situs anomalies. Meanwhile, various extracardiac defects were found, such as polydactyly, craniofacial defects, exencephaly, omphalocele-cleft palate, most of which were associated with cardiac defects. Our analyses showed the UBM was better at assessing cardiac structure and blood flow profiles, while conventional ultrasound allowed higher throughput low-resolution screening. Our study showed the integration of conventional clinical ultrasound imaging with the UBM for fetal mouse cardiovascular phenotyping can maximize the detection and recovery of CHD mutants.

  18. Adiposity Indexes as Phenotype-Specific Markers of Preclinical Metabolic Alterations and Cardiovascular Risk in Polycystic Ovary Syndrome: A Cross-Sectional Study.

    Science.gov (United States)

    Mario, Fernanda Missio; Graff, Scheila Karen; Spritzer, Poli Mara

    2017-05-01

    Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. 2 PCOS phenotypes (classic and ovulatory) are currently recognized as the most prevalent, with important differences in terms of cardiometabolic features. We studied the performance of different adiposity indexes to predict preclinical metabolic alterations and cardiovascular risk in 234 women with PCOS (173 with classic and 61 with ovulatory PCOS) and 129 controls. Performance of waist circumference, waist-to-height ratio, conicity index, lipid accumulation product, and visceral adiposity index was assessed based on HOMA-IR ≥ 3.8 as reference standard for screening preclinical metabolic alterations and cardiovascular risk factors in each group. Lipid accumulation product had the best accuracy for classic PCOS, and visceral adiposity index had the best accuracy for ovulatory PCOS. By applying the cutoff point of lipid accumulation productcardiometabolic alterations (Prisk for hypertension, dyslipidemia, and impaired glucose tolerance. In ovulatory PCOS, visceral adiposity index ≥ 1.32 was capable of detecting women with significantly higher blood pressure and less favorable glycemic and lipid variables as compared to ovulatory PCOS with lower visceral adiposity index (Pcardiometabolic risk and secure early interventions. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Prenatal Air Pollution Exposure and Early Cardiovascular Phenotypes in Young Adults.

    Directory of Open Access Journals (Sweden)

    Carrie V Breton

    Full Text Available Exposure to ambient air pollutants increases risk for adverse cardiovascular health outcomes in adults. We aimed to evaluate the contribution of prenatal air pollutant exposure to cardiovascular health, which has not been thoroughly evaluated. The Testing Responses on Youth (TROY study consists of 768 college students recruited from the University of Southern California in 2007-2009. Participants attended one study visit during which blood pressure, heart rate and carotid artery arterial stiffness (CAS and carotid artery intima-media thickness (CIMT were assessed. Prenatal residential addresses were geocoded and used to assign prenatal and postnatal air pollutant exposure estimates using the U.S. Environmental Protection Agency's Air Quality System (AQS database. The associations between CAS, CIMT and air pollutants were assessed using linear regression analysis. Prenatal PM10 and PM2.5 exposures were associated with increased CAS. For example, a 2 SD increase in prenatal PM2.5 was associated with CAS indices, including a 5% increase (β = 1.05, 95% CI 1.00-1.10 in carotid stiffness index beta, a 5% increase (β = 1.05, 95% CI 1.01-1.10 in Young's elastic modulus and a 5% decrease (β = 0.95, 95% CI 0.91-0.99 in distensibility. Mutually adjusted models of pre- and postnatal PM2.5 further suggested the prenatal exposure was most relevant exposure period for CAS. No associations were observed for CIMT. In conclusion, prenatal exposure to elevated air pollutants may increase carotid arterial stiffness in a young adult population of college students. Efforts aimed at limiting prenatal exposures are important public health goals.

  20. Professor: A motorized field-based phenotyping cart

    Science.gov (United States)

    An easy-to-customize, low-cost, low disturbance, motorized proximal sensing cart for field-based high-throughput phenotyping is described. General dimensions, motor specifications, and a remote operation application are given. The cart, named Professor, supports mounting multiple proximal sensors an...

  1. Agreement in cardiovascular risk rating based on anthropometric parameters

    International Nuclear Information System (INIS)

    Dantas, Endilly Maria da Silva; Pinto, Cristiane Jordânia; Freitas, Rodrigo Pegado de Abreu; Medeiros, Anna Cecília Queiroz de

    2015-01-01

    To investigate the agreement in evaluation of risk of developing cardiovascular diseases based on anthropometric parameters in young adults. The study included 406 students, measuring weight, height, and waist and neck circumferences. Waist-to-height ratio and the conicity index. The kappa coefficient was used to assess agreement in risk classification for cardiovascular diseases. The positive and negative specific agreement values were calculated as well. The Pearson chi-square (χ"2) test was used to assess associations between categorical variables (p<0.05). The majority of the parameters assessed (44%) showed slight (k=0.21 to 0.40) and/or poor agreement (k<0.20), with low values of negative specific agreement. The best agreement was observed between waist circumference and waist-to-height ratio both for the general population (k=0.88) and between sexes (k=0.93 to 0.86). There was a significant association (p<0.001) between the risk of cardiovascular diseases and females when using waist circumference and conicity index, and with males when using neck circumference. This resulted in a wide variation in the prevalence of cardiovascular disease risk (5.5%-36.5%), depending on the parameter and the sex that was assessed. The results indicate variability in agreement in assessing risk for cardiovascular diseases, based on anthropometric parameters, and which also seems to be influenced by sex. Further studies in the Brazilian population are required to better understand this issue

  2. Agreement in cardiovascular risk rating based on anthropometric parameters

    Energy Technology Data Exchange (ETDEWEB)

    Dantas, Endilly Maria da Silva; Pinto, Cristiane Jordânia; Freitas, Rodrigo Pegado de Abreu; Medeiros, Anna Cecília Queiroz de [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil)

    2015-07-01

    To investigate the agreement in evaluation of risk of developing cardiovascular diseases based on anthropometric parameters in young adults. The study included 406 students, measuring weight, height, and waist and neck circumferences. Waist-to-height ratio and the conicity index. The kappa coefficient was used to assess agreement in risk classification for cardiovascular diseases. The positive and negative specific agreement values were calculated as well. The Pearson chi-square (χ{sup 2}) test was used to assess associations between categorical variables (p<0.05). The majority of the parameters assessed (44%) showed slight (k=0.21 to 0.40) and/or poor agreement (k<0.20), with low values of negative specific agreement. The best agreement was observed between waist circumference and waist-to-height ratio both for the general population (k=0.88) and between sexes (k=0.93 to 0.86). There was a significant association (p<0.001) between the risk of cardiovascular diseases and females when using waist circumference and conicity index, and with males when using neck circumference. This resulted in a wide variation in the prevalence of cardiovascular disease risk (5.5%-36.5%), depending on the parameter and the sex that was assessed. The results indicate variability in agreement in assessing risk for cardiovascular diseases, based on anthropometric parameters, and which also seems to be influenced by sex. Further studies in the Brazilian population are required to better understand this issue.

  3. 1H NMR spectroscopy-based interventional metabolic phenotyping

    DEFF Research Database (Denmark)

    Lauridsen, Michael B; Bliddal, Henning; Christensen, Robin

    2010-01-01

    1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow-up with a......1H NMR spectroscopy-based metabolic phenotyping was used to identify biomarkers in the plasma of patients with rheumatoid arthritis (RA). Forty-seven patients with RA (23 with active disease at baseline and 24 in remission) and 51 healthy subjects were evaluated during a one-year follow......-up with assessments of disease activity (DAS-28) and 1H NMR spectroscopy of plasma samples. Discriminant analysis provided evidence that the metabolic profiles predicted disease severity. Cholesterol, lactate, acetylated glycoprotein, and lipid signatures were found to be candidate biomarkers for disease severity.......0007). However, after 31 days of optimized therapy, the two patient groups were not significantly different (P=0.91). The metabolic profiles of both groups of RA patients were different from the healthy subjects. 1H NMR-based metabolic phenotyping of plasma samples in patients with RA is well suited...

  4. Changes in smoking during a community-based cardiovascular ...

    African Journals Online (AJOL)

    Changes in smoking during a community-based cardiovascular disease intervention programme - The Coronary Risk Factor Study. ... South African Medical Journal ... Smoking quit rates were strongly " associated with initial smoking level, with light smokers being significanty more successful quitters than heavy smokers.

  5. Cardiovascular imaging environment: will the future be cloud-based?

    Science.gov (United States)

    Kawel-Boehm, Nadine; Bluemke, David A

    2017-07-01

    In cardiovascular CT and MR imaging large datasets have to be stored, post-processed, analyzed and distributed. Beside basic assessment of volume and function in cardiac magnetic resonance imaging e.g., more sophisticated quantitative analysis is requested requiring specific software. Several institutions cannot afford various types of software and provide expertise to perform sophisticated analysis. Areas covered: Various cloud services exist related to data storage and analysis specifically for cardiovascular CT and MR imaging. Instead of on-site data storage, cloud providers offer flexible storage services on a pay-per-use basis. To avoid purchase and maintenance of specialized software for cardiovascular image analysis, e.g. to assess myocardial iron overload, MR 4D flow and fractional flow reserve, evaluation can be performed with cloud based software by the consumer or complete analysis is performed by the cloud provider. However, challenges to widespread implementation of cloud services include regulatory issues regarding patient privacy and data security. Expert commentary: If patient privacy and data security is guaranteed cloud imaging is a valuable option to cope with storage of large image datasets and offer sophisticated cardiovascular image analysis for institutions of all sizes.

  6. Family-Based Approaches to Cardiovascular Health Promotion.

    Science.gov (United States)

    Vedanthan, Rajesh; Bansilal, Sameer; Soto, Ana Victoria; Kovacic, Jason C; Latina, Jacqueline; Jaslow, Risa; Santana, Maribel; Gorga, Elio; Kasarskis, Andrew; Hajjar, Roger; Schadt, Eric E; Björkegren, Johan L; Fayad, Zahi A; Fuster, Valentin

    2016-04-12

    Cardiovascular disease is the leading cause of mortality in the world, and the increasing burden is largely a consequence of modifiable behavioral risk factors that interact with genomics and the environment. Continuous cardiovascular health promotion and disease prevention throughout the lifespan is critical, and the family is a central entity in this process. In this review, we describe the potential rationale and mechanisms that contribute to the importance of family for cardiovascular health promotion, focusing on: 1) mutual interdependence of the family system; 2) shared environment; 3) parenting style; 4) caregiver perceptions; and 5) genomics. We conclude that family-based approaches that target both caregivers and children, encourage communication among the family unit, and address the structural and environmental conditions in which families live and operate are likely to be the most effective approach to promote cardiovascular health. We describe lessons learned, future implications, and applications to ongoing and planned studies. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. Novel blood protein based scaffolds for cardiovascular tissue engineering

    Directory of Open Access Journals (Sweden)

    Kuhn Antonia I.

    2016-09-01

    Full Text Available A major challenge in cardiovascular tissue engineering is the fabrication of scaffolds, which provide appropriate morphological and mechanical properties while avoiding undesirable immune reactions. In this study electrospinning was used to fabricate scaffolds out of blood proteins for cardiovascular tissue engineering. Lyophilised porcine plasma was dissolved in deionised water at a final concentration of 7.5% m/v and blended with 3.7% m/v PEO. Electrospinning resulted in homogeneous fibre morphologies with a mean fibre diameter of 151 nm, which could be adapted to create macroscopic shapes (mats, tubes. Cross-linking with glutaraldehyde vapour improved the long-term stability of protein based scaffolds in comparison to untreated scaffolds, resulting in a mass loss of 41% and 96% after 28 days of incubation in aqueous solution, respectively.

  8. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population.

    Science.gov (United States)

    Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; Ali, Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A; Kissebah, Ahmed H

    2013-03-19

    Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (pmetabolism (βWHR=-0.72; βLDL-c=-0.53) while positively correlated with plasma adiponectin (β=0.24). Further, we show that differential methylation of FABP3 affects binding activity with

  9. Risk prediction of cardiovascular death based on the QTc interval

    DEFF Research Database (Denmark)

    Nielsen, Jonas B; Graff, Claus; Rasmussen, Peter V

    2014-01-01

    electrocardiograms from 173 529 primary care patients aged 50-90 years were collected during 2001-11. The Framingham formula was used for heart rate-correction of the QT interval. Data on medication, comorbidity, and outcomes were retrieved from administrative registries. During a median follow-up period of 6......AIMS: Using a large, contemporary primary care population we aimed to provide absolute long-term risks of cardiovascular death (CVD) based on the QTc interval and to test whether the QTc interval is of value in risk prediction of CVD on an individual level. METHODS AND RESULTS: Digital...

  10. Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

    Science.gov (United States)

    Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

    2017-11-01

    To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

  11. Linking human diseases to animal models using ontology-based phenotype annotation.

    Directory of Open Access Journals (Sweden)

    Nicole L Washington

    2009-11-01

    Full Text Available Scientists and clinicians who study genetic alterations and disease have traditionally described phenotypes in natural language. The considerable variation in these free-text descriptions has posed a hindrance to the important task of identifying candidate genes and models for human diseases and indicates the need for a computationally tractable method to mine data resources for mutant phenotypes. In this study, we tested the hypothesis that ontological annotation of disease phenotypes will facilitate the discovery of new genotype-phenotype relationships within and across species. To describe phenotypes using ontologies, we used an Entity-Quality (EQ methodology, wherein the affected entity (E and how it is affected (Q are recorded using terms from a variety of ontologies. Using this EQ method, we annotated the phenotypes of 11 gene-linked human diseases described in Online Mendelian Inheritance in Man (OMIM. These human annotations were loaded into our Ontology-Based Database (OBD along with other ontology-based phenotype descriptions of mutants from various model organism databases. Phenotypes recorded with this EQ method can be computationally compared based on the hierarchy of terms in the ontologies and the frequency of annotation. We utilized four similarity metrics to compare phenotypes and developed an ontology of homologous and analogous anatomical structures to compare phenotypes between species. Using these tools, we demonstrate that we can identify, through the similarity of the recorded phenotypes, other alleles of the same gene, other members of a signaling pathway, and orthologous genes and pathway members across species. We conclude that EQ-based annotation of phenotypes, in conjunction with a cross-species ontology, and a variety of similarity metrics can identify biologically meaningful similarities between genes by comparing phenotypes alone. This annotation and search method provides a novel and efficient means to identify

  12. Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing.

    Science.gov (United States)

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie L; Boston, Raymond C

    2015-12-01

    (1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2) To develop an HC phenotype-specific dosing strategy for HC that accounts for HM production using clinical pharmacokinetics integrated with pharmacogenetics for patient safety. In silico clinical trial simulation. Healthy white men and women without comorbidities or history of opioid, or any other drug or nutraceutical use, age 26.3±5.7 years (mean±SD; range, 19 to 36 y) and weight 71.9±16.8 kg (range, 50 to 108 kg). CYP2D6 phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype-specific percentages of HM formed from HC. PMs had lower indices of HC disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and the t1/2 was increased by about 68% compared with EMs. The canonical order for HC clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke, was reduced about 70% in PM. However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects. Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

  13. Similarity-based search of model organism, disease and drug effect phenotypes

    KAUST Repository

    Hoehndorf, Robert

    2015-02-19

    Background: Semantic similarity measures over phenotype ontologies have been demonstrated to provide a powerful approach for the analysis of model organism phenotypes, the discovery of animal models of human disease, novel pathways, gene functions, druggable therapeutic targets, and determination of pathogenicity. Results: We have developed PhenomeNET 2, a system that enables similarity-based searches over a large repository of phenotypes in real-time. It can be used to identify strains of model organisms that are phenotypically similar to human patients, diseases that are phenotypically similar to model organism phenotypes, or drug effect profiles that are similar to the phenotypes observed in a patient or model organism. PhenomeNET 2 is available at http://aber-owl.net/phenomenet. Conclusions: Phenotype-similarity searches can provide a powerful tool for the discovery and investigation of molecular mechanisms underlying an observed phenotypic manifestation. PhenomeNET 2 facilitates user-defined similarity searches and allows researchers to analyze their data within a large repository of human, mouse and rat phenotypes.

  14. Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

    Science.gov (United States)

    Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

  15. Detection of Cardiovascular Anomalies: An Observer-Based Approach

    KAUST Repository

    Ledezma, Fernando

    2012-07-01

    In this thesis, a methodology for the detection of anomalies in the cardiovascular system is presented. The cardiovascular system is one of the most fascinating and complex physiological systems. Nowadays, cardiovascular diseases constitute one of the most important causes of mortality in the world. For instance, an estimate of 17.3 million people died in 2008 from cardiovascular diseases. Therefore, many studies have been devoted to modeling the cardiovascular system in order to better understand its behavior and find new reliable diagnosis techniques. The lumped parameter model of the cardiovascular system proposed in [1] is restructured using a hybrid systems approach in order to include a discrete input vector that represents the influence of the mitral and aortic valves in the different phases of the cardiac cycle. Parting from this model, a Taylor expansion around the nominal values of a vector of parameters is conducted. This expansion serves as the foundation for a component fault detection process to detect changes in the physiological parameters of the cardiovascular system which could be associated with cardiovascular anomalies such as atherosclerosis, aneurysm, high blood pressure, etc. An Extended Kalman Filter is used in order to achieve a joint estimation of the state vector and the changes in the considered parameters. Finally, a bank of filters is, as in [2], used in order to detect the appearance of heart valve diseases, particularly stenosis and regurgitation. The first numerical results obtained are presented.

  16. Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis

    NARCIS (Netherlands)

    Lee, Jessica J. Y.; Gottlieb, Michael M.; Lever, Jake; Jones, Steven J. M.; Blau, Nenad; van Karnebeek, Clara D. M.; Wasserman, Wyeth W.

    2018-01-01

    Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze

  17. Clinical neurocardiology defining the value of neuroscience‐based cardiovascular therapeutics

    Science.gov (United States)

    Ajijola, Olujimi A.; Anand, Inder; Armour, J. Andrew; Chen, Peng‐Sheng; Esler, Murray; De Ferrari, Gaetano M.; Fishbein, Michael C.; Goldberger, Jeffrey J.; Harper, Ronald M.; Joyner, Michael J.; Khalsa, Sahib S.; Kumar, Rajesh; Lane, Richard; Mahajan, Aman; Po, Sunny; Schwartz, Peter J.; Somers, Virend K.; Valderrabano, Miguel; Vaseghi, Marmar; Zipes, Douglas P.

    2016-01-01

    Abstract The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience‐based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases. PMID:27114333

  18. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives

    Directory of Open Access Journals (Sweden)

    Guijun Yang

    2017-06-01

    Full Text Available Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI, chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping.

  19. Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

    Directory of Open Access Journals (Sweden)

    Maki Fukami

    2012-01-01

    Full Text Available Aromatase excess syndrome (AEXS is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon. These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.

  20. Identifying novel phenotypes of vulnerability and resistance to activity-based anorexia in adolescent female rats.

    Science.gov (United States)

    Barbarich-Marsteller, Nicole C; Underwood, Mark D; Foltin, Richard W; Myers, Michael M; Walsh, B Timothy; Barrett, Jeffrey S; Marsteller, Douglas A

    2013-11-01

    Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats. Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30-35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes. Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit. The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa. Copyright © 2013 Wiley Periodicals, Inc.

  1. A community-based exercise intervention transitions metabolically abnormal obese adults to a metabolically healthy obese phenotype

    Science.gov (United States)

    Dalleck, Lance C; Van Guilder, Gary P; Richardson, Tara B; Bredle, Donald L; Janot, Jeffrey M

    2014-01-01

    Background Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO) phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1) whether community-based exercise training transitions MAO adults to metabolically healthy, and 2) whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness. Methods and results Metabolic syndrome components were measured in 332 adults (190 women, 142 men) before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index ≥30 kg · m2) adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals (Pmetabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1–65.4; Pexercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the greatest increase in fitness were significantly more likely to become metabolically healthy. Community exercise may be an effective model for primary prevention of cardiovascular disease. PMID:25120373

  2. Pathophysiology-based phenotyping in type 2 diabetes

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Henriksen, Jan E; Olsen, Michael H

    2018-01-01

    clinically diagnosed type 2 diabetes. METHODS: We first identified all patients with rare subtypes of diabetes, latent autoimmune diabetes of adults (LADA), secondary diabetes, or glucocorticoid-associated diabetes. We then used the homeostatic assessment model to subphenotype all remaining patients......BACKGROUND: Type 2 diabetes may be a more heterogeneous disease than previously thought. Better understanding of pathophysiological subphenotypes could lead to more individualized diabetes treatment. We examined the characteristics of different phenotypes among 5813 Danish patients with new...... into insulinopenic (high insulin sensitivity and low beta cell function), classical (low insulin sensitivity and low beta cell function), or hyperinsulinemic (low insulin sensitivity and high beta cell function) type 2 diabetes. RESULTS: Among 5813 patients diagnosed with incident type 2 diabetes in the community...

  3. Menopause management: a cardiovascular risk-based approach.

    Science.gov (United States)

    Haines, C J; Farrell, E

    2010-08-01

    Hormone replacement therapy (HRT) remains the gold standard for the management of menopausal symptoms; however, HRT use has declined due to concerns over possible adverse side-effects. Approaches to menopause management are continually being revised and these extend beyond the control of recognized menopausal symptoms to encompass wider aspects of menopausal women's health. Hypertension and associated cardiovascular risk are particularly important unmet needs in postmenopausal women, especially in the Asia-Pacific region which has a rapidly aging population and bears around half of the global burden of cardiovascular disease, two-thirds of which has been attributed to elevated blood pressure. As first point of contact for women with menopausal symptoms, gynecologists play a gatekeeper role in assessing women's health, providing appropriate lifestyle counseling, and, where appropriate, implementing treatment or referral to relevant specialists. This paper, with contributions by gynecologists and cardiologists from Asia Pacific and beyond, summarizes available evidence and provides a treatment algorithm that employs a flexible blood pressure classification strategy to assist physicians in their decision-making for the individualized management of menopausal symptoms in women with low, moderate and high cardiovascular risk, and also for women with diabetes. Individualized HRT according to cardiovascular risk may yield improvements in cardiovascular health, as well as managing menopausal symptoms.

  4. Fine mapping quantitative trait loci under selective phenotyping strategies based on linkage and linkage disequilibrium criteria

    DEFF Research Database (Denmark)

    Ansari-Mahyari, S; Berg, P; Lund, M S

    2009-01-01

    disequilibrium-based sampling criteria (LDC) for selecting individuals to phenotype are compared to random phenotyping in a quantitative trait loci (QTL) verification experiment using stochastic simulation. Several strategies based on LAC and LDC for selecting the most informative 30%, 40% or 50% of individuals...... for phenotyping to extract maximum power and precision in a QTL fine mapping experiment were developed and assessed. Linkage analyses for the mapping was performed for individuals sampled on LAC within families and combined linkage disequilibrium and linkage analyses was performed for individuals sampled across...... the whole population based on LDC. The results showed that selecting individuals with similar haplotypes to the paternal haplotypes (minimum recombination criterion) using LAC compared to random phenotyping gave at least the same power to detect a QTL but decreased the accuracy of the QTL position. However...

  5. Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.

    Science.gov (United States)

    Deva, Djeven Parameshvara; Hanneman, Kate; Li, Qin; Ng, Ming Yen; Wasim, Syed; Morel, Chantal; Iwanochko, Robert M; Thavendiranathan, Paaladinesh; Crean, Andrew Michael

    2016-03-31

    Although it is known that Anderson-Fabry Disease (AFD) can mimic the morphologic manifestations of hypertrophic cardiomyopathy (HCM) on echocardiography, there is a lack of cardiovascular magnetic resonance (CMR) literature on this. There is limited information in the published literature on the distribution of myocardial fibrosis in patients with AFD, with scar reported principally in the basal inferolateral midwall. All patients with confirmed AFD undergoing CMR at our center were included. Left ventricular (LV) volumes, wall thicknesses and scar were analyzed offline. Patients were categorized into 4 groups: (1) no wall thickening; (2) concentric hypertrophy; (3) asymmetric septal hypertrophy (ASH); and (4) apical hypertrophy. Charts were reviewed for clinical information. Thirty-nine patients were included (20 males [51%], median age 45.2 years [range 22.3-64.4]). Almost half (17/39) had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three quarters of these (13/17) had typical inferolateral midwall scar. A quarter (9/39) had both concentric wall thickening and typical inferolateral scar. A subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall thickness, total LV scar, apical scar and mid-ventricular scar than those with concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and sustained ventricular tachycardia (p = 0.008). Concentric thickening and inferolateral mid-myocardial scar are the most common manifestations of AFD, but the spectrum includes cases morphologically identical to apical and ASH subtypes of HCM and these have more apical and mid-ventricular LV scar. Significant LVH is associated with ventricular arrhythmia.

  6. GenomeRNAi: a database for cell-based RNAi phenotypes.

    Science.gov (United States)

    Horn, Thomas; Arziman, Zeynep; Berger, Juerg; Boutros, Michael

    2007-01-01

    RNA interference (RNAi) has emerged as a powerful tool to generate loss-of-function phenotypes in a variety of organisms. Combined with the sequence information of almost completely annotated genomes, RNAi technologies have opened new avenues to conduct systematic genetic screens for every annotated gene in the genome. As increasing large datasets of RNAi-induced phenotypes become available, an important challenge remains the systematic integration and annotation of functional information. Genome-wide RNAi screens have been performed both in Caenorhabditis elegans and Drosophila for a variety of phenotypes and several RNAi libraries have become available to assess phenotypes for almost every gene in the genome. These screens were performed using different types of assays from visible phenotypes to focused transcriptional readouts and provide a rich data source for functional annotation across different species. The GenomeRNAi database provides access to published RNAi phenotypes obtained from cell-based screens and maps them to their genomic locus, including possible non-specific regions. The database also gives access to sequence information of RNAi probes used in various screens. It can be searched by phenotype, by gene, by RNAi probe or by sequence and is accessible at http://rnai.dkfz.de.

  7. An office-based approach to emotional and behavioral risk factor reduction for cardiovascular disease.

    Science.gov (United States)

    Hochman, Daniel M; Feinstein, Robert E; Stauter, Erinn C

    2013-01-01

    There are many psychological risk factors for cardiovascular disease, and the ability to reduce mortality depends on an ability to integrate care of these risk factors with traditional Framingham cardiovascular risk and use them both in routine practice. The aim of this article is to provide an update of all the major emotional and behavioral cardiovascular risk factors along with a practical treatment model for implementation. First, we provide a review of major emotional and behavioral cardiovascular risk factors, the associated primary effect, and proposed mechanism of action. Second, we provide an office-based approach to cardiovascular risk factor reduction and methods of reducing barriers to implementation, called Prevention Oriented Primary Care-Abridged. The approach integrates several forms of detection, assessment using the 3As (ask, assess, assist), and Stages of Change approaches, and subsequent efficient and targeted treatment with either Motivational Interviewing or further office intervention. A case example is provided to help illustrate this process.

  8. Clinical phenotype-based gene prioritization: an initial study using semantic similarity and the human phenotype ontology.

    Science.gov (United States)

    Masino, Aaron J; Dechene, Elizabeth T; Dulik, Matthew C; Wilkens, Alisha; Spinner, Nancy B; Krantz, Ian D; Pennington, Jeffrey W; Robinson, Peter N; White, Peter S

    2014-07-21

    Exome sequencing is a promising method for diagnosing patients with a complex phenotype. However, variant interpretation relative to patient phenotype can be challenging in some scenarios, particularly clinical assessment of rare complex phenotypes. Each patient's sequence reveals many possibly damaging variants that must be individually assessed to establish clear association with patient phenotype. To assist interpretation, we implemented an algorithm that ranks a given set of genes relative to patient phenotype. The algorithm orders genes by the semantic similarity computed between phenotypic descriptors associated with each gene and those describing the patient. Phenotypic descriptor terms are taken from the Human Phenotype Ontology (HPO) and semantic similarity is derived from each term's information content. Model validation was performed via simulation and with clinical data. We simulated 33 Mendelian diseases with 100 patients per disease. We modeled clinical conditions by adding noise and imprecision, i.e. phenotypic terms unrelated to the disease and terms less specific than the actual disease terms. We ranked the causative gene against all 2488 HPO annotated genes. The median causative gene rank was 1 for the optimal and noise cases, 12 for the imprecision case, and 60 for the imprecision with noise case. Additionally, we examined a clinical cohort of subjects with hearing impairment. The disease gene median rank was 22. However, when also considering the patient's exome data and filtering non-exomic and common variants, the median rank improved to 3. Semantic similarity can rank a causative gene highly within a gene list relative to patient phenotype characteristics, provided that imprecision is mitigated. The clinical case results suggest that phenotype rank combined with variant analysis provides significant improvement over the individual approaches. We expect that this combined prioritization approach may increase accuracy and decrease effort for

  9. Exercise for prevention of cardiovascular disease: Evidence-based recommendations

    Directory of Open Access Journals (Sweden)

    Geevar Zachariah

    2017-01-01

    Full Text Available Sedentary lifestyle is one of the major risk factors for cardiovascular disease (CVD. In India, a large percentage of the people are physically inactive with fewer than 10% engaging in recreational physical activity. Physical activity has many beneficial effects on the risk factors for CVD. Apart from improving fitness level, it decreases myocardial oxygen demand and improves myocardial perfusion. There is an inverse association between physical activity and all-cause mortality. In primary prevention, physical inactivity is associated with a two-fold increase in the risk for coronary events. In secondary prevention, data confirm the existence of an inverse dose–response relationship between cardiovascular fitness and the all-cause mortality in large populations of cardiovascular patients. Guidelines from the American authorities as well as the European Society of Cardiology provide specific recommendations for exercise depending on the clinical setting (primary or secondary prevention of CVD and the patient-specific factors (the patient's physical activity level and the perceived CVD risk. The present review summarizes the clinical evidence regarding the role of exercise in CVD prevention and the exercise recommendations from the leading Cardiac societies.

  10. Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature

    Science.gov (United States)

    Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

    2018-01-01

    Background Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. Objective The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. Methods PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET’s phenotype representation with PheKnow-Cloud’s by using PheKnow-Cloud’s experimental setup. In PIVET’s framework, we also introduce a statistical model trained on domain expert–verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. Results PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with

  11. Phenotype Instance Verification and Evaluation Tool (PIVET): A Scaled Phenotype Evidence Generation Framework Using Web-Based Medical Literature.

    Science.gov (United States)

    Henderson, Jette; Ke, Junyuan; Ho, Joyce C; Ghosh, Joydeep; Wallace, Byron C

    2018-05-04

    Researchers are developing methods to automatically extract clinically relevant and useful patient characteristics from raw healthcare datasets. These characteristics, often capturing essential properties of patients with common medical conditions, are called computational phenotypes. Being generated by automated or semiautomated, data-driven methods, such potential phenotypes need to be validated as clinically meaningful (or not) before they are acceptable for use in decision making. The objective of this study was to present Phenotype Instance Verification and Evaluation Tool (PIVET), a framework that uses co-occurrence analysis on an online corpus of publically available medical journal articles to build clinical relevance evidence sets for user-supplied phenotypes. PIVET adopts a conceptual framework similar to the pioneering prototype tool PheKnow-Cloud that was developed for the phenotype validation task. PIVET completely refactors each part of the PheKnow-Cloud pipeline to deliver vast improvements in speed without sacrificing the quality of the insights PheKnow-Cloud achieved. PIVET leverages indexing in NoSQL databases to efficiently generate evidence sets. Specifically, PIVET uses a succinct representation of the phenotypes that corresponds to the index on the corpus database and an optimized co-occurrence algorithm inspired by the Aho-Corasick algorithm. We compare PIVET's phenotype representation with PheKnow-Cloud's by using PheKnow-Cloud's experimental setup. In PIVET's framework, we also introduce a statistical model trained on domain expert-verified phenotypes to automatically classify phenotypes as clinically relevant or not. Additionally, we show how the classification model can be used to examine user-supplied phenotypes in an online, rather than batch, manner. PIVET maintains the discriminative power of PheKnow-Cloud in terms of identifying clinically relevant phenotypes for the same corpus with which PheKnow-Cloud was originally developed, but

  12. iBeetle-Base: a database for RNAi phenotypes in the red flour beetle Tribolium castaneum.

    Science.gov (United States)

    Dönitz, Jürgen; Schmitt-Engel, Christian; Grossmann, Daniela; Gerischer, Lizzy; Tech, Maike; Schoppmeier, Michael; Klingler, Martin; Bucher, Gregor

    2015-01-01

    The iBeetle-Base (http://ibeetle-base.uni-goettingen.de) makes available annotations of RNAi phenotypes, which were gathered in a large scale RNAi screen in the red flour beetle Tribolium castaneum (iBeetle screen). In addition, it provides access to sequence information and links for all Tribolium castaneum genes. The iBeetle-Base contains the annotations of phenotypes of several thousands of genes knocked down during embryonic and metamorphic epidermis and muscle development in addition to phenotypes linked to oogenesis and stink gland biology. The phenotypes are described according to the EQM (entity, quality, modifier) system using controlled vocabularies and the Tribolium morphological ontology (TrOn). Furthermore, images linked to the respective annotations are provided. The data are searchable either for specific phenotypes using a complex 'search for morphological defects' or a 'quick search' for gene names and IDs. The red flour beetle Tribolium castaneum has become an important model system for insect functional genetics and is a representative of the most species rich taxon, the Coleoptera, which comprise several devastating pests. It is used for studying insect typical development, the evolution of development and for research on metabolism and pest control. Besides Drosophila, Tribolium is the first insect model organism where large scale unbiased screens have been performed. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Estimating cardiovascular disease incidence from prevalence: a spreadsheet based model

    Directory of Open Access Journals (Sweden)

    Xue Feng Hu

    2017-01-01

    Full Text Available Abstract Background Disease incidence and prevalence are both core indicators of population health. Incidence is generally not as readily accessible as prevalence. Cohort studies and electronic health record systems are two major way to estimate disease incidence. The former is time-consuming and expensive; the latter is not available in most developing countries. Alternatively, mathematical models could be used to estimate disease incidence from prevalence. Methods We proposed and validated a method to estimate the age-standardized incidence of cardiovascular disease (CVD, with prevalence data from successive surveys and mortality data from empirical studies. Hallett’s method designed for estimating HIV infections in Africa was modified to estimate the incidence of myocardial infarction (MI in the U.S. population and incidence of heart disease in the Canadian population. Results Model-derived estimates were in close agreement with observed incidence from cohort studies and population surveillance systems. This method correctly captured the trend in incidence given sufficient waves of cross-sectional surveys. The estimated MI declining rate in the U.S. population was in accordance with the literature. This method was superior to closed cohort, in terms of the estimating trend of population cardiovascular disease incidence. Conclusion It is possible to estimate CVD incidence accurately at the population level from cross-sectional prevalence data. This method has the potential to be used for age- and sex- specific incidence estimates, or to be expanded to other chronic conditions.

  14. Towards precision medicine-based therapies for glioblastoma: interrogating human disease genomics and mouse phenotypes.

    Science.gov (United States)

    Chen, Yang; Gao, Zhen; Wang, Bingcheng; Xu, Rong

    2016-08-22

    Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.

  15. Beyond the Central Dogma: Model-Based Learning of How Genes Determine Phenotypes

    Science.gov (United States)

    Reinagel, Adam; Speth, Elena Bray

    2016-01-01

    In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population…

  16. DeepPVP: phenotype-based prioritization of causative variants using deep learning

    KAUST Repository

    Boudellioua, Imene; Kulmanov, Maxat; Schofield, Paul N; Gkoutos, Georgios V; Hoehndorf, Robert

    2018-01-01

    phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp Conclusions: DeepPVP further improves on existing variant prioritization methods both in terms of speed as well

  17. DeepPVP: phenotype-based prioritization of causative variants using deep learning

    KAUST Repository

    Boudellioua, Imene

    2018-05-02

    Background: Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient\\'s phenotype. Results: We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp Conclusions: DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.

  18. Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries

    DEFF Research Database (Denmark)

    Ueda, Peter; Woodward, Mark; Lu, Yuan

    2017-01-01

    BACKGROUND: Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and ...

  19. The rationale/design of the Guimarães/Vizela study: a multimodal population-based cohort study to determine global cardiovascular risk and disease.

    Science.gov (United States)

    Cunha, Pedro Guimarães; Cotter, Jorge; Oliveira, Pedro; Vila, Isabel; Sousa, Nuno

    2014-06-01

    Cardiovascular disease and dementia are growing medical and social problems in aging societies. Appropriate knowledge of cardiovascular disease and cognitive decline risk factors (RFs) are critical for global CVR health preventive intervention. Many epidemiological studies use case definition based on data collected/measured in a single visit, a fact that can overestimate prevalence rates and distant from clinical practice demanding criteria. Portugal displays an elevated stroke mortality rate. However, population's global CV risk characterization is limited, namely, considering traditional/nontraditional RF and new intermediate phenotypes of CV and renal disease. Association of hemodynamic variables (pulse wave velocity and central blood pressure) with global CVR stratification, cognitive performance, and kidney disease are practically inexistent at a dwelling population level. After reviewing published data, we designed a population-based cohort study to analyze the prevalence of these cardiovascular RFs and intermediate phenotypes, using random sampling of adult dwellers living in 2 adjacent cities. Strict definition of phenotypes was planned: subjects were observed twice, and several hemodynamic and other biological variables measured at least 3 months apart. Three thousand thirty-eight subjects were enrolled, and extensive data collection (including central and peripheral blood pressure, pulse wave velocity), sample processing, and biobank edification were carried out. One thousand forty-seven cognitive evaluations were performed. Seeking for CV risk reclassification, early identification of subjects at risk, and evidence of early vascular aging and cognitive and renal function decline, using the strict daily clinical practice criteria, will lead to better resource allocation in preventive measures at a population level.

  20. Prediction of quantitative phenotypes based on genetic networks: a case study in yeast sporulation

    Directory of Open Access Journals (Sweden)

    Shen Li

    2010-09-01

    Full Text Available Abstract Background An exciting application of genetic network is to predict phenotypic consequences for environmental cues or genetic perturbations. However, de novo prediction for quantitative phenotypes based on network topology is always a challenging task. Results Using yeast sporulation as a model system, we have assembled a genetic network from literature and exploited Boolean network to predict sporulation efficiency change upon deleting individual genes. We observe that predictions based on the curated network correlate well with the experimentally measured values. In addition, computational analysis reveals the robustness and hysteresis of the yeast sporulation network and uncovers several patterns of sporulation efficiency change caused by double gene deletion. These discoveries may guide future investigation of underlying mechanisms. We have also shown that a hybridized genetic network reconstructed from both temporal microarray data and literature is able to achieve a satisfactory prediction accuracy of the same quantitative phenotypes. Conclusions This case study illustrates the value of predicting quantitative phenotypes based on genetic network and provides a generic approach.

  1. Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits.

    Science.gov (United States)

    Blaazer, Antoni R; Orrling, Kristina M; Shanmugham, Anitha; Jansen, Chimed; Maes, Louis; Edink, Ewald; Sterk, Geert Jan; Siderius, Marco; England, Paul; Bailey, David; de Esch, Iwan J P; Leurs, Rob

    2015-01-01

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. © 2014 Society for Laboratory Automation and Screening.

  2. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study.

    Science.gov (United States)

    Di Dalmazi, Guido; Vicennati, Valentina; Garelli, Silvia; Casadio, Elena; Rinaldi, Eleonora; Giampalma, Emanuela; Mosconi, Cristina; Golfieri, Rita; Paccapelo, Alexandro; Pagotto, Uberto; Pasquali, Renato

    2014-05-01

    Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome. From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18-30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50-138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline. 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were

  3. Deep machine learning provides state-of-the-art performance in image-based plant phenotyping.

    Science.gov (United States)

    Pound, Michael P; Atkinson, Jonathan A; Townsend, Alexandra J; Wilson, Michael H; Griffiths, Marcus; Jackson, Aaron S; Bulat, Adrian; Tzimiropoulos, Georgios; Wells, Darren M; Murchie, Erik H; Pridmore, Tony P; French, Andrew P

    2017-10-01

    In plant phenotyping, it has become important to be able to measure many features on large image sets in order to aid genetic discovery. The size of the datasets, now often captured robotically, often precludes manual inspection, hence the motivation for finding a fully automated approach. Deep learning is an emerging field that promises unparalleled results on many data analysis problems. Building on artificial neural networks, deep approaches have many more hidden layers in the network, and hence have greater discriminative and predictive power. We demonstrate the use of such approaches as part of a plant phenotyping pipeline. We show the success offered by such techniques when applied to the challenging problem of image-based plant phenotyping and demonstrate state-of-the-art results (>97% accuracy) for root and shoot feature identification and localization. We use fully automated trait identification using deep learning to identify quantitative trait loci in root architecture datasets. The majority (12 out of 14) of manually identified quantitative trait loci were also discovered using our automated approach based on deep learning detection to locate plant features. We have shown deep learning-based phenotyping to have very good detection and localization accuracy in validation and testing image sets. We have shown that such features can be used to derive meaningful biological traits, which in turn can be used in quantitative trait loci discovery pipelines. This process can be completely automated. We predict a paradigm shift in image-based phenotyping bought about by such deep learning approaches, given sufficient training sets. © The Authors 2017. Published by Oxford University Press.

  4. Obesity and Cardiovascular Risk: Variations in Visfatin Gene Can Modify the Obesity Associated Cardiovascular Risk. Results from the Segovia Population Based-Study. Spain.

    Directory of Open Access Journals (Sweden)

    María Teresa Martínez Larrad

    Full Text Available Our aim was to investigate if genetic variations in the visfatin gene (SNPs rs7789066/ rs11977021/rs4730153 could modify the cardiovascular-risk (CV-risk despite the metabolic phenotype (obesity and glucose tolerance. In addition, we investigated the relationship between insulin sensitivity and variations in visfatin gene.A population-based study in rural and urban areas of the Province of Segovia, Spain, was carried out in the period of 2001-2003 years. A total of 587 individuals were included, 25.4% subjects were defined as obese (BMI ≥30 Kg/m2.Plasma visfatin levels were significantly higher in obese subjects with DM2 than in other categories of glucose tolerance. The genotype AA of the rs4730153 SNP was significantly associated with fasting glucose, fasting insulin and HOMA-IR (Homeostasis model assessment-insulin resistance after adjustment for gender, age, BMI and waist circumference. The obese individuals carrying the CC genotype of the rs11977021 SNP showed higher circulating levels of fasting proinsulin after adjustment for the same variables. The genotype AA of the rs4730153 SNP seems to be protective from CV-risk either estimated by Framingham or SCORE charts in general population; and in obese and non-obese individuals. No associations with CV-risk were observed for other studied SNPs (rs11977021/rs7789066.In summary, this is the first study which concludes that the genotype AA of the rs4730153 SNP appear to protect against CV-risk in obese and non-obese individuals, estimated by Framingham and SCORE charts. Our results confirm that the different polymorphisms in the visfatin gene might be influencing the glucose homeostasis in obese individuals.

  5. Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

    NARCIS (Netherlands)

    Boekel, Naomi B.; Schaapveld, Michael; Gietema, Jourik A.; Russell, Nicola S.; Poortmans, Philip; Theuws, Jacqueline C. M.; Schinagl, Dominic A. X.; Rietveld, Derek H. F.; Versteegh, Michel I. M.; Visser, Otto; Rutgers, Emiel J. T.; Aleman, Berthe M. P.; van Leeuwen, Flora E.

    2016-01-01

    Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between

  6. Individual-based models for adaptive diversification in high-dimensional phenotype spaces.

    Science.gov (United States)

    Ispolatov, Iaroslav; Madhok, Vaibhav; Doebeli, Michael

    2016-02-07

    Most theories of evolutionary diversification are based on equilibrium assumptions: they are either based on optimality arguments involving static fitness landscapes, or they assume that populations first evolve to an equilibrium state before diversification occurs, as exemplified by the concept of evolutionary branching points in adaptive dynamics theory. Recent results indicate that adaptive dynamics may often not converge to equilibrium points and instead generate complicated trajectories if evolution takes place in high-dimensional phenotype spaces. Even though some analytical results on diversification in complex phenotype spaces are available, to study this problem in general we need to reconstruct individual-based models from the adaptive dynamics generating the non-equilibrium dynamics. Here we first provide a method to construct individual-based models such that they faithfully reproduce the given adaptive dynamics attractor without diversification. We then show that a propensity to diversify can be introduced by adding Gaussian competition terms that generate frequency dependence while still preserving the same adaptive dynamics. For sufficiently strong competition, the disruptive selection generated by frequency-dependence overcomes the directional evolution along the selection gradient and leads to diversification in phenotypic directions that are orthogonal to the selection gradient. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses.

    Science.gov (United States)

    Darrow, Sabrina M; Illmann, Cornelia; Gauvin, Caitlin; Osiecki, Lisa; Egan, Crystelle A; Greenberg, Erica; Eckfield, Monika; Hirschtritt, Matthew E; Pauls, David L; Batterson, James R; Berlin, Cheston M; Malaty, Irene A; Woods, Douglas W; Scharf, Jeremiah M; Mathews, Carol A

    2015-08-30

    Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants' diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Phenotype-Based Screening of Small Molecules to Modify Plant Cell Walls Using BY-2 Cells.

    Science.gov (United States)

    Okubo-Kurihara, Emiko; Matsui, Minami

    2018-01-01

    The plant cell wall is an important and abundant biomass with great potential for use as a modern recyclable resource. For effective utilization of this cellulosic biomass, its ability to degrade efficiently is key point. With the aim of modifying the cell wall to allow easy decomposition, we used chemical biological technology to alter its structure. As a first step toward evaluating the chemicals in the cell wall we employed a phenotype-based approach using high-throughput screening. As the plant cell wall is essential in determining cell morphology, phenotype-based screening is particularly effective in identifying compounds that bring about alterations in the cell wall. For rapid and reproducible screening, tobacco BY-2 cell is an excellent system in which to observe cell morphology. In this chapter, we provide a detailed chemical biological methodology for studying cell morphology using tobacco BY-2 cells.

  9. Comparison of cardiovascular risk factors in maintenance hemodialysis patients based on phase angle of bioimpedance analysis

    Science.gov (United States)

    Muzasti, R. A.; Lubis, H. R.

    2018-03-01

    Mortality and morbidity rate, especially from cardiovascular disease in hemodialysis patients in Indonesia is still quite high. One of indicator to assess the predictive value of mortality is the phase angle (PhA) of bioimpedance analysis (BIA) scan examination. Determining the comparison of BMI and laboratory data as cardiovascular risk factors in hemodialysis patients based on PhA.A cross-sectional analytical study was done on 155 outpatientsin RasyidaRenal Hospital, Medan in 2016. Patients were two groups, namely PhAcardiovascular risk factors of hemodialysis patients were determined by age, BMI, and hemoglobin.

  10. Evaluation of HeartSmarts, a Faith-Based Cardiovascular Health Education Program.

    Science.gov (United States)

    Tettey, Naa-Solo; Duran, Pedro A; Andersen, Holly S; Boutin-Foster, Carla

    2017-02-01

    In order to effectively address cardiovascular disease among African Americans, evidence-based health information must be disseminated within a context aligned with the values and beliefs of the population. Faith-based organizations play a critical role in meeting the religious and spiritual needs of many African Americans. Additionally, faith-based organizations can be effective in health promotion. A manual was created by incorporating biblical scriptures relating to health messages drawn from existing health manuals oriented toward African Americans. Lay health educators active in their churches participated in a 12-week training to learn the basics of cardiovascular disease and methods for delivering the program to their congregations' members. After the completion of the training, these lay health educators recruited participants from their respective churches and administered their own 12-week HeartSmarts program. Measurements of participants' systolic and diastolic blood pressure (mmHg), height (in.), weight (lbs.), and waist circumference (in.) were taken, and cardiovascular disease knowledge assessments (based on 20 open-ended questions) were administered at the start and end of the 12-week programs. Fourteen predominantly African American churches in NYC participated. Of the 221 participants, 199 completed the program. There were significant reductions in pretest and posttest total participant averages for systolic BP (4.48 mmHg, p health assessment scores had an average increase of 12.74 correct responses (p health messages and reducing cardiovascular risk among African Americans.

  11. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

    Science.gov (United States)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed; White, Jacqui; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Fray, Martin; Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl Mj; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve Dm

    2015-09-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.

  12. Microarray-based mutation detection and phenotypic characterization in Korean patients with retinitis pigmentosa

    Science.gov (United States)

    Kim, Cinoo; Kim, Kwang Joong; Bok, Jeong; Lee, Eun-Ju; Kim, Dong-Joon; Oh, Ji Hee; Park, Sung Pyo; Shin, Joo Young; Lee, Jong-Young

    2012-01-01

    Purpose To evaluate microarray-based genotyping technology for the detection of mutations responsible for retinitis pigmentosa (RP) and to perform phenotypic characterization of patients with pathogenic mutations. Methods DNA from 336 patients with RP and 360 controls was analyzed using the GoldenGate assay with microbeads containing 95 previously reported disease-associated mutations from 28 RP genes. Mutations identified by microarray-based genotyping were confirmed by direct sequencing. Segregation analysis and phenotypic characterization were performed in patients with mutations. The disease severity was assessed by visual acuity, electroretinography, optical coherence tomography, and kinetic perimetry. Results Ten RP-related mutations of five RP genes (PRP3 pre-mRNA processing factor 3 homolog [PRPF3], rhodopsin [RHO], phosphodiesterase 6B [PDE6B], peripherin 2 [PRPH2], and retinitis pigmentosa 1 [RP1]) were identified in 26 of the 336 patients (7.7%) and in six of the 360 controls (1.7%). The p.H557Y mutation in PDE6B, which was homozygous in four patients and heterozygous in nine patients, was the most frequent mutation (2.5%). Mutation segregation was assessed in four families. Among the patients with missense mutations, the most severe phenotype occurred in patients with p.D984G in RP1; less severe phenotypes occurred in patients with p.R135W in RHO; a relatively moderate phenotype occurred in patients with p.T494M in PRPF3, p.H557Y in PDE6B, or p.W316G in PRPH2; and a mild phenotype was seen in a patient with p.D190N in RHO. Conclusions The results reveal that the GoldenGate assay may not be an efficient method for molecular diagnosis in RP patients with rare mutations, although it has proven to be reliable and efficient for high-throughput genotyping of single-nucleotide polymorphisms. The clinical features varied according to the mutations. Continuous effort to identify novel RP genes and mutations in a population is needed to improve the efficiency and

  13. A new Web-based medical tool for assessment and prevention of comprehensive cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Daniele Franchi

    2011-02-01

    Full Text Available Daniele Franchi1,2, Davide Cini1, Giorgio Iervasi11Istituto di Fisiologia Clinica, CNR, Pisa, Italy; 2Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina, Università di Pisa, Pisa, ItalyBackground: Multifactor cardiovascular disease is the leading cause of death; besides well-known cardiovascular risk factors, several emerging factors such as mental stress, diet type, and physical inactivity, have been associated to cardiovascular disease. To date, preventive strategies are based on the concept of absolute risk calculated by different algorithms and scoring systems. However, in general practice the patient's data collection represents a critical issue.Design: A new multipurpose computer-based program has been developed in order to:1 easily calculate and compare the absolute cardiovascular risk by the Framingham, Procam, and Progetto Cuore algorithms; 2 to design a web-based computerized tool for prospective collection of structured data; 3 to support the doctor in the decision-making process for patients at risk according to recent international guidelines.Methods: During a medical consultation the doctor utilizes a common computer connected by Internet to a medical server where all the patient's data and software reside. The program evaluates absolute and relative cardiovascular risk factors, personalized patient's goals, and multiparametric trends, monitors critical parameter values, and generates an automated medical report.Results: In a pilot study on 294 patients (47% males; mean age 60 ± 12 years [± SD] the global time to collect data at first consultation was 13 ± 11 minutes which declined to 8 ± 7 minutes at the subsequent consultation. In 48.2% of cases the program revealed 2 or more primary risk factor parameters outside guideline indications and gave specific clinical suggestions to return altered parameters to target values.Conclusion: The web-based system proposed here may represent a feasible and

  14. Network Based Integrated Analysis of Phenotype-Genotype Data for Prioritization of Candidate Symptom Genes

    Directory of Open Access Journals (Sweden)

    Xing Li

    2014-01-01

    Full Text Available Background. Symptoms and signs (symptoms in brief are the essential clinical manifestations for individualized diagnosis and treatment in traditional Chinese medicine (TCM. To gain insights into the molecular mechanism of symptoms, we develop a computational approach to identify the candidate genes of symptoms. Methods. This paper presents a network-based approach for the integrated analysis of multiple phenotype-genotype data sources and the prediction of the prioritizing genes for the associated symptoms. The method first calculates the similarities between symptoms and diseases based on the symptom-disease relationships retrieved from the PubMed bibliographic database. Then the disease-gene associations and protein-protein interactions are utilized to construct a phenotype-genotype network. The PRINCE algorithm is finally used to rank the potential genes for the associated symptoms. Results. The proposed method gets reliable gene rank list with AUC (area under curve 0.616 in classification. Some novel genes like CALCA, ESR1, and MTHFR were predicted to be associated with headache symptoms, which are not recorded in the benchmark data set, but have been reported in recent published literatures. Conclusions. Our study demonstrated that by integrating phenotype-genotype relationships into a complex network framework it provides an effective approach to identify candidate genes of symptoms.

  15. Validity of selected cardiovascular field-based test among Malaysian ...

    African Journals Online (AJOL)

    Based on emerge obese problem among Malaysian, this research is formulated to validate published tests among healthy female adult. Selected test namely; 20 meter multi-stage shuttle run, 2.4km run test, 1 mile walk test and Harvard Step test were correlated with laboratory test (Bruce protocol) to find the criterion validity ...

  16. Design of PREVENCION: a population-based study of cardiovascular disease in Peru.

    Science.gov (United States)

    Medina-Lezama, Josefina; Chirinos, Julio A; Zea Díaz, Humberto; Morey, Oscar; Bolanos, Juan F; Munoz-Atahualpa, Edgar; Chirinos-Pacheco, Julio

    2005-11-02

    Latin America is undergoing the epidemiologic transition that occurred earlier in developed countries, and is likely to face a gigantic epidemic of heart disease in the next few years unless urgent action is taken. The first essential component of any effective cardiovascular disease (CVD) control program is to establish reliable estimates of cardiovascular disease-related morbidity and mortality. However, such data from population-based studies in Latin America are still lacking. In this paper, we present the design and operation of PREVENCION (Estudio Peruano de Prevalencia de Enfermedades Cardiovasculares, for Peruvian Study of the Prevalence of Cardiovascular diseases). PREVENCION is an ongoing population-based study on a representative sample of the civilian non-institutionalized population of the second largest city in Peru. Its population is comparable to the rest of the Peruvian urban population and closely resembles other Latin American populations in countries such as Bolivia and Ecuador. Our study will contribute to the enormous task of understanding and preventing CVD in Latin America.

  17. Cardiovascular disease in patients with osteogenesis imperfecta — a nationwide, register-based cohort study

    OpenAIRE

    Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe; Langdahl, Bente L.; Hermann, Anne Pernille; Diederichsen, Axel CP; Abrahamsen, Bo; Brixen, Kim

    2016-01-01

    BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI.OBJECTIVE: To investigate the risk of symptomatic CVD in OI.DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study.PARTICIPANTS: All patients registered with the diag...

  18. An XML-based interchange format for genotype-phenotype data.

    Science.gov (United States)

    Whirl-Carrillo, M; Woon, M; Thorn, C F; Klein, T E; Altman, R B

    2008-02-01

    Recent advances in high-throughput genotyping and phenotyping have accelerated the creation of pharmacogenomic data. Consequently, the community requires standard formats to exchange large amounts of diverse information. To facilitate the transfer of pharmacogenomics data between databases and analysis packages, we have created a standard XML (eXtensible Markup Language) schema that describes both genotype and phenotype data as well as associated metadata. The schema accommodates information regarding genes, drugs, diseases, experimental methods, genomic/RNA/protein sequences, subjects, subject groups, and literature. The Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB; www.pharmgkb.org) has used this XML schema for more than 5 years to accept and process submissions containing more than 1,814,139 SNPs on 20,797 subjects using 8,975 assays. Although developed in the context of pharmacogenomics, the schema is of general utility for exchange of genotype and phenotype data. We have written syntactic and semantic validators to check documents using this format. The schema and code for validation is available to the community at http://www.pharmgkb.org/schema/index.html (last accessed: 8 October 2007). (c) 2007 Wiley-Liss, Inc.

  19. Research on cardiovascular disease prediction based on distance metric learning

    Science.gov (United States)

    Ni, Zhuang; Liu, Kui; Kang, Guixia

    2018-04-01

    Distance metric learning algorithm has been widely applied to medical diagnosis and exhibited its strengths in classification problems. The k-nearest neighbour (KNN) is an efficient method which treats each feature equally. The large margin nearest neighbour classification (LMNN) improves the accuracy of KNN by learning a global distance metric, which did not consider the locality of data distributions. In this paper, we propose a new distance metric algorithm adopting cosine metric and LMNN named COS-SUBLMNN which takes more care about local feature of data to overcome the shortage of LMNN and improve the classification accuracy. The proposed methodology is verified on CVDs patient vector derived from real-world medical data. The Experimental results show that our method provides higher accuracy than KNN and LMNN did, which demonstrates the effectiveness of the Risk predictive model of CVDs based on COS-SUBLMNN.

  20. Research on Improved Depth Belief Network-Based Prediction of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Peng Lu

    2018-01-01

    Full Text Available Quantitative analysis and prediction can help to reduce the risk of cardiovascular disease. Quantitative prediction based on traditional model has low accuracy. The variance of model prediction based on shallow neural network is larger. In this paper, cardiovascular disease prediction model based on improved deep belief network (DBN is proposed. Using the reconstruction error, the network depth is determined independently, and unsupervised training and supervised optimization are combined. It ensures the accuracy of model prediction while guaranteeing stability. Thirty experiments were performed independently on the Statlog (Heart and Heart Disease Database data sets in the UCI database. Experimental results showed that the mean of prediction accuracy was 91.26% and 89.78%, respectively. The variance of prediction accuracy was 5.78 and 4.46, respectively.

  1. The cardiovascular effects of a chimeric opioid peptide based on morphiceptin and PFRTic-NH2.

    Science.gov (United States)

    Li, Meixing; Zhou, Lanxia; Ma, Guoning; Cao, Shuo; Dong, Shouliang

    2013-01-01

    MCRT (YPFPFRTic-NH(2)) is a chimeric opioid peptide based on morphiceptin and PFRTic-NH(2). In order to assess the cardiovascular effect of MCRT, it was administered by intravenous (i.v.) injection targeting at the peripheral nervous system and by intracerebroventricular (i.c.v.) injection targeting at the central nervous system. Naloxone and L-NAME were injected before MCRT to investigate possible interactions with MCRT. Results show that administration of MCRT by i.v. or i.c.v. injection could induce bradycardia and decrease in mean arterial pressure (MAP) at a greater degree than that with morphiceptin and PFRTic-NH(2). When MCRT and NPFF were coinjected, we observed a dose-dependent weakening of these cardiovascular effects by MCRT. Because naloxone completely abolished the cardiovascular effects of MCRT, we conclude that opioid receptors are involved in regulating the MAP of MCRT regardless of modes of injection. The effect of MCRT on heart rate is completely dependent on opioid receptors when MCRT was administered by i.c.v. instead of i.v. The central nitric oxide (NO) pathway is involved in regulating blood pressure by MCRT under both modes of injection, but the peripheral NO pathway had no effect on lowering blood pressure mediated by MCRT when it was administered by i.c.v. Based on the results from different modes of injection, the regulation of heart rate by MCRT mainly involves in the central NO pathway. Lastly, we observed that the cardiovascular effects of MCRT such as bradycardia and decrease of blood pressure, were stronger than that of its parent peptides. Opioid receptors and the NO pathway are involved in the cardiovascular regulation by MCRT, and their degree of involvement differs between intravenous and intracerebroventricular injection. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Network-based association of hypoxia-responsive genes with cardiovascular diseases

    International Nuclear Information System (INIS)

    Wang, Rui-Sheng; Oldham, William M; Loscalzo, Joseph

    2014-01-01

    Molecular oxygen is indispensable for cellular viability and function. Hypoxia is a stress condition in which oxygen demand exceeds supply. Low cellular oxygen content induces a number of molecular changes to activate regulatory pathways responsible for increasing the oxygen supply and optimizing cellular metabolism under limited oxygen conditions. Hypoxia plays critical roles in the pathobiology of many diseases, such as cancer, heart failure, myocardial ischemia, stroke, and chronic lung diseases. Although the complicated associations between hypoxia and cardiovascular (and cerebrovascular) diseases (CVD) have been recognized for some time, there are few studies that investigate their biological link from a systems biology perspective. In this study, we integrate hypoxia genes, CVD genes, and the human protein interactome in order to explore the relationship between hypoxia and cardiovascular diseases at a systems level. We show that hypoxia genes are much closer to CVD genes in the human protein interactome than that expected by chance. We also find that hypoxia genes play significant bridging roles in connecting different cardiovascular diseases. We construct a hypoxia-CVD bipartite network and find several interesting hypoxia-CVD modules with significant gene ontology similarity. Finally, we show that hypoxia genes tend to have more CVD interactors in the human interactome than in random networks of matching topology. Based on these observations, we can predict novel genes that may be associated with CVD. This network-based association study gives us a broad view of the relationships between hypoxia and cardiovascular diseases and provides new insights into the role of hypoxia in cardiovascular biology. (paper)

  3. Cardiovascular risk profile and frailty in a population-based study of older British men.

    Science.gov (United States)

    Ramsay, S E; Arianayagam, D S; Whincup, P H; Lennon, L T; Cryer, J; Papacosta, A O; Iliffe, S; Wannamethee, S G

    2015-04-01

    Frailty in older age is known to be associated with cardiovascular disease (CVD) risk. However, the extent to which frailty is associated with the CVD risk profile has been little studied. Our aim was to examine the associations of a range of cardiovascular risk factors with frailty and to assess whether these are independent of established CVD. Cross-sectional study of a socially representative sample of 1622 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Frailty was defined using the Fried phenotype, including weight loss, grip strength, exhaustion, slowness and low physical activity. Among 1622 men, 303 (19%) were frail and 876 (54%) were pre-frail. Compared with non-frail, those with frailty had a higher odds of obesity (OR 2.03, 95% CI 1.38 to 2.99), high waist circumference (OR 2.30, 95% CI 1.67 to 3.17), low high-density lipoprotein-cholesterol (HDL-C) (OR 2.28, 95% CI 1.47 to 3.54) and hypertension (OR 1.79, 95% CI 1.27 to 2.54). Prevalence of these factors was also higher in those with frailty (prevalence in frail vs non-frail groups was 46% vs 31% for high waist circumference, 20% vs 11% for low HDL and 78% vs 65% for hypertension). Frail individuals had a worse cardiovascular risk profile with an increased risk of high heart rate, poor lung function (forced expiratory volume in 1 s (FEV1)), raised white cell count (WCC), poor renal function (low estimated glomerular filtration rate), low alanine transaminase and low serum sodium. Some risk factors (HDL-C, hypertension, WCC, FEV1, renal function and albumin) were also associated with being pre-frail. These associations remained when men with prevalent CVD were excluded. Frailty was associated with increased risk of a range of cardiovascular factors (including obesity, HDL-C, hypertension, heart rate, lung function, renal function) in older people; these associations were independent of established CVD. Published by the BMJ

  4. A Model-Based Joint Identification of Differentially Expressed Genes and Phenotype-Associated Genes.

    Directory of Open Access Journals (Sweden)

    Samuel Sunghwan Cho

    Full Text Available Over the last decade, many analytical methods and tools have been developed for microarray data. The detection of differentially expressed genes (DEGs among different treatment groups is often a primary purpose of microarray data analysis. In addition, association studies investigating the relationship between genes and a phenotype of interest such as survival time are also popular in microarray data analysis. Phenotype association analysis provides a list of phenotype-associated genes (PAGs. However, it is sometimes necessary to identify genes that are both DEGs and PAGs. We consider the joint identification of DEGs and PAGs in microarray data analyses. The first approach we used was a naïve approach that detects DEGs and PAGs separately and then identifies the genes in an intersection of the list of PAGs and DEGs. The second approach we considered was a hierarchical approach that detects DEGs first and then chooses PAGs from among the DEGs or vice versa. In this study, we propose a new model-based approach for the joint identification of DEGs and PAGs. Unlike the previous two-step approaches, the proposed method identifies genes simultaneously that are DEGs and PAGs. This method uses standard regression models but adopts different null hypothesis from ordinary regression models, which allows us to perform joint identification in one-step. The proposed model-based methods were evaluated using experimental data and simulation studies. The proposed methods were used to analyze a microarray experiment in which the main interest lies in detecting genes that are both DEGs and PAGs, where DEGs are identified between two diet groups and PAGs are associated with four phenotypes reflecting the expression of leptin, adiponectin, insulin-like growth factor 1, and insulin. Model-based approaches provided a larger number of genes, which are both DEGs and PAGs, than other methods. Simulation studies showed that they have more power than other methods

  5. A Model-Based Joint Identification of Differentially Expressed Genes and Phenotype-Associated Genes

    Science.gov (United States)

    Seo, Minseok; Shin, Su-kyung; Kwon, Eun-Young; Kim, Sung-Eun; Bae, Yun-Jung; Lee, Seungyeoun; Sung, Mi-Kyung; Choi, Myung-Sook; Park, Taesung

    2016-01-01

    Over the last decade, many analytical methods and tools have been developed for microarray data. The detection of differentially expressed genes (DEGs) among different treatment groups is often a primary purpose of microarray data analysis. In addition, association studies investigating the relationship between genes and a phenotype of interest such as survival time are also popular in microarray data analysis. Phenotype association analysis provides a list of phenotype-associated genes (PAGs). However, it is sometimes necessary to identify genes that are both DEGs and PAGs. We consider the joint identification of DEGs and PAGs in microarray data analyses. The first approach we used was a naïve approach that detects DEGs and PAGs separately and then identifies the genes in an intersection of the list of PAGs and DEGs. The second approach we considered was a hierarchical approach that detects DEGs first and then chooses PAGs from among the DEGs or vice versa. In this study, we propose a new model-based approach for the joint identification of DEGs and PAGs. Unlike the previous two-step approaches, the proposed method identifies genes simultaneously that are DEGs and PAGs. This method uses standard regression models but adopts different null hypothesis from ordinary regression models, which allows us to perform joint identification in one-step. The proposed model-based methods were evaluated using experimental data and simulation studies. The proposed methods were used to analyze a microarray experiment in which the main interest lies in detecting genes that are both DEGs and PAGs, where DEGs are identified between two diet groups and PAGs are associated with four phenotypes reflecting the expression of leptin, adiponectin, insulin-like growth factor 1, and insulin. Model-based approaches provided a larger number of genes, which are both DEGs and PAGs, than other methods. Simulation studies showed that they have more power than other methods. Through analysis of

  6. Evaluation of the performance of existing non-laboratory based cardiovascular risk assessment algorithms

    Science.gov (United States)

    2013-01-01

    Background The high burden and rising incidence of cardiovascular disease (CVD) in resource constrained countries necessitates implementation of robust and pragmatic primary and secondary prevention strategies. Many current CVD management guidelines recommend absolute cardiovascular (CV) risk assessment as a clinically sound guide to preventive and treatment strategies. Development of non-laboratory based cardiovascular risk assessment algorithms enable absolute risk assessment in resource constrained countries. The objective of this review is to evaluate the performance of existing non-laboratory based CV risk assessment algorithms using the benchmarks for clinically useful CV risk assessment algorithms outlined by Cooney and colleagues. Methods A literature search to identify non-laboratory based risk prediction algorithms was performed in MEDLINE, CINAHL, Ovid Premier Nursing Journals Plus, and PubMed databases. The identified algorithms were evaluated using the benchmarks for clinically useful cardiovascular risk assessment algorithms outlined by Cooney and colleagues. Results Five non-laboratory based CV risk assessment algorithms were identified. The Gaziano and Framingham algorithms met the criteria for appropriateness of statistical methods used to derive the algorithms and endpoints. The Swedish Consultation, Framingham and Gaziano algorithms demonstrated good discrimination in derivation datasets. Only the Gaziano algorithm was externally validated where it had optimal discrimination. The Gaziano and WHO algorithms had chart formats which made them simple and user friendly for clinical application. Conclusion Both the Gaziano and Framingham non-laboratory based algorithms met most of the criteria outlined by Cooney and colleagues. External validation of the algorithms in diverse samples is needed to ascertain their performance and applicability to different populations and to enhance clinicians’ confidence in them. PMID:24373202

  7. Crop 3D-a LiDAR based platform for 3D high-throughput crop phenotyping.

    Science.gov (United States)

    Guo, Qinghua; Wu, Fangfang; Pang, Shuxin; Zhao, Xiaoqian; Chen, Linhai; Liu, Jin; Xue, Baolin; Xu, Guangcai; Li, Le; Jing, Haichun; Chu, Chengcai

    2018-03-01

    With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis. As an important part in breeding, high-throughput phenotyping can accelerate the breeding process effectively. Light detection and ranging (LiDAR) is an active remote sensing technology that is capable of acquiring three-dimensional (3D) data accurately, and has a great potential in crop phenotyping. Given that crop phenotyping based on LiDAR technology is not common in China, we developed a high-throughput crop phenotyping platform, named Crop 3D, which integrated LiDAR sensor, high-resolution camera, thermal camera and hyperspectral imager. Compared with traditional crop phenotyping techniques, Crop 3D can acquire multi-source phenotypic data in the whole crop growing period and extract plant height, plant width, leaf length, leaf width, leaf area, leaf inclination angle and other parameters for plant biology and genomics analysis. In this paper, we described the designs, functions and testing results of the Crop 3D platform, and briefly discussed the potential applications and future development of the platform in phenotyping. We concluded that platforms integrating LiDAR and traditional remote sensing techniques might be the future trend of crop high-throughput phenotyping.

  8. Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria

    DEFF Research Database (Denmark)

    Rettedal, Elizabeth; Gumpert, Heidi; Sommer, Morten

    2014-01-01

    The human gut microbiota is linked to a variety of human health issues and implicated in antibiotic resistance gene dissemination. Most of these associations rely on culture-independent methods, since it is commonly believed that gut microbiota cannot be easily or sufficiently cultured. Here, we...... microbiota. Based on the phenotypic mapping, we tailor antibiotic combinations to specifically select for previously uncultivated bacteria. Utilizing this method we cultivate and sequence the genomes of four isolates, one of which apparently belongs to the genus Oscillibacter; uncultivated Oscillibacter...

  9. Labview Based ECG Patient Monitoring System for Cardiovascular Patient Using SMTP Technology

    OpenAIRE

    Singh, Om Prakash; Mekonnen, Dawit; Malarvili, M. B.

    2015-01-01

    This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has ...

  10. Nursing care in patients with cardiovascular risk based on the theory of Nola J. Pender

    OpenAIRE

    Cadena Estrada, Julio César; Instituto Nacional de Cardiología Ignacio Chávez; González Ortega, Yariela; Universidad de Panamá

    2017-01-01

    Introduction: chronic degenerative diseases such as coronary heart disease are caused by various risk factors, habits and styles of unhealthy life, so that prevention and health promotion based on theories or models of nursing, play an essential role in solving public health problems. Objective: To develop a proposal for implementation of nursing care to patients with cardiovascular risk supported by the Health Promotion Model (HPM) of Nola J Pender. Proposal: The care of people is proposed b...

  11. Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study.

    Science.gov (United States)

    Skjaerven, Rolv; Wilcox, Allen J; Klungsøyr, Kari; Irgens, Lorentz M; Vikse, Bjørn Egil; Vatten, Lars J; Lie, Rolv Terje

    2012-11-27

    To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child. Prospective, population based cohort study. Medical Birth Registry of Norway. We followed 836,147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23,000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first

  12. Similarity-based search of model organism, disease and drug effect phenotypes

    KAUST Repository

    Hoehndorf, Robert; Gruenberger, Michael; Gkoutos, Georgios V; Schofield, Paul N

    2015-01-01

    Background: Semantic similarity measures over phenotype ontologies have been demonstrated to provide a powerful approach for the analysis of model organism phenotypes, the discovery of animal models of human disease, novel pathways, gene functions

  13. A monolithic glass chip for active single-cell sorting based on mechanical phenotyping.

    Science.gov (United States)

    Faigle, Christoph; Lautenschläger, Franziska; Whyte, Graeme; Homewood, Philip; Martín-Badosa, Estela; Guck, Jochen

    2015-03-07

    The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custom-built optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications.

  14. Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics

    Directory of Open Access Journals (Sweden)

    Kalle Kilk

    2018-02-01

    Full Text Available Apart from the refined management-oriented clinical stratification of chronic obstructive pulmonary disease (COPD, the molecular pathologies behind this highly prevalent disease have remained obscure. The aim of this study was the characterization of patients with COPD, based on the metabolomic profiling of peripheral blood and exhaled breath condensate (EBC within the context of defined clinical and demographic variables. Mass-spectrometry-based targeted analysis of serum metabolites (mainly amino acids and lipid species, untargeted profiles of serum and EBC of patients with COPD of different clinical characteristics (n = 25 and control individuals (n = 21 were performed. From the combined clinical/demographic and metabolomics data, associations between clinical/demographic and metabolic parameters were searched and a de novo phenotyping for COPD was attempted. Adjoining the clinical parameters, sphingomyelins were the best to differentiate COPD patients from controls. Unsaturated fatty acid-containing lipids, ornithine metabolism and plasma protein composition-associated signals from the untargeted analysis differentiated the Global Initiative for COPD (GOLD categories. Hierarchical clustering did not reveal a clinical-metabolomic stratification superior to the strata set by the GOLD consensus. We conclude that while metabolomics approaches are good for finding biomarkers and clarifying the mechanism of the disease, there are no distinct co-variate independent clinical-metabolic phenotypes.

  15. Microarray-based bioinformatics analysis of the combined effects of SiNPs and PbAc on cardiovascular system in zebrafish.

    Science.gov (United States)

    Hu, Hejing; Zhang, Yannan; Shi, Yanfeng; Feng, Lin; Duan, Junchao; Sun, Zhiwei

    2017-10-01

    With rapid development of nanotechnology and growing environmental pollution, the combined toxic effects of SiNPs and pollutants of heavy metals like lead have received global attentions. The aim of this study was to explore the cardiovascular effects of the co-exposure of SiNPs and lead acetate (PbAc) in zebrafish using microarray and bioinformatics analysis. Although there was no other obvious cardiovascular malformation except bleeding phenotype, bradycardia, angiogenesis inhibition and declined cardiac output in zebrafish co-exposed of SiNPs and PbAc at NOAEL level, significant changes were observed in mRNA and microRNA (miRNA) expression patterns. STC-GO analysis indicated that the co-exposure might have more toxic effects on cardiovascular system than that exposure alone. Key differentially expressed genes were discerned out based on the Dynamic-gene-network, including stxbp1a, ndfip2, celf4 and gsk3b. Furthermore, several miRNAs obtained from the miRNA-Gene-Network might play crucial roles in cardiovascular disease, such as dre-miR-93, dre-miR-34a, dre-miR-181c, dre-miR-7145, dre-miR-730, dre-miR-129-5p, dre-miR-19d, dre-miR-218b, dre-miR-221. Besides, the analysis of miRNA-pathway-network indicated that the zebrafish were stimulated by the co-exposure of SiNPs and PbAc, which might cause the disturbance of calcium homeostasis and endoplasmic reticulum stress. As a result, cardiac muscle contraction might be deteriorated. In general, our data provide abundant fundamental research clues to the combined toxicity of environmental pollutants and further in-depth verifications are needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. How to utilize Ca²⁺ signals to rejuvenate the repairative phenotype of senescent endothelial progenitor cells in elderly patients affected by cardiovascular diseases: a useful therapeutic support of surgical approach?

    Science.gov (United States)

    Moccia, Francesco; Dragoni, Silvia; Cinelli, Mariapia; Montagnani, Stefania; Amato, Bruno; Rosti, Vittorio; Guerra, Germano; Tanzi, Franco

    2013-01-01

    Endothelial dysfunction or loss is the early event that leads to a host of severe cardiovascular diseases, such as atherosclerosis, hypertension, brain stroke, myocardial infarction, and peripheral artery disease. Ageing is regarded among the most detrimental risk factor for vascular endothelium and predisposes the subject to atheroscleorosis and inflammatory states even in absence of traditional comorbid conditions. Standard treatment to restore blood perfusion through stenotic arteries are surgical or endovascular revascularization. Unfortunately, ageing patients are not the most amenable candidates for such interventions, due to high operative risk or unfavourable vascular involvement. It has recently been suggested that the transplantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) might constitute an alternative and viable therapeutic option for these individuals. Albeit pre-clinical studies demonstrated the feasibility of EPC-based therapy to recapitulate the diseased vasculature of young and healthy animals, clinical studies provided less impressive results in old ischemic human patients. One hurdle associated to this kind of approach is the senescence of autologous EPCs, which are less abundant in peripheral blood and display a reduced pro-angiogenic activity. Conversely, umbilical cord blood (UCB)-derived EPCs are more suitable for cellular therapeutics due to their higher frequency and sensitivity to growth factors, such as vascular endothelial growth factor (VEGF). An increase in intracellular Ca(2+) concentration is central to EPC activation by VEGF. We have recently demonstrated that the Ca(2+) signalling machinery driving the oscillatory Ca(2+) response to this important growth factor is different in UCB-derived EPCs as compared to their peripheral counterparts. In particular, we focussed on the so-called endothelial colony forming cells (ECFCs), which are the only EPC population belonging to the endothelial lineage and able

  17. Image-based phenotyping for non-destructive screening of different salinity tolerance traits in rice

    KAUST Repository

    Hairmansis, Aris

    2014-08-14

    Background Soil salinity is an abiotic stress wide spread in rice producing areas, limiting both plant growth and yield. The development of salt-tolerant rice requires efficient and high-throughput screening techniques to identify promising lines for salt affected areas. Advances made in image-based phenotyping techniques provide an opportunity to use non-destructive imaging to screen for salinity tolerance traits in a wide range of germplasm in a reliable, quantitative and efficient way. However, the application of image-based phenotyping in the development of salt-tolerant rice remains limited. Results A non-destructive image-based phenotyping protocol to assess salinity tolerance traits of two rice cultivars (IR64 and Fatmawati) has been established in this study. The response of rice to different levels of salt stress was quantified over time based on total shoot area and senescent shoot area, calculated from visible red-green-blue (RGB) and fluorescence images. The response of rice to salt stress (50, 75 and 100 mM NaCl) could be clearly distinguished from the control as indicated by the reduced increase of shoot area. The salt concentrations used had only a small effect on the growth of rice during the initial phase of stress, the shoot Na+ accumulation independent phase termed the ‘osmotic stress’ phase. However, after 20 d of treatment, the shoot area of salt stressed plants was reduced compared with non-stressed plants. This was accompanied by a significant increase in the concentration of Na+ in the shoot. Variation in the senescent area of the cultivars IR64 and Fatmawati in response to a high concentration of Na+ in the shoot indicates variation in tissue tolerance mechanisms between the cultivars. Conclusions Image analysis has the potential to be used for high-throughput screening procedures in the development of salt-tolerant rice. The ability of image analysis to discriminate between the different aspects of salt stress (shoot ion

  18. A new powerful non-parametric two-stage approach for testing multiple phenotypes in family-based association studies

    NARCIS (Netherlands)

    Lange, C; Lyon, H; DeMeo, D; Raby, B; Silverman, EK; Weiss, ST

    2003-01-01

    We introduce a new powerful nonparametric testing strategy for family-based association studies in which multiple quantitative traits are recorded and the phenotype with the strongest genetic component is not known prior to the analysis. In the first stage, using a population-based test based on the

  19. Simplified method of clinical phenotyping for older men and women using established field-based measures.

    Science.gov (United States)

    Fukuda, David H; Smith-Ryan, Abbie E; Kendall, Kristina L; Moon, Jordan R; Stout, Jeffrey R

    2013-12-01

    The purpose of this investigation was to determine body composition classification using field-based testing measurements in healthy elderly men and women. The use of isoperformance curves is presented as a method for this determination. Baseline values from 107 healthy Caucasian men and women, over the age of 65years old, who participated in a separate longitudinal study, were used for this investigation. Field-based measurements of age, height, weight, body mass index (BMI), and handgrip strength were recorded on an individual basis. Relative skeletal muscle index (RSMI) and body fat percentage (FAT%) were determined by dual-energy X-ray absorptiometry (DXA) for each participant. Sarcopenia cut-off values for RSMI of 7.26kg·m(-2) for men and 5.45kg·m(-2) for women and elderly obesity cut-off values for FAT% of 27% for men and 38% for women were used. Individuals above the RSMI cut-off and below the FAT% cut-off were classified in the normal phenotype category, while individuals below the RSMI cut-off and above the FAT% cut-off were classified in the sarcopenic-obese phenotype category. Prediction equations for RSMI and FAT% from sex, BMI, and handgrip strength values were developed using multiple regression analysis. The prediction equations were validated using double cross-validation. The final regression equation developed to predict FAT% from sex, BMI, and handgrip strength resulted in a strong relationship (adjusted R(2)=0.741) to DXA values with a low standard error of the estimate (SEE=3.994%). The final regression equation developed to predict RSMI from the field-based testing measures also resulted in a strong relationship (adjusted R(2)=0.841) to DXA values with a low standard error of the estimate (SEE=0.544kg·m(-2)). Isoperformance curves were developed from the relationship between BMI and handgrip strength for men and women with the aforementioned clinical phenotype classification criteria. These visual representations were used to aid in the

  20. 2015 ACC Health Policy Statement on Cardiovascular Team-Based Care and the Role of Advanced Practice Providers.

    Science.gov (United States)

    Brush, John E; Handberg, Eileen M; Biga, Cathleen; Birtcher, Kim K; Bove, Alfred A; Casale, Paul N; Clark, Michael G; Garson, Arthur; Hines, Jerome L; Linderbaum, Jane A; Rodgers, George P; Shor, Robert A; Thourani, Vinod H; Wyman, Janet F

    2015-05-19

    The mission of the American College of Cardiology is "to transform cardiovascular care and improve heart health." Cardiovascular team-based care is a paradigm for practice that can transform care, improve heart health, and help meet the demands of the future. One strategic goal of the College is to help members successfully transition their clinical practices to the future, with all its complexity, challenges, and opportunities. The ACC's strategic plan is aligned with the triple aim of improved care, improved population health, and lower costs per capita. The traditional understanding of quality, access, and cost is that you cannot improve one component without diminishing the others. With cardiovascular team-based care, it is possible to achieve the triple aim of improving quality, access, and cost simultaneously to also improve cardiovascular health. Striving to serve the best interests of patients is the true north of our guiding principles. Cardiovascular team-based care is a model that can improve care coordination and communication and allow each team member to focus more on the quality of care. In addition, the cardiovascular team-based care model increases access to cardiovascular care and allows expansion of services to populations and geographic areas that are currently underserved. This document will increase awareness of the important components of cardiovascular team-based care and create an opportunity for more discussion about the most creative and effective means of implementing it. We hope that this document will stimulate further discussions and activities within the ACC and beyond about team-based care. We have identified areas that need improvement, specifically in APP education and state regulation. The document encourages the exploration of collaborative care models that should enable team members to optimize their education, training, experience, and talent. Improved team leadership, coordination, collaboration, engagement, and efficiency

  1. Comparing deep learning and concept extraction based methods for patient phenotyping from clinical narratives.

    Science.gov (United States)

    Gehrmann, Sebastian; Dernoncourt, Franck; Li, Yeran; Carlson, Eric T; Wu, Joy T; Welt, Jonathan; Foote, John; Moseley, Edward T; Grant, David W; Tyler, Patrick D; Celi, Leo A

    2018-01-01

    In secondary analysis of electronic health records, a crucial task consists in correctly identifying the patient cohort under investigation. In many cases, the most valuable and relevant information for an accurate classification of medical conditions exist only in clinical narratives. Therefore, it is necessary to use natural language processing (NLP) techniques to extract and evaluate these narratives. The most commonly used approach to this problem relies on extracting a number of clinician-defined medical concepts from text and using machine learning techniques to identify whether a particular patient has a certain condition. However, recent advances in deep learning and NLP enable models to learn a rich representation of (medical) language. Convolutional neural networks (CNN) for text classification can augment the existing techniques by leveraging the representation of language to learn which phrases in a text are relevant for a given medical condition. In this work, we compare concept extraction based methods with CNNs and other commonly used models in NLP in ten phenotyping tasks using 1,610 discharge summaries from the MIMIC-III database. We show that CNNs outperform concept extraction based methods in almost all of the tasks, with an improvement in F1-score of up to 26 and up to 7 percentage points in area under the ROC curve (AUC). We additionally assess the interpretability of both approaches by presenting and evaluating methods that calculate and extract the most salient phrases for a prediction. The results indicate that CNNs are a valid alternative to existing approaches in patient phenotyping and cohort identification, and should be further investigated. Moreover, the deep learning approach presented in this paper can be used to assist clinicians during chart review or support the extraction of billing codes from text by identifying and highlighting relevant phrases for various medical conditions.

  2. CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola

    Directory of Open Access Journals (Sweden)

    João M. Pedro

    2016-03-01

    Full Text Available Abstract Background Cardiovascular diseases and other non-communicable diseases are major causes of morbidity and mortality, responsible for 38 million deaths in 2012, 75 % occurring in low- and middle-income countries. Most of these countries are facing a period of epidemiological transition, being confronted with an increased burden of non-communicable diseases, which challenge health systems mainly designed to deal with infectious diseases. With the adoption of the World Health Organization “Global Action Plan for the Prevention and Control of non-communicable diseases, 2013–2020”, the national dimension of risk factors for non-communicable diseases must be reported on a regular basis. Angola has no national surveillance system for non-communicable diseases, and periodic population-based studies can help to overcome this lack of information. CardioBengo will collect information on risk factors, awareness rates and prevalence of symptoms relevant to cardiovascular diseases, to assist decision makers in the implementation of prevention and treatment policies and programs. Methods CardioBengo is designed as a research structure that comprises a cross-sectional component, providing baseline information and the assembling of a cohort to follow-up the dynamics of cardiovascular diseases risk factors in the catchment area of the Dande Health and Demographic Surveillance System of the Health Research Centre of Angola, in Bengo Province, Angola. The World Health Organization STEPwise approach to surveillance questionnaires and procedures will be used to collect information on a representative sex-age stratified sample, aged between 15 and 64 years old. Discussion CardioBengo will recruit the first population cohort in Angola designed to evaluate cardiovascular diseases risk factors. Using the structures in place of the Dande Health and Demographic Surveillance System and a reliable methodology that generates comparable results with other

  3. CardioBengo study protocol: a population based cardiovascular longitudinal study in Bengo Province, Angola.

    Science.gov (United States)

    Pedro, João M; Rosário, Edite; Brito, Miguel; Barros, Henrique

    2016-03-01

    Cardiovascular diseases and other non-communicable diseases are major causes of morbidity and mortality, responsible for 38 million deaths in 2012, 75 % occurring in low- and middle-income countries. Most of these countries are facing a period of epidemiological transition, being confronted with an increased burden of non-communicable diseases, which challenge health systems mainly designed to deal with infectious diseases. With the adoption of the World Health Organization "Global Action Plan for the Prevention and Control of non-communicable diseases, 2013-2020", the national dimension of risk factors for non-communicable diseases must be reported on a regular basis. Angola has no national surveillance system for non-communicable diseases, and periodic population-based studies can help to overcome this lack of information. CardioBengo will collect information on risk factors, awareness rates and prevalence of symptoms relevant to cardiovascular diseases, to assist decision makers in the implementation of prevention and treatment policies and programs. CardioBengo is designed as a research structure that comprises a cross-sectional component, providing baseline information and the assembling of a cohort to follow-up the dynamics of cardiovascular diseases risk factors in the catchment area of the Dande Health and Demographic Surveillance System of the Health Research Centre of Angola, in Bengo Province, Angola. The World Health Organization STEPwise approach to surveillance questionnaires and procedures will be used to collect information on a representative sex-age stratified sample, aged between 15 and 64 years old. CardioBengo will recruit the first population cohort in Angola designed to evaluate cardiovascular diseases risk factors. Using the structures in place of the Dande Health and Demographic Surveillance System and a reliable methodology that generates comparable results with other regions and countries, this study will constitute a useful tool for

  4. What is the Current Knowledge About the Cardiovascular Risk for Users of Cannabis-Based Products? A Systematic Review.

    Science.gov (United States)

    Jouanjus, Emilie; Raymond, Valentin; Lapeyre-Mestre, Maryse; Wolff, Valérie

    2017-06-01

    The purpose of the study was to examine the published evidence on the cardiovascular risk related to the use of cannabis-based products by performing a systematic review of recent literature. The World Health Organization (WHO) emphasizes that cannabis use represents a risky behavior as it may lead to many adverse effects, and in particular, cardiovascular effects. A systematic review of articles published between January 1, 2011 and May 31, 2016 was performed in agreement with the PRISMA statement. Articles presenting data on humans exposed to cannabis-based products and suffering from any cardiovascular condition were eligible for inclusion. The inclusion process was based on a search algorithm and performed in a blinded standardized manner. Overall, 826 articles were found in the literature search, 115 of which remained after performing the inclusion procedure. These were 81 case reports, 29 observational studies, 3 clinical trials, and 2 experimental studies. A total of 116 individuals was the subject of case reports. The mean age was 31 years (95%CI = 29-34), and patients were more frequently men (81.9%) than women (18.1%). They mainly suffered from ischemic strokes or myocardial infarctions. Data provided by the 29 included observational studies evidenced an association between exposure to cannabis-based products and cardiovascular disease. Currently, this evidence is stronger for ischemic strokes than for any other cardiovascular diseases. While the data are limited, there is some suggestion that cannabis use may have negative cardiovascular consequences, particularly at large doses.

  5. Wearable Wireless Cardiovascular Monitoring Using Textile-Based Nanosensor and Nanomaterial Systems

    Directory of Open Access Journals (Sweden)

    Prashanth Shyamkumar

    2014-08-01

    Full Text Available Wearable and ultraportable electronics coupled with pervasive computing are poised to revolutionize healthcare services delivery. The potential cost savings in both treatment, as well as preventive care are the focus of several research efforts across the globe. In this review, we describe the motivations behind wearable solutions to real-time cardiovascular monitoring from a perspective of current healthcare services, as well as from a systems design perspective. We identify areas where emerging research is underway, namely: nanotechnology in textile-based wearable monitors and healthcare solutions targeted towards smart devices, like smartphones and tablets.

  6. Improving advanced cardiovascular life support skills in medical students: simulation-based education approach

    Directory of Open Access Journals (Sweden)

    Hamidreza Reihani

    2015-01-01

    Full Text Available Objective: In this trial, we intend to assess the effect of simulation-based education approach on advanced cardiovascular life support skills among medical students. Methods: Through convenient sampling method, 40 interns of Mashhad University of Medical Sciences in their emergency medicine rotation (from September to December 2012 participated in this study. Advanced Cardiovascular Life Support (ACLS workshops with pretest and post-test exams were performed. Workshops and checklists for pretest and post-test exams were designed according to the latest American Heart Association (AHA guidelines. Results: The total score of the students increased significantly after workshops (24.6 out of 100 to 78.6 out of 100. This demonstrates 53.9% improvement in the skills after the simulation-based education (P< 0.001. Also the mean score of each station had a significant improvement (P< 0.001. Conclusion: Pretests showed that interns had poor performance in practical clinical matters while their scientific knowledge, such as ECG interpretation was acceptable. The overall results of the study highlights that Simulation based-education approach is highly effective in Improving ACLS skills among medical students.

  7. Investigating properties of the cardiovascular system using innovative analysis algorithms based on ensemble empirical mode decomposition.

    Science.gov (United States)

    Yeh, Jia-Rong; Lin, Tzu-Yu; Chen, Yun; Sun, Wei-Zen; Abbod, Maysam F; Shieh, Jiann-Shing

    2012-01-01

    Cardiovascular system is known to be nonlinear and nonstationary. Traditional linear assessments algorithms of arterial stiffness and systemic resistance of cardiac system accompany the problem of nonstationary or inconvenience in practical applications. In this pilot study, two new assessment methods were developed: the first is ensemble empirical mode decomposition based reflection index (EEMD-RI) while the second is based on the phase shift between ECG and BP on cardiac oscillation. Both methods utilise the EEMD algorithm which is suitable for nonlinear and nonstationary systems. These methods were used to investigate the properties of arterial stiffness and systemic resistance for a pig's cardiovascular system via ECG and blood pressure (BP). This experiment simulated a sequence of continuous changes of blood pressure arising from steady condition to high blood pressure by clamping the artery and an inverse by relaxing the artery. As a hypothesis, the arterial stiffness and systemic resistance should vary with the blood pressure due to clamping and relaxing the artery. The results show statistically significant correlations between BP, EEMD-based RI, and the phase shift between ECG and BP on cardiac oscillation. The two assessments results demonstrate the merits of the EEMD for signal analysis.

  8. Mitogen-activated protein kinase phosphatase 1 (MKP-1) in macrophage biology and cardiovascular disease. A redox-regulated master controller of monocyte function and macrophage phenotype.

    Science.gov (United States)

    Kim, Hong Seok; Asmis, Reto

    2017-08-01

    MAPK pathways play a critical role in the activation of monocytes and macrophages by pathogens, signaling molecules and environmental cues and in the regulation of macrophage function and plasticity. MAPK phosphatase 1 (MKP-1) has emerged as the main counter-regulator of MAPK signaling in monocytes and macrophages. Loss of MKP-1 in monocytes and macrophages in response to metabolic stress leads to dysregulation of monocyte adhesion and migration, and gives rise to dysfunctional, proatherogenic monocyte-derived macrophages. Here we review the properties of this redox-regulated dual-specificity MAPK phosphatase and the role of MKP-1 in monocyte and macrophage biology and cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Impact of Web-Based Feedback on Physical Activity and Cardiovascular Health of Nurses Working in a Cardiovascular Setting: A Randomized Trial

    Directory of Open Access Journals (Sweden)

    Jennifer L. Reed

    2018-03-01

    Full Text Available A disconcerting proportion of Canadian nurses are physically inactive and report poor cardiovascular health. Web-based interventions incorporating feedback and group features may represent opportune, convenient, and cost-effective methods for encouraging physical activity (PA in order to improve the levels of PA and cardiovascular health of nurses. The purpose of this parallel-group randomized trial was to examine the impact of an intervention providing participants with feedback from an activity monitor coupled with a web-based individual, friend or team PA challenge, on the PA and cardiovascular health of nurses working in a cardiovascular setting.Methods: Nurses were randomly assigned in a 1:1:1 ratio to one of the following intervention “challenge” groups: (1 individual, (2 friend or (3 team. Nurses wore a Tractivity® activity monitor throughout a baseline week and 6-week intervention. Height, body mass, body fat percentage, waist circumference, resting blood pressure (BP and heart rate were assessed, and body mass index (BMI was calculated, during baseline and within 1 week post-intervention. Data were analyzed using descriptive statistics and general linear model procedures for repeated measures.Results: 76 nurses (97% female; age: 46 ± 11 years participated. Weekly moderate-to-vigorous intensity PA (MVPA changed over time (F = 4.022, df = 4.827, p = 0.002, η2 = 0.055, and was greater during intervention week 2 when compared to intervention week 6 (p = 0.011. Daily steps changed over time (F = 7.668, df = 3.910, p < 0.001, η2 = 0.100, and were greater during baseline and intervention weeks 1, 2, 3, and 5 when compared to intervention week 6 (p < 0.05. No differences in weekly MVPA or daily steps were observed between groups (p > 0.05. No changes in body mass, BMI or waist circumference were observed within or between groups (p > 0.05. Decreases in body fat percentage (−0.8 ± 4.8%, p = 0.015 and resting systolic BP (−2.6 ± 8

  10. Cell-based Therapies for Cardiovascular Repair: How small things matter

    NARCIS (Netherlands)

    H.J. Houtgraaf (Jaco)

    2014-01-01

    markdownabstract__Abstract__ Cardiovascular disease accounts for almost half of the deaths in the Western world and 25% in developing countries, despite significant therapeutic and interventional advances. It is estimated that by the year 2020, cardiovascular disease will surpass infectious

  11. GeneYenta: a phenotype-based rare disease case matching tool based on online dating algorithms for the acceleration of exome interpretation.

    Science.gov (United States)

    Gottlieb, Michael M; Arenillas, David J; Maithripala, Savanie; Maurer, Zachary D; Tarailo Graovac, Maja; Armstrong, Linlea; Patel, Millan; van Karnebeek, Clara; Wasserman, Wyeth W

    2015-04-01

    Advances in next-generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology-based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching. © 2015 WILEY PERIODICALS, INC.

  12. Towards measurement of the Healthy Ageing Phenotype in lifestyle-based intervention studies.

    Science.gov (United States)

    Lara, Jose; Godfrey, Alan; Evans, Elizabeth; Heaven, Ben; Brown, Laura J E; Barron, Evelyn; Rochester, Lynn; Meyer, Thomas D; Mathers, John C

    2013-10-01

    Given the biological complexity of the ageing process, there is no single, simple and reliable measure of how healthily someone is ageing. Intervention studies need a panel of measures which capture key features of healthy ageing. To help guide our research in this area, we have adopted the concept of the "Healthy Ageing Phenotype" (HAP) and this study aimed to (i) identify the most important features of the HAP and (ii) identify/develop tools for measurement of those features. After a comprehensive assessment of the literature we selected the following domains: physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we hoped would provide a reasonably holistic characterisation of the HAP. We reviewed the literature and identified systematic reviews and/or meta-analysis of cohort studies, and clinical guidelines on outcome measures of these domains relevant to the HAP. Selection criteria for these measures included: frequent use in longitudinal studies of ageing; expected to change with age; evidence for strong association with/prediction of ageing-related phenotypes such as morbidity, mortality and lifespan; whenever possible, focus on studies measuring these outcomes in populations rather than on individuals selected on the basis of a particular disease; (bio)markers that respond to (lifestyle-based) intervention. Proposed markers were exposed to critique in a Workshop held in Newcastle, UK in October 2012. We have selected a tentative panel of (bio)markers of physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we propose may be useful in characterising the HAP and which may have utility as outcome measures in intervention studies. In addition, we have identified a number of tools which could be applied in community-based intervention studies designed to enhance healthy ageing. We have proposed, tentatively, a panel

  13. The CoLaus study: a population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Stirnadel Heide A

    2008-03-01

    Full Text Available Abstract Background Cardiovascular diseases and their associated risk factors remain the main cause of mortality in western societies. In order to assess the prevalence of cardiovascular risk factors (CVRFs in the Caucasian population of Lausanne, Switzerland, we conducted a population-based study (Colaus Study. A secondary aim of the CoLaus study will be to determine new genetic determinants associated with CVRFs. Methods Single-center, cross-sectional study including a random sample of 6,188 extensively phenotyped Caucasian subjects (3,251 women and 2,937 men aged 35 to 75 years living in Lausanne, and genotyped using the 500 K Affymetrix chip technology. Results Obesity (body mass index ≥ 30 kg/m2, smoking, hypertension (blood pressure ≥ 140/90 mmHg and/or treatment, dyslipidemia (high LDL-cholesterol and/or low HDL-cholesterol and/or high triglyceride levels and diabetes (fasting plasma glucose ≥ 7 mmol/l and/or treatment were present in 947 (15.7%, 1673 (27.0%, 2268 (36.7%, 2113 (34.2% and 407 (6.6% of the participants, respectively, and the prevalence was higher in men than in women. In both genders, the prevalence of obesity, hypertension and diabetes increased with age. Conclusion The prevalence of major CVRFs is high in the Lausanne population in particular in men. We anticipate that given its size, the depth of the phenotypic analysis and the availability of dense genome-wide genetic data, the CoLaus Study will be a unique resource to investigate not only the epidemiology of isolated, or aggregated CVRFs like the metabolic syndrome, but can also serve as a discovery set, as well as replication set, to identify novel genes associated with these conditions.

  14. Hydra: A web-based system for cardiovascular analysis, diagnosis and treatment.

    Science.gov (United States)

    Novo, J; Hermida, A; Ortega, M; Barreira, N; Penedo, M G; López, J E; Calvo, C

    2017-02-01

    Cardiovascular (CV) risk stratification is a highly complex process involving an extensive set of clinical trials to support the clinical decision-making process. There are many clinical conditions (e.g. diabetes, obesity, stress, etc.) that can lead to the early diagnosis or establishment of cardiovascular disease. In order to determine all these clinical conditions, a complete set of clinical patient analyses is typically performed, including a physical examination, blood analysis, electrocardiogram, blood pressure (BP) analysis, etc. This article presents a web-based system, called Hydra, which integrates a full and detailed set of services and functionalities for clinical decision support in order to help and improve the work of clinicians in cardiovascular patient diagnosis, risk assessment, treatment and monitoring over time. Hydra integrates a number of different services: a service for inputting all the information gathered by specialists (physical examination, habits, BP, blood analysis, electrocardiogram, etc.); a tool to automatically determine the CV risk stratification, including well-known standard risk stratification tables; and, finally, various tools to incorporate, analyze and graphically present the records of the ambulatory BP monitoring that provides BP analysis over a given period of time (24 or 48 hours). In addition, the platform presents a set of reports derived from all the information gathered from the patient in order to support physicians in their clinical decisions. Hydra was tested and validated in a real domain. In particular, internal medicine specialists at the Hypertension Unit of the Santiago de Compostela University Hospital (CHUS) validated the platform and used it in different clinical studies to demonstrate its utility. It was observed that the platform increased productivity and accuracy in the assessment of patient data yielding a cost reduction in clinical practice. This paper proposes a complete platform that includes

  15. Inferring gene dependency network specific to phenotypic alteration based on gene expression data and clinical information of breast cancer.

    Science.gov (United States)

    Zhou, Xionghui; Liu, Juan

    2014-01-01

    Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for

  16. Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

    Directory of Open Access Journals (Sweden)

    Julia Günter

    2016-01-01

    Full Text Available More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.

  17. Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Seung Taek Ji

    2017-01-01

    Full Text Available The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

  18. Corn and sorghum phenotyping using a fixed-wing UAV-based remote sensing system

    Science.gov (United States)

    Shi, Yeyin; Murray, Seth C.; Rooney, William L.; Valasek, John; Olsenholler, Jeff; Pugh, N. Ace; Henrickson, James; Bowden, Ezekiel; Zhang, Dongyan; Thomasson, J. Alex

    2016-05-01

    Recent development of unmanned aerial systems has created opportunities in automation of field-based high-throughput phenotyping by lowering flight operational cost and complexity and allowing flexible re-visit time and higher image resolution than satellite or manned airborne remote sensing. In this study, flights were conducted over corn and sorghum breeding trials in College Station, Texas, with a fixed-wing unmanned aerial vehicle (UAV) carrying two multispectral cameras and a high-resolution digital camera. The objectives were to establish the workflow and investigate the ability of UAV-based remote sensing for automating data collection of plant traits to develop genetic and physiological models. Most important among these traits were plant height and number of plants which are currently manually collected with high labor costs. Vegetation indices were calculated for each breeding cultivar from mosaicked and radiometrically calibrated multi-band imagery in order to be correlated with ground-measured plant heights, populations and yield across high genetic-diversity breeding cultivars. Growth curves were profiled with the aerial measured time-series height and vegetation index data. The next step of this study will be to investigate the correlations between aerial measurements and ground truth measured manually in field and from lab tests.

  19. Robust Microplate-Based Methods for Culturing and in Vivo Phenotypic Screening of Chlamydomonas reinhardtii

    Directory of Open Access Journals (Sweden)

    Timothy C. Haire

    2018-03-01

    Full Text Available Chlamydomonas reinhardtii (Cr, a unicellular alga, is routinely utilized to study photosynthetic biochemistry, ciliary motility, and cellular reproduction. Its minimal culture requirements, unicellular morphology, and ease of transformation have made it a popular model system. Despite its relatively slow doubling time, compared with many bacteria, it is an ideal eukaryotic system for microplate-based studies utilizing either, or both, absorbance as well as fluorescence assays. Such microplate assays are powerful tools for researchers in the areas of toxicology, pharmacology, chemical genetics, biotechnology, and more. However, while microplate-based assays are valuable tools for screening biological systems, these methodologies can significantly alter the conditions in which the organisms are cultured and their subsequent physiology or morphology. Herein we describe a novel method for the microplate culture and in vivo phenotypic analysis of growth, viability, and photosynthetic pigments of C. reinhardtii. We evaluated the utility of our assay by screening silver nanoparticles for their effects on growth and viability. These methods are amenable to a wide assortment of studies and present a significant advancement in the methodologies available for research involving this model organism.

  20. Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study.

    Science.gov (United States)

    Patorno, Elisabetta; Goldfine, Allison B; Schneeweiss, Sebastian; Everett, Brendan M; Glynn, Robert J; Liu, Jun; Kim, Seoyoung C

    2018-02-06

    To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice. Population based retrospective cohort study. Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart). Three pairwise 1:1 propensity score matched cohorts of patients with type 2 diabetes 18 years and older who initiated canagliflozin or a comparator non-gliflozin antidiabetic agent (ie, a DPP-4i, a GLP-1RA, or a sulfonylurea) between April 2013 and September 2015. The primary outcomes were heart failure admission to hospital and a composite cardiovascular endpoint (comprised of being admitted to hospital for acute myocardial infarction, ischemic stroke, or hemorrhagic stroke). Hazard ratios and 95% confidence intervals were estimated in each propensity score matched cohort controlling for more than 100 baseline characteristics. During a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ). The hazard ratio for the composite cardiovascular endpoint associated with canagliflozin was 0.89 (0.68 to 1.17) versus a DPP-4i, 1.03 (0.79 to 1.35) versus a GLP-1RA, and 0.86 (0.65 to 1.13) versus a sulfonylurea. Results were similar in sensitivity analyses further adjusting for baseline hemoglobin A1c levels and in subgroups of patients with and without prior cardiovascular disease or heart failure. In this large cohort study, canagliflozin was associated with a lower risk of heart failure admission to hospital and with a similar risk of myocardial infarction or stroke in

  1. Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

    Energy Technology Data Exchange (ETDEWEB)

    Boekel, Naomi B.; Schaapveld, Michael [Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands); Gietema, Jourik A. [Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Russell, Nicola S. [Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Poortmans, Philip [Radiation Oncology, Institute Verbeeten, Tilburg (Netherlands); Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Theuws, Jacqueline C.M. [Radiotherapy, Catharina Hospital Eindhoven, Eindhoven (Netherlands); Schinagl, Dominic A.X. [Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Rietveld, Derek H.F. [Radiation Oncology, VU University Medical Center Amsterdam, Amsterdam (Netherlands); Versteegh, Michel I.M. [Steering Committee Cardiac Interventions Netherlands, Leiden University Medical Center, Leiden (Netherlands); Visser, Otto [Registration and Research, Comprehensive Cancer Center The Netherlands, Utrecht (Netherlands); Rutgers, Emiel J.T. [Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Aleman, Berthe M.P. [Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Leeuwen, Flora E. van, E-mail: f.v.leeuwen@nki.nl [Epidemiology, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2016-04-01

    Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Results: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1

  2. Cardiovascular Disease Risk in a Large, Population-Based Cohort of Breast Cancer Survivors

    International Nuclear Information System (INIS)

    Boekel, Naomi B.; Schaapveld, Michael; Gietema, Jourik A.; Russell, Nicola S.; Poortmans, Philip; Theuws, Jacqueline C.M.; Schinagl, Dominic A.X.; Rietveld, Derek H.F.; Versteegh, Michel I.M.; Visser, Otto; Rutgers, Emiel J.T.; Aleman, Berthe M.P.; Leeuwen, Flora E. van

    2016-01-01

    Purpose: To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. Methods and Materials: A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Results: Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1

  3. [Pediatric cardiovascular surgical data base registry in México. First report].

    Science.gov (United States)

    Cervantes-Salazar, Jorge; Calderón-Colmenero, Juan; Ramírez-Marroquín, Samuel; Palacios-Macedo, Alexis; Bolio-Cerdán, Alejandro; Vizcaíno Alarcón, Alfredo; Curi-Curi, Pedro; de la Llata, Manuel; Erdmenger-Orellana, Julio; González, Julieta; García-Soriano, Federico; Calderón, Alejandro; Casillas, Luis; Villanueva, Filiberto; Sánchez-Ramírez, Roberto; Osnaya, Héctor; Necoechea, Juan Carlos; Alva-Espinoza, Carlos; Prado-Villegas, Guillermo

    2013-01-01

    Current world tendency is the detection of health problems in order to offer solution alternatives by means of the development of computarized data bases. To present the results of a computerized data base developed for the registry of pediatric cardiac surgery with the support of Asociación Mexicana de Especialistas en Cardiopatías Congénitas (AMECC, A.C.). A one-year analysis (from August 1, 2011 to July 31, 2012) of a computerized data base was performed with the support of AMECC and the participation of the most important Mexican institutions for pediatric surgical heart disease health care, particularly for the uninsured population. There were 7 health institutions voluntarily incorporated to the national data base registry, and in the first year of observation, 943 surgical procedures in 880 patients and 7% re-operations (n = 63), were reported. Patients up to one-year old accounted for 38%. The most frequent types of operated congenital heart diseases were: patent ductus arteriosus (n = 96), ventricular septal defect (n = 86), tetralogy of Fallot (n = 72), atrial septal defect (n = 68), and aortic coarctation (n = 54). Elective procedures were 90%, and 62% of them were performed with the use of cardiopulmonary bypass. Overall mortality was 7.5% with the following RACHS-1 score risk distribution: 1 (n = 4.2%), 2 (n = 19.6%), 3 (n = 22.8%), 4 (n = 12.19%), 5 (n = 1.25%), 6 (n = 6.44%) and not classifiable (n = 2.9%). Although this analysis gives a representative vision of the cardiovascular surgical health care for the uninsured national pediatric population, the incorporation of other health institutions to this data base may lead us to have a most realistic overview in relation to the surgical cardiovascular health care for the up to 18 year-old population.

  4. Polyphenol-based nutraceuticals for the prevention and treatment of cardiovascular disease: Review of human evidence.

    Science.gov (United States)

    Tomé-Carneiro, Joao; Visioli, Francesco

    2016-10-15

    In addition to prescription drugs, nutraceuticals/functional foods/medical foods are being increasingly added as adjunct treatment of cardiovascular disease (CVD), even though most of them have been exclusively studied in vitro. We review the available evidence (focusing on when the amount of polyphenols' intake was measured) coming from randomized controlled trials (RCTs) of (poly)phenol-based supplements. We conclude that (poly)phenol-based nutraceuticals and functional foods might be indeed used as adjunct therapy of CVD, but additional long-term RCTs with adequate numerosity and with clinically relevant end points are needed to provide unequivocal evidence of their clinical usefulness. Copyright © 2015. Published by Elsevier GmbH.

  5. Remote health monitoring: predicting outcome success based on contextual features for cardiovascular disease.

    Science.gov (United States)

    Alshurafa, Nabil; Eastwood, Jo-Ann; Pourhomayoun, Mohammad; Liu, Jason J; Sarrafzadeh, Majid

    2014-01-01

    Current studies have produced a plethora of remote health monitoring (RHM) systems designed to enhance the care of patients with chronic diseases. Many RHM systems are designed to improve patient risk factors for cardiovascular disease, including physiological parameters such as body mass index (BMI) and waist circumference, and lipid profiles such as low density lipoprotein (LDL) and high density lipoprotein (HDL). There are several patient characteristics that could be determining factors for a patient's RHM outcome success, but these characteristics have been largely unidentified. In this paper, we analyze results from an RHM system deployed in a six month Women's Heart Health study of 90 patients, and apply advanced feature selection and machine learning algorithms to identify patients' key baseline contextual features and build effective prediction models that help determine RHM outcome success. We introduce Wanda-CVD, a smartphone-based RHM system designed to help participants with cardiovascular disease risk factors by motivating participants through wireless coaching using feedback and prompts as social support. We analyze key contextual features that secure positive patient outcomes in both physiological parameters and lipid profiles. Results from the Women's Heart Health study show that health threat of heart disease, quality of life, family history, stress factors, social support, and anxiety at baseline all help predict patient RHM outcome success.

  6. Dyslipidemias and Elevated Cardiovascular Risk on Lopinavir-Based Antiretroviral Therapy in Cambodia

    Science.gov (United States)

    Ly, Sowath; Ouk, Vara; Chanroeurn, Hak; Thavary, Saem; Boroath, Ban; Canestri, Ana; Viretto, Gérald; Delfraissy, Jean-François; Ségéral, Olivier

    2016-01-01

    Background Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. Methods We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG). Results Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention. PMID:27579612

  7. Genetic and Computational Approaches for Studying Plant Development and Abiotic Stress Responses Using Image-Based Phenotyping

    Science.gov (United States)

    Campbell, M. T.; Walia, H.; Grondin, A.; Knecht, A.

    2017-12-01

    The development of abiotic stress tolerant crops (i.e. drought, salinity, or heat stress) requires the discovery of DNA sequence variants associated with stress tolerance-related traits. However, many traits underlying adaptation to abiotic stress involve a suite of physiological pathways that may be induced at different times throughout the duration of stress. Conventional single-point phenotyping approaches fail to fully capture these temporal responses, and thus downstream genetic analysis may only identify a subset of the genetic variants that are important for adaptation to sub-optimal environments. Although genomic resources for crops have advanced tremendously, the collection of phenotypic data for morphological and physiological traits is laborious and remains a significant bottleneck in bridging the phenotype-genotype gap. In recent years, the availability of automated, image-based phenotyping platforms has provided researchers with an opportunity to collect morphological and physiological traits non-destructively in a highly controlled environment. Moreover, these platforms allow abiotic stress responses to be recorded throughout the duration of the experiment, and have facilitated the use of function-valued traits for genetic analyses in major crops. We will present our approaches for addressing abiotic stress tolerance in cereals. This talk will focus on novel open-source software to process and extract biological meaningful data from images generated from these phenomics platforms. In addition, we will discuss the statistical approaches to model longitudinal phenotypes and dissect the genetic basis of dynamic responses to these abiotic stresses throughout development.

  8. Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders : Interpretation in the Light of the DSM-5

    NARCIS (Netherlands)

    Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

    This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental

  9. Empirically Based Phenotypic Profiles of Children with Pervasive Developmental Disorders: Interpretation in the Light of the DSM-5

    Science.gov (United States)

    Greaves-Lord, Kirstin; Eussen, Mart L. J. M.; Verhulst, Frank C.; Minderaa, Ruud B.; Mandy, William; Hudziak, James J.; Steenhuis, Mark Peter; de Nijs, Pieter F.; Hartman, Catharina A.

    2013-01-01

    This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to…

  10. Gracob: a novel graph-based constant-column biclustering method for mining growth phenotype data

    KAUST Repository

    Alzahrani, Majed A.; Kuwahara, Hiroyuki; Wang, Wei; Gao, Xin

    2017-01-01

    Growth phenotype profiling of genome-wide genedeletion strains over stress conditions can offer a clear picture that the essentiality of genes depends on environmental conditions. Systematically identifying groups of genes from such high-throughput data that share similar patterns of conditional essentiality and dispensability under various environmental conditions can elucidate how genetic interactions of the growth phenotype are regulated in response to the environment.We first demonstrate that detecting such\\co-fit

  11. Gracob: a novel graph-based constant-column biclustering method for mining growth phenotype data

    KAUST Repository

    Alzahrani, Majed A.

    2017-04-05

    Growth phenotype profiling of genome-wide genedeletion strains over stress conditions can offer a clear picture that the essentiality of genes depends on environmental conditions. Systematically identifying groups of genes from such high-throughput data that share similar patterns of conditional essentiality and dispensability under various environmental conditions can elucidate how genetic interactions of the growth phenotype are regulated in response to the environment.We first demonstrate that detecting such\\\\co-fit

  12. Toward a Reasoned Classification of Diseases Using Physico-Chemical Based Phenotypes

    Directory of Open Access Journals (Sweden)

    Laurent Schwartz

    2018-02-01

    Full Text Available Background: Diseases and health conditions have been classified according to anatomical site, etiological, and clinical criteria. Physico-chemical mechanisms underlying the biology of diseases, such as the flow of energy through cells and tissues, have been often overlooked in classification systems.Objective: We propose a conceptual framework toward the development of an energy-oriented classification of diseases, based on the principles of physical chemistry.Methods: A review of literature on the physical chemistry of biological interactions in a number of diseases is traced from the point of view of the fluid and solid mechanics, electricity, and chemistry.Results: We found consistent evidence in literature of decreased and/or increased physical and chemical forces intertwined with biological processes of numerous diseases, which allowed the identification of mechanical, electric and chemical phenotypes of diseases.Discussion: Biological mechanisms of diseases need to be evaluated and integrated into more comprehensive theories that should account with principles of physics and chemistry. A hypothetical model is proposed relating the natural history of diseases to mechanical stress, electric field, and chemical equilibria (ATP changes. The present perspective toward an innovative disease classification may improve drug-repurposing strategies in the future.

  13. Deconstructing oppositional defiant disorder: clinic-based evidence for an anger/irritability phenotype.

    Science.gov (United States)

    Drabick, Deborah A G; Gadow, Kenneth D

    2012-04-01

    To examine risk factors and co-occurring symptoms associated with mother-reported versus teacher-reported anger/irritability symptoms (AIS) of oppositional defiant disorder (ODD) in a clinic-based sample of 1,160 youth aged 6 through 18 years. Participants completed a background history questionnaire (mothers), school functioning questionnaire (mothers, teachers), and DSM-IV-referenced symptom checklists (mothers, teachers). Youth meeting AIS criteria for ODD were compared to youth with ODD who met criteria for noncompliant symptoms (NS) but not AIS and to clinic controls. Compared with NS youth, youth with AIS were rated as exhibiting higher levels of anxiety and mood symptoms for both mother- and teacher-defined groups, and higher levels of conduct disorder symptoms for mother-defined younger and older youth. The remaining group differences for developmental, psychosocial, and psychiatric correlates varied as a function of informant and youth's age. Evidence suggests that AIS may constitute a more severe and qualitatively different ODD clinical phenotype, but informant and age of youth appear to be important considerations. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Network-based analysis of genotype-phenotype correlations between different inheritance modes.

    Science.gov (United States)

    Hao, Dapeng; Li, Chuanxing; Zhang, Shaojun; Lu, Jianping; Jiang, Yongshuai; Wang, Shiyuan; Zhou, Meng

    2014-11-15

    Recent studies on human disease have revealed that aberrant interaction between proteins probably underlies a substantial number of human genetic diseases. This suggests a need to investigate disease inheritance mode using interaction, and based on which to refresh our conceptual understanding of a series of properties regarding inheritance mode of human disease. We observed a strong correlation between the number of protein interactions and the likelihood of a gene causing any dominant diseases or multiple dominant diseases, whereas no correlation was observed between protein interaction and the likelihood of a gene causing recessive diseases. We found that dominant diseases are more likely to be associated with disruption of important interactions. These suggest inheritance mode should be understood using protein interaction. We therefore reviewed the previous studies and refined an interaction model of inheritance mode, and then confirmed that this model is largely reasonable using new evidences. With these findings, we found that the inheritance mode of human genetic diseases can be predicted using protein interaction. By integrating the systems biology perspectives with the classical disease genetics paradigm, our study provides some new insights into genotype-phenotype correlations. haodapeng@ems.hrbmu.edu.cn or biofomeng@hotmail.com Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Insomnia Phenotypes Based on Objective Sleep Duration in Adolescents: Depression Risk and Differential Behavioral Profiles

    Directory of Open Access Journals (Sweden)

    Julio Fernandez-Mendoza

    2016-12-01

    Full Text Available Based on previous studies on the role of objective sleep duration in predicting morbidity in individuals with insomnia, we examined the role of objective sleep duration in differentiating behavioral profiles in adolescents with insomnia symptoms. Adolescents from the Penn State Child Cohort (n = 397, ages 12–23, 54.7% male underwent a nine-hour polysomnography (PSG, clinical history, physical examination and psychometric testing, including the Child or Adult Behavior Checklist and Pediatric Behavior Scale. Insomnia symptoms were defined as a self-report of difficulty falling and/or staying asleep and objective “short” sleep duration as a PSG total sleep time ≤7 h. A significant interaction showed that objective short sleep duration modified the association of insomnia symptoms with internalizing problems. Consistently, adolescents with insomnia symptoms and short sleep duration were characterized by depression, rumination, mood dysregulation and social isolation, while adolescents with insomnia symptoms and normal sleep duration were characterized by rule-breaking and aggressive behaviors and, to a lesser extent, rumination. These findings indicate that objective sleep duration is useful in differentiating behavioral profiles among adolescents with insomnia symptoms. The insomnia with objective short sleep duration phenotype is associated with an increased risk of depression earlier in the lifespan than previously believed.

  16. Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.

    Science.gov (United States)

    Dobroff, Andrey S; D'Angelo, Sara; Eckhardt, Bedrich L; Ferrara, Fortunato; Staquicini, Daniela I; Cardó-Vila, Marina; Staquicini, Fernanda I; Nunes, Diana N; Kim, Kisu; Driessen, Wouter H P; Hajitou, Amin; Lomo, Lesley C; Barry, Marc; Krishnamurthy, Savitri; Sahin, Aysegul; Woodward, Wendy A; Prossnitz, Eric R; Anderson, Robin L; Dias-Neto, Emmanuel; Brown-Glaberman, Ursa A; Royce, Melanie E; Ueno, Naoto T; Cristofanilli, Massimo; Hortobagyi, Gabriel N; Marchiò, Serena; Gelovani, Juri G; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-10-24

    Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.

  17. Toward a Reasoned Classification of Diseases Using Physico-Chemical Based Phenotypes

    Science.gov (United States)

    Schwartz, Laurent; Lafitte, Olivier; da Veiga Moreira, Jorgelindo

    2018-01-01

    Background: Diseases and health conditions have been classified according to anatomical site, etiological, and clinical criteria. Physico-chemical mechanisms underlying the biology of diseases, such as the flow of energy through cells and tissues, have been often overlooked in classification systems. Objective: We propose a conceptual framework toward the development of an energy-oriented classification of diseases, based on the principles of physical chemistry. Methods: A review of literature on the physical chemistry of biological interactions in a number of diseases is traced from the point of view of the fluid and solid mechanics, electricity, and chemistry. Results: We found consistent evidence in literature of decreased and/or increased physical and chemical forces intertwined with biological processes of numerous diseases, which allowed the identification of mechanical, electric and chemical phenotypes of diseases. Discussion: Biological mechanisms of diseases need to be evaluated and integrated into more comprehensive theories that should account with principles of physics and chemistry. A hypothetical model is proposed relating the natural history of diseases to mechanical stress, electric field, and chemical equilibria (ATP) changes. The present perspective toward an innovative disease classification may improve drug-repurposing strategies in the future. PMID:29541031

  18. Automated recognition of cell phenotypes in histology images based on membrane- and nuclei-targeting biomarkers

    International Nuclear Information System (INIS)

    Karaçalı, Bilge; Vamvakidou, Alexandra P; Tözeren, Aydın

    2007-01-01

    Three-dimensional in vitro culture of cancer cells are used to predict the effects of prospective anti-cancer drugs in vivo. In this study, we present an automated image analysis protocol for detailed morphological protein marker profiling of tumoroid cross section images. Histologic cross sections of breast tumoroids developed in co-culture suspensions of breast cancer cell lines, stained for E-cadherin and progesterone receptor, were digitized and pixels in these images were classified into five categories using k-means clustering. Automated segmentation was used to identify image regions composed of cells expressing a given biomarker. Synthesized images were created to check the accuracy of the image processing system. Accuracy of automated segmentation was over 95% in identifying regions of interest in synthesized images. Image analysis of adjacent histology slides stained, respectively, for Ecad and PR, accurately predicted regions of different cell phenotypes. Image analysis of tumoroid cross sections from different tumoroids obtained under the same co-culture conditions indicated the variation of cellular composition from one tumoroid to another. Variations in the compositions of cross sections obtained from the same tumoroid were established by parallel analysis of Ecad and PR-stained cross section images. Proposed image analysis methods offer standardized high throughput profiling of molecular anatomy of tumoroids based on both membrane and nuclei markers that is suitable to rapid large scale investigations of anti-cancer compounds for drug development

  19. Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing

    Directory of Open Access Journals (Sweden)

    Srinivasan Sivasubramanian

    2017-07-01

    Full Text Available The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented

  20. PCL-PDMS-PCL copolymer-based microspheres mediate cardiovascular differentiation from embryonic stem cells

    Science.gov (United States)

    Song, Liqing

    Poly-epsilon-caprolactone (PCL) based copolymers have received much attention as drug or growth factor delivery carriers and tissue engineering scaffolds due to their biocompatibility, biodegradability, and tunable biophysical properties. Copolymers of PCL and polydimethylsiloxane (PDMS) also have shape memory behaviors and can be made into thermoresponsive shape memory polymers for various biomedical applications such as smart sutures and vascular stents. However, the influence of biophysical properties of PCL-PDMS-PCL copolymers on stem cell lineage commitment is not well understood. In this study, PDMS was used as soft segments of varying length to tailor the biophysical properties of PCL-based co-polymers. While low elastic modulus (affected cardiovascular differentiation of embryonic stem cells, the range of 60-100 MPa PCL-PDMS-PCL showed little influence on the differentiation. Then different size (30-140 mum) of microspheres were fabricated from PCL-PDMS-PCL copolymers and incorporated within embryoid bodies (EBs). Mesoderm differentiation was induced using bone morphogenetic protein (BMP)-4 for cardiovascular differentiation. Differential expressions of mesoderm progenitor marker KDR and vascular markers CD31 and VE-cadherin were observed for the cells differentiated from EBs incorporated with microspheres of different size, while little difference was observed for cardiac marker alpha-actinin expression. Small size of microspheres (30 mum) resulted in higher expression of KDR while medium size of microspheres (94 mum) resulted in higher CD31 and VE-cadherin expression. This study indicated that the biophysical properties of PCL-based copolymers impacted stem cell lineage commitment, which should be considered for drug delivery and tissue engineering applications.

  1. The effectiveness of integrative medicine interventions on pain and anxiety in cardiovascular inpatients: a practice-based research evaluation.

    Science.gov (United States)

    Johnson, Jill R; Crespin, Daniel J; Griffin, Kristen H; Finch, Michael D; Rivard, Rachael L; Baechler, Courtney J; Dusek, Jeffery A

    2014-12-13

    Pain and anxiety occurring from cardiovascular disease are associated with long-term health risks. Integrative medicine (IM) therapies reduce pain and anxiety in small samples of hospitalized cardiovascular patients within randomized controlled trials; however, practice-based effectiveness research has been limited. The goal of the study is to evaluate the effectiveness of IM interventions (i.e., bodywork, mind-body and energy therapies, and traditional Chinese medicine) on pain and anxiety measures across a cardiovascular population. Retrospective data obtained from medical records identified patients with a cardiovascular ICD-9 code admitted to a large Midwestern hospital between 7/1/2009 and 12/31/2012. Outcomes were changes in patient-reported pain and anxiety, rated before and after IM treatments based on a numeric scale (0-10). Of 57,295 hospital cardiovascular admissions, 6,589 (11.5%) included IM. After receiving IM therapy, patients averaged a 46.5% (p-value value value medicine (p-value value value value based research to investigate the best approach for incorporating these therapies into an acute care setting such that IM therapies are most appropriately provided to patient populations.

  2. Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

    Science.gov (United States)

    Katada, Y; Nakagawa, S; Minakata, K; Odaka, M; Taue, H; Sato, Y; Yonezawa, A; Kayano, Y; Yano, I; Nakatsu, T; Sakamoto, K; Uehara, K; Sakaguchi, H; Yamazaki, K; Minatoya, K; Sakata, R; Matsubara, K

    2017-10-01

    Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, PWarfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

  3. Classification of cardiovascular tissues using LBP based descriptors and a cascade SVM.

    Science.gov (United States)

    Mazo, Claudia; Alegre, Enrique; Trujillo, Maria

    2017-08-01

    Histological images have characteristics, such as texture, shape, colour and spatial structure, that permit the differentiation of each fundamental tissue and organ. Texture is one of the most discriminative features. The automatic classification of tissues and organs based on histology images is an open problem, due to the lack of automatic solutions when treating tissues without pathologies. In this paper, we demonstrate that it is possible to automatically classify cardiovascular tissues using texture information and Support Vector Machines (SVM). Additionally, we realised that it is feasible to recognise several cardiovascular organs following the same process. The texture of histological images was described using Local Binary Patterns (LBP), LBP Rotation Invariant (LBPri), Haralick features and different concatenations between them, representing in this way its content. Using a SVM with linear kernel, we selected the more appropriate descriptor that, for this problem, was a concatenation of LBP and LBPri. Due to the small number of the images available, we could not follow an approach based on deep learning, but we selected the classifier who yielded the higher performance by comparing SVM with Random Forest and Linear Discriminant Analysis. Once SVM was selected as the classifier with a higher area under the curve that represents both higher recall and precision, we tuned it evaluating different kernels, finding that a linear SVM allowed us to accurately separate four classes of tissues: (i) cardiac muscle of the heart, (ii) smooth muscle of the muscular artery, (iii) loose connective tissue, and (iv) smooth muscle of the large vein and the elastic artery. The experimental validation was conducted using 3000 blocks of 100 × 100 sized pixels, with 600 blocks per class and the classification was assessed using a 10-fold cross-validation. using LBP as the descriptor, concatenated with LBPri and a SVM with linear kernel, the main four classes of tissues were

  4. Impact of a pedometer-based workplace health program on cardiovascular and diabetes risk profile

    DEFF Research Database (Denmark)

    Freak-Poli, Rosanne; Wolfe, Rory; Backholer, Kathryn

    2011-01-01

    %, OR: 1.3(1.0, 1.8)), sitting time (-0.6(-0.9, -0.3) hours/day), blood pressure (systolic: -1.8(-3.1, -.05) mmHg; diastolic: -1.8(-2.4, -1.3) mmHg) and waist circumference (-1.6(-2.4, -0.7) cm). In contrast, an increase was found for fasting total cholesterol (0.3(0.1, 0.4) mmol/L) and triglycerides (0......OBJECTIVE: To evaluate whether participation in a four-month, pedometer-based, physical activity, workplace health programme results in an improvement in risk factors for diabetes and cardiovascular disease. METHODS: Adults employed within Australia in primarily sedentary occupations...

  5. Labview Based ECG Patient Monitoring System for Cardiovascular Patient Using SMTP Technology.

    Science.gov (United States)

    Singh, Om Prakash; Mekonnen, Dawit; Malarvili, M B

    2015-01-01

    This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has been processed in Labview where the digital filter techniques have been implemented to remove the noise from the acquired signal. After processing, the algorithm was developed to calculate the heart rate and to analyze the arrhythmia condition. Finally, SMTP technology has been added in our work to make device more communicative and much more cost-effective solution in telemedicine technology which has been key-problem to realize the telediagnosis and monitoring of ECG signals. The technology also can be easily implemented over already existing Internet.

  6. Nature-Based Tourism Elicits a Phenotypic Shift in the Coping Abilities of Fish.

    Science.gov (United States)

    Geffroy, Benjamin; Sadoul, Bastien; Bouchareb, Amine; Prigent, Sylvain; Bourdineaud, Jean-Paul; Gonzalez-Rey, Maria; Morais, Rosana N; Mela, Maritana; Nobre Carvalho, Lucélia; Bessa, Eduardo

    2018-01-01

    Nature-based tourism is gaining extensive popularity, increasing the intensity and frequency of human-wildlife contacts. As a consequence, behavioral and physiological alterations were observed in most exposed animals. However, while the majority of these studies investigated the effects of punctual exposure to tourists, the consequences of constant exposition to humans in the wild remains overlooked. This is an important gap considering the exponential interest for recreational outdoor activities. To infer long-term effects of intensive tourism, we capitalized on Odontostilbe pequira , a short-lived sedentary Tetra fish who spends its life close to humans, on which it feeds on dead skin. Hence, those fish are constantly exposed to tourists throughout their lifecycle. Here we provide an integrated picture of the whole phenomenon by investigating, for the first time, the expression of genes involved in stress response and neurogenesis, as well as behavioral and hormonal responses of animals consistently exposed to tourists. Gene expression of the mineralocorticoid (and cortisol) receptor ( mr ) and the neurogenic differentiation factor ( NeuroD ) were significantly higher in fish sampled in the touristic zone compared to those sampled in the control zone. Additionally, after a simulated stress in artificial and controlled conditions, those fish previously exposed to visitors produced more cortisol and presented increased behavioral signs of stress compared to their non-exposed conspecifics. Overall, nature-based tourism appeared to shift selection pressures, favoring a sensitive phenotype that does not thrive under natural conditions. The ecological implications of this change in coping style remain, nevertheless, an open question.

  7. Nature-Based Tourism Elicits a Phenotypic Shift in the Coping Abilities of Fish

    Directory of Open Access Journals (Sweden)

    Benjamin Geffroy

    2018-02-01

    Full Text Available Nature-based tourism is gaining extensive popularity, increasing the intensity and frequency of human-wildlife contacts. As a consequence, behavioral and physiological alterations were observed in most exposed animals. However, while the majority of these studies investigated the effects of punctual exposure to tourists, the consequences of constant exposition to humans in the wild remains overlooked. This is an important gap considering the exponential interest for recreational outdoor activities. To infer long-term effects of intensive tourism, we capitalized on Odontostilbe pequira, a short-lived sedentary Tetra fish who spends its life close to humans, on which it feeds on dead skin. Hence, those fish are constantly exposed to tourists throughout their lifecycle. Here we provide an integrated picture of the whole phenomenon by investigating, for the first time, the expression of genes involved in stress response and neurogenesis, as well as behavioral and hormonal responses of animals consistently exposed to tourists. Gene expression of the mineralocorticoid (and cortisol receptor (mr and the neurogenic differentiation factor (NeuroD were significantly higher in fish sampled in the touristic zone compared to those sampled in the control zone. Additionally, after a simulated stress in artificial and controlled conditions, those fish previously exposed to visitors produced more cortisol and presented increased behavioral signs of stress compared to their non-exposed conspecifics. Overall, nature-based tourism appeared to shift selection pressures, favoring a sensitive phenotype that does not thrive under natural conditions. The ecological implications of this change in coping style remain, nevertheless, an open question.

  8. Nature-Based Tourism Elicits a Phenotypic Shift in the Coping Abilities of Fish

    Science.gov (United States)

    Geffroy, Benjamin; Sadoul, Bastien; Bouchareb, Amine; Prigent, Sylvain; Bourdineaud, Jean-Paul; Gonzalez-Rey, Maria; Morais, Rosana N.; Mela, Maritana; Nobre Carvalho, Lucélia; Bessa, Eduardo

    2018-01-01

    Nature-based tourism is gaining extensive popularity, increasing the intensity and frequency of human-wildlife contacts. As a consequence, behavioral and physiological alterations were observed in most exposed animals. However, while the majority of these studies investigated the effects of punctual exposure to tourists, the consequences of constant exposition to humans in the wild remains overlooked. This is an important gap considering the exponential interest for recreational outdoor activities. To infer long-term effects of intensive tourism, we capitalized on Odontostilbe pequira, a short-lived sedentary Tetra fish who spends its life close to humans, on which it feeds on dead skin. Hence, those fish are constantly exposed to tourists throughout their lifecycle. Here we provide an integrated picture of the whole phenomenon by investigating, for the first time, the expression of genes involved in stress response and neurogenesis, as well as behavioral and hormonal responses of animals consistently exposed to tourists. Gene expression of the mineralocorticoid (and cortisol) receptor (mr) and the neurogenic differentiation factor (NeuroD) were significantly higher in fish sampled in the touristic zone compared to those sampled in the control zone. Additionally, after a simulated stress in artificial and controlled conditions, those fish previously exposed to visitors produced more cortisol and presented increased behavioral signs of stress compared to their non-exposed conspecifics. Overall, nature-based tourism appeared to shift selection pressures, favoring a sensitive phenotype that does not thrive under natural conditions. The ecological implications of this change in coping style remain, nevertheless, an open question. PMID:29459828

  9. A semantic-based method for extracting concept definitions from scientific publications: evaluation in the autism phenotype domain

    OpenAIRE

    Hassanpour, Saeed; O?Connor, Martin J; Das, Amar K

    2013-01-01

    Background A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based t...

  10. Genome profiling (GP method based classification of insects: congruence with that of classical phenotype-based one.

    Directory of Open Access Journals (Sweden)

    Shamim Ahmed

    Full Text Available Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP. The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species.

  11. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

    Science.gov (United States)

    Alford, Sara K; van Beek, Edwin J R; McLennan, Geoffrey; Hoffman, Eric A

    2010-04-20

    Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

  12. Associations between screen-based sedentary behavior and cardiovascular disease risk factors in Korean youth.

    Science.gov (United States)

    Byun, Wonwoo; Dowda, Marsha; Pate, Russell R

    2012-04-01

    The purposes of this study were to: 1) describe the patterns of screen-based sedentary behaviors, and 2) examine the association between screen-based sedentary behavior and cardiovascular disease (CVD) risk factors in representative Korean children and adolescents, aged 12 to 18 yr, in the Korean National Health and Nutrition Examination Survey. Screen-based sedentary behavior was measured using self-report questionnaires that included items for time spent watching TV and playing PC/video games. Physical activity was measured using items for frequency and duration of moderate-to-vigorous physical activity (MVPA). CVD risk factors such as body mass index (BMI), waist circumference, LDL cholesterol, HDL cholesterol, total cholesterol, triglycerides, glucose, systolic blood pressure, and diastolic blood pressure were measured. Boys spent more time playing PC/video games, and girls spent more time watching TV. After adjusting for age, gender, annual household income, and MVPA, an additional hour of watching TV was significantly associated with the risk of overweight (OR 1.17 [95% CI 1.03-1.33]), high abdominal adiposity (OR 1.27 [1.06-1.51]), and low HDL cholesterol (OR 1.27 [1.10-1.47]). An additional hour spent playing PC/video games also increased the risk of high abdominal adiposity (OR 1.20 [1.03-1.40]). Prospective observations and interventions are needed to determine causal relationships between screen-based sedentary behavior and CVD risk profiles in Korean youth.

  13. Genomic Influence in the Prevention of Cardiovascular Diseases with a Sterol-Based Treatment

    Directory of Open Access Journals (Sweden)

    Ismael San Mauro Martín

    2018-04-01

    Full Text Available Raised serum cholesterol concentration is a well-established risk factor in cardiovascular disease. In addition, genetic load may have an indirect influence on cardiovascular risk. Plant-based sterol-supplemented foods are recommended to help reduce the serum low-density lipoprotein cholesterol level. The objective was to analyse the influence of different polymorphisms in hypercholesterolemia patients following a dietary treatment with plant sterols. A randomised double-blind cross-over controlled clinical trial was carried out in 45 people (25 women. Commercial milk, containing 2.24 g of sterols, was ingested daily during a 3-week period, and then the same amount of skim milk, without sterols, was consumed daily during the 3-week placebo phase. Both phases were separated by a washout period of 2 weeks. At the beginning and end of each phase, blood draws were performed. Genes LIPC C-514T and APOA5 C56G are Ser19Trp carriers and greatly benefit from sterol intake in the diet. LIPC C-514T TT homozygous carriers had lower low-density lipoprotein cholesterol (LDL-c levels than CC homozygote and CT heterozygote carriers after the ingestion of plant sterols (p = 0.001. These two genes also showed statistically significant changes in total cholesterol levels (p = 0.025; p = 0.005, and no significant changes in high-density lipoprotein (HDL cholesterol levels (p = 0.032; p = 0.003, respectively. No statistically significant differences were observed for other genes. Further studies are needed to establish which genotype combinations would be the most protective against hypercholesterolemia.

  14. Predictive Accuracy of a Cardiovascular Disease Risk Prediction Model in Rural South India – A Community Based Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Farah N Fathima

    2015-03-01

    Full Text Available Background: Identification of individuals at risk of developing cardiovascular diseases by risk stratification is the first step in primary prevention. Aims & Objectives: To assess the five year risk of developing a cardiovascular event from retrospective data and to assess the predictive accuracy of the non laboratory based National Health and Nutrition Examination Survey (NHANES risk prediction model among individuals in a rural South Indian population. Materials & Methods: A community based retrospective cohort study was conducted in three villages where risk stratification was done for all eligible adults aged between 35-74 years at the time of initial assessment using the NHANES risk prediction charts. Household visits were made after a period of five years by trained doctors to determine cardiovascular outcomes. Results: 521 people fulfilled the eligibility criteria of whom 486 (93.3% could be traced after five years. 56.8% were in low risk, 36.6% were in moderate risk and 6.6% were in high risk categories. 29 persons (5.97% had had cardiovascular events over the last five years of which 24 events (82.7% were nonfatal and five (17.25% were fatal. The mean age of the people who developed cardiovascular events was 57.24 ± 9.09 years. The odds ratios for the three levels of risk showed a linear trend with the odds ratios for the moderate risk and high risk category being 1.35 and 1.94 respectively with the low risk category as baseline. Conclusion: The non laboratory based NHANES charts did not accurately predict the occurrence of cardiovascular events in any of the risk categories.

  15. Multi-source and ontology-based retrieval engine for maize mutant phenotypes

    Science.gov (United States)

    In the midst of this genomics era, major plant genome databases are collecting massive amounts of heterogeneous information, including sequence data, gene product information, images of mutant phenotypes, etc., as well as textual descriptions of many of these entities. While basic browsing and sear...

  16. Effect of a group-based rehabilitation programme on glycaemic control and cardiovascular risk factors in type 2 diabetes patients: The Copenhagen Type 2 Diabetes Rehabilitation Project

    DEFF Research Database (Denmark)

    Vadstrup, Eva Soelberg; Frølich, Anne; Perrild, Hans Jørgen Duckert

    2011-01-01

    To compare the effectiveness of a group-based rehabilitation programme with an individual counselling programme at improving glycaemic control and cardiovascular risk factors among patients with type 2 diabetes.......To compare the effectiveness of a group-based rehabilitation programme with an individual counselling programme at improving glycaemic control and cardiovascular risk factors among patients with type 2 diabetes....

  17. A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges & opportunities.

    Science.gov (United States)

    Aneni, Ehimen C; Roberson, Lara L; Maziak, Wasim; Agatston, Arthur S; Feldman, Theodore; Rouseff, Maribeth; Tran, Thinh H; Blumenthal, Roger S; Blaha, Michael J; Blankstein, Ron; Al-Mallah, Mouaz H; Budoff, Matthew J; Nasir, Khurram

    2014-01-01

    The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose. A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

  18. A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges & opportunities.

    Directory of Open Access Journals (Sweden)

    Ehimen C Aneni

    Full Text Available CONTEXT: The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. EVIDENCE ACQUISITION: We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose. EVIDENCE SYNTHESIS: A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. CONCLUSION: Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

  19. Discrimination of plant root zone water status in greenhouse production based on phenotyping and machine learning techniques

    OpenAIRE

    Guo, Doudou; Juan, Jiaxiang; Chang, Liying; Zhang, Jingjin; Huang, Danfeng

    2017-01-01

    Plant-based sensing on water stress can provide sensitive and direct reference for precision irrigation system in greenhouse. However, plant information acquisition, interpretation, and systematical application remain insufficient. This study developed a discrimination method for plant root zone water status in greenhouse by integrating phenotyping and machine learning techniques. Pakchoi plants were used and treated by three root zone moisture levels, 40%, 60%, and 80% relative water content...

  20. A wearable smartphone-based platform for real-time cardiovascular disease detection via electrocardiogram processing.

    Science.gov (United States)

    Oresko, Joseph J; Duschl, Heather; Cheng, Allen C

    2010-05-01

    Cardiovascular disease (CVD) is the single leading cause of global mortality and is projected to remain so. Cardiac arrhythmia is a very common type of CVD and may indicate an increased risk of stroke or sudden cardiac death. The ECG is the most widely adopted clinical tool to diagnose and assess the risk of arrhythmia. ECGs measure and display the electrical activity of the heart from the body surface. During patients' hospital visits, however, arrhythmias may not be detected on standard resting ECG machines, since the condition may not be present at that moment in time. While Holter-based portable monitoring solutions offer 24-48 h ECG recording, they lack the capability of providing any real-time feedback for the thousands of heart beats they record, which must be tediously analyzed offline. In this paper, we seek to unite the portability of Holter monitors and the real-time processing capability of state-of-the-art resting ECG machines to provide an assistive diagnosis solution using smartphones. Specifically, we developed two smartphone-based wearable CVD-detection platforms capable of performing real-time ECG acquisition and display, feature extraction, and beat classification. Furthermore, the same statistical summaries available on resting ECG machines are provided.

  1. Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease.

    Science.gov (United States)

    Azuaje, Francisco; Zheng, Huiru; Camargo, Anyela; Wang, Haiying

    2011-08-01

    The discovery of novel disease biomarkers is a crucial challenge for translational bioinformatics. Demonstration of both their classification power and reproducibility across independent datasets are essential requirements to assess their potential clinical relevance. Small datasets and multiplicity of putative biomarker sets may explain lack of predictive reproducibility. Studies based on pathway-driven discovery approaches have suggested that, despite such discrepancies, the resulting putative biomarkers tend to be implicated in common biological processes. Investigations of this problem have been mainly focused on datasets derived from cancer research. We investigated the predictive and functional concordance of five methods for discovering putative biomarkers in four independently-generated datasets from the cardiovascular disease domain. A diversity of biosignatures was identified by the different methods. However, we found strong biological process concordance between them, especially in the case of methods based on gene set analysis. With a few exceptions, we observed lack of classification reproducibility using independent datasets. Partial overlaps between our putative sets of biomarkers and the primary studies exist. Despite the observed limitations, pathway-driven or gene set analysis can predict potentially novel biomarkers and can jointly point to biomedically-relevant underlying molecular mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.

    Science.gov (United States)

    Adelborg, Kasper; Szépligeti, Szimonetta Komjáthiné; Holland-Bill, Louise; Ehrenstein, Vera; Horváth-Puhó, Erzsébet; Henderson, Victor W; Sørensen, Henrik Toft

    2018-01-31

    To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. Nationwide, population based cohort study. All Danish hospitals and hospital outpatient clinics from 1995 to 2013. 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking

  3. Manganese ferrite-based nanoparticles induce ex vivo, but not in vivo, cardiovascular effects

    Directory of Open Access Journals (Sweden)

    Nunes ADC

    2014-07-01

    Full Text Available Allancer DC Nunes,1 Laylla S Ramalho,2 Álvaro PS Souza,1 Elizabeth P Mendes,1,3 Diego B Colugnati,1 Nícholas Zufelato,2 Marcelo H Sousa,4 Andris F Bakuzis,2 Carlos H Castro1,3 1Department of Physiological Sciences, 2Physics Institute, Federal University of Goiás, Goiânia, Brazil; 3National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte, Brazil; 4Faculty of Ceilândia, University of Brasília, Brasília-DF, Brazil Abstract: Magnetic nanoparticles (MNPs have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have useful magnetic resonance imaging characteristics and potential for hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of three different types of manganese ferrite-based magnetic nanoparticles: citrate-coated (CiMNPs; tripolyphosphate-coated (PhMNPs; and bare magnetic nanoparticles (BaMNPs. The samples were characterized by vibrating sample magnetometer, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The CiMNPs, but not PhMNPs and BaMNPs, induced a transient decrease in the left ventricular end-systolic pressure. The PhMNPs and BaMNPs, but not CiMNPs, induced an increase in left ventricular end-diastolic pressure, which resulted in a decrease in a left ventricular end developed pressure. Indeed, PhMNPs and BaMNPs also caused a decrease in the maximal rate of left ventricular pressure rise (+dP/dt and maximal rate of left ventricular pressure decline (–dP/dt. The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. BaMNPs, but not PhMNPs or CiMNPs, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart

  4. Asthma phenotypes in childhood.

    Science.gov (United States)

    Reddy, Monica B; Covar, Ronina A

    2016-04-01

    This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly.

  5. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

    DEFF Research Database (Denmark)

    Simoni, Yannick; Fehlings, Michael; Kloverpris, Henrik N.

    2017-01-01

    Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors...... to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells...... that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals...

  6. DISPARITIES IN CARDIOVASCULAR RISK FROM ORGANOPHOSPHATE-BASED PESTICIDE EXPOSURE IN SUSCEPTIBLE POPULATIONS.

    Science.gov (United States)

    High blood pressure (hypertension), the most common of all cardiovascular (CVD) diseases, is a major cause of morbidity and mortality in the United States, and a large percentage of the population manifests a genetic predisposition. Hypertension is polygenetically inherited, envi...

  7. Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T, p.(Arg312Cys) mutation in COL1A1: Report on a three-generation family without cardiovascular events, and literature review.

    Science.gov (United States)

    Colombi, Marina; Dordoni, Chiara; Venturini, Marina; Zanca, Arianna; Calzavara-Pinton, Piergiacomo; Ritelli, Marco

    2017-02-01

    Classical Ehlers-Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in COL5A1 and COL5A2 encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C>T mutation in COL1A1 that results in an uncommon substitution of a non-glycine residue in one Gly-Xaa-Yaa repeat of the pro-α1(I)-chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N-propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as "(classic) vascular-like" EDS patients. Herein, we describe a three-generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) COL1A1 mutation from those with COL5A1 and COL5A2 defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in COL1A1 should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Population-based investigations to study the association of cardiovascular polymorphisms and adverse pregnancy outcome

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Young, Bradford

    2007-01-01

    Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauteri......-thrombotic and cardiovascular genetic polymorphisms. These studies are urgently needed to accurately assess the linkage between family history, presence of adverse pregnancy outcome, and long-term cardiovascular risk....

  9. Advanced Cell Classifier: User-Friendly Machine-Learning-Based Software for Discovering Phenotypes in High-Content Imaging Data.

    Science.gov (United States)

    Piccinini, Filippo; Balassa, Tamas; Szkalisity, Abel; Molnar, Csaba; Paavolainen, Lassi; Kujala, Kaisa; Buzas, Krisztina; Sarazova, Marie; Pietiainen, Vilja; Kutay, Ulrike; Smith, Kevin; Horvath, Peter

    2017-06-28

    High-content, imaging-based screens now routinely generate data on a scale that precludes manual verification and interrogation. Software applying machine learning has become an essential tool to automate analysis, but these methods require annotated examples to learn from. Efficiently exploring large datasets to find relevant examples remains a challenging bottleneck. Here, we present Advanced Cell Classifier (ACC), a graphical software package for phenotypic analysis that addresses these difficulties. ACC applies machine-learning and image-analysis methods to high-content data generated by large-scale, cell-based experiments. It features methods to mine microscopic image data, discover new phenotypes, and improve recognition performance. We demonstrate that these features substantially expedite the training process, successfully uncover rare phenotypes, and improve the accuracy of the analysis. ACC is extensively documented, designed to be user-friendly for researchers without machine-learning expertise, and distributed as a free open-source tool at www.cellclassifier.org. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Cost-effectiveness of aspirin treatment in the primary prevention of cardiovascular disease events in subgroups based on age, gender, and varying cardiovascular risk

    NARCIS (Netherlands)

    Greving, Jacoba P.; Buskens, Erik; Koffijberg, Hendrik; Algra, Ale

    2008-01-01

    BACKGROUND - Aspirin is effective for the primary prevention of cardiovascular events, but it remains unclear for which subgroups of individuals aspirin is beneficial. We assessed the cost-effectiveness of aspirin separately for men and women of different ages with various levels of cardiovascular

  11. Cost-effectiveness of aspirin treatment in the primary prevention of cardiovascular disease events in subgroups based on age, gender, and varying cardiovascular risk

    NARCIS (Netherlands)

    Greving, J.P.; Buskens, E.; Koffijberg, H.; Algra, A.

    2008-01-01

    Background-Aspirin is effective for the primary prevention of cardiovascular events, but it remains unclear for which subgroups of individuals aspirin is beneficial. We assessed the cost-effectiveness of aspirin separately for men and women of different ages with various levels of cardiovascular

  12. Frailty and cardiovascular risk in community-dwelling elderly: a population-based study

    Directory of Open Access Journals (Sweden)

    Ricci NA

    2014-10-01

    Full Text Available Natalia Aquaroni Ricci,1 Germane Silva Pessoa,1 Eduardo Ferriolli,2 Rosangela Correa Dias,3 Monica Rodrigues Perracini1 1Master’s and Doctoral Programs in Physical Therapy, Universidade Cidade de São Paulo (UNICID, São Paulo, 2Faculty of Medicine, Universidade de São Paulo (USP, Ribeirão Preto, 3Department of Physiotherapy, Universidade Federal de Minas Gerais (UFMG, Belo Horizonte, Brazil Background: Evidence suggests a possible bidirectional connection between cardiovascular disease (CVD and the frailty syndrome in older people.Purpose: To verify the relationship between CVD risk factors and the frailty syndrome in community-dwelling elderly.Methods: This population-based study used data from the Fragilidade em Idosos Brasileiros (FIBRA Network Study, a cross-sectional study designed to investigate frailty profiles among Brazilian older adults. Frailty status was defined as the presence of three or more out of five of the following criteria: unintentional weight loss, weakness, self-reported fatigue, slow walking speed, and low physical activity level. The ascertained CVD risk factors were self-reported and/or directly measured hypertension, diabetes mellitus, obesity, waist circumference ­measurement, and smoking.Results: Of the 761 participants, 9.7% were characterized as frail, 48.0% as pre-frail, and 42.3% as non-frail. The most prevalent CVD risk factor was hypertension (84.4% and the lowest one was smoking (10.4%. It was observed that among those participants with four or five risk factors there was a higher proportion of frail and pre-frail compared with non-frail (Fisher’s exact test: P=0.005; P=0.021. Self-reported diabetes mellitus was more prevalent among frail and pre-frail participants when compared with non-frail participants (Fisher’s exact test: P≤0.001; P≤0.001. There was little agreement between self-reported hypertension and hypertension identified by blood pressure measurement.Conclusion: Hypertension was

  13. Biodegradable, elastomeric coatings with controlled anti-proliferative agent release for magnesium-based cardiovascular stents.

    Science.gov (United States)

    Gu, Xinzhu; Mao, Zhongwei; Ye, Sang-Ho; Koo, Youngmi; Yun, Yeoheung; Tiasha, Tarannum R; Shanov, Vesselin; Wagner, William R

    2016-08-01

    Vascular stent design continues to evolve to further improve the efficacy and minimize the risks associated with these devices. Drug-eluting coatings have been widely adopted and, more recently, biodegradable stents have been the focus of extensive evaluation. In this report, biodegradable elastomeric polyurethanes were synthesized and applied as drug-eluting coatings for a relatively new class of degradable vascular stents based on Mg. The dynamic degradation behavior, hemocompatibility and drug release were investigated for poly(carbonate urethane) urea (PCUU) and poly(ester urethane) urea (PEUU) coated magnesium alloy (AZ31) stents. Poly(lactic-co-glycolic acid) (PLGA) coated and bare stents were employed as control groups. The PCUU coating effectively slowed the Mg alloy corrosion in dynamic degradation testing compared to PEUU-coated, PLGA-coated and bare Mg alloy stents. This was confirmed by electron microscopy, energy-dispersive x-ray spectroscopy and magnesium ion release experiments. PCUU-coating of AZ31 was also associated with significantly reduced platelet adhesion in acute blood contact testing. Rat vascular smooth muscle cell (rSMC) proliferation was successfully inhibited when paclitaxel was released from pre-loaded PCUU coatings. The corrosion retardation, low thrombogenicity, drug loading capacity, and high elasticity make PCUU an attractive option for drug eluting coating on biodegradable metallic cardiovascular stents. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Oximeter-based autonomic state indicator algorithm for cardiovascular risk assessment.

    Science.gov (United States)

    Grote, Ludger; Sommermeyer, Dirk; Zou, Ding; Eder, Derek N; Hedner, Jan

    2011-02-01

    Cardiovascular (CV) risk assessment is important in clinical practice. An autonomic state indicator (ASI) algorithm based on pulse oximetry was developed and validated for CV risk assessment. One hundred forty-eight sleep clinic patients (98 men, mean age 50 ± 13 years) underwent an overnight study using a novel photoplethysmographic sensor. CV risk was classified according to the European Society of Hypertension/European Society of Cardiology (ESH/ESC) risk factor matrix. Five signal components reflecting cardiac and vascular activity (pulse wave attenuation, pulse rate acceleration, pulse propagation time, respiration-related pulse oscillation, and oxygen desaturation) extracted from 99 randomly selected subjects were used to train the classification algorithm. The capacity of the algorithm for CV risk prediction was validated in 49 additional patients. Each signal component contributed independently to CV risk prediction. The sensitivity and specificity of the algorithm to distinguish high/low CV risk in the validation group were 80% and 77%, respectively. The area under the receiver operating characteristic curve for high CV risk classification was 0.84. β-Blocker treatment was identified as an important factor for classification that was not in line with the ESH/ESC reference matrix. Signals derived from overnight oximetry recording provide a novel potential tool for CV risk classification. Prospective studies are warranted to establish the value of the ASI algorithm for prediction of outcome in CV disease.

  15. Internet-based system for simulation-based medical planning for cardiovascular disease.

    Science.gov (United States)

    Steele, Brooke N; Draney, Mary T; Ku, Joy P; Taylor, Charles A

    2003-06-01

    Current practice in vascular surgery utilizes only diagnostic and empirical data to plan treatments, which does not enable quantitative a priori prediction of the outcomes of interventions. We have previously described simulation-based medical planning methods to model blood flow in arteries and plan medical treatments based on physiologic models. An important consideration for the design of these patient-specific modeling systems is the accessibility to physicians with modest computational resources. We describe a simulation-based medical planning environment developed for the World Wide Web (WWW) using the Virtual Reality Modeling Language (VRML) and the Java programming language.

  16. GUESS-ing polygenic associations with multiple phenotypes using a GPU-based evolutionary stochastic search algorithm.

    Directory of Open Access Journals (Sweden)

    Leonardo Bottolo

    Full Text Available Genome-wide association studies (GWAS yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-phenotype GWAS where detection and interpretability of complex SNP(s-trait(s associations are complicated by complex Linkage Disequilibrium patterns between SNPs and correlation between traits. Here we propose a computationally efficient algorithm (GUESS to explore complex genetic-association models and maximize genetic variant detection. We integrated our algorithm with a new Bayesian strategy for multi-phenotype analysis to identify the specific contribution of each SNP to different trait combinations and study genetic regulation of lipid metabolism in the Gutenberg Health Study (GHS. Despite the relatively small size of GHS (n  =  3,175, when compared with the largest published meta-GWAS (n > 100,000, GUESS recovered most of the major associations and was better at refining multi-trait associations than alternative methods. Amongst the new findings provided by GUESS, we revealed a strong association of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic groups, which were overlooked in the larger meta-GWAS and not revealed by competing approaches, associations that we replicated in two independent cohorts. Moreover, we demonstrated the increased power of GUESS over alternative multi-phenotype approaches, both Bayesian and non-Bayesian, in a simulation study that mimics real-case scenarios. We showed that our parallel implementation based on Graphics Processing Units outperforms alternative multi-phenotype methods. Beyond multivariate modelling of multi-phenotypes, our Bayesian model employs a flexible hierarchical prior structure for genetic effects that adapts to any correlation structure of the predictors and increases the power to identify

  17. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.

    Science.gov (United States)

    Domingo, Laia; Salas, Dolores; Zubizarreta, Raquel; Baré, Marisa; Sarriugarte, Garbiñe; Barata, Teresa; Ibáñez, Josefa; Blanch, Jordi; Puig-Vives, Montserrat; Fernández, Ana; Castells, Xavier; Sala, Maria

    2014-01-10

    Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; cancers, extreme breast density being strongly associated with occult tumors (OR

  18. Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study.

    Science.gov (United States)

    Dekkers, Olaf M; Horváth-Puhó, Erzsébet; Cannegieter, Suzanne C; Vandenbroucke, Jan P; Sørensen, Henrik Toft; Jørgensen, Jens Otto L

    2017-01-01

    Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40-4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33-1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58-8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30-8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism. © 2017 European Society of Endocrinology.

  19. Statistical Validation of a Web-Based GIS Application and Its Applicability to Cardiovascular-Related Studies.

    Science.gov (United States)

    Lee, Jae Eun; Sung, Jung Hye; Malouhi, Mohamad

    2015-12-22

    There is abundant evidence that neighborhood characteristics are significantly linked to the health of the inhabitants of a given space within a given time frame. This study is to statistically validate a web-based GIS application designed to support cardiovascular-related research developed by the NIH funded Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN) Data Coordinating Center (DCC) and discuss its applicability to cardiovascular studies. Geo-referencing, geocoding and geospatial analyses were conducted for 500 randomly selected home addresses in a U.S. southeastern Metropolitan area. The correlation coefficient, factor analysis and Cronbach's alpha (α) were estimated to quantify measures of the internal consistency, reliability and construct/criterion/discriminant validity of the cardiovascular-related geospatial variables (walk score, number of hospitals, fast food restaurants, parks and sidewalks). Cronbach's α for CVD GEOSPATIAL variables was 95.5%, implying successful internal consistency. Walk scores were significantly correlated with number of hospitals (r = 0.715; p restaurants (r = 0.729; p application were internally consistent and demonstrated satisfactory validity. Therefore, the GIS application may be useful to apply to cardiovascular-related studies aimed to investigate potential impact of geospatial factors on diseases and/or the long-term effect of clinical trials.

  20. Feasibility of community-based screening for cardiovascular disease risk in an ethnic community: the South Asian Cardiovascular Health Assessment and Management Program (SA-CHAMP).

    Science.gov (United States)

    Jones, Charlotte A; Nanji, Alykhan; Mawani, Shefina; Davachi, Shahnaz; Ross, Leanne; Vollman, Ardene; Aggarwal, Sandeep; King-Shier, Kathryn; Campbell, Norman

    2013-02-21

    South Asian Canadians experience disproportionately high rates of cardiovascular disease (CVD). The goal of this qualitative study was to determine the feasibility of implementing a sustainable, culturally adapted, community-based CVD risk factor screening program for this population. South Asians (≥ 45 years) in Calgary, Alberta underwent opportunistic cardiovascular risk factor screening by lay trained volunteers at local religious facilities. Those with elevated blood pressure (BP) or ≥ 1 risk factor underwent point of care cholesterol testing, 10-year CVD risk calculation, counseling, and referral to family physicians and local culturally tailored chronic disease management (CDM) programs. Participants were invited for re-screening and were surveyed about health system follow-up, satisfaction with the program and suggestions for improvement. Changes in risk factors from baseline were estimated using McNemar's test (proportions) and paired t-tests (continuous measures). Baseline assessment was completed for 238 participants (median age 64 years, 51% female). Mean TC, HDL and TC/HDL were 5.41 mmol/L, 1.12 mmol/L and 4.7, respectively. Mean systolic and diastolic blood pressures (mmHg) were 129 and 75 respectively. Blood pressure and TC/HDL ratios exceeded recommended targets in 36% and 58%, respectively, and 76% were at high risk for CVD. Ninety-nine participants (47% female) attended re-screening. 82% had accessed health care providers, 22% reported medication changes and 3.5% had attended the CDM programs. While BP remained unchanged, TC and TC/HDL decreased and HDL increased significantly (mean differences: -0.52 mmol/L, -1.04 and +0.07 mmol/L, respectively). Participants were very satisfied (80%) or satisfied (20%) with the project. Participants suggested screening sessions and CDM programs be more accessible by: delivering evening or weekends programs at more sites, providing transportation, offering multilingual programs/translation assistance, reducing

  1. Acid-base status and cardiovascular function in mink (Mustela vison) anaesthetized with ketamine/midazolam.

    Science.gov (United States)

    Wamberg, S; Svendsen, P; Johansen, B

    1996-01-01

    Heart rate, arterial blood pressure and blood acid-base status were determined in 18 adult female mink (mean (+/- SEM) body weight 1052 +/- 34 g) during long-term anaesthesia with either controlled ventilation (n=12) or spontaneous respiration (n=6). Surgical anaesthesia was induced by intramuscular injection of ketamine hydrochloride (Ketaminol Vet, 40.0 +/- 1.7 mg/kg) and midazolam hydrochloride (Dormicum 2.8 +/- 0.1 mg/kg) and maintained for at least 5 h by continuous intravenous infusion of this drug combination in 0.9% saline. For all animals, the mean rates of infusion of ketamine and midazolam were 48.4 +/- 1.6 and 1.61 +/- 0.12 mg/h, respectively. Following continuous infusion of the anaesthetics in isotonic saline, at a rate of 20 ml/h, a moderate 'dilution acidosis' developed, which could be corrected by replacement of part of the saline with sodium bicarbonate to a final concentration of approximately 25 mmol NaHCO3 per litre. However, when the animals were allowed to breathe spontaneously, an increase in heart rate and a combined respiratory and metabolic acidosis occurred, due to severe respiratory depression. Apart from these effects and a few cases of increased salivation, no adverse effects over time were observed on the arterial blood acid-base status and cardiovascular function of the animals during ketamine/midazolam anaesthesia. It is concluded that the procedure described for long-term anaesthesia in mink is convenient and safe for acute physiological experiments in this species, provided normal body temperature and pulmonary gas exchange is sufficiently maintained. Thus, the need for an adequately controlled artificial ventilation is strongly emphasized. Finally, a proposal for the composition of an intravenous solution, containing ketamine and midazolam hydrochloride, and sodium bicarbonate in saline, suitable for long-term anaesthesia in adult mink is presented.

  2. Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Muhammad Saeed Ahmad

    Full Text Available Skin auto fluorescence (SAF is used as a proxy for the accumulation of advanced glycation end products (AGEs and has been proposed to stratify patients into cardiovascular disease (CVD and diabetes mellitus (DM risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens'd is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.

  3. [Phenotype-based primary screening for drugs promoting neuronal subtype differentiation in embryonic stem cells with light microscope].

    Science.gov (United States)

    Gao, Yi-ning; Wang, Dan-ying; Pan, Zong-fu; Mei, Yu-qin; Wang, Zhi-qiang; Zhu, Dan-yan; Lou, Yi-jia

    2012-07-01

    To set up a platform for phenotype-based primary screening of drug candidates promoting neuronal subtype differentiation in embryonic stem cells (ES) with light microscope. Hanging drop culture 4-/4+ method was employed to harvest the cells around embryoid body (EB) at differentiation endpoint. Morphological evaluation for neuron-like cells was performed with light microscope. Axons for more than three times of the length of the cell body were considered as neuron-like cells. The compound(s) that promote neuron-like cells was further evaluated. Icariin (ICA, 10(-6)mol/L) and Isobavachin (IBA, 10(-7)mol/L) were selected to screen the differentiation-promoting activity on ES cells. Immunofluorescence staining with specific antibodies (ChAT, GABA) was used to evaluate the neuron subtypes. The cells treated with IBA showed neuron-like phenotype, but the cells treated with ICA did not exhibit the morphological changes. ES cells treated with IBA was further confirmed to be cholinergic and GABAergic neurons. Phenotypic screening with light microscope for molecules promoting neuronal differentiation is an effective method with advantages of less labor and material consuming and time saving, and false-positive results derived from immunofluorescence can be avoided. The method confirms that IBA is able to facilitate ES cells differentiating into neuronal cells, including cholinergic neurons and GABAergic neurons.

  4. Characterization of Carambola (Averrhoa carambola L. Plant Collection of Cibinong Plant Germplasm Garden Based on Phenotypic and Genetic Characters

    Directory of Open Access Journals (Sweden)

    Dody Priadi

    2016-04-01

    Full Text Available Indonesia as a rich biodiversity country has many superior fruit plant germplasms such as sweet star fruit or carambola (Averrhoa carambola L.. Some varieties of carambola which collected at the Germplasm Garden of Research Center for Biotechnology-LIPI have been used for parent trees of fruit plant production. Therefore, they have to be characterized both phenotypically and genetically. The objective of the study was to analyze the relationship between eight varieties of carambola i.e. Malaysia, Penang, Rawasari, Bangkok, Sembiring, Dewabaru, Demak and Dewimurni at the germplasm garden based on phenotypic and genetic characters. Phenotypic characters were observed directly in the field, whereas genetic characters were observed with RAPD markers using 10 primers. Phylogenetic analysis was done using NT-SYS software showed that there were three clusters of carambola varieties. Meanwhile, Malaysia and Penang varieties have closed relationships (96% compared with the other varieties. The result of the study would be dedicated to updating and completing the existing fruit plant collection database of Plants Germplasm Garden. 

  5. A web-based intervention for health professionals and patients to decrease cardiovascular risk attributable to physical inactivity: development process.

    Science.gov (United States)

    Sassen, Barbara; Kok, Gerjo; Mesters, Ilse; Crutzen, Rik; Cremers, Anita; Vanhees, Luc

    2012-12-14

    Patients with cardiovascular risk factors can reduce their risk of cardiovascular disease by increasing their physical activity and their physical fitness. According to the guidelines for cardiovascular risk management, health professionals should encourage their patients to engage in physical activity. In this paper, we provide insight regarding the systematic development of a Web-based intervention for both health professionals and patients with cardiovascular risk factors using the development method Intervention Mapping. The different steps of Intervention Mapping are described to open up the "black box" of Web-based intervention development and to support future Web-based intervention development. The development of the Professional and Patient Intention and Behavior Intervention (PIB2 intervention) was initiated with a needs assessment for both health professionals (ie, physiotherapy and nursing) and their patients. We formulated performance and change objectives and, subsequently, theory- and evidence-based intervention methods and strategies were selected that were thought to affect the intention and behavior of health professionals and patients. The rationale of the intervention was based on different behavioral change methods that allowed us to describe the scope and sequence of the intervention and produced the Web-based intervention components. The Web-based intervention consisted of 5 modules, including individualized messages and self-completion forms, and charts and tables. The systematic and planned development of the PIB2 intervention resulted in an Internet-delivered behavior change intervention. The intervention was not developed as a substitute for face-to-face contact between professionals and patients, but as an application to complement and optimize health services. The focus of the Web-based intervention was to extend professional behavior of health care professionals, as well as to improve the risk-reduction behavior of patients with

  6. A Web-Based Intervention for Health Professionals and Patients to Decrease Cardiovascular Risk Attributable to Physical Inactivity: Development Process

    Science.gov (United States)

    2012-01-01

    Background Patients with cardiovascular risk factors can reduce their risk of cardiovascular disease by increasing their physical activity and their physical fitness. According to the guidelines for cardiovascular risk management, health professionals should encourage their patients to engage in physical activity. Objective In this paper, we provide insight regarding the systematic development of a Web-based intervention for both health professionals and patients with cardiovascular risk factors using the development method Intervention Mapping. The different steps of Intervention Mapping are described to open up the “black box” of Web-based intervention development and to support future Web-based intervention development. Methods The development of the Professional and Patient Intention and Behavior Intervention (PIB2 intervention) was initiated with a needs assessment for both health professionals (ie, physiotherapy and nursing) and their patients. We formulated performance and change objectives and, subsequently, theory- and evidence-based intervention methods and strategies were selected that were thought to affect the intention and behavior of health professionals and patients. The rationale of the intervention was based on different behavioral change methods that allowed us to describe the scope and sequence of the intervention and produced the Web-based intervention components. The Web-based intervention consisted of 5 modules, including individualized messages and self-completion forms, and charts and tables. Results The systematic and planned development of the PIB2 intervention resulted in an Internet-delivered behavior change intervention. The intervention was not developed as a substitute for face-to-face contact between professionals and patients, but as an application to complement and optimize health services. The focus of the Web-based intervention was to extend professional behavior of health care professionals, as well as to improve the risk

  7. Anabolic steroids and cardiovascular risk: A national population-based cohort study.

    Science.gov (United States)

    Thiblin, Ingemar; Garmo, Hans; Garle, Mats; Holmberg, Lars; Byberg, Liisa; Michaëlsson, Karl; Gedeborg, Rolf

    2015-07-01

    Non-therapeutic use of anabolic androgenic steroids (AAS) has been associated with various adverse effects; one of the most serious being direct cardiovascular effects with unknown long-term consequences. Therefore, large studies of the association between AAS and cardiovascular outcomes are warranted. We investigated cardiovascular morbidity and mortality in individuals who tested positive for AAS. Between 2002 and 2009, a total of 2013 men were enrolled in a cohort on the date of their first AAS test. Mortality and morbidity after cohort entry was retrieved from national registries. Of the 2013 individuals, 409 (20%) tested positive for AAS. These men had twice the cardiovascular morbidity and mortality rate as those with negative tests (adjusted hazard ratio (aHR) 2.0; 95% confidence interval (CI) 1.2-3.3). Compared to the Swedish population, all tested men had an increased risk of premature death from all causes (standardized mortality ratio for AAS-positive: 19.3, 95% CI 12.4-30.0; for AAS-negative: 8.3, 95% CI 6.1-11.0). Non-therapeutic exposure to AAS appears to be an independent risk factor for cardiovascular morbidity and premature death. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Marginalisation and cardiovascular disease among rural Sami in Northern Norway: a population-based cross-sectional study.

    Science.gov (United States)

    Eliassen, Bent-Martin; Melhus, Marita; Hansen, Ketil Lenert; Broderstad, Ann Ragnhild

    2013-05-29

    Like other indigenous peoples, the Sami have been exposed to the huge pressures of colonisation, rapid modernisation and subsequent marginalisation. Previous studies among indigenous peoples show that colonialism, rapid modernisation and marginalisation is accompanied by increased stress, an unhealthy cardiovascular risk factor profile and disease burden. Updated data on the general burden of cardiovascular disease among the Sami is lacking. The primary objective of this study was to assess the relationship between marginalisation and self-reported lifetime cardiovascular disease (CVD) by minority/majority status in the rural Sami population of Norway. A cross-sectional population-based study (the SAMINOR study) was carried out in 2003-2004. The overall participation rate was 60.9% and a total of 4027 Sami individuals aged 36-79 years were included in the analyses. Data was collected by self-administrated questionnaires and a clinical examination. The logistic regression showed that marginalised Sami living in Norwegian dominated areas were more than twice as likely to report CVD as non-marginalised Sami living in Sami majority areas (OR 2.10, 95% CI: 1.40-3.14). No sex difference was found in the effects of marginalisation on self-reported life-time cardiovascular disease. Moderate to no intermediate effects were seen after including established CVD risk factors. This study showed that marginalised Sami living in Norwegian dominated areas were more than twice as likely as non-marginalised Sami from Sami majority areas to report lifetime cardiovascular disease (CVD). Moderate to no intermediate effects were seen after including established CVD risk factors, which suggest little difference in lifestyle related factors. Chronic stress exposure following marginalisation may however be a plausible explanation for some of the observed excess of CVD.

  9. Time series modeling of live-cell shape dynamics for image-based phenotypic profiling.

    Science.gov (United States)

    Gordonov, Simon; Hwang, Mun Kyung; Wells, Alan; Gertler, Frank B; Lauffenburger, Douglas A; Bathe, Mark

    2016-01-01

    Live-cell imaging can be used to capture spatio-temporal aspects of cellular responses that are not accessible to fixed-cell imaging. As the use of live-cell imaging continues to increase, new computational procedures are needed to characterize and classify the temporal dynamics of individual cells. For this purpose, here we present the general experimental-computational framework SAPHIRE (Stochastic Annotation of Phenotypic Individual-cell Responses) to characterize phenotypic cellular responses from time series imaging datasets. Hidden Markov modeling is used to infer and annotate morphological state and state-switching properties from image-derived cell shape measurements. Time series modeling is performed on each cell individually, making the approach broadly useful for analyzing asynchronous cell populations. Two-color fluorescent cells simultaneously expressing actin and nuclear reporters enabled us to profile temporal changes in cell shape following pharmacological inhibition of cytoskeleton-regulatory signaling pathways. Results are compared with existing approaches conventionally applied to fixed-cell imaging datasets, and indicate that time series modeling captures heterogeneous dynamic cellular responses that can improve drug classification and offer additional important insight into mechanisms of drug action. The software is available at http://saphire-hcs.org.

  10. (1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors

    OpenAIRE

    Vázquez Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez Martínez, Miguel Ángel; Vinaixa Crevillent, Maria; Chiva Blanch, Gemma; Estruch Riba, Ramon; Correig Blanchar, Xavier; Andrés Lacueva, Ma. Cristina

    2012-01-01

    Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100m...

  11. Pre-historic eating patterns in Latin America and protective effects of plant-based diets on cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Julio C. Acosta Navarro

    2010-01-01

    Full Text Available In this review, we present the contributions to nutrition science from Latin American native peoples and scientists, appreciated from a historic point of view since pre-historic times to the modern age. Additionally, we present epidemiological and clinical studies on the area of plant-based diets and their relation with the prevention and treatment of cardiovascular diseases conducted in recent decades, and we discuss challenges and perspectives regarding aspects of nutrition in the region

  12. A semantic-based method for extracting concept definitions from scientific publications: evaluation in the autism phenotype domain.

    Science.gov (United States)

    Hassanpour, Saeed; O'Connor, Martin J; Das, Amar K

    2013-08-12

    A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based text-mining approach that can automatically identify such definitions within text. Using an existing knowledge base of 156 autism phenotype definitions and an annotated corpus of 26 source articles containing such definitions, we evaluated and compared the average rank of correctly identified rule definition or corresponding rule template using both our semantic-based approach and a standard term-based approach. We examined three separate scenarios: (1) the snippet of text contained a definition already in the knowledge base; (2) the snippet contained an alternative definition for a concept in the knowledge base; and (3) the snippet contained a definition not in the knowledge base. Our semantic-based approach had a higher average rank than the term-based approach for each of the three scenarios (scenario 1: 3.8 vs. 5.0; scenario 2: 2.8 vs. 4.9; and scenario 3: 4.5 vs. 6.2), with each comparison significant at the p-value of 0.05 using the Wilcoxon signed-rank test. Our work shows that leveraging existing domain knowledge in the information extraction of biomedical definitions significantly improves the correct identification of such knowledge within sentences. Our method can thus help researchers rapidly acquire knowledge about biomedical definitions that are specified and evolving within an ever-growing corpus of scientific publications.

  13. Cardiovascular events in patients with atherothrombotic disease: a population-based longitudinal study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Wen-Hsien Lee

    Full Text Available BACKGROUND: Atherothrombotic diseases including cerebrovascular disease (CVD, coronary artery disease (CAD, and peripheral arterial disease (PAD, contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV outcomes in Asian population, there was no large-scale study to validate this relationship in this population. METHODS AND RESULTS: This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001-2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS, all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2% was higher than that of acute myocardial infarction (5.7% in our patients (P = 0.0006. In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169. CONCLUSIONS: This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score.

  14. Cardiovascular and metabolic risks in psoriasis and psoriatic arthritis: pragmatic clinical management based on available evidence.

    Science.gov (United States)

    Johnsson, Hanna; McInnes, Iain B; Sattar, Naveed

    2012-04-01

    Several studies suggest that patients with psoriasis and, in particular, psoriatic arthritis (PsA) are at increased risk of cardiovascular disease. These patients are also more likely to be obese and to have diabetes and fatty liver disease. This article discusses the association between psoriasis and PsA and cardiometabolic disorders, emphasising the need for better consideration of simple lifestyle interventions. It also highlights areas for future research and proposes a simple and pragmatic test portfolio to screen for cardiovascular risk and metabolic disorders in patients at higher risk.

  15. Current status of cardiovascular surgery in Japan, 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database (JCVSD). 1: Mission and history of JCVSD.

    Science.gov (United States)

    Takamoto, Shinichi; Motomura, Noboru; Miyata, Hiroaki; Tsukihara, Hiroyuki

    2018-01-01

    The Japan Cardiovascular Surgery Database (JCVSD) was created in 2000 with the support of the Society of Thoracic Surgeons (STS). The STS database content was translated to Japanese using the same disease criteria and in 2001, data entry for adult cardiac surgeries was initiated online using the University Hospital Medical Information Network (UMIN). In 2008, data entry for congenital heart surgeries was initiated in the congenital section of JCVSD and preoperative expected mortality (JapanSCORE) in adult cardiovascular surgeries was first calculated using the risk model of JCVSD. The Japan Surgical Board system merged with JCVSD in 2011, and all cardiovascular surgical data were registered in the JCVSD from 2012 onward. The reports resulting from the data analyses of the JCVSD will encourage further improvements in the quality of cardiovascular surgeries, patient safety, and medical care in Japan.

  16. Obesity and Cardiovascular Disease.

    Science.gov (United States)

    Ortega, Francisco B; Lavie, Carl J; Blair, Steven N

    2016-05-27

    The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-size-fits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis. © 2016 American Heart Association, Inc.

  17. Effectiveness of a Web-Based Protocol for the Screening and Phenotyping of Individuals with Tourette Syndrome for Genetic Studies

    Science.gov (United States)

    Egan, Crystelle; Marakovitz, Susan; O’Rourke, Julia; Osiecki, Lisa; Illmann, Cornelia; Barton, Lauren; McLaughlin, Elizabeth; Proujansky, Rachel; Royal, Justin; Cowley, Heather; Rangel-Lugo, Martha; Pauls, David; Scharf, Jeremiah M.; Mathews, Carol A.

    2014-01-01

    Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette Syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13 month period through the membership of the Tourette Syndrome Association (TSA) (n=28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. PMID:23090870

  18. Personalized therapy algorithms for type 2 diabetes: a phenotype-based approach

    Directory of Open Access Journals (Sweden)

    Ceriello A

    2014-06-01

    Full Text Available Antonio Ceriello,1,2 Marco Gallo,3 Riccardo Candido,4 Alberto De Micheli,5 Katherine Esposito,6 Sandro Gentile,6 Gerardo Medea71Department of Endocrinology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi iSunyer, 2Centro de Investigacion Biomèdica en Red de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain; 3Oncological Endocrinology, AOU Città della Salute e della Scienza-Molinette, Turin, 4Diabetes Center, ASS 1 Triestina, Trieste, 5Ligurian Health Agency, Genoa, 6Department of Clinical and Experimental Medicine, Second University of Naples, Naples, 7Italian College of General Practitioners, Florence, ItalyAbstract: Type 2 diabetes is a progressive disease with a complex and multifactorial pathophysiology. Patients with type 2 diabetes show a variety of clinical features, including different "phenotypes" of hyperglycemia (eg, fasting/preprandial or postprandial. Thus, the best treatment choice is sometimes difficult to make, and treatment initiation or optimization is postponed. This situation may explain why, despite the existing complex therapeutic armamentarium and guidelines for the treatment of type 2 diabetes, a significant proportion of patients do not have good metabolic control and at risk of developing the late complications of diabetes. The Italian Association of Medical Diabetologists has developed an innovative personalized algorithm for the treatment of type 2 diabetes, which is available online. According to the main features shown by the patient, six algorithms are proposed, according to glycated hemoglobin (HbA1c, ≥9% or ≤9%, body mass index (≤30 kg/m2 or ≥30 kg/m2, occupational risk potentially related to hypoglycemia, chronic renal failure, and frail elderly status. Through self-monitoring of blood glucose, patients are phenotyped according to the occurrence of fasting/preprandial or postprandial hyperglycemia. In each of these six algorithms, the gradual choice of

  19. Assessing the impact of the heart of New Ulm Project on cardiovascular disease risk factors: A population-based program to reduce cardiovascular disease.

    Science.gov (United States)

    Sidebottom, Abbey C; Sillah, Arthur; Vock, David M; Miedema, Michael D; Pereira, Raquel; Benson, Gretchen; Lindberg, Rebecca; Boucher, Jackie L; Knickelbine, Thomas; VanWormer, Jeffrey J

    2018-04-07

    The Heart of New Ulm Project (HONU), is a population-based project designed to reduce modifiable cardiovascular disease (CVD) risk factors in the rural community of New Ulm, MN. HONU interventions address multiple levels of the social-ecological model. The community is served by one health system, enabling the use of electronic health record (EHR) data for surveillance. The purpose of this study was to assess if trends in CVD risk factors and healthcare utilization differed between a cohort of New Ulm residents age 40-79 and matched controls selected from a similar community, using EHR data from baseline (2008-2009) through three follow up time periods (2010-2011, 2012-2013, 2014-2015). Matching, using covariate balance sparse technique, yielded a sample of 4077 New Ulm residents and 4077 controls. We used mixed effects longitudinal models to examine trends over time between the two groups. Blood pressure, total cholesterol, low-density lipoprotein-cholesterol, and triglycerides showed better management in New Ulm over time compared to the controls. The proportion of residents in New Ulm with controlled blood pressure increased by 6.2 percentage points compared to an increase of 2 points in controls (p risk scores increased less in New Ulm (5.1) than the comparison community (5.9). The intervention and control community did not differ with regard to inpatient stays, smoking, or glucose. Findings suggest efficacy for the HONU project interventions for some outcomes. Copyright © 2017. Published by Elsevier Inc.

  20. Comparative analysis of distinct phenotypes in gambling disorder based on gambling preferences.

    Science.gov (United States)

    Moragas, Laura; Granero, Roser; Stinchfield, Randy; Fernández-Aranda, Fernando; Fröberg, Frida; Aymamí, Neus; Gómez-Peña, Mónica; Fagundo, Ana B; Islam, Mohammed A; Del Pino-Gutiérrez, Amparo; Agüera, Zaida; Savvidou, Lamprini G; Arcelus, Jon; Witcomb, Gemma L; Sauchelli, Sarah; Menchón, José M; Jiménez-Murcia, Susana

    2015-04-15

    Studies examining gambling preferences have identified the importance of the type of gambling practiced on distinct individual profiles. The objectives were to compare clinical, psychopathological and personality variables between two different groups of individuals with a gambling disorder (strategic and non-strategic gamblers) and to evaluate the statistical prediction capacity of these preferences with respect to the severity of the disorder. A total sample of 2010 treatment-seeking patients with a gambling disorder participated in this stand-alone study. All were recruited from a single Pathological Gambling Unit in Spain (1709 strategic and 301 non-strategic gamblers). The design of the study was cross-sectional and data were collected at the start of treatment. Data was analysed using logistic regression for binary outcomes and analysis of variance (ANOVA) for quantitative responses. There were significant differences in several socio-demographic and clinical variables, as well as in personality traits (novelty seeking and cooperativeness). Multiple regression analysis showed harm avoidance and self-directedness were the main predictors of gambling severity and psychopathology, while age at assessment and age of onset of gambling behaviour were predictive of gambling severity. Strategic gambling (as opposed to non-strategic) was significantly associated with clinical outcomes, but the effect size of the relationships was small. It is possible to identify distinct phenotypes depending on the preference of gambling. While these phenotypes differ in relation to the severity of the gambling disorder, psychopathology and personality traits, they can be useful from a clinical and therapeutic perspective in enabling risk factors to be identified and prevention programs targeting specific individual profiles to be developed.

  1. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Hansen, T.W.; Olsen, M.H.; Rasmussen, S.

    2008-01-01

    BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  2. Cardiovascular tissue engineering and regeneration based on adipose tissue-derived stem/stromal cells

    NARCIS (Netherlands)

    Parvizi, Mojtaba

    2016-01-01

    Currently, the pre-clinical field is rapidly progressing in search of new therapeutic modalities that replace or complement current medication to treat cardiovascular disease. Among these are the single or combined use of stem cells, biomaterials and instructive factors, which together form the

  3. Cardiovascular disease in patients with osteogenesis imperfecta - a nationwide, register-based cohort study

    DEFF Research Database (Denmark)

    Folkestad, Lars; Hald, Jannie Dahl; Gram, Jeppe

    2016-01-01

    BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI...

  4. Association between alcohol and cardiovascular disease : Mendelian randomisation analysis based on individual participant data

    NARCIS (Netherlands)

    Holmes, Michael V.; Dale, Caroline E.; Zuccolo, Luisa; Silverwood, Richard J.; Guo, Yiran; Ye, Zheng; Prieto-Merino, David; Dehghan, Abbas; Trompet, Stella; Wong, Andrew; Cavadino, Alana; Drogan, Dagmar; Padmanabhan, Sandosh; Li, Shanshan; Yesupriya, Ajay; Leusink, Maarten|info:eu-repo/dai/nl/357581164; Sundstrom, Johan; Hubacek, Jaroslav A.; Pikhart, Hynek; Swerdlow, Daniel I.; Panayiotou, Andrie G.; Borinskaya, Svetlana A.; Finan, Chris; Shah, Sonia; Kuchenbaecker, Karoline B.; Shah, Tina; Engmann, Jorgen; Folkersen, Lasse; Eriksson, Per; Ricceri, Fulvio; Melander, Olle; Sacerdote, Carlotta; Gamble, Dale M.; Rayaprolu, Sruti; Ross, Owen A.; McLachlan, Stela; Vikhireva, Olga; Sluijs, Ivonne; Scott, Robert A.; Adamkova, Vera; Flicker, Leon; Van Bockxmeer, Frank M.; Power, Christine; Marques-Vidal, Pedro; Meade, Tom; Marmot, Michael G.; Ferro, Jose M.; Paulos-Pinheiro, Sofia; Humphries, Steve E.; Talmud, Philippa J.; Leach, Irene Mateo; Verweij, Niek; Linneberg, Allan; Skaaby, Tea; Doevendans, Pieter A.; Cramer, Maarten J.; Van Der Harst, Pim; Klungel, Olaf H.|info:eu-repo/dai/nl/181447649; Dowling, Nicole F.; Dominiczak, Anna F.; Kumari, Meena; Nicolaides, Andrew N.; Weikert, Cornelia; Boeing, Heiner; Ebrahim, Shah; Gaunt, Tom R.; Price, Jackie F.; Lannfelt, Lars; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Malyutina, Sofia; Voevoda, Mikhail I.; Tamosiunas, Abdonas; Maitland-van Der Zee, Anke H.|info:eu-repo/dai/nl/255164688; Norman, Paul E.; Hankey, Graeme J.; Bergmann, Manuela M.; Hofman, Albert; Franco, Oscar H.; Cooper, Jackie; Palmen, Jutta; Spiering, Wilko; De Jong, Pim A.; Kuh, Diana; Hardy, Rebecca; Uitterlinden, Andre G.; Ikram, M. Arfan; Ford, Ian; Hyppönen, Elina; Almeida, Osvaldo P.; Wareham, Nicholas J.; Khaw, Kay Tee; Hamsten, Anders; Husemoen, Lise Lotte N; Tjønneland, Anne; Tolstrup, Janne S.; Rimm, Eric; Beulens, Joline W J; Verschuren, W. M Monique; Onland-Moret, N. Charlotte; Hofker, Marten H.; Wannamethee, S. Goya; Whincup, Peter H.; Morris, Richard; Vicente, Astrid M.; Watkins, Hugh; Farrall, Martin; Jukema, J. Wouter; Meschia, James; Cupples, L. Adrienne; Sharp, Stephen J.; Fornage, Myriam; Kooperberg, Charles; LaCroix, Andrea Z.; Dai, James Y.; Lanktree, Matthew B.; Siscovick, David S.; Jorgenson, Eric; Spring, Bonnie; Coresh, Josef; Li, Yun R.; Buxbaum, Sarah G.; Schreiner, Pamela J.; Ellison, R. Curtis; Tsai, Michael Y.; Patel, Sanjay R.; Redline, Susan; Johnson, Andrew D.; Hoogeveen, Ron C.; Hakonarson, Hakon; Rotter, Jerome I.; Boerwinkle, Eric; De Bakker, Paul I W; Kivimaki, Mika; Asselbergs, Folkert W.; Sattar, Naveed; Lawlor, Debbie A.; Whittaker, John; Smith, George Davey; Mukamal, Kenneth; Psaty, Bruce M.; Wilson, James G.; Lange, Leslie A.; Hamidovic, Ajna; Nordestgaard, Børge G.; Bobak, Martin; Leon, David A.; Langenberg, Claudia; Palmer, Tom M.; Reiner, Alex P.; Keating, Brendan J.; Dudbridge, Frank; Casas, Juan P.

    2014-01-01

    Objective: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design: Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants: 261 991 individuals of European

  5. Validation of an imaging based cardiovascular risk score in a Scottish population.

    Science.gov (United States)

    Kockelkoren, Remko; Jairam, Pushpa M; Murchison, John T; Debray, Thomas P A; Mirsadraee, Saeed; van der Graaf, Yolanda; Jong, Pim A de; van Beek, Edwin J R

    2018-01-01

    A radiological risk score that determines 5-year cardiovascular disease (CVD) risk using routine care CT and patient information readily available to radiologists was previously developed. External validation in a Scottish population was performed to assess the applicability and validity of the risk score in other populations. 2915 subjects aged ≥40 years who underwent routine clinical chest CT scanning for non-cardiovascular diagnostic indications were followed up until first diagnosis of, or death from, CVD. Using a case-cohort approach, all cases and a random sample of 20% of the participant's CT examinations were visually graded for cardiovascular calcifications and cardiac diameter was measured. The radiological risk score was determined using imaging findings, age, gender, and CT indication. Performance on 5-year CVD risk prediction was assessed. 384 events occurred in 2124 subjects during a mean follow-up of 4.25 years (0-6.4 years). The risk score demonstrated reasonable performance in the studied population. Calibration showed good agreement between actual and 5-year predicted risk of CVD. The c-statistic was 0.71 (95%CI:0.67-0.75). The radiological CVD risk score performed adequately in the Scottish population offering a potential novel strategy for identifying patients at high risk for developing cardiovascular disease using routine care CT data. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Quantification of scientific output in cardiovascular medicine: A perspective based on global data

    NARCIS (Netherlands)

    G.A. Rodriguez-Granillo (Gaston); A. Rodriguez (Alfredo Chapin); N. Bruining (Nico); J. Milei (José); J. Aoki (Jiro); K. Tsuchida (Keiichi); R. del Valle-Fernández (Raquel); C.A. Arampatzis (Chourmouzios); A.T.L. Ong (Andrew); P.A. Lemos Neto (Pedro); R. Ayala (Rosa); H.M. Garcia-Garcia (Hector); F. Saia (Francesco); M. Valgimigli (Marco); E.S. Regar (Eveline); E. McFadden (Eugene); G.G. Biondi-Zoccai (Giuseppe); E. Barbenza (Ezequiel); P. Schoenhagen (Paul); P.W.J.C. Serruys (Patrick)

    2013-01-01

    textabstractAims: We sought to explore whether global and regional scientific output in cardiovascular medicine is associated with economic variables and follows the same trend as medicine and as science overall. Methods and results: We registered the number of documents, number of citations,

  7. Moving towards patient-centered medicine for COPD management: multidimensional approaches versus phenotype-based medicine--a critical view.

    Science.gov (United States)

    Lopez-Campos, Jose Luis; Bustamante, Víctor; Muñoz, Xavier; Barreiro, Esther

    2014-09-01

    For decades, chronic obstructive pulmonary disease (COPD) has been considered a relentlessly progressive disease in which the deterioration of lung function is associated with an increase in symptoms, interrupted only by periods of exacerbation. However, this paradigm of COPD severity based on FEV1 has been challenged by currently available evidence. So far, three main approaches, though with contradictory aspects, have been proposed in order to address the complexity of COPD as well as to develop appropriate diagnostic, prognostic and therapeutic strategies for the disease: 1) the use of independent, clinically relevant variables, 2) the use of multidimensional indices, and 3) disease approaches based on clinical phenotypes. Multivariable systems seem superior to FEV1 in predicting prognosis and defining disease severity. However, selection of variables available from current literature must be confronted with issues of medical practice. Future evidence will be needed to reveal their effective relationship with disease long-term prognosis and to demonstrate the most adequate cutoff values to be used in clinical settings. Multidimensional scores provide a good prognostic instrument for the identification of patients with a particular degree of disease severity. Clinical phenotyping can help clinicians identify the patients who respond to specific pharmacological interventions; however, there is some controversy about the phenotypes to select and their long-term implications. Although these approaches are not perfect, they represent the first step towards patient-centered medicine for COPD. In the near-future, these different approaches should converge towards one new field to focus on the better management of COPD patients.

  8. A diet based on high-heat-treated foods promotes risk factors for diabetes mellitus and cardiovascular diseases.

    Science.gov (United States)

    Birlouez-Aragon, Inès; Saavedra, Giselle; Tessier, Frédéric J; Galinier, Anne; Ait-Ameur, Lamia; Lacoste, Florence; Niamba, Claude-Narcisse; Alt, Nadja; Somoza, Veronika; Lecerf, Jean-Michel

    2010-05-01

    The modern Western lifestyle is characterized by the consumption of high-heat-treated foods because of their characteristic taste and flavor. However, it has been shown that treating food at high temperatures can generate potentially harmful compounds that promote inflammation and cardiovascular disease in subjects with diabetes. The aim of this study was to determine whether high-heat-treated foods also pose a risk for healthy subjects. A randomized, crossover, diet-controlled intervention trial with 62 volunteers was designed to compare the potential metabolic effects of 2 diets, one that was based on mild steam cooking and another that was based on high-temperature cooking. These 2 diets differed mainly in their contents of Maillard reaction products (MRPs). MRPs were assessed in the diet and in subjects' feces, blood, and urine samples, with N(epsilon)-carboxymethyllysine as an indicator of MRPs. Biological indicators of glucose and lipid metabolism as well as oxidative stress were analyzed in subjects after 1 mo on each diet. In comparison with the steamed diet, 1 mo of consuming the high-heat-treated diet induced significantly lower insulin sensitivity and plasma concentrations of long-chain n-3 (omega-3) fatty acids and vitamins C and E [-17% (P markers associated with an enhanced risk of type 2 diabetes and cardiovascular diseases in healthy people. Replacing high-heat-treatment techniques by mild cooking techniques may help to positively modulate biomarkers associated with an increased risk of diabetes mellitus and cardiovascular diseases.

  9. Association between Coffee Consumption and Its Polyphenols with Cardiovascular Risk Factors: A Population-Based Study

    Directory of Open Access Journals (Sweden)

    Andreia Machado Miranda

    2017-03-01

    Full Text Available Epidemiological studies have examined the effect of coffee intake on cardiovascular disease, but the benefits and risks for the cardiovascular system remain controversial. Our objective was to evaluate the association between coffee consumption and its polyphenols on cardiovascular risk factors. Data came from the “Health Survey of São Paulo (ISA-Capital” among 557 individuals, in São Paulo, Brazil. Diet was assessed by two 24-h dietary recalls. Coffee consumption was categorized into <1, 1–3, and ≥3 cups/day. Polyphenol intake was calculated by matching food consumption data with the Phenol-Explorer database. Multiple logistic regression models were used to assess the associations between cardiovascular risk factors (blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL-c, high-density lipoprotein cholesterol (HDL-c, triglycerides, fasting glucose, and homocysteine and usual coffee intake. The odds were lower among individuals who drank 1–3 cups of coffee/day to elevated systolic blood pressure (SBP (Odds Ratio (OR = 0.45; 95% Confidence Interval (95% CI: 0.26, 0.78, elevated diastolic blood pressure (DBP (OR = 0.44; 95% CI: 0.20, 0.98, and hyperhomocysteinemia (OR = 0.32; 95% CI: 0.11, 0.93. Furthermore, significant inverse associations were also observed between moderate intake of coffee polyphenols and elevated SBP (OR = 0.46; 95% CI: 0.24, 0.87, elevated DBP (OR = 0.51; 95% CI: 0.26, 0.98, and hyperhomocysteinemia (OR = 0.29; 95% CI: 0.11, 0.78. In conclusion, coffee intake of 1–3 cups/day and its polyphenols were associated with lower odds of elevated SBP, DBP, and hyperhomocysteinemia. Thus, the moderate consumption of coffee, a polyphenol-rich beverage, could exert a protective effect against some cardiovascular risk factors.

  10. Proteomic-based detection of a protein cluster dysregulated during cardiovascular development identifies biomarkers of congenital heart defects.

    Directory of Open Access Journals (Sweden)

    Anjali K Nath

    Full Text Available Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy and congenital heart defects (CHDs. However, the molecular pathways that underlie these structural defects in humans remain largely unknown hindering the development of molecular-based diagnostic tools and novel therapies.Murine embryos were exposed to high glucose, a condition known to induce cardiovascular defects in both animal models and humans. We further employed a mass spectrometry-based proteomics approach to identify proteins differentially expressed in embryos with defects from those with normal cardiovascular development. The proteins detected by mass spectrometry (WNT16, ST14, Pcsk1, Jumonji, Morca2a, TRPC5, and others were validated by Western blotting and immunoflorescent staining of the yolk sac and heart. The proteins within the proteomic dataset clustered to adhesion/migration, differentiation, transport, and insulin signaling pathways. A functional role for several proteins (WNT16, ADAM15 and NOGO-A/B was demonstrated in an ex vivo model of heart development. Additionally, a successful application of a cluster of protein biomarkers (WNT16, ST14 and Pcsk1 as a prenatal screen for CHDs was confirmed in a study of human amniotic fluid (AF samples from women carrying normal fetuses and those with CHDs.The novel finding that WNT16, ST14 and Pcsk1 protein levels increase in fetuses with CHDs suggests that these proteins may play a role in the etiology of human CHDs. The information gained through this bed-side to bench translational approach contributes to a more complete understanding of the protein pathways dysregulated during cardiovascular development and provides novel avenues for diagnostic and therapeutic interventions, beneficial to fetuses at risk for CHDs.

  11. Statistical Validation of a Web-Based GIS Application and Its Applicability to Cardiovascular-Related Studies

    Directory of Open Access Journals (Sweden)

    Jae Eun Lee

    2015-12-01

    Full Text Available Purpose: There is abundant evidence that neighborhood characteristics are significantly linked to the health of the inhabitants of a given space within a given time frame. This study is to statistically validate a web-based GIS application designed to support cardiovascular-related research developed by the NIH funded Research Centers in Minority Institutions (RCMI Translational Research Network (RTRN Data Coordinating Center (DCC and discuss its applicability to cardiovascular studies. Methods: Geo-referencing, geocoding and geospatial analyses were conducted for 500 randomly selected home addresses in a U.S. southeastern Metropolitan area. The correlation coefficient, factor analysis and Cronbach’s alpha (α were estimated to quantify measures of the internal consistency, reliability and construct/criterion/discriminant validity of the cardiovascular-related geospatial variables (walk score, number of hospitals, fast food restaurants, parks and sidewalks. Results: Cronbach’s α for CVD GEOSPATIAL variables was 95.5%, implying successful internal consistency. Walk scores were significantly correlated with number of hospitals (r = 0.715; p < 0.0001, fast food restaurants (r = 0.729; p < 0.0001, parks (r = 0.773; p < 0.0001 and sidewalks (r = 0.648; p < 0.0001 within a mile from homes. It was also significantly associated with diversity index (r = 0.138, p = 0.0023, median household incomes (r = −0.181; p < 0.0001, and owner occupied rates (r = −0.440; p < 0.0001. However, its non-significant correlation was found with median age, vulnerability, unemployment rate, labor force, and population growth rate. Conclusion: Our data demonstrates that geospatial data generated by the web-based application were internally consistent and demonstrated satisfactory validity. Therefore, the GIS application may be useful to apply to cardiovascular-related studies aimed to investigate potential impact of geospatial factors on diseases and/or the long

  12. An automated, high-throughput plant phenotyping system using machine learning-based plant segmentation and image analysis.

    Science.gov (United States)

    Lee, Unseok; Chang, Sungyul; Putra, Gian Anantrio; Kim, Hyoungseok; Kim, Dong Hwan

    2018-01-01

    A high-throughput plant phenotyping system automatically observes and grows many plant samples. Many plant sample images are acquired by the system to determine the characteristics of the plants (populations). Stable image acquisition and processing is very important to accurately determine the characteristics. However, hardware for acquiring plant images rapidly and stably, while minimizing plant stress, is lacking. Moreover, most software cannot adequately handle large-scale plant imaging. To address these problems, we developed a new, automated, high-throughput plant phenotyping system using simple and robust hardware, and an automated plant-imaging-analysis pipeline consisting of machine-learning-based plant segmentation. Our hardware acquires images reliably and quickly and minimizes plant stress. Furthermore, the images are processed automatically. In particular, large-scale plant-image datasets can be segmented precisely using a classifier developed using a superpixel-based machine-learning algorithm (Random Forest), and variations in plant parameters (such as area) over time can be assessed using the segmented images. We performed comparative evaluations to identify an appropriate learning algorithm for our proposed system, and tested three robust learning algorithms. We developed not only an automatic analysis pipeline but also a convenient means of plant-growth analysis that provides a learning data interface and visualization of plant growth trends. Thus, our system allows end-users such as plant biologists to analyze plant growth via large-scale plant image data easily.

  13. Accumulated environmental risk determining age at schizophrenia onset: a deep phenotyping-based study.

    Science.gov (United States)

    Stepniak, Beata; Papiol, Sergi; Hammer, Christian; Ramin, Anna; Everts, Sarah; Hennig, Lena; Begemann, Martin; Ehrenreich, Hannelore

    2014-11-01

    Schizophrenia is caused by a combination of genetic and environmental factors, as first evidenced by twin studies. Extensive efforts have been made to identify the genetic roots of schizophrenia, including large genome-wide association studies, but these yielded very small effect sizes for individual markers. In this study, we aimed to assess the relative contribution of genome-wide association study-derived genetic versus environmental risk factors to crucial determinants of schizophrenia severity: disease onset, disease severity, and socioeconomic measures. In this parallel analysis, we studied 750 male patients from the Göttingen Research Association for Schizophrenia (GRAS) dataset (Germany) with schizophrenia for whom both genome-wide coverage of single-nucleotide polymorphisms and deep clinical phenotyping data were available. Specifically, we investigated the potential effect of schizophrenia risk alleles as identified in the most recent large genome-wide association study versus the effects of environmental hazards (ie, perinatal brain insults, cannabis use, neurotrauma, psychotrauma, urbanicity, and migration), alone and upon accumulation, on age at disease onset, age at prodrome, symptom expression, and socioeconomic parameters. In this study, we could show that frequent environmental factors become a major risk for early schizophrenia onset when accumulated (prodrome begins up to 9 years earlier; p=2·9×10(-10)). In particular, cannabis use-an avoidable environmental risk factor-is highly significantly associated with earlier age at prodrome (p=3·8×10(-20)). By contrast, polygenic genome-wide association study risk scores did not have any detectable effects on schizophrenia phenotypes. These findings should be translated to preventive measures to reduce environmental risk factors, since age at onset of schizophrenia is a crucial determinant of an affected individual's fate and the total socioeconomic cost of the illness. German Research Foundation

  14. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy

    Science.gov (United States)

    Lech, Wioletta; Figiel-Dabrowska, Anna; Drela, Katarzyna; Obtulowicz, Patrycja; Noszczyk, Bartlomiej Henryk; Buzanska, Leonora

    2016-01-01

    Mesenchymal stem cells (MSC) exhibit enormous heterogeneity which can modify their regenerative properties and therefore influence therapeutic effectiveness as well as safety of these cells transplantation. In addition the high phenotypic plasticity of MSC population makes it enormously sensitive to any changes in environmental properties including fluctuation in oxygen concentration. We have shown here that lowering oxygen level far below air atmosphere has a beneficial impact on various parameters characteristic for umbilical cord Wharton Jelly- (WJ-) MSC and adipose tissue- (AD-) derived MSC cultures. This includes their cellular composition, rate of proliferation, and maintenance of stemness properties together with commitment to cell differentiation toward mesodermal and neural lineages. In addition, the culture genomic stability increased significantly during long-term cell passaging and eventually protected cells against spontaneous transformation. Also by comparing of two routinely used methods of MSCs isolation (mechanical versus enzymatic) we have found substantial divergence arising between cell culture properties increasing along the time of cultivation in vitro. Thus, in this paper we highlight the urgent necessity to develop the more sensitive and selective methods for prediction and control cells fate and functioning during the time of growth in vitro. PMID:27651796

  15. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy.

    Science.gov (United States)

    Lech, Wioletta; Figiel-Dabrowska, Anna; Sarnowska, Anna; Drela, Katarzyna; Obtulowicz, Patrycja; Noszczyk, Bartlomiej Henryk; Buzanska, Leonora; Domanska-Janik, Krystyna

    2016-01-01

    Mesenchymal stem cells (MSC) exhibit enormous heterogeneity which can modify their regenerative properties and therefore influence therapeutic effectiveness as well as safety of these cells transplantation. In addition the high phenotypic plasticity of MSC population makes it enormously sensitive to any changes in environmental properties including fluctuation in oxygen concentration. We have shown here that lowering oxygen level far below air atmosphere has a beneficial impact on various parameters characteristic for umbilical cord Wharton Jelly- (WJ-) MSC and adipose tissue- (AD-) derived MSC cultures. This includes their cellular composition, rate of proliferation, and maintenance of stemness properties together with commitment to cell differentiation toward mesodermal and neural lineages. In addition, the culture genomic stability increased significantly during long-term cell passaging and eventually protected cells against spontaneous transformation. Also by comparing of two routinely used methods of MSCs isolation (mechanical versus enzymatic) we have found substantial divergence arising between cell culture properties increasing along the time of cultivation in vitro. Thus, in this paper we highlight the urgent necessity to develop the more sensitive and selective methods for prediction and control cells fate and functioning during the time of growth in vitro.

  16. A population-based screening study for cardiovascular diseases and diabetes in Danish postmenopausal women

    DEFF Research Database (Denmark)

    Dahl, Marie; Frost, Lars; Søgaard, Rikke

    2018-01-01

    of this study was to investigate the prevalence of CVD and DM as well as the acceptability toward screening and preventive actions. Methods: An observational study was performed among all women born in 1936, 1941, 1946 and 1951 living in Viborg Municipality, Denmark, from October 2011. In total, 1984 were...... and/or CP. Participants with AAA ≥ 50 mm were referred to specialists in vascular surgery. Women with AF or potential familial hypercholesterolaemia (FH) were referred to cardiology work-up. Results: Among those invited, 1474 (74.3%) attended screening, but the attendees’ share decreased......Abstract Background: Reducing women’s cardiovascular risk and the economic costs associated with cardiovascular diseases (CVD) and diabetes (DM) continues to be a challenge. Whether a multifaceted CVD screening programme is beneficial as a preventive strategy in women remains uncertain. The aim...

  17. Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system.

    Science.gov (United States)

    Gómez-Pérez, Francisco J; Rojas, Rosalba; Villalpando, Salvador; Barquera, Simón; Rull, Juan; Aguilar-Salinas, Carlos A

    2010-01-01

    To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. A cardiovascular risk equivalent was found in 13.8% and >or=2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >or=2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%).

  18. Role of Garlic Usage in Cardiovascular Disease Prevention: An Evidence-Based Approach

    Science.gov (United States)

    Ashfaq, Tabinda

    2013-01-01

    Introduction. Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. This study was done to find out the role of garlic usage in cardiovascular disease prevention. Methodology. Major databases including Google, PubMed, MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing role of garlic usage in cardiovascular disease prevention and the possible mechanisms responsible for such therapeutic actions were assessed. Results. Various clinical trials and meta-analyses conducted have shown positive impact of garlic in cardiovascular-disease prevention especially its effects on lipid levels; however, some contradictory results are also reported. Similarly, its effects on hypertension control, and platelet are also mild with limited data availability. The possible reason for these inconsistent results is the difference in preparations with diverse composition, variations in sulphur content present in different garlic preparations used, and methodological variations in subject recruitment, duration of study, dietary control and so forth. Conclusion. Garlic can be used as an adjuvant with lipid-lowering drugs for control of lipids, however, its role as a main therapeutic agent cannot be recommended and it is suggested that more meta-analyses using standardized preparations with a close watch on methodological shortfalls should be conducted to prove its role. PMID:23690831

  19. Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

    Science.gov (United States)

    2014-01-01

    Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; screening-detected cancers, extreme breast density

  20. UAV-Based Thermal Imaging for High-Throughput Field Phenotyping of Black Poplar Response to Drought.

    Science.gov (United States)

    Ludovisi, Riccardo; Tauro, Flavia; Salvati, Riccardo; Khoury, Sacha; Mugnozza Scarascia, Giuseppe; Harfouche, Antoine

    2017-01-01

    Poplars are fast-growing, high-yielding forest tree species, whose cultivation as second-generation biofuel crops is of increasing interest and can efficiently meet emission reduction goals. Yet, breeding elite poplar trees for drought resistance remains a major challenge. Worldwide breeding programs are largely focused on intra/interspecific hybridization, whereby Populus nigra L. is a fundamental parental pool. While high-throughput genotyping has resulted in unprecedented capabilities to rapidly decode complex genetic architecture of plant stress resistance, linking genomics to phenomics is hindered by technically challenging phenotyping. Relying on unmanned aerial vehicle (UAV)-based remote sensing and imaging techniques, high-throughput field phenotyping (HTFP) aims at enabling highly precise and efficient, non-destructive screening of genotype performance in large populations. To efficiently support forest-tree breeding programs, ground-truthing observations should be complemented with standardized HTFP. In this study, we develop a high-resolution (leaf level) HTFP approach to investigate the response to drought of a full-sib F 2 partially inbred population (termed here 'POP6'), whose F 1 was obtained from an intraspecific P. nigra controlled cross between genotypes with highly divergent phenotypes. We assessed the effects of two water treatments (well-watered and moderate drought) on a population of 4603 trees (503 genotypes) hosted in two adjacent experimental plots (1.67 ha) by conducting low-elevation (25 m) flights with an aerial drone and capturing 7836 thermal infrared (TIR) images. TIR images were undistorted, georeferenced, and orthorectified to obtain radiometric mosaics. Canopy temperature ( T c ) was extracted using two independent semi-automated segmentation techniques, eCognition- and Matlab-based, to avoid the mixed-pixel problem. Overall, results showed that the UAV platform-based thermal imaging enables to effectively assess genotype

  1. UAV-Based Thermal Imaging for High-Throughput Field Phenotyping of Black Poplar Response to Drought

    Directory of Open Access Journals (Sweden)

    Riccardo Ludovisi

    2017-09-01

    Full Text Available Poplars are fast-growing, high-yielding forest tree species, whose cultivation as second-generation biofuel crops is of increasing interest and can efficiently meet emission reduction goals. Yet, breeding elite poplar trees for drought resistance remains a major challenge. Worldwide breeding programs are largely focused on intra/interspecific hybridization, whereby Populus nigra L. is a fundamental parental pool. While high-throughput genotyping has resulted in unprecedented capabilities to rapidly decode complex genetic architecture of plant stress resistance, linking genomics to phenomics is hindered by technically challenging phenotyping. Relying on unmanned aerial vehicle (UAV-based remote sensing and imaging techniques, high-throughput field phenotyping (HTFP aims at enabling highly precise and efficient, non-destructive screening of genotype performance in large populations. To efficiently support forest-tree breeding programs, ground-truthing observations should be complemented with standardized HTFP. In this study, we develop a high-resolution (leaf level HTFP approach to investigate the response to drought of a full-sib F2 partially inbred population (termed here ‘POP6’, whose F1 was obtained from an intraspecific P. nigra controlled cross between genotypes with highly divergent phenotypes. We assessed the effects of two water treatments (well-watered and moderate drought on a population of 4603 trees (503 genotypes hosted in two adjacent experimental plots (1.67 ha by conducting low-elevation (25 m flights with an aerial drone and capturing 7836 thermal infrared (TIR images. TIR images were undistorted, georeferenced, and orthorectified to obtain radiometric mosaics. Canopy temperature (Tc was extracted using two independent semi-automated segmentation techniques, eCognition- and Matlab-based, to avoid the mixed-pixel problem. Overall, results showed that the UAV platform-based thermal imaging enables to effectively assess genotype

  2. Discrimination of plant root zone water status in greenhouse production based on phenotyping and machine learning techniques.

    Science.gov (United States)

    Guo, Doudou; Juan, Jiaxiang; Chang, Liying; Zhang, Jingjin; Huang, Danfeng

    2017-08-15

    Plant-based sensing on water stress can provide sensitive and direct reference for precision irrigation system in greenhouse. However, plant information acquisition, interpretation, and systematical application remain insufficient. This study developed a discrimination method for plant root zone water status in greenhouse by integrating phenotyping and machine learning techniques. Pakchoi plants were used and treated by three root zone moisture levels, 40%, 60%, and 80% relative water content. Three classification models, Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) were developed and validated in different scenarios with overall accuracy over 90% for all. SVM model had the highest value, but it required the longest training time. All models had accuracy over 85% in all scenarios, and more stable performance was observed in RF model. Simplified SVM model developed by the top five most contributing traits had the largest accuracy reduction as 29.5%, while simplified RF and NN model still maintained approximately 80%. For real case application, factors such as operation cost, precision requirement, and system reaction time should be synthetically considered in model selection. Our work shows it is promising to discriminate plant root zone water status by implementing phenotyping and machine learning techniques for precision irrigation management.

  3. Cardiovascular Effects of Long-Term Exposure to Air Pollution: A Population-Based Study With 900 845 Person-Years of Follow-up.

    Science.gov (United States)

    Kim, Hyeanji; Kim, Joonghee; Kim, Sunhwa; Kang, Si-Hyuck; Kim, Hee-Jun; Kim, Ho; Heo, Jongbae; Yi, Seung-Muk; Kim, Kyuseok; Youn, Tae-Jin; Chae, In-Ho

    2017-11-08

    Studies have shown that long-term exposure to air pollution such as fine particulate matter (≤2.5 μm in aerodynamic diameter [PM 2.5 ]) increases the risk of all-cause and cardiovascular mortality. To date, however, there are limited data on the impact of air pollution on specific cardiovascular diseases. This study aimed to evaluate cardiovascular effects of long-term exposure to air pollution among residents of Seoul, Korea. Healthy participants with no previous history of cardiovascular disease were evaluated between 2007 and 2013. Exposure to air pollutants was estimated by linking the location of outdoor monitors to the ZIP code of each participant's residence. Crude and adjusted analyses were performed using Cox regression models to evaluate the risk for composite cardiovascular events including cardiovascular mortality, acute myocardial infarction, congestive heart failure, and stroke. A total of 136 094 participants were followed for a median of 7.0 years (900 845 person-years). The risk of major cardiovascular events increased with higher mean concentrations of PM 2.5 in a linear relationship, with a hazard ratio of 1.36 (95% confidence interval, 1.29-1.43) per 1 μg/m 3 PM 2.5 . Other pollutants including PM 2.5-10 of CO, SO 2 , and NO 2 , but not O 3 , were significantly associated with increased risk of cardiovascular events. The burden from air pollution was comparable to that from hypertension and diabetes mellitus. This large-scale population-based study demonstrated that long-term exposure to air pollution including PM 2.5 increases the risk of major cardiovascular disease and mortality. Air pollution should be considered an important modifiable environmental cardiovascular risk factor. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. Evolution of the rate of biological aging using a phenotype based computational model.

    Science.gov (United States)

    Kittas, Aristotelis

    2010-10-07

    In this work I introduce a simple model to study how natural selection acts upon aging, which focuses on the viability of each individual. It is able to reproduce the Gompertz law of mortality and can make predictions about the relation between the level of mutation rates (beneficial/deleterious/neutral), age at reproductive maturity and the degree of biological aging. With no mutations, a population with low age at reproductive maturity R stabilizes at higher density values, while with mutations it reaches its maximum density, because even for large pre-reproductive periods each individual evolves to survive to maturity. Species with very short pre-reproductive periods can only tolerate a small number of detrimental mutations. The probabilities of detrimental (P(d)) or beneficial (P(b)) mutations are demonstrated to greatly affect the process. High absolute values produce peaks in the viability of the population over time. Mutations combined with low selection pressure move the system towards weaker phenotypes. For low values in the ratio P(d)/P(b), the speed at which aging occurs is almost independent of R, while higher values favor significantly species with high R. The value of R is critical to whether the population survives or dies out. The aging rate is controlled by P(d) and P(b) and the amount of the viability of each individual is modified, with neutral mutations allowing the system more "room" to evolve. The process of aging in this simple model is revealed to be fairly complex, yielding a rich variety of results. 2010 Elsevier Ltd. All rights reserved.

  5. Quantitative mouse brain phenotyping based on single and multispectral MR protocols

    Science.gov (United States)

    Badea, Alexandra; Gewalt, Sally; Avants, Brian B.; Cook, James J.; Johnson, G. Allan

    2013-01-01

    Sophisticated image analysis methods have been developed for the human brain, but such tools still need to be adapted and optimized for quantitative small animal imaging. We propose a framework for quantitative anatomical phenotyping in mouse models of neurological and psychiatric conditions. The framework encompasses an atlas space, image acquisition protocols, and software tools to register images into this space. We show that a suite of segmentation tools (Avants, Epstein et al., 2008) designed for human neuroimaging can be incorporated into a pipeline for segmenting mouse brain images acquired with multispectral magnetic resonance imaging (MR) protocols. We present a flexible approach for segmenting such hyperimages, optimizing registration, and identifying optimal combinations of image channels for particular structures. Brain imaging with T1, T2* and T2 contrasts yielded accuracy in the range of 83% for hippocampus and caudate putamen (Hc and CPu), but only 54% in white matter tracts, and 44% for the ventricles. The addition of diffusion tensor parameter images improved accuracy for large gray matter structures (by >5%), white matter (10%), and ventricles (15%). The use of Markov random field segmentation further improved overall accuracy in the C57BL/6 strain by 6%; so Dice coefficients for Hc and CPu reached 93%, for white matter 79%, for ventricles 68%, and for substantia nigra 80%. We demonstrate the segmentation pipeline for the widely used C57BL/6 strain, and two test strains (BXD29, APP/TTA). This approach appears promising for characterizing temporal changes in mouse models of human neurological and psychiatric conditions, and may provide anatomical constraints for other preclinical imaging, e.g. fMRI and molecular imaging. This is the first demonstration that multiple MR imaging modalities combined with multivariate segmentation methods lead to significant improvements in anatomical segmentation in the mouse brain. PMID:22836174

  6. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    Science.gov (United States)

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  7. 74. Cardiovascular risk assessment for Saudi university employees and their families: Developing a framework for provision of an evidence-based cardiovascular disease preventative programme

    Directory of Open Access Journals (Sweden)

    R. Alzeidan

    2016-07-01

    Full Text Available In the Kingdom of Saudi Arabia (KSA, cardiovascular diseases (CVDs are the primary cause of death among adults, representing 46% of total mortality in 2014. This study’s objectives were to assess the prevalence of cardiovascular risk factors (CVRFs, and calculate the cardiovascular risk (CVR among King Saud University employees and their families. Moreover, it aimed at assessing the possible effects of living in KSA on the heart health of expatriate employees and their families. A cross-sectional study was conducted on 4500 university employees and their families aged ⩾18 years old, using the World Health Organization STEPwise approach to surveillance of CVRFs. CVR was then calculated for participants using the Framingham Coronary Heart Risk Score calculator. The mean age of participants was 39.3 ± 13.4 years. The prevalence of CVRFs was as follows: low fruit/vegetable consumption of 10% risk to develop CVD within the following 10-years. Furthermore, this study showed that expatriates had significant negative effects on behavioural risk factors after residing in KSA, namely: high rate of physical inactivity, high consumption of fast food, low consumption of fruit and vegetable. However, there was no effect on the pattern of tobacco use. The prevalence of CVRFs is substantially high among the study population. To combat the future expected burden of CVDs, a proposed prevention programme for employees’ cardiovascular wellness is designed and recommended to be implemented and institutionalized within the university.

  8. 26. Cardiovascular risk assessment for Saudi university employees and their families: developing a framework for provision of an evidence-based cardiovascular disease preventative programme.

    Directory of Open Access Journals (Sweden)

    R. Alzeidan

    2016-07-01

    Full Text Available In the Kingdom of Saudi Arabia (KSA, cardiovascular diseases (CVDs are the primary cause of death among adults, representing 46% of total mortality in 2014. This study’s objectives were to assess the prevalence of cardiovascular risk factors (CVRFs, and calculate the cardiovascular risk (CVR among King Saud University employees and their families. Moreover, it aimed at assessing the possible effects of living in KSA on the heart health of expatriate employees and their families.A cross-sectional study was conducted on 4500 university employees and their families aged ⩾18 years old, using the World Health Organization STEPwise approach to surveillance of CVRFs. CVR was then calculated for participants using the Framingham Coronary Heart Risk Score calculator. The mean age of participants was 39.3±13.4 years. The prevalence of CVRFs was as follows: low fruit/vegetable consumption of 10% risk to develop CVD within the following 10-years. Furthermore, this study showed that expatriates had significant negative effects on behavioural risk factors after residing in KSA, namely: high rate of physical inactivity, high consumption of fast food, low consumption of fruit and vegetable. However, there was no effect on the pattern of tobacco use. The prevalence of CVRFs is substantially high among the study population. To combat the future expected burden of CVDs, a proposed prevention programme for employees’ cardiovascular wellness is designed and recommended to be implemented and institutionalized within the university.

  9. Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis

    DEFF Research Database (Denmark)

    Wu, Jashin J; Strober, Bruce E; Hansen, Peter R

    2016-01-01

    BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV even...

  10. Genotype, phenotype and in silico pathogenicity analysis of HEXB mutations: Panel based sequencing for differential diagnosis of gangliosidosis.

    Science.gov (United States)

    Mahdieh, Nejat; Mikaeeli, Sahar; Tavasoli, Ali Reza; Rezaei, Zahra; Maleki, Majid; Rabbani, Bahareh

    2018-04-01

    Gangliosidosis is an inherited metabolic disorder causing neurodegeneration and motor regression. Preventive diagnosis is the first choice for the affected families due to lack of straightforward therapy. Genetic studies could confirm the diagnosis and help families for carrier screening and prenatal diagnosis. An update of HEXB gene variants concerning genotype, phenotype and in silico analysis are presented. Panel based next generation sequencing and direct sequencing of four cases were performed to confirm the clinical diagnosis and for reproductive planning. Bioinformatic analyses of the HEXB mutation database were also performed. Direct sequencing of HEXA and HEXB genes showed recurrent homozygous variants at c.509G>A (p.Arg170Gln) and c.850C>T (p.Arg284Ter), respectively. A novel variant at c.416T>A (p.Leu139Gln) was identified in the GLB1 gene. Panel based next generation sequencing was performed for an undiagnosed patient which showed a novel mutation at c.1602C>A (p.Cys534Ter) of HEXB gene. Bioinformatic analysis of the HEXB mutation database showed 97% consistency of in silico genotype analysis with the phenotype. Bioinformatic analysis of the novel variants predicted to be disease causing. In silico structural and functional analysis of the novel variants showed structural effect of HEXB and functional effect of GLB1 variants which would provide fast analysis of novel variants. Panel based studies could be performed for overlapping symptomatic patients. Consequently, genetic testing would help affected families for patients' management, carrier detection, and family planning's. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Engaging Community Leaders in the Development of a Cardiovascular Health Behavior Survey Using Focus Group–Based Cognitive Interviewing

    Directory of Open Access Journals (Sweden)

    Gwenyth R Wallen

    2017-04-01

    Full Text Available Establishing the validity of health behavior surveys used in community-based participatory research (CBPR in diverse populations is often overlooked. A novel, group-based cognitive interviewing method was used to obtain qualitative data for tailoring a survey instrument designed to identify barriers to improved cardiovascular health in at-risk populations in Washington, DC. A focus group–based cognitive interview was conducted to assess item comprehension, recall, and interpretation and to establish the initial content validity of the survey. Thematic analysis of verbatim transcripts yielded 5 main themes for which participants (n = 8 suggested survey modifications, including survey item improvements, suggestions for additional items, community-specific issues, changes in the skip logic of the survey items, and the identification of typographical errors. Population-specific modifications were made, including the development of more culturally appropriate questions relevant to the community. Group-based cognitive interviewing provided an efficient and effective method for piloting a cardiovascular health survey instrument using CBPR.

  12. Impact of the Japanese Diagnosis Procedure Combination-based Payment System on cardiovascular medicine-related costs.

    Science.gov (United States)

    Yasunaga, Hideo; Ide, Hiroo; Imamura, Tomoaki; Ohe, Kazuhiko

    2005-09-01

    In 2003, a lump-sum payment system based on Diagnosis Procedure Combinations (DPC) was introduced to 82 specific function hospitals in Japan. While the US DRG/PPS system is a "per case payment" system, the DPC based payment system adopts a "per day payment." It is generally believed that the Japanese system provides as much of an incentive as the DRG/PPS system to shorten the average length of stay (LOS). We performed an empirical analysis of the effect of LOS shortening on hospital revenue and expenditure under the DPC-based payment system, particularly in cardiovascular diseases. We also point out fundamentally controversial aspects of the current system. A total 109 cases were selected from patients hospitalized at the University of Tokyo Hospital from May to July, 2003 and classified into one of three categories: (1) cardiac catheter interventions, (2) cardiac catheter examinations, and (3) other conservative treatments. We analyzed the changes in profit per day in cases of a reduction in average LOS and an increase in the number of cases. In category (1) profit increased significantly in conjunction with reduced LOS. In category (2) profit increased only minimally. In category (3), profit increased rarely and sometimes decreased. In cases of conservative treatment, profits sometimes decreased because an increase in material costs exceeded the increase in revenue. It therefore became clear that the DPC-based payment system does not decisively provide an economic incentive to reduce LOS in cardiovascular medicine.

  13. Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

    Directory of Open Access Journals (Sweden)

    Straand Jørund

    2011-03-01

    Full Text Available Abstract Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK, 4.4% (SCORE and 14.5% (Framingham had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females.

  14. Phenotypes of sleep-disordered breathing symptoms to two years of age based on age of onset and duration of symptoms.

    Science.gov (United States)

    Kamal, Muna; Tamana, Sukhpreet K; Smithson, Lisa; Ding, Linda; Lau, Amanda; Chikuma, Joyce; Mariasine, Jennifer; Lefebvre, Diana L; Subbarao, Padmaja; Becker, Allan B; Turvey, Stuart E; Sears, Malcolm R; Pei, Jacqueline; Mandhane, Piush J

    2018-05-03

    Childhood sleep-disordered breathing (SDB) symptoms may comprise multiple phenotypes depending on craniofacial anatomy, tonsil and adenoid growth, body habitus, and rhinitis symptoms. The primary objective of this study is to identify and characterize the different SDB phenotypes to two years of age. Data from 770 infants in the Edmonton sub-cohort of the Canadian Healthy Infant Longitudinal Study (CHILD) were analyzed to identify SDB phenotypes based on age of onset and duration of symptoms. Parents completed the 22-item sleep-related breathing disorder (SRBD) scale. Children with a SRBD ratio greater than 0.33 were considered positive for SDB at each quarterly assessment between three months and two years. The STATA Proc trajectory extension identified SDB phenotypes based on their age of onset and duration of symptoms and attributed the percentage chance of a participant being assigned to each phenotype. Multivariate linear regression identified factors associated with increased risk of being assigned to each SDB phenotype. Trajectory analysis identified four phenotypes: no SDB (65.7%), early-onset SDB (15.7%) with peak symptoms at nine months, late-onset SDB (14.2%) with peak symptoms at 18 months, and persistent SDB (5.3%) with symptoms from 3 to 24 months. Rhinitis was associated with all three SDB symptom trajectories (p sleep apnea syndrome (OSAS) was associated with persistent (p = 0.01) and late SDB (p < 0.001). Atopy (positive skin prick test at one year) was associated with persistent SDB (p = 0.04). Infants born prior to 36.5 weeks gestational age were more likely to present with late SDB (p = 0.03). Childhood SDB symptoms, rather than being a homogenous disorder, may comprise multiple overlapping phenotypes each with unique risk factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Micro-computed tomography-based phenotypic approaches in embryology: procedural artifacts on assessments of embryonic craniofacial growth and development

    Directory of Open Access Journals (Sweden)

    Logan C Cairine

    2010-02-01

    Full Text Available Abstract Background Growing demand for three dimensional (3D digital images of embryos for purposes of phenotypic assessment drives implementation of new histological and imaging techniques. Among these micro-computed tomography (μCT has recently been utilized as an effective and practical method for generating images at resolutions permitting 3D quantitative analysis of gross morphological attributes of developing tissues and organs in embryonic mice. However, histological processing in preparation for μCT scanning induces changes in organ size and shape. Establishing normative expectations for experimentally induced changes in size and shape will be an important feature of 3D μCT-based phenotypic assessments, especially if quantifying differences in the values of those parameters between comparison sets of developing embryos is a primary aim. Toward that end, we assessed the nature and degree of morphological artifacts attending μCT scanning following use of common fixatives, using a two dimensional (2D landmark geometric morphometric approach to track the accumulation of distortions affecting the embryonic head from the native, uterine state through to fixation and subsequent scanning. Results Bouin's fixation reduced average centroid sizes of embryonic mouse crania by approximately 30% and substantially altered the morphometric shape, as measured by the shift in Procrustes distance, from the unfixed state, after the data were normalized for naturally occurring shape variation. Subsequent μCT scanning produced negligible changes in size but did appear to reduce or even reverse fixation-induced random shape changes. Mixtures of paraformaldehyde + glutaraldehyde reduced average centroid sizes by 2-3%. Changes in craniofacial shape progressively increased post-fixation. Conclusions The degree to which artifacts are introduced in the generation of random craniofacial shape variation relates to the degree of specimen dehydration during the

  16. Micro-computed tomography-based phenotypic approaches in embryology: procedural artifacts on assessments of embryonic craniofacial growth and development.

    Science.gov (United States)

    Schmidt, Eric J; Parsons, Trish E; Jamniczky, Heather A; Gitelman, Julian; Trpkov, Cvett; Boughner, Julia C; Logan, C Cairine; Sensen, Christoph W; Hallgrímsson, Benedikt

    2010-02-17

    Growing demand for three dimensional (3D) digital images of embryos for purposes of phenotypic assessment drives implementation of new histological and imaging techniques. Among these micro-computed tomography (microCT) has recently been utilized as an effective and practical method for generating images at resolutions permitting 3D quantitative analysis of gross morphological attributes of developing tissues and organs in embryonic mice. However, histological processing in preparation for microCT scanning induces changes in organ size and shape. Establishing normative expectations for experimentally induced changes in size and shape will be an important feature of 3D microCT-based phenotypic assessments, especially if quantifying differences in the values of those parameters between comparison sets of developing embryos is a primary aim. Toward that end, we assessed the nature and degree of morphological artifacts attending microCT scanning following use of common fixatives, using a two dimensional (2D) landmark geometric morphometric approach to track the accumulation of distortions affecting the embryonic head from the native, uterine state through to fixation and subsequent scanning. Bouin's fixation reduced average centroid sizes of embryonic mouse crania by approximately 30% and substantially altered the morphometric shape, as measured by the shift in Procrustes distance, from the unfixed state, after the data were normalized for naturally occurring shape variation. Subsequent microCT scanning produced negligible changes in size but did appear to reduce or even reverse fixation-induced random shape changes. Mixtures of paraformaldehyde + glutaraldehyde reduced average centroid sizes by 2-3%. Changes in craniofacial shape progressively increased post-fixation. The degree to which artifacts are introduced in the generation of random craniofacial shape variation relates to the degree of specimen dehydration during the initial fixation. Fixation methods that

  17. Survey of Network-Based Approaches to Research of Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Anida Sarajlić

    2014-01-01

    Full Text Available Cardiovascular diseases (CVDs are the leading health problem worldwide. Investigating causes and mechanisms of CVDs calls for an integrative approach that would take into account its complex etiology. Biological networks generated from available data on biomolecular interactions are an excellent platform for understanding interconnectedness of all processes within a living cell, including processes that underlie diseases. Consequently, topology of biological networks has successfully been used for identifying genes, pathways, and modules that govern molecular actions underlying various complex diseases. Here, we review approaches that explore and use relationships between topological properties of biological networks and mechanisms underlying CVDs.

  18. (S)Partners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students

    OpenAIRE

    Carlson, Joseph J; Eisenmann, Joey C; Pfeiffer, Karin A; Jager, Kathleen B; Sehnert, Scott T; Yee, Kimbo E; Klavinski, Rita A; Feltz, Deborah L

    2008-01-01

    Abstract Background The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD) through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA). In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-discipl...

  19. MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system.

    Science.gov (United States)

    Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe; Lee, Jane; Thompson, Marjorie H; Monstad-Rios, Adrian T; Watson, Claire J; McMenamin, Sarah K; Willaert, Andy; Parichy, David M; Coucke, Paul; Kwon, Ronald Y

    2017-09-08

    Phenomics, which ideally involves in-depth phenotyping at the whole-organism scale, may enhance our functional understanding of genetic variation. Here, we demonstrate methods to profile hundreds of phenotypic measures comprised of morphological and densitometric traits at a large number of sites within the axial skeleton of adult zebrafish. We show the potential for vertebral patterns to confer heightened sensitivity, with similar specificity, in discriminating mutant populations compared to analyzing individual vertebrae in isolation. We identify phenotypes associated with human brittle bone disease and thyroid stimulating hormone receptor hyperactivity. Finally, we develop allometric models and show their potential to aid in the discrimination of mutant phenotypes masked by alterations in growth. Our studies demonstrate virtues of deep phenotyping in a spatially distributed organ system. Analyzing phenotypic patterns may increase productivity in genetic screens, and facilitate the study of genetic variants associated with smaller effect sizes, such as those that underlie complex diseases.

  20. A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.

    Science.gov (United States)

    Kang, Tianyu; Ding, Wei; Zhang, Luoyan; Ziemek, Daniel; Zarringhalam, Kourosh

    2017-12-19

    Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

  1. Toward a Low-Cost System for High-Throughput Image-Based Phenotyping of Root System Architecture

    Science.gov (United States)

    Davis, T. W.; Schneider, D. J.; Cheng, H.; Shaw, N.; Kochian, L. V.; Shaff, J. E.

    2015-12-01

    Root system architecture is being studied more closely for improved nutrient acquisition, stress tolerance and carbon sequestration by relating the genetic material that corresponds to preferential physical features. This information can help direct plant breeders in addressing the growing concerns regarding the global demand on crops and fossil fuels. To help support this incentive comes a need to make high-throughput image-based phenotyping of plant roots, at the individual plant scale, simpler and more affordable. Our goal is to create an affordable and portable product for simple image collection, processing and management that will extend root phenotyping to institutions with limited funding (e.g., in developing countries). Thus, a new integrated system has been developed using the Raspberry Pi single-board computer. Similar to other 3D-based imaging platforms, the system utilizes a stationary camera to photograph a rotating crop root system (e.g., rice, maize or sorghum) that is suspended either in a gel or on a mesh (for hydroponics). In contrast, the new design takes advantage of powerful open-source hardware and software to reduce the system costs, simplify the imaging process, and manage the large datasets produced by the high-resolution photographs. A newly designed graphical user interface (GUI) unifies the system controls (e.g., adjusting camera and motor settings and orchestrating the motor motion with image capture), making it easier to accommodate a variety of experiments. During each imaging session, integral metadata necessary for reproducing experiment results are collected (e.g., plant type and age, growing conditions and treatments, camera settings) using hierarchical data format files. These metadata are searchable within the GUI and can be selected and extracted for further analysis. The GUI also supports an image previewer that performs limited image processing (e.g., thresholding and cropping). Root skeletonization, 3D reconstruction and

  2. An integrated approach to preventing cardiovascular disease: community-based approaches, health system initiatives, and public health policy.

    Science.gov (United States)

    Karwalajtys, Tina; Kaczorowski, Janusz

    2010-01-01

    Cardiovascular disease (CVD) is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD.

  3. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies.

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2011-09-01

    Full Text Available BACKGROUND: Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. METHODS AND FINDINGS: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study analyses, generating ratios of RRs (RRRs. Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies, the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59, and diclofenac, 1.40 (1.27, 1.55, and the lowest with ibuprofen, 1.18 (1.11, 1.25, and naproxen, 1.09 (1.02, 1.16. In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57, celecoxib, 1.26 (1.09, 1.47, and diclofenac, 1.22 (1.12, 1.33, and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88, etodolac, 1.55 (1.28, 1.87, and indomethacin, 1.30 (1.19, 1.41, had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49, and naproxen, RRR = 1.75 (1.16, 2.64; etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99. RR estimates were constant with different background risks for

  4. A Systematic Review of Cardiovascular Outcomes-Based Cost-Effectiveness Analyses of Lipid-Lowering Therapies.

    Science.gov (United States)

    Wei, Ching-Yun; Quek, Ruben G W; Villa, Guillermo; Gandra, Shravanthi R; Forbes, Carol A; Ryder, Steve; Armstrong, Nigel; Deshpande, Sohan; Duffy, Steven; Kleijnen, Jos; Lindgren, Peter

    2017-03-01

    Previous reviews have evaluated economic analyses of lipid-lowering therapies using lipid levels as surrogate markers for cardiovascular disease. However, drug approval and health technology assessment agencies have stressed that surrogates should only be used in the absence of clinical endpoints. The aim of this systematic review was to identify and summarise the methodologies, weaknesses and strengths of economic models based on atherosclerotic cardiovascular disease event rates. Cost-effectiveness evaluations of lipid-lowering therapies using cardiovascular event rates in adults with hyperlipidaemia were sought in Medline, Embase, Medline In-Process, PubMed and NHS EED and conference proceedings. Search results were independently screened, extracted and quality checked by two reviewers. Searches until February 2016 retrieved 3443 records, from which 26 studies (29 publications) were selected. Twenty-two studies evaluated secondary prevention (four also assessed primary prevention), two considered only primary prevention and two included mixed primary and secondary prevention populations. Most studies (18) based treatment-effect estimates on single trials, although more recent evaluations deployed meta-analyses (5/10 over the last 10 years). Markov models (14 studies) were most commonly used and only one study employed discrete event simulation. Models varied particularly in terms of health states and treatment-effect duration. No studies used a systematic review to obtain utilities. Most studies took a healthcare perspective (21/26) and sourced resource use from key trials instead of local data. Overall, reporting quality was suboptimal. This review reveals methodological changes over time, but reporting weaknesses remain, particularly with respect to transparency of model reporting.

  5. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Sex Differences in Cardiovascular Mortality in Diabetics and Nondiabetic Subjects: A Population-Based Study (Italy

    Directory of Open Access Journals (Sweden)

    Paola Ballotari

    2015-01-01

    Full Text Available The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20–84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60–1.78; CVD: IRR = 1.61; 95%CI 1.47–1.76; AMI: IRR = 1.59; 95%CI 1.27–1.99; renal causes: IRR = 1.71; 95%CI 1.22–2.38. The impact of diabetes is greater in females than males for all causes (P=0.0321 and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males.

  7. Can atrophic-erosive oral lichen planus promote cardiovascular diseases? A population-based study.

    Science.gov (United States)

    Conrotto, D; Barattero, R; Carbone, M; Gambino, A; Sciannameo, V; Ricceri, F; Conrotto, F; Broccoletti, R; Arduino, P-G

    2018-03-01

    Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic and erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs. Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event-acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis, was performed. A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odds ratio 5.83; 95% CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of Oral lichen planus OLP (odds ratio 4.23; 95% CI: 0.66-27.23). Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort is however warranted. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  8. Sex differences in cardiovascular mortality in diabetics and nondiabetic subjects: a population-based study (Italy).

    Science.gov (United States)

    Ballotari, Paola; Ranieri, Sofia Chiatamone; Luberto, Ferdinando; Caroli, Stefania; Greci, Marina; Giorgi Rossi, Paolo; Manicardi, Valeria

    2015-01-01

    The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20-84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60-1.78; CVD: IRR = 1.61; 95%CI 1.47-1.76; AMI: IRR = 1.59; 95%CI 1.27-1.99; renal causes: IRR = 1.71; 95%CI 1.22-2.38). The impact of diabetes is greater in females than males for all causes (P = 0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males.

  9. Cardiovascular Events in Cancer Patients Treated with Highly or Moderately Emetogenic Chemotherapy: Results from a Population-Based Study

    International Nuclear Information System (INIS)

    Vo, T. T.; Nelson, J. J.

    2012-01-01

    Studies on cardiovascular safety in cancer patients treated with highly or moderately emetogenic chemotherapy (HEC or MEC), who may have taken the antiemetic, aprepitant, have been limited to clinical trials and postmarketing spontaneous reports. Our study explored background rates of cardiovascular disease (CVD) events among HEC- or MEC-treated cancer patients in a population-based setting to contextualize events seen in a new drug development program and to determine at a high level whether rates differed by aprepitant usage. Medical and pharmacy claims data from the 2005-2007 IMPACT National Benchmark Database were classified into emetogenic chemotherapy categories and CVD outcomes. Among 5827 HEC/MEC-treated patients, frequencies were highest for hypertension (16-21%) and composites of venous (7-12%) and arterial thromboembolic events (4-7%). Aprepitant users generally did not experience higher frequencies of events compared to nonusers. Our study serves as a useful benchmark of background CVD event rates in a population-based setting of cancer patients.

  10. Regression trees for predicting mortality in patients with cardiovascular disease: What improvement is achieved by using ensemble-based methods?

    Science.gov (United States)

    Austin, Peter C; Lee, Douglas S; Steyerberg, Ewout W; Tu, Jack V

    2012-01-01

    In biomedical research, the logistic regression model is the most commonly used method for predicting the probability of a binary outcome. While many clinical researchers have expressed an enthusiasm for regression trees, this method may have limited accuracy for predicting health outcomes. We aimed to evaluate the improvement that is achieved by using ensemble-based methods, including bootstrap aggregation (bagging) of regression trees, random forests, and boosted regression trees. We analyzed 30-day mortality in two large cohorts of patients hospitalized with either acute myocardial infarction (N = 16,230) or congestive heart failure (N = 15,848) in two distinct eras (1999–2001 and 2004–2005). We found that both the in-sample and out-of-sample prediction of ensemble methods offered substantial improvement in predicting cardiovascular mortality compared to conventional regression trees. However, conventional logistic regression models that incorporated restricted cubic smoothing splines had even better performance. We conclude that ensemble methods from the data mining and machine learning literature increase the predictive performance of regression trees, but may not lead to clear advantages over conventional logistic regression models for predicting short-term mortality in population-based samples of subjects with cardiovascular disease. PMID:22777999

  11. Super-Resolution of Plant Disease Images for the Acceleration of Image-based Phenotyping and Vigor Diagnosis in Agriculture.

    Science.gov (United States)

    Yamamoto, Kyosuke; Togami, Takashi; Yamaguchi, Norio

    2017-11-06

    Unmanned aerial vehicles (UAVs or drones) are a very promising branch of technology, and they have been utilized in agriculture-in cooperation with image processing technologies-for phenotyping and vigor diagnosis. One of the problems in the utilization of UAVs for agricultural purposes is the limitation in flight time. It is necessary to fly at a high altitude to capture the maximum number of plants in the limited time available, but this reduces the spatial resolution of the captured images. In this study, we applied a super-resolution method to the low-resolution images of tomato diseases to recover detailed appearances, such as lesions on plant organs. We also conducted disease classification using high-resolution, low-resolution, and super-resolution images to evaluate the effectiveness of super-resolution methods in disease classification. Our results indicated that the super-resolution method outperformed conventional image scaling methods in spatial resolution enhancement of tomato disease images. The results of disease classification showed that the accuracy attained was also better by a large margin with super-resolution images than with low-resolution images. These results indicated that our approach not only recovered the information lost in low-resolution images, but also exerted a beneficial influence on further image analysis. The proposed approach will accelerate image-based phenotyping and vigor diagnosis in the field, because it not only saves time to capture images of a crop in a cultivation field but also secures the accuracy of these images for further analysis.

  12. Super-Resolution of Plant Disease Images for the Acceleration of Image-based Phenotyping and Vigor Diagnosis in Agriculture

    Directory of Open Access Journals (Sweden)

    Kyosuke Yamamoto

    2017-11-01

    Full Text Available Unmanned aerial vehicles (UAVs or drones are a very promising branch of technology, and they have been utilized in agriculture—in cooperation with image processing technologies—for phenotyping and vigor diagnosis. One of the problems in the utilization of UAVs for agricultural purposes is the limitation in flight time. It is necessary to fly at a high altitude to capture the maximum number of plants in the limited time available, but this reduces the spatial resolution of the captured images. In this study, we applied a super-resolution method to the low-resolution images of tomato diseases to recover detailed appearances, such as lesions on plant organs. We also conducted disease classification using high-resolution, low-resolution, and super-resolution images to evaluate the effectiveness of super-resolution methods in disease classification. Our results indicated that the super-resolution method outperformed conventional image scaling methods in spatial resolution enhancement of tomato disease images. The results of disease classification showed that the accuracy attained was also better by a large margin with super-resolution images than with low-resolution images. These results indicated that our approach not only recovered the information lost in low-resolution images, but also exerted a beneficial influence on further image analysis. The proposed approach will accelerate image-based phenotyping and vigor diagnosis in the field, because it not only saves time to capture images of a crop in a cultivation field but also secures the accuracy of these images for further analysis.

  13. Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Shimizu, Kenji; Wakui, Keiko; Kosho, Tomoki; Okamoto, Nobuhiko; Mizuno, Seiji; Itomi, Kazuya; Hattori, Shigeto; Nishio, Kimio; Samura, Osamu; Kobayashi, Yoshiyuki; Kako, Yuko; Arai, Takashi; Tsutomu, Oh-ishi; Kawame, Hiroshi; Narumi, Yoko; Ohashi, Hirofumi; Fukushima, Yoshimitsu

    2014-03-01

    Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the distal 4p chromosome, characterized by craniofacial features, growth impairment, intellectual disability, and seizures. Although genotype-phenotype correlation studies have previously been published, several important issues remain to be elucidated including seizure severity. We present detailed clinical and molecular-cytogenetic findings from a microarray and fluorescence in situ hybridization (FISH)-based genotype-phenotype analysis of 22 Japanese WHS patients, the first large non-Western series. 4p deletions were terminal in 20 patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42 Mb. The new Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and duplication of other chromosomal regions occurred in four. Complex mosaicism was identified in two cases: two different 4p terminal deletions; a simple 4p terminal deletion and an unbalanced translocation with the same 4p breakpoint. Seizures began in infancy in 33% (2/6) of cases with small (6 Mb). Status epilepticus occurred in 17% (1/6) with small deletions and in 87% (13/15) with larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were more prevalent in those with larger deletions. A new susceptible region for seizure occurrence is suggested between 0.76 and 1.3 Mb from 4 pter, encompassing CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The usefulness of bromide therapy for seizures and additional clinical features including hypercholesterolemia are also described. © 2013 Wiley Periodicals, Inc.

  14. No association of CpG island methylator phenotype and colorectal cancer survival: population-based study.

    Science.gov (United States)

    Jia, Min; Jansen, Lina; Walter, Viola; Tagscherer, Katrin; Roth, Wilfried; Herpel, Esther; Kloor, Matthias; Bläker, Hendrik; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael

    2016-11-22

    Previous studies have shown adverse effects of CpG island methylator phenotype (CIMP) on colorectal cancer (CRC) prognosis. However, sample sizes were often limited and only few studies were able to adjust for relevant molecular features associated with CIMP. The aim of this study was to investigate the impact of CIMP on CRC survival in a large population-based study with comprehensive adjustment. The CIMP status and other molecular tumour features were analysed in 1385 CRC patients diagnosed between 2003 and 2010. Detailed information were obtained from standardised personal interviews and medical records. During follow-up (median: 4.9 years), we assessed vital status, cause of death and therapy details. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of survival after CRC. The CIMP-H occurred more frequently in patients with older age, female gender, cancer in the proximal colon, BRAF mutation and microsatellite instability-high (MSI-H). However, CIMP status was not associated with CRC prognosis in CRC patients (HR=1.00; 95% CI=0.72-1.40 for overall survival; HR=0.96; 95% CI=0.65-1.41 for disease-specific survival) or in any of the subgroups. Although CIMP status was associated with the presence of MSI-H and BRAF mutation, the prognostic effects of MSI-H (HR=0.49; 95% CI=0.27-0.90) and BRAF mutation (HR=1.78; 95% CI=1.10-2.84) were independent of CIMP status. Similar benefit of chemotherapy was found for CRC outcomes in both the CIMP-low/negative group and the CIMP-high group. CpG island methylator phenotype was not associated with CRC prognosis after adjusting for other important clinical factors and associated mutations.

  15. Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts

    DEFF Research Database (Denmark)

    Garcia-Aymerich, J; Benet, M; Saeys, Y

    2015-01-01

    at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age...

  16. Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study.

    Science.gov (United States)

    Hermanns, M Iris; Grossmann, Vera; Spronk, Henri M H; Schulz, Andreas; Jünger, Claus; Laubert-Reh, Dagmar; Mazur, Johanna; Gori, Tommaso; Zeller, Tanja; Pfeiffer, Norbert; Beutel, Manfred; Blankenberg, Stefan; Münzel, Thomas; Lackner, Karl J; Ten Cate-Hoek, Arina J; Ten Cate, Hugo; Wild, Philipp S

    2015-01-01

    Elevated levels of c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma c and its cardiovascular determinants is available. c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. Females (126.6% (95% CI: 125.2/128)) showed higher c levels than males (121.2% (119.8/122.7)). c levels increased with age in both sexes (ß per decade: 5.67% (4.22/7.13) male, 6.15% (4.72/7.57) female; p<0.001). Sex-specific reference limits and categories indicating the grade of deviation from the reference were calculated, and nomograms for c were created. c was approximately 25% higher in individuals with non-O blood type. Adjusted for sex and age, ABO-blood group accounted for 18.3% of c variation. In multivariable analysis, c was notably positively associated with diabetes mellitus, obesity, hypertension and dyslipidemia and negatively with current smoking. In a fully adjusted multivariable model, the strongest associations observed were of elevated c with diabetes and peripheral artery disease in both sexes and with obesity in males. Effects of SNPs in the vWF, STAB2 and SCARA5 gene were stronger in females than in males. The use of nomograms for valuation of c might be useful to identify high-risk cohorts for thromboembolism. Additionally, the prospective evaluation of c as a risk predictor becomes feasible. Copyright © 2015. Published by Elsevier Ireland Ltd.

  17. Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based sample of Working Adults

    Directory of Open Access Journals (Sweden)

    Cecilia Ulrika Dagsdotter Stenfors

    2016-10-01

    Full Text Available Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD, and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulationThe aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women, from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability measures, including the Standard Deviation of NN, here heart beats (SDNN, root of the mean squares of successive differences (RMSSD, high frequency (HF power band from spectral analyses, and QT variability index (QTVI, a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by 7 neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables and mental health symptoms.Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder, only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity. Conclusion: Poorer cardiovascular autonomic regulation in terms of lower SDNN & RMSSD and higher QTVI was associated with poorer

  18. Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress.

    Science.gov (United States)

    Fernández, Jesús; Toro, Miguel Á; Sonesson, Anna K; Villanueva, Beatriz

    2014-01-01

    The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

  19. Stoichiometric Representation of Gene–Protein–Reaction Associations Leverages Constraint-Based Analysis from Reaction to Gene-Level Phenotype Prediction

    DEFF Research Database (Denmark)

    Machado, Daniel; Herrgard, Markus; Rocha, Isabel

    2016-01-01

    only describe the metabolic phenotype at the reaction level, understanding the mechanistic link between genotype and phenotype is still hampered by the complexity of gene-protein-reaction associations. We implement a model transformation that enables constraint-based methods to be applied at the gene...... design methods are not actually feasible, and show how our approach allows using the same methods to obtain feasible gene-based designs. We also show, by extensive comparison with experimental 13C-flux data, how simple reformulations of different simulation methods with gene-wise objective functions...

  20. Neonatal Death Dwarfism in a Girl with Distinctive Bone Dysplasia Compatible with Grebe Chondrodysplasia: Analysis by CT Scan-based Phenotype

    Directory of Open Access Journals (Sweden)

    Ali Al Kaissi

    2014-01-01

    Full Text Available We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (consanguineous marriage strongly suggests autosomal recessive pattern of inheritance. To our knowledge, this is the first report of neonatal death dwarfism of Grebe syndrome analyzed by CT scan-based phenotype.

  1. Neonatal Death Dwarfism in a Girl with Distinctive Bone Dysplasia Compatible with Grebe Chondrodysplasia: Analysis by CT Scan-based Phenotype.

    Science.gov (United States)

    Al Kaissi, Ali; Chehida, Farid Ben; Ganger, Rudolf; Grill, Franz

    2014-01-01

    We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT) scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (consanguineous marriage) strongly suggests autosomal recessive pattern of inheritance. To our knowledge, this is the first report of neonatal death dwarfism of Grebe syndrome analyzed by CT scan-based phenotype.

  2. The application of flexible unmanned aerial vehicle remote sensing for field-based crop phenotyping: Current status and perspectives

    Science.gov (United States)

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypi...

  3. Modelo del Costo Basado en la Actividad aplicado a consultas por trazadores de enfermedades cardiovasculares Activity-based cost model applied to tracer cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Silvia A. Marteau

    2001-02-01

    consecuencia, se cargan a los costos de las consultas. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlOBJECTIVE: To analyze the costs of outpatient care on tracer ischemic cardiovascular diseases events in public healthcare institutions. MATERIALS AND METHODS: The study was carried out from April to October 1998, on a sample of 2 000 (290 tracer diseases and 1 710 non-tracer diseases first-time outpatient visits at the San Roque de Connet General Hospital, Buenos Aires, Argentina. Costs were evaluated using the Activity-Based Cost (ABC method. RESULTS: Outpatient care activity improvements would result in significant savings in indirect costs of 7.11% on average for products defined as high blood pressure, dyslipemia and diabetes. Total savings in unit cost per product from elimination of activities would be 11.78% for high blood pressure, 13.96% for dyslipemia, 19.05% for diabetes, and 11.45% for non-tracer diseases. A total of 66.26% of the total indirect costs corresponding to dyslipemia and 61.80% of the total indirect costs corresponding to diabetes were inefficiently allocated or misspent. The total unit cost of medical care assessed by the traditional method is $22.98, a figure that in some cases is quite below the cost obtained by the ABC method used in this study. CONCLUSIONS: It is necessary to work on re-designing the patient healthcare process, to evaluate the activities which do not add any value, and that turn out to be a nuisance and delay for the patient. These activities make the system inefficient since resources are allocated to activities that hinder the process and that are therefore charged to the cost of medical visits. The English version of this paper is available at: http://www.insp.mx/salud/index.html

  4. Danish register-based study on the association between specific cardiovascular drugs and fragility fractures

    DEFF Research Database (Denmark)

    Torstensson, Maia; Hansen, Annette Højmann; Leth-Møller, Katja

    2015-01-01

    OBJECTIVE: To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. DESIGN: Retrospective nationwide cohort study. SETTING: Danish nationwide national registers...... and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. RESULTS: Overall, 1 586 554 persons were included......, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides...

  5. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine Willum; Olsen, Michael H

    2008-01-01

    were recorded at baseline. CRP was determined by a high-sensitivity assay, and IR was determined by the homoeostasis model assessment (HOMA-IR) method. RESULTS: Over a median follow-up of 9.4 years, the incidence of the prespecified CV event, defined as the composite event of CV death, nonfatal...... and HOMA-IR, the hazard ratio (95% confidence interval) of a CV event was 1.33 (1.14-1.55; PHOMA-IR level. CONCLUSION......BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  6. Evaluation of cardiovascular risk-lowering health benefits accruing from laboratory-based, community-based and exercise-referral exercise programmes.

    Science.gov (United States)

    Webb, R; Thompson, J E S; Ruffino, J-S; Davies, N A; Watkeys, L; Hooper, S; Jones, P M; Walters, G; Clayton, D; Thomas, A W; Morris, K; Llewellyn, D H; Ward, M; Wyatt-Williams, J; McDonnell, B J

    2016-01-01

    To evaluate the ability of community-based exercise programmes to facilitate public participation in exercise and hence improved cardiovascular health, we assessed the respective impacts of: a continuously monitored exercise programme based within our university (study 1); a Valleys Regional Park-facilitated community-based outdoor exercise programme (study 2); a Wales National Exercise Referral Scheme-delivered exercise-referral programme (study 3). Biomolecular (monocytic PPARγ target gene expression), vascular haemodynamic (central/peripheral blood pressure, arterial stiffness), clinical (insulin sensitivity, blood lipids) and anthropometric (body mass index, waist circumference, heart rate) parameters were investigated using RT-PCR, applanation tonometry, chemical analysis and standard anthropometric techniques. In studies 1-3, 22/28, 32/65 and 11/14 participants adhered to their respective exercise programmes, and underwent significant increases in physical activity levels. Importantly, beneficial effects similar to those seen in our previous studies (eg, modulations in expression of monocytic PPARγ target genes, decreases in blood pressure/arterial stiffness, improvements in blood lipids/insulin sensitivity) were observed (albeit to slightly differing extents) only in participants who adhered to their respective exercise programmes. While study 1 achieved more intense exercise and more pronounced beneficial effects, significant cardiovascular risk-lowering health benefits related to biomolecular markers, blood pressure, arterial stiffness and blood lipids were achieved via community/referral-based delivery modes in studies 2 and 3. Because cardiovascular health benefits were observed in all 3 studies, we conclude that the majority of benefits previously reported in laboratory-based studies can also be achieved in community-based/exercise-referral settings. These findings may be of use in guiding policymakers with regard to introduction and/or continued

  7. Distribution and Outcomes of a Phenotype-Based Approach to Guide COPD Management: Results from the CHAIN Cohort.

    Directory of Open Access Journals (Sweden)

    Borja G Cosio

    Full Text Available The Spanish guideline for COPD (GesEPOC recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE, asthma-COPD overlap syndrome (ACOS, frequent exacerbator phenotype with emphysema (FEE or frequent exacerbator phenotype with chronic bronchitis (FECB. However, little is known on the distribution and outcomes of the four suggested phenotypes.We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes.We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT, BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes.Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%; ACOS, 125 (15.0%; FEE, 38 (4.6%; and FECB, 99 (11.9%; additionally 19 (2.3% COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05. The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes. Frequent exacerbator groups (FEE and FECB were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05 with no differences in one-year mortality. Most of NE (93% and half of exacerbators were stable after one year.There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use.

  8. Prediction of maize phenotype based on whole-genome single nucleotide polymorphisms using deep belief networks

    Science.gov (United States)

    Rachmatia, H.; Kusuma, W. A.; Hasibuan, L. S.

    2017-05-01

    Selection in plant breeding could be more effective and more efficient if it is based on genomic data. Genomic selection (GS) is a new approach for plant-breeding selection that exploits genomic data through a mechanism called genomic prediction (GP). Most of GP models used linear methods that ignore effects of interaction among genes and effects of higher order nonlinearities. Deep belief network (DBN), one of the architectural in deep learning methods, is able to model data in high level of abstraction that involves nonlinearities effects of the data. This study implemented DBN for developing a GP model utilizing whole-genome Single Nucleotide Polymorphisms (SNPs) as data for training and testing. The case study was a set of traits in maize. The maize dataset was acquisitioned from CIMMYT’s (International Maize and Wheat Improvement Center) Global Maize program. Based on Pearson correlation, DBN is outperformed than other methods, kernel Hilbert space (RKHS) regression, Bayesian LASSO (BL), best linear unbiased predictor (BLUP), in case allegedly non-additive traits. DBN achieves correlation of 0.579 within -1 to 1 range.

  9. Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

    Science.gov (United States)

    Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

  10. Cardiovascular radiology

    International Nuclear Information System (INIS)

    VanAman, M.; Mueller, C.F.

    1985-01-01

    Soon after Roentgen documented the uses of x-rays in 1895, fluoroscopic and film evaluation of the heart began. Even today the chest roentgenogram remains one of the first and most frequently used studies for the evaluation of the normal and abnormal heart and great vessels. This chapter gives an overview of plain film evaluation of the cardiovascular system and follow up with comments on the newer imaging modalities of computed tomography, and digital subtraction angiography, in the cardiovascular disease workup. The authors present an evaluation of plain films of the chest, which remains their most cost effective, available, simple, and reliable initial screening tool in the evaluation of cardiovascular disease

  11. Omics AnalySIs System for PRecision Oncology (OASISPRO): A Web-based Omics Analysis Tool for Clinical Phenotype Prediction.

    Science.gov (United States)

    Yu, Kun-Hsing; Fitzpatrick, Michael R; Pappas, Luke; Chan, Warren; Kung, Jessica; Snyder, Michael

    2017-09-12

    Precision oncology is an approach that accounts for individual differences to guide cancer management. Omics signatures have been shown to predict clinical traits for cancer patients. However, the vast amount of omics information poses an informatics challenge in systematically identifying patterns associated with health outcomes, and no general-purpose data-mining tool exists for physicians, medical researchers, and citizen scientists without significant training in programming and bioinformatics. To bridge this gap, we built the Omics AnalySIs System for PRecision Oncology (OASISPRO), a web-based system to mine the quantitative omics information from The Cancer Genome Atlas (TCGA). This system effectively visualizes patients' clinical profiles, executes machine-learning algorithms of choice on the omics data, and evaluates the prediction performance using held-out test sets. With this tool, we successfully identified genes strongly associated with tumor stage, and accurately predicted patients' survival outcomes in many cancer types, including mesothelioma and adrenocortical carcinoma. By identifying the links between omics and clinical phenotypes, this system will facilitate omics studies on precision cancer medicine and contribute to establishing personalized cancer treatment plans. This web-based tool is available at http://tinyurl.com/oasispro ;source codes are available at http://tinyurl.com/oasisproSourceCode . © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  12. Development of breeding strategy based on body coloration and phenotype in Holstein Friesian crossbreds for sustainable milk production

    Directory of Open Access Journals (Sweden)

    Md. Shahjahan

    2018-08-01

    Full Text Available In this study, Holstein Friesian crossbreds were categorized based on white coloring in different body parts, hump status, and known generations derived from controlled breeding and recording. The aim of this study was to reveal the effects of morphological features on milk production; grading of Holstein Friesian crossbreds and implement a sustainable breeding strategy based on phenotypic grading. Data of peak milk production and morphological characteristics were collected on 51 Holstein Friesian crossbred cows after primary sorting from three districts (Sirajganj, Chittagong and Mymensingh of Bangladesh. The data analyses were conducted following one-way ANOVA with descriptive statistics. The animals were graded according to the white coloring pattern (absent or present in horn, eyelid and eyelash, muzzle, hoof, tail switch, and the presence of a hump. It was observed that the presence of white color (18.86±1.01 to 22.00±1.57 liters in different body parts of Holstein Friesian crossbreds were significantly (p [Fundam Appl Agric 2018; 3(2.000: 498-504

  13. Recognition of Wheat Spike from Field Based Phenotype Platform Using Multi-Sensor Fusion and Improved Maximum Entropy Segmentation Algorithms

    Directory of Open Access Journals (Sweden)

    Chengquan Zhou

    2018-02-01

    Full Text Available To obtain an accurate count of wheat spikes, which is crucial for estimating yield, this paper proposes a new algorithm that uses computer vision to achieve this goal from an image. First, a home-built semi-autonomous multi-sensor field-based phenotype platform (FPP is used to obtain orthographic images of wheat plots at the filling stage. The data acquisition system of the FPP provides high-definition RGB images and multispectral images of the corresponding quadrats. Then, the high-definition panchromatic images are obtained by fusion of three channels of RGB. The Gram–Schmidt fusion algorithm is then used to fuse these multispectral and panchromatic images, thereby improving the color identification degree of the targets. Next, the maximum entropy segmentation method is used to do the coarse-segmentation. The threshold of this method is determined by a firefly algorithm based on chaos theory (FACT, and then a morphological filter is used to de-noise the coarse-segmentation results. Finally, morphological reconstruction theory is applied to segment the adhesive part of the de-noised image and realize the fine-segmentation of the image. The computer-generated counting results for the wheat plots, using independent regional statistical function in Matlab R2017b software, are then compared with field measurements which indicate that the proposed method provides a more accurate count of wheat spikes when compared with other traditional fusion and segmentation methods mentioned in this paper.

  14. Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

    Science.gov (United States)

    Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

    2015-03-09

    Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

  15. Refractory versus resistant hypertension: Novel distinctive phenotypes

    Science.gov (United States)

    Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

    2017-01-01

    Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

  16. Unmanned Aerial System (UAS)-based phenotyping of soybean using multi-sensor data fusion and extreme learning machine

    Science.gov (United States)

    Maimaitijiang, Maitiniyazi; Ghulam, Abduwasit; Sidike, Paheding; Hartling, Sean; Maimaitiyiming, Matthew; Peterson, Kyle; Shavers, Ethan; Fishman, Jack; Peterson, Jim; Kadam, Suhas; Burken, Joel; Fritschi, Felix

    2017-12-01

    Estimating crop biophysical and biochemical parameters with high accuracy at low-cost is imperative for high-throughput phenotyping in precision agriculture. Although fusion of data from multiple sensors is a common application in remote sensing, less is known on the contribution of low-cost RGB, multispectral and thermal sensors to rapid crop phenotyping. This is due to the fact that (1) simultaneous collection of multi-sensor data using satellites are rare and (2) multi-sensor data collected during a single flight have not been accessible until recent developments in Unmanned Aerial Systems (UASs) and UAS-friendly sensors that allow efficient information fusion. The objective of this study was to evaluate the power of high spatial resolution RGB, multispectral and thermal data fusion to estimate soybean (Glycine max) biochemical parameters including chlorophyll content and nitrogen concentration, and biophysical parameters including Leaf Area Index (LAI), above ground fresh and dry biomass. Multiple low-cost sensors integrated on UASs were used to collect RGB, multispectral, and thermal images throughout the growing season at a site established near Columbia, Missouri, USA. From these images, vegetation indices were extracted, a Crop Surface Model (CSM) was advanced, and a model to extract the vegetation fraction was developed. Then, spectral indices/features were combined to model and predict crop biophysical and biochemical parameters using Partial Least Squares Regression (PLSR), Support Vector Regression (SVR), and Extreme Learning Machine based Regression (ELR) techniques. Results showed that: (1) For biochemical variable estimation, multispectral and thermal data fusion provided the best estimate for nitrogen concentration and chlorophyll (Chl) a content (RMSE of 9.9% and 17.1%, respectively) and RGB color information based indices and multispectral data fusion exhibited the largest RMSE 22.6%; the highest accuracy for Chl a + b content estimation was

  17. Cross-platform analysis of cancer microarray data improves gene expression based classification of phenotypes

    Directory of Open Access Journals (Sweden)

    Eils Roland

    2005-11-01

    Full Text Available Abstract Background The extensive use of DNA microarray technology in the characterization of the cell transcriptome is leading to an ever increasing amount of microarray data from cancer studies. Although similar questions for the same type of cancer are addressed in these different studies, a comparative analysis of their results is hampered by the use of heterogeneous microarray platforms and analysis methods. Results In contrast to a meta-analysis approach where results of different studies are combined on an interpretative level, we investigate here how to directly integrate raw microarray data from different studies for the purpose of supervised classification analysis. We use median rank scores and quantile discretization to derive numerically comparable measures of gene expression from different platforms. These transformed data are then used for training of classifiers based on support vector machines. We apply this approach to six publicly available cancer microarray gene expression data sets, which consist of three pairs of studies, each examining the same type of cancer, i.e. breast cancer, prostate cancer or acute myeloid leukemia. For each pair, one study was performed by means of cDNA microarrays and the other by means of oligonucleotide microarrays. In each pair, high classification accuracies (> 85% were achieved with training and testing on data instances randomly chosen from both data sets in a cross-validation analysis. To exemplify the potential of this cross-platform classification analysis, we use two leukemia microarray data sets to show that important genes with regard to the biology of leukemia are selected in an integrated analysis, which are missed in either single-set analysis. Conclusion Cross-platform classification of multiple cancer microarray data sets yields discriminative gene expression signatures that are found and validated on a large number of microarray samples, generated by different laboratories and

  18. Internet-Based Device-Assisted Remote Monitoring of Cardiovascular Implantable Electronic Devices

    Science.gov (United States)

    Pron, G; Ieraci, L; Kaulback, K

    2012-01-01

    Executive Summary Objective The objective of this Medical Advisory Secretariat (MAS) report was to conduct a systematic review of the available published evidence on the safety, effectiveness, and cost-effectiveness of Internet-based device-assisted remote monitoring systems (RMSs) for therapeutic cardiac implantable electronic devices (CIEDs) such as pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. The MAS evidence-based review was performed to support public financing decisions. Clinical Need: Condition and Target Population Sudden cardiac death (SCD) is a major cause of fatalities in developed countries. In the United States almost half a million people die of SCD annually, resulting in more deaths than stroke, lung cancer, breast cancer, and AIDS combined. In Canada each year more than 40,000 people die from a cardiovascular related cause; approximately half of these deaths are attributable to SCD. Most cases of SCD occur in the general population typically in those without a known history of heart disease. Most SCDs are caused by cardiac arrhythmia, an abnormal heart rhythm caused by malfunctions of the heart’s electrical system. Up to half of patients with significant heart failure (HF) also have advanced conduction abnormalities. Cardiac arrhythmias are managed by a variety of drugs, ablative procedures, and therapeutic CIEDs. The range of CIEDs includes pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. Bradycardia is the main indication for PMs and individuals at high risk for SCD are often treated by ICDs. Heart failure (HF) is also a significant health problem and is the most frequent cause of hospitalization in those over 65 years of age. Patients with moderate to severe HF may also have cardiac arrhythmias, although the cause may be related more to heart pump or haemodynamic failure. The presence of HF, however

  19. In-car particles and cardiovascular health: an air conditioning-based intervention study.

    Science.gov (United States)

    Chuang, Hsiao-Chi; Lin, Lian-Yu; Hsu, Ya-Wen; Ma, Chih-Ming; Chuang, Kai-Jen

    2013-05-01

    Exposure to traffic-related particulate matter (PM) is considered a potential risk for cardiovascular events. Little is known about whether improving air quality in car can modify cardiovascular effects among human subjects during commuting. We recruited a panel of 60 healthy subjects to commute for 2 h by a car equipped with an air conditioning (AC) system during the morning rush hour in Taipei. Operation modes of AC system using outside air (OA-mode), circulating inside air (IA-mode) and turning off (Off-mode) were examined. Repeated measurements of heart rate variability (HRV) indices, PM≤2.5 μm in aerodynamic diameter (PM2.5) and noise level were conducted for each participant in different modes during the commute. We used linear mixed-effects models to associate HRV indices with in-car PM2.5. We found that decreases in HRV indices were associated with increased levels of in-car PM2.5. For Off-mode, an interquartile range (IQR) increase in in-car PM2.5 with 15-min moving average was associated with 2.7% and 4.1% decreases in standard deviation of NN intervals (SDNN) and the square root of the mean of the sum of the squares of differences between adjacent NN intervals (r-MSSD), respectively. During OA and IA modes, participants showed slight decreases in SDNN (OA mode: 0.1%; IA mode: 1.3%) and r-MSSD (OA mode: 1.1%; IA mode: 1.8%) by an IQR increase in in-car PM2.5 with 15-min moving average. We concluded that in-car PM2.5 is associated with autonomic alteration. Utilization of the car's AC system can improve air quality and modify the effects of in-car PM2.5 on HRV indices among human subjects during the commute. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Executive Cognitive Functioning and Cardiovascular Autonomic Regulation in a Population-Based Sample of Working Adults.

    Science.gov (United States)

    Stenfors, Cecilia U D; Hanson, Linda M; Theorell, Töres; Osika, Walter S

    2016-01-01

    Objective: Executive cognitive functioning is essential in private and working life and is sensitive to stress and aging. Cardiovascular (CV) health factors are related to cognitive decline and dementia, but there is relatively few studies of the role of CV autonomic regulation, a key component in stress responses and risk factor for cardiovascular disease (CVD), and executive processes. An emerging pattern of results from previous studies suggest that different executive processes may be differentially associated with CV autonomic regulation. The aim was thus to study the associations between multiple measures of CV autonomic regulation and measures of different executive cognitive processes. Method: Participants were 119 healthy working adults (79% women), from the Swedish Longitudinal Occupational Survey of Health. Electrocardiogram was sampled for analysis of heart rate variability (HRV) measures, including the Standard Deviation of NN, here heart beats (SDNN), root of the mean squares of successive differences (RMSSD), high frequency (HF) power band from spectral analyses, and QT variability index (QTVI), a measure of myocardial repolarization patterns. Executive cognitive functioning was measured by seven neuropsychological tests. The relationships between CV autonomic regulation measures and executive cognitive measures were tested with bivariate and partial correlational analyses, controlling for demographic variables, and mental health symptoms. Results: Higher SDNN and RMSSD and lower QTVI were significantly associated with better performance on cognitive tests tapping inhibition, updating, shifting, and psychomotor speed. After adjustments for demographic factors however (age being the greatest confounder), only QTVI was clearly associated with these executive tests. No such associations were seen for working memory capacity . Conclusion: Poorer CV autonomic regulation in terms of lower SDNN and RMSSD and higher QTVI was associated with poorer executive

  1. Deep Learning for Plant Phenotyping

    OpenAIRE

    Mori, Matteo

    2016-01-01

    Plant Phenotyping is an emerging science which provides us the knowledge to better understand plants. Indeed, the study of the link between genetic background and environment in which plants develop can help us to determine cures for plants’ sicknesses and new ways to improve yields using limited resources. In this regard, one of the main aspects of Plant Phenotyping that were studied in the past, was Root Phenotyping, which is based on the study of the root architectures. In particular, toda...

  2. A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

    Science.gov (United States)

    VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

    2017-12-01

    Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver

  3. Comparative performance of diabetes-specific and general population-based cardiovascular risk assessment models in people with diabetes mellitus.

    Science.gov (United States)

    Echouffo-Tcheugui, J-B; Kengne, A P

    2013-10-01

    Multivariable models for estimating cardiovascular disease (CVD) risk in people with diabetes comprise general population-based models and those from diabetic cohorts. Whether one set of models should receive preference is unclear. We evaluated the evidence on direct comparisons of the performance of general population vs diabetes-specific CVD risk models in people with diabetes. MEDLINE and EMBASE databases were searched up to March 2013. Two reviewers independently identified studies that compared the performance of general CVD models vs diabetes-specific ones in the same group of people with diabetes. Independent, dual data extraction on study design, risk models, outcomes; and measures of performance was conducted. Eleven articles reporting on 22 pair wise comparisons of a diabetes-specific model (UKPDS, ADVANCE and DCS risk models) to a general population model (three variants of the Framingham model, Prospective Cardiovascular Münster [PROCAM] score, CardioRisk Manager [CRM], Joint British Societies Coronary Risk Chart [JBSRC], Progetto Cuore algorithm and the CHD-Riskard algorithm) were eligible. Absolute differences in C-statistic of diabetes-specific vs general population-based models varied from -0.13 to 0.09. Comparisons for other performance measures were unusual. Outcomes definitions were congruent with those applied during model development. In 14 comparisons, the UKPDS, ADVANCE or DCS diabetes-specific models were superior to the general population CVD risk models. Authors reported better C-statistic for models they developed. The limited existing evidence suggests a possible discriminatory advantage of diabetes-specific over general population-based models for CVD risk stratification in diabetes. More robust head-to-head comparisons are needed to confirm this trend and strengthen recommendations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. An integrated approach to preventing cardiovascular disease: community-based approaches, health system initiatives, and public health policy

    Directory of Open Access Journals (Sweden)

    Tina Karwalajtys

    2010-09-01

    Full Text Available Tina Karwalajtys1, Janusz Kaczorowski2,31Department of Family Medicine, McMaster University, Hamilton, ON, Canada; 2Primary Care & Community Research, Child & Family Research Institute, Vancouver, BC, Canada; 3Department of Family Practice, University of British Columbia, Vancouver, BC, CanadaAbstract: Cardiovascular disease (CVD is largely the product of interactions among modifiable risk factors that are common in developed nations and increasingly of concern in developing countries. Hypertension is an important precursor to the development of CVD, and although detection and treatment rates have improved in recent years in some jurisdictions, effective strategies and policies supporting a shift in distribution of risk factors at the population level remain paramount. Challenges in managing cardiovascular health more effectively include factors at the patient, provider, and system level. Strategies to reduce hypertension and CVD should be population based, incorporate multilevel, multicomponent, and socioenvironmental approaches, and integrate community resources with public health and clinical care. There is an urgent need to improve monitoring and management of risk factors through community-wide, primary care-linked initiatives, increase the evidence base for community-based prevention strategies, further develop and evaluate promising program components, and develop new approaches to support healthy lifestyle behaviors in diverse age, socioeconomic, and ethnocultural groups. Policy and system changes are critical to reduce risk in populations, including legislation and public education to reduce dietary sodium and trans-fatty acids, food pricing policies, and changes to health care delivery systems to explicitly support prevention and management of CVD.Keywords: risk factors, blood pressure determination, community health services, community health planning, public health practice

  5. Feasibility and quality of cardiovascular disease prevention within a community-based health insurance program in rural Nigeria: an operational cohort study

    NARCIS (Netherlands)

    Hendriks, Marleen E.; Bolarinwa, Oladimeji A.; Wit, Ferdinand W. N. W.; Brewster, Lizzy M.; Odusola, Aina O.; Rosendaal, Nicole T. A.; Bindraban, Navin R.; Adenusi, Peju; Agbede, Kayode; Lange, Joep M. A.; Akande, Tanimola M.; Schultsz, Constance

    2015-01-01

    To assess the feasibility of providing guideline-based cardiovascular disease (CVD) prevention care within the context of a community-based health insurance program (CBHI) in rural Nigeria. A prospective operational cohort study was conducted in a primary healthcare clinic in rural Nigeria,

  6. Atherosclerosis profile and incidence of cardiovascular events: a population-based survey

    Directory of Open Access Journals (Sweden)

    Bullano Michael F

    2009-09-01

    Full Text Available Abstract Background Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. Methods Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization. Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. Results Of 17,640 respondents, 488 (2.8% reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2 [all p Conclusion Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

  7. Defining Value-Based Care in Cardiac and Vascular Anesthesiology: The Past, Present, and Future of Perioperative Cardiovascular Care.

    Science.gov (United States)

    Kolarczyk, Lavinia M; Arora, Harendra; Manning, Michael W; Zvara, David A; Isaak, Robert S

    2018-02-01

    Health care reimbursement models are transitioning from volume-based to value-based models. Value-based models focus on patient outcomes both during the hospital admission and postdischarge. These models place emphasis on cost, quality of care, and coordination of multidisciplinary services. Perioperative physicians are challenged to evaluate traditional practices to ensure coordinated, cost-effective, and evidence-based care. With the Centers for Medicare and Medicaid Services planned introduction of bundled payments for coronary artery bypass graft surgery, cardiovascular anesthesiologists are financially responsible for postdischarge outcomes. In order to meet these patient outcomes, multidisciplinary care pathways must be designed, implemented, and sustained, a process that is challenging at best. This review (1) provides a historical perspective of health care reimbursement; (2) defines value as it pertains to quality, service, and cost; (3) reviews the history of value-based care for cardiac surgery; (4) describes the drive toward optimization for vascular surgery patients; and (5) discusses how programs like Enhanced Recovery After Surgery assist with the delivery of value-based care. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Array-based FMR1 sequencing and deletion analysis in patients with a fragile X syndrome-like phenotype.

    Directory of Open Access Journals (Sweden)

    Stephen C Collins

    2010-03-01

    Full Text Available Fragile X syndrome (FXS is caused by loss of function mutations in the FMR1 gene. Trinucleotide CGG-repeat expansions, resulting in FMR1 gene silencing, are the most common mutations observed at this locus. Even though the repeat expansion mutation is a functional null mutation, few conventional mutations have been identified at this locus, largely due to the clinical laboratory focus on the repeat tract.To more thoroughly evaluate the frequency of conventional mutations in FXS-like patients, we used an array-based method to sequence FMR1 in 51 unrelated males exhibiting several features characteristic of FXS but with normal CGG-repeat tracts of FMR1. One patient was identified with a deletion in FMR1, but none of the patients were found to have other conventional mutations.These data suggest that missense mutations in FMR1 are not a common cause of the FXS phenotype in patients who have normal-length CGG-repeat tracts. However, screening for small deletions of FMR1 may be of clinically utility.

  9. Aspirin and the Primary Prevention of Cardiovascular Diseases: An Approach Based on Individualized, Integrated Estimation of Risk.

    Science.gov (United States)

    Volpe, Massimo; Battistoni, Allegra; Gallo, Giovanna; Coluccia, Roberta; De Caterina, Raffaele

    2017-09-01

    While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio.

  10. Pattern-based approach to fetal congenital cardiovascular anomalies using the transverse aortic arch view on prenatal cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Su-Zhen; Zhu, Ming [Shanghai Jiaotong University School of Medicine, Department of Radiology, Shanghai Children' s Medical Center, Shanghai (China)

    2015-05-01

    Fetal echocardiography is the imaging modality of choice for prenatal diagnosis of congenital cardiovascular anomalies. However, echocardiography has limitations. Fetal cardiac magnetic resonance imaging (MRI) has the potential to complement US in detecting congenital cardiovascular anomalies. This article draws on our experience; it describes the transverse aortic arch view on fetal cardiac MRI and important clues on an abnormal transverse view at the level of the aortic arch to the diagnosis of fetal congenital cardiovascular anomalies. (orig.)

  11. Pattern-based approach to fetal congenital cardiovascular anomalies using the transverse aortic arch view on prenatal cardiac MRI

    International Nuclear Information System (INIS)

    Dong, Su-Zhen; Zhu, Ming

    2015-01-01

    Fetal echocardiography is the imaging modality of choice for prenatal diagnosis of congenital cardiovascular anomalies. However, echocardiography has limitations. Fetal cardiac magnetic resonance imaging (MRI) has the potential to complement US in detecting congenital cardiovascular anomalies. This article draws on our experience; it describes the transverse aortic arch view on fetal cardiac MRI and important clues on an abnormal transverse view at the level of the aortic arch to the diagnosis of fetal congenital cardiovascular anomalies. (orig.)

  12. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

    particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. The evolution of this definition and the diagnostic criteria currently in use are discussed. COPD is increasingly divided in subgroups or phenotypes based on specific features and association...

  13. Cardiovascular reactivity in young adults with hypertensive and normotensive parents: A gender based comparative study

    Directory of Open Access Journals (Sweden)

    Anjali Verma

    2017-01-01

    Full Text Available Introduction: Essential hypertension begins due to mutation of specific genes that contribute to the risk of developing hypertension. Genetic contribution was recognized 25 years ago, now formulated from time to time. Some studies have also proven that the hypertension in father had strong contribution in their individual than mother. The aim of the study is to compare the cardiovascular reactivity in male and female subjects with hypertensive and normotensive parents. Materials and methods: This comparative study was conducted in physiology department of Teerthanker Mahaveer medical college and research center, Moradabad. The research work was initiated after taken the ethical clearance from the ethical committee of the college. Three different stressors: cold pressor task, cycling and videogame were used. Total 120 subjects were taken for the study in which 77 were male and 43 were female. Result: Male subjects of normotensive parents had slightly higher HR rate (mean: 76.73/min compared to the female subjects (mean: 75/min with p value >0.05. Female subjects of hypertensive parents had higher HR rate (mean: 82.72/min compared to the male subjects (mean: 73.95/min with p value <0.001. Conclusion: Male subjects with normotensive parents had higher resting HR, SBP &DBP than Female subjects with normotensive parents, but the difference was significant only in SBP. Female subjects with hypertensive parents group was showing higher resting HR than male subjects with hypertensive parents group, remains higher after stress also with insignificant difference. Thus, subjects with hypertensive parents showing increased CVR to stress are more likely to develop future hypertension, and the risk is greater for male subjects.

  14. Pharmacists’ Attitudes and Perceived Barriers about Community Pharmacy-Based Cardiovascular Risk Screening Services

    Directory of Open Access Journals (Sweden)

    Zahra Jahangard-Rafsanjani

    2015-10-01

    Full Text Available  Background: Community pharmacies are considered as ideal settings to provide cardiovascular risk screening (CRS. However, little is known about pharmacists’ views on providing such services in developing countries including Iran. In the present study, we evaluated the pharmacists’ attitudes and perceived barriers to providing CRS services. Methods:In a cross-sectional study, a questionnaire in three sections was developed by the investigators (attitudes, perceived barriers, and demographics. Five likert items (5 points bipolar scale were designed to evaluate pharmacists’ attitudes about their professional role in providing CRS services in community pharmacies. Seven likert items were designed to assess the pharmacists’ perceived importance of possible barriers to providing the services. The study tool was distributed among a convenient sample of 500 pharmacists, who had participated in a national continuing education event. Results:The response rate was 44% and descriptive statistics and Chi squared test were used to analyze data. Results showed that 70.4% participants had an overall positive attitude to providing CRS services. Pharmacists who were pharmacy owner and pharmacist-in-charge simultaneously were more positive about providing CRS services. Lack of regulatory policy and compensation mechanism, limited physical space in pharmacy and time limitation were reported to be the most important barriers to providing CRS services (> 50% rated as highly important. Low human resource and time limitation were significantly associated with negative attitudes (P: 0.02 and 0.001, respectively.Conclusion:The Iranian pharmacists’ attitudes seem to be positive about providing CRS services; however, their perceived barriers should be addressed prior to CRS service implementation.

  15. Cardiovascular health among two ethnic groups living in the same region: A population-based study.

    Science.gov (United States)

    Benderly, Michal; Chetrit, Angela; Murad, Havi; Abu-Saad, Kathleen; Gillon-Keren, Michal; Rogowski, Ori; Sela, Ben-Ami; Kanety, Hannah; Harats, Dror; Atamna, Ahmed; Alpert, Gershon; Goldbourt, Uri; Kalter-Leibovici, Ofra

    2017-02-01

    Poor cardiovascular health (CVH) among ethnic/racial minorities, studied primarily in the USA, may reflect lower access to healthcare. We examined factors associated with minority CVH in a setting of universal access to healthcare. CVH behaviors and factors were evaluated in a random population sample (551 Arabs, 553 Jews) stratified by sex, ethnicity and age. More Jews (10%) than Arabs (3%) had 3 ideal health behaviors. Only one participant had all four. Although ideal diet was rare (≤1.5%) across groups, Arabs were more likely to meet intake recommendations for whole grains, but less likely to meet intake recommendations for fruits/vegetables and fish. Arabs had lower odds of attaining ideal levels for body mass index and physical activity. Smoking prevalence was 57% among Arab men and 6% among Arab women. Having four ideal health factors (cholesterol, blood pressure, glucose, smoking) was observed in 2% and 8% of Arab and Jewish men, respectively, and 13% of Arab and Jewish women. Higher prevalence of ideal total-cholesterol corresponded to lower high-density lipoprotein cholesterol among Arabs. No participant met ideal levels for all 7 metrics and only 1.8% presented with 6. Accounting for age and lower socioeconomic status, Arabs were less likely to meet a greater number of metric goals (odds ratio (95% confidence interval): 0.62 (0.42-0.92) for men, and 0.73 (0.48-1.12) for women). Ideal CVH, rare altogether, was less prevalent among the Arab minority albeit universal access to healthcare. Health behaviors were the main contributors to the CVH disparity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Current status of cardiovascular surgery in Japan 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database. 2: Congenital heart surgery.

    Science.gov (United States)

    Hirata, Yasutaka; Hirahara, Norimichi; Murakami, Arata; Motomura, Noboru; Miyata, Hiroaki; Takamoto, Shinichi

    2018-01-01

    We analyzed the mortality and morbidity of congenital heart surgery in Japan using the Japan Cardiovascular Surgery Database (JCVSD). Data regarding congenital heart surgery performed between January 2013 and December 2014 were obtained from JCVSD. The 20 most frequent procedures were selected and the mortality rates and major morbidities were analyzed. The mortality rates of atrial septal defect repair and ventricular septal defect repair were less than 1%, and the mortality rates of tetralogy of Fallot repair, complete atrioventricular septal defect repair, bidirectional Glenn, and total cavopulmonary connection were less than 2%. The mortality rates of the Norwood procedure and total anomalous pulmonary venous connection repair were more than 10%. The rates of unplanned reoperation, pacemaker implantation, chylothorax, deep sternal infection, phrenic nerve injury, and neurological deficit were shown for each procedure. Using JCVSD, the national data for congenital heart surgery, including postoperative complications, were analyzed. Further improvements of the database and feedback for clinical practice are required.

  17. A SCHOOL-BASED INTERVENTION PROGRAM FOR IMPROVING THE RISK FACTORS FOR CARDIOVASCULAR DISEASE AT AGES 12 TO 16.

    Directory of Open Access Journals (Sweden)

    Konstantinos Laparidis

    2010-06-01

    Full Text Available Background. Cardiovascular disease begins in childhood and this can be correlated with the presence of risk factors in adults. It is reasonable to initiate healthful lifestyle training in childhood to promote improved cardiovascular health in adult life. The purpose of the study was to evaluate the effectiveness of a school-basedprogram designed to reduce specific modifiable risk factors for preventing cardiovascular diseases.Methods. The sample was 343 students (160 boys, 183 girls aged 12–16 years from the prefecture of Larissa, Greece. The duration of intervention was 1 school year. The practical part of intervention took place during the class of physical education, while the theoretical part took place in the classroom. Measurements weretaken at the beginning, in the middle and at the end of the intervention. The following parameters were measured: weight, height, blood pressure, heart rate, components of the Healthy Eating Index, VO2max,Fitnessgram test battery (1 mile run-walk, trunk lift, push up, curl up, back saver sit and reach.Results. There were significant differences between the school-groups in the 1 mile run walk (p<0,001,90o push up test (p<0,001, Healthy Eating Index (p<0,001, fruit component (p<0,001, saturated fat intake(p<0,05 and variety component (p<0,001. In the intervention group there was significant increase in VO2max(p<0,05, in the weight (p<0,001, in the Healthy Eating Index (p<0,05, in the trunk lift test (p<0,001, in the push up test (p<0,05, in the sit and reach test (p<0,001 and in the component of fruits (p<0,001, while there was significant reduction in the 1 mile run walk test (p<0,001, in the body mass index (p<0,05 and in the component of saturated fat (p<0,05.Conclusion. The intervention program was successfully implemented in schools and there were many significant and positive effects. These results highlight the importance of multicomponent programs for theprevention of CVD in schools. Additional

  18. Phenotypic transition maps of 3D breast acini obtained by imaging-guided agent-based modeling

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jonathan; Enderling, Heiko; Becker-Weimann, Sabine; Pham, Christopher; Polyzos, Aris; Chen, Chen-Yi; Costes, Sylvain V

    2011-02-18

    We introduce an agent-based model of epithelial cell morphogenesis to explore the complex interplay between apoptosis, proliferation, and polarization. By varying the activity levels of these mechanisms we derived phenotypic transition maps of normal and aberrant morphogenesis. These maps identify homeostatic ranges and morphologic stability conditions. The agent-based model was parameterized and validated using novel high-content image analysis of mammary acini morphogenesis in vitro with focus on time-dependent cell densities, proliferation and death rates, as well as acini morphologies. Model simulations reveal apoptosis being necessary and sufficient for initiating lumen formation, but cell polarization being the pivotal mechanism for maintaining physiological epithelium morphology and acini sphericity. Furthermore, simulations highlight that acinus growth arrest in normal acini can be achieved by controlling the fraction of proliferating cells. Interestingly, our simulations reveal a synergism between polarization and apoptosis in enhancing growth arrest. After validating the model with experimental data from a normal human breast line (MCF10A), the system was challenged to predict the growth of MCF10A where AKT-1 was overexpressed, leading to reduced apoptosis. As previously reported, this led to non growth-arrested acini, with very large sizes and partially filled lumen. However, surprisingly, image analysis revealed a much lower nuclear density than observed for normal acini. The growth kinetics indicates that these acini grew faster than the cells comprising it. The in silico model could not replicate this behavior, contradicting the classic paradigm that ductal carcinoma in situ is only the result of high proliferation and low apoptosis. Our simulations suggest that overexpression of AKT-1 must also perturb cell-cell and cell-ECM communication, reminding us that extracellular context can dictate cellular behavior.

  19. Interoperability between phenotype and anatomy ontologies.

    Science.gov (United States)

    Hoehndorf, Robert; Oellrich, Anika; Rebholz-Schuhmann, Dietrich

    2010-12-15

    Phenotypic information is important for the analysis of the molecular mechanisms underlying disease. A formal ontological representation of phenotypic information can help to identify, interpret and infer phenotypic traits based on experimental findings. The methods that are currently used to represent data and information about phenotypes fail to make the semantics of the phenotypic trait explicit and do not interoperate with ontologies of anatomy and other domains. Therefore, valuable resources for the analysis of phenotype studies remain unconnected and inaccessible to automated analysis and reasoning. We provide a framework to formalize phenotypic descriptions and make their semantics explicit. Based on this formalization, we provide the means to integrate phenotypic descriptions with ontologies of other domains, in particular anatomy and physiology. We demonstrate how our framework leads to the capability to represent disease phenotypes, perform powerful queries that were not possible before and infer additional knowledge. http://bioonto.de/pmwiki.php/Main/PheneOntology.

  20. The prevalence of metabolic disorders in various phenotypes of polycystic ovary syndrome: a community based study in Southwest of Iran.

    Science.gov (United States)

    Tehrani, Fahimeh Ramezani; Rashidi, Homeira; Khomami, Mahnaz Bahri; Tohidi, Maryam; Azizi, Fereidoun

    2014-09-16

    Polycystic ovary syndrome (PCOS) is a common endocrinopathy, associated with metabolic abnormalities. Metabolic features of various phenotypes of this syndrome are still debatable. The aim of present study hence was to evaluate the metabolic and hormonal features of PCOS phenotypes in comparison to a group of healthy control. A total of 646 reproductive-aged women were randomly selected using the stratified, multistage probability cluster sampling method. The subjects were divided into five phenotypes: A (oligo/anovulation + hyperandrogenism + polycystic ovaries), B (oligo/anovulation + hyperandrogenism), C (hyperandrogenism + polycystic ovaries) and D (oligo/anovulation + polycystic ovaries). Hormonal and metabolic profiles and the prevalence of metabolic syndrome among these groups were compared using ANCOVA adjusted for age and body mass index. Among women with PCOS (n = 85), those of groups A and C had higher serum levels of insulin and homeostatic model assessment for insulin resistance (HOMA-IR), compared to PCOS women of group D. Serum concentrations of cholesterol, low density lipoprotein, triglycerides and glucose in group A were higher than in other phenotypes, whereas the metabolic syndrome was more prevalent among group B. Women who had all three components of the syndrome showed the highest level of metabolic disturbances indicating that metabolic screening of the severest phenotype of PCOS may be necessary.

  1. Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

    Science.gov (United States)

    Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

    2018-06-01

    Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Are women with polycystic ovary syndrome at increased cardiovascular disease risk later in life?

    Science.gov (United States)

    Gunning, M N; Fauser, B C J M

    2017-06-01

    To date, the world's leading cause of death amongst women is cardiovascular disease. Polycystic ovary syndrome (PCOS) is associated with an unfavorable cardiometabolic profile in early life. Apart from dyslipidemia, obesity and onset of type 2 diabetes mellitus, androgens are thought to influence cardiovascular health. The question rises whether women with PCOS are truly at risk for cardiovascular disease in later life. In this review paper, we aim to reflect on this assumed relation based on studies in different stages of life in women with PCOS. Cardiovascular risk factors (type 2 diabetes mellitus, obesity and metabolic syndrome), surrogate outcomes (flow-mediated dilation, carotid intima-media thickness and coronary artery calcium) and clinical long-term outcomes (cardiovascular disease and mortality) will be summarized. Data on cardiovascular disease and mortality in peri- and postmenopausal women with PCOS appear to be controversial. Whether androgens have a protective or unfavorable influence on the manifestation of cardiovascular disease remains uncertain. The need for large, prospective, well-phenotyped cohort studies of women with PCOS is high. Only then will we be able to answer this research question.

  3. The Role of Mesolimbic Reward Neurocircuitry in Prevention and Rescue of the Activity-Based Anorexia (ABA) Phenotype in Rats.

    Science.gov (United States)

    Foldi, Claire J; Milton, Laura K; Oldfield, Brian J

    2017-11-01

    Patients suffering from anorexia nervosa (AN) become anhedonic; unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The activity-based anorexia (ABA) model recapitulates many of the characteristics of the human condition, including anhedonia, and allows investigation of the underlying neurobiology of AN. The potential for increased neuronal activity in reward/hedonic circuits to prevent and rescue weight loss is investigated in this model. The mesolimbic pathway extending from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) was activated using a dual viral strategy, involving retrograde transport of Cre (CAV-2-Cre) to the VTA and coincident injection of DREADD receptors (AAV-hSyn-DIO-hM3D(Gq)-mCherry). Systemic clozapine-n-oxide (CNO; 0.3 mg/kg) successfully recruited a large proportion of the VTA-NAc dopaminergic projections, with activity evidenced by colocalization with elevated levels of Fos protein. The effects of reward circuit activation on energy balance and predicted survival was investigated in female Sprague-Dawley rats, where free access to running wheels was paired with time-limited (90 min) access to food, a paradigm (ABA) which will cause anorexia and death if unchecked. Excitation of the reward pathway substantially increased food intake and food anticipatory activity (FAA) to prevent ABA-associated weight loss, while overall locomotor activity was unchanged. Similar activation of reward circuitry, delayed until establishment of the ABA phenotype, rescued rats from their precipitous weight loss. Although these data are consistent with shifts primarily in food intake, the contribution of mechanisms including energy expenditure to survival remains to be determined. These results will inform the neurobiological underpinnings of AN, and provide insight into the mechanisms of reward circuitry relevant to feeding and weight loss.

  4. Effects of a general practice-based intervention on diet, body mass index and blood lipids in patients at cardiovascular risk

    NARCIS (Netherlands)

    Woollard, J.; Burke, V.; Beilin, L.J.; Verheijden, M.W.; Bulsara, M.K.

    2003-01-01

    Background General practice-based health-promotion programmes implemented by nurse-counsellors may reduce cardiovascular risk factors, particularly in patients at increased risk. Neither change in fat intake nor serum cholesterol differed significantly between groups. Body mass index increased in

  5. Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

    Science.gov (United States)

    Wu, Jashin J; Strober, Bruce E; Hansen, Peter R; Ahlehoff, Ole; Egeberg, Alexander; Qureshi, Abrar A; Robertson, Debbie; Valdez, Hernan; Tan, Huaming; Wolk, Robert

    2016-11-01

    Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. There was relatively short follow-up time for patients who had MACEs. While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  6. Precision Medicine in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yan Liu

    2017-02-01

    Full Text Available Since President Obama announced the Precision Medicine Initiative in the United States, more and more attention has been paid to precision medicine. However, clinicians have already used it to treat conditions such as cancer. Many cardiovascular diseases have a familial presentation, and genetic variants are associated with the prevention, diagnosis, and treatment of cardiovascular diseases, which are the basis for providing precise care to patients with cardiovascular diseases. Large-scale cohorts and multiomics are critical components of precision medicine. Here we summarize the application of precision medicine to cardiovascular diseases based on cohort and omic studies, and hope to elicit discussion about future health care.

  7. Phenotype- and SSR-Based Estimates of Genetic Variation between and within Two Important Elymus Species in Western and Northern China

    Directory of Open Access Journals (Sweden)

    Zongyu Zhang

    2018-03-01

    Full Text Available Elymus nutans and Elymus sibiricus are two important perennial forage grasses of the genus Elymus, widely distributed in high altitude regions of Western and Northern China, especially on the Qinghai-Tibetan Plateau. Information on phenotypic and genetic diversity is limited, but necessary for Elymus germplasm collection, conservation, and utilization. In the present study, the phenotypic and genetic differentiation of 73 accessions of the two species were evaluated using 15 phenotypic traits and 40 expressed sequence tag derived simple sequence repeat markers (EST-SSRs. The results showed that only 7.23% phenotypic differentiation (Pst existed between the two Elymus species based on fifteen quantitative traits. Principal component analysis (PCA revealed that leaf traits, spike traits, and some seed traits were dominant factors in phenotypic variation. Moreover, 396 (97.8% and 331 (87.1% polymorphic bands were generated from 40 EST-SSR primers, suggesting high levels of genetic diversity for the two species. The highest genetic diversity was found in the Northeastern Qinghai-Tibetan Plateau groups. Clustering analysis based on molecular data showed that most accessions of each Elymus species tended to group together. Similar results were described by principal coordinates analysis (PCoA and structure analysis. The molecular variance analysis (AMOVA revealed that 81.47% and 89.32% variation existed within the geographical groups for the two species, respectively. Pearson’s correlation analyses showed a strong positive correlation between Nei’s genetic diversity and annual mean temperature. These results could facilitate Elymus germplasm collection, conservation, and future breeding.

  8. Cardiovascular diseases

    International Nuclear Information System (INIS)

    Kodama, Kazunori

    1992-01-01

    This paper is aimed to discuss the involvement of delayed radiation effects of A-bomb exposure in cardiovascular diseases. First, the relationship between radiation and cardiovascular diseases is reviewed in the literature. Animal experiments have confirmed the relationship between ionizing radiation and vascular lesions. There are many reports which describe ischemic heart disease, cervical and cerebrovascular diseases, and peripheral disease occurring after radiation therapy. The previous A-bomb survivor cohort studies, i.e., the RERF Life Span Study and Adult Health Study, have dealt with the mortality rate from cardiovascular diseases, the prevalence or incidence of cardiovascular diseases, pathological findings, clinical observation of arteriosclerosis, ECG abnormality, blood pressure abnormality, and cardiac function. The following findings have been suggested: (1) A-bomb exposure is likely to be involved in the mortality rate and incidence of ischemic heart disease and cerebrovascular diseases; (2) similarly, the involvement of A-bomb exposure is considered in the prevalence of the arch of aorta; (3) ECG abnormality corresponding to ischemic heart disease may reflect the involvement of A-bomb exposure. To confirm the above findings, further studies are required on the basis of more accurate information and the appropriate number of cohort samples. Little evidence has been presented for the correlation between A-bomb exposure and both rheumatic heart disease and congenital heart disease. (N.K.) 88 refs

  9. Detection of cardiovascular anomalies: Hybrid systems approach

    KAUST Repository

    Ledezma, Fernando; Laleg-Kirati, Taous-Meriem

    2012-01-01

    In this paper, we propose a hybrid interpretation of the cardiovascular system. Based on a model proposed by Simaan et al. (2009), we study the problem of detecting cardiovascular anomalies that can be caused by variations in some physiological

  10. Residual generator for cardiovascular anomalies detection

    KAUST Repository

    Belkhatir, Zehor; Laleg-Kirati, Taous-Meriem; Tadjine, Mohamed

    2014-01-01

    This paper discusses the possibility of using observer-based approaches for cardiovascular anomalies detection and isolation. We consider a lumped parameter model of the cardiovascular system that can be written in a form of nonlinear state

  11. Evaluation of a community-based participatory physical activity promotion project: effect on cardiovascular disease risk profiles of school employees

    Directory of Open Access Journals (Sweden)

    Kobza Cee E

    2010-06-01

    Full Text Available Abstract Background The efficacy of physical activity in improving cardiovascular disease (CVD risk profiles has been well established. However, the effectiveness of health promotion programs implemented at the community level remains controversial. This study evaluated a school-based work-site physical activity program. Methods Using a community-based participatory research model, a work-site wellness intervention was implemented in a rural public school system in Southwestern Oklahoma. During the 2005-2006 school year, 187 participants (mean age 45 years completed a pre intervention screening for CVD risk factors followed by a physical activity promotion program. Post intervention screening was conducted after a 6 month period. During both screening sessions, body composition, blood pressure, lipids, glucose and self-reported physical activity levels were assessed. The focus of the intervention was on promoting physical activity. Opportunities for in school physical activity were created by marking hallways, adding a treadmill in each school, and allowing teachers to use planning periods for physical activity. Results During the post intervention screening, compared to pre intervention levels, participants had lower total, low, and high density lipoprotein-cholesterol (t = 5.9, p Conclusions A successful participatory program was associated with improvements in several CVD risk factors among school employees. Limitations of this study such as seasonal variation in the outcome variables and lack of a control group limit our ability to draw solid conclusions about the effectiveness of the intervention.

  12. Adapting Phonological Awareness Interventions for Children with Down Syndrome Based on the Behavioral Phenotype: A Promising Approach?

    Science.gov (United States)

    Lemons, Christopher J.; King, Seth A.; Davidson, Kimberly A.; Puranik, Cynthia S.; Fulmer, Deborah; Mrachko, Alicia A.; Partanen, Jane; Al Otaiba, Stephanie; Fidler, Deborah J.

    2015-01-01

    Many children with Down syndrome demonstrate deficits in phonological awareness, a prerequisite to learning to read in an alphabetic language. The purpose of this study was to determine whether adapting a commercially available phonological awareness program to better align with characteristics associated with the behavioral phenotype of Down…

  13. SORTA : a system for ontology-based re-coding and technical annotation of biomedical phenotype data

    NARCIS (Netherlands)

    Pang, Chao; Sollie, Annet; Sijtsma, Anna; Hendriksen, Dennis; Charbon, Bart; Haan, Mark de; de Boer, Tommy; Kelpin, Fleur; Jetten, Jonathan; van der Velde, Joeri K.; Smidt, Nynke; Sijmons, Rolf; Hillege, Hans; Swertz, Morris A.

    2015-01-01

    There is an urgent need to standardize the semantics of biomedical data values, such as phenotypes, to enable comparative and integrative analyses. However, it is unlikely that all studies will use the same data collection protocols. As a result, retrospective standardization is often required,

  14. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics

    DEFF Research Database (Denmark)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies...

  15. Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.

    Science.gov (United States)

    Ng, Siew C; Tang, Whitney; Ching, Jessica Y; Wong, May; Chow, Chung Mo; Hui, A J; Wong, T C; Leung, Vincent K; Tsang, Steve W; Yu, Hon Ho; Li, Mo Fong; Ng, Ka Kei; Kamm, Michael A; Studd, Corrie; Bell, Sally; Leong, Rupert; de Silva, H Janaka; Kasturiratne, Anuradhani; Mufeena, M N F; Ling, Khoon Lin; Ooi, Choon Jin; Tan, Poh Seng; Ong, David; Goh, Khean L; Hilmi, Ida; Pisespongsa, Pises; Manatsathit, Sathaporn; Rerknimitr, Rungsun; Aniwan, Satimai; Wang, Yu Fang; Ouyang, Qin; Zeng, Zhirong; Zhu, Zhenhua; Chen, Min Hu; Hu, Pin Jin; Wu, Kaichun; Wang, Xin; Simadibrata, Marcellus; Abdullah, Murdani; Wu, Justin Cy; Sung, Joseph J Y; Chan, Francis K L

    2013-07-01

    Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn's and Colitis Epidemiology Study aimed to determine the incidence and phenotype of IBD in 8 countries across Asia and in Australia. We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. We identified 419 new cases of IBD (232 of ulcerative colitis [UC], 166 of Crohn's disease [CD], and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25-1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46-29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4-15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Subclinical cardiovascular disease assessment and its relationship with cardiovascular risk SCORE in a healthy adult population: A cross-sectional community-based study.

    Science.gov (United States)

    Mitu, Ovidiu; Roca, Mihai; Floria, Mariana; Petris, Antoniu Octavian; Graur, Mariana; Mitu, Florin

    The aim of this study is to evaluate the relationship and the accuracy of SCORE (Systematic Coronary Risk Evaluation Project) risk correlated to multiple methods for determining subclinical cardiovascular disease (CVD) in a healthy population. This cross-sectional study included 120 completely asymptomatic subjects, with an age range 35-75 years, and randomly selected from the general population. The individuals were evaluated clinically and biochemical, and the SCORE risk was computed. Subclinical atherosclerosis was assessed by various methods: carotid ultrasound for intima-media thickness (cIMT) and plaque detection; aortic pulse wave velocity (aPWV); echocardiography - left ventricular mass index (LVMI) and aortic atheromatosis (AA); ankle-brachial index (ABI). SCORE mean value was 2.95±2.71, with 76% of subjects having SCORE <5. Sixty-four percent of all subjects have had increased subclinical CVD changes, and SCORE risk score was correlated positively with all markers, except for ABI. In the multivariate analysis, increased cIMT and aPWV were significantly associated with high value of SCORE risk (OR 4.14, 95% CI: 1.42-12.15, p=0.009; respectively OR 1.41, 95% CI: 1.01-1.96, p=0.039). A positive linear relationship was observed between 3 territories of subclinical CVD (cIMT, LVMI, aPWV) and SCORE risk (p<0.0001). There was evidence of subclinical CVD in 60% of subjects with a SCORE value <5. As most subjects with a SCORE value <5 have subclinical CVD abnormalities, a more tailored subclinical CVD primary prevention program should be encouraged. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. HIV and Cardiovascular Disease

    Science.gov (United States)

    ... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

  18. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  19. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry.

    Science.gov (United States)

    Papa, Riccardo; Doglio, Matteo; Lachmann, Helen J; Ozen, Seza; Frenkel, Joost; Simon, Anna; Neven, Bénédicte; Kuemmerle-Deschner, Jasmin; Ozgodan, Huri; Caorsi, Roberta; Federici, Silvia; Finetti, Martina; Trachana, Maria; Brunner, Jurgen; Bezrodnik, Liliana; Pinedo Gago, Mari Carmen; Maggio, Maria Cristina; Tsitsami, Elena; Al Suwairi, Wafaa; Espada, Graciela; Shcherbina, Anna; Aksu, Guzide; Ruperto, Nicolino; Martini, Alberto; Ceccherini, Isabella; Gattorno, Marco

    2017-10-18

    Hereditary recurrent fevers (HRF) are a group of rare monogenic diseases leading to recurrent inflammatory flares. A large number of variants has been described for the four genes associated with the best known HRF, namely MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database ( http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry collecting variants reported in these genes. However, no genotype-phenotype associations are provided, but only the clinical phenotype of the first patient(s) described for each mutation. The aim of this study is to develop a registry of genotype-phenotype associations observed in patients with HRF, enrolled and validated in the Eurofever registry. Genotype-phenotype associations observed in all the patients with HRF enrolled in the Eurofever registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and TRAPS), all mutations were individually analyzed. For autosomal recessive diseases (FMF and MKD), homozygous and heterozygous combinations were described. Mean age of onset, disease course (recurrent or chronic), mean duration of fever episodes, clinical manifestations associated with fever episodes, atypical manifestations, complications and response to treatment were also studied. Data observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the Eurofever registry and validated by experts were summarized in Tables. A total of 149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as various combinations of 48 MVK and 28 MEFV variants were available. We provide a potentially useful tool for physicians dealing with HRF, namely a registry of genotype-phenotype associations for patients enrolled in the Eurofever registry. This tool is complementary to the Infevers database and will be available at the Eurofever and Infevers websites.

  20. Evaluation of Cardiovascular Risk Factors and Restless Legs Syndrome in Women and Men: A Preliminary Population-Based Study in China.

    Science.gov (United States)

    Liu, Yuqiong; Liu, Gangqiong; Li, Ling; Yang, Jing; Ma, Shengli

    2018-03-15

    Many studies have investigated the association between restless legs syndrome (RLS) and cardiovascular risk factors, leading to conflicting results. Therefore, the aim of the current study was to determine whether RLS is associated with cardiovascular risk factors and disease. This cross-sectional study included 5,324 consecutive subjects who visited the Physical Examination Center of The First Affiliated Hospital of Zhengzhou University for their yearly routine physical examination. Participants underwent a face-to-face interview with a neurologist for the assessment of RLS, based on the International Restless Legs Study Group criteria. They also completed a questionnaire related to cardiovascular risk factors and other health-related and demographic information. Logistic regression was used to assess which of the demographic and cardiovascular risk factors increased the odds of RLS. Then, unadjusted and adjusted models were designed to determine whether RLS was associated with increased odds of cardiovascular disease, coronary artery disease, or hypertension. RLS was observed in 9.2% of the participants. Multivariable logistic regression models, which included the covariates age, sex, body mass index, smoking status, hypercholesterolemia, and Pittsburgh Sleep Quality Index score (dichotomized at 5), demonstrated that female sex (odds ratio [OR]: 2.42, 95% confidence interval [CI]: 1.99-2.95), smoking (OR: 1.96, 95% CI: 1.31-2.92), high cholesterol (OR: 1.30, 95% CI: 1.03-1.64), and PSQI score > 5 (OR: 5.61, 95% CI: 2.14-14.69) are significantly associated with RLS. Additionally, RLS was associated with hypertension, after adjusting for age, sex, body mass index, smoking, hypercholesterolemia, Pittsburgh Sleep Quality Index score > 5, diabetes, anemia, and decreased renal function. RLS is associated with the prevalence of hypertension but not with that of cardiovascular disease or coronary artery disease. © 2018 American Academy of Sleep Medicine.

  1. Cardiovascular protective properties of incretin-based therapies in type 2 diabetes

    NARCIS (Netherlands)

    Simsek, S.; de Galan, B.E.

    2012-01-01

    PURPOSE OF REVIEW: Type 2 diabetes mellitus is a chronic dysmetabolic condition characterized by hyperglycemia and accompanied by dyslipidemia (low HDL, high triglycerides), and hypertension associated with insulin resistance in obesity. In addition to the glucose-reducing effects, incretin-based

  2. Neonatal Death Dwarfism in a Girl with Distinctive Bone Dysplasia Compatible with Grebe Chondrodysplasia: Analysis by CT Scan-based Phenotype

    OpenAIRE

    Ali Al Kaissi; Farid Ben Chehida; Rudolf Ganger; Franz Grill

    2014-01-01

    We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT) scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (con...

  3. Mobile Phone-Based Lifestyle Intervention for Reducing Overall Cardiovascular Disease Risk in Guangzhou, China: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Zhiting Liu

    2015-12-01

    Full Text Available With the rapid and widespread adoption of mobile devices, mobile phones offer an opportunity to deliver cardiovascular disease (CVD interventions. This study evaluated the efficacy of a mobile phone-based lifestyle intervention aimed at reducing the overall CVD risk at a health management center in Guangzhou, China. We recruited 589 workers from eight work units. Based on a group-randomized design, work units were randomly assigned either to receive the mobile phone-based lifestyle interventions or usual care. The reduction in 10-year CVD risk at 1-year follow-up for the intervention group was not statistically significant (–1.05%, p = 0.096. However, the mean risk increased significantly by 1.77% (p = 0.047 for the control group. The difference of the changes between treatment arms in CVD risk was –2.83% (p = 0.001. In addition, there were statistically significant changes for the intervention group relative to the controls, from baseline to year 1, in systolic blood pressure (–5.55 vs. 6.89 mmHg; p < 0.001, diastolic blood pressure (–6.61 vs. 5.62 mmHg; p < 0.001, total cholesterol (–0.36 vs. –0.10 mmol/L; p = 0.005, fasting plasma glucose (–0.31 vs. 0.02 mmol/L; p < 0.001, BMI (–0.57 vs. 0.29 kg/m2; p < 0.001, and waist hip ratio (–0.02 vs. 0.01; p < 0.001. Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China.

  4. Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

    Science.gov (United States)

    de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

    2018-01-23

    High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  5. Cardiovascular diseases and diabetes

    DEFF Research Database (Denmark)

    Green, A.; Sortso, C.; Jensen, Peter Bjødstrup

    2016-01-01

    We present an investigation of the occurrence of cardiovascular disease in patients with diabetes in Denmark 2000 through 2011. The Diabetes Impact Study 2013 is based on all registrants in the Danish National Diabetes Register as of July 3rd 2013 (n=497,232). Record linkage with the Danish...... National Patient Register was used to defining the first date of experiencing a cardiovascular event by means of a discharge diagnosis and/or having performed a coronary bypass operation or revascularization of the coronary arteries. The proportion of patients with already established CVD at the diagnosis...

  6. MR-based full-body preventative cardiovascular and tumor imaging: technique and preliminary experience

    International Nuclear Information System (INIS)

    Goyen, Mathias; Goehde, Susanne C.; Herborn, Christoph U.; Hunold, Peter; Vogt, Florian M.; Gizewski, Elke R.; Lauenstein, Thomas C.; Ajaj, Waleed; Forsting, Michael; Debatin, Joerg F.; Ruehm, Stefan G.

    2004-01-01

    Recent improvements in hardware and software, lack of side effects, as well as diagnostic accuracy make magnetic resonance imaging a natural candidate for preventative imaging. Thus, the purpose of the study was to evaluate the feasibility of a comprehensive 60-min MR-based screening examination in healthy volunteers and a limited number of patients with known target disease. In ten healthy volunteers (7 men, 3 women; mean age, 32.4 years) and five patients (4 men, 1 woman; mean age, 56.2 years) with proven target disease we evaluated the performance of a comprehensive MR screening strategy by combining well-established organ-based MR examination components encompassing the brain, the arterial system, the heart, the lungs, and the colon. All ten volunteers and five patients tolerated the comprehensive MR examination well. The mean in-room time was 63 min. In one volunteer, insufficient colonic cleansing on the part of the volunteer diminished the diagnostic reliability of MR colonography. All remaining components of the comprehensive MR examination were considered diagnostic in all volunteers and patients. In the five patients, the examination revealed the known pathologies [aneurysm of the anterior communicating artery (n=1), renal artery stenosis (n=1), myocardial infarct (n=1), and colonic polyp (n=2)]. The outlined MR screening strategy encompassing the brain, the arterial system, the heart, the lung, and the colon is feasible. Further studies have to show that MR-based screening programs are cost-effective in terms of the life-years saved. (orig.)

  7. Microalbuminuria and its relation to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals

    DEFF Research Database (Denmark)

    Jensen, J S; Feldt-Rasmussen, B; Borch-Johnsen, K

    1997-01-01

    subjects. The frequency of cardiovascular disease was similar in the two groups. In contrast, when analysed as a continuous variable, a one unit increase in the logarithmically transformed urinary albumin excretion significantly increased the likelihood of cardiovascular disease (odds ratio [95% confidence....... It is concluded that slightly elevated albumin excretion in the urine is not only a pressure-dependent functional phenomenon in the glomerular vessel walls, but associated with permanent atherosclerotic abnormalities in the entire vascular system....

  8. Cardiovascular risk calculation

    African Journals Online (AJOL)

    James A. Ker

    2014-08-20

    Aug 20, 2014 ... smoking and elevated blood sugar levels (diabetes mellitus). These risk ... These are risk charts, e.g. FRS, a non-laboratory-based risk calculation, and ... for hard cardiovascular end-points, such as coronary death, myocardial ...

  9. Cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Graversen, Peter; Abildstrøm, Steen Z.; Jespersen, Lasse

    2016-01-01

    Aim European society of cardiology (ESC) guidelines recommend that cardiovascular disease (CVD) risk stratification in asymptomatic individuals is based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, which estimates individual 10-year risk of death from CVD. We assessed the potential...

  10. Contribution of dietary amino acids composition to incidence of cardiovascular outcomes: A prospective population-based study.

    Science.gov (United States)

    Mirmiran, P; Bahadoran, Z; Ghasemi, A; Azizi, F

    2017-07-01

    Considering the limited data on the cardiovascular effects of dietary amino acid intakes, we assessed possible association of dietary amino acids with the risk of cardiovascular (CVD) events in a prospective population-based study. Participants without CVD (n = 2369) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 6.7 years. Dietary protein and amino acid intakes were assessed at baseline (2006-2008); demographic, lifestyle and biochemical variables were evaluated at baseline and follow-up examination (2012-2014). Multivariate Cox proportional hazard regression models, adjusted for potential confounders, were used to estimate risk of CVD across tertiles of dietary amino acids. Mean total protein intake was 76.9 ± 27.5 g/d, and dietary protein had no significant association with the risk of CVD (HR = 1.23, 95% CI = 0.65-2.31, and HR = 0.52, 95% CI = 0.19-1.41, in the second and third tertiles, respectively). After adjustment of potential confounders, the amino acid pattern with higher load of glycine, cysteine, arginine and tryptophan, was negatively associated with CVD (HR = 0.28, 95% CI = 0.09-0.88, P for trend = 0.08). Higher intake of sulfur-containing amino acids (cysteine and methionine), and potentially cardioprotective amino acids (arginine, cysteine, glutamic acid, glycine, histidine, leucine and tyrosine) corresponded to 73% (HR = 0.27, 95% CI = 0.09-0.86) and 74% (HR = 0.26, 95% CI = 0.09-0.78) decreased risk of CVD events. Higher intake of glutamic acid and proline (% of dietary total protein) increased the risk of CVD (HR = 1.30, 95% CI = 1.03-1.64, and HR = 1.33, 95% CI = 1.10-1.60, respectively). These novel data provide evidence to suggest that amino acid composition of diet may modify the risk of CVD events. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of

  11. Life course socioeconomic position, alcohol drinking patterns in midlife, and cardiovascular mortality: Analysis of Norwegian population-based health surveys.

    Directory of Open Access Journals (Sweden)

    Eirik Degerud

    2018-01-01

    Full Text Available Socioeconomically disadvantaged groups tend to experience more harm from the same level of exposure to alcohol as advantaged groups. Alcohol has multiple biological effects on the cardiovascular system, both potentially harmful and protective. We investigated whether the diverging relationships between alcohol drinking patterns and cardiovascular disease (CVD mortality differed by life course socioeconomic position (SEP.From 3 cohorts (the Counties Studies, the Cohort of Norway, and the Age 40 Program, 1987-2003 containing data from population-based cardiovascular health surveys in Norway, we included participants with self-reported information on alcohol consumption frequency (n = 207,394 and binge drinking episodes (≥5 units per occasion, n = 32,616. We also used data from national registries obtained by linkage. Hazard ratio (HR with 95% confidence intervals (CIs for CVD mortality was estimated using Cox models, including alcohol, life course SEP, age, gender, smoking, physical activity, body mass index (BMI, systolic blood pressure, heart rate, triglycerides, diabetes, history of CVD, and family history of coronary heart disease (CHD. Analyses were performed in the overall sample and stratified by high, middle, and low strata of life course SEP. A total of 8,435 CVD deaths occurred during the mean 17 years of follow-up. Compared to infrequent consumption (

  12. Cardiovascular system

    International Nuclear Information System (INIS)

    Soulen, R.L.; Grosh, J.

    1984-01-01

    Invasive cardiovascular diagnostic procedures involve a finite risk and therefore can be recommended only when the benefit appears to exceed the risk by a substantial margin. The risk/benefit ratio varies not only with the procedure concerned but with the status of the vascular system, concomitant diseases, and the risks of both the suspected illness and its treatment. The risks inherent in the procedures per se are detailed in the sections to follow

  13. (1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors.

    Science.gov (United States)

    Vázquez-Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez, Miguel Ángel; Vinaixa, Maria; Chiva-Blanch, Gemma; Estruch, Ramon; Correig, Xavier; Andrés-Lacueva, Cristina

    2012-08-01

    Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24-h urine samples were collected and analyzed by (1) H-NMR. According to the results of a one-way ANOVA, significant markers were grouped in four categories: alcohol-related markers (ethanol); gin-related markers; wine-related markers; and gut microbiota markers (hippurate and 4-hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched-chain amino acid (BCAA) metabolite (3-methyl-oxovalerate). Additionally, a possible interaction between alcohol and gut-related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Epidemiology of cardiovascular malformations among newborns in Monchegorsk (north-west Russia: a register-based study

    Directory of Open Access Journals (Sweden)

    Vitaly A. Postoev

    2014-08-01

    Full Text Available Background. Cardiovascular malformations (CVM are one of the most prevalent groups of birth defects. Knowledge about the prevalence, distribution and survival in Russia has been limited. The aim of our study was to assess the perinatal prevalence, structure and risk factors for CVM among newborns in Monchegorsk (Murmansk Oblast, Russia and the mortality among the affected newborns in the period 1973-2008. Design and methods. A register-based study on data from the Kola and Murmansk County Birth Registers. The study included 28,511 births. Results. The registered perinatal prevalence was 3.0 per 1000 newborns, with septal defects as the most prevalent. CVM was twenty times more prevalent among stillborn than live born, and one-third of the live born with a CVM died during the first week of life. The perinatal mortality rate with CVM was 442 per 1000 newborns. This indicator decreased over time. The mothers of newborns with a CVM were ten times more likely to have stillbirth in their anamnesis. The adjusted odds ratio between maternal smoking during pregnancy and CVM was 4.09 [95% confidence interval: 1.75-9.53]. Conclusions. The diagnosed perinatal prevalence was relatively low. A previous stillbirth by the mother was highly associated with being born with a CVM. An adjusted elevated risk was also observed among smoking mothers. Perinatal survival increased over time, but varied to a large extent between the different types of CVM.

  15. Optimization of cardiovascular stent against restenosis: factorial design-based statistical analysis of polymer coating conditions.

    Directory of Open Access Journals (Sweden)

    Gayathri Acharya

    Full Text Available The objective of this study was to optimize the physicodynamic conditions of polymeric system as a coating substrate for drug eluting stents against restenosis. As Nitric Oxide (NO has multifunctional activities, such as regulating blood flow and pressure, and influencing thrombus formation, a continuous and spatiotemporal delivery of NO loaded in the polymer based nanoparticles could be a viable option to reduce and prevent restenosis. To identify the most suitable carrier for S-Nitrosoglutathione (GSNO, a NO prodrug, stents were coated with various polymers, such as poly (lactic-co-glycolic acid (PLGA, polyethylene glycol (PEG and polycaprolactone (PCL, using solvent evaporation technique. Full factorial design was used to evaluate the effects of the formulation variables in polymer-based stent coatings on the GSNO release rate and weight loss rate. The least square regression model was used for data analysis in the optimization process. The polymer-coated stents were further assessed with Differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy analysis (FTIR, Scanning electron microscopy (SEM images and platelet adhesion studies. Stents coated with PCL matrix displayed more sustained and controlled drug release profiles than those coated with PLGA and PEG. Stents coated with PCL matrix showed the least platelet adhesion rate. Subsequently, stents coated with PCL matrix were subjected to the further optimization processes for improvement of surface morphology and enhancement of the drug release duration. The results of this study demonstrated that PCL matrix containing GSNO is a promising system for stent surface coating against restenosis.

  16. Accordance to the Dietary Approaches to Stop Hypertension diet pattern and cardiovascular disease in a British, population-based cohort.

    Science.gov (United States)

    Jones, Nicholas R V; Forouhi, Nita G; Khaw, Kay-Tee; Wareham, Nicholas J; Monsivais, Pablo

    2018-02-01

    The dietary approaches to stop hypertension (DASH) diet could be an important population-level strategy to reduce cardiovascular disease (CVD) in the UK, but there is little UK-based evidence on this diet pattern in relation to CVD risk. We tested whether dietary accordance with DASH was associated with risk of CVD in a population-based sample of 23,655 UK adults. This prospective analysis of the EPIC-Norfolk cohort study analysed dietary intake (assessed using a validated food frequency questionnaire) to measure accordance with DASH, based on intakes of eight food groups and nutrients, ranking the sample into quintiles. Cox proportional hazards regression models tested for association between DASH accordance and incident stroke, ischemic heart disease (IHD) and total incident CVD (stroke and IHD only), as well as CVD mortality, non-CVD mortality and total mortality. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated adjusting for age, sex, behavioral and clinical risk factors and socioeconomic status. Over an average of 12.4 years follow-up, we ascertained 4129 incident CVD events, of which stroke accounted for 1011. Compared to participants with the least DASH-accordant diets, those with the most DASH-accordant diets had 20% lower risk of incident stroke (HR, 95% CI 0.80, 0.65-0.99) and 13% lower risk of total incident CVD (0.88, 0.79-0.99) but no lower risk of CHD (0.90, 0.79-1.02). CVD-related mortality also showed strong inverse associations with DASH accordance (0.72, 0.60-0.85). This study provides evidence for the cardioprotective effects of DASH diet in a UK context.

  17. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    Science.gov (United States)

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-09-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

  18. Population-based intervention for cardiovascular diseases related knowledge and behaviours in Asian Indian women.

    Science.gov (United States)

    Pandey, Ravindra Mohan; Agrawal, Aachu; Misra, Anoop; Vikram, Naval Kishore; Misra, Puneet; Dey, Sanjit; Rao, Shobha; Vasantha Devi, K P; Usha Menon, V; Revathi, R; Sharma, Vinita; Gupta, Rajeev

    2013-01-01

    There is poor knowledge and behaviors regarding chronic diseases related nutritional and lifestyle factors among women in low income countries. To evaluate efficacy of a multilevel population-based intervention in improving knowledge and practices for related factors we performed a study in India. Population based study among women 35-70 years was performed in four urban and five rural locations. Stratified sampling was performed and we enrolled 4624 (rural 2616, urban 2008) of eligible 8000 women (58%). Demographic details, medical history, diet, physical activity and anthropometry were recorded and blood hemoglobin, glucose and total cholesterol determined. Knowledge and behaviors regarding diet in chronic diseases were inquired in a randomly selected 100 women at each site (n = 900). A systematic multilevel population based intervention (using posters, handouts, street plays, public lectures, group lectures and focused group discussions) was administered over 6 months at each site. The questionnaire was re-administered at the end in random 100 women (n = 900) and differences determined. Descriptive statistics are reported. Comparison of parameters before and after intervention was assessed using Mann Whitney test. Prevalence (%) of chronic disease related lifestyles and risk factors in rural/urban women, respectively, was illiteracy in 63.6/29.4, smoking/tobacco use 39.3/18.9, high fat intake 93.6/93.4, high salt intake 18.2/12.6, low physical activity 59.5/70.2, overweight/obesity 22.5/45.6, truncal obesity 13.0/44.3, hypertension 31.6/48.2, hypercholesterolemia 13.5/27.7, and diabetes in 4.3/15.1 percent. Composite chronic diseases knowledge at baseline vs after intervention increased significantly in overall (32.0 vs 62.0), rural (29.0 vs 63.5) and urban (39.5 vs 60.5) groups (p women in rural and urban locations in India increased chronic disease knowledge but failed to influence practices. Copyright © 2013. Published by Elsevier B.V.

  19. Liquid pressure wireless sensor based on magnetostrictive microwires for applications in cardiovascular localized diagnostic

    Directory of Open Access Journals (Sweden)

    A. M. Aragón

    2015-08-01

    Full Text Available In this letter, we report a method to measure changes in a fluid pressure, flowing through a flexible pipeline, by means of a ring of magnetic microwire concentric to the pipeline. The detection is based on the modulated scattering of electromagnetic waves by the magnetoelastic ring. This modulation is driven by applying a low frequency bias magnetic field able to tune the magnetic permeability of the ferromagnetic microwire. Pressure detection, by means of magnetic permeability changes, is possible due to the magnetostrictive character of the sample. The experimental work developed has, also, allowed fluid pressure detection in a hydraulic circuit connected to ventricular assist system where a fluid with a viscosity close to blood flows.

  20. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data.

    Science.gov (United States)

    2014-08-16

    We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy. This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (21%). 11 trials and 26 randomised groups met the inclusion criteria, and included 67,475 individuals, of whom 51,917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4·0 years (IQR 3·4-4·4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6·0% (SD 2·0), 12·1% (1·5), 17·7% (1·7), and 26·8% (5·4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p=0·30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61) cardiovascular events, respectively (p=0·04 for trend). Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular

  1. Pro-angiogenic cell-based therapy for the treatment of ischemic cardiovascular diseases.

    Science.gov (United States)

    Silvestre, Jean-Sébastien

    2012-10-01

    Pro-angiogenic cell therapy has emerged as a promising option to treat patients with acute myocardial infarction or with critical limb ischemia. Exciting pre-clinical studies have prompted the initiation of numerous clinical trials based on administration of stem/progenitor cells with pro-angiogenic potential. Most of the clinical studies performed so far have used bone marrow-derived or peripheral blood-derived mononuclear cells and showed, overall, a modest but significant benefit on tissue remodeling and function in patients with ischemic diseases. These mixed results pave the way for the development of strategies to overcome the limitation of autologous cell therapy and to propose more efficient approaches. Such strategies include pretreatment of cells with activators to augment cell recruitment and survival in the ischemic target area and/or the improvement of cell functions such as their paracrine ability to release proangiogenic factors and vasoactive molecules. In addition, efforts should be directed towards stimulation of both angiogenesis and vessel maturation, the development of a composite product consisting of stem/progenitor cells encapsulated in a biomaterial and the use of additional sources of regenerative cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Cost-effectiveness analysis of population-based tobacco control strategies in the prevention of cardiovascular diseases in Tanzania.

    Directory of Open Access Journals (Sweden)

    Frida Ngalesoni

    Full Text Available Tobacco consumption contributes significantly to the global burden of disease. The prevalence of smoking is estimated to be increasing in many low-income countries, including Tanzania, especially among women and youth. Even so, the implementation of tobacco control measures has been discouraging in the country. Efforts to foster investment in tobacco control are hindered by lack of evidence on what works and at what cost.We aim to estimate the cost and cost-effectiveness of population-based tobacco control strategies in the prevention of cardiovascular diseases (CVD in Tanzania.A cost-effectiveness analysis was performed using an Excel-based Markov model, from a governmental perspective. We employed an ingredient approach and step-down methodologies in the costing exercise following a government perspective. Epidemiological data and efficacy inputs were derived from the literature. We used disability-adjusted life years (DALYs averted as the outcome measure. A probabilistic sensitivity analysis was carried out with Ersatz to incorporate uncertainties in the model parameters.Our model results showed that all five tobacco control strategies were very cost-effective since they fell below the ceiling ratio of one GDP per capita suggested by the WHO. Increase in tobacco taxes was the most cost-effective strategy, while a workplace smoking ban was the least cost-effective option, with a cost-effectiveness ratio of US$5 and US$267, respectively.Even though all five interventions are deemed very cost-effective in the prevention of CVD in Tanzania, more research on budget impact analysis is required to further assess the government's ability to implement these interventions.

  3. Effects of music on cardiovascular responses in men with essential hypertension compared with healthy men based on introversion and extraversion.

    Science.gov (United States)

    Namdar, Hossein; Taban Sadeghi, Mohammadreza; Sabourimoghaddam, Hassan; Sadeghi, Babak; Ezzati, Davoud

    2014-01-01

    The present research investigated the effects of two different types of music on cardiovascular responses in essential hypertensive men in comparison with healthy men based on introversion and extraversion. One hundred and thirteen hypertensive men referred to Madani Heart Hospital in Tabriz completed the NEO-FFI Questionnaire and after obtaining acceptable scores were classified in four groups: introvert patients, extravert patients, introvert healthy subjects, and extravert healthy subjects (each group with 25 samples with age range 31-50). Baseline blood pressure and heart rate of each subject was recorded without any stimulus. Then subjects were exposed to slow-beat music and blood pressure and heart rate were recorded. After15 minute break, and a little cognitive task for distraction, subjects were exposed to fast-beat music and blood pressure and heart rate were recorded again. Multivariate analysis of covariance (MANCOVA) test showed that extravert patient subjects obtained greater reduction in systolic blood pressure and heart rate after presenting slow-beat music compared with introvert patients (P= 0.035, and P= 0.033 respectively). And extravert healthy subjects obtained greater reduction in heart rate after presenting slow-beat music compared with introvert healthy subjects (P= 0.036). However, there are no significant differences between introvert and extravert groups in systolic and diastolic blood pressure and heart rate after presenting fast-beat music. Based on our results, introvert subjects experience negative emotions more than extravert subjects and negative emotions cause less change in blood pressure in these subjects compared with extravert subjects.

  4. Effects of Music on Cardiovascular Responses in Men with Essential Hypertension Compared with Healthy Men Based on Introversion and Extraversion

    Directory of Open Access Journals (Sweden)

    Hossein Namdar

    2014-10-01

    Full Text Available Introduction: The present research investigated the effects of two different types of music on cardiovascular responses in essential hypertensive men in comparison with healthy men based on introversion and extraversion. Methods: One hundred and thirteen hypertensive men referred to Madani Heart Hospital in Tabriz completed the NEO-FFI Questionnaire and after obtaining acceptable scores were classified in four groups: introvert patients, extravert patients, introvert healthy subjects, and extravert healthy subjects (each group with 25 samples with age range 31-50. Baseline blood pressure and heart rate of each subject was recorded without any stimulus. Then subjects were exposed to slow-beat music and blood pressure and heart rate were recorded. After15 minute break, and a little cognitive task for distraction, subjects were exposed to fast-beat music and blood pressure and heart rate were recorded again. Results: Multivariate analysis of covariance (MANCOVA test showed that extravert patient subjects obtained greater reduction in systolic blood pressure and heart rate after presenting slow-beat music compared with introvert patients (P= 0.035, and P= 0.033 respectively. And extravert healthy subjects obtained greater reduction in heart rate after presenting slow-beat music compared with introvert healthy subjects (P= 0.036. However, there are no significant differences between introvert and extravert groups in systolic and diastolic blood pressure and heart rate after presenting fast-beat music. Conclusion: Based on our results, introvert subjects experience negative emotions more than extravert subjects and negative emotions cause less change in blood pressure in these subjects compared with extravert subjects.

  5. Prevalence of arterial stiffness in North China, and associations with risk factors of cardiovascular disease: a community-based study

    Directory of Open Access Journals (Sweden)

    Wang Jin-Wen

    2012-12-01

    Full Text Available Abstract Background Brachial-ankle pulse wave velocity (baPWV, which reflects the stiffness of both central and peripheral muscular arteries, has been frequently used as a simple index for assessing arterial stiffness. The aim of the present study was to investigate the prevalence of arterial stiffness in North China based on baPWV measurements, and explore the associations between increased arterial stiffness and risk factors of cardiovascular diseases (CVD. Methods Twenty-three community populations were established in North China. For each participant, parameters for calculating baPWV, including blood pressures and pressure waveforms, were measured using a non-invasive automatic device. All participants were required to respond to an interviewer-led questionnaire including medical histories and demographic data, and to receive blood tests on biochemical indictors. Results A total of 2,852 participants were finally investigated. Among them, 1,201 people with low burden of CVD risk factors were chosen to be the healthy reference sample. The cut-off point of high baPWV was defined as age-specific 90th percentile of the reference sample. Thus, the prevalence of high baPWV was found to be 22.3% and 26.4% in men and women respectively. After adjusted for age, heart rate (HR, systolic blood pressure (SBP, fasting glucose level, and smoking were significantly associated with high baPWV in men; while level of serum total cholesterol (TC, HR, SBP, and diabetes were significantly associated with high baPWV in women. Conclusions Based on the age-specific cut-off points, the middle-aged population has a higher prevalence of high baPWV in North China. There exists a difference between men and women in terms of the potential risk factors associated with arterial stiffness.

  6. A Simulation-Based Program to Train Medical Residents to Lead and Perform Advanced Cardiovascular Life Support

    Science.gov (United States)

    Stefan, Mihaela S.; Belforti, Raquel K.; Langlois, Gerard; Rothberg, Michael B.

    2014-01-01

    Background Medical residents are often responsible for leading and performing cardiopulmonary resuscitation; however, their levels of expertise and comfort as leaders of advanced cardiovascular life support (ACLS) teams vary widely. While the current American Heart Association ACLS course provides education in recommended resuscitative protocols, training in leadership skills is insufficient. In this article, we describe the design and implementation in our institution of a formative curriculum aimed at improving residents’ readiness for being leaders of ACLS teams using human patient simulation. Human patient simulation refers to a variety of technologies using mannequins with realistic features, which allows learners to practice through scenarios without putting patients at risk. We discuss the limitations of the program and the challenges encountered in implementation. We also provide a description of the initiation and organization of the program. Case scenarios and assessment tools are provided. Description of the Institutional Training Program Our simulation-based training curriculum consists of 8 simulated patient scenarios during four 1-hour sessions. Postgraduate year–2 and 3 internal medicine residents participate in this program in teams of 4. Assessment tools are utilized only for formative evaluation. Debriefing is used as a teaching strategy for the individual resident leader of the ACLS team to facilitate learning and improve performance. To evaluate the impact of the curriculum, we administered a survey before and after the intervention. The survey consisted of 10 questions answered on a 5-point Likert scale, which addressed residents’ confidence in leading ACLS teams, management of the equipment, and management of cardiac rhythms. Respondents’ mean presimulation (ie, baseline) and postsimulation (outcome) scores were compared using a 2-sample t test. Residents’ overall confidence score improved from 2.8 to 3.9 (P simulation-based training

  7. Temporal trends in cardiovascular disease risk factors among white, South Asian, Chinese and black groups in Ontario, Canada, 2001 to 2012: a population-based study.

    Science.gov (United States)

    Chiu, Maria; Maclagan, Laura C; Tu, Jack V; Shah, Baiju R

    2015-08-10

    To determine ethnic-specific temporal trends in cardiovascular risk factors in Ontario between 2001 and 2012. A population-based repeated cross-sectional study. Ontario, Canada. 219,276 participants of the Canadian Community Health Survey (205,326 white, 5620 South Asian, 4368 Chinese and 3962 black) during the period 2001 to 2012. Age-standardised ethnic-sex-specific prevalence of cardiovascular risk factors for three time periods: 2001-2004, 2005-2008 and 2009-2012 among Canada's four major ethnic groups: white, South Asian, Chinese and black. During the study period, the prevalence of diabetes increased 2.3-fold (p = 0.0001) among South Asian males and 1.9-fold (p = 0.02) among black females. The prevalence of obesity (body mass index ≥ 30 kg/m(2)) increased over time across all ethnic groups, with the largest relative increases observed among males of Chinese (2.1-fold increase, p = 0.04) and black (1.7-fold increase, p = 0.06) descent. The prevalence of hypertension increased the most among black females. Smoking prevalence decreased by more than 20% among South Asian, Chinese and white females. Overall, South Asian males and black males and females showed the greatest declines in cardiovascular health over the study period. We observed important ethnic differences in the temporal trends in cardiovascular risk factor profiles in Ontario. Awareness of the direction and magnitude of these risk factor trends may be useful in informing targeted strategies for preventing cardiovascular diseases in multiethnic populations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases.

    Directory of Open Access Journals (Sweden)

    Ronan Roussel

    Full Text Available According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk.Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09 with a follow-up of up to 30 months.Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and > 50 (men or 60 (women, but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death.Of the 31,652 patients enrolled, 4,058 (12.8% received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates and 2.21% (statins. The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR 540 of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR 540 = 1.73 (1.28-2.32.Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.

  9. Dietary patterns and all-cause, cancer, and cardiovascular disease mortality in Japanese men and women: The Japan public health center-based prospective study.

    Directory of Open Access Journals (Sweden)

    Akiko Nanri

    Full Text Available A meta-analysis showed an inverse association of a prudent/healthy dietary pattern with all-cause mortality and no association of a western/unhealthy dietary pattern. However, the association of distinctive dietary patterns of Japanese population with mortality remains unclear. We prospectively investigated the association between dietary patterns and all-cause, cancer, and cardiovascular disease mortality among Japanese adults.Participants were 36,737 men and 44,983 women aged 45-74 years who participated in the second survey of the Japan Public Health Center-based Prospective Study (1995-1998 and who had no history of serious disease. Dietary patterns were derived from principal component analysis of the consumption of 134 food and beverage items ascertained by a food frequency questionnaire. Hazard ratios of death from the second survey to December 2012 were estimated using cox proportional hazard regression analysis.A prudent dietary pattern, which was characterized by high intake of vegetables, fruit, soy products, potatoes, seaweed, mushrooms, and fish, was significantly associated with decreased risk of all-cause and cardiovascular disease mortality. The multivariable-adjusted hazard ratios (95% confidence intervals of all-cause and cardiovascular disease mortality for the highest versus lowest quartile of the prudent dietary pattern score were 0.82 (0.77 to 0.86 and 0.72 (0.64 to 0.79, respectively (P for trend <0.001 in both. A Westernized dietary pattern, characterized by high intake of meat, processed meat, bread, and dairy products, was also inversely associated with risk of all-cause, cancer, and cardiovascular disease mortality. A traditional Japanese dietary pattern was not associated with these risks.The prudent and Westernized dietary patterns were associated with a decreased risk of all-cause and cardiovascular disease mortality in Japanese adults.

  10. BreedVision — A Multi-Sensor Platform for Non-Destructive Field-Based Phenotyping in Plant Breeding

    Science.gov (United States)

    Busemeyer, Lucas; Mentrup, Daniel; Möller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans Peter; Reif, Jochen C.; Würschum, Tobias; Müller, Joachim; Rahe, Florian; Ruckelshausen, Arno

    2013-01-01

    To achieve the food and energy security of an increasing World population likely to exceed nine billion by 2050 represents a major challenge for plant breeding. Our ability to measure traits under field conditions has improved little over the last decades and currently constitutes a major bottleneck in crop improvement. This work describes the development of a tractor-pulled multi-sensor phenotyping platform for small grain cereals with a focus on the technological development of the system. Various optical sensors like light curtain imaging, 3D Time-of-Flight cameras, laser distance sensors, hyperspectral imaging as well as color imaging are integrated into the system to collect spectral and morphological information of the plants. The study specifies: the mechanical design, the system architecture for data collection and data processing, the phenotyping procedure of the integrated system, results from field trials for data quality evaluation, as well as calibration results for plant height determination as a quantified example for a platform application. Repeated measurements were taken at three developmental stages of the plants in the years 2011 and 2012 employing triticale (×Triticosecale Wittmack L.) as a model species. The technical repeatability of measurement results was high for nearly all different types of sensors which confirmed the high suitability of the platform under field conditions. The developed platform constitutes a robust basis for the development and calibration of further sensor and multi-sensor fusion models to measure various agronomic traits like plant moisture content, lodging, tiller density or biomass yield, and thus, represents a major step towards widening the bottleneck of non-destructive phenotyping for crop improvement and plant genetic studies. PMID:23447014

  11. Genotyping using whole-genome sequencing is a realistic alternative to surveillance based on phenotypic antimicrobial susceptibility testing

    DEFF Research Database (Denmark)

    Zankari, Ea; Hasman, Henrik; Kaas, Rolf Sommer

    2013-01-01

    -genome sequencing (WGS) may soon be within reach even for routine surveillance and clinical diagnostics. The aim of this study was to evaluate WGS as a routine tool for surveillance of antimicrobial resistance compared with current phenotypic procedures. Methods: Antimicrobial susceptibility tests were performed...... to the categorizing of isolates as resistant and 2569 as susceptible. Seven cases of disagreement between tested and predicted susceptibility were observed, six of which were related to spectinomycin resistance in Escherichia coli. Correlation between MLST type and resistance profiles was only observed in Salmonella...

  12. GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm

    DEFF Research Database (Denmark)

    Bottolo, Leonardo; Chadeau-Hyam, Marc; Hastie, David I

    2013-01-01

    Genome-wide association studies (GWAS) yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-phe...... of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic groups, which were overlooked in the larger meta-GWAS and not revealed by competing approaches, associations that we replicated in two independent cohorts. Moreover, we demonstrated the increased power of GUESS over alternative multi...

  13. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis

    OpenAIRE

    Jardine, Meg J; Kang, Amy; Zoungas, Sophia; Navaneethan, Sankar D; Ninomiya, Toshiharu; Nigwekar, Sagar U; Gallagher, Martin P; Cass, Alan; Strippoli, Giovanni; Perkovic, Vlado

    2012-01-01

    Objective To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease. Design Systematic review and meta-analysis. Data sources Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011. Study selection Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and a...

  14. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

    Science.gov (United States)

    Sundström, Johan; Hedberg, Jakob; Thuresson, Marcus; Aarskog, Pernilla; Johannesen, Kasper Munk; Oldgren, Jonas

    2017-09-26

    There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal. © 2017 American Heart Association, Inc.

  15. Cardiovascular health: associations with race-ethnicity, nativity, and education in a diverse, population-based sample of Californians.

    Science.gov (United States)

    Bostean, Georgiana; Roberts, Christian K; Crespi, Catherine M; Prelip, Michael; Peters, Anne; Belin, Thomas R; McCarthy, William J

    2013-07-01

    This study examined how race-ethnicity, nativity, and education interact to influence disparities in cardiovascular (CV) health, a new concept defined by the American Heart Association. We assessed whether race-ethnicity and nativity disparities in CV health vary by education and whether the foreign-born differ in CV health from their U.S.-born race-ethnic counterparts with comparable education. We used data from the 2009 California Health Interview Survey to determine the prevalence of optimal CV health metrics (based on selected American Heart Association guidelines) among adults ages 25 and older (n = 42,014). We examined the interaction between education and ethnicity-nativity, comparing predicted probabilities of each CV health measure between U.S.-born and foreign-born White, Asian, and Latino respondents. All groups were at high risk of suboptimal physical activity levels, fruit and vegetable and fast food consumption, and overweight/obesity. Those with greater education were generally better off except among Asian respondents. Ethnicity-nativity differences were more pronounced among those with less than a college degree. The foreign-born respondents exhibited both advantages and disadvantages in CV health compared with their U.S.-born counterparts that varied by ethnicity-nativity. Education influences ethnicity-nativity disparities in CV health, with most race-ethnic and nativity differences occurring among the less educated. Studies of nativity differences in CV health should stratify by education in order to adequately address SES differences. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Prevalence of hypertension and associated cardiovascular risk factors in an urban slum in Nairobi, Kenya: a population-based survey.

    Science.gov (United States)

    Joshi, Mark David; Ayah, Richard; Njau, Elijah Kaharo; Wanjiru, Rosemary; Kayima, Joshua Kyateesa; Njeru, Erastus Kennedy; Mutai, Kenneth Kipyegon

    2014-11-18

    Urbanisation has been described as a key driver of the evolving non-communicable disease (NCD) epidemic. In Africa, hypertension is the commonest cardiovascular problem. We determined the prevalence and risk factor correlates of hypertension in the largest Nairobi slum. In 2010 we conducted a population-based household survey in Kibera, a large informal settlement in Nairobi City; utilising cluster sampling with probability proportional to size. Households were selected using a random walk method. The WHO instrument for stepwise surveillance (STEPS) of chronic disease risk factors was administered by trained medical assistants, who also recorded blood pressure (BP) and anthropometric measures. BP was recorded using a mercury sphygmomanometer utilising the American Heart Association guidelines. Hypertension was defined as per the 7th Report of the Joint National Committee or use of prescribed antihypertensive medication. Those with hypertension or with random capillary blood sugar (RCBS) >11.1 mmol/l had an 8 hours fasting venous blood sugar sample drawn. Age standardised prevalence was computed and multivariate analysis to assess associations. We screened 2200 and enrolled 2061 adults; 50.9% were males; mean age was 33.4 years and 87% had primary level education. The age-standardised prevalence of hypertension (95% CI) was 22.8% (20.7, 24.9). 20% (53/258) were aware of their hypertensive status; 59.3% had pre-hypertension; 80% reported high levels of physical activity and 52% were classified as harmful alcohol drinkers; 10% were current smokers and 5% had diabetes. Majority of males had normal BMI and waist circumference, whereas a third of females were obese or overweight and 40% had central obesity. Older age, higher general and central obesity were independently associated with hypertension and higher SBP and DBP readings. Our findings of high prevalence of hypertension, in association with excess body weight in this poor urban slum community, point to the need

  17. Effect of goal attainment theory based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: Randomized study.

    Science.gov (United States)

    Park, Moonkyoung; Song, Rhayun; Jeong, Jin-Ok

    2017-06-01

    Effect of goal-attainment-theory-based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: randomized study BACKGROUND: The behavioral modification strategies should be explored at the time of admission to lead the maximum effect of cardiovascular risk management. This randomized study aimed to elucidate the effects of a nurse-led theory-based education program in individuals with a first episode of acute myocardial infarction on cardiovascular risks, health behaviors, and quality of life over 6 months. The study involved a convenience sample of 64 patients with acute myocardial infarction who were randomly assigned to either the education group or the control group. The goal-attainment-based education program was designed to set the mutually agreed goals of risk management and the behavioral modification strategies for achieving those goals. Those in the control group received routine management only. The participants in both groups were contacted at 6-8 weeks and at 6 months after discharge to measure outcome variables. Repeated measure ANOVA was conducted using SPSSWIN (version 20.0) to determine the significance of differences in outcome variables over 6 months between the groups. Both groups showed significant positive changes in cardiovascular risks, health behaviors, and quality of life over 6 months. The 2-year risk of cardiovascular disease was significantly reduced in both study groups, but with no significant interaction effect (F=2.01, p=0.142). The performance and maintenance of health behaviors (F=3.75, p=0.029) and the mental component of quality of life (F=4.03, p=0.020) were significantly better in the education group than the control group. Applying a goal-oriented education program at an early stage of hospital management improved and maintained blood glucose, health behaviors, and mental component of the quality of life up to six months in

  18. Caracterización mecánica de materiales de base colágeno para aplicaciones cardiovasculares

    OpenAIRE

    Tobaruela Arnedo, María de la Almudena

    2016-01-01

    Las enfermedades cardiovasculares son una de las principales causas de muerte en el mundo. Este hecho ha propiciado que numerosas investigaciones se hayan centrado en la mejora de las prótesis cardiovasculares ya existentes así como en la búsqueda de nuevos materiales más resistentes, duraderos y biocompatibles. Actualmente, existen dos tipos principales de prótesis valvulares: las mecánicas y las biológicas. En muchos países cada vez es más frecuente el uso de estas últimas. Las válvulas bio...

  19. Community Engagement to Optimize the Use of Web-Based and Wearable Technology in a Cardiovascular Health and Needs Assessment Study: A Mixed Methods Approach.

    Science.gov (United States)

    Yingling, Leah R; Brooks, Alyssa T; Wallen, Gwenyth R; Peters-Lawrence, Marlene; McClurkin, Michael; Cooper-McCann, Rebecca; Wiley, Kenneth L; Mitchell, Valerie; Saygbe, Johnetta N; Johnson, Twanda D; Curry, Rev Kendrick E; Johnson, Allan A; Graham, Avis P; Graham, Lennox A; Powell-Wiley, Tiffany M

    2016-04-25

    Resource-limited communities in Washington, D.C. have high rates of obesity-related cardiovascular disease in addition to inadequate physical activity (PA) facilities and limited Internet access. Engaging community members in the design and implementation of studies to address these health disparities is essential to the success of community-based PA interventions. The objective of the study was to use qualitative and quantitative methods to evaluate the feasibility and acceptability of PA-monitoring wristbands and Web-based technology by predominantly African American, church-based populations in resource-limited Washington, D.C. neighborhoods. To address cardiovascular health in at-risk populations in Washington, D.C., we joined community leaders to establish a community advisory board, the D.C. Cardiovascular Health and Obesity Collaborative (D.C. CHOC). As their first initiative, the Washington, D.C. Cardiovascular Health and Needs Assessment intends to evaluate cardiovascular health, social determinants of health, and PA-monitoring technologies. At the recommendation of D.C. CHOC members, we conducted a focus group and piloted the proposed PA-monitoring system with community members representing churches that would be targeted by the Cardiovascular Health and Needs Assessment. Participants (n=8) agreed to wear a PA-monitoring wristband for two weeks and to log cardiovascular health factors on a secure Internet account. Wristbands collected accelerometer-based data that participants uploaded to a wireless hub at their church. Participants agreed to return after two weeks to participate in a moderated focus group to share experiences using this technology. Feasibility was measured by Internet account usage, wristband utilization, and objective PA data. Acceptability was evaluated through thematic analysis of verbatim focus group transcripts. Study participants (5 males, 3 females) were African American and age 28-70 years. Participant wristbands recorded data on

  20. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    Science.gov (United States)

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  1. From volume to value? Can a value-based approach help deliver the ambitious aims of the NHS cardiovascular disease outcomes strategy?

    Science.gov (United States)

    Dunbar-Rees, Rupert; Panch, Trishan; Dancy, Mark

    2014-06-01

    The last year has seen the publication of two papers which will radically shape the future organisation of healthcare in general, and cardiovascular disease in particular: Cardiovascular Outcomes Strategy (Department of Health) and The Strategy That Will Fix Healthcare (Harvard Business Review). Both publications set out a health delivery mechanism based around improvement of outcomes for groups of patients with similar needs. Instead of organising care around disease categories, it is proposed that the cardiovascular diseases are treated as a single family of diseases. We are reaching the limits of what an activity-based system organised around existing provider structures can sustainably deliver. Unless we find delivery systems which reduce costs while at the same time improving outcomes that are meaningful to patients, then we will be faced with a future of healthcare rationing. The increasing burden of chronic disease and ongoing quality concerns in delivery systems has created a 'burning platform', which must be addressed if we are to maintain a system which offers high-quality care free at the point of delivery. This paper explores what an outcomes and value-based system could look like when applied to cardiovascular disease. It explores what it means for providers and patients if we start to think about outcomes by patients with similar needs, rather than by intervention, or by clinical specialty. As a specific example, the paper explores the features of an Integrated Circulation Service, what the challenges and implications might be, and whether there is any evidence that this would deliver improved outcomes, at a lower cost to the system.

  2. Nutrition and cardiovascular health.

    Science.gov (United States)

    Berciano, Silvia; Ordovás, José M

    2014-09-01

    A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  3. Blood pressure-lowering treatment based on cardiovascular risk : a meta-analysis of individual patient data

    NARCIS (Netherlands)

    Sundström, Johan; Arima, Hisatomi; Woodward, Mark; Jackson, Rod; Karmali, Kunal; Lloyd-Jones, Donald; Baigent, Colin; Emberson, Jonathan; Rahimi, Kazem; MacMahon, Stephen; Patel, Anushka; Perkovic, Vlado; Turnbull, Fiona; Neal, Bruce; de Zeeuw, Dick

    2014-01-01

    BACKGROUND: We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering

  4. A 30-month worksite-based lifestyle program to promote cardiovascular health in middle-aged bank employees: Design of the TANSNIP-PESA randomized controlled trial.

    Science.gov (United States)

    Coffeng, Jennifer K; van der Ploeg, Hidde P; Castellano, José M; Fernández-Alvira, Juan M; Ibáñez, Borja; García-Lunar, Inés; van der Beek, Allard J; Fernández-Ortiz, Antonio; Mocoroa, Agustín; García-Leal, Laura; Cárdenas, Evelyn; Rojas, Carolina; Martínez-Castro, María I; Santiago-Sacristán, Silvia; Fernández-Gallardo, Miriam; Mendiguren, José M; Bansilal, Sameer; van Mechelen, Willem; Fuster, Valentín

    2017-02-01

    Cardiovascular disease (CVD) is the leading cause of death worldwide. With atherosclerosis as the underlying cause for many CVD events, prevention or reduction of subclinical atherosclerotic plaque burden (SAPB) through a healthier lifestyle may have substantial public health benefits. The objective was to describe the protocol of a randomized controlled trial investigating the effectiveness of a 30-month worksite-based lifestyle program aimed to promote cardiovascular health in participants having a high or a low degree of SAPB compared with standard care. We will conduct a randomized controlled trial including middle-aged bank employees from the Progression of Early Subclinical Atherosclerosis cohort, stratified by SAPB (high SAPB n=260, low SAPB n=590). Within each stratum, participants will be randomized 1:1 to receive a lifestyle program or standard care. The program consists of 3 elements: (a) 12 personalized lifestyle counseling sessions using Motivational Interviewing over a 30-month period, (b) a wrist-worn physical activity tracker, and (c) a sit-stand workstation. Primary outcome measure is a composite score of blood pressure, physical activity, sedentary time, body weight, diet, and smoking (ie, adapted Fuster-BEWAT score) measured at baseline and at 1-, 2-, and 3-year follow-up. The study will provide insights into the effectiveness of a 30-month worksite-based lifestyle program to promote cardiovascular health compared with standard care in participants with a high or low degree of SAPB. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. New modalities of ultrasound-based intima-media thickness, arterial stiffness and non-coronary vascular calcifications detection to assess cardiovascular risk.

    Science.gov (United States)

    Flore, R; Ponziani, F R; Tinelli, G; Arena, V; Fonnesu, C; Nesci, A; Santoro, L; Tondi, P; Santoliquido, A

    2015-04-01

    Carotid intima-media thickness (c-IMT), arterial stiffness (AS) and vascular calcification (VC) are now considered important new markers of atherosclerosis and have been associated with increased prevalence of cardiovascular events. An accurate, reproducible and easy detection of these parameters could increase the prognostic value of the traditional cardiovascular risk factors in many subjects at low and intermediate risk. Today, c-IMT and AS can be measured by ultrasound, while cardiac computed tomography is the gold standard to quantify coronary VC, although concern about the reproducibility of the former and the safety of the latter have been raised. Nevertheless, a safe and reliable method to quantify non-coronary (i.e., peripheral) VC has not been detected yet. To review the most innovative and accurate ultrasound-based modalities of c-IMT and AS detection and to describe a novel UltraSound-Based Carotid, Aortic and Lower limbs Calcification Score (USB-CALCs, simply named CALC), allowing to quantify peripheral calcifications. Finally, to propose a system for cardiovascular risk reclassification derived from the global evaluation of "Quality Intima-Media Thickness", "Quality Arterial Stiffness", and "CALC score" in addition to the Framingham score.

  6. A Systematic Review of Evidence-Based Community Pharmacy Services Aimed at the Prevention of Cardiovascular Disease.

    Science.gov (United States)

    Sabater-Hernández, Daniel; Sabater-Galindo, Marta; Fernandez-Llimos, Fernando; Rotta, Inajara; Hossain, Lutfun N; Durks, Desire; Franco-Trigo, Lucia; Lopes, Livia A; Correr, Cassyano J; Benrimoj, Shalom I

    2016-06-01

    Cardiovascular disease (CVD) is the leading cause of death worldwide and has a substantial impact on people's health and quality of life. CVD also causes an increased use of health care resources and services, representing a significant proportion of health care expenditure. Integrating evidence-based community pharmacy services is seen as an asset to reduce the burden of CVD on individuals and the health care system. To (a) identify community pharmacy evidence-based services designed to help prevent CVD and (b) provide fundamental information that is needed to assess their potential adaptation to other community pharmacy settings. This review used the DEPICT database, which includes 488 randomized controlled trials (RCT) that address the evaluation of pharmacy services. Articles reviewing these RCTs were identified for the DEPICT database through a systematic search of the following databases: MEDLINE, Scopus, SciELO (Scientific Electronic Library Online), and DOAJ (Directory of Open Access Journals). The DEPICT database was reviewed to identify evidence-based services delivered in the community pharmacy setting with the purpose of preventing CVD. An evidence-based service was defined as a service that has been shown to have a positive effect (compared with usual care) in a high-quality RCT. From each evidence-based service, fundamental information was retrieved to facilitate adaptation to other community pharmacy settings. From the DEPICT database, 14 evidence-based community pharmacy services that addressed the prevention of CVD were identified. All services, except 1, targeted populations with a mean age above 60 years. Pharmacy services encompassed a wide range of practical applications or techniques that can be classified into 3 groups: activities directed at patients, activities directed at health care professionals, and assessments to gather patient-related information in order to support the previous activities. This review provides pharmacy service

  7. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Directory of Open Access Journals (Sweden)

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  8. O perfil de saúde cardiovascular dos idosos brasileiros precisa melhorar: estudo de base populacional The profile of cardiovascular health of elderly brazilian people needs to improve: a population-based study

    Directory of Open Access Journals (Sweden)

    Janaina Caldeira Pereira

    2008-07-01

    Full Text Available FUNDAMENTO: No Brasil, existe pouca informação de base populacional sobre a aglomeração de fatores de risco e sua relação com doenças cardiovasculares em idosos. OBJETIVO: Estimar prevalência e aglomeração de fatores de risco e investigar associação com doença isquêmica do coração (DIC em idosos. MÉTODOS: Foram incluídos todos os participantes > 60 anos do "Inquérito domiciliar sobre comportamentos de risco e morbidade referida de doenças e agravos não-transmissíveis", realizado pelo Ministério da Saúde em 2002/2003, em quinze capitais e no Distrito Federal. Investigou-se a prevalência de fatores de risco (tabagismo, consumo de álcool, inatividade física, dieta inadequada e obesidade e de morbidade referida (hipertensão, hipercolesterolemia e diabete, além da associação entre DIC e aglomeração desses fatores pela regressão de Poisson. RESULTADOS: Os idosos representaram 13,4% (3.142/23.457, 59,4% mulheres e 40,6% homens. A idade média foi de 69,5 anos. Prevalências de dieta inadequada, inatividade física, obesidade, tabagismo e consumo de risco de álcool foram 94,4%, 40%, 17%, 12,7%e 3,2%, respectivamente. Cerca de 50% referiram hipertensão; 33% hipercolesterolemia e 18%, diabete. Tabagismo e hipercolesterolemia reduziram significativamente com a idade. Hipertensão, inatividade física, obesidade e hipercolesterolemia foram mais prevalentes em mulheres. Aglomeração de dois ou mais fatores foi observada em 71,3% dos idosos e reduziu com o avançar da idade. Idosos com DIC apresentaram uma prevalência quatro vezes maior de aglomeração de quatro ou mais fatores (RP = 4,1; IC_95%: 2,6-6,4. CONCLUSÃO: A associação entre DIC e maior aglomeração de fatores de risco expressa, provavelmente, maior risco acumulado ao longo da vida, mas indica também a necessidade de melhorar o perfil de risco desses idosos.BACKGROUND: In Brazil, population-based information on risk factors and their relationship with

  9. Prospective association between a dietary quality index based on a nutrient profiling system and cardiovascular disease risk.

    Science.gov (United States)

    Adriouch, Solia; Julia, Chantal; Kesse-Guyot, Emmanuelle; Méjean, Caroline; Ducrot, Pauline; Péneau, Sandrine; Donnenfeld, Mathilde; Deschasaux, Mélanie; Menai, Mehdi; Hercberg, Serge; Touvier, Mathilde; Fezeu, Léopold K

    2016-10-01

    Public health strategies are essential to guide consumers' choices and produce a substantial population impact on cardiovascular disease risk prevention through nutrition. Our aim was to investigate the prospective association between the Food Standards Agency nutrient profiling system dietary index (FSA-NPS DI) and cardiovascular disease risk. The FSA-NPS has been proposed to serve as a basis for a five-colour nutrition label suggested in France to be put on the front of pack of food products. A total of 6515 participants to the SU.VI.MAX cohort (1994-2007), who completed at least six 24-hour dietary records during the first two years of the study, were followed for a median of 12.4 years (25th-75th percentiles: 11.0-12.6). Multivariable Cox proportional hazards models were used to characterise the associations between FSA-NPS DI (continuous and sex-specific quartiles) and the incidence of cardiovascular diseases. Interactions with individual characteristics were tested; 181 major cardiovascular events were reported (59 myocardial infarctions, 43 strokes, 79 anginas). A higher FSA-NPS DI, characterising poorer food choices, was associated with an overall increase in cardiovascular disease risk (HRfor a 1-point increment = 1.14 (1.03-1.27); HRQ4vs.Q1 = 1.61 (1.05-2.47), Ptrend Q4-Q1 = 0.03). This association tended to be stronger in smokers (HRfor a 1-point increment = 1.39 (1.11-1.73); Pinteraction = 0.01) and those less physically active (HRfor a 1-point increment = 1.26 (1.08-1.46); Pinteraction = 0.04). Our results suggest that poorer food choices, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (smokers and physically inactive persons). This score could be a useful tool for public health prevention strategies. ClinicalTrials.gov identifier: NCT00272428. © The European Society of Cardiology 2016.

  10. Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management.

    Science.gov (United States)

    Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

    2017-06-01

    The best way to select individuals for lipid-lowering treatment in the population is controversial. In healthy individuals in primary prevention: to assess the relationship between cardiovascular risk categorized according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by the pooled cohort equations (PCE); to compare the proportion of individuals eligible for statins, according to different criteria. In individuals aged 40-75 years consecutively submitted to routine health assessment at one single center, four criteria of eligibility for statin were defined: BR-1, BR-2 (LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE ≥ 5.0% or ≥ 7.5%, respectively). The final sample consisted of 13,947 individuals (48 ± 6 years, 71% men). Most individuals at intermediate or high risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and more than 70% of those who were considered at high risk had this categorization because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2% were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2 criteria, respectively (p valores para os homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das mulheres e 60% dos homens elegíveis para estatina pelo critério BR-1 não seriam candidatos pelo critério EUA-1. Comparada à diretriz norte-americana, a V Diretriz Brasileira considera uma proporção substancialmente maior da população como elegível para estatina em prevenção primária. Isso se relaciona com discrepâncias entre o risco estratificado pela diretriz brasileira e o calculado pelas PCE, particularmente devido à reclassificação de risco baseada em fatores agravantes.

  11. Effect of 1-week yoga-based residential program on cardiovascular variables of hypertensive patients: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Kashinath G Metri

    2018-01-01

    Full Text Available Introduction: Hypertension (HTN is an important public health concern and a leading cause of morbidity and mortality worldwide. Yoga is a form of mind–body medicine shown to be effective in controlling blood pressure (BP and reduces cardiac risk factors in HTN. Integrated approach of Yoga therapy (IAYT is a residential yoga-based lifestyle intervention proven to be beneficial in several health conditions. Aim: To study the efficacy of 1 week of residential IAYT intervention on cardiovascular parameters in hypertensive patients. Methodology: Twenty hypertensive individuals (7 females within age range between 30 and 60 years (average; 46.62 ± 9.9 years, who underwent 1 week of IAYT treatment for HTN, were compared with age- gender-matched non-IAYT group (5 females; average age; 47.08 ± 9.69 years in terms of systolic BP (SBP, diastolic BP (DBP, mean arterial pressure (MAP, cardiac output (CO, stroke volume (SV, baroreflex sensitivity (BRS, and total peripheral vascular resistance (TPVR, IAYT program consisted of sessions of asanas, breathing practices, meditation and relaxation techniques, low salt, low-calorie diet, devotional session, and counseling. Individuals in non-IAYT group followed their normal routine. All the variables were assessed before and after one week. Data were analyzed using SPSS version 16. RM-ANOVA was applied to assess within group and between group changes after intervention. Results: There was a significant improvement in SBP (P = 0.004, DBP (P = 0.008, MAP (0.03, BRS (P < 0.001, and TPVR (P = 0.007 in IAYT, group whereas in control group, we did not find significant difference in any of the variables. Between-group comparison showed a significant improvement in SBP (P = 0.038, BRS (P = 0.034, and TPVR (P = 0.015 in IAYT group as compared to non-IAYT group. Conclusion: One-week IAYT intervention showed an improvement in baroreflex sensitivity, systolic BP, and total peripheral vascular resistance in hypertensive

  12. Effect of 1-Week Yoga-Based Residential Program on Cardiovascular Variables of Hypertensive Patients: A Comparative Study.

    Science.gov (United States)

    Metri, Kashinath G; Pradhan, Balaram; Singh, Amit; Nagendra, H R

    2018-01-01

    Hypertension (HTN) is an important public health concern and a leading cause of morbidity and mortality worldwide. Yoga is a form of mind-body medicine shown to be effective in controlling blood pressure (BP) and reduces cardiac risk factors in HTN. Integrated approach of Yoga therapy (IAYT) is a residential yoga-based lifestyle intervention proven to be beneficial in several health conditions. Aim: To study the efficacy of 1 week of residential IAYT intervention on cardiovascular parameters in hypertensive patients. Twenty hypertensive individuals (7 females) within age range between 30 and 60 years (average; 46.62 ± 9.9 years), who underwent 1 week of IAYT treatment for HTN, were compared with age- gender-matched non-IAYT group (5 females; average age; 47.08 ± 9.69 years) in terms of systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), baroreflex sensitivity (BRS), and total peripheral vascular resistance (TPVR), IAYT program consisted of sessions of asanas, breathing practices, meditation and relaxation techniques, low salt, low-calorie diet, devotional session, and counseling. Individuals in non-IAYT group followed their normal routine. All the variables were assessed before and after one week. Data were analyzed using SPSS version 16. RM-ANOVA was applied to assess within group and between group changes after intervention. There was a significant improvement in SBP ( P = 0.004), DBP ( P = 0.008), MAP (0.03), BRS ( P < 0.001), and TPVR ( P = 0.007) in IAYT, group whereas in control group, we did not find significant difference in any of the variables. Between-group comparison showed a significant improvement in SBP ( P = 0.038), BRS ( P = 0.034), and TPVR ( P = 0.015) in IAYT group as compared to non-IAYT group. One-week IAYT intervention showed an improvement in baroreflex sensitivity, systolic BP, and total peripheral vascular resistance in hypertensive patients. However, further randomized control

  13. Electronic health record-based patient identification and individualized mailed outreach for primary cardiovascular disease prevention: a cluster randomized trial.

    Science.gov (United States)

    Persell, Stephen D; Lloyd-Jones, Donald M; Friesema, Elisha M; Cooper, Andrew J; Baker, David W

    2013-04-01

    Many individuals at higher risk for cardiovascular disease (CVD) do not receive recommended treatments. Prior interventions using personalized risk information to promote prevention did not test clinic-wide effectiveness. To perform a 9-month cluster-randomized trial, comparing a strategy of electronic health record-based identification of patients with increased CVD risk and individualized mailed outreach to usual care. Patients of participating physicians with a Framingham Risk Score of at least 5 %, low-density lipoprotein (LDL)-cholesterol level above guideline threshold for drug treatment, and not prescribed a lipid-lowering medication were included in the intention-to-treat analysis. Patients of physicians randomized to the intervention group were mailed individualized CVD risk messages that described benefits of using a statin (and controlling hypertension or quitting smoking when relevant). The primary outcome was occurrence of a LDL-cholesterol level, repeated in routine practice, that was at least 30 mg/dl lower than prior. A secondary outcome was lipid-lowering drug prescribing. Clinicaltrials.gov identifier: NCT01286311. Fourteen physicians with 218 patients were randomized to intervention, and 15 physicians with 217 patients to control. The mean patient age was 60.7 years and 77% were male. There was no difference in the primary outcome (11.0 % vs. 11.1 %, OR 0.99, 95 % CI 0.56-1.74, P = 0.96), but intervention group patients were twice as likely to receive a prescription for lipid-lowering medication (11.9 %, vs. 6.0 %, OR 2.13, 95 % CI 1.05-4.32, p = 0.038). In post hoc analysis with extended follow-up to 18 months, the primary outcome occurred more often in the intervention group (22.5 % vs. 16.1 %, OR 1.59, 95 % CI 1.05-2.41, P = 0.029). In this effectiveness trial, individualized mailed CVD risk messages increased the frequency of new lipid-lowering drug prescriptions, but we observed no difference in proportions lowering LDL

  14. Assessment of cardiovascular risk and target organ damage among adult patients with primary hypertension in Thika Level 5 Hospital, Kenya: a criteria-based clinical audit.

    Science.gov (United States)

    Mwita, Clifford Chacha; Akello, Walter; Sisenda, Gloria; Ogoti, Evans; Tivey, David; Munn, Zachary; Mbogo, David

    2013-06-01

    Appropriate management of hypertension reduces the risk of death from stroke and cardiac disease and includes routine assessment for target organ damage and estimation of cardiovascular risk. However, implementation of evidence-based hypertension management guidelines is unsatisfactory. We explore the use of audit and feedback as a quality improvement (QI) strategy for reducing the knowledge practice gap in hypertension care in a resource poor setting. The aim of this study is to determine the level of compliance to evidence-based guidelines on assessment of cardiovascular risk and target organ damage among patients with hypertension in Thika Level 5 Hospital in central Kenya and to implement best practice with regard to evidence utilisation among clinicians in the hospital. A retrospective clinical audit done in three phases spread over 5 months. Phase one involved identifying five audit criteria on assessment of cardiovascular risk and target organ damage in patients with hypertension and conducting a baseline audit in which compliance to audit criteria, blood pressure control and drug prescription practices were assessed. Phase two involved identifying barriers to compliance to audit criteria and strategies to overcoming these barriers. The third phase was a follow-up audit. There was no use of a cardiovascular risk assessment tool in both audits (0% vs. 0%; P = 1.00). Testing urine for haematuria and proteinuria reduced from 13% to 8% (P = 0.230) while taking a blood sample for measuring blood glucose, electrolytes and creatinine levels improved from 11% to 17% (P = 0.401). Performance of fundoscopy and electrocardiography remained unchanged at 2% and 8%, respectively (P = 0.886 and P = 0.898). High patient load was identified as the biggest barrier to implementation of best practice. Blood pressure control improved from 33% to 70% (P ≤ 0.001), whereas the proportion of patients on two or more recommended antihypertensive drugs rose

  15. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events.

    Science.gov (United States)

    Kario, Kazuomi

    2016-07-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events.

  16. Impact of change in neighborhood racial/ethnic segregation on cardiovascular health in minority youth attending a park-based afterschool program.

    Science.gov (United States)

    D'Agostino, Emily M; Patel, Hersila H; Ahmed, Zafar; Hansen, Eric; Sunil Mathew, M; Nardi, Maria I; Messiah, Sarah E

    2018-05-01

    Research on the mechanistic factors associating racial/ethnic residential segregation with health is needed to identify effective points of intervention to ultimately reduce health disparities in youth. We examined the association of changes in racial/ethnic segregation and cardiovascular health outcomes including body mass index percentile, sum of skinfold thicknesses, systolic and diastolic blood pressure percentile, and 400 m run time in non-Hispanic Black (NHB) and Hispanic youth (n = 2,250, mean age 9.1 years, 54% male; 51% Hispanic, 49% NHB; 49% high area poverty; 25% obese) attending Fit2Play™, a multisite park-based afterschool program in Miami, Florida, USA. A series of crude and adjusted two-level longitudinal generalized linear mixed models with random intercepts for park effects were fit to assess the association of change in segregation between home and program/park site and cardiovascular health outcomes for youth who participated for up to two school years in Fit2Play™. After adjusting for individual-level factors (sex, age, time, and park-area poverty) models showed significantly greater improvements in cardiovascular health if youth attended Fit2Play™ in an area less segregated than their home area (p < 0.05 for all outcomes) except 400 m run time and diastolic blood pressure percentile in Hispanics (p<.001 and p = 0.11, respectively). Area poverty was not found to confound or significantly modify this association. These findings have implications for youth programming focused on reducing health disparities and improving cardiovascular outcomes in NHB and Hispanic youth, particularly in light of a continually expanding obesity epidemic in these groups. Parks and Recreation Departments have potential to expand geographic mobility for minorities, therein supporting the national effort to reduce health inequalities. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model.

    Science.gov (United States)

    Choi, In Young; Lim, HoTae; Estrellas, Kenneth; Mula, Jyothi; Cohen, Tatiana V; Zhang, Yuanfan; Donnelly, Christopher J; Richard, Jean-Philippe; Kim, Yong Jun; Kim, Hyesoo; Kazuki, Yasuhiro; Oshimura, Mitsuo; Li, Hongmei Lisa; Hotta, Akitsu; Rothstein, Jeffrey; Maragakis, Nicholas; Wagner, Kathryn R; Lee, Gabsang

    2016-06-07

    Duchenne muscular dystrophy (DMD) remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs). Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our "chemical-compound-based" strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological "dual-SMAD" inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form "rescued" multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human "DMD-in-a-dish" model using hiPSC-based disease modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.

    Science.gov (United States)

    Kamada, Fumiaki; Kure, Shigeo; Kudo, Takayuki; Suzuki, Yoichi; Oshima, Takeshi; Ichinohe, Akiko; Kojima, Kanako; Niihori, Tetsuya; Kanno, Junko; Narumi, Yoko; Narisawa, Ayumi; Kato, Kumi; Aoki, Yoko; Ikeda, Katsuhisa; Kobayashi, Toshimitsu; Matsubara, Yoichi

    2006-01-01

    Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic hearing loss was inherited in an autosomal-dominant fashion. A genome-wide linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion in exon 1, c.211delC, which generated a profoundly truncated protein without transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one 13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the KCNQ4 missense mutations had younger-onset and more profound hearing loss than patients with the 211_223del mutation. In our current study, 12 individuals with the c.211delC mutation manifested late-onset and pure high-frequency hearing loss. Our results support the genotype-phenotype correlation that the KCNQ4 deletions are associated with later-onset and milder hearing impairment than the missense mutations. The phenotypic difference may be caused by the difference in pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative effect in missense mutations.

  19. Performance of an electronic health record-based phenotype algorithm to identify community associated methicillin-resistant Staphylococcus aureus cases and controls for genetic association studies

    Directory of Open Access Journals (Sweden)

    Kathryn L. Jackson

    2016-11-01

    Full Text Available Abstract Background Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA is one of the most common causes of skin and soft tissue infections in the United States, and a variety of genetic host factors are suspected to be risk factors for recurrent infection. Based on the CDC definition, we have developed and validated an electronic health record (EHR based CA-MRSA phenotype algorithm utilizing both structured and unstructured data. Methods The algorithm was validated at three eMERGE consortium sites, and positive predictive value, negative predictive value and sensitivity, were calculated. The algorithm was then run and data collected across seven total sites. The resulting data was used in GWAS analysis. Results Across seven sites, the CA-MRSA phenotype algorithm identified a total of 349 cases and 7761 controls among the genotyped European and African American biobank populations. PPV ranged from 68 to 100% for cases and 96 to 100% for controls; sensitivity ranged from 94 to 100% for cases and 75 to 100% for controls. Frequency of cases in the populations varied widely by site. There were no plausible GWAS-significant (p < 5 E −8 findings. Conclusions Differences in EHR data representation and screening patterns across sites may have affected identification of cases and controls and accounted for varying frequencies across sites. Future work identifying these patterns is necessary.

  20. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer by a large population-based sample.

    Science.gov (United States)

    Ogino, Shuji; Kawasaki, Takako; Kirkner, Gregory J; Kraft, Peter; Loda, Massimo; Fuchs, Charles S

    2007-07-01

    The CpG island methylator phenotype (CIMP or CIMP-high) with extensive promoter methylation is a distinct phenotype in colorectal cancer. However, a choice of markers for CIMP has been controversial. A recent extensive investigation has selected five methylation markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1) as surrogate markers for epigenomic aberrations in tumor. The use of these markers as a CIMP-specific panel needs to be validated by an independent, large dataset. Using MethyLight assays on 920 colorectal cancers from two large prospective cohort studies, we quantified DNA methylation in eight CIMP-specific markers [the above five plus CDKN2A (p16), CRABP1, and MLH1]. A CIMP-high cutoff was set at > or = 6/8 or > or = 5/8 methylated promoters, based on tumor distribution and BRAF/KRAS mutation frequencies. All but two very specific markers [MLH1 (98% specific) and SOCS1 (93% specific)] demonstrated > or = 85% sensitivity and > or = 80% specificity, indicating overall good concordance in methylation patterns and good performance of these markers. Based on sensitivity, specificity, and false positives and negatives, the eight markers were ranked in order as: RUNX3, CACNA1G, IGF2, MLH1, NEUROG1, CRABP1, SOCS1, and CDKN2A. In conclusion, a panel of markers including at least RUNX3, CACNA1G, IGF2, and MLH1 can serve as a sensitive and specific marker panel for CIMP-high.

  1. Phenotypic and functional characterization of earthworm coelomocyte subsets: Linking light scatter-based cell typing and imaging of the sorted populations.

    Science.gov (United States)

    Engelmann, Péter; Hayashi, Yuya; Bodó, Kornélia; Ernszt, Dávid; Somogyi, Ildikó; Steib, Anita; Orbán, József; Pollák, Edit; Nyitrai, Miklós; Németh, Péter; Molnár, László

    2016-12-01

    Flow cytometry is a common approach to study invertebrate immune cells including earthworm coelomocytes. However, the link between light-scatter- and microscopy-based phenotyping remains obscured. Here we show, by means of light scatter-based cell sorting, both subpopulations (amoebocytes and eleocytes) can be physically isolated with good sort efficiency and purity confirmed by downstream morphological and cytochemical applications. Immunocytochemical analysis using anti-EFCC monoclonal antibodies combined with phalloidin staining has revealed antigenically distinct, sorted subsets. Screening of lectin binding capacity indicated wheat germ agglutinin (WGA) as the strongest reactor to amoebocytes. This is further evidenced by WGA inhibition assays that suggest high abundance of N-acetyl-d-glucosamine in amoebocytes. Post-sort phagocytosis assays confirmed the functional differences between amoebocytes and eleocytes, with the former being in favor of bacterial engulfment. This study has proved successful in linking flow cytometry and microscopy analysis and provides further experimental evidence of phenotypic and functional heterogeneity in earthworm coelomocyte subsets. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The association between cardiovascular risk factors and high blood pressure in adolescents: a school-based study.

    Science.gov (United States)

    Christofaro, Diego G D; Fernandes, Rômulo A; Oliveira, Arli R; Freitas Júnior, Ismael Forte; Barros, Mauro V G; Ritti-Dias, Raphael M

    2014-01-01

    Although previous studies have analyzed the association between cardiovascular risk factors and blood pressure in adolescents, few studies conducted in developing countries analyzed whether the aggregation of risk factors contributes to an increased risk of high blood pressure in adolescents. The objective of this study was to assess the association between cardiovascular risk factors (including general overweight, abdominal obesity, high consumption of foods rich in fats, and insufficient physical activity levels) and high blood pressure in adolescents. This study was carried out from 2007 to 2008 with 1021 adolescents (528 girls) from primary schools located in the city of Londrina- Brazil. Blood pressure was assessed using an oscillometric device. General overweight was obtained through body mass index, abdominal obesity was assessed using waist circumference, and the consumption of foods rich in fat and physical activity were assessed using a questionnaire. The sum of these risk factors was determined. Adolescents with three or four aggregated risk factors were more likely to have higher values of systolic and diastolic blood pressure when compared with adolescents who did not have any cardiovascular risk factors (P = 0.001 for both). Logistic regression indicated that groups of adolescents with 2 (OR= 2.46 [1.11-5.42]; P = 0.026), 3 (OR= 4.97 [2.07-11.92]; P = 0.001) or 4 risk factors (OR= 6.79 [2.24-19.9]; P = 0.001) presented an increased likelihood of high blood pressure. The number of cardiovascular risk factors was found to be related to high blood pressure in adolescents. Copyright © 2014 Wiley Periodicals, Inc.

  3. The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison

    Directory of Open Access Journals (Sweden)

    Kahn Henry S

    2005-09-01

    Full Text Available Abstract Background Body mass index (BMI, kg/m2 may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC and fasting triglycerides (TG concentration to describe lipid overaccumulation. Methods The WC (estimated population minimum 65 cm for men and 58 cm for women and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults were used to compute a "lipid accumulation product" [LAP = (WC-65 × TG for men and (WC-58 × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. Results Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex the former had more adverse risk levels than the latter (p 0.1. As continuous variables, LAP provided a consistently more adverse beta coefficient (slope than BMI for nine cardiovascular risk variables (p 0.2. Conclusion LAP (describing lipid overaccumulation performed better than BMI (describing weight overaccumulation for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing.

  4. Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample.

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    Full Text Available The CpG island methylator phenotype (CIMP is a distinct phenotype associated with microsatellite instability (MSI and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. METHOLODOLOGY/PRINCIPAL FINDINGS: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16, CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight. In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1, CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel (including the 5 markers, multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1 activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status.Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also

  5. Waste the waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk.

    Science.gov (United States)

    Greaves, Colin; Gillison, Fiona; Stathi, Afroditi; Bennett, Paul; Reddy, Prasuna; Dunbar, James; Perry, Rachel; Messom, Daniel; Chandler, Roger; Francis, Margaret; Davis, Mark; Green, Colin; Evans, Philip; Taylor, Gordon

    2015-01-16

    In the UK, thousands of people with high cardiovascular risk are being identified by a national risk-assessment programme (NHS Health Checks). Waste the Waist is an evidence-informed, theory-driven (modified Health Action Process Approach), group-based intervention designed to promote healthy eating and physical activity for people with high cardiovascular risk. This pilot randomised controlled trial aimed to assess the feasibility of delivering the Waste the Waist intervention in UK primary care and of conducting a full-scale randomised controlled trial. We also conducted exploratory analyses of changes in weight. Patients aged 40-74 with a Body Mass Index of 28 or more and high cardiovascular risk were identified from risk-assessment data or from practice database searches. Participants were randomised, using an online computerised randomisation algorithm, to receive usual care and standardised information on cardiovascular risk and lifestyle (Controls) or nine sessions of the Waste the Waist programme (Intervention). Group allocation was concealed until the point of randomisation. Thereafter, the statistician, but not participants or data collectors were blinded to group allocation. Weight, physical activity (accelerometry) and cardiovascular risk markers (blood tests) were measured at 0, 4 and 12 months. 108 participants (22% of those approached) were recruited (55 intervention, 53 controls) from 6 practices and 89% provided data at both 4 and 12 months. Participants had a mean age of 65 and 70% were male. Intervention participants attended 72% of group sessions. Based on last observations carried forward, the intervention group did not lose significantly more weight than controls at 12 months, although the difference was significant when co-interventions and co-morbidities that could affect weight were taken into account (Mean Diff 2.6Kg. 95%CI: -4.8 to -0.3, p = 0.025). No significant differences were found in physical activity. The Waste the Waist

  6. Experimental and analytical variation in human urine in 1H NMR spectroscopy-based metabolic phenotyping studies.

    Science.gov (United States)

    Maher, Anthony D; Zirah, Séverine F M; Holmes, Elaine; Nicholson, Jeremy K

    2007-07-15

    1H NMR spectroscopy potentially provides a robust approach for high-throughput metabolic screening of biofluids such as urine and plasma, but sample handling and preparation need careful optimization to ensure that spectra accurately report biological status or disease state. We have investigated the effects of storage temperature and time on the 1H NMR spectral profiles of human urine from two participants, collected three times a day on four different days. These were analyzed using modern chemometric methods. Analytical and preparation variation (tested between -40 degrees C and room temperature) and time of storage (to 24 h) were found to be much less influential than biological variation in sample classification. Statistical total correlation spectroscopy and discriminant function methods were used to identify the specific metabolites that were hypervariable due to preparation and biology. Significant intraindividual variation in metabolite profiles were observed even for urine collected on the same day and after at least 6 h fasting. The effect of long-term storage at different temperatures was also investigated, showing urine is stable if frozen for at least 3 months and that storage at room temperature for long periods (1-3 months) results in a metabolic profile explained by bacterial activity. Presampling (e.g., previous day) intake of food and medicine can also strongly influence the urinary metabolic profiles indicating that collective detailed participant historical meta data are important for interpretation of metabolic phenotypes and for avoiding false biomarker discovery.

  7. Cell-Based Phenotyping Reveals QTL for Membrane Potential Maintenance Associated with Hypoxia and Salinity Stress Tolerance in Barley

    Directory of Open Access Journals (Sweden)

    Muhammad B. Gill

    2017-11-01

    Full Text Available Waterlogging and salinity are two major abiotic stresses that hamper crop production world-wide resulting in multibillion losses. Plant abiotic stress tolerance is conferred by many interrelated mechanisms. Amongst these, the cell’s ability to maintain membrane potential (MP is considered to be amongst the most crucial traits, a positive relationship between the ability of plants to maintain highly negative MP and its tolerance to both salinity and waterlogging stress. However, no attempts have been made to identify quantitative trait loci (QTL conferring this trait. In this study, the microelectrode MIFE technique was used to measure the plasma membrane potential of epidermal root cells of 150 double haploid (DH lines of barley (Hordeum vulgare L. from a cross between a Chinese landrace TX9425 and Japanese malting cultivar Naso Nijo under hypoxic conditions. A major QTL for the MP in the epidermal root cells in hypoxia-exposed plants was identified. This QTL was located on 2H, at a similar position to the QTL for waterlogging and salinity tolerance reported in previous studies. Further analysis confirmed that MP showed a significant contribution to both waterlogging and salinity tolerance. The fact that the QTL for MP was controlled by a single major QTL illustrates the power of the single-cell phenotyping approach and opens prospects for fine mapping this QTL and thus being more effective in marker assisted selection.

  8. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

    International Nuclear Information System (INIS)

    Roychoudhuri, Rahul; Robinson, David; Putcha, Venkata; Cuzick, Jack; Darby, Sarah; Møller, Henrik

    2007-01-01

    Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD) or any cardiovascular disease (CVD). A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001) and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006). When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014). We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long-term cardiac toxicity. In absolute terms, the increase in

  9. Cardiovascular nuclear medicine and MRI

    International Nuclear Information System (INIS)

    Reiber, J.H.C.; Wall, E.E. van der

    1992-01-01

    This book is based on a meeting of the Working Group on Nuclear Cardiology, which held March 22-23,1991 under the auspices of the European Society of Cardiology and the Interuniversity Cardiology Institute of the Netherlands, and on the Second International Symposium on Computer Applications in Nuclear Medicine and Cardiac Magnetic Resonance Imaging, which was held March 20-22,1991 in Rotterdam, the Netherlands. It covers almost every aspect of quantitative cardio-vascular nuclear medicine and magnetic resonance imaging. The main topics are: single photon emission computed tomography (technical aspects); new development in cardiovascular nuclear medicine; advances in cardiovascular imaging; cardiovascular clinical applications; and cardiac magnetic resonance imaging. (A.S.). refs.; figs.; tabs

  10. Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model

    Directory of Open Access Journals (Sweden)

    In Young Choi

    2016-06-01

    Full Text Available Duchenne muscular dystrophy (DMD remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs. Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our “chemical-compound-based” strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological “dual-SMAD” inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form “rescued” multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human “DMD-in-a-dish” model using hiPSC-based disease modeling.

  11. Cowpea mosaic virus-based chimaeras Effects of inserted peptides on the phenotype, host range, and transmissibility of the modified viruses

    International Nuclear Information System (INIS)

    Porta, Claudine; Spall, Valerie E.; Findlay, Kim C.; Gergerich, Rose C.; Farrance, Christine E.; Lomonossoff, George P.

    2003-01-01

    Expression of foreign peptides on the surface of cowpea mosaic virus particles leads to the creation of chimaeras with a variety of phenotypes and yields. Two factors were shown to be particularly significant in determining the properties of a given chimaera: the length of the inserted sequence and its isoelectric point. The deleterious effect of high isoelectric point on the ability of chimeras to produce a systemic infection occurs irrespective of the site of insertion of the peptide. Ultrastructural analysis of tissue infected with chimaeras with different phenotypes showed that all produced particles with a tendency to aggregate, irrespective of the size or isoelectric point of the insert. Host range and transmission studies revealed that the expression of a foreign peptide did not (1) alter the virus host range, (2) increase the rate of transmission by beetles or through seed, or (3) change the insect vector specificity. These findings have implications for both the utility and the biosafety of Cowpea mosaic virus-based chimaeras

  12. Sleep apnea and cardiovascular risk.

    Science.gov (United States)

    Floras, John S

    2014-01-01

    Sleep apnea is evident in approximately 10% of adults in the general population, but in certain cardiovascular diseases, and in particular those characterized by sodium and water retention, its prevalence can exceed 50%. Although sleep apnea is not as yet integrated into formal cardiovascular risk assessment algorithms, there is increasing awareness of its importance in the causation or promotion of hypertension, coronary artery disease, heart failure, atrial arrhythmias, and stroke, and thus, not surprisingly, as a predictor of premature cardiovascular death. Sleep apnea manifests as two principal phenotypes, both characterized by respiratory instability: obstructive (OSA), which arises when sleep-related withdrawal of respiratory drive to the upper airway dilator muscles is superimposed upon a narrow and highly compliant airway predisposed to collapse, and central (CSA), which occurs when the partial pressure of arterial carbon dioxide falls below the apnea threshold, resulting in withdrawal of central drive to respiratory muscles. The present objectives are to: (1) review the epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the role of renal sodium retention in initiating and promoting these processes, and on population studies that reveal the long-term consequences of untreated OSA and CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms by which OSA and CSA can increase cardiovascular risk and event rates by initiating or promoting hypertension, atherosclerosis, coronary artery disease, heart failure, arrhythmias, and stroke; (3) highlight insights from randomized trials in which treating sleep apnea was the specific target of therapy; (4) emphasize the present lack of evidence that treating sleep apnea reduces cardiovascular risk and the current clinical equipoise concerning treatment of asymptomatic patients with sleep apnea; and (5) consider clinical implications and future directions of clinical

  13. Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype

    Directory of Open Access Journals (Sweden)

    James C. Hart

    2017-09-01

    Full Text Available Here, we present and characterize the spontaneous X-linked recessive mutation casper, which causes oculocutaneous albinism in threespine sticklebacks (Gasterosteus aculeatus. In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO, the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19 near the stickleback ortholog of Hermansky-Pudlak syndrome 5 (Hps5. casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5, predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish.

  14. Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data.

    Science.gov (United States)

    Karmali, Kunal N; Lloyd-Jones, Donald M; van der Leeuw, Joep; Goff, David C; Yusuf, Salim; Zanchetti, Alberto; Glasziou, Paul; Jackson, Rodney; Woodward, Mark; Rodgers, Anthony; Neal, Bruce C; Berge, Eivind; Teo, Koon; Davis, Barry R; Chalmers, John; Pepine, Carl; Rahimi, Kazem; Sundström, Johan

    2018-03-01

    Clinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD) prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP) level. We used individual participant data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants). During a median of 4.0 y of follow-up, 3,566 participants (7.5%) experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI) 0.70-0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53-0.55] for the SBP strategy). Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%-31%) fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%-18%) more events for the same number of persons treated. Compared with treating

  15. Blood pressure-lowering treatment strategies based on cardiovascular risk versus blood pressure: A meta-analysis of individual participant data.

    Directory of Open Access Journals (Sweden)

    Kunal N Karmali

    2018-03-01

    Full Text Available Clinical practice guidelines have traditionally recommended blood pressure treatment based primarily on blood pressure thresholds. In contrast, using predicted cardiovascular risk has been advocated as a more effective strategy to guide treatment decisions for cardiovascular disease (CVD prevention. We aimed to compare outcomes from a blood pressure-lowering treatment strategy based on predicted cardiovascular risk with one based on systolic blood pressure (SBP level.We used individual participant data from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC from 1995 to 2013. Trials randomly assigned participants to either blood pressure-lowering drugs versus placebo or more intensive versus less intensive blood pressure-lowering regimens. We estimated 5-y risk of CVD events using a multivariable Weibull model previously developed in this dataset. We compared the two strategies at specific SBP thresholds and across the spectrum of risk and blood pressure levels studied in BPLTTC trials. The primary outcome was number of CVD events avoided per persons treated. We included data from 11 trials (47,872 participants. During a median of 4.0 y of follow-up, 3,566 participants (7.5% experienced a major cardiovascular event. Areas under the curve comparing the two treatment strategies throughout the range of possible thresholds for CVD risk and SBP demonstrated that, on average, a greater number of CVD events would be avoided for a given number of persons treated with the CVD risk strategy compared with the SBP strategy (area under the curve 0.71 [95% confidence interval (CI 0.70-0.72] for the CVD risk strategy versus 0.54 [95% CI 0.53-0.55] for the SBP strategy. Compared with treating everyone with SBP ≥ 150 mmHg, a CVD risk strategy would require treatment of 29% (95% CI 26%-31% fewer persons to prevent the same number of events or would prevent 16% (95% CI 14%-18% more events for the same number of persons treated. Compared with

  16. Bebida à base de subproduto da uva: efeitos sobre o estresse oxidativo e marcadores de risco de doenças cardiovasculares em mulheres saudáveis

    OpenAIRE

    Marcela Piedade Monteiro

    2011-01-01

    Introdução: Estudos epidemiológicos sugerem que o consumo de vinho, produtos de uva e outros alimentos contendo polifenóis está associado à diminuição do risco de doenças cardiovasculares. Na produção de vinhos e suco de uva são geradas quantidades expressivas de bagaço residual, que é prejudicial ao meio ambiente. Por outro lado, este subproduto possui alto teor de antioxidantes e de fibras. Objetivo: Produzir uma bebida à base de farinha de bagaço de uva proveniente do processamento de suco...

  17. Effects of a 2-year school-based daily physical activity intervention on cardiovascular disease risk factors: the Sogndal school-intervention study

    DEFF Research Database (Denmark)

    Resaland, G K; Anderssen, S A; Holme, I M

    2011-01-01

    at the I-school carried out 60 min of PA daily. The PA lessons were planned, organized and led by expert physical education (PE) teachers. In the C-school, children were offered the normal 45 min of PE twice weekly. The intervention resulted in a greater beneficial development in systolic (P=0......The aim of this study was to investigate the effect of a 2-year school-based physical activity (PA) intervention in 9-year-old children on cardiovascular disease (CVD) risk factors. One intervention school (I-school) (n=125) and one control school (C-school) (n=131) were included. The children...

  18. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping.

    Science.gov (United States)

    Laughlin, Maren R; Lloyd, K C Kent; Cline, Gary W; Wasserman, David H

    2012-10-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community's needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses.

  19. A simple algorithm for the identification of clinical COPD phenotypes

    DEFF Research Database (Denmark)

    Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim

    2017-01-01

    This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification...... of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative...... International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated...

  20. COACH CV: The Seven Clinical Phenotypes of Concussion

    Directory of Open Access Journals (Sweden)

    Neil Craton

    2017-09-01

    Full Text Available Our understanding of the diverse physiological manifestations of concussion is changing rapidly. This has an influence on the clinical assessment of patients who have sustained a concussion. The 2017 Consensus Statement on Concussion in Sport states that numerous post-injury clinical findings, such as cognitive deficits, post-traumatic headaches, dizziness, difficulties with oculomotor function, and depression have all been associated with a poorer prognosis in concussed patients. This demonstrates that there are several potential clinical manifestations after head injury warranting clinical evaluation. We have developed an acronym to guide the office-based assessment of concussed patients to consider each of the potential clinical phenotypes. “COACH CV” prompts the clinician to evaluate for cognitive problems, oculomotor dysfunction, affective disturbances, cervical spine disorders, headaches, and cardiovascular and vestibular anomalies.

  1. Low dose ionizing radiation exposure and cardiovascular disease mortality: cohort study based on Canadian national dose registry of radiation workers

    International Nuclear Information System (INIS)

    Zielinski, J. M.; Band, P. R.; Ashmore, P. J.; Jiang, H.; Shilnikova, N. S.; Tait, V. K.; Krewski, D.

    2009-01-01

    The purpose of our study was to assess the risk of cardiovascular disease (CVD) mortality in a Canadian cohort of 337 397 individuals (169 256 men and 168 141 women) occupationally exposed to ionizing radiation and included in the National Dose Registry (NDR) of Canada. Material and Methods: Exposure to high doses of ionizing radiation, such as those received during radiotherapy, leads to increased risk of cardiovascular diseases. The emerging evidence of excess risk of CVDs after exposure to doses well below those previously considered as safe warrants epidemiological studies of populations exposed to low levels of ionizing radiation. In the present study, the cohort consisted of employees at nuclear power stations (nuclear workers) as well as medical, dental and industrial workers. The mean whole body radiation dose was 8.6 mSv for men and 1.2 mSv for women. Results: During the study period (1951 - 1995), as many as 3 533 deaths from cardiovascular diseases have been identified (3 018 among men and 515 among women). In the cohort, CVD mortality was significantly lower than in the general population of Canada. The cohort showed a significant dose response both among men and women. Risk estimates of CVD mortality in the NDR cohort, when expressed as excess relative risk per unit dose, were higher than those in most other occupational cohorts and higher than in the studies of Japanese atomic bomb survivors. Conclusions: The study has demonstrated a strong positive association between radiation dose and the risk of CVD mortality. Caution needs to be exercised when interpreting these results, due to the potential bias introduced by dosimetry uncertainties, the possible record linkage errors, and especially by the lack of adjustment for non-radiation risk factors. (authors)

  2. Cardiovascular Risk Factors Among Low-Income Women: A Population-Based Study in China from 1991 to 2011.

    Science.gov (United States)

    Lu, Hongyan; Bai, Lingling; Zhan, Changqing; Yang, Li; Tu, Jun; Gu, Hongfei; Shi, Min; Wang, Jinghua; Ning, Xianjia

    2016-12-01

    Data on long-term trends in the prevalence and clustering of cardiovascular disease (CVD) risk factors among women in China are rare, especially among low-income women. The aim of this study was to investigate the secular trends in the prevalence of CVD risk factors among low-income women in northern China. The prevalence and clustering of CVD risk factors, including hypertension, diabetes, obesity, current smoking status, and alcohol consumption, were assessed and compared in women aged 35-74 years in northern China in 1991 and 2011. The age-adjusted prevalence of cardiovascular risk factors among women was significantly higher in 2011 than in 1991, with increases of 31% (53.6% vs. 41.1%) for hypertension, 148% (20.9% vs. 8.4%) for obesity, 256% (11.7% vs. 3.3%) for diabetes, and 1634% (4.5% vs. 0.3%) for alcohol consumption. Over the 21-year period, there were significant differences in the prevalence of clustering of ≥1, ≥2, and 3 risk factors in all age groups. The greatest increase was observed among women aged 35-44 years, with a 7.3-fold increase in the prevalence of clustering of three risk factors. Simultaneously, the prevalence of clustering of ≥1 risk factors among women aged 35-44 years was 1.7-fold higher in 2011 than in 1991; the prevalence of clustering of ≥2 risk factors was raised by 5.5-fold among elderly women. Our findings suggest that it is crucial to emphasize the prevention and control of cardiovascular risk factors among young women in rural China to reduce the burden of CVDs.

  3. Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt.

    Science.gov (United States)

    Gadallah, Mohsen; Kandil, Sahar; Mohsen, Amira

    2018-05-03

    To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications. © 2018 John Wiley & Sons Ltd.

  4. The relation of metabolic syndrome according to five definitions to cardiovascular risk factors - a population-based study

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    Lai Ming-May

    2009-12-01

    Full Text Available Abstract Background Although National Cholesterol Education Program (NCEP, International Diabetes Federation (IDF, American Heart Association and National Heart, Lung and Blood Institute (AHA/NHLBI, World Health Organization (WHO, and the European Group for the Study of Insulin Resistance (EGIR definitions of metabolic syndrome (MetS have been commonly used by studies, little is known about agreement among these five definitions. We examined the agreement among these five definitions and explored their relationship with risk factors of cardiovascular disease in a Taiwan population. Methods A total of 1305 subjects aged 40 years and over in Taiwan were analyzed. Biomedical markers and anthropometric indices were measured. Agreement among definitions was determined by the kappa statistic. Logistic regression models were fit to estimate the odds of a high cardiovascular risk group for five definitions of MetS. Results The agreement among the NCEP, IDF, and AHA/NHLBI definitions was from substantial to very good, and agreement between the WHO and EGIR definitions was also substantial. All MetS definitions were significantly associated prevalence of microalbuminuria, elevated highly sensitive CRP (hs-CRP, and arterial stiffness only in women. In men, MetS by NCEP and AHA/NHLBI was associated with elevated level of hs-CRP and arterial stiffness. MetS by WHO and EGIR were significantly associated with microalbuminuria. And MetS by WHO was the only MetS definition that significantly associated with prevalence of arterial stiffness (OR: 2.75, 95% CI: 1.22-6.19. Conclusions The associations of these five definitions with cardiovascular risk factors were similar in women, and it was evident that the five definitions performed better in women than in men, with higher ORs observed in relation to arterial stiffness, elevated hs-CRP, and higher Framingham risk scores.

  5. "It's Like Backing up Science with Scripture": Lessons Learned from the Implementation of HeartSmarts, a Faith-Based Cardiovascular Disease Health Education Program.

    Science.gov (United States)

    Tettey, Naa-Solo; Duran, Pedro A; Andersen, Holly S; Washington, Niajee; Boutin-Foster, Carla

    2016-06-01

    African-Americans are disproportionately impacted by cardiovascular disease (CVD). Faith-based institutions provide a non-traditional route for health education targeted at African-Americans. This paper describes HeartSmarts, a faith-based CVD education program. Evidence-based literature was used to develop a curriculum, which was tailored by integrating biblical scripture representing aspects of health behaviors. Eighteen church peer-educators were recruited to participate in a 12-week training. They then disseminated the faith-based curriculum to members of their congregations. There were 199 participants of which 137 provided feedback via open-ended surveys indicating that HeartSmarts was well accepted and effective for disseminating CVD health messages while engaging spirituality.

  6. A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.

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    Johanna Hass

    Full Text Available Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328. A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170 on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10 had p-values between 6.75×10(-6 and 8.3×10(-7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings

  7. Phenotyping Drought Tolerance and Yield Potential of Warm-Season Legumes Through Field- and Airborne-Based Hyperspectral VSWIR Sensing

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    Drewry, D.; Berny-Mier y Teran, J. C.; Dutta, D.; Gepts, P.

    2017-12-01

    Hyperspectral sensing in the visible through shortwave infrared (VSWIR) portion of the spectrum has been demonstrated to provide significant information on the structural and functional properties of vegetation, resulting in powerful techniques to discern species differences, characterize crop nutrient or water stress, and quantify the density of foliage in agricultural fields. Modern machine-learning techniques allow for the entire set of spectral bands, on the order of hundreds with modern field and airborne spectrometers, to be used to develop models that can simultaneously retrieve a variety of foliar chemical compounds and hydrological and structural states. The application of these techniques, in the context of leaf-level measurements of VSWIR reflectance, or more complicated remote airborne surveys, has the potential to revolutionize high-throughput methods to phenotype germplasm that optimizes yield, resource-use efficiencies, or alternate objectives related to disease resistance or biomass accumulation, for example. Here we focus on breeding trials for a set of warm-season legumes, conducted in both greenhouse and field settings, and spanning a set of diverse genotypes providing a range of adaptation to drought and yield potential in the context of the semi-arid climate cultivation. At the leaf-level, a large set of spectral reflectance measurements spanning 400-2500 nanometers were made for plants across various growth stages in field experiments that induced severe drought, along with sampling for relevant trait values. Here we will discuss the development and performance of algorithms for a range of leaf traits related to gas exchange, leaf structure, hydrological status, nutrient contents and stable isotope discrimination, along with their relationships to drought resistance and yield. We likewise discuss the effectiveness of quantifying relevant foliar and canopy traits through airborne imaging spectroscopy from small unmanned vehicles (sUAVs), and

  8. Association between a dietary quality index based on the food standard agency nutrient profiling system and cardiovascular disease risk among French adults.

    Science.gov (United States)

    Adriouch, Solia; Julia, Chantal; Kesse-Guyot, Emmanuelle; Ducrot, Pauline; Péneau, Sandrine; Méjean, Caroline; Assmann, Karen E; Deschasaux, Mélanie; Hercberg, Serge; Touvier, Mathilde; Fezeu, Léopold K

    2017-05-01

    In France, the implementation of a front-of-pack (FOP) nutrition label-the 5-Colour Nutrition Label (5-CNL) is currently under consideration as a strategic tool to allow consumers making healthier food choices. This FOP label is based on the British Food Standards Agency Nutrient Profiling System (FSA-NPS), reflecting the overall nutritional quality of foods. At the individual level, an energy-weighted mean of all FSA-NPS scores of foods usually consumed has been elaborated (FSA-NPS DI). Our objective was to investigate the prospective association between the FSA-NPS DI and cardiovascular disease (CVD) risk. 75,801 participants to the NutriNet-Santé cohort, who completed at least three 24h dietary records during the first 2y of the follow-up, were followed between 2009 and 2016. Multivariable Cox proportional hazards models were used to characterize the associations between FSA-NPS DI and the incidence of CVDs. 509 major cardiovascular events were diagnosed (262 coronary heart diseases and 247 strokes). A higher FSA-NPS DI, characterizing lower dietary quality, was associated with increased CVD risk (HR for a 1-point increment =1.08 (1.03-1.13); HR Q4vs.Q1 =1.40 (1.06-1.84), P trend Q4-Q1 =0.01). This association tended to be stronger in overweight subjects (HR for a 1-point increment =1.12 (1.04-1.19); P interaction =0.003). These results suggest that lower dietary quality, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (overweight population). They support the public health relevance of developing a front-of-pack nutrition label based on this score. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Image-Based Computational Fluid Dynamics in Blood Vessel Models: Toward Developing a Prognostic Tool to Assess Cardiovascular Function Changes in Prolonged Space Flights

    Science.gov (United States)

    Chatzimavroudis, George P.; Spirka, Thomas A.; Setser, Randolph M.; Myers, Jerry G.

    2004-01-01

    One of NASA's objectives is to be able to perform a complete, pre-flight, evaluation of cardiovascular changes in astronauts scheduled for prolonged space missions. Computational fluid dynamics (CFD) has shown promise as a method for estimating cardiovascular function during reduced gravity conditions. For this purpose, MRI can provide geometrical information, to reconstruct vessel geometries, and measure all spatial velocity components, providing location specific boundary conditions. The objective of this study was to investigate the reliability of MRI-based model reconstruction and measured boundary conditions for CFD simulations. An aortic arch model and a carotid bifurcation model were scanned in a 1.5T Siemens MRI scanner. Axial MRI acquisitions provided images for geometry reconstruction (slice thickness 3 and 5 mm; pixel size 1x1 and 0.5x0.5 square millimeters). Velocity acquisitions provided measured inlet boundary conditions and localized three-directional steady-flow velocity data (0.7-3.0 L/min). The vessel walls were isolated using NIH provided software (ImageJ) and lofted to form the geometric surface. Constructed and idealized geometries were imported into a commercial CFD code for meshing and simulation. Contour and vector plots of the velocity showed identical features between the MRI velocity data, the MRI-based CFD data, and the idealized-geometry CFD data, with less than 10% differences in the local velocity values. CFD results on models reconstructed from different MRI resolution settings showed insignificant differences (less than 5%). This study illustrated, quantitatively, that reliable CFD simulations can be performed with MRI reconstructed models and gives evidence that a future, subject-specific, computational evaluation of the cardiovascular system alteration during space travel is feasible.

  10. Association between Floods and Acute Cardiovascular Diseases: A Population-Based Cohort Study Using a Geographic Information System Approach.

    Science.gov (United States)

    Vanasse, Alain; Cohen, Alan; Courteau, Josiane; Bergeron, Patrick; Dault, Roxanne; Gosselin, Pierre; Blais, Claudia; Bélanger, Diane; Rochette, Louis; Chebana, Fateh

    2016-01-28

    Floods represent a serious threat to human health beyond the immediate risk of drowning. There is few data on the potential link between floods and direct consequences on health such as on cardiovascular health. This study aimed to explore the impact of one of the worst floods in the history of Quebec, Canada on acute cardiovascular diseases (CVD). A cohort study with a time series design with multiple control groups was built with the adult population identified in the Quebec Integrated Chronic Disease Surveillance System. A geographic information system approach was used to define the study areas. Logistic regressions were performed to compare the occurrence of CVD between groups. The results showed a 25%-27% increase in the odds in the flooded population in spring 2011 when compared with the population in the same area in springs 2010 and 2012. Besides, an increase up to 69% was observed in individuals with a medical history of CVD. Despite interesting results, the association was not statistically significant. A possible explanation to this result can be that the population affected by the flood was probably too small to provide the statistical power to answer the question, and leaves open a substantial possibility for a real and large effect.

  11. Differences in cardiovascular risk profile based on relationship between post-load plasma glucose and fasting plasma levels.

    Science.gov (United States)

    Succurro, Elena; Marini, Maria Adelaide; Grembiale, Alessandro; Lugarà, Marina; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Lauro, Renato; Perticone, Francesco; Sesti, Giorgio

    2009-05-01

    It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose returns to, or drops below, the fasting level (Group I). However, it is still unsettled whether individuals in Group II have a more atherogenic profile than Group I subjects. To address this issue, we examined 266 non-diabetic offspring of type 2 diabetic patients, recruited in the context of EUGENE2 cross-sectional study. All subjects underwent an euglycaemic-hyperinsulinemic clamp to assess glucose tolerance and insulin sensitivity. Furthermore, cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. Individuals in Group II exhibited significantly higher waist circumference, blood pressure, triglycerides, 2-h post-load PG, hsC-reactive protein, interleukin-6, insulin-like growth factor-1 (IGF-1), IMT, and lower insulin sensitivity than subjects in Group I. Subjects with NGT, whose PG concentration does not return to their fasting PG level within 2 h during OGTT, have an atherogenic profile, suggesting that performing OGTT with measurement of PG every 30 min may be useful to assess the risk for cardiovascular disease in glucose-tolerant subjects.

  12. Socioeconomic Impact on the Prevalence of Cardiovascular Risk Factors in Wallonia, Belgium: A Population-Based Study.

    Science.gov (United States)

    Streel, Sylvie; Donneau, Anne-Françoise; Hoge, Axelle; Majerus, Sven; Kolh, Philippe; Chapelle, Jean-Paul; Albert, Adelin; Guillaume, Michèle

    2015-01-01

    Background. Monitoring the epidemiology of cardiovascular risk factors (CRFs) and their determinants is important to develop appropriate recommendations to prevent cardiovascular diseases in specific risk groups. The NESCaV study was designed to collect standardized data to estimate the prevalence of CRFs in relation to socioeconomic parameters among the general adult population in the province of Liège, Wallonia, Belgium. Methods. A representative stratified random sample of 1017 subjects, aged 20-69 years, participated in the NESCaV study (2010-2012). A self-administered questionnaire, a clinical examination, and laboratory tests were performed on participants. CRFs included hypertension, dyslipidemia, global obesity, abdominal obesity, diabetes, current smoking, and physical inactivity. Covariates were education and subjective and objective socioeconomic levels. Data were analyzed by weighted logistic regression. Results. The prevalence of hypertension, abdominal obesity, global obesity, current smoking, and physical inactivity was higher in subjects with low education and who considered themselves "financially in need." Living below poverty threshold also increased the risk of global and abdominal obesity, current smoking, and physical inactivity. Conclusion. The study shows that socioeconomic factors impact the prevalence of CRFs in the adult population of Wallonia. Current public health policies should be adjusted to reduce health inequalities in specific risk groups.

  13. The association between creatinine versus cystatin C-based eGFR and cardiovascular risk in children with chronic kidney disease using a modified PDAY risk score.

    Science.gov (United States)

    Sharma, Sheena; Denburg, Michelle R; Furth, Susan L

    2017-08-01

    Children with chronic kidney disease (CKD) have a high prevalence of cardiovascular disease (CVD) risk factors which may contribute to the development of cardiovascular events in adulthood. Among adults with CKD, cystatin C-based estimates of glomerular filtration rate (eGFR) demonstrate a stronger predictive value for cardiovascular events than creatinine-based eGFR. The PDAY (Pathobiological Determinants of Atherosclerosis in Youth) risk score is a validated tool used to estimate the probability of advanced coronary atherosclerotic lesions in young adults. To assess the association between cystatin C-based versus creatinine-based eGFR (eGFR cystatin C and eGFR creatinine, respectively) and cardiovascular risk using a modified PDAY risk score as a proxy for CVD in children and young adults. We performed a cross-sectional study of 71 participants with CKD [median age 15.5 years; inter-quartile range (IQR) 13, 17], and 33 healthy controls (median age 15.1 years; IQR 13, 17). eGFR was calculated using age-appropriate creatinine- and cystatin C-based formulas. Median eGFR creatinine and eGFR cystatin C for CKD participants were 50 (IQR 30, 75) and 53 (32, 74) mL/min/1.73 m 2 , respectively. For the healthy controls, median eGFR creatinine and eGFR cystatin were 112 (IQR 85, 128) and 106 mL/min/1.73m 2 (95, 123) mL/min/1.73 m 2 , respectively. A modified PDAY risk score was calculated based on sex, age, serum lipoprotein concentrations, obesity, smoking status, hypertension, and hyperglycemia. Modified PDAY scores ranged from -2 to 20. The Spearman's correlations of eGFR creatinine and eGFR cystatin C with coronary artery PDAY scores were -0.23 (p = 0.02) and -0.28 (p = 0.004), respectively. Ordinal logistic regression also showed a similar association of higher eGFR creatinine and higher eGFR cystatin C with lower PDAY scores. When stratified by age creatinine and eGFR cystatin C with PDAY score were modest and similar in children [-0.29 (p = 0.008) vs. -0.32 (p = 0

  14. Childhood asthma-predictive phenotype.

    Science.gov (United States)

    Guilbert, Theresa W; Mauger, David T; Lemanske, Robert F

    2014-01-01

    Wheezing is a fairly common symptom in early childhood, but only some of these toddlers will experience continued wheezing symptoms in later childhood. The definition of the asthma-predictive phenotype is in children with frequent, recurrent wheezing in early life who have risk factors associated with the continuation of asthma symptoms in later life. Several asthma-predictive phenotypes were developed retrospectively based on large, longitudinal cohort studies; however, it can be difficult to differentiate these phenotypes clinically as the expression of symptoms, and risk factors can change with time. Genetic, environmental, developmental, and host factors and their interactions may contribute to the development, severity, and persistence of the asthma phenotype over time. Key characteristics that distinguish the childhood asthma-predictive phenotype include the following: male sex; a history of wheezing, with lower respiratory tract infections; history of parental asthma; history of atopic dermatitis; eosinophilia; early sensitization to food or aeroallergens; or lower lung function in early life. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  16. ISFAHAN HEALTHY HEART PROGRAM:A COMPREHENSIVE INTEGRATED COMMUNITY-BASED PROGRAM FOR CARDIOVASCULAR DISEASE PREVENTION AND CONTROL. DESIGN, METHODS AND INITIAL EXPERIENCE 2000-2001

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    N MOHAMMADI FARD

    2002-03-01

    Full Text Available Isfahan Healthy Heart Program (IHHP is a five to six year comprehensive integrated community based program for preventing and controlling of cardiovascular diseases (CVD via reducing CVD risk factors and improvement of cardiovascular healthy behavior in target population. IHHP has been started in 1999 and will be last since 2004. Primary survey was done to collect baseline data from interventional (Isfahan and Najafabad Cities and reference (Arak communities. In a multistage sampling method, we select randomly 5 to 10 percent of households in clusters. Then individuals aged equal or higher than 19 years old were selected for entering to survey. In this way, data from 12600 individuals (6300 in interventional counties and 6300 in reference county was collected and stratified due to their living area (urban vs. rural and different age and sex groups. Cardiovascular risk factors (Hypercholesterolemia, Smoking, Hypertension, Diabetes Mellitus, Obesity were investigated by laboratory tests (Lipid profile, FBS, OGTT, physical exam and standard questionnaires, in all ones. Nutritional habits, socioeconomic states, physical activity profiles and other healthy behaviors regarding to cardiovascular disease were assessed by validated questionnaires via interviewing to all individuals. Twelve leads electrocardiogram was done in all persons older than 35 years old. The prevalence of CVDs and distribution of CVD risk factors were estimated in this phase. In the 2nd phase, based on primary survey findings, we arranged a series of teams (worksite, children, women, health personnel, high risk patients, nutrition for planning and implementation of program through interventional community for a 5-year period. Every team has its own target population and objectives and monitors its process during the study. At intervals (annually, some local and small surveys with a random sampling will be conducted to assess and monitor the program and its potency to cope with

  17. Increased long-term risk of major adverse cardiovascular events in patients with carbon monoxide poisoning: A population-based study in Taiwan.

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    Chung-Shun Wong

    Full Text Available Carbon monoxide (CO poisoning may cause toxicity to the cardiovascular system. However, the association between CO poisoning and the risk of major adverse cardiovascular events (MACE remains unestablished. We investigated the incidence of MACE after CO poisoning in Taiwan and evaluated whether CO-poisoned individuals had a higher risk of MACE than did the general population.Using Taiwan's National Health Insurance Research Database (NHIRD during 2005-2013, a nationwide population-based cohort study was conducted among patients who experienced CO poisoning between 2005 and 2013. CO poisoning was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. The study cohort comprised patients with CO poisoning between 2005 and 2010 (N = 13,939. Each patient was matched according to age, sex and index date with four randomly selected controls from the comparison cohort (N = 55,756. All patients were followed from the study date until MACE development, death, or the end of 2013. The hazard ratios for MACE were compared between the two cohorts by using Cox proportional hazards regressions analyses.Incident cases of MACE were identified from the NHIRD. After adjustment for potential confounders, the study cohort was independently associated with a higher MACE risk (adjusted hazard ratio, 2.00; 95% confidence interval, 1.83-2.18.This population-based cohort study indicated that patients with CO poisoning have a higher risk of MACE than do individuals without CO poisoning.

  18. Is an unfavourable cardiovascular risk profile a risk factor for vasomotor menopausal symptoms? Results of a population-based cohort study.

    Science.gov (United States)

    van den Berg, M J; Herber-Gast, G C M; van der Schouw, Y T

    2015-08-01

    Evidence suggests an association between vasomotor menopausal symptoms (VMSs), i.e. hot flushes and night sweats, and cardiovascular disease. However, the causal pathway is unclear. We investigated whether an unfavourable cardiovascular risk profile is a risk factor for VMS later in life. Retrospective cohort study. Women aged 50-70 from the general population. The Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort is a population-based cohort of women who enrolled between 1993 and 1997. Follow-up questionnaires were sent at 5-year intervals for 15 years. Women who returned the third questionnaire, answered questions regarding lifetime VMS and did not report VMS prior to baseline were included in this study (n = 1295). At baseline, the Framingham Risk Score (FRS) was determined. We used logistic regression analysis to calculate odds ratios (ORs) for the association between baseline FRS and incident VMS. Incident VMS. At baseline (mean age ± standard deviation, 52.2 ± 3.6 years), 21.2% had a FRS > 10%. During follow-up, 40.2% of women reported the onset of VMS. Adjusted for body mass index, physical activity, education and alcohol consumption, each point increase in FRS was associated with a decreased incidence of VMS [OR, 0.94 (95% CI, 0.91-0.97)]. Additional adjustment for menopausal status attenuated the OR to null [OR, 0.98 (95% CI, 0.95-1.01)]. None of the separate FRS variables were associated with VMS after adjustment for age. In our cohort, an unfavourable cardiovascular risk profile was not associated with VMS, and therefore we found no evidence for the involvement of a vascular mechanism in the etiology of VMS. © 2014 Royal College of Obstetricians and Gynaecologists.

  19. Seasonality of cardiovascular risk factors

    DEFF Research Database (Denmark)

    Marti-Soler, Helena; Gubelmann, Cédric; Aeschbacher, Stefanie

    2014-01-01

    OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist...

  20. The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

    Science.gov (United States)

    Sáez, María E.; González-Sánchez, José L.; Ramírez-Lorca, Reposo; Martínez-Larrad, María T.; Zabena, Carina; González, Alejandro; Morón, Francisco J.; Ruiz, Agustín; Serrano-Ríos, Manuel

    2008-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PMID:18698425

  1. The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

    Directory of Open Access Journals (Sweden)

    María E Sáez

    Full Text Available Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10 has been associated with type 2 diabetes (T2DM, a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS in T2DM and in polycystic ovary syndrome (PCOS. In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population.

  2. A new image-based tool for the high throughput phenotyping of pollen viability: evaluation of inter- and intra-cultivar diversity in grapevine.

    Science.gov (United States)

    Tello, Javier; Montemayor, María Ignacia; Forneck, Astrid; Ibáñez, Javier

    2018-01-01

    Low pollen viability may limit grapevine yield under certain conditions, causing relevant economic losses to grape-growers. It is usually evaluated by the quantification of the number of viable and non-viable pollen grains that are present in a sample after an adequate pollen grain staining procedure. Although the manual counting of both types of grains is the simplest and most sensitive approach, it is a laborious and time-demanding process. In this regard, novel image-based approaches can assist in the objective, accurate and cost-effective phenotyping of this trait. Here, we introduce PollenCounter, an open-source macro implemented as a customizable Fiji tool for the high-throughput phenotyping of pollen viability. This tool splits RGB images of stained pollen grains into its primary channels, retaining red and green color fractionated images (which contain information on total and only viable pollen grains, respectively) for the subsequent isolation and counting of the regions of interest (pollen grains). This framework was successfully used for the analysis of pollen viability of a high number of samples collected in a large collection of grapevine cultivars. Results revealed a great genetic variability, from cultivars having very low pollen viability (like Corinto Bianco; viability: 14.1 ± 1.3%) to others with a very low presence of sterile pollen grains (Cuelga; viability: 98.2 ± 0.5%). A wide range of variability was also observed among several clones of cv. Tempranillo Tinto (from 97.9 ± 0.9 to 60.6 ± 5.9%, in the first season). Interestingly, the evaluation of this trait in a second season revealed differential genotype-specific sensitivity to environment. The use of PollenCounter is expected to aid