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Sample records for cardiovascular phenotypes based

  1. 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

  2. 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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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.

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

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    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.

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

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    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.

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

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    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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

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    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.

  19. 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.

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    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

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

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    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.

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

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    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.

  2. Preeclampsia, prematurity and cardiovascular health in adult life.

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    Lewandowski, Adam J; Leeson, Paul

    2014-11-01

    Investigations into how perinatal growth and intrauterine environment may 'programme' risk of later cardiovascular disease have been ongoing for over two decades. One of the more recent outcomes of these studies is the observation that certain pregnancy-related conditions, such as preterm birth, have an unusually large impact on the long-term cardiovascular health of the offspring. In the present paper, we review the current literature of how preterm birth affects the long-term cardiovascular structure and function of the offspring, considering three major areas of investigation: firstly, outlining the long-term cardiovascular phenotypic changes in preterm-born individuals; secondly, investigating factors related to preterm birth that may be modifying cardiovascular phenotype, such as preeclampsia, perinatal interventions, and physiological disturbances; and thirdly, the expected clinical relevance of these cardiovascular changes. This review discusses the importance of continued research focused on the mechanistic understanding of these cardiovascular alterations in order to develop specific primary prevention strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  4. [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.

  5. 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.

  6. 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.

  7. 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.

  8. Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

    Science.gov (United States)

    Miljkovic, Milica; Kotur-Stevuljevic, Jelena; Stefanovic, Aleksandra; Zeljkovic, Aleksandra; Vekic, Jelena; Gojkovic, Tamara; Bogavac-Stanojevic, Natasa; Nikolic, Milan; Simic-Ogrizovic, Sanja; Spasojevic-Kalimanovska, Vesna; Jelic-Ivanovic, Zorana

    2016-10-01

    Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). Renal patients with LDL A phenotype had increased oxidative stress (TOS: p LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p LDL B phenotype (p LDL B phenotype was characterized with increased TBARS (p LDL A phenotype in control group. Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

  9. 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.

  10. Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

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

    Science.gov (United States)

    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

  13. 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

  14. 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.

  15. Register-based studies of cardiovascular disease

    DEFF Research Database (Denmark)

    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...

  16. Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.

    Science.gov (United States)

    Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.

  17. Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Philip W. Connelly

    2012-01-01

    Full Text Available South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2=7.72, P=0.02. PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P=0.0001, HDL cholesterol (P=0.009, LDL cholesterol (P=0.02, and diabetes status (P<0.05. Arylesterase activity was only associated with HDL cholesterol (P=0.003. Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

  18. Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients.

    Science.gov (United States)

    Connelly, Philip W; Maguire, Graham F; Nash, Michelle M; Rapi, Lindita; Yan, Andrew T; Prasad, G V Ramesh

    2012-01-01

    South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ(2) = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients.

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. Association between alcohol and cardiovascular disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Dale, Caroline E; Zuccolo, Luisa

    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...... descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals...... disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health....

  4. 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.

  5. 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

  6. Artificial Intelligence in Precision Cardiovascular Medicine.

    Science.gov (United States)

    Krittanawong, Chayakrit; Zhang, HongJu; Wang, Zhen; Aydar, Mehmet; Kitai, Takeshi

    2017-05-30

    Artificial intelligence (AI) is a field of computer science that aims to mimic human thought processes, learning capacity, and knowledge storage. AI techniques have been applied in cardiovascular medicine to explore novel genotypes and phenotypes in existing diseases, improve the quality of patient care, enable cost-effectiveness, and reduce readmission and mortality rates. Over the past decade, several machine-learning techniques have been used for cardiovascular disease diagnosis and prediction. Each problem requires some degree of understanding of the problem, in terms of cardiovascular medicine and statistics, to apply the optimal machine-learning algorithm. In the near future, AI will result in a paradigm shift toward precision cardiovascular medicine. The potential of AI in cardiovascular medicine is tremendous; however, ignorance of the challenges may overshadow its potential clinical impact. This paper gives a glimpse of AI's application in cardiovascular clinical care and discusses its potential role in facilitating precision cardiovascular medicine. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  7. 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...

  8. 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

  9. 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.

  10. Critical Windows of Cardiovascular Susceptibility to Developmental Hypoxia in Common Snapping Turtle (Chelydra serpentina) Embryos.

    Science.gov (United States)

    Tate, Kevin B; Kohl, Zachary F; Eme, John; Rhen, Turk; Crossley, Dane A

    2015-01-01

    Environmental conditions fluctuate dramatically in some reptilian nests. However, critical windows of environmental sensitivity for cardiovascular development have not been identified. Continuous developmental hypoxia has been shown to alter cardiovascular form and function in embryonic snapping turtles (Chelydra serpentina), and we used this species to identify critical periods during which hypoxia modifies the cardiovascular phenotype. We hypothesized that incubation in 10% O2 during specific developmental periods would have differential effects on the cardiovascular system versus overall somatic growth. Two critical windows were identified with 10% O2 from 50% to 70% of incubation, resulting in relative heart enlargement, either via preservation of or preferential growth of this tissue, while exposure to 10% O2 from 20% to 70% of incubation resulted in a reduction in arterial pressure. The deleterious or advantageous aspects of these embryonic phenotypes in posthatching snapping turtles have yet to be explored. However, identification of these critical windows has provided insight into how the developmental environment alters the phenotype of reptiles and will also be pivotal in understanding its impact on the fitness of egg-laying reptiles.

  11. Identification of quantitative trait loci for fibrin clot phenotypes: the EuroCLOT study

    DEFF Research Database (Denmark)

    Williams, Frances M K; Carter, Angela M; Kato, Bernet

    2009-01-01

    OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs as...

  12. 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.

    Science.gov (United States)

    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.

  13. Hypertriglyceridemic waist phenotype in primary health care: comparison of two cutoff points

    Directory of Open Access Journals (Sweden)

    Braz MAD

    2017-09-01

    Full Text Available Marina Augusta Dias Braz,1 Jallyne Nunes Vieira,1 Flayane Oliveira Gomes,1 Priscilla Rafaella da Silva,1 Ohanna Thays de Medeiros Santos,1 Ilanna Marques Gomes da Rocha,2 Iasmin Matias de Sousa,2 Ana Paula Trussardi Fayh2 1Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte (UFRN, Santa Cruz, 2Department of Nutrition, Centro de Ciências da Saúde, UFRN, Natal, Rio Grande do Norte, Brazil Objective: We aimed to evaluate the prevalence of hypertriglyceridemic waist (HTGW phenotype among users of primary health care using two different cutoff points used in the literature. Methods: We evaluated adults and elderly individuals of both sexes who attended the same level of primary health care. HTGW phenotype was determined with measurements of waist circumference (WC and triglyceride levels and compared using cutoff points proposed by the National Cholesterol Education Program – NCEP/ATP III (WC ≥102 cm for men and ≥88 cm for women; triglyceride levels ≥150 mg/dL for both sexes and by Lemieux et al (WC ≥90 cm for men and ≥85 cm for women; triglyceride levels ≥177 mg/dL for both. Results: Within the sample of 437 individuals, 73.7% was female. The prevalence of HTGW phenotype was high and statistically different with the use of different cutoff points from the literature. The prevalence was higher using the NCEP/ATP III criteria compared to those proposed by Lemieux et al (36.2% and 32.5%, respectively, p<0.05. Individuals with the presence of the phenotype also presented alterations in other traditional cardiovascular risk markers. Conclusion: The HTGW phenotype identified high prevalence of cardiovascular risk in the population, with higher cutoff points from the NCEP/ATP III criteria. The difference in frequency of risk alerts us to the need to establish cutoff points for the Brazilian population. Keywords: abdominal obesity, cardiovascular disease, dyslipidemia, cardiovascular risk

  14. Association of various blood pressure variables and vascular phenotypes with coronary, stroke and renal deaths: Potential implications for prevention.

    Science.gov (United States)

    Harbaoui, Brahim; Courand, Pierre-Yves; Milon, Hughes; Fauvel, Jean-Pierre; Khettab, Fouad; Mechtouff, Laura; Cassar, Emmanuel; Girerd, Nicolas; Lantelme, Pierre

    2015-11-01

    The relationship between blood pressure (BP) and cardiovascular diseases has been extensively documented. However, the benefit of anti-hypertensive drugs differs according to the type of cardiovascular event. Aortic stiffness is tightly intertwined with BP and aorta cross-talk with small arteries. We endeavored to elucidate which BP component and type of vessel remodeling was predictive of the following outcomes: fatal myocardial infarction (MI), fatal stroke, renal -, coronary- or cerebrovascular-related deaths. Large vessel remodeling was estimated by an aortography-based aortic atherosclerosis score (ATS) while small vessel disease was documented by the presence of a hypertensive retinopathy. We included 1031 subjects referred for hypertension workup and assessed outcomes 30 years later. After adjustment for major risk factors, ATS and pulse pressure (PP) were predictive of coronary events while mean BP (MBP) and retinopathy were not. On the contrary, MBP was predictive of cerebrovascular and renal related deaths while ATS and PP were not. Retinopathy was only predictive of cerebrovascular related deaths. Lastly, the aortic atherosclerosis phenotype and increased PP identified patients prone to develop fatal MI whereas the retinopathy phenotype and increased MBP identified patients at higher risk of fatal stroke. These results illustrate the particular feature of the resistive coronary circulation comparatively to the brain and kidneys' low-resistance circulation. Our results advocate for a rational preventive strategy based on the identification of distinct clinical phenotypes. Accordingly, decreasing MBP levels could help preventing stroke in retinopathy phenotypes whereas targeting PP is possibly more efficient in preventing MI in atherosclerotic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. 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

  16. 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.

  17. 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.

  18. Is cardiovascular risk in women with PCOS a real risk? Current insights.

    Science.gov (United States)

    Papadakis, Georgios; Kandaraki, Eleni; Papalou, Olga; Vryonidou, Andromachi; Diamanti-Kandarakis, Evanthia

    2017-12-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. PCOS incorporates not only symptoms related to the reproductive system but also a clustering of systemic metabolic abnormalities that are linked with increased risk for cardiovascular disease (CVD). More specifically, metabolic aberrations such as impaired glucose and lipid metabolism, accompanied by increased low-grade inflammation as well as elevated coagulation factors appear to contribute to the increased cardiovascular risk. Even though many studies have indicated a rise in surrogate biomarkers of CVD in women with PCOS, it is still doubtful to what extent and magnitude this elevation can be translated to real cardiovascular events. Furthermore, the cardiovascular risk factors appear to vary significantly in the different phenotypes of the syndrome. Women with PCOS have the potential for early atherosclerosis, myocardial and endothelial dysfunction. Whether PCOS women are at real cardiovascular risk compared to controls remains between the verge of theoretical and real threat for the PCOS women at any age but particularly in the post-menopausal state. Interestingly, although the presence of the CVD risk factors is well documented in PCOS women, their combination on different phenotypes may play a role, which eventually results in a spectrum of clinical manifestations of CVD with variable degree of severity. The present manuscript aims to review the interaction between PCOS and the combination of several cardiovascular risk factors.

  19. 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)

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.

    Science.gov (United States)

    Voruganti, V Saroja; Lopez-Alvarenga, Juan C; Nath, Subrata D; Rainwater, David L; Bauer, Richard; Cole, Shelley A; Maccluer, Jean W; Blangero, John; Comuzzie, Anthony G

    2008-03-01

    Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans. The homeostatic model assessment method (HOMA-IR) is one of several approaches that are used to measure insulin resistance and was used here to generate a quantitative phenotype for genetic analysis. For 644 adults who had participated in the San Antonio Family Heart Study (SAFHS), estimates of genetic contribution were computed using a variance components method implemented in SOLAR. Traits that exhibited significant heritabilities were body mass index (BMI) (h (2) = 0.43), waist circumference (h (2) = 0.48), systolic blood pressure (h (2) = 0.30), diastolic blood pressure (h (2) = 0.21), pulse pressure (h (2) = 0.32), triglycerides (h (2) = 0.51), LDL cholesterol (h (2) = 0.31), HDL cholesterol (h (2) = 0.24), C-reactive protein (h (2) = 0.17), and HOMA-IR (h (2) = 0.33). A genome-wide scan for HOMA-IR revealed significant evidence of linkage on chromosome 12q24 (close to PAH (phenylalanine hydroxylase), LOD = 3.01, p HOMA-IR with BMI (rho (G) = 0.36), waist circumference (rho (G) = 0.47), pulse pressure (rho (G) = 0.39), and HDL cholesterol (rho (G) = -0.18). Identification of significant linkage for HOMA-IR on chromosome 12q replicates previous family-based studies reporting linkage of phenotypes associated with type 2 diabetes in the same chromosomal region. Significant genetic correlations between HOMA-IR and phenotypes related to CVD risk factors suggest that a common set of gene(s) influence the regulation of these phenotypes.

  5. Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

    Science.gov (United States)

    McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

    2017-12-10

    The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. 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.

  7. 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.

  8. 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.

  9. Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients

    Science.gov (United States)

    Windemuth, Andreas; de Leon, Jose; Goethe, John W.; Schwartz, Harold I.; Woolley, Stephen; Susce, Margaret; Kocherla, Mohan; Bogaard, Kali; Holford, Theodore R.; Seip, Richard L.; Ruaño, Gualberto

    2016-01-01

    The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms. Patients were assessed for fasting serum lipid (low density lipoprotein cholesterol [LDLc], high density lipoprotein cholesterol [HDLc], and triglycerides) and obesity phenotypes (body mass index, BMI). Thirteen candidate genes from previous studies of the same phenotypes in non-psychiatric populations were tested for association. We confirmed 8 of the 13 candidate genes at the 95% confidence level. An increased genetic effect size was observed for triglycerides in the psychiatric population compared to that in the cardiovascular population. PMID:21851846

  10. 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.

  11. 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

  12. 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.

  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. Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability.

    Directory of Open Access Journals (Sweden)

    Tania I Fuentes

    Full Text Available Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.

  15. 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.

  16. The interplay between adipose tissue and the cardiovascular system: is fat always bad?

    Science.gov (United States)

    Akoumianakis, Ioannis; Antoniades, Charalambos

    2017-07-01

    Obesity is a risk factor for cardiovascular disease (CVD). However, clinical research has revealed a paradoxically protective role for obesity in patients with chronic diseases including CVD, suggesting that the biological 'quality' of adipose tissue (AT) may be more important than overall AT mass or body weight. Importantly, AT is recognised as a dynamic organ secreting a wide range of biologically active adipokines, microRNAs, gaseous messengers, and other metabolites that affect the cardiovascular system in both endocrine and paracrine ways. Despite being able to mediate normal cardiovascular function under physiological conditions, AT undergoes a phenotypic shift characterised by acquisition of pro-oxidant and pro-inflammatory properties in cases of CVD. Crucially, recent evidence suggests that AT depots such as perivascular AT and epicardial AT are able to modify their phenotype in response to local signals of vascular and myocardial origin, respectively. Utilisation of this unique property of certain AT depots to dynamically track cardiovascular biology may reveal novel diagnostic and prognostic tools against CVD. Better understanding of the mechanisms controlling the 'quality' of AT secretome, as well as the communication links between AT and the cardiovascular system, is required for the efficient management of CVD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

  17. 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.

  18. 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...

  19. 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.

  20. Cardiac Phenotype of Prehypertrophic Fabry Disease.

    Science.gov (United States)

    Nordin, Sabrina; Kozor, Rebecca; Baig, Shanat; Abdel-Gadir, Amna; Medina-Menacho, Katia; Rosmini, Stefania; Captur, Gabriella; Tchan, Michel; Geberhiwot, Tarekegn; Murphy, Elaine; Lachmann, Robin; Ramaswami, Uma; Edwards, Nicola C; Hughes, Derralynn; Steeds, Richard P; Moon, James C

    2018-06-01

    Fabry disease (FD) is a rare and treatable X-linked lysosomal storage disorder. Cardiac involvement determines outcomes; therefore, detecting early changes is important. Native T1 by cardiovascular magnetic resonance is low, reflecting sphingolipid storage. Early phenotype development is familiar in hypertrophic cardiomyopathy but unexplored in FD. We explored the prehypertrophic cardiac phenotype of FD and the role of storage. A prospective, international multicenter observational study of 100 left ventricular hypertrophy-negative FD patients (mean age: 39±15 years; 19% male) and 35 age- and sex-matched healthy volunteers (mean age: 40±14 years; 25% male) who underwent cardiovascular magnetic resonance, including native T1 and late gadolinium enhancement, and 12-lead ECG. In FD, 41% had a low native T1 using a single septal region of interest, but this increased to 59% using a second slice because early native T1 lowering was patchy. ECG abnormalities were present in 41% and twice as common with low native T1 (53% versus 24%; P =0.005). When native T1 was low, left ventricular maximum wall thickness, indexed mass, and ejection fraction were higher (maximum wall thickness 9±1.5 versus 8±1.4 mm, P gadolinium enhancement was more likely when native T1 was low (27% versus 6%; P =0.01). FD had higher maximal apical fractal dimensions compared with healthy volunteers (1.27±0.06 versus 1.24±0.04; P <0.005) and longer anterior mitral valve leaflets (23±2 mm versus 21±3 mm; P <0.005). There is a detectable prehypertrophic phenotype in FD consisting of storage (low native T1), structural, functional, and ECG changes. © 2018 The Authors.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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 ...

  6. Clinical phenotype in relation to the distance-to-index-patient in familial hypercholesterolemia

    NARCIS (Netherlands)

    Besseling, Joost; Huijgen, Roeland; Martin, Seth S.; Hutten, Barbara A.; Kastelein, John J. P.; Hovingh, G. Kees

    2016-01-01

    We evaluated whether the severity of the familial hypercholesterolemia (FH) phenotype, i.e. increased levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) risk, decreases in more distantly related patients within one family. We included heterozygous FH patients

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Camiciottoli G

    2016-09-01

    Full Text Available Gianna Camiciottoli,1,2 Francesca Bigazzi,1 Chiara Magni,1 Viola Bonti,1 Stefano Diciotti,3 Maurizio Bartolucci,4 Mario Mascalchi,5 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, 2Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, 3Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, 4Department of Diagnostic Imaging, Careggi University Hospital, 5Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy Background: In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD. Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH, ischemic heart disease, heart failure, peripheral vascular disease (PVD, diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema and severity (mild and severe diseases were determined by clinical and functional parameters. Methods: A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide % and sputum characteristics. Comorbidities were assessed by objective medical records. Results: Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively. IAH prevailed significantly in predominant airway disease, osteoporosis prevailed

  12. 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.

  13. 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

  14. OBESITY PHENOTYPES IN URBAN MIDDLE-CLASS COHORTS; THE PRIT-LINDAVISTA MERGING EVIDENCE IN MEXICO: THE OPUS PRIME STUDY.

    Science.gov (United States)

    Fanghänel-Salmón, Guillermo; Gutiérrez-Salmeán, Gabriela; Samaniego, Virginia; Meaney, Alejandra; Sánchez-Reyes, Leticia; Navarrete, Ulises; Alcocer, Luis; Olivares-Corichi, Ivonne; Najera, Nayeli; Ceballos, Guillermo; Meaney, Eduardo

    2015-07-01

    even though overweight and obesity (O/O) are stated diseases, there is still a claim for a so-called "healthy obese" phenotype. Only few reports have explored the presence of different metabolic phenotypes along the body mass index (BMI) range and their corresponding associations to cardiovascular risks. as of BMI, and according to the presence of metabolic syndrome (MS) features (waist circumference, blood pressure, fasting glycemia, and lipid profile), phenotypes were determined. Cardiovascular risk was estimated with atherogenic quotients: total cholesterol/ HDL-c, LDL-c/HDL-c and the triglycerides (TG)/HDL-c index. in 8 405 mexican adults, 36% lean, 43% overweighed and 21% obese, nine phenotypes were identified: for each weight category there were subjects with normal metabolism (none MS factors), intermediate (≤ 2) and dysmetabolic (≥ 3). Only 10.8% of O/O had normal metabolism, and 5.8% of the lean persons were dysmetabolic. Atherogenic risk was higher in dysmetabolic obese persons, but the risk was high among all dysmetabolic people, independently of the weight status. TG/HDL-c showed the same trend. elevated cardiometabolic risk derives from the high prevalence of O/O. A great proportion of non-obese people have intermediate dysmetabolism. A genetic predisposition to obesity, insulin resistance, diabetes and dyslipidemia in Mexican population is blended to an unhealthy lifestyle, yielding to a catastrophic epidemic of diabetes, and cardiovascular diseases. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. 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.

  16. 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

  17. 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...

  18. 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.

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

    Science.gov (United States)

    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

  20. 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.

  1. 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...

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease and risk factors

    OpenAIRE

    van der Ende, M. Yldau; Hartman, Minke H. T.; Hagemeijer, Yanick; Meems, Laura M. G.; de Vries, Hendrik Sierd; Stolk, Ronald P.; de Boer, Rudolf A.; Sijtsma, Anna; van der Meer, Peter; Rienstra, Michiel; van der Harst, Pim

    2017-01-01

    Background: The LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30 years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented. Methods and results: Baseline cardiovascular phenotypeswere defined in 9700 juvenile (8-18 years) and 152,1...

  11. The impact of metabolic syndrome and CRP on vascular phenotype in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Alizadeh Dehnavi, R.; Beishuizen, E.D.; Ree, M.A. van de; Le Cessie, S.; Huisman, M.V.; Kluft, C.; Princen, H.M.G.; Tamsma, J.T.

    2008-01-01

    Background: The burden of cardiovascular disease in diabetes mellitus type 2 (DM2) patients is variable. We hypothesize that metabolic syndrome (MS) and low-grade systemic inflammation modify the extent of atherosclerosis in DM2. Methods: Vascular phenotype was determined using the following

  12. 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)

  13. Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype.

    Science.gov (United States)

    Armeni, Eleni; Stamatelopoulos, Kimon; Rizos, Demetrios; Georgiopoulos, George; Kazani, Maria; Kazani, Aikaterini; Kolyviras, Athanasios; Stellos, Konstantinos; Panoulis, Konstantinos; Alexandrou, Andreas; Creatsa, Maria; Papamichael, Christos; Lambrinoudaki, Irene

    2013-10-01

    The metabolic dysfunction accompanying the polycystic ovary syndrome (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD). Although menopause per se may be an additional risk factor of CVD, the association between PCOS in postmenopausal women and cardiovascular risk has not been adequately investigated. We aimed to evaluate the effect of PCOS on markers of subclinical atherosclerosis in nondiabetic postmenopausal women. This cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS phenotype was defined if three of the following were present: insulin resistance, current hyperandrogenism or history of clinical androgen excess, history of infertility, central obesity and history of irregular menses. Traditional CVD risk factors, as well as indices of arterial structure (intima-media thickness, atheromatous plaques presence) and function [flow-mediated dilation, pulse wave velocity (PWV), augmentation index] were compared between women with a PCOS phenotype and the rest of the sample, who served as controls. Women with the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed significantly between PCOS cases and controls (9.46±1.74 vs. 8.60±1.51 m/s, P=0.001, univariate). Multivariate regression analysis showed that the PCOS phenotype, age and SBP were the only independent predictors of PWV. Arterial stiffness is increased in asymptomatic, nondiabetic women with a putative PCOS phenotype, independently of age, BMI or blood pressure. This might present one mechanism through which PCOS increases the risk of CVD and hypertension later in life.

  14. 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

  15. 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.

  16. Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

    International Nuclear Information System (INIS)

    Ghadimi Mahani, Maryam; Morani, Ajaykumar C.; Lu, Jimmy C.; Dorfman, Adam L.; Fazeli Dehkordy, Soudabeh; Jeph, Sunil; Agarwal, Prachi P.

    2016-01-01

    With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

  17. Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

    Energy Technology Data Exchange (ETDEWEB)

    Ghadimi Mahani, Maryam [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Morani, Ajaykumar C. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); Fazeli Dehkordy, Soudabeh [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Providence Hospital and Medical Centers, Department of Graduate Medical Education, Southfield, MI (United States); Jeph, Sunil [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Geisinger Medical Center, Department of Radiology, Danville, PA (United States); Agarwal, Prachi P. [University of Michigan Health System, Department of Radiology, Division of Cardiothoracic Radiology, Ann Arbor, MI (United States)

    2016-04-15

    With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

  18. 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

  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. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers.

    Science.gov (United States)

    Kaluarachchi, Manuja R; Boulangé, Claire L; Garcia-Perez, Isabel; Lindon, John C; Minet, Emmanuel F

    2016-10-01

    Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC-MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment.

  14. A broad phenotypic screen identifies novel phenotypes driven by a single mutant allele in Huntington's disease CAG knock-in mice.

    Directory of Open Access Journals (Sweden)

    Sabine M Hölter

    Full Text Available Huntington's disease (HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in the HTT gene encoding huntingtin. The disease has an insidious course, typically progressing over 10-15 years until death. Currently there is no effective disease-modifying therapy. To better understand the HD pathogenic process we have developed genetic HTT CAG knock-in mouse models that accurately recapitulate the HD mutation in man. Here, we describe results of a broad, standardized phenotypic screen in 10-46 week old heterozygous HdhQ111 knock-in mice, probing a wide range of physiological systems. The results of this screen revealed a number of behavioral abnormalities in HdhQ111/+ mice that include hypoactivity, decreased anxiety, motor learning and coordination deficits, and impaired olfactory discrimination. The screen also provided evidence supporting subtle cardiovascular, lung, and plasma metabolite alterations. Importantly, our results reveal that a single mutant HTT allele in the mouse is sufficient to elicit multiple phenotypic abnormalities, consistent with a dominant disease process in patients. These data provide a starting point for further investigation of several organ systems in HD, for the dissection of underlying pathogenic mechanisms and for the identification of reliable phenotypic endpoints for therapeutic testing.

  15. 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

  16. The nature of stable insomnia phenotypes.

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L

    2015-01-01

    We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Longitudinal. Urban, community-based. Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). None. At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the 'neither criterion' phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With the exception of daytime sleepiness, few clinical differences are apparent across stable phenotypes.

  17. Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome.

    Science.gov (United States)

    Lambrinoudaki, Irene

    2011-01-01

    Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders, affecting 5-10% of the female population of reproductive age. "Classic" PCOS is characterized by clinical or biochemical hyperandrogenism and oligo-ovulation. According to the 2003 Rotterdam criteria, two additional phenotypes are recognized: (1) the ovulatory patient with androgen excess and polycystic ovarian morphology and (2) the anovulatory patient with polycystic ovarian morphology without androgen excess. PCOS is associated with an adverse cardiometabolic profile, consisting of increased total or central adiposity, increased blood pressure, a pro-atherogenic lipid profile, increased inflammatory markers, insulin resistance and abnormal glucose metabolism. Furthermore, the incidence of overt or gestational diabetes mellitus, as well as of preeclampsia is significantly higher in PCOS patients. Among the various PCOS phenotypes, those with evidence of androgen excess have the highest burden of cardiovascular risk. Studies evaluating the incidence of cardiovascular disease in postmenopausal women with PCOS are extremely sparse. The available data so far indicate that coronary heart disease, as well as cerebrovascular disease is more common in postmenopausal PCOS patients. Persisting high androgen levels through the menopause, obesity and maturity onset diabetes mellitus are proposed as the main mechanisms accounting for the increased risk. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

  19. Can genetic pleiotropy replicate common clinical constellations of cardiovascular disease and risk?

    Directory of Open Access Journals (Sweden)

    Omri Gottesman

    Full Text Available The relationship between obesity, diabetes, hyperlipidemia, hypertension, kidney disease and cardiovascular disease (CVD is established when looked at from a clinical, epidemiological or pathophysiological perspective. Yet, when viewed from a genetic perspective, there is comparatively little data synthesis that these conditions have an underlying relationship. We sought to investigate the overlap of genetic variants independently associated with each of these commonly co-existing conditions from the NHGRI genome-wide association study (GWAS catalog, in an attempt to replicate the established notion of shared pathophysiology and risk. We used pathway-based analyses to detect subsets of pleiotropic genes involved in similar biological processes. We identified 107 eligible GWAS studies related to CVD and its established comorbidities and risk factors and assigned genes that correspond to the associated signals based on their position. We found 44 positional genes shared across at least two CVD-related phenotypes that independently recreated the established relationship between the six phenotypes, but only if studies representing non-European populations were included. Seven genes revealed pleiotropy across three or more phenotypes, mostly related to lipid transport and metabolism. Yet, many genes had no relationship to each other or to genes with established functional connection. Whilst we successfully reproduced established relationships between CVD risk factors using GWAS findings, interpretation of biological pathways involved in the observed pleiotropy was limited. Further studies linking genetic variation to gene expression, as well as describing novel biological pathways will be needed to take full advantage of GWAS results.

  20. 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.

  1. 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

  2. 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

  3. Marfan syndrome--a diagnostic challenge caused by phenotypic and genetic heterogeneity.

    Science.gov (United States)

    Baumgartner, C; Mátyás, G; Steinmann, B; Baumgartner, D

    2005-01-01

    Marfan syndrome (MFS) is an autosomal dominant inherited connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene with variable clinical manifestations in the cardiovascular, musculoskeletal and ocular systems. Data of moleculor genetic analysis and a catalogue of clinical manifestations including aortic elastic parameters were mined in order to (i) assess aortic abnormality before and during medical treatment, and to (ii) identify novel correlations between the genotype and phenotype of the disease using hierarchical cluster analysis and logistic regression analysis. A score measure describing the similarity between a patient's clinical symptoms and a characteristic phenotype class was introduced. A probabilistic model for monitoring the loss of aortic elasticity was built on merely aortic parameters of 34 patients with classic MFS and 43 control subjects showing a sensitivity of 82% and a specificity of 96%. The clinical phenotypes of 100 individuals with classical or suspected MFS were clustered yielding four different phenotypic expressions. The highest correlation was found between FBN1 missense mutations, which manifested as ectopia lentis, skeletal major and skin minor criteria, and two out of four clustered phenotypes. The probability of the presence of a missense mutation in both phenotype classes is approximately 70%. Monitoring of aortic elastic properties during medical treatment may serve as additional criterion to indicate elective surgical interventions. Genotype-phenotype correlation may contribute to anticipate the clinical consequences of specific FBN1 mutations more comprehensively and may be helpful to identify MFS patients at risk at on early stage of disease.

  4. The Nature of Stable Insomnia Phenotypes

    Science.gov (United States)

    Pillai, Vivek; Roth, Thomas; Drake, Christopher L.

    2015-01-01

    Study Objectives: We examined the 1-y stability of four insomnia symptom profiles: sleep onset insomnia; sleep maintenance insomnia; combined onset and maintenance insomnia; and neither criterion (i.e., insomnia cases that do not meet quantitative thresholds for onset or maintenance problems). Insomnia cases that exhibited the same symptom profile over a 1-y period were considered to be phenotypes, and were compared in terms of clinical and demographic characteristics. Design: Longitudinal. Setting: Urban, community-based. Participants: Nine hundred fifty-four adults with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based current insomnia (46.6 ± 12.6 y; 69.4% female). Interventions: None. Measurements and results: At baseline, participants were divided into four symptom profile groups based on quantitative criteria. Follow-up assessment 1 y later revealed that approximately 60% of participants retained the same symptom profile, and were hence judged to be phenotypes. Stability varied significantly by phenotype, such that sleep onset insomnia (SOI) was the least stable (42%), whereas combined insomnia (CI) was the most stable (69%). Baseline symptom groups (cross-sectionally defined) differed significantly across various clinical indices, including daytime impairment, depression, and anxiety. Importantly, however, a comparison of stable phenotypes (longitudinally defined) did not reveal any differences in impairment or comorbid psychopathology. Another interesting finding was that whereas all other insomnia phenotypes showed evidence of an elevated wake drive both at night and during the day, the “neither criterion” phenotype did not; this latter phenotype exhibited significantly higher daytime sleepiness despite subthreshold onset and maintenance difficulties. Conclusions: By adopting a stringent, stability-based definition, this study offers timely and important data on the longitudinal trajectory of specific insomnia phenotypes. With

  5. Anti-atherosclerotic plants which modulate the phenotype of vascular smooth muscle cells.

    Science.gov (United States)

    Saleh Al-Shehabi, Tuqa; Iratni, Rabah; Eid, Ali H

    2016-10-15

    Cardiovascular disease (CVD) remains the leading cause of global death, with atherosclerosis being a major contributor to this mortality. Several mechanisms are implicated in the pathogenesis of this disease. A key element in the development and progression of atherosclerotic lesions is the phenotype of vascular smooth muscle cells. Under pathophysiologic conditions such as injury, these cells switch from a contractile to a synthetic phenotype that often possesses high proliferative and migratory capacities. Despite major advances made in the management and treatment of atherosclerosis, mortality associated with this disease remains high. This mandates that other approaches be sought. Herbal medicine, especially for the treatment of CVD, has been gaining more attention in recent years. This is in no small part due to the evidence-based values associated with the consumption of many plants as well as the relatively cheaper prices, easier access and conventional folk medicine "inherited" over generations. Sections: In this review, we provide a brief introduction about the pathogenesis of atherosclerosis then we highlight the role of vascular smooth muscle cells in this disease, especially when a phenotypic switch of these cells arises. We then thoroughly discuss the various plants that show potentially beneficial effects as anti-atherosclerotic, with prime attention given to herbs and plants that inhibit the phenotypic switch of vascular smooth muscle cells. Accumulating evidence provides the justification for the use of botanicals in the treatment or prevention of atherosclerosis. However, further studies, especially clinical ones, are warranted to better define several pharmacological parameters of these herbs, such as toxicity, tolerability, and efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Landscape of Innovation for Cardiovascular Pharmaceuticals: From Basic Science to New Molecular Entities.

    Science.gov (United States)

    Beierlein, Jennifer M; McNamee, Laura M; Walsh, Michael J; Kaitin, Kenneth I; DiMasi, Joseph A; Ledley, Fred D

    2017-07-01

    This study examines the complete timelines of translational science for new cardiovascular therapeutics from the initiation of basic research leading to identification of new drug targets through clinical development and US Food and Drug Administration (FDA) approval of new molecular entities (NMEs) based on this research. This work extends previous studies by examining the association between the growth of research on drug targets and approval of NMEs associated with these targets. Drawing on research on innovation in other technology sectors, where technological maturity is an important determinant in the success or failure of new product development, an analytical model was used to characterize the growth of research related to the known targets for all 168 approved cardiovascular therapeutics. Categorizing and mapping the technological maturity of cardiovascular therapeutics reveal that (1) there has been a distinct transition from phenotypic to targeted methods for drug discovery, (2) the durations of clinical and regulatory processes were significantly influenced by changes in FDA practice, and (3) the longest phase of the translational process was the time required for technology to advance from initiation of research to a statistically defined established point of technology maturation (mean, 30.8 years). This work reveals a normative association between metrics of research maturation and approval of new cardiovascular therapeutics and suggests strategies for advancing translational science by accelerating basic and applied research and improving the synchrony between the maturation of this research and drug development initiatives. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  7. Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

    Science.gov (United States)

    Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

    2013-06-01

    Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

  8. 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

  9. 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

  10. 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

  11. 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…

  12. 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

  13. Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry.

    Science.gov (United States)

    Bourbon, Mafalda; Alves, Ana Catarina; Alonso, Rodrigo; Mata, Nelva; Aguiar, Pedro; Padró, Teresa; Mata, Pedro

    2017-07-01

    Familial hypercholesterolemia (FH) is an autosomal dominant disease of cholesterol metabolism that confers an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Therefore, early identification and treatment of these patients can improve prognosis and reduce the burden of cardiovascular mortality. The aim of this work was to perform the mutational analysis of the SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) registry. The study recruited 2938 individuals with genetic diagnosis of FH belonging to 775 families. Statistical analysis was performed using SPSS v23. A total of 194 variants have been detected in this study, 24 of them were never described before. About 88% of the patients have a pathogenic or likely pathogenic variant. Patients with null variants have a more severe phenotype than patients with defective variants, presenting with significantly higher levels of atherogenic particles (total cholesterol, LDL-cholesterol and apolipoprotein B). This study shows the molecular characteristics of the FH patients included in the SAFEHEART registry and the relationship with the phenotypic expression. The majority of the genetic variants are considered to be pathogenic or likely pathogenic, which confers a high level of confidence to the entry and follow-up data analysis performed with this registry concerning FH patients' prognosis, treatment and survival. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Kullo Iftikhar J

    2011-04-01

    Full Text Available Abstract Background We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants. Methods From the database of genome-wide association studies (GWAS, we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels. We identified 292 SNPs in 270 genes associated with a disease or trait at P -8. As part of the Human Genome-Diversity Project (HGDP, 158 (54.1% of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, FST, was calculated to quantify differences in risk allele frequencies (RAFs among populations and geographic areas. Results Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global FST (0.1042 for 158 SNPs among the populations was not significantly higher than the mean global FST of 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global FST (P FST of 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score. Conclusion Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.

  15. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  16. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    International Nuclear Information System (INIS)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei; Lv, Ruijuan; Wang, Zhihao; Shang, Yuanyuan; Zhang, Yun; Zhong, Ming; Chen, Yuguo; Tang, Mengxiong

    2013-01-01

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

  17. 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.

  18. 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

  19. Advanced phenotyping and phenotype data analysis for the plant growth and development study

    Directory of Open Access Journals (Sweden)

    Md. Matiur eRahaman

    2015-08-01

    Full Text Available Due to increase in the consumption of food, feed, fuel and to ensure global food security for rapidly growing human population, there is need to breed high yielding crops that can adapt to future climate. To solve these global issues, novel approaches are required to provide quantitative phenotypes to elucidate the genetic basis of agriculturally import traits and to screen germplasm with super performance in function under resource-limited environment. At present, plant phenomics has offered and integrated suite technologies for understanding the complete set of phenotypes of plants, towards the progression of the full characteristics of plants with whole sequenced genomes. In this aspect, high-throughput phenotyping platforms have been developed that enables to capture extensive and intensive phenotype data from non-destructive imaging over time. These developments advance our view on plant growth and performance with responses to the changing climate and environment. In this paper, we present a brief review on currently developed high-throughput plant phenotyping infrastructures based on imaging techniques and corresponding principles for phenotype data analysis.

  20. 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.

  1. 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.

  2. Cardiovascular investigations of airline pilots with excessive cardiovascular risk.

    Science.gov (United States)

    Wirawan, I Made Ady; Aldington, Sarah; Griffiths, Robin F; Ellis, Chris J; Larsen, Peter D

    2013-06-01

    This study examined the prevalence of airline pilots who have an excessive cardiovascular disease (CVD) risk score according to the New Zealand Guideline Group (NZGG) Framingham-based Risk Chart and describes their cardiovascular risk assessment and investigations. A cross-sectional study was performed among 856 pilots employed in an Oceania based airline. Pilots with elevated CVD risk that had been previously evaluated at various times over the previous 19 yr were reviewed retrospectively from the airline's medical records, and the subsequent cardiovascular investigations were then described. There were 30 (3.5%) pilots who were found to have 5-yr CVD risk score of 10-15% or higher. Of the 29 pilots who had complete cardiac investigations data, 26 pilots underwent exercise electrocardiography (ECG), 2 pilots progressed directly to coronary angiograms and 1 pilot with abnormal echocardiogram was not examined further. Of the 26 pilots, 7 had positive or borderline exercise tests, all of whom subsequently had angiograms. One patient with a negative exercise test also had a coronary angiogram. Of the 9 patients who had coronary angiograms as a consequence of screening, 5 had significant disease that required treatment and 4 had either trivial disease or normal coronary arteries. The current approach to investigate excessive cardiovascular risk in pilots relies heavily on exercise electrocardiograms as a diagnostic test, and may not be optimal either to detect disease or to protect pilots from unnecessary invasive procedures. A more comprehensive and accurate cardiac investigation algorithm to assess excessive CVD risk in pilots is required.

  3. 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.

  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. Federated Tensor Factorization for Computational Phenotyping

    Science.gov (United States)

    Kim, Yejin; Sun, Jimeng; Yu, Hwanjo; Jiang, Xiaoqian

    2017-01-01

    Tensor factorization models offer an effective approach to convert massive electronic health records into meaningful clinical concepts (phenotypes) for data analysis. These models need a large amount of diverse samples to avoid population bias. An open challenge is how to derive phenotypes jointly across multiple hospitals, in which direct patient-level data sharing is not possible (e.g., due to institutional policies). In this paper, we developed a novel solution to enable federated tensor factorization for computational phenotyping without sharing patient-level data. We developed secure data harmonization and federated computation procedures based on alternating direction method of multipliers (ADMM). Using this method, the multiple hospitals iteratively update tensors and transfer secure summarized information to a central server, and the server aggregates the information to generate phenotypes. We demonstrated with real medical datasets that our method resembles the centralized training model (based on combined datasets) in terms of accuracy and phenotypes discovery while respecting privacy. PMID:29071165

  6. Effects of Estrogen in Gender-dependent Fetal Programming of Adult Cardiovascular Dysfunction.

    Science.gov (United States)

    Chen, Zewen; Wang, Lei; Ke, Jun; Xiao, DaLiao

    2018-03-01

    Epidemiological studies and experimental studies have demonstrated that intrauterine adverse environment increases the risk of cardiovascular disease (CVD) in adulthood. However, whether an individual develops a cardiovascular dysfunctional phenotype may depend on genetic background, age, and sex. In this review, we summarize some of the recent experimental animal studies in the developmental programming of adult CVD with an emphasis on sex differences and the potential role of estrogen in mediating sexual dimorphism. Few epidemiological studies report the effect of sex on the developmental programming of CVD. However, numerous experimental animal studies have shown a sex difference in fetal programming of adult cardiovascular dysfunction. Most of the animal studies indicate that male offspring develop cardiovascular dysfunction and CVD in adulthood, whereas adult females appear to be protected. Estrogen is one of the key factors that contributes to the sex difference of adult CVD. Estrogen/its receptor (ER) may interact with the RAS system by changes of DNA methylation patterns at the target gene promoter, serve as an antioxidant to counteract the prenatal insults-induced heightened ROS, and function as an eNOS activator to increase vasodilation, resulting in the protection of female offspring from the development of hypertension and other CVDs. These studies suggest that estrogen/ER may contribute to sex differences in cardiovascular response to an adverse intrauterine environment and play a significant role in modulating the cardiovascular response in adulthood. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Recent advances in cardiovascular aspects of polycystic ovary syndrome.

    Science.gov (United States)

    Sathyapalan, T; Atkin, S L

    2012-04-01

    Polycystic ovary syndrome (PCOS) has been associated with increased cardiovascular risk (CVR) markers, but population studies have not clarified whether there is an increase in cardiovascular morbidity and mortality. Four different PCOS phenotypes resulted from the Rotterdam criteria that may differ in their CVR potential, thus introducing further complexity. This has led to studies using surrogate CVR markers including biomarkers in blood and imaging such as flow-mediated vasodilatation. In PCOS, both peripheral and central insulin resistance (IR) have been shown. Weight loss has been shown to improve IR and visceral fat, while insulin sensitizer therapies with metformin or thiazolidinediones improve IR and endothelial dysfunction. IR is also found in non-alcoholic fatty liver disease that in turn is very common in PCOS; studies have suggested that IR may be improved by treatment with metformin and omega-3 fish oils. PCOS patients have a more dyslipidemic phenotype that is worse in 'classical PCOS' associated with a higher CVR. Studies with atorvastatin and simvastatin have reported a decrease in the lipid parameters and an improvement in CVR indices including IR, but it is unclear whether this is due to their lipid-lowering action or a pleiotropic effect of the statin. In this expert opinion review, the relevant literature published during the last 2 years was considered. It focuses on some recent important data that has emerged while also exposing the gaps that remain in our knowledge that need to be addressed.

  8. 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

  9. 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.

  10. Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

    Science.gov (United States)

    Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

    2015-12-01

    Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

  11. 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

  12. 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.

  13. 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...

  14. 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.

  15. Worm Phenotype Ontology: Integrating phenotype data within and beyond the C. elegans community

    Directory of Open Access Journals (Sweden)

    Yook Karen

    2011-01-01

    Full Text Available Abstract Background Caenorhabditis elegans gene-based phenotype information dates back to the 1970's, beginning with Sydney Brenner and the characterization of behavioral and morphological mutant alleles via classical genetics in order to understand nervous system function. Since then C. elegans has become an important genetic model system for the study of basic biological and biomedical principles, largely through the use of phenotype analysis. Because of the growth of C. elegans as a genetically tractable model organism and the development of large-scale analyses, there has been a significant increase of phenotype data that needs to be managed and made accessible to the research community. To do so, a standardized vocabulary is necessary to integrate phenotype data from diverse sources, permit integration with other data types and render the data in a computable form. Results We describe a hierarchically structured, controlled vocabulary of terms that can be used to standardize phenotype descriptions in C. elegans, namely the Worm Phenotype Ontology (WPO. The WPO is currently comprised of 1,880 phenotype terms, 74% of which have been used in the annotation of phenotypes associated with greater than 18,000 C. elegans genes. The scope of the WPO is not exclusively limited to C. elegans biology, rather it is devised to also incorporate phenotypes observed in related nematode species. We have enriched the value of the WPO by integrating it with other ontologies, thereby increasing the accessibility of worm phenotypes to non-nematode biologists. We are actively developing the WPO to continue to fulfill the evolving needs of the scientific community and hope to engage researchers in this crucial endeavor. Conclusions We provide a phenotype ontology (WPO that will help to facilitate data retrieval, and cross-species comparisons within the nematode community. In the larger scientific community, the WPO will permit data integration, and

  16. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome.

    Science.gov (United States)

    Vryonidou, Andromachi; Papatheodorou, Athanasios; Tavridou, Anna; Terzi, Thomais; Loi, Vasiliki; Vatalas, Ioannis-Anastasios; Batakis, Nikolaos; Phenekos, Constantinos; Dionyssiou-Asteriou, Amalia

    2005-05-01

    Polycystic ovary syndrome (PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower delta4-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall.

  17. 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.

  18. 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.

  19. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery.

    Science.gov (United States)

    Lykke, Jacob A; Langhoff-Roos, Jens; Lockwood, Charles J; Triche, Elizabeth W; Paidas, Michael J

    2010-07-01

    The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy complications on early maternal death in a registry-based retrospective cohort study of 782 287 women with a first singleton delivery in Denmark 1978-2007, followed for a median of 14.8 years (range 0.25-30.2) accruing 11.6 million person-years. We employed Cox proportional hazard models of early death from cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery and small-for-gestational-age offspring 3.30 [2.25, 4.84]; preterm delivery, small-for-gestational-age offspring and pre-eclampsia 3.85 [2.07, 7.19]. Thus, we conclude that, separately and combined, preterm delivery and small-for-gestational-age are strong markers of early maternal death from both cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes.

  20. [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.

  1. Machine learning in cardiovascular medicine: are we there yet?

    Science.gov (United States)

    Shameer, Khader; Johnson, Kipp W; Glicksberg, Benjamin S; Dudley, Joel T; Sengupta, Partho P

    2018-01-19

    Artificial intelligence (AI) broadly refers to analytical algorithms that iteratively learn from data, allowing computers to find hidden insights without being explicitly programmed where to look. These include a family of operations encompassing several terms like machine learning, cognitive learning, deep learning and reinforcement learning-based methods that can be used to integrate and interpret complex biomedical and healthcare data in scenarios where traditional statistical methods may not be able to perform. In this review article, we discuss the basics of machine learning algorithms and what potential data sources exist; evaluate the need for machine learning; and examine the potential limitations and challenges of implementing machine in the context of cardiovascular medicine. The most promising avenues for AI in medicine are the development of automated risk prediction algorithms which can be used to guide clinical care; use of unsupervised learning techniques to more precisely phenotype complex disease; and the implementation of reinforcement learning algorithms to intelligently augment healthcare providers. The utility of a machine learning-based predictive model will depend on factors including data heterogeneity, data depth, data breadth, nature of modelling task, choice of machine learning and feature selection algorithms, and orthogonal evidence. A critical understanding of the strength and limitations of various methods and tasks amenable to machine learning is vital. By leveraging the growing corpus of big data in medicine, we detail pathways by which machine learning may facilitate optimal development of patient-specific models for improving diagnoses, intervention and outcome in cardiovascular medicine. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. 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.

  3. Enabling phenotypic big data with PheNorm.

    Science.gov (United States)

    Yu, Sheng; Ma, Yumeng; Gronsbell, Jessica; Cai, Tianrun; Ananthakrishnan, Ashwin N; Gainer, Vivian S; Churchill, Susanne E; Szolovits, Peter; Murphy, Shawn N; Kohane, Isaac S; Liao, Katherine P; Cai, Tianxi

    2018-01-01

    Electronic health record (EHR)-based phenotyping infers whether a patient has a disease based on the information in his or her EHR. A human-annotated training set with gold-standard disease status labels is usually required to build an algorithm for phenotyping based on a set of predictive features. The time intensiveness of annotation and feature curation severely limits the ability to achieve high-throughput phenotyping. While previous studies have successfully automated feature curation, annotation remains a major bottleneck. In this paper, we present PheNorm, a phenotyping algorithm that does not require expert-labeled samples for training. The most predictive features, such as the number of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or mentions of the target phenotype, are normalized to resemble a normal mixture distribution with high area under the receiver operating curve (AUC) for prediction. The transformed features are then denoised and combined into a score for accurate disease classification. We validated the accuracy of PheNorm with 4 phenotypes: coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. The AUCs of the PheNorm score reached 0.90, 0.94, 0.95, and 0.94 for the 4 phenotypes, respectively, which were comparable to the accuracy of supervised algorithms trained with sample sizes of 100-300, with no statistically significant difference. The accuracy of the PheNorm algorithms is on par with algorithms trained with annotated samples. PheNorm fully automates the generation of accurate phenotyping algorithms and demonstrates the capacity for EHR-driven annotations to scale to the next level - phenotypic big data. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. The impact of cardiovascular disease prevalence on women's enrollment in landmark randomized cardiovascular trials: a systematic review.

    Science.gov (United States)

    Tsang, Wendy; Alter, David A; Wijeysundera, Harindra C; Zhang, Tony; Ko, Dennis T

    2012-01-01

    Many studies have demonstrated that women are substantially underrepresented in cardiovascular trials, but few have considered that women develop cardiovascular disease at older ages than men. The extent to which observed gender enrollment inequalities persist after accounting for age-gender differences in disease prevalence is unknown. The purpose of the study was to compare observed rates of women participating in cardiovascular clinical trials with expected rates of female participation based on age- and gender-specific population disease prevalence. Publications between 1997 and 2009 in the three leading medical journals were included to calculate observed women's enrollment rates. Population-based data in Canada were used to determine the expected enrollment rates of women. Multicenter, randomized cardiovascular clinical trials that enrolled both men and women were analyzed. Two reviewers independently extracted data on women's enrollment and important clinical trial characteristics. The female enrollment rate was 30% in the included 325 trials, which ranged from 27% in trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to 45% in primary prevention. Increased female enrollment correlated strongly with increasing age at recruitment in cardiovascular clinical trials (P disease prevalence, gaps in female enrollment were much lower than the expected enrollment rates estimated by 5% in coronary artery disease, 13% in heart failure, 9% in arrhythmia, and 3% in primary prevention. Only cardiovascular trials were evaluated in our study. Female underrepresentation in cardiovascular clinical trials is smaller than conventionally believed after accounting for age- and gender-specific population disease prevalence. Our findings suggest that greater representation of women in cardiovascular clinical trials can be achieved through the recruitment of older populations.

  9. 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.

  10. 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...

  11. 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...

  12. Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells.

    Science.gov (United States)

    Ryan, Alan J; O'Brien, Fergal J

    2015-12-01

    Biomaterials with the capacity to innately guide cell behaviour while also displaying suitable mechanical properties remain a challenge in tissue engineering. Our approach to this has been to utilise insoluble elastin in combination with collagen as the basis of a biomimetic scaffold for cardiovascular tissue engineering. Elastin was found to markedly alter the mechanical and biological response of these collagen-based scaffolds. Specifically, during extensive mechanical assessment elastin was found to reduce the specific tensile and compressive moduli of the scaffolds in a concentration dependant manner while having minimal effect on scaffold microarchitecture with both scaffold porosity and pore size still within the ideal ranges for tissue engineering applications. However, the viscoelastic properties were significantly improved with elastin addition with a 3.5-fold decrease in induced creep strain, a 6-fold increase in cyclical strain recovery, and with a four-parameter viscoelastic model confirming the ability of elastin to confer resistance to long term deformation/creep. Furthermore, elastin was found to result in the modulation of SMC phenotype towards a contractile state which was determined via reduced proliferation and significantly enhanced expression of early (α-SMA), mid (calponin), and late stage (SM-MHC) contractile proteins. This allows the ability to utilise extracellular matrix proteins alone to modulate SMC phenotype without any exogenous factors added. Taken together, the ability of elastin to alter the mechanical and biological response of collagen scaffolds has led to the development of a biomimetic biomaterial highly suitable for cardiovascular tissue engineering. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 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.

  14. Investigation of the 5q33.3 longevity locus and age-related phenotypes

    DEFF Research Database (Denmark)

    Nygaard, Marianne; Thinggaard, Mikael; Christensen, Kaare

    2017-01-01

    A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation and cardi......A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongside APOE and FOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation...... and cardiovascular diseases in middle-aged individuals. However, part of the influence on mortality appears to be independent of cardiovascular phenotypes, and the role of the 5q33.3 locus in longevity and survival is therefore still partly unknown. We investigated the association between the longevity......-associated variant rs2149954 on chromosome 5q33.3 and age-related phenotypes in two cohorts of 1,588 and 1,271 long-lived individuals (mean ages 93.1 and 95.9 years, respectively) as well as in 700 middle-aged and 677 elderly individuals (mean ages 52.5 and 78.7 years). Altogether, nominally significant associations...

  15. Racism and cardiovascular disease: implications for nursing.

    Science.gov (United States)

    Jackson, Jennifer; McGibbon, Elizabeth; Waldron, Ingrid

    2013-01-01

    The social determinants of health (SDH) are recognized as a prominent influence on health outcomes across the lifespan. Racism is identified as a key SDH. In this article, the authors describe the concept of racism as an SDH, its impact in discriminatory actions and inactions, and the implications for cardiovascular nurses. Although research in Canada on the links among racism, stress, and cardiovascular disease is limited, there is growing evidence about the stress of racism and its long-term impact on cardiovascular health. The authors discuss how cardiovascular nursing could be enhanced through an understanding of racism-related stress, and race-based differences in cardiovascular care. The authors conclude with strategies for action to address this nursing concern.

  16. Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes.

    Science.gov (United States)

    Carmina, E; Lobo, R A

    2007-02-01

    Serum DHEAS has been found to be elevated in some women with polycystic ovary syndrome (PCOS). We wished to determine whether this prevalence is different in women with androgen excess who have different phenotypes and to correlate these findings with various cardiovascular and metabolic parameters. Two hundred and thirty-eight young hyperandrogenic women categorized into various diagnostic groups were evaluated for elevations in serum DHEAS, testosterone, glucose, insulin, quantitative insulin-sensitivity check index (QUICKI), cholesterol, HDL-C, LDL-C, triglycerides and C-reactive protein (CRP). Data were stratified based on elevations in DHEAS. Serum DHEAS was elevated in 39.5% for the entire group [36.7% in PCOS and 48.3% in idiopathic hyperandrogenism (IHA)]. In classic (C)-PCOS, the prevalence was 39.6% and in ovulatory (OV) PCOS it was 29.1%. These differences were not statistically significant. Women with elevated DHEAS had higher testosterone but lower insulin, higher QUICKI, lower total and LDL-cholesterol and higher HDL-cholesterol, pPCOS. The prevalence of adrenal hyperandrogenism, as determined by elevations in DHEAS, appears to be statistically similar in IHA, C-PCOS and compared to OV-PCOS. Metabolic and cardiovascular parameters were noted to be more favorable in those women who have higher DHEAS levels.

  17. Developmental plasticity and epigenetic mechanisms underpinning metabolic and cardiovascular diseases.

    Science.gov (United States)

    Low, Felicia M; Gluckman, Peter D; Hanson, Mark A

    2011-06-01

    The importance of developmental factors in influencing the risk of later-life disease has a strong evidence base derived from multiple epidemiological, clinical and experimental studies in animals and humans. During early life, an organism is able to adjust its phenotypic development in response to environmental cues. Such developmentally plastic responses evolved as a fitness-maximizing strategy to cope with variable environments. There are now increasing data that these responses are, at least partially, underpinned by epigenetic mechanisms. A mismatch between the early and later-life environments may lead to inappropriate early life-course epigenomic changes that manifest in later life as increased vulnerability to disease. There is also growing evidence for the transgenerational transmission of epigenetic marks. This article reviews the evidence that susceptibility to metabolic and cardiovascular disease in humans is linked to changes in epigenetic marks induced by early-life environmental cues, and discusses the clinical, public health and therapeutic implications that arise.

  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. 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.

  20. 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 ...

  1. Riesgo cardiovascular, una herramienta útil para la prevención de las enfermedades cardiovasculares Cardiovascular risk, a useful tool for prevention of cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Jorge Vega Abascal

    2011-03-01

    Full Text Available El riesgo cardiovascular se define como la probabilidad de padecer un evento cardiovascular en un determinado período. Mejorar la exactitud en la predicción del riesgo requiere la evaluación y el tratamiento de múltiples factores de riesgo cardiovascular, los que tienen un efecto sinérgico, más que aditivo, sobre el riesgo cardiovascular total. El cálculo utilizando métodos cuantitativos es más preciso que el obtenido con métodos cualitativos. La predicción del riesgo cardiovascular ha constituido, en los últimos años, la piedra angular en las guías clínicas de prevención cardiovascular, y deviene una herramienta útil del Médico de Familia para establecer prioridades en la atención primaria, mejorando la atención a los pacientes y eligiendo más eficazmente la terapéutica a seguir, con el objetivo de acercarnos más a la realidad multifactorial de las enfermedades cardiovasculares y a su prevención.The cardiovascular risk is defined like a probability of suffering a cardiovascular event in a determined period. To improve the accuracy in risk prediction requires the assessment and treatment of different cardiovascular risk factors, which have a synergistic effect more than additive on the total cardiovascular risk. The calculus using quantitative methods is more accurate than that obtained with qualitative methods. The prediction of cardiovascular risk has been in past years the cornerstone in clinical guidances of cardiovascular prevention and becomes an useful tool for Family Physician to establish priorities in the primary care, improving the patients care and selecting in a more effective way the therapy to be followed to bring closer more to multifactor reality of cardiovascular diseases and its prevention.

  2. 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

  3. 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

  4. 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

  5. Spice: discovery of phenotype-determining component interplays

    Directory of Open Access Journals (Sweden)

    Chen Zhengzhang

    2012-05-01

    Full Text Available Abstract Background A latent behavior of a biological cell is complex. Deriving the underlying simplicity, or the fundamental rules governing this behavior has been the Holy Grail of systems biology. Data-driven prediction of the system components and their component interplays that are responsible for the target system’s phenotype is a key and challenging step in this endeavor. Results The proposed approach, which we call System Phenotype-related Interplaying Components Enumerator (Spice, iteratively enumerates statistically significant system components that are hypothesized (1 to play an important role in defining the specificity of the target system’s phenotype(s; (2 to exhibit a functionally coherent behavior, namely, act in a coordinated manner to perform the phenotype-specific function; and (3 to improve the predictive skill of the system’s phenotype(s when used collectively in the ensemble of predictive models. Spice can be applied to both instance-based data and network-based data. When validated, Spice effectively identified system components related to three target phenotypes: biohydrogen production, motility, and cancer. Manual results curation agreed with the known phenotype-related system components reported in literature. Additionally, using the identified system components as discriminatory features improved the prediction accuracy by 10% on the phenotype-classification task when compared to a number of state-of-the-art methods applied to eight benchmark microarray data sets. Conclusion We formulate a problem—enumeration of phenotype-determining system component interplays—and propose an effective methodology (Spice to address this problem. Spice improved identification of cancer-related groups of genes from various microarray data sets and detected groups of genes associated with microbial biohydrogen production and motility, many of which were reported in literature. Spice also improved the predictive skill of the

  6. The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants

    KAUST Repository

    Hoehndorf, Robert

    2016-11-14

    Background The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text. Results We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities. Conclusions The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established

  7. The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants.

    Science.gov (United States)

    Hoehndorf, Robert; Alshahrani, Mona; Gkoutos, Georgios V; Gosline, George; Groom, Quentin; Hamann, Thomas; Kattge, Jens; de Oliveira, Sylvia Mota; Schmidt, Marco; Sierra, Soraya; Smets, Erik; Vos, Rutger A; Weiland, Claus

    2016-11-14

    The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text. We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities. The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established vocabularies or ontologies, but rather

  8. Lipid accumulation product as a marker of cardiometabolic susceptibility in women with different phenotypes of polycystic ovary syndrome.

    Science.gov (United States)

    Božić-Antić, Ivana; Ilić, Dušan; Bjekić-Macut, Jelica; Bogavac, Tamara; Vojnović-Milutinović, Danijela; Kastratovic-Kotlica, Biljana; Milić, Nataša; Stanojlović, Olivera; Andrić, Zoran; Macut, Djuro

    2016-12-01

    There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the study was to analyze metabolic characteristics and the ability of LAP to predict MetS in different PCOS phenotypes. Cross-sectional clinical study analyzing 365 women with PCOS divided into four phenotypes according to the ESHRE/ASRM criteria, and 125 healthy BMI-matched controls. In all subjects, LAP was determined and MetS was diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF) and the Joint Interim Statement (JIS) criteria. Logistic regression and ROC curve analyses were used to determine predictors of MetS in each PCOS phenotype. All analyses were performed with age and BMI adjustment. All PCOS phenotypes in comparison to controls had higher prevalence of MetS assessed by NCEP-ATP III criteria, and only classic phenotypes when IDF and JIS criteria were used. All phenotypes had the same prevalence of MetS irrespective of used definition. LAP and exhibited the highest diagnostic accuracy and was an independent predictor of MetS in all phenotypes. LAP is an independent and accurate clinical determinant of MetS in all PCOS phenotypes in our Caucasian population. All PCOS phenotypes, including non-classic ones, are metabolically challenged and with cardiovascular risk, particularly phenotype B. © 2016 European Society of Endocrinology.

  9. 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

  10. 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 ...

  11. Decomposing phenotype descriptions for the human skeletal phenome.

    Science.gov (United States)

    Groza, Tudor; Hunter, Jane; Zankl, Andreas

    2013-01-01

    Over the course of the last few years there has been a significant amount of research performed on ontology-based formalization of phenotype descriptions. The intrinsic value and knowledge captured within such descriptions can only be expressed by taking advantage of their inner structure that implicitly combines qualities and anatomical entities. We present a meta-model (the Phenotype Fragment Ontology) and a processing pipeline that enable together the automatic decomposition and conceptualization of phenotype descriptions for the human skeletal phenome. We use this approach to showcase the usefulness of the generic concept of phenotype decomposition by performing an experimental study on all skeletal phenotype concepts defined in the Human Phenotype Ontology.

  12. 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.

  13. Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.

    Science.gov (United States)

    Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M Shawkat; Nabeshima, Yo-ichi

    2014-08-01

    Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.

  14. Residual generator for cardiovascular anomalies detection

    KAUST Repository

    Belkhatir, Zehor

    2014-06-01

    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-space representation. We show that residuals that are sensitive to variations in some cardiovascular parameters and to abnormal opening and closure of the valves, can be generated. Since the whole state is not easily available for measurement, we propose to associate the residual generator to a robust extended kalman filter. Numerical results performed on synthetic data are provided.

  15. Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Cheng, Susan; Fernandes, Verônica R S; Bluemke, David A; McClelland, Robyn L; Kronmal, Richard A; Lima, João A C

    2009-05-01

    Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood. We used cardiac MRI to examine age-related differences in LV structure and function in 5004 participants without overt cardiovascular disease when enrolled in the Multi-Ethnic Study of Atherosclerosis; 1099 participants received additional strain analyses by MRI tagging. We also assessed the relation of age-associated remodeling with cardiovascular outcomes using Cox proportional hazard models adjusting for cardiovascular risk factors. Although LV mass decreased with age (-0.3 g per year), the mass-to-volume ratio markedly increased (+5 mg/mL per year, Pfall in stroke volume (-0.4 mL per year, P or =65 years; hazard ratio, 1.68 [CI 0.77 to 3.68]) individuals with the highest compared to lowest mass-to-volume ratio quintile (P(interaction)=0.013). Age is associated with a phenotype of LV remodeling marked by increased mass-to-volume ratio and accompanied by systolic as well as diastolic myocardial dysfunction that is not reflected by preserved ejection fraction. This pattern of ventricular remodeling confers significant cardiovascular risk, particularly when present earlier in life.

  16. Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chang Hyun Byon

    2016-10-01

    Full Text Available Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS, which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2 exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC.

  17. 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

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. Text mining applied to electronic cardiovascular procedure reports to identify patients with trileaflet aortic stenosis and coronary artery disease.

    Science.gov (United States)

    Small, Aeron M; Kiss, Daniel H; Zlatsin, Yevgeny; Birtwell, David L; Williams, Heather; Guerraty, Marie A; Han, Yuchi; Anwaruddin, Saif; Holmes, John H; Chirinos, Julio A; Wilensky, Robert L; Giri, Jay; Rader, Daniel J

    2017-08-01

    Interrogation of the electronic health record (EHR) using billing codes as a surrogate for diagnoses of interest has been widely used for clinical research. However, the accuracy of this methodology is variable, as it reflects billing codes rather than severity of disease, and depends on the disease and the accuracy of the coding practitioner. Systematic application of text mining to the EHR has had variable success for the detection of cardiovascular phenotypes. We hypothesize that the application of text mining algorithms to cardiovascular procedure reports may be a superior method to identify patients with cardiovascular conditions of interest. We adapted the Oracle product Endeca, which utilizes text mining to identify terms of interest from a NoSQL-like database, for purposes of searching cardiovascular procedure reports and termed the tool "PennSeek". We imported 282,569 echocardiography reports representing 81,164 individuals and 27,205 cardiac catheterization reports representing 14,567 individuals from non-searchable databases into PennSeek. We then applied clinical criteria to these reports in PennSeek to identify patients with trileaflet aortic stenosis (TAS) and coronary artery disease (CAD). Accuracy of patient identification by text mining through PennSeek was compared with ICD-9 billing codes. Text mining identified 7115 patients with TAS and 9247 patients with CAD. ICD-9 codes identified 8272 patients with TAS and 6913 patients with CAD. 4346 patients with AS and 6024 patients with CAD were identified by both approaches. A randomly selected sample of 200-250 patients uniquely identified by text mining was compared with 200-250 patients uniquely identified by billing codes for both diseases. We demonstrate that text mining was superior, with a positive predictive value (PPV) of 0.95 compared to 0.53 by ICD-9 for TAS, and a PPV of 0.97 compared to 0.86 for CAD. These results highlight the superiority of text mining algorithms applied to electronic

  3. 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...

  4. Preeclampsia: at risk for remote cardiovascular disease

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Zeeman, Gerda G.

    2007-01-01

    Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (CVD) later in life. Population-based studies relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and cardiovascular morbidity/mortality (RR, 1.3 to

  5. Preeclampsia : At risk for remote cardiovascular disease

    NARCIS (Netherlands)

    Harskamp, Ralf E.; Zeeman, Gerda G.

    2007-01-01

    Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (CVD) later in life. Population-based studies relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and cardiovascular morbidity/mortality (RR, 1.3 to

  6. Holistic and component plant phenotyping using temporal image sequence.

    Science.gov (United States)

    Das Choudhury, Sruti; Bashyam, Srinidhi; Qiu, Yumou; Samal, Ashok; Awada, Tala

    2018-01-01

    Image-based plant phenotyping facilitates the extraction of traits noninvasively by analyzing large number of plants in a relatively short period of time. It has the potential to compute advanced phenotypes by considering the whole plant as a single object (holistic phenotypes) or as individual components, i.e., leaves and the stem (component phenotypes), to investigate the biophysical characteristics of the plants. The emergence timing, total number of leaves present at any point of time and the growth of individual leaves during vegetative stage life cycle of the maize plants are significant phenotypic expressions that best contribute to assess the plant vigor. However, image-based automated solution to this novel problem is yet to be explored. A set of new holistic and component phenotypes are introduced in this paper. To compute the component phenotypes, it is essential to detect the individual leaves and the stem. Thus, the paper introduces a novel method to reliably detect the leaves and the stem of the maize plants by analyzing 2-dimensional visible light image sequences captured from the side using a graph based approach. The total number of leaves are counted and the length of each leaf is measured for all images in the sequence to monitor leaf growth. To evaluate the performance of the proposed algorithm, we introduce University of Nebraska-Lincoln Component Plant Phenotyping Dataset (UNL-CPPD) and provide ground truth to facilitate new algorithm development and uniform comparison. The temporal variation of the component phenotypes regulated by genotypes and environment (i.e., greenhouse) are experimentally demonstrated for the maize plants on UNL-CPPD. Statistical models are applied to analyze the greenhouse environment impact and demonstrate the genetic regulation of the temporal variation of the holistic phenotypes on the public dataset called Panicoid Phenomap-1. The central contribution of the paper is a novel computer vision based algorithm for

  7. Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

    Science.gov (United States)

    Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja

    2017-05-01

    Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

  8. 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.

  9. Nordic research infrastructures for plant phenotyping

    Directory of Open Access Journals (Sweden)

    Kristiina Himanen

    2018-03-01

    Full Text Available Plant phenomics refers to the systematic study of plant phenotypes. Together with closely monitored, controlled climates, it provides an essential component for the integrated analysis of genotype-phenotype-environment interactions. Currently, several plant growth and phenotyping facilities are under establishment globally, and numerous facilities are already in use. Alongside the development of the research infrastructures, several national and international networks have been established to support shared use of the new methodology. In this review, an overview is given of the Nordic plant phenotyping and climate control facilities. Since many areas of phenomics such as sensor-based phenotyping, image analysis and data standards are still developing, promotion of educational and networking activities is especially important. These facilities and networks will be instrumental in tackling plant breeding and plant protection challenges. They will also provide possibilities to study wild species and their ecological interactions under changing Nordic climate conditions.

  10. 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...

  11. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  12. Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene

    Energy Technology Data Exchange (ETDEWEB)

    Putnam, E.A.; Cho, M.; Milewicz, D.M. [Univ. of Texas-Houston Medical School, Houston, TX (United States)] [and others

    1996-03-29

    Marfan syndrome is a dominantly inherited connective tissue disorder with a wide range of phenotypic severity. The condition is the result of mutations in FBN1, a large gene composed of 65 exons encoding the fibrillin-1 protein. While mutations causing classic manifestations of Marfan syndrome have been identified throughout the FBN1 gene, the six previously characterized mutations resulting in the severe, perinatal lethal form of Marfan syndrome have clustered in exons 24-32 of the gene. We screened 8 patients with either neonatal Marfan syndrome or severe cardiovascular complications of Marfan syndrome for mutations in this region of the gene. Using intron-based exon-specific primers, we amplified exons 23-32 from genomic DNAs, screened these fragments by single-stranded conformational polymorphism analysis, and sequenced indicated exons. This analysis documented mutations in exons 25-27 of the FBN1 mutations in 6 of these patients. These results, taken together with previously published FBN1 mutations in this region, further define the phenotype associated with mutations in exons 24-32 of the FBN1 gene, information important for the development of possible diagnostic tests and genetic counseling. 49 refs., 4 figs., 2 tabs.

  13. 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.

  14. Cardiovascular and Metabolic Heterogeneity of Obesity: Clinical Challenges and Implications for Management.

    Science.gov (United States)

    Neeland, Ian J; Poirier, Paul; Després, Jean-Pierre

    2018-03-27

    The prevalence of obesity has increased globally over the last 2 decades. Although the body mass index has been a convenient and simple index of obesity at the population level, studies have shown that obesity defined by body mass index alone is a remarkably heterogeneous condition with varying cardiovascular and metabolic manifestations across individuals. Adipose tissue is an exquisitely active metabolic organ engaged in cross-talk between various systems; perturbation of adipose tissue results in a pathological response to positive caloric balance in susceptible individuals that directly and indirectly contributes to cardiovascular and metabolic disease. Inadequate subcutaneous adipose tissue expansion in the face of dietary triglycerides leads to visceral and ectopic fat deposition, inflammatory/adipokine dysregulation, and insulin resistance. Conversely, preferential fat storage in the lower body depot may act as a metabolic buffer and protect other tissues from lipotoxicity caused by lipid overflow and ectopic fat. Translational, epidemiological, and clinical studies over the past 30 years have clearly demonstrated a strong link between visceral and ectopic fat and the development of a clinical syndrome characterized by atherogenic dyslipidemia, hyperinsulinemia/glucose intolerance, hypertension, atherosclerosis, and adverse cardiac remodeling/heart failure. This relationship is even more nuanced when clinical entities such as metabolically healthy obesity phenotype and the obesity paradox are considered. Although it is clear that the accumulation of visceral/ectopic fat is a major contributor to cardiovascular and metabolic risk above and beyond the body mass index, implementation of fat distribution assessment into clinical practice remains a challenge. Anthropometric indexes of obesity are easily implemented, but newer imaging-based methods offer improved sensitivity and specificity for measuring specific depots. Lifestyle, pharmacological, and surgical

  15. klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes.

    Directory of Open Access Journals (Sweden)

    Peter Novodvorsky

    Full Text Available The zinc-finger transcription factor Krϋppel-like factor 2 (KLF2 transduces blood flow into molecular signals responsible for a wide range of responses within the vasculature. KLF2 maintains a healthy, quiescent endothelial phenotype. Previous studies report a range of phenotypes following morpholino antisense oligonucleotide-induced klf2a knockdown in zebrafish. Targeted genome editing is an increasingly applied method for functional assessment of candidate genes. We therefore generated a stable klf2a mutant zebrafish and characterised its cardiovascular and haematopoietic development.Using Transcription Activator-Like Effector Nucleases (TALEN we generated a klf2a mutant (klf2ash317 with a 14bp deletion leading to a premature stop codon in exon 2. Western blotting confirmed loss of wild type Klf2a protein and the presence of a truncated protein in klf2ash317 mutants. Homozygous klf2ash317 mutants exhibit no defects in vascular patterning, survive to adulthood and are fertile, without displaying previously described morphant phenotypes such as high-output cardiac failure, reduced haematopoetic stem cell (HSC development or impaired formation of the 5th accessory aortic arch. Homozygous klf2ash317 mutation did not reduce angiogenesis in zebrafish with homozygous mutations in von Hippel Lindau (vhl, a form of angiogenesis that is dependent on blood flow. We examined expression of three klf family members in wildtype and klf2ash317 zebrafish. We detected vascular expression of klf2b (but not klf4a or biklf/klf4b/klf17 in wildtypes but found no differences in expression that might account for the lack of phenotype in klf2ash317 mutants. klf2b morpholino knockdown did not affect heart rate or impair formation of the 5th accessory aortic arch in either wildtypes or klf2ash317 mutants.The klf2ash317 mutation produces a truncated Klf2a protein but, unlike morpholino induced klf2a knockdown, does not affect cardiovascular development.

  16. 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

  17. 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

  18. Recommendations for using standardised phenotypes in genetic association studies

    Directory of Open Access Journals (Sweden)

    Naylor Melissa G

    2009-07-01

    Full Text Available Abstract Genetic association studies of complex traits often rely on standardised quantitative phenotypes, such as percentage of predicted forced expiratory volume and body mass index to measure an underlying trait of interest (eg lung function, obesity. These phenotypes are appealing because they provide an easy mechanism for comparing subjects, although such standardisations may not be the best way to control for confounders and other covariates. We recommend adjusting raw or standardised phenotypes within the study population via regression. We illustrate through simulation that optimal power in both population- and family-based association tests is attained by using the residuals from within-study adjustment as the complex trait phenotype. An application of family-based association analysis of forced expiratory volume in one second, and obesity in the Childhood Asthma Management Program data, illustrates that power is maintained or increased when adjusted phenotype residuals are used instead of typical standardised quantitative phenotypes.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Cardiovascular assessment of patients with Ullrich-Turner's Syndrome on Doppler echocardiography and magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Castro Ana Valéria Barros de

    2002-01-01

    Full Text Available OBJECTIVE: To assess the cardiovascular features of Ullrich-Turner's syndrome using echocardiography and magnetic resonance imaging, and to correlate them with the phenotype and karyotype of the patients. The diagnostic concordance between the 2 methods was also assessed. METHODS: Fifteen patients with the syndrome were assessed by echocardiography and magnetic resonance imaging (cardiac chambers, valves, and aorta. Their ages ranged from 10 to 28 (mean of 16.7 years. The karyotype was analyzed in 11 or 25 metaphases of peripheral blood lymphocytes, or both. RESULTS: The most common phenotypic changes were short stature and spontaneous absence of puberal development (100%; 1 patient had a cardiac murmur. The karyotypes detected were as follows: 45,X (n=7, mosaics (n=5, and deletions (n=3. No echocardiographic changes were observed. In regard to magnetic resonance imaging, coarctation and dilation of the aorta were found in 1 patient, and isolated dilation of the aorta was found in 4 patients. CONCLUSION: The frequencies of coarctation and dilation of the aorta detected on magnetic resonance imaging were similar to those reported in the literature (5.5% to 20%, and 6.3% to 29%, respectively. This confirmed the adjuvant role of magnetic resonance imaging to Doppler echocardiography for diagnosing cardiovascular alterations in patients with Ullrich-Turner's syndrome.

  4. Elucidating the genotype-phenotype map by automatic enumeration and analysis of the phenotypic repertoire.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Starting with a system's relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy.

  5. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

    2015-01-01

    There is an unmet need for new cardiovascular biomarkers. Despite this only few biomarkers for the diagnosis or screening of cardiovascular diseases have been implemented in the clinic. Thousands of proteins can be analysed in plasma by mass spectrometry-based proteomics technologies. Therefore......, this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  6. Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

    Science.gov (United States)

    Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

    2018-01-01

    Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

  7. EMPReSS: European mouse phenotyping resource for standardized screens.

    Science.gov (United States)

    Green, Eain C J; Gkoutos, Georgios V; Lad, Heena V; Blake, Andrew; Weekes, Joseph; Hancock, John M

    2005-06-15

    Standardized phenotyping protocols are essential for the characterization of phenotypes so that results are comparable between different laboratories and phenotypic data can be related to ontological descriptions in an automated manner. We describe a web-based resource for the visualization, searching and downloading of standard operating procedures and other documents, the European Mouse Phenotyping Resource for Standardized Screens-EMPReSS. Direct access: http://www.empress.har.mrc.ac.uk e.green@har.mrc.ac.uk.

  8. 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.

  9. Principal component analysis of cardiovascular risk traits in three generations cohort among Indian Punjabi population

    Directory of Open Access Journals (Sweden)

    Badaruddoza

    2015-09-01

    Full Text Available The current study focused to determine significant cardiovascular risk factors through principal component factor analysis (PCFA among three generations on 1827 individuals in three generations including 911 males (378 from offspring, 439 from parental and 94 from grand-parental generations and 916 females (261 from offspring, 515 from parental and 140 from grandparental generations. The study performed PCFA with orthogonal rotation to reduce 12 inter-correlated variables into groups of independent factors. The factors have been identified as 2 for male grandparents, 3 for male offspring, female parents and female grandparents each, 4 for male parents and 5 for female offspring. This data reduction method identified these factors that explained 72%, 84%, 79%, 69%, 70% and 73% for male and female offspring, male and female parents and male and female grandparents respectively, of the variations in original quantitative traits. The factor 1 accounting for the largest portion of variations was strongly loaded with factors related to obesity (body mass index (BMI, waist circumference (WC, waist to hip ratio (WHR, and thickness of skinfolds among all generations with both sexes, which has been known to be an independent predictor for cardiovascular morbidity and mortality. The second largest components, factor 2 and factor 3 for almost all generations reflected traits of blood pressure phenotypes loaded, however, in male offspring generation it was observed that factor 2 was loaded with blood pressure phenotypes as well as obesity. This study not only confirmed but also extended prior work by developing a cumulative risk scale from factor scores. Till today, such a cumulative and extensive scale has not been used in any Indian studies with individuals of three generations. These findings and study highlight the importance of global approach for assessing the risk and need for studies that elucidate how these different cardiovascular risk factors

  10. Principal component analysis of cardiovascular risk traits in three generations cohort among Indian Punjabi population.

    Science.gov (United States)

    Badaruddoza; Kumar, Raman; Kaur, Manpreet

    2015-09-01

    The current study focused to determine significant cardiovascular risk factors through principal component factor analysis (PCFA) among three generations on 1827 individuals in three generations including 911 males (378 from offspring, 439 from parental and 94 from grand-parental generations) and 916 females (261 from offspring, 515 from parental and 140 from grandparental generations). The study performed PCFA with orthogonal rotation to reduce 12 inter-correlated variables into groups of independent factors. The factors have been identified as 2 for male grandparents, 3 for male offspring, female parents and female grandparents each, 4 for male parents and 5 for female offspring. This data reduction method identified these factors that explained 72%, 84%, 79%, 69%, 70% and 73% for male and female offspring, male and female parents and male and female grandparents respectively, of the variations in original quantitative traits. The factor 1 accounting for the largest portion of variations was strongly loaded with factors related to obesity (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), and thickness of skinfolds) among all generations with both sexes, which has been known to be an independent predictor for cardiovascular morbidity and mortality. The second largest components, factor 2 and factor 3 for almost all generations reflected traits of blood pressure phenotypes loaded, however, in male offspring generation it was observed that factor 2 was loaded with blood pressure phenotypes as well as obesity. This study not only confirmed but also extended prior work by developing a cumulative risk scale from factor scores. Till today, such a cumulative and extensive scale has not been used in any Indian studies with individuals of three generations. These findings and study highlight the importance of global approach for assessing the risk and need for studies that elucidate how these different cardiovascular risk factors interact with

  11. Beyond the Cholesterol-Lowering Effect of Soy Protein: A Review of the Effects of Dietary Soy and Its Constituents on Risk Factors for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    D. Dan Ramdath

    2017-03-01

    Full Text Available The hypocholesterolemic effect of soy is well-documented and this has led to the regulatory approval of a health claim relating soy protein to a reduced risk of cardiovascular disease (CVD. However, soybeans contain additional components, such as isoflavones, lecithins, saponins and fiber that may improve cardiovascular health through independent mechanisms. This review summarizes the evidence on the cardiovascular benefits of non-protein soy components in relation to known CVD risk factors such as hypertension, hyperglycemia, inflammation, and obesity beyond cholesterol lowering. Overall, the available evidence suggests non-protein soy constituents improve markers of cardiovascular health; however, additional carefully designed studies are required to independently elucidate these effects. Further, work is also needed to clarify the role of isoflavone-metabolizing phenotype and gut microbiota composition on biological effect.

  12. Nutrition and Cardiovascular Disease: Finding the Perfect Recipe for Cardiovascular Health

    Directory of Open Access Journals (Sweden)

    Alice Ravera

    2016-06-01

    Full Text Available The increasing burden of cardiovascular disease (CVD despite the progress in management entails the need of more effective preventive and curative strategies. As dietary-associated risk is the most important behavioral factor influencing global health, it appears the best target in the challenge against CVD. Although for many years, since the formulation of the cholesterol hypothesis, a nutrient-based approach was attempted for CVD prevention and treatment, in recent years a dietary-based approach resulted more effective in reducing cardiovascular risk worldwide. After the publication of randomized trials on the remarkable effects of the Mediterranean diet and the Dietary Approach to Stop Hypertension (DASH diet on CVD, new efforts were put on research about the effects of complex dietary interventions on CVD. The purpose of this paper is to review the evidence on dietary interventions in the prevention and disease modification of CVD, focusing on coronary artery disease and heart failure, the main disease responsible for the enormous toll taken by CVD worldwide.

  13. Detection of cardiovascular anomalies: Hybrid systems approach

    KAUST Repository

    Ledezma, Fernando

    2012-06-06

    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 parameters, using an observerbased approach. We present the first numerical results obtained. © 2012 IFAC.

  14. Healthy lifestyle factors and risk of cardiovascular events and mortality in treatment-resistant hypertension: the Reasons for Geographic and Racial Differences in Stroke study.

    Science.gov (United States)

    Diaz, Keith M; Booth, John N; Calhoun, David A; Irvin, Marguerite R; Howard, George; Safford, Monika M; Muntner, Paul; Shimbo, Daichi

    2014-09-01

    Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95), respectively (P-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment

  15. [Cooperative Cardiovascular Disease Research Network (RECAVA)].

    Science.gov (United States)

    García-Dorado, David; Castro-Beiras, Alfonso; Díez, Javier; Gabriel, Rafael; Gimeno-Blanes, Juan R; Ortiz de Landázuri, Manuel; Sánchez, Pedro L; Fernández-Avilés, Francisco

    2008-01-01

    Today, cardiovascular disease is the principal cause of death and hospitalization in Spain, and accounts for an annual healthcare budget of more than 4000 million euros. Consequently, early diagnosis, effective prevention, and the optimum treatment of cardiovascular disease present a significant social and healthcare challenge for the country. In this context, combining all available resources to increase the efficacy and healthcare benefits of scientific research is a priority. This rationale prompted the establishment of the Spanish Cooperative Cardiovascular Disease Research Network, or RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares), 5 years ago. Since its foundation, RECAVA's activities have focused on achieving four objectives: a) to facilitate contacts between basic, clinical and epidemiological researchers; b) to promote the shared use of advanced technological facilities; c) to apply research results to clinical practice, and d) to train a new generation of translational cardiovascular researchers in Spain. At present, RECAVA consists of 41 research groups and seven shared technological facilities. RECAVA's research strategy is based on a scientific design matrix centered on the most important cardiovascular processes. The level of RECAVA's research activity is reflected in the fact that 28 co-authored articles were published in international journals during the first six months of 2007, with each involving contributions from at least two groups in the network. Finally, RECAVA also participates in the work of the Spanish National Center for Cardiovascular Research, or CNIC (Centro Nacional de Investigación Cardiovascular), and some established Biomedical Research Network Centers, or CIBER (Centros de Investigación Biomédica en RED), with the aim of consolidating the development of a dynamic multidisciplinary research framework that is capable of meeting the growing challenge that cardiovascular disease will present

  16. Elucidating the genotype–phenotype map by automatic enumeration and analysis of the phenotypic repertoire

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2015-01-01

    Background: The gap between genotype and phenotype is filled by complex biochemical systems most of which are poorly understood. Because these systems are complex, it is widely appreciated that quantitative understanding can only be achieved with the aid of mathematical models. However, formulating models and measuring or estimating their numerous rate constants and binding constants is daunting. Here we present a strategy for automating difficult aspects of the process. Methods: The strategy, based on a system design space methodology, is applied to a class of 16 designs for a synthetic gene oscillator that includes seven designs previously formulated on the basis of experimentally measured and estimated parameters. Results: Our strategy provides four important innovations by automating: (1) enumeration of the repertoire of qualitatively distinct phenotypes for a system; (2) generation of parameter values for any particular phenotype; (3) simultaneous realization of parameter values for several phenotypes to aid visualization of transitions from one phenotype to another, in critical cases from functional to dysfunctional; and (4) identification of ensembles of phenotypes whose expression can be phased to achieve a specific sequence of functions for rationally engineering synthetic constructs. Our strategy, applied to the 16 designs, reproduced previous results and identified two additional designs capable of sustained oscillations that were previously missed. Conclusions: Starting with a system’s relatively fixed aspects, its architectural features, our method enables automated analysis of nonlinear biochemical systems from a global perspective, without first specifying parameter values. The examples presented demonstrate the efficiency and power of this automated strategy. PMID:26998346

  17. 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

  18. 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

  19. Educational inequality in cardiovascular disease depends on diagnosis

    DEFF Research Database (Denmark)

    Christensen, Anne V; Koch, Mette B; Davidsen, Michael

    2016-01-01

    BACKGROUND: Social inequality is present in the morbidity as well as the mortality of cardiovascular diseases. This paper aims to quantify and compare the level of educational inequality across different cardiovascular diagnoses. DESIGN: Register based study. METHODS: Comparison of the extent...... index of inequality: -29 (-35.1; -21.9) to -1 (-4.8; -3.8)). CONCLUSION: The degree of educational inequality in cardiovascular diseases depends on the diagnosis, with the highest inequality in ischaemic heart disease, acute myocardial infarction, heart failure and stroke. Small differences were found...... of inequality across different cardiovascular diagnoses requires a measure of inequality which is comparable across subgroups with different educational distributions. The slope index of inequality and the relative index of inequality were applied for measuring inequalities in incidence of six cardiovascular...

  20. Cardiovascular Risk, Drugs and Erectile Function -A Systematic Analysis

    OpenAIRE

    Baumhäkel , Magnus; Schlimmer , Nils; Kratz , Mario; Hackett , Geoffrey; Jackson , Graham; Böhm , Michael

    2011-01-01

    Abstract Aims Erectile dysfunction is a major problem with an increasing prevalence in cardiovascular high-risk patients due to the association with cardiovascular risk factors. Drugs used for evidenced based treatment of cardiovascular diseases have been reported to decrease erectile function, but possible mechanisms are poorly characterized. Methods MEDLINE, EMBASE and Cochrane Registry search was performed including manuscripts until January 2010. Searching terms are: ...

  1. 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.

  2. 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.

  3. 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

  4. Cardiovascular Update: Risk, Guidelines, and Recommendations.

    Science.gov (United States)

    Pearson, Tamera

    2015-09-01

    This article provides an update of the current status of cardiovascular disease (CVD) in the United States, including a brief review of the underlying pathophysiology and epidemiology. This article presents a discussion of the latest American Heart Association guidelines that introduce the concept of promoting ideal cardiovascular health, defined by seven identified metrics. Specific CVD risk factors and utilization of the 10-year CVD event prediction calculator are discussed. In addition, current management recommendations of health-related conditions that increase risk for CVD, such as hypertension and hypercholesterolemia, are provided. Finally, a discussion of detailed evidence-based lifestyle recommendations to promote cardiovascular health and reduce CVD risks concludes the update. © 2015 The Author(s).

  5. Toxic urban waste's assault on cardiovascular risk

    Directory of Open Access Journals (Sweden)

    M.L. De Rosa

    2015-03-01

    Full Text Available A cardiovascular health survey of 1203 persons in households located near the hazardous waste disposal sites and in a reference community, was conducted from 2009 until today to assess whether rates of adverse cardiovascular health outcomes were elevated among persons living near the sites. Data included medical records of reported cardiovascular disease certificates and hospital admission for cardiovascular diseases from hospital database. The study areas appeared similar with respect to mortality, cancer incidence, and pregnancy outcomes. In contrast, rate ratios were greater than 1.5 for 2 of 19 reported diseases, i.e., angina pectoris, and strokes. The apparent broad-based elevation in reported diseases and symptoms may reflect increased perception or recall of conditions by respondents living near the sites. Our study found that cardiovascular risk is associated only with PM2.5 concentrations, derived from uncontrolled burning of municipal solid waste in particular sites of our country. Their analysis demonstrated a relationship between increased levels of eventual fine particulate pollution and higher rates of death and complications from cardiovascular and cerebrovascular diseases. Management of solid waste releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Future community-based health studies should include medical and psychosocial assessment instruments sufficient to distinguish between changes in health status and effects of resident reporting tendency.

  6. 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

  7. 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

  8. Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals

    DEFF Research Database (Denmark)

    Soerensen, Mette; Nygaard, Marianne; Dato, Serena

    2015-01-01

    -old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease......FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest...... borderline significance (P = 0.054), while ADL did not (P = 0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n = 1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis...

  9. 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.

  10. 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.

  11. Semi-supervised Learning for Phenotyping Tasks.

    Science.gov (United States)

    Dligach, Dmitriy; Miller, Timothy; Savova, Guergana K

    2015-01-01

    Supervised learning is the dominant approach to automatic electronic health records-based phenotyping, but it is expensive due to the cost of manual chart review. Semi-supervised learning takes advantage of both scarce labeled and plentiful unlabeled data. In this work, we study a family of semi-supervised learning algorithms based on Expectation Maximization (EM) in the context of several phenotyping tasks. We first experiment with the basic EM algorithm. When the modeling assumptions are violated, basic EM leads to inaccurate parameter estimation. Augmented EM attenuates this shortcoming by introducing a weighting factor that downweights the unlabeled data. Cross-validation does not always lead to the best setting of the weighting factor and other heuristic methods may be preferred. We show that accurate phenotyping models can be trained with only a few hundred labeled (and a large number of unlabeled) examples, potentially providing substantial savings in the amount of the required manual chart review.

  12. 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.

  13. 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

  14. Cardiovascular health benefits of some locally adoptable exercise ...

    African Journals Online (AJOL)

    ... access the much evidence based benefit of exercise on cardiovascular health because they hold the believe that effective exercise can only be done in the organized gymnasium. We compared the cardiovascular effect of riding bicycle ergometer, a commonly used gymnasium equipment with that of jogging and walking ...

  15. Supplementary Material for: The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants

    KAUST Repository

    Hoehndorf, Robert

    2016-01-01

    Abstract Background The systematic analysis of a large number of comparable plant trait data can support investigations into phylogenetics and ecological adaptation, with broad applications in evolutionary biology, agriculture, conservation, and the functioning of ecosystems. Floras, i.e., books collecting the information on all known plant species found within a region, are a potentially rich source of such plant trait data. Floras describe plant traits with a focus on morphology and other traits relevant for species identification in addition to other characteristics of plant species, such as ecological affinities, distribution, economic value, health applications, traditional uses, and so on. However, a key limitation in systematically analyzing information in Floras is the lack of a standardized vocabulary for the described traits as well as the difficulties in extracting structured information from free text. Results We have developed the Flora Phenotype Ontology (FLOPO), an ontology for describing traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based on phenotype description patterns and automated reasoning to generate the FLOPO. The resulting ontology consists of 25,407 classes and is based on the PO and PATO. The classified ontology closely follows the structure of Plant Ontology in that the primary axis of classification is the observed plant anatomical structure, and more specific traits are then classified based on parthood and subclass relations between anatomical structures as well as subclass relations between phenotypic qualities. Conclusions The FLOPO is primarily intended as a framework based on which plant traits can be integrated computationally across all species and higher taxa of flowering plants. Importantly, it is not intended to replace established

  16. 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.

  17. Cardiovascular magnetic resonance in adults with previous cardiovascular surgery.

    Science.gov (United States)

    von Knobelsdorff-Brenkenhoff, Florian; Trauzeddel, Ralf Felix; Schulz-Menger, Jeanette

    2014-03-01

    Cardiovascular magnetic resonance (CMR) is a versatile non-invasive imaging modality that serves a broad spectrum of indications in clinical cardiology and has proven evidence. Most of the numerous applications are appropriate in patients with previous cardiovascular surgery in the same manner as in non-surgical subjects. However, some specifics have to be considered. This review article is intended to provide information about the application of CMR in adults with previous cardiovascular surgery. In particular, the two main scenarios, i.e. following coronary artery bypass surgery and following heart valve surgery, are highlighted. Furthermore, several pictorial descriptions of other potential indications for CMR after cardiovascular surgery are given.

  18. Unmet needs for cardiovascular care in Indonesia.

    Science.gov (United States)

    Maharani, Asri; Tampubolon, Gindo

    2014-01-01

    In the past twenty years the heaviest burden of cardiovascular diseases has begun to shift from developed to developing countries. However, little is known about the real needs for cardiovascular care in these countries and how well those needs are being met. This study aims to investigate the prevalence and determinants of unmet needs for cardiovascular care based on objective assessment. Multilevel analysis is used to analyse the determinants of met needs and multilevel multiple imputation is applied to manage missing data. The 2008 Indonesian Family Life Survey (IFLS4) survey is the source of the household data used in this study, while district data is sourced from the Ministry of Health and Ministry of Finance. The data shows that nearly 70% of respondents with moderate to high cardiovascular risk failed to receive cardiovascular care. Higher income, possession of health insurance and residence in urban areas are significantly associated with met needs for cardiovascular care, while health facility density and physician density show no association with them. The prevalence of unmet needs for cardiovascular care is considerable in Indonesia. Inequality persists as a factor in meeting needs for cardiovascular care as the needs of people with higher incomes and those living in urban areas are more likely to be met. Alleviation of poverty, provision of health care insurance for the poor, and improvement in the quality of healthcare providers are recommended in order to meet this ever-increasing need.

  19. Unmet needs for cardiovascular care in Indonesia.

    Directory of Open Access Journals (Sweden)

    Asri Maharani

    Full Text Available In the past twenty years the heaviest burden of cardiovascular diseases has begun to shift from developed to developing countries. However, little is known about the real needs for cardiovascular care in these countries and how well those needs are being met. This study aims to investigate the prevalence and determinants of unmet needs for cardiovascular care based on objective assessment.Multilevel analysis is used to analyse the determinants of met needs and multilevel multiple imputation is applied to manage missing data. The 2008 Indonesian Family Life Survey (IFLS4 survey is the source of the household data used in this study, while district data is sourced from the Ministry of Health and Ministry of Finance. The data shows that nearly 70% of respondents with moderate to high cardiovascular risk failed to receive cardiovascular care. Higher income, possession of health insurance and residence in urban areas are significantly associated with met needs for cardiovascular care, while health facility density and physician density show no association with them.The prevalence of unmet needs for cardiovascular care is considerable in Indonesia. Inequality persists as a factor in meeting needs for cardiovascular care as the needs of people with higher incomes and those living in urban areas are more likely to be met. Alleviation of poverty, provision of health care insurance for the poor, and improvement in the quality of healthcare providers are recommended in order to meet this ever-increasing need.

  20. 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...

  1. 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.

  2. Pheno-phenotypes: a holistic approach to the psychopathology of schizophrenia.

    Science.gov (United States)

    Stanghellini, Giovanni; Rossi, Rodolfo

    2014-05-01

    Mental disorders are mainly characterized via symptom assessment. Symptoms are state-like macroscopic anomalies of behaviour, experience, and expression that are deemed relevant for diagnostic purposes. An alternative approach is based on the concept of endophenotypes, which are physiological or behavioural measures occupying the terrain between symptoms and risk genotypes. We will critically discuss these two approaches, and later focus on the concept of pheno-phenotype as it is revealed by recent phenomenological research on schizophrenia. Several studies have been recently published on the schizophrenic pheno-phenotype mainly addressing self-disorders, as well as disorders of time and bodily experience. The mainstream approach to psychopathological phenotypes is focussed on easy-to-assess operationalizable symptoms. Thinness of phenotypes and simplification of clinical constructs are the consequences of this. Also, this approach has not been successful in investigating the biological causes of mental disorders. An integrative approach is based on the concept of 'endophenotype'. Endophenotypes were conceptualized as a supportive tool for the genetic dissection of psychiatric disorders. The underlying rationale states that disease-specific phenotypes should be the upstream phenotypic manifestation of a smaller genotype than the whole disease-related genotype. Psychopathological phenotypes can also be characterized in terms of pheno-phenotypes. This approach aims at delineating the manifold phenomena experienced by patients in all of their concrete and distinctive features, so that the features of a pathological condition emerge, while preserving their peculiar feel, meaning, and value for the patient. Systematic explorations of anomalies in the patients' experience, for example, of time, space, body, self, and otherness, may provide a useful integration to the symptom-based and endophenotype-based approaches. These abnormal phenomena can be used as pointers to the

  3. 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...

  4. Hypertriglyceridemic-waist phenotype predicts diabetes: a cohort study in Chinese urban adults

    Directory of Open Access Journals (Sweden)

    Zhang Meilin

    2012-12-01

    Full Text Available Abstract Background Hypertriglycedemic-waist (HTGW phenotype is a simple and inexpensive screening parameter to identify people at increased risk for cardiovascular disease. We evaluated whether the HTGW phenotype predicts prediabetes and diabetes in Chinese urban adults. Methods Two thousand nine hundred and eight (2908 subjects including 1957 men and 951 women, aged 20 years and older, free of prediabetes and diabetes at baseline were enrolled in 2008 and followed for 3 years. Meanwhile, new cases of prediabetes and diabetes were identified via annual physical examination. Cox proportional hazards models were used to assess the association of HTGW phenotype with the incidence of prediabetes and diabetes. Results One thousand five hundred and thirty-three (1533 new prediabetes and 90 new diabetes cases were diagnosed during the follow-up period. The accumulated incidence of prediabetes and diabetes was 52.7% and 3.1%, respectively. Compared with the normal waist normal triglyceride (NWNT group, those in the HTGW group had higher incidence of prediabetes and diabetes for both men and women. The hazard ratio (HR for developing prediabetes in the presence of HTGW phenotype at baseline was 1.51 (95% confidence interval [CI] =1.04-2.19 in women, not in men (HR=1.01; 95% CI = 0.82-1.24, after adjusting for age, body mass index, systolic blood pressure, total cholesterol and low density lipoprotein-cholesterol. The HR for developing diabetes were 4.46 (95% CI = 1.88-10.60 in men and 4.64 (95% CI = 1.20-17.97 in women for people who were HTGW phenotype at baseline, after adjusting for age, body mass index, systolic blood pressure, total cholesterol and low density lipoprotein-cholesterol. Conclusions The HTGW phenotype can be used as a simple screening approach to predict diabetes. By using this approach, it is possible to identify individuals at high-risk for diabetes, which is of great significance in reducing the incidence of diabetes among Chinese

  5. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

    Science.gov (United States)

    Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

    2013-07-01

    Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

  6. 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....

  7. Cardiovascular risk factors and events in women with androgen excess.

    Science.gov (United States)

    Macut, D; Antić, I B; Bjekić-Macut, J

    2015-03-01

    Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

  8. 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

  9. SGLT-2 Inhibitors and Cardiovascular Risk

    DEFF Research Database (Denmark)

    Cavender, Matthew A; Norhammar, Anna; Birkeland, Kåre I

    2018-01-01

    BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought...... to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes...... evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)....

  10. Phenotypic profiles of Armenian grape cultivars

    Directory of Open Access Journals (Sweden)

    Aroutiounian Rouben

    2015-01-01

    Full Text Available The conservation and sustainable use of grapevine biodiversity in Armenia is particularly important due to the large number of traditional local varieties. Being partially different from European grapevine gene pool, the material of Armenian local cultivars significantly contributes to the understanding of the genetic variation and is valuable source for target selection. During last years many Armenian grapevine cultivars have been already described and their genotypes determined, but some local varieties and wild accessions remain unidentified and their phenotypic characteristics overlooked. The comprehensive analysis of phenotypes is essential for research, including genetic association studies, cultivar evaluation and selection. The goal of our research was the phenotyping on the base of reproductive, carpological and analytical characteristics of 80 Armenian aboriginal and new grape cultivars. Description of phenotypic profiles is important step towards identification and conservation of genetic resources of Armenian grapes. In future, these data can be applied for breeding of improved grape varieties targeted to fresh consumption and wine production.

  11. Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease.

    Science.gov (United States)

    Larsen, Hege E; Lefkimmiatis, Konstantinos; Paterson, David J

    2016-12-14

    Many therapeutic interventions in disease states of heightened cardiac sympathetic activity are targeted to the myocytes. However, emerging clinical data highlights a dominant role in disease progression by the neurons themselves. Here we describe a novel experimental model of the peripheral neuro-cardiac axis to study the neuron's ability to drive a myocyte cAMP phenotype. We employed a co-culture of neonatal ventricular myocytes and sympathetic stellate neurons from normal (WKY) and pro-hypertensive (SHR) rats that are sympathetically hyper-responsive and measured nicotine evoked cAMP responses in the myocytes using a fourth generation FRET cAMP sensor. We demonstrated the dominant role of neurons in driving the myocyte ß-adrenergic phenotype, where SHR cultures elicited heightened myocyte cAMP responses during neural activation. Moreover, cross-culturing healthy neurons onto diseased myocytes rescued the diseased cAMP response of the myocyte. Conversely, healthy myocytes developed a diseased cAMP response if diseased neurons were introduced. Our results provide evidence for a dominant role played by the neuron in driving the adrenergic phenotype seen in cardiovascular disease. We also highlight the potential of using healthy neurons to turn down the gain of neurotransmission, akin to a smart pre-synaptic ß-blocker.

  12. 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 ...

  13. 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.

  14. The association between self-reported cardiovascular disorders and troublesome neck pain

    DEFF Research Database (Denmark)

    Nolet, Paul S; Côté, Pierre; Cassidy, John David

    2012-01-01

    The purpose of this population-based cohort study was to investigate the association between self-reported cardiovascular disorders and troublesome neck pain.......The purpose of this population-based cohort study was to investigate the association between self-reported cardiovascular disorders and troublesome neck pain....

  15. 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.

  16. Postirradiation cardiovascular dysfunction

    International Nuclear Information System (INIS)

    Hawkins, R.N.; Cockerham, L.G.

    1987-01-01

    Cardiovascular dysfunction may be defined as the inability of any element of the cardiovascular system to perform adequately upon demand, leading to inadequate performance and nutritive insufficiency of various parts of the body. Exposure to supralethal doses of radiation (accidental and therapeutic) has been show to induce significant alterations in cardiovascular function in man. These findings indicate that, after irradiation, cardiovascular function is a major determinant of continued performance and even survival. For the two persons who received massive radiation doses (45 and 88 Gy, respectively) in criticality accidents, the inability to maintain systematic arterial blood pressure (AP) was the immediate cause of death. In a study of cancer patients given partial-body irradiation, two acute lethalities were attributed to myocardial infarction after an acute hypotensive episode during the first few hours postexposure. Although radiation-induced cardiovascular dysfunction has been observed in many species, its severity, duration, and even etiology may vary with the species, level of exposure, and dose rate. For this reason, our consideration of the effects of radiation on cardiovascular performance is limited to the circulatory derangements that occur in rat, dog, and monkey after supralethal doses and lead to radiation-induced cardiovascular dysfunction in these experimental models. The authors consider other recent data as they pertain to the etiology of cardiovascular dysfunction in irradiated animals

  17. The Mediterranean diet, its components, and cardiovascular disease.

    Science.gov (United States)

    Widmer, R Jay; Flammer, Andreas J; Lerman, Lilach O; Lerman, Amir

    2015-03-01

    One of the best-studied diets for cardiovascular health is the Mediterranean diet. This consists of fish, monounsaturated fats from olive oil, fruits, vegetables, whole grains, legumes/nuts, and moderate alcohol consumption. The Mediterranean diet has been shown to reduce the burden, or even prevent the development, of cardiovascular disease, breast cancer, depression, colorectal cancer, diabetes, obesity, asthma, erectile dysfunction, and cognitive decline. This diet is also known to improve surrogates of cardiovascular disease, such as waist-to-hip ratio, lipids, and markers of inflammation, as well as primary cardiovascular disease outcomes such as death and events in both observational and randomized controlled trial data. These enhancements easily rival those seen with more established tools used to fight cardiovascular disease such as aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and exercise. However, it is unclear if the Mediterranean diet offers cardiovascular disease benefit from its individual constituents or in aggregate. Furthermore, the potential benefit of the Mediterranean diet or its components is not yet validated by concrete cardiovascular disease endpoints in randomized trials or observational studies. This review will focus on the effects of the whole and parts of the Mediterranean diet with regard to both population-based and experimental data highlighting cardiovascular disease morbidity or mortality and cardiovascular disease surrogates when hard outcomes are not available. Our synthesis will highlight the potential for the Mediterranean diet to act as a key player in cardiovascular disease prevention, and attempt to identify certain aspects of the diet that are particularly beneficial for cardioprotection. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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.

  19. Differential association between sarcopenia and metabolic phenotype in Korean young and older adults with and without obesity.

    Science.gov (United States)

    Hwang, You-Cheol; Cho, In-Jin; Jeong, In-Kyung; Ahn, Kyu Jeung; Chung, Ho Yeon

    2017-01-01

    To determine whether sarcopenia was associated with metabolic phenotype in subjects with and without obesity. A total of 6,021 participants (2,592 men, 3,429 women) aged 30 to 93 years were assessed using data from the 2009 Korea National Health and Nutrition Examination Survey. Sarcopenia was defined as appendicular skeletal muscle mass divided by weight (%) that is young adults. Metabolically unhealthy was defined as ≥2 components of metabolic syndrome or the presence of hypertension, diabetes, or cardiovascular disease. Obesity was defined as body mass index ≥25.0 kg/m 2 . Sarcopenia was associated with a metabolically unhealthy phenotype in nonobese men independent of age, smoking, regular physical activity, daily energy intake, total body fat, fasting insulin, non-HDL cholesterol, white blood cell count, ferritin level, and 25(OH) vitamin D level (OR per 1 SD increment (95% CI) 1.88 (1.28-2.75), P obesity. Sarcopenia was independently associated with a metabolically unhealthy phenotype in nonobese men, but this association was not evident in nonobese women or subjects with obesity. © 2016 The Obesity Society.

  20. Phenotypic and functional characterization of earthworm coelomocyte subsets

    DEFF Research Database (Denmark)

    Engelmann, Péter; Hayashi, Yuya; Bodo, Kornélia

    2016-01-01

    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...... 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....

  1. 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

  2. The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

    Directory of Open Access Journals (Sweden)

    Giuseppe Maltese

    2012-01-01

    Full Text Available Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s. Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease.

  3. Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

    Science.gov (United States)

    Sharma, Arun; Wu, Joseph C; Wu, Sean M

    2013-12-24

    Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

  4. Exosomes as agents of change in the cardiovascular system.

    Science.gov (United States)

    Poe, A J; Knowlton, A A

    2017-10-01

    Exosomes have an evolving role in paracrine and autocrine signaling, which is enhanced because these lipid vesicles are quite stable and can deliver miRNA, DNA, protein and other molecules to cells throughout the body. Most cell types release exosomes, and exosomes are found in all biological fluids, making them accessible biomarkers. Significantly, exosomes can carry a biologically potent cargo, which can alter the phenotype of recipient cells. In the cardiovascular system exosomes have been primarily studied for their role in mediating the beneficial effects of mesenchymal stem cells after myocardial injury. Exosomes released by cardiac cells in disease states, such as myocardial ischemia, can potentially have important pathophysiologic effects on other cardiac cells as well as on distant organs. Published by Elsevier Ltd.

  5. Doença cardiovascular e fatores de risco cardiovascular em candidatos a transplante renal Cardiovascular disease and risk factors in candidates for renal transplantation

    Directory of Open Access Journals (Sweden)

    Luís Henrique Wolff Gowdak

    2005-02-01

    evaluation for inclusion on the renal transplantation list. METHODS: One hundred ninety-five patients with dialytic chronic renal failure underwent clinical evaluation and complementary tests and were compared with a group of 334 hypertensive patients paired for age. The Framingham equations were used for calculating the absolute risk (AR. The relative risk (RR was calculated based on the absolute risk of the low-risk Framingham cohort. RESULTS: Thirty-seven percent of the patients had some sort of cardiovascular disease on the initial evaluation, peripheral vascular disease (23% being the most prevalent. Patients with cardiovascular disease were excluded. Regarding traditional risk factors, a significant difference was observed in systolic blood pressure and total cholesterol (greater in the hypertensive group, and in the prevalence of men, diabetes, and smoking, which were greater in the chronic renal failure group. The latter had a greater degree of left ventricular hypertrophy, lower diastolic blood pressure, and a lower prevalence of familial history of cardiovascular disease and obesity. The relative risk for cardiovascular disease in patients with chronic renal failure was greater compared with that in the Framingham control population, but it did not differ from that observed in the group of hypertensive individuals. CONCLUSION: The prevalence of cardiovascular disease and traditional risk factors is high among candidates for renal transplantation; the Framingham equations do not adequately quantify the real cardiovascular risk, and other risk factors specific for that population should contribute for their greater cardiovascular risk.

  6. 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

  7. Eating competence of elderly Spanish adults is associated with a healthy diet and a favorable cardiovascular disease risk profile.

    Science.gov (United States)

    Lohse, Barbara; Psota, Tricia; Estruch, Ramón; Zazpe, Itziar; Sorli, José V; Salas-Salvadó, Jordi; Serra, Mercè; Krall, Jodi Stotts; Márquez, Fabiola; Ros, Emilio

    2010-07-01

    Eating competence (EC), a bio-psychosocial model for intrapersonal approaches to eating and food-related behaviors, is associated with less weight dissatisfaction, lower BMI, and increased HDL-cholesterol in small U.S. studies, but its relationship to nutrient quality and overall cardiovascular risk have not been examined. Prevención con Dieta Mediterránea (PREDIMED) is a 5-y controlled clinical trial evaluating Mediterranean diet efficacy on the primary prevention of cardiovascular diseases (CVD) in Spain. In a cross-sectional study, 638 PREDIMED participants (62% women, mean age 67 y) well phenotyped for cardiovascular risk factors were assessed for food intake and EC using validated questionnaires. Overall, 45.6% were eating-competent. EC was associated with being male and energy intake (P diet (P 5.6 mmol/L (0.71; 95% CI 0.51-0.98) and HDL-cholesterol or =3.4 mmol/L were 0.1). Our findings support further examination of EC as a strategy for enhancing diet quality and CVD prevention.

  8. DNA Phenotyping: The prediction of human pigmentation traits from genetic data

    NARCIS (Netherlands)

    S. Walsh (Susan)

    2013-01-01

    textabstractPhenotyping is the ability to assign characteristics to an organism based on certain measurable parameters. In the case of DNA phenotyping, it is limited to the sole use of DNA to determine a phenotype such as an externally visible characteristic. In a forensic setting, it encompasses

  9. 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.

  10. 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

  11. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults

    Science.gov (United States)

    Background: Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality. We examined the association between flavonoid intake and cardiovascular disease (CVD) mortalit...

  12. Effects of Vegetables on Cardiovascular Diseases and Related Mechanisms

    Directory of Open Access Journals (Sweden)

    Guo-Yi Tang

    2017-08-01

    Full Text Available Epidemiological studies have shown that vegetable consumption is inversely related to the risk of cardiovascular diseases. Moreover, research has indicated that many vegetables like potatoes, soybeans, sesame, tomatoes, dioscorea, onions, celery, broccoli, lettuce and asparagus showed great potential in preventing and treating cardiovascular diseases, and vitamins, essential elements, dietary fibers, botanic proteins and phytochemicals were bioactive components. The cardioprotective effects of vegetables might involve antioxidation; anti-inflammation; anti-platelet; regulating blood pressure, blood glucose, and lipid profile; attenuating myocardial damage; and modulating relevant enzyme activities, gene expression, and signaling pathways as well as some other biomarkers associated to cardiovascular diseases. In addition, several vegetables and their bioactive components have been proven to protect against cardiovascular diseases in clinical trials. In this review, we analyze and summarize the effects of vegetables on cardiovascular diseases based on epidemiological studies, experimental research, and clinical trials, which are significant to the application of vegetables in prevention and treatment of cardiovascular diseases.

  13. Cardiovascular-Active Venom Toxins: An Overview.

    Science.gov (United States)

    Rebello Horta, Carolina Campolina; Chatzaki, Maria; Rezende, Bruno Almeida; Magalhães, Bárbara de Freitas; Duarte, Clara Guerra; Felicori, Liza Figueiredo; Ribeiro Oliveira-Mendes, Bárbara Bruna; do Carmo, Anderson Oliveira; Chávez-Olórtegui, Carlos; Kalapothakis, Evanguedes

    2016-01-01

    Animal venoms are a mixture of bioactive compounds produced as weapons and used primarily to immobilize and kill preys. As a result of the high potency and specificity for various physiological targets, many toxins from animal venoms have emerged as possible drugs for the medication of diverse disorders, including cardiovascular diseases. Captopril, which inhibits the angiotensin-converting enzyme (ACE), was the first successful venom-based drug and a notable example of rational drug design. Since captopril was developed, many studies have discovered novel bradykinin-potentiating peptides (BPPs) with actions on the cardiovascular system. Natriuretic peptides (NPs) have also been found in animal venoms and used as template to design new drugs with applications in cardiovascular diseases. Among the anti-arrhythmic peptides, GsMTx-4 was discovered to be a toxin that selectively inhibits the stretch-activated cation channels (SACs), which are involved in atrial fibrillation. The present review describes the main components isolated from animal venoms that act on the cardiovascular system and presents a brief summary of venomous animals and their venom apparatuses.

  14. 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.

  15. A comparative study on genetic and environmental influences on metabolic phenotypes in Eastern (Chinese) and Western (Danish) populations

    DEFF Research Database (Denmark)

    Li, Shuxia

    2015-01-01

    the risk of clinic diseases e.g. diabetes, atherosclerosis, stroke and cardiovascular disease. Metabolic phenotypes, similar to most complex traits, can be influenced by both genetic and environmental factors as well as their interplay. Many family and twin studies have demonstrated both genetic...... and environmental factors play important role in the variation of metabolic phenotypes and intra-individual change over time. Although both genetic and environmental factors are involved the development of metabolic disorders, the role of environment should be emphasized as the expression or function of gene can...... be regulated to adapt to existing environmental circumstance. In other words, adaptive evolution in populations under distinct environmental and cultural circumstances could have resulted in varying genetic basis of metabolic factors and development of metabolic disorders or diseases. Thus, it can...

  16. 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.

  17. 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

  18. 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

  19. Cocoa, chocolate, and cardiovascular disease.

    Science.gov (United States)

    Galleano, Monica; Oteiza, Patricia I; Fraga, Cesar G

    2009-12-01

    A significant body of evidence demonstrates that diets rich in fruits and vegetables promote health and attenuate, or delay, the onset of various diseases, including cardiovascular disease, diabetes, certain cancers, and several other age-related degenerative disorders. The concept that moderate chocolate consumption could be part of a healthy diet has gained acceptance in past years based on the health benefits ascribed to selected cocoa components. Specifically, cocoa as a plant and chocolate as food contain a series of chemicals that can interact with cell and tissue components, providing protection against the development and amelioration of pathological conditions. The most relevant effects of cocoa and chocolate have been related to cardiovascular disease. The mechanisms behind these effects are still under investigation. However, the maintenance or restoration of vascular NO production and bioavailability and the antioxidant effects are the mechanisms most consistently supported by experimental data. This review will summarize the most recent research on the cardiovascular effects of cocoa flavanols and related compounds.

  20. Phenotypic plasticity, costs of phenotypes, and costs of plasticity

    DEFF Research Database (Denmark)

    Callahan, Hilary S; Maughan, Heather; Steiner, Uli

    2008-01-01

    Why are some traits constitutive and others inducible? The term costs often appears in work addressing this issue but may be ambiguously defined. This review distinguishes two conceptually distinct types of costs: phenotypic costs and plasticity costs. Phenotypic costs are assessed from patterns...... of covariation, typically between a focal trait and a separate trait relevant to fitness. Plasticity costs, separable from phenotypic costs, are gauged by comparing the fitness of genotypes with equivalent phenotypes within two environments but differing in plasticity and fitness. Subtleties associated with both...... types of costs are illustrated by a body of work addressing predator-induced plasticity. Such subtleties, and potential interplay between the two types of costs, have also been addressed, often in studies involving genetic model organisms. In some instances, investigators have pinpointed the mechanistic...

  1. 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

  2. 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.

  3. 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...

  4. Adverse metabolic phenotype of female offspring exposed to preeclampsia in utero: a characterization of the BPH/5 mouse in postnatal life.

    Science.gov (United States)

    Sutton, Elizabeth F; Lob, Heinrich E; Song, Jiunn; Xia, YunWei; Butler, Scott; Liu, Chin-Chi; Redman, Leanne M; Sones, Jenny L

    2017-04-01

    Preeclampsia (PE) is a devastating disorder of pregnancy that classically presents with maternal hypertension and proteinuria after 20 wk of gestation. In addition to being a leading cause of maternal and fetal morbidity/mortality, epidemiological and prospective studies have revealed long-term consequences for both the mother and baby of preeclamptic pregnancies, including chronic hypertension as well as other cardiovascular diseases and metabolic derangements. To better understand the effect of in utero exposure of PE on offspring, we utilized the BPH/5 mouse, a spontaneous model of the maternal and fetal PE syndrome. We hypothesized that young BPH/5 offspring would have altered metabolic and cardiovascular phenotypes. Indeed, BPH/5 growth-restricted offspring showed excess catch-up growth by early adulthood due to hyperphagia and increased white adipose tissue (WAT) accumulation, with inflammation markers isolated to the reproductive WAT depot only. Both excessive WAT accumulation and the inflammatory WAT phenotype were corrected by pair-feeding young BPH/5 female mice. We also found that young BPH/5 female mice showed evidence of leptin resistance. Indeed, chronic hyperleptinemia has been shown to characterize other rodent models of PE; however, the maternal metabolic profile before pregnancy has not been fully understood. Furthermore, we found that these mice show signs of cardiovascular anomalies (hypertension and cardiomegaly) and altered signaling within the reproductive axis in early life. Future studies will involve challenging the physiological metabolic state of BPH/5 mice through pair-feeding to reduce WAT before pregnancy and determining its causal role in adverse pregnancy outcomes. Copyright © 2017 the American Physiological Society.

  5. Accurate phenotyping: Reconciling approaches through Bayesian model averaging.

    Directory of Open Access Journals (Sweden)

    Carla Chia-Ming Chen

    Full Text Available Genetic research into complex diseases is frequently hindered by a lack of clear biomarkers for phenotype ascertainment. Phenotypes for such diseases are often identified on the basis of clinically defined criteria; however such criteria may not be suitable for understanding the genetic composition of the diseases. Various statistical approaches have been proposed for phenotype definition; however our previous studies have shown that differences in phenotypes estimated using different approaches have substantial impact on subsequent analyses. Instead of obtaining results based upon a single model, we propose a new method, using Bayesian model averaging to overcome problems associated with phenotype definition. Although Bayesian model averaging has been used in other fields of research, this is the first study that uses Bayesian model averaging to reconcile phenotypes obtained using multiple models. We illustrate the new method by applying it to simulated genetic and phenotypic data for Kofendred personality disorder-an imaginary disease with several sub-types. Two separate statistical methods were used to identify clusters of individuals with distinct phenotypes: latent class analysis and grade of membership. Bayesian model averaging was then used to combine the two clusterings for the purpose of subsequent linkage analyses. We found that causative genetic loci for the disease produced higher LOD scores using model averaging than under either individual model separately. We attribute this improvement to consolidation of the cores of phenotype clusters identified using each individual method.

  6. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Lockwood, Charles J

    2010-01-01

    cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non...... cardiovascular and non-cardiovascular causes, while hypertensive disorders of pregnancy are markers of early death of mothers from cardiovascular causes....

  7. The Cardiovascular Health in Ambulatory Care Research Team performance indicators for the primary prevention of cardiovascular disease: a modified Delphi panel study.

    Science.gov (United States)

    Tu, Jack V; Maclagan, Laura C; Ko, Dennis T; Atzema, Clare L; Booth, Gillian L; Johnston, Sharon; Tu, Karen; Lee, Douglas S; Bierman, Arlene; Hall, Ruth; Bhatia, R Sacha; Gershon, Andrea S; Tobe, Sheldon W; Sanmartin, Claudia; Liu, Peter; Chu, Anna

    2017-04-25

    High-quality ambulatory care can reduce cardiovascular disease risk, but important gaps exist in the provision of cardiovascular preventive care. We sought to develop a set of key performance indicators that can be used to measure and improve cardiovascular care in the primary care setting. As part of the Cardiovascular Health in Ambulatory Care Research Team initiative, we established a 14-member multidisciplinary expert panel to develop a set of indicators for measuring primary prevention performance in ambulatory cardiovascular care. We used a 2-stage modified Delphi panel process to rate potential indicators, which were identified from the literature and national cardiovascular organizations. The top-rated indicators were pilot tested to determine their measurement feasibility with the use of data routinely collected in the Canadian health care system. A set of 28 indicators of primary prevention performance were identified, which were grouped into 5 domains: risk factor prevalence, screening, management, intermediate outcomes and long-term outcomes. The indicators reflect the major cardiovascular risk factors including smoking, obesity, hypertension, diabetes, dyslipidemia and atrial fibrillation. All indicators were determined to be amenable to measurement with the use of population-based administrative (physician claims, hospital admission, laboratory, medication), survey or electronic medical record databases. The Cardiovascular Health in Ambulatory Care Research Team indicators of primary prevention performance provide a framework for the measurement of cardiovascular primary prevention efforts in Canada. The indicators may be used by clinicians, researchers and policy-makers interested in measuring and improving the prevention of cardiovascular disease in ambulatory care settings. Copyright 2017, Joule Inc. or its licensors.

  8. 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.

  9. 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.

  10. A study of cardiovascular risk factors and its knowledge among school children of Delhi

    Directory of Open Access Journals (Sweden)

    Grace Mary George

    2014-05-01

    Conclusion: Cardiovascular risk factors are highly prevalent among school children. Importantly, school children lack adequate knowledge regarding cardiovascular risk factors. School based interventions are required for cardiovascular risk reduction in childhood.

  11. Cell and small animal models for phenotypic drug discovery

    Directory of Open Access Journals (Sweden)

    Szabo M

    2017-06-01

    Full Text Available Mihaly Szabo,1 Sara Svensson Akusjärvi,1 Ankur Saxena,1 Jianping Liu,2 Gayathri Chandrasekar,1 Satish S Kitambi1 1Department of Microbiology Tumor, and Cell Biology, 2Department of Biochemistry and Biophysics, Karolinska Institutet, Solna, Sweden Abstract: The phenotype-based drug discovery (PDD approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed. In addition, a higher order of PDD screening setup using small animal models is also explored. As PDD screens integrate physiology and multiple signaling mechanisms during the screening process, the identified hits have higher biomedical applicability. Taken together, this review highlights the advantages gained by adopting a PDD approach in drug discovery. Such a PDD platform can complement target-based systems that are currently in practice to accelerate drug discovery. Keywords: phenotype, screening, PDD, discovery, zebrafish, drug

  12. Garlic for Cardiovascular Disease: Prevention or Treatment?

    Science.gov (United States)

    Alali, Feras Q; El-Elimat, Tamam; Khalid, Lila; Hudaib, Reema; Al-Shehabi, Tuqa Saleh; Eid, Ali H

    2017-01-01

    Cardiovascular disease (CVD) is the leading cause of global mortality with a substantial economic impact. The annual deaths are expected to increase in the next decade. An array of dietary supplements is being used by people worldwide to ameliorate cardiovascular risk factors. Garlic (Allium sativum L.), a top-selling herbal dietary supplement, is renowned for its wide range beneficial effects, particularly in the treatment and prevention of CVD. This review aims to present a thorough discussion of the available evidence-based data which support the use of garlic in the treatment or prevention of cardiovascular diseases, including atherosclerosis, hypertension, and hyperlipidemia. The molecular mechanisms underlying these effects are dissected as well. This review supports the notion that garlic has the potential to treat mild hypertension, to decrease hypercholesterolemia, and to prevent atherosclerosis. More clinical studies are essential to unequivocally understand the mechanisms underlying treatment or prevention of these cardiovascular conditions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Sortilin and the risk of cardiovascular disease.

    Science.gov (United States)

    Coutinho, Maria Francisca; Bourbon, Mafalda; Prata, Maria João; Alves, Sandra

    2013-10-01

    Plasma low-density lipoprotein cholesterol (LDL-C) levels are a key determinant of the risk of cardiovascular disease, which is why many studies have attempted to elucidate the pathways that regulate its metabolism. Novel latest-generation sequencing techniques have identified a strong association between the 1p13 locus and the risk of cardiovascular disease caused by changes in plasma LDL-C levels. As expected for a complex phenotype, the effects of variation in this locus are only moderate. Even so, knowledge of the association is of major importance, since it has unveiled a new metabolic pathway regulating plasma cholesterol levels. Crucial to this discovery was the work of three independent teams seeking to clarify the biological basis of this association, who succeeded in proving that SORT1, encoding sortilin, was the gene in the 1p13 locus involved in LDL metabolism. SORT1 was the first gene identified as determining plasma LDL levels to be mechanistically evaluated and, although the three teams used different, though appropriate, experimental methods, their results were in some ways contradictory. Here we review all the experiments that led to the identification of the new pathway connecting sortilin with plasma LDL levels and risk of myocardial infarction. The regulatory mechanism underlying this association remains unclear, but its discovery has paved the way for considering previously unsuspected therapeutic targets and approaches. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Would male hormonal contraceptives affect cardiovascular risk?

    Directory of Open Access Journals (Sweden)

    Michael Zitzmann

    2018-01-01

    Full Text Available The aim of hormonal male contraception is to prevent unintended pregnancies by suppressing spermatogenesis. Hormonal male contraception is based on the principle that exogenous administration of androgens and other hormones such as progestins suppress circulating gonadotropin concentrations, decreasing testicular Leydig cell and Sertoli cell activity and spermatogenesis. In order to achieve more complete suppression of circulating gonadotropins and spermatogenesis, a progestin has been added testosterone to the most recent efficacy trials of hormonal male contraceptives. This review focusses on the potential effects of male hormonal contraceptives on cardiovascular risk factors, lipids and body composition, mainly in the target group of younger to middle-aged men. Present data suggest that hormonal male contraception can be reasonably regarded as safe in terms of cardiovascular risk. However, as all trials have been relatively short (< 3 years, a final statement regarding the cardiovascular safety of hormonal male contraception, especially in long-term use, cannot be made. Older men with at high risk of cardiovascular event might not be good candidates for hormonal male contraception. The potential adverse effects of hormonal contraceptives on cardiovascular risk appear to depend greatly on the choice of the progestin in regimens for hormonal male contraceptives. In the development of prospective hormonal male contraception, data on longer-term cardiovascular safety will be essential.

  15. 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,

  16. Cardiovascular Nursing: From Florence to Melbourne.

    Science.gov (United States)

    Thompson, David R

    2016-08-01

    This paper, based on the 2015 CSANZ Cardiovascular Nursing Lecture, takes its title from the invitation to give this lecture in Melbourne being received when the author was visiting Florence, after whom Florence Nightingale, the founder of modern nursing, is named. Her work has indirectly shaped and influenced cardiovascular nursing, which has developed over the past 50 years. Despite its relatively short history, cardiovascular nursing has made a major contribution to improving the cardiovascular health and well-being of patients and families through health promotion, risk reduction and disease prevention. Examples include cardiac rehabilitation and secondary prevention and chronic heart failure disease management. Challenges, however, remain, including nurses practising to the full extent of their education and training, working as full partners with physicians and other health professionals in redesigning healthcare, ensuring better data collection and being more active in advocacy and policy initiatives. Cardiovascular nursing has a strong record of innovation but should always remember that it is there to serve the public and, bearing in mind the risk of potential harm versus benefit, be mindful of Florence Nightingale's wise counsel, "First, do no harm". Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  17. 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.

  18. HIV coreceptor phenotyping in the clinical setting.

    Science.gov (United States)

    Low, Andrew J; Swenson, Luke C; Harrigan, P Richard

    2008-01-01

    The introduction of CCR5 antagonists increases the options available for constructing antiretroviral regimens. However, this option is coupled with the caveat that patients should be tested for HIV coreceptor tropism prior to initiating CCR5 antagonist-based therapy. Failure to screen for CXCR4 usage increases the risk of using an ineffective drug, thus reducing the likelihood of viral suppression and increasing their risk for developing antiretroviral resistance. This review discusses current and future methods of determining HIV tropism, with a focus on their utility in the clinical setting for screening purposes. Some of these methods include recombinant phenotypic tests, such as the Monogram Trofile assay, as well as genotype-based predictors, heteroduplex tracking assays, and flow cytometry based methods. Currently, the best evidence supports the use of phenotypic methods, although other methods of screening for HIV coreceptor usage prior to the administration of CCR5 antagonists may reduce costs and increase turnaround time over phenotypic methods. The presence of low levels of X4 virus is a challenge to all assay methods, resulting in reduced sensitivity in clinical, patient-derived samples when compared to clonally derived samples. Gaining a better understanding of the output of these assays and correlating them with clinical progression and therapy response will provide some indication on how both genotype-based, and phenotypic assays for determining HIV coreceptor usage can be improved. In addition, leveraging new technologies capable of detecting low-level minority species may provide the most significant advances in ensuring that individuals with low levels of dual/mixed tropic virus are not inadvertently prescribed CCR5 antagonists.

  19. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    2016-06-01

    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  20. 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.

  1. 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.

  2. Evaluation of malposition of the branch pulmonary arteries using cardiovascular computed tomography angiography

    International Nuclear Information System (INIS)

    Liu, Hui; Juan, Yu-Hsiang; Wang, Qiushi; Huang, Hongfei; Yang, Lin; Xie, Zhaofeng; Chen, Jimei; Zhang, Xiaoshen; Liang, Changhong; Chung, Taylor; Kwong, Raymond Y.; Saboo, Sachin S.

    2014-01-01

    To analyze 15 cases of malposition of branch pulmonary arteries (MBPA) for the hospital-based prevalence, clinical information, surgical outcome, imaging findings, associated cardiovascular and airway abnormalities on cardiovascular computed tomography angiography (CCTA). We retrospectively searched for patients with MBPA from our database consisting of patients referred for CCTA due to known or suspected congenital heart disease and also from all patients receiving chest computed tomography (CT) during the same time period. We analyzed the hospital-based prevalence, image findings, associated cardiovascular anomalies, airway compression, and recorded the clinical information and surgical outcome. Our study showed 15 patients with MBPA (hospital-based prevalence: 0.33 % among patients with congenital heart disease and 0.06 % in all patients receiving chest CT or CCTA). Classic type was more common than lesser type (67 % versus 33 %). All patients had associated cardiovascular anomalies, including aortic arch abnormalities (80 %) and secondary airway compression (33 %). Surgery was performed in 67 % of cardiovascular anomalies and 60 % of airway stenoses. MBPA has a hospital-based prevalence of 0.33 % among patients with congenital heart disease and 0.06 % in all patients receiving either chest CT or CCTA. CCTA can delineate the anatomy of MBPA, associated cardiovascular and airway abnormalities for preoperative evaluation. (orig.)

  3. Evaluation of malposition of the branch pulmonary arteries using cardiovascular computed tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hui [Guangdong Academy of Medical Sciences, Department of Radiology, Guangdong General Hospital, GuangZhou, GuangDong (China); Brigham and Women' s Hospital, Harvard Medical School, Cardiovascular Imaging Program, Department of Medicine (Division of Cardiovascular Medicine) and Radiology, Boston, MA (United States); Juan, Yu-Hsiang [Brigham and Women' s Hospital, Harvard Medical School, Cardiovascular Imaging Program, Department of Medicine (Division of Cardiovascular Medicine) and Radiology, Boston, MA (United States); Chang Gung Memorial Hospital, Linkou and Chang Gung University, Department of Medical Imaging and Intervention, Taoyuan (China); Wang, Qiushi; Huang, Hongfei; Yang, Lin [Guangdong Academy of Medical Sciences, Department of Radiology, Guangdong General Hospital, GuangZhou, GuangDong (China); Xie, Zhaofeng [Guangdong Academy of Medical Sciences, Department of Pediatric Cardiology, Guangdong General Hospital, GuangZhou, GuangDong (China); Chen, Jimei; Zhang, Xiaoshen [Guangdong Academy of Medical Sciences, Department of Cardiovascular Surgery, Guangdong General Hospital, GuangZhou, GuangDong (China); Liang, Changhong [Guangdong Academy of Medical Sciences, Department of Radiology, Guangdong General Hospital, GuangZhou, GuangDong (China); Guangdong Academy of Medical Sciences, Department of Radiology, Guangdong General Hospital, Guangzhou (China); Chung, Taylor [Children' s Hospital and Research Center Oakland, Department of Diagnostic Imaging, Oakland, CA (United States); Kwong, Raymond Y.; Saboo, Sachin S. [Brigham and Women' s Hospital, Harvard Medical School, Cardiovascular Imaging Program, Department of Medicine (Division of Cardiovascular Medicine) and Radiology, Boston, MA (United States)

    2014-12-15

    To analyze 15 cases of malposition of branch pulmonary arteries (MBPA) for the hospital-based prevalence, clinical information, surgical outcome, imaging findings, associated cardiovascular and airway abnormalities on cardiovascular computed tomography angiography (CCTA). We retrospectively searched for patients with MBPA from our database consisting of patients referred for CCTA due to known or suspected congenital heart disease and also from all patients receiving chest computed tomography (CT) during the same time period. We analyzed the hospital-based prevalence, image findings, associated cardiovascular anomalies, airway compression, and recorded the clinical information and surgical outcome. Our study showed 15 patients with MBPA (hospital-based prevalence: 0.33 % among patients with congenital heart disease and 0.06 % in all patients receiving chest CT or CCTA). Classic type was more common than lesser type (67 % versus 33 %). All patients had associated cardiovascular anomalies, including aortic arch abnormalities (80 %) and secondary airway compression (33 %). Surgery was performed in 67 % of cardiovascular anomalies and 60 % of airway stenoses. MBPA has a hospital-based prevalence of 0.33 % among patients with congenital heart disease and 0.06 % in all patients receiving either chest CT or CCTA. CCTA can delineate the anatomy of MBPA, associated cardiovascular and airway abnormalities for preoperative evaluation. (orig.)

  4. The Impact of NSAID Treatment on Cardiovascular Risk

    DEFF Research Database (Denmark)

    Olsen, A. M. S.; Fosbol, E. L.; Gislason, Gunnar H.

    2014-01-01

    This MiniReview describes the present evidence for the relationship between cardiovascular risk and use of non-steroidal anti-inflammatory drugs (NSAIDs) with special focus using Danish register-based data. NSAIDs are among the most widely used drugs worldwide and mainly used for management of pain...... and inflammatory conditions. Through the past decade, much attention has been given to the cardiovascular safety of these drugs, and several studies have shown increased risk of adverse cardiovascular effects associated with NSAID use. Current guidelines discourage any use of NSAIDs in patients with cardiovascular...... observational studies is accumulating, suggesting that NSAIDs are a major public health concern due to the widespread use of these drugs. Although it seems unlikely that we can completely avoid use of NSAIDs, even among high-risk patients, these results highlight the importance of balancing the benefit versus...

  5. Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine.

    Science.gov (United States)

    Della Corte, Vittoriano; Tuttolomondo, Antonino; Pecoraro, Rosaria; Di Raimondo, Domenico; Vassallo, Valerio; Pinto, Antonio

    2016-01-01

    In the last decades, many factors thought to be associated with the atherosclerotic process and cardiovascular events have been studied, and some of these have been shown to correlate with clinical outcome, such as arterial stiffness, endothelial dysfunction and immunoinflammatory markers. Arterial stiffness is an important surrogate marker that describes the capability of an artery to expand and contract in response to pressure changes. It can be assessed with different techniques, such as the evaluation of PWV and AIx. It is related to central systolic pressure and it is an independent predictor of cardiovascular morbidity and mortality in hypertensive patients, type 2 diabetes, end-stage renal disease and in elderly populations. The endothelium has emerged as the key regulator of vascular homeostasis, in fact, it has not merely a barrier function but also acts as an active signal transducer for circulating influences that modify the vessel wall phenotype. When its function is lost, it predisposes the vasculature to vasoconstriction, leukocyte adherence, platelet activation, thrombosis and atherosclerosis. Non-invasive methods were developed to evaluate endothelial function, such as the assesment of FMD, L-FMC and RHI. Moreover in the last years, a large number of studies have clarified the role of inflammation and the underlying cellular and molecular mechanisms that contribute to atherogenesis. For clinical purposes, the most promising inflammatory biomarker appears to be CRP and a variety of population-based studies have showed that baseline CRP levels predict future cardiovascular events. Each of the markers listed above has its importance from the pathophysiological and clinical point of view, and those can also be good therapeutic targets. However, it must be stressed that assessments of these vascular markers are not mutually exclusive, but rather complementary and those can offer different views of the same pathology. The purpose of this review is to

  6. Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome.

    Science.gov (United States)

    Bajuk Studen, Katica; Jensterle Sever, Mojca; Pfeifer, Marija

    2013-01-01

    In addition to its effects on reproductive health, it is now well recognized that polycystic ovary syndrome (PCOS) is a metabolic disorder, characterized by decreased insulin sensitivity which leads to an excess lifetime risk of type 2 diabetes and cardiovascular disease. PCOS patients are often obese, hypertensive, dyslipidemic and insulin resistant; they have obstructive sleep apnea and have been reported to have higher aldosterone levels in comparison to normal healthy controls. These are all components of an adverse cardiovascular risk profile. Many studies exploring subclinical atherosclerosis using different methods (flow-mediated dilatation, intima media thickness, arterial stiffness, coronary artery calcification) as well as assessing circulating cardiovascular risk markers, point toward an increased cardiovascular risk and early atherogenesis in PCOS. The risk and early features of subclinical atherosclerosis can be reversed by non-medical (normalization of weight, healthy lifestyle) and medical (metformin, thiazolidinediones, spironolactone, and statins) interventions. However, the long-term risk for cardiovascular morbidity and mortality as well as the clinical significance of different interventions still need to be properly addressed in a large prospective study. Copyright © 2013 S. Karger AG, Basel.

  7. 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.

  8. 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.

  9. Quantification of Imaging Biomarkers For Cardiovascular Disease in CT(A)

    NARCIS (Netherlands)

    Shahzad, R.

    2013-01-01

    For better management of cardiovascular disease, it is of utmost importance to categorize the subjects into different risk groups. This categorization can be made based on cardiovascular risk factors including the family history of the subject. Imaging techniques play an increasing role in order to

  10. [Statement of the Spanish Interdisciplinary Cardiovascular Prevention Committee (CEIPC) on the 2012 European Cardiovascular Prevention Guidelines].

    Science.gov (United States)

    Royo-Bordonada, Miguel Ángel; Lobos Bejarano, José María; Villar Alvarez, Fernando; Sans, Susana; Pérez, Antonio; Pedro-Botet, Juan; Moreno Carriles, Rosa María; Maiques, Antonio; Lizcano, Angel; Lizarbe, Vicenta; Gil Núñez, Antonio; Fornés Ubeda, Francisco; Elosua, Roberto; de Santiago Nocito, Ana; de Pablo Zarzosa, Carmen; de Álvaro Moreno, Fernando; Cortés, Olga; Cordero, Alberto; Camafort Babkowski, Miguel; Brotons Cuixart, Carlos; Armario, Pedro

    2013-01-01

    Based on the two main frameworks for evaluating scientific evidence--SEC and GRADE--European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions, led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions--such as smoking ban in public areas or the elimination of trans fatty acids from the food chain--are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure (BP) within the 130-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

  11. Prognostic factors of congenital diaphragmatic hernia accompanied by cardiovascular malformation.

    Science.gov (United States)

    Takahashi, Shigehiro; Sago, Haruhiko; Kanamori, Yutaka; Hayakawa, Masahiro; Okuyama, Hiroomi; Inamura, Noboru; Fujino, Yuji; Usui, Noriaki; Taguchi, Tomoaki

    2013-08-01

    Congenital diaphragmatic hernia is associated with cardiovascular malformation. Many prognostic factors have been identified for isolated congenital diaphragmatic hernia; however, reports of concurrent congenital diaphragmatic hernia and cardiovascular malformation in infants are limited. This study evaluated congenital diaphragmatic hernia associated with cardiovascular malformation in infants. Factors associated with prognosis for patients were also identified. This retrospective cohort study was based on a Japanese survey of congenital diaphragmatic hernia patients between 2006 and 2010. Frequency and outcome of cardiovascular malformation among infants with congenital diaphragmatic hernia were examined. Severity of congenital diaphragmatic hernia and cardiovascular malformation were compared as predictors of mortality and morbidity. Cardiovascular malformation was identified in 76 (12.3%) of 614 infants with congenital diaphragmatic hernia. Mild cardiovascular malformation was detected in 19 (33.9%) and severe cardiovascular malformation in 37 (66.1%). Their overall survival rate at discharge was 46.4%, and the survival rate without morbidity was 23.2%. Mortality and morbidity at discharge were more strongly associated with severity of cardiovascular malformation (adjusted OR 7.69, 95%CI 1.96-30.27; adjusted OR 7.93, 95%CI 1.76-35.79, respectively) than with severity of congenital diaphragmatic hernia. The prognosis for infants with both congenital diaphragmatic hernia and cardiovascular malformation remains poor. Severity of cardiovascular malformation is a more important predictive factor for mortality and morbidity than severity of congenital diaphragmatic hernia. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  12. Mining skeletal phenotype descriptions from scientific literature.

    Directory of Open Access Journals (Sweden)

    Tudor Groza

    Full Text Available Phenotype descriptions are important for our understanding of genetics, as they enable the computation and analysis of a varied range of issues related to the genetic and developmental bases of correlated characters. The literature contains a wealth of such phenotype descriptions, usually reported as free-text entries, similar to typical clinical summaries. In this paper, we focus on creating and making available an annotated corpus of skeletal phenotype descriptions. In addition, we present and evaluate a hybrid Machine Learning approach for mining phenotype descriptions from free text. Our hybrid approach uses an ensemble of four classifiers and experiments with several aggregation techniques. The best scoring technique achieves an F-1 score of 71.52%, which is close to the state-of-the-art in other domains, where training data exists in abundance. Finally, we discuss the influence of the features chosen for the model on the overall performance of the method.

  13. Cardiovascular outcomes of pregnancy in Marfan's syndrome patients: A literature review.

    Science.gov (United States)

    Kim, So Yeon; Wolfe, Diana S; Taub, Cynthia C

    2018-03-01

    Pregnancy in patients with Marfan's syndrome (MFS) carries an increased risk of cardiovascular complications, resulting in increased maternal and fetal mortality and morbidity. Literature on MFS pregnant patients is relatively sparse, and there has yet to be a concrete consensus on the management of this unique patient population. The purpose of our paper is to provide a literature review of case reports and studies on MFS during pregnancy (published between 2005 and 2015) and to explore cardiovascular outcomes of patients with MFS. Of the 852 women in our review, there were 1112 pregnancies, with an aortic dissection rate of 7.9% and mortality of 1.2%. Data demonstrated a trend that patients whose aortic diameter ≥40 mm had a greater rate of dissection than MFS patients whose aortic diameter pregnancy or currently pregnant should be carefully counseled about the maternal and fetal risks throughout pregnancy. MFS patients whose aortic diameters ≥40 mm should be advised to ideally await pregnancy until prophylactic aortic surgery. As MFS varies in its phenotypic expression, each patient's risk of adverse cardiac events should be assessed individually through a joint Maternal Fetal Medicine and Cardiology Center. © 2017 Wiley Periodicals, Inc.

  14. Disease Human - MDC_CardiovascularMortality2006

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Polygon feature class based on Zip Code boundaries showing the rate of deaths due to major cardiovascular diseases per 1000 residents of Miami-Dade County in 2006.

  15. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    2015-08-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

  16. Utilization of genomic signatures to identify phenotype-specific drugs.

    Directory of Open Access Journals (Sweden)

    Seiichi Mori

    2009-08-01

    Full Text Available Genetic and genomic studies highlight the substantial complexity and heterogeneity of human cancers and emphasize the general lack of therapeutics that can match this complexity. With the goal of expanding opportunities for drug discovery, we describe an approach that makes use of a phenotype-based screen combined with the use of multiple cancer cell lines. In particular, we have used the NCI-60 cancer cell line panel that includes drug sensitivity measures for over 40,000 compounds assayed on 59 independent cells lines. Targets are cancer-relevant phenotypes represented as gene expression signatures that are used to identify cells within the NCI-60 panel reflecting the signature phenotype and then connect to compounds that are selectively active against those cells. As a proof-of-concept, we show that this strategy effectively identifies compounds with selectivity to the RAS or PI3K pathways. We have then extended this strategy to identify compounds that have activity towards cells exhibiting the basal phenotype of breast cancer, a clinically-important breast cancer characterized as ER-, PR-, and Her2- that lacks viable therapeutic options. One of these compounds, Simvastatin, has previously been shown to inhibit breast cancer cell growth in vitro and importantly, has been associated with a reduction in ER-, PR- breast cancer in a clinical study. We suggest that this approach provides a novel strategy towards identification of therapeutic agents based on clinically relevant phenotypes that can augment the conventional strategies of target-based screens.

  17. 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

  18. Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology.

    Science.gov (United States)

    Jackson, Neville; Atar, Dan; Borentain, Maria; Breithardt, Günter; van Eickels, Martin; Endres, Matthias; Fraass, Uwe; Friede, Tim; Hannachi, Hakima; Janmohamed, Salim; Kreuzer, Jörg; Landray, Martin; Lautsch, Dominik; Le Floch, Chantal; Mol, Peter; Naci, Huseyin; Samani, Nilesh J; Svensson, Anders; Thorstensen, Cathrine; Tijssen, Jan; Vandzhura, Victoria; Zalewski, Andrew; Kirchhof, Paulus

    2016-03-01

    Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines. The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development. A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier

  19. Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.

    Science.gov (United States)

    Riley, Callum James; Gavin, Matthew

    2017-06-01

    Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 18:102-113, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.

  20. Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy

    OpenAIRE

    Gruner, Christiane; Chan, Raymond H.; Crean, Andrew; Rakowski, Harry; Rowin, Ethan J.; Care, Melanie; Deva, Djeven; Williams, Lynne; Appelbaum, Evan; Gibson, C. Michael; Lesser, John R.; Haas, Tammy S.; Udelson, James E.; Manning, Warren J.; Siminovitch, Katherine

    2017-01-01

    Aims Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). Methods and results CMR was performed in 230 genotyped HCM patients (48 ± 15...

  1. 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...

  2. Cardiovascular issues in boxing and contact sports.

    Science.gov (United States)

    Siegel, Stephen A

    2009-10-01

    Despite the inherent risks associated with exercise in general and boxing in particular, the sport has had a limited number of catastrophic cardiovascular events. Screening should be based on risks involved and become more extensive with the advancement of the athlete. Anatomic and electrophysiologic risks need to be assessed and may preclude participation with resultant life style and economic complications. There should be adequate preparation for the rare potential cardiovascular complication at all events, with the ability to rapidly assess and treat arrhythmias.

  3. Distribution of Kell phenotype among pregnant women in Sokoto ...

    African Journals Online (AJOL)

    The distribution of Kell phenotype among the pregnant subjects was compared based on ethnicity. The prevalence of Kell antigen was significantly higher among the Hausa ethnic group (3.2%) compared to other ethnic groups which indicated zero prevalence (p=0.001). Kell negative phenotype was ≥ 96.8% among all the ...

  4. 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.

  5. 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

  6. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Directory of Open Access Journals (Sweden)

    Héctor Rincón-Arévalo

    2016-06-01

    Full Text Available Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/− mice fed or not with high-fat diet (HFD, by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410 [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia.

  7. Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis

    Science.gov (United States)

    Rincón-Arévalo, Héctor; Castaño, Diana; Villa-Pulgarín, Janny; Rojas, Mauricio; Vásquez, Gloria; Correa, Luis A.; Ramírez-Pineda, José R.; Yassin, Lina M.

    2016-01-01

    Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE−/−) mice fed or not with high-fat diet (HFD), by flow cytometry. Here, we provide the information about the materials, methods, analysis and additional information related to our study published in Atherosclerosis (DOI: 10.1016/j.atherosclerosis.2015.12.022, article reference: ATH14410) [1]. The data contained in this article shows and supports that mice with advanced atherosclerosis have a variety of alterations in frequency and phenotype of B cell subsets, most of which associated with dyslipidemia. PMID:27081674

  8. The Expected Cardiovascular Benefit of Plasma Cholesterol Lowering with or Without LDL-C Targets in Healthy Individuals at Higher Cardiovascular Risk

    Directory of Open Access Journals (Sweden)

    Fernando Henpin Yue Cesena

    Full Text Available Abstract Background: There is controversy whether management of blood cholesterol should be based or not on LDL-cholesterol (LDL-c target concentrations. Objectives: To compare the estimated impact of different lipid-lowering strategies, based or not on LDL-c targets, on the risk of major cardiovascular events in a population with higher cardiovascular risk. Methods: We included consecutive individuals undergoing a routine health screening in a single center who had a 10-year risk for atherosclerotic cardiovascular disease (ASCVD ≥ 7.5% (pooled cohort equations, ACC/AHA, 2013. For each individual, we simulated two strategies based on LDL-c target (≤ 100 mg/dL [Starget-100] or ≤ 70 mg/dL [Starget-70] and two strategies based on percent LDL-c reduction (30% [S30%] or 50% [S50%]. Results: In 1,897 subjects (57 ± 7 years, 96% men, 10-year ASCVD risk 13.7 ± 7.1%, LDL-c would be lowered from 141 ± 33 mg/dL to 99 ± 23 mg/dL in S30%, 71 ± 16 mg/dL in S50%, 98 ± 9 mg/dL in Starget-100, and 70 ± 2 mg/dL in Starget-70. Ten-year ASCVD risk would be reduced to 8.8 ± 4.8% in S50% and 8.9 ± 5.2 in Starget-70. The number of major cardiovascular events prevented in 10 years per 1,000 individuals would be 32 in S30%, 31 in Starget-100, 49 in S50%, and 48 in Starget-70. Compared with Starget-70, S50% would prevent more events in the lower LDL-c tertile and fewer events in the higher LDL-c tertile. Conclusions: The more aggressive lipid-lowering approaches simulated in this study, based on LDL-c target or percent reduction, may potentially prevent approximately 50% more hard cardiovascular events in the population compared with the less intensive treatments. Baseline LDL-c determines which strategy (based or not on LDL-c target is more appropriate at the individual level.

  9. Association of diastolic blood pressure with cardiovascular events in older people varies upon cardiovascular history

    DEFF Research Database (Denmark)

    Wijsman, Liselotte W.; Muller, Majon; de Craen, Anton J .M.

    2018-01-01

    with those with normal DBP. After further adjusting for cardiovascular factors, this association attenuated to 1.05 (0.86; 1.28). A previous history of cardiovascular disease significantly modified the relation between DBP and risk of cardiovascular events (P-interaction 0.042). In participants without......BACKGROUND: In older age, a low DBP has been associated with increased risk of cardiovascular events, especially in frail older people. We tested the hypothesis that low DBP is associated with a high risk of cardiovascular events in people with a previous history of cardiovascular disease......-90 mmHg) or high (>90 mmHg). Cox proportional hazards analyses were used to estimate hazard ratio with 95% confidence intervals (CI); analyses were stratified for cardiovascular history. RESULTS: Participants with low DBP had a 1.24-fold (1.04; 1.49) increased risk of cardiovascular events compared...

  10. 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.

  11. 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

  12. Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

    Directory of Open Access Journals (Sweden)

    Douglas J Conrad

    Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

  13. 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.

  14. Qingdao Port Cardiovascular Health Study: a prospective cohort study.

    Science.gov (United States)

    Spatz, Erica S; Jiang, Xianyan; Lu, Jiapeng; Masoudi, Frederick A; Spertus, John A; Wang, Yongfei; Li, Xi; Downing, Nicholas S; Nasir, Khurram; Du, Xue; Li, Jing; Krumholz, Harlan M; Liu, Xiancheng; Jiang, Lixin

    2015-12-09

    In China, efforts are underway to respond to rapidly increasing rates of heart disease and stroke. Yet the epidemiology of cardiovascular disease in China may be different from that of other populations. Thus, there is a critical need for population-based studies that provide insight into the risk factors, incidence and outcomes of cardiovascular disease in China. The Qingdao Port Cardiovascular Health Study is designed to investigate the burden of cardiovascular disease and the sociodemographic, biological, environmental and clinical risk factors associated with disease onset and outcomes. For this study, from 2000 through 2013, 32,404 employees aged 18 years or older were recruited from the Qingdao Port Group in China, contributing 221,923 annual health assessments. The mean age at recruitment was 43.4 (SD=12.9); 79% were male. In this ongoing study, annual health assessments, governed by extensive quality control mechanisms, include a questionnaire (capturing demographic and employment information, medical history, medication use, health behaviours and health outcomes), physical examination, ECG, and blood and urine analysis. Additional non-annual assessments include an X-ray, echocardiogram and carotid ultrasound; bio-samples will be collected for future genetic and proteomic analyses. Cardiovascular outcomes are accessed via self-report and are actively being verified with medical insurance claims; efforts are underway to adjudicate outcomes with hospital medical records. Early findings reveal a significant increase in cardiovascular risk factors from 2000 to 2010 (hypertension: 26.4-39.4%; diabetes: 3.3-8.9%; hyperlipidaemia: 5.0-33.6%; body mass index >28 m/kg(2): 14.1-18.6%). We aim to generate novel insights about the epidemiology and outcomes of cardiovascular disease in China, with specific emphasis on the potentially unique risk factor profiles of this Chinese population. Knowledge generated will be disseminated in the peer-reviewed literature, and will

  15. Qingdao Port Cardiovascular Health Study: a prospective cohort study

    Science.gov (United States)

    Spatz, Erica S; Jiang, Xianyan; Lu, Jiapeng; Masoudi, Frederick A; Spertus, John A; Wang, Yongfei; Li, Xi; Downing, Nicholas S; Nasir, Khurram; Du, Xue; Li, Jing; Krumholz, Harlan M; Liu, Xiancheng; Jiang, Lixin

    2015-01-01

    Purpose In China, efforts are underway to respond to rapidly increasing rates of heart disease and stroke. Yet the epidemiology of cardiovascular disease in China may be different from that of other populations. Thus, there is a critical need for population-based studies that provide insight into the risk factors, incidence and outcomes of cardiovascular disease in China. The Qingdao Port Cardiovascular Health Study is designed to investigate the burden of cardiovascular disease and the sociodemographic, biological, environmental and clinical risk factors associated with disease onset and outcomes. Participants For this study, from 2000 through 2013, 32 404 employees aged 18 years or older were recruited from the Qingdao Port Group in China, contributing 221 923 annual health assessments. The mean age at recruitment was 43.4 (SD=12.9); 79% were male. In this ongoing study, annual health assessments, governed by extensive quality control mechanisms, include a questionnaire (capturing demographic and employment information, medical history, medication use, health behaviours and health outcomes), physical examination, ECG, and blood and urine analysis. Additional non-annual assessments include an X-ray, echocardiogram and carotid ultrasound; bio-samples will be collected for future genetic and proteomic analyses. Cardiovascular outcomes are accessed via self-report and are actively being verified with medical insurance claims; efforts are underway to adjudicate outcomes with hospital medical records. Findings to date Early findings reveal a significant increase in cardiovascular risk factors from 2000 to 2010 (hypertension: 26.4–39.4%; diabetes: 3.3–8.9%; hyperlipidaemia: 5.0–33.6%; body mass index >28 m/kg2: 14.1–18.6%). Future Plans We aim to generate novel insights about the epidemiology and outcomes of cardiovascular disease in China, with specific emphasis on the potentially unique risk factor profiles of this Chinese population. Knowledge

  16. 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…

  17. 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.

  18. 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.

  19. Cardiovascular oscillations: in search of a nonlinear parametric model

    Science.gov (United States)

    Bandrivskyy, Andriy; Luchinsky, Dmitry; McClintock, Peter V.; Smelyanskiy, Vadim; Stefanovska, Aneta; Timucin, Dogan

    2003-05-01

    We suggest a fresh approach to the modeling of the human cardiovascular system. Taking advantage of a new Bayesian inference technique, able to deal with stochastic nonlinear systems, we show that one can estimate parameters for models of the cardiovascular system directly from measured time series. We present preliminary results of inference of parameters of a model of coupled oscillators from measured cardiovascular data addressing cardiorespiratory interaction. We argue that the inference technique offers a very promising tool for the modeling, able to contribute significantly towards the solution of a long standing challenge -- development of new diagnostic techniques based on noninvasive measurements.

  20. Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Lockwood, Charles J

    2010-01-01

    The combined effects of preterm delivery, small-for-gestational-age offspring, hypertensive disorders of pregnancy, placental abruption and stillbirth on early maternal death from cardiovascular causes have not previously been described in a large cohort. We investigated the effects of pregnancy...... cardiovascular and non-cardiovascular causes following preterm delivery, small-for-gestational-age offspring and hypertensive disorders of pregnancy. We found that preterm delivery and small-for-gestational-age were both associated with subsequent death of mothers from cardiovascular and non......-cardiovascular causes. Severe pre-eclampsia was associated with death from cardiovascular causes only. There was a less than additive effect on cardiovascular mortality hazard ratios with increasing number of pregnancy complications: preterm delivery 1.90 [95% confidence intervals 1.49, 2.43]; preterm delivery...

  1. Advances in Integrating Traditional and Omic Biomarkers When Analyzing the Effects of the Mediterranean Diet Intervention in Cardiovascular Prevention

    Science.gov (United States)

    Fitó, Montserrat; Melander, Olle; Martínez, José Alfredo; Toledo, Estefanía; Carpéné, Christian; Corella, Dolores

    2016-01-01

    Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition. PMID:27598147

  2. 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

  3. 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....

  4. Triglycerides and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Varbo, Anette

    2014-01-01

    cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...... of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence...

  5. 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

  6. (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...

  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. Carbon dioxide balneotherapy and cardiovascular disease

    Science.gov (United States)

    Pagourelias, Efstathios D.; Zorou, Paraskevi G.; Tsaligopoulos, Miltiadis; Athyros, Vasilis G.; Karagiannis, Asterios; Efthimiadis, Georgios K.

    2011-09-01

    Carbon dioxide (CO2) balneotherapy is a kind of remedy with a wide spectrum of applications which have been used since the Middle Ages. However, its potential use as an adjuvant therapeutic option in patients with cardiovascular disease is not yet fully clarified. We performed a thorough review of MEDLINE Database, EMBASE, ISI WEB of Knowledge, COCHRANE database and sites funded by balneotherapy centers across Europe in order to recognize relevant studies and aggregate evidence supporting the use of CO2 baths in various cardiovascular diseases. The three main effects of CO2 hydrotherapy during whole body or partial immersion, including decline in core temperature, an increase in cutaneous blood flow, and an elevation of the score on thermal sensation, are analyzed on a pathophysiology basis. Additionally, the indications and contra-indications of the method are presented in an evidence-based way, while the need for new methodologically sufficient studies examining the use of CO2 baths in other cardiovascular substrates is discussed.

  9. Microalbuminuria and obesity: impact on cardiovascular disease and mortality

    DEFF Research Database (Denmark)

    Klausen, Klaus Peder; Parving, Hans-Henrik; Scharling, Henrik

    2008-01-01

    P>Objective Microalbuminuria and obesity are both associated with cardiovascular disease (CVD). The aim of this study was to determine the association between obesity (measured by body mass index, waist-to-hip ratio, waist circumference) and different levels of microalbuminuria. We also aimed...... to determine the risk of death and CVD at different levels of microalbuminuria and obesity. Design Population-based observational study based on 2696 men and women, 30-70 years of age. Urinary albumin excretion (UAE), body mass index, waist-to-hip ratio, waist circumference and other cardiovascular risk...

  10. 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.

  11. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.

    Science.gov (United States)

    Majumdar, Arunabha; Witte, John S; Ghosh, Saurabh

    2015-12-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE

  12. Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment.

    Science.gov (United States)

    Palmeiro, Christopher; Davila, Maria I; Bhat, Mallika; Frishman, William H; Weiss, Irene A

    2013-01-01

    Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels effects of SHy on all-cause and cardiovascular mortality are not clear, but recent meta-analyses suggest a modest increase in mortality, with the risk increasing with age and associated with the lowest TSH levels. The long-term consequences of SHy in young- and middle-aged adults, and in those with TSH levels are mildly low, are uncertain. For these reasons, guidelines for treatment are based on patient age, the degree of TSH suppression, symptoms consistent with hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.

  13. A new paradigm of cardiovascular risk factor modification

    Directory of Open Access Journals (Sweden)

    Muhammad Firdaus

    2005-07-01

    Full Text Available Muhammad Firdaus1, Jeffery M Asbury2, Dwight W Reynolds21Donald W Reynolds Department of Geriatric Medicine, University of Oklahoma, Oklahoma City, OK, USA; 2Department of Medicine, Cardiovascular Section, University of Oklahoma, Oklahoma City, OK, USAAbstract: Atherosclerotic cardiovascular diseases (CVDs are the leading cause of death and disability in the United States. While multiple studies have demonstrated that modification of atherosclerotic cardiovascular risk factors (CVRFs significantly reduces morbidity and mortality rates, clinical control of CVDs and CVRFs remains poor. By 2010, the American Heart Association seeks to reduce coronary heart disease, stroke, and risk by 25%. To meet this goal, clinical practitioners must establish new treatment paradigms for CVDs and CVRFs. This paper discusses one such treatment model – a comprehensive atherosclerosis program run by physician extenders (under physician supervision, which incorporates evidence-based CVD and CVRF interventions to achieve treatment goals.Keywords: atherosclerosis, cardiovascular risk factors, prevention, modification

  14. [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.

  15. Relationships Between Glycemic Control and Cardiovascular Fitness.

    Science.gov (United States)

    Moxley, Elizabeth W; Smith, Donald; Quinn, Lauretta; Park, Chang

    2018-07-01

    Diabetes is a serious health problem affecting approximately 29.1 million individuals in the United States. Another 86 million have prediabetes. The development and implementation of lifestyle modifications such as physical activity for these persons are among the most effective methods for prevention and treatment. The aim of this study was to examine relationships between glycemic control (HbA1c) and cardiovascular fitness (peak maximal oxygen uptake [VO 2 peak] and ventilatory threshold [VT]) in overweight/obese subjects with and without type 2 diabetes (T2DM). In addition, the influences of body mass index (BMI) and insulin sensitivity (homeostasis model assessment [HOMA %S]) on the relationship between glycemic control and cardiovascular fitness were explored. Data were abstracted from a completed study that included 51 overweight or obese subjects with T2DM ( n = 18), impaired glucose tolerance ( n = 8), or normal glucose tolerance ( n = 25). Relationships between glycemic control (HbA1c) and cardiovascular fitness (VO 2 peak and VT) were determined using correlational analysis and multiple linear regression analyses. A statistically significant relationship was observed between HbA1c and cardiovascular fitness. However, BMI and HOMA %S did not influence the relationship between glycemic control and cardiovascular fitness. HbA1c contributes to VO 2 peak and VT in obese and overweight subjects across glucose tolerance categories. Significant results were achieved despite the fact that there was a limited range of HbA1c based on the study inclusion criteria. This finding suggests that even a mild decrease in glycemic control can negatively influence cardiovascular fitness.

  16. New insights on the maternal diet induced-hypertension: potential role of the phenotypic plasticity and sympathetic-respiratory overactivity

    Directory of Open Access Journals (Sweden)

    JOAO HENRIQUE eDA COSTA SILVA

    2015-11-01

    Full Text Available Systemic arterial hypertension (SAH is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental input without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity.

  17. Understanding cardiovascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000759.htm Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...

  18. 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.

  19. Projections of Demand for Cardiovascular Surgery and Supply of Surgeons.

    Science.gov (United States)

    Lee, Jung Jeung; Park, Nam Hee; Lee, Kun Sei; Chee, Hyun Keun; Sim, Sung Bo; Kim, Myo Jeong; Choi, Ji Suk; Kim, Myunghwa; Park, Choon Seon

    2016-12-01

    While demand for cardiovascular surgery is expected to increase gradually along with the rapid increase in cardiovascular diseases with respect to the aging population, the supply of thoracic and cardiovascular surgeons has been continuously decreasing over the past 10 years. Consequently, this study aims to achieve guidance in establishing health care policy by analyzing the supply and demand for cardiovascular surgeries in the medical service area of Korea. After investigating the actual number of cardiovascular surgeries performed using the National Health Insurance claim data of the Health Insurance Review and Assessment Service, as well as drawing from national statistics concerning the elderly population aged 65 and over, this study estimated the number of future cardiovascular surgeries by using a cell-based model. To be able to analyze the supply and demand of surgeons, the recent status of new surgeons specializing in thoracic and cardiovascular surgeries and the ratio of their subspecialties in cardiovascular surgeries were investigated. Then, while taking three different scenarios into account, the number of cardiovascular surgeons expected be working in 5-year periods was projected. The number of cardiovascular surgeries, which was recorded at 10,581 cases in 2014, is predicted to increase consistently to reach a demand of 15,501 cases in 2040-an increase of 46.5%. There was a total of 245 cardiovascular surgeons at work in 2014. Looking at 5 year spans in the future, the number of surgeons expected to be supplied in 2040 is 184, to retire is 249, and expected to be working is 309-an increase of -24.9%, 1.6%, and 26.1%, respectively compared to those in 2014. This forecasts a demand-supply imbalance in every scenario. Cardiovascular surgeons are the most central resource in the medical service of highly specialized cardiovascular surgeries, and fostering the surgeons requires much time, effort, and resources; therefore, by analyzing the various factors

  20. CKD Self-management: Phenotypes and Associations With Clinical Outcomes.

    Science.gov (United States)

    Schrauben, Sarah J; Hsu, Jesse Y; Rosas, Sylvia E; Jaar, Bernard G; Zhang, Xiaoming; Deo, Rajat; Saab, Georges; Chen, Jing; Lederer, Swati; Kanthety, Radhika; Hamm, L Lee; Ricardo, Ana C; Lash, James P; Feldman, Harold I; Anderson, Amanda H

    2018-03-24

    To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. The objective of this study was to classify CKD self-management behaviors into phenotypes and assess the association of these phenotypes with clinical outcomes. Prospective cohort study. Adults with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. 3,939 participants in the CRIC Study recruited between 2003 and 2008 served as the derivation cohort and 1,560 participants recruited between 2013 and 2015 served as the validation cohort. CKD self-management behavior phenotypes. CKD progression, atherosclerotic events, heart failure events, death from any cause. Latent class analysis stratified by diabetes was used to identify CKD self-management phenotypes based on measures of body mass index, diet, physical activity, blood pressure, smoking status, and hemoglobin A 1c concentration (if diabetic); Cox proportional hazards models. 3 identified phenotypes varied according to the extent of implementation of recommended CKD self-management behaviors: phenotype I characterized study participants with the most recommended behaviors; phenotype II, participants with a mixture of recommended and not recommended behaviors; and phenotype III, participants with minimal recommended behaviors. In multivariable-adjusted models for those with and without diabetes, phenotype III was strongly associated with CKD progression (HRs of 1.82 and 1.49), death (HRs of 1.95 and 4.14), and atherosclerotic events (HRs of 2.54 and 1.90; each P diabetes. No consensus definition of CKD self-management; limited to baseline behavior data. There are potentially 3 CKD self-management behavior phenotypes that distinguish risk for clinical outcomes. These phenotypes may inform the development of studies and guidelines regarding optimal self-management. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights

  1. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Vollert, Jan

    2014-01-01

    In neuropathic pain it has been suggested that pain phenotype based on putative pain mechanisms may predict response to treatment. This was a randomised, double-blind, placebo-controlled, and phenotype-stratified study with 2 6-week treatment periods of oxcarbazepine (1800-2400mg) and placebo...... patients: 31 with the irritable and 52 with the nonirritable nociceptor phenotype. In the total sample, oxcarbazepine relieved pain of 0.7 points (on a numeric rating scale 0-10; 95% confidence interval [CI] 0.4-1.4) more than placebo (P=0.015) and there was a significant interaction between treatment....... The primary efficacy measure was change in median pain intensity between baseline and the last week of treatment measured on an 11-point numeric rating scale, and the primary objective was to compare the effect of oxcarbazepine in patients with and without the irritable nociceptor phenotype as defined...

  2. Phenotypic deconstruction of gene circuitry.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  3. Phenotypic deconstruction of gene circuitry

    Science.gov (United States)

    Lomnitz, Jason G.; Savageau, Michael A.

    2013-06-01

    It remains a challenge to obtain a global perspective on the behavioral repertoire of complex nonlinear gene circuits. In this paper, we describe a method for deconstructing complex systems into nonlinear sub-systems, based on mathematically defined phenotypes, which are then represented within a system design space that allows the repertoire of qualitatively distinct phenotypes of the complex system to be identified, enumerated, and analyzed. This method efficiently characterizes large regions of system design space and quickly generates alternative hypotheses for experimental testing. We describe the motivation and strategy in general terms, illustrate its use with a detailed example involving a two-gene circuit with a rich repertoire of dynamic behavior, and discuss experimental means of navigating the system design space.

  4. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    NARCIS (Netherlands)

    Kohler, S.; Doelken, S.C.; Mungall, C.J.; Bauer, S.; Firth, H.V.; Bailleul-Forestier, I.; Black, G.C.M.; Brown, D.L.; Brudno, M.; Campbell, J.; FitzPatrick, D.R.; Eppig, J.T.; Jackson, A.P.; Freson, K.; Girdea, M.; Helbig, I.; Hurst, J.A.; Jahn, J.; Jackson, L.G.; Kelly, A.M.; Ledbetter, D.H.; Mansour, S.; Martin, C.L.; Moss, C.; Mumford, A.; Ouwehand, W.H.; Park, S.M.; Riggs, E.R.; Scott, R.H.; Sisodiya, S.; Vooren, S. van der; Wapner, R.J.; Wilkie, A.O.; Wright, C.F.; Silfhout, A.T. van; Leeuw, N. de; Vries, B. de; Washingthon, N.L.; Smith, C.L.; Westerfield, M.; Schofield, P.; Ruef, B.J.; Gkoutos, G.V.; Haendel, M.; Smedley, D.; Lewis, S.E.; Robinson, P.N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have

  5. Slow breathing and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ashish Chaddha

    2015-01-01

    Full Text Available Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  6. Estudi sobre l´hostilitat i la reactivitat cardiovascular en dones

    OpenAIRE

    Porras Clavero, Mª Salud

    2007-01-01

    INTRODUCCIÓN: La hostilidad se ha estudiado tradicionalmente en muestras masculinas o mixtas como un factor de riesgo de enfermar, especialmente de enfermedades cardiovasculares (Fredickson, 2000; Christensen, 2004; Olson et al., 2005). La reactividad cardiovascular (aumento significativo de TA y FC respecto a la línea base) ante una condición de estrés se ha observado como un posible marcador de riesgo de enfermedades cardiovasculares (ECV), especialmente de HTA (Lovallo y Gerin, 2003; Treib...

  7. Against Genetic Tests for Athletic Talent: The Primacy of the Phenotype.

    Science.gov (United States)

    Loland, Sigmund

    2015-09-01

    New insights into the genetics of sport performance lead to new areas of application. One area is the use of genetic tests to identify athletic talent. Athletic performances involve a high number of complex phenotypical traits. Based on the ACCE model (review of Analytic and Clinical validity, Clinical utility, and Ethical, legal and social implications), a critique is offered of the lack of validity and predictive power of genetic tests for talent. Based on the ideal of children's right to an open future, a moral argument is given against such tests on children and young athletes. A possible role of genetic tests in sport is proposed in terms of identifying predisposition for injury. In meeting ACCE requirements, such tests could improve individualised injury prevention and increase athlete health. More generally, limitations of science are discussed in the identification of talent and in the understanding of complex human performance phenotypes. An alternative approach to talent identification is proposed in terms of ethically sensitive, systematic and evidence-based holistic observation over time of relevant phenotypical traits by experienced observers. Talent identification in sport should be based on the primacy of the phenotype.

  8. 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...

  9. The evolution of phenotypic plasticity in fish swimming

    Science.gov (United States)

    Oufiero, Christopher E.; Whitlow, Katrina R.

    2016-01-01

    Abstract Fish have a remarkable amount of variation in their swimming performance, from within species differences to diversity among major taxonomic groups. Fish swimming is a complex, integrative phenotype and has the ability to plastically respond to a myriad of environmental changes. The plasticity of fish swimming has been observed on whole-organismal traits such as burst speed or critical swimming speed, as well as underlying phenotypes such as muscle fiber types, kinematics, cardiovascular system, and neuronal processes. Whether the plastic responses of fish swimming are beneficial seems to depend on the environmental variable that is changing. For example, because of the effects of temperature on biochemical processes, alterations of fish swimming in response to temperature do not seem to be beneficial. In contrast, changes in fish swimming in response to variation in flow may benefit the fish to maintain position in the water column. In this paper, we examine how this plasticity in fish swimming might evolve, focusing on environmental variables that have received the most attention: temperature, habitat, dissolved oxygen, and carbon dioxide variation. Using examples from previous research, we highlight many of the ways fish swimming can plastically respond to environmental variation and discuss potential avenues of future research aimed at understanding how plasticity of fish swimming might evolve. We consider the direct and indirect effects of environmental variation on swimming performance, including changes in swimming kinematics and suborganismal traits thought to predict swimming performance. We also discuss the role of the evolution of plasticity in shaping macroevolutionary patterns of diversity in fish swimming. PMID:29491937

  10. The Prevalence of Cardiovascular Disease in the Lagos State, Nigeria

    African Journals Online (AJOL)

    The analysis, which examines the prevalence of cardiovascular diseases (ICD 9: 390-459) in Lagos State of Nigeria, was based on records obtained from the register of deaths in four Local Government Areas of the State. The result shows that there is general increase in death rates due to cardiovascular diseases over the ...

  11. Optimizing Cardiovascular Benefits of Exercise: A Review of Rodent Models

    Science.gov (United States)

    Davis, Brittany; Moriguchi, Takeshi; Sumpio, Bauer

    2013-01-01

    Although research unanimously maintains that exercise can ward off cardiovascular disease (CVD), the optimal type, duration, intensity, and combination of forms are yet not clear. In our review of existing rodent-based studies on exercise and cardiovascular health, we attempt to find the optimal forms, intensities, and durations of exercise. Using Scopus and Medline, a literature review of English language comparative journal studies of cardiovascular benefits and exercise was performed. This review examines the existing literature on rodent models of aerobic, anaerobic, and power exercise and compares the benefits of various training forms, intensities, and durations. The rodent studies reviewed in this article correlate with reports on human subjects that suggest regular aerobic exercise can improve cardiac and vascular structure and function, as well as lipid profiles, and reduce the risk of CVD. Findings demonstrate an abundance of rodent-based aerobic studies, but a lack of anaerobic and power forms of exercise, as well as comparisons of these three components of exercise. Thus, further studies must be conducted to determine a truly optimal regimen for cardiovascular health. PMID:24436579

  12. Barriers to lifestyle changes for prevention of cardiovascular disease

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Leppin, Anja; Gyrd-Hansen, Dorte

    2017-01-01

    BACKGROUND: Elimination of modifiable risk factors including unhealthy lifestyle has the potential for prevention of 80% of cardiovascular disease cases. The present study focuses on disclosing barriers for maintaining specific lifestyle changes by exploring associations between perceiving...... inequality even in populations with equal and cost-free access to health care. Our study suggests supplementing traditional public campaigns to counter cardiovascular disease by using individualized and targeted initiatives....... these barriers and various sociodemographic and health-related characteristics. METHODS: Data were collected through a web-based questionnaire survey and included 962 respondents who initially accepted treatment for a hypothetical cardiovascular risk, and who subsequently stated that they preferred lifestyle...

  13. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

  14. Molecular cardiovascular imaging

    International Nuclear Information System (INIS)

    Schaefers, M.

    2007-01-01

    Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

  15. Metformin treatment in different phenotypes of polycystic ovary syndrome.

    Science.gov (United States)

    Hosseini, Marzieh Agha; Alleyassin, Ashraf; Sarvi, Fatemeh; Safdarian, Leila; Kokab, Abas; Fanisalek, Mehran

    2013-11-01

    The aim of this study was to evaluate the effectiveness of Metformin on ovulation and eventual clinical pregnancy in different phenotypes of polycystic ovary syndrome (PCOS). A total of 359 subjects who had proven PCOS according to Rotterdam criteria were prospectively selected. Patients' PCOS phenotypes were determined and recorded. All patients were younger than 35 years. Clinical and biochemical assays in all patients were initially obtained. Then patients were divided into two separate groups. One group received both 1,500 mg of Metformin and 1 mg of folic acid per day and the other group received only 1 mg of folic acid for a total of 2 months. Subsequently, all patients underwent ovulation stimulation with 5 mg of Letrozole per day for 5 days followed by an intra-uterine insemination. Finally, ovulation and pregnancy rates were evaluated for all four PCOS phenotypes. Effect of Metformin therapy was evaluated for each group and each phenotype. The pregnancy rate in Metformin and non-Metformin groups were, respectively, as follows: in phenotype A (39.2 vs. 33.7 %, p = 0.270), phenotype B (43.8 vs. 20 %, p = 0.210), phenotype C (44 vs. 20 %, p = 0.064), and phenotype D (36.5 vs. 28.6 %, p = 0.279). Although there was a little improvement in ovulation and pregnancy rates among patients with B and C phenotypes, there was not a statistically significant difference between the two groups. Based on our study, Metformin therapy does not change the ovulation and pregnancy rate.

  16. Novel biomarkers with potential for cardiovascular risk reclassification.

    Science.gov (United States)

    Mallikethi-Reddy, Sagar; Briasoulis, Alexandros; Akintoye, Emmanuel; Afonso, Luis

    Precise estimation of the absolute risk for CVD events is necessary when making treatment recommendations for patients. A number of multivariate risk models have been developed for estimation of cardiovascular risk in asymptomatic individuals based upon assessment of multiple variables. Due to the inherent limitation of risk models, several novel risk markers including serum biomarkers have been studied in an attempt to improve the cardiovascular risk prediction above and beyond the established risk factors. In this review, we discuss the role of underappreciated biomarkers such as red cell distribution width (RDW), cystatin C (cysC), and homocysteine (Hcy) as well as imaging biomarkers in cardiovascular risk reclassification, and highlight their utility as additional source of information in patients with intermediate risk.

  17. 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. 

  18. Cardiovascular event-free survival after adjuvant radiation therapy in breast cancer patients stratified by cardiovascular risk

    International Nuclear Information System (INIS)

    Onwudiwe, Nneka C; Kwok, Young; Onukwugha, Eberechukwu; Sorkin, John D; Zuckerman, Ilene H; Shaya, Fadia T; Daniel Mullins, C

    2014-01-01

    The objective of this study was to estimate the risk of a cardiovascular event or death associated with modern radiation in a population of elderly female breast cancer patients with varying baseline cardiovascular risk. The data used for this analysis are from the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The retrospective cohort study included women aged 66 years and older with stage 0–III breast cancer diagnosed between 2000 and 2005. Women were grouped as low, intermediate, or high cardiovascular risk based on the presence of certain clinical diagnoses. The risk for the combined outcome of a hospitalization for a cardiovascular event or death within 6 months and 24 months of diagnosis was estimated using a multivariable Cox model. The median follow-up time was 24 months. Among the 91,612 women with American Joint Committee on Cancer (AJCC) stage 0–III breast cancer: 39,555 (43.2%) were treated with radiation therapy and 52,057 (56.8%) were not. The receipt of radiation therapy in the first 6 months was associated with a statistically significant increased risk for the combined outcome in women categorized as high risk (HR = 1.510; 95% CI, 1.396–1.634) or intermediate risk (HR = 1.415; 95% CI, 1.188–1.686) but not low risk (HR = 1.027; 95% CI, 0.798–1.321). Women with a prior medical history of cardiovascular disease treated with radiation therapy are at increased risk for an event and should be monitored for at least 6 months following treatment with radiation therapy

  19. Phenotypic equilibrium as probabilistic convergence in multi-phenotype cell population dynamics.

    Directory of Open Access Journals (Sweden)

    Da-Quan Jiang

    Full Text Available We consider the cell population dynamics with n different phenotypes. Both the Markovian branching process model (stochastic model and the ordinary differential equation (ODE system model (deterministic model are presented, and exploited to investigate the dynamics of the phenotypic proportions. We will prove that in both models, these proportions will tend to constants regardless of initial population states ("phenotypic equilibrium" under weak conditions, which explains the experimental phenomenon in Gupta et al.'s paper. We also prove that Gupta et al.'s explanation is the ODE model under a special assumption. As an application, we will give sufficient and necessary conditions under which the proportion of one phenotype tends to 0 (die out or 1 (dominate. We also extend our results to non-Markovian cases.

  20. Caffeine and cardiovascular health.

    Science.gov (United States)

    Turnbull, Duncan; Rodricks, Joseph V; Mariano, Gregory F; Chowdhury, Farah

    2017-10-01

    This report evaluates the scientific literature on caffeine with respect to potential cardiovascular outcomes, specifically relative risks of total cardiovascular disease (CVD), coronary heart disease (CHD) and acute myocardial infarction (AMI), effects on arrhythmia, heart failure, sudden cardiac arrest, stroke, blood pressure, hypertension, and other biomarkers of effect, including heart rate, cerebral blood flow, cardiac output, plasma homocysteine levels, serum cholesterol levels, electrocardiogram (EKG) parameters, heart rate variability, endothelial/platelet function and plasma/urine catecholamine levels. Caffeine intake has been associated with a range of reversible and transient physiological effects broadly and cardiovascular effects specifically. This report attempts to understand where the delineations exist in caffeine intake and corresponding cardiovascular effects among various subpopulations. The available literature suggests that cardiovascular effects experienced by caffeine consumers at levels up to 600 mg/day are in most cases mild, transient, and reversible, with no lasting adverse effect. The point at which caffeine intake may cause harm to the cardiovascular system is not readily identifiable in part because data on the effects of daily intakes greater than 600 mg is limited. However, the evidence considered within this review suggests that typical moderate caffeine intake is not associated with increased risks of total cardiovascular disease; arrhythmia; heart failure; blood pressure changes among regular coffee drinkers; or hypertension in baseline populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

    Directory of Open Access Journals (Sweden)

    Jennifer G. Robinson

    2008-01-01

    Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

  2. 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...

  3. Metabolic syndrome and cardiovascular risk among adults

    Directory of Open Access Journals (Sweden)

    Reem Hunain

    2018-03-01

    Full Text Available Background: Mortality and morbidity due cardiovascular diseases in India is on the rise. Metabolic Syndrome which is a collection of risk factors of metabolic origin, can greatly contribute to its rising burden. Aims & Objectives: The present study was conducted with the objective of estimating the prevalence of metabolic syndrome and 10-year cardiovascular risk among adults. Material & Methods: This hospital-based study included 260 adults aged 20-60 years. Metabolic Syndrome was defined using National Cholesterol Education Program –Adult Treatment Panel -3 criteria. The 10 year cardiovascular risk was estimated using Framingham risk scoring. Results: The overall prevalence of metabolic syndrome among the study participants was 38.8%. Age (41-60yrs, male gender and daily consumption of high salt items were positively associated with metabolic syndrome whereas consumption of occasional high sugar items showed an inverse association with metabolic syndrome. According to Framingham Risk Scoring, 14.3% of the participants belonged to intermediate/high risk category. Conclusion: With a high prevalence of metabolic syndrome and a considerable proportion of individuals with intermediate to high 10 yr CVD risk, there is a need to design strategies to prevent future cardiovascular events.

  4. Development of Type 2 Diabetes Mellitus Phenotyping Framework Using Expert Knowledge and Machine Learning Approach.

    Science.gov (United States)

    Kagawa, Rina; Kawazoe, Yoshimasa; Ida, Yusuke; Shinohara, Emiko; Tanaka, Katsuya; Imai, Takeshi; Ohe, Kazuhiko

    2017-07-01

    Phenotyping is an automated technique that can be used to distinguish patients based on electronic health records. To improve the quality of medical care and advance type 2 diabetes mellitus (T2DM) research, the demand for T2DM phenotyping has been increasing. Some existing phenotyping algorithms are not sufficiently accurate for screening or identifying clinical research subjects. We propose a practical phenotyping framework using both expert knowledge and a machine learning approach to develop 2 phenotyping algorithms: one is for screening; the other is for identifying research subjects. We employ expert knowledge as rules to exclude obvious control patients and machine learning to increase accuracy for complicated patients. We developed phenotyping algorithms on the basis of our framework and performed binary classification to determine whether a patient has T2DM. To facilitate development of practical phenotyping algorithms, this study introduces new evaluation metrics: area under the precision-sensitivity curve (AUPS) with a high sensitivity and AUPS with a high positive predictive value. The proposed phenotyping algorithms based on our framework show higher performance than baseline algorithms. Our proposed framework can be used to develop 2 types of phenotyping algorithms depending on the tuning approach: one for screening, the other for identifying research subjects. We develop a novel phenotyping framework that can be easily implemented on the basis of proper evaluation metrics, which are in accordance with users' objectives. The phenotyping algorithms based on our framework are useful for extraction of T2DM patients in retrospective studies.

  5. [Strategies for cardiovascular disease prevention].

    Science.gov (United States)

    Gabus, Vincent; Wuerzner, Grégoire; Saubade, Mathieu; Favre, Lucie; Jacot Sadowski, Isabelle; Nanchen, David

    2018-02-28

    Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

  6. 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.

  7. In-treatment stroke volume predicts cardiovascular risk in hypertension

    DEFF Research Database (Denmark)

    Lønnebakken, Mai T; Gerdts, Eva; Boman, Kurt

    2011-01-01

    , the prespecified primary study endpoint, was assessed in Cox regression analysis using data from baseline and annual follow-up visits in 855 patients during 4.8 years of randomized losartan-based or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography...... with higher risk of cardiovascular events {hazard ratio 1.69 per 1 SD (6 ml/m2.04) lower stroke volume [95% confidence interval (CI) 1.35–2.11], P secondary model also independent of stress-corrected midwall shortening......, hence, adds information on cardiovascular risk in treated hypertensive patients beyond assessment of left ventricular structure alone....

  8. The Cardiovascular Risk of White-Coat Hypertension

    DEFF Research Database (Denmark)

    Franklin, Stanley; Thijs, Lutgarde; Asayama, Kei

    2016-01-01

    BACKGROUND: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring...... in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS: European Society Hypertension guidelines were used as a 5-stage risk score...

  9. Acute Cardiovascular Care Association Position Paper on Intensive Cardiovascular Care Units

    DEFF Research Database (Denmark)

    Bonnefoy-Cudraz, Eric; Bueno, Hector; Casella, Gianni

    2018-01-01

    , the recommended management structure, the optimal number of staff, the need for specially trained cardiologists and cardiovascular nurses, the desired equipment and architecture, and the interaction with other departments in the hospital and other intensive cardiovascular care units in the region...

  10. Phenotypic subgroups of polycystic ovary syndrome have different intra-renal resistance symptoms.

    Science.gov (United States)

    Ciftci, Ceylan F; Uckuyu, Ayla; Karadeli, Elif; Turhan, Erdem; Toprak, Erzat; Ozcimen, Emel E

    2012-12-01

    The polycystic ovary syndrome (PCOS) is known to be related with increased metabolic and cardiovascular risks. Various phenotypic subgroups of PCOS have been proven to have metabolic and endocrine disorders with varying degrees of severity However, intra-renal vascular resistance, which is an indirect indication of atherosclerosis, remains unknown in PCOS subgroups. In this study we examined whether PCOS subgroups have different intra-renal resistance symptoms. 98 PCOS patients (diagnosed according to the Rotterdam criteria) 30 controls were included in the study The diagnosis of PCOS was established in the presence of at least two of the following criteria: 1-oligo and/or amenorrhea (OM); 2-clinic and/or biochemical signs of hyperandrogenism (HA); 3-polycystic ovarian morphology (PCO) detected by transvaginal ultrasonography 37 patients (Group 1) met all three criteria (HA+OM+PCO), 29 patients (Group 2) met two of the criteria including hyperandrogenism (HA+OM or HA+PCO) and the remaining 32 patients (Group 3) had no hyperandrogenism but fulfilled the other two criteria; PCO+OM. Renal Doppler ultrasonography and hormonal/biochemical analyses were carried out. The first outcome measure was designated as the differences in the renal resistive index (RRI) values of the groups, and the second outcome measure was designated as the relation of RRI with the insulin resistance and lipid profile. In Group 1, the RRI and the homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly higher than in Group 3 and controls (P PCOS subgroups have metabolic and endocrine disorders and cardiovascular risks of varying degrees of severity Moreover, we showed that there was no increase of metabolic and cardiovascular risks in PCOS patients without hyperandrogenism.

  11. Calcium supplementation and cardiovascular risk: A rising concern.

    Science.gov (United States)

    Tankeu, Aurel T; Ndip Agbor, Valirie; Noubiap, Jean Jacques

    2017-06-01

    Over the past decade, the number of individuals taking calcium supplementation worldwide has been on the rise, especially with the emergence of new pharmaceutical companies specialized in the marketing of dietary supplements; with calcium supplementation being their main business axis. This is mostly because of the established role of calcium in the prevention and treatment of osteoporosis and, to a lesser extent, its role in the prevention of fractures. Recently, a rising body of evidence on the adverse effect of calcium supplementation on nonskeletal, especially cardiovascular, health has been a cause for concern. In fact, a significant number of studies have reported an association between calcium supplementation and adverse cardiovascular events, even though high dietary calcium intake was shown to have a protective effect. The mechanism by which calcium supplementation could cause a cardiovascular event was still unclear until a recent study published in the Journal of the American Heart Association. Combining this recent finding with available data associating calcium supplementation with cardiovascular mortality and all-cause mortality, we call on the need for an evidence-based approach to calcium supplementation, while stressing on the safety of dietary calcium intake over the former on cardiovascular health. ©2017 Wiley Periodicals, Inc.

  12. Integration of curated databases to identify genotype-phenotype associations

    Directory of Open Access Journals (Sweden)

    Li Jianrong

    2006-10-01

    Full Text Available Abstract Background The ability to rapidly characterize an unknown microorganism is critical in both responding to infectious disease and biodefense. To do this, we need some way of anticipating an organism's phenotype based on the molecules encoded by its genome. However, the link between molecular composition (i.e. genotype and phenotype for microbes is not obvious. While there have been several studies that address this challenge, none have yet proposed a large-scale method integrating curated biological information. Here we utilize a systematic approach to discover genotype-phenotype associations that combines phenotypic information from a biomedical informatics database, GIDEON, with the molecular information contained in National Center for Biotechnology Information's Clusters of Orthologous Groups database (NCBI COGs. Results Integrating the information in the two databases, we are able to correlate the presence or absence of a given protein in a microbe with its phenotype as measured by certain morphological characteristics or survival in a particular growth media. With a 0.8 correlation score threshold, 66% of the associations found were confirmed by the literature and at a 0.9 correlation threshold, 86% were positively verified. Conclusion Our results suggest possible phenotypic manifestations for proteins biochemically associated with sugar metabolism and electron transport. Moreover, we believe our approach can be extended to linking pathogenic phenotypes with functionally related proteins.

  13. FeNO as biomarker for asthma phenotyping and management.

    Science.gov (United States)

    Ricciardolo, Fabio L M; Sorbello, Valentina; Ciprandi, Giorgio

    2015-01-01

    The current review aims to revisit literature on exhaled nitric oxide (FeNO) in asthma phenotyping and management to clarify the utility of this test in clinical practice. It is increasingly evident that multiple profiles characterize asthma as a complex disease for which is necessary to find tools able to discriminate among these phenotypes to achieve the best therapeutic strategy for all asthmatic patients. Current findings indicate that FeNO, a noninvasive and easy-to-obtain biomarker, can be considered a useful tool in predicting asthma developing and exacerbation, in identifying specific asthma phenotypes, in improving asthma diagnosis and management in a selected population, and in monitoring efficacy of standard corticosteroid and biologic therapy. Based on this evidence, FeNO might become an appropriate tool for physicians to better define specific asthma phenotypes and to better deal with asthma worsening.

  14. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III).

    Science.gov (United States)

    Vanhees, L; Rauch, B; Piepoli, M; van Buuren, F; Takken, T; Börjesson, M; Bjarnason-Wehrens, B; Doherty, P; Dugmore, D; Halle, M

    2012-12-01

    The beneficial effect of exercise training and exercise-based cardiac rehabilitation on symptom-free exercise capacity,cardiovascular and skeletal muscle function, quality of life, general healthy lifestyle, and reduction of depressive symptoms and psychosocial stress is nowadays well recognized. However, it remains largely obscure, which characteristics of physical activity (PA) and exercise training--frequency, intensity, time (duration), type (mode), and volume (dose: intensity x duration) of exercise--are the most effective. The present paper, therefore, will deal with these exercise characteristics in the management of individuals with cardiovascular disease, i.e. coronary artery disease and chronic heart failure patients, but also in patients with congenital or valvular heart disease. Based on the current literature, and if sufficient evidence is available, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding frequency, intensity, time and type of PA, and safety aspects during exercise inpatients with cardiovascular disease. This paper is the third in a series of three papers, all devoted to the same theme: the importance of the exercise characteristics in the management of cardiovascular health. Part I is directed to the general population and Part II to individuals with cardiovascular risk factors. In general, PA recommendations and exercise training programmes for patients with coronary artery disease or chronic heart failure need to be tailored to the individual's exercise capacity and risk profile, with the aim to reach and maintain the individually highest fitness level possible and to perform endurance exercise training 30–60 min daily (3–5 days per week) in combination with resistance training 2–3 times a week. Because of the frequently reported dose–response relationship between training effect and exercise intensity, one should seek sufficiently high training intensities

  15. A new mouse model for marfan syndrome presents phenotypic variability associated with the genetic background and overall levels of Fbn1 expression.

    Directory of Open Access Journals (Sweden)

    Bruno L Lima

    2010-11-01

    Full Text Available Marfan syndrome is an autosomal dominant disease of connective tissue caused by mutations in the fibrillin-1 encoding gene FBN1. Patients present cardiovascular, ocular and skeletal manifestations, and although being fully penetrant, MFS is characterized by a wide clinical variability both within and between families. Here we describe a new mouse model of MFS that recapitulates the clinical heterogeneity of the syndrome in humans. Heterozygotes for the mutant Fbn1 allele mgΔloxPneo, carrying the same internal deletion of exons 19-24 as the mgΔ mouse model, present defective microfibrillar deposition, emphysema, deterioration of aortic wall and kyphosis. However, the onset of a clinical phenotypes is earlier in the 129/Sv than in C57BL/6 background, indicating the existence of genetic modifiers of MFS between these two mouse strains. In addition, we characterized a wide clinical variability within the 129/Sv congenic heterozygotes, suggesting involvement of epigenetic factors in disease severity. Finally, we show a strong negative correlation between overall levels of Fbn1 expression and the severity of the phenotypes, corroborating the suggested protective role of normal fibrillin-1 in MFS pathogenesis, and supporting the development of therapies based on increasing Fbn1 expression.

  16. Trace Elements in Cardiovascular Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Masironi, R. [Cardiovascular Diseases Unit, World Health Organization, Geneva (Switzerland)

    1970-07-01

    Cardiovascular diseases are the leading cause of death in industrialized countries. Their incidence increases, apparently, as a, function of technological progress so that in the future they may become a major public health problem in developing countries too. Early diagnosis and prevention are the tools best suited to curb such an alarming trend, but our knowledge of these topics is unsatisfactory, Valuable information would be obtained through a systematic investigation of trace elements in relation to cardiovascular function and to various types of cardiovascular diseases. Such studies would provide clues to the following questions: 1. Why does the incidence and type of cardiovascular disease differ from one country to another? May this be related to differences in tissue mineral concentrations among various population groups? 2. Which trace elements if any are beneficial to cardiovascular health, and which are harmful ones that may act as aetiological agents for some cardiovascular diseases? 3. Is it possible to utilize measurements of mineral element concentration for diagnostic purposes in cardiovascular disease? (author)

  17. Cardiovascular Disease in Survivors of Adolescent and Young Adult Cancer

    DEFF Research Database (Denmark)

    Rugbjerg, Kathrine; Mellemkjaer, Lene; Boice, John D

    2014-01-01

    BACKGROUND: Cardiovascular disease has emerged as a serious late effect in survivors of adolescent and young adult cancer, but risk has not been quantified comprehensively in a population-based setting. METHODS: In the Danish Cancer Registry, we identified 43153 1-year survivors of cancer diagnosed...... at ages 15 to 39 years (1943-2009) and alive in 1977; from the Danish Civil Registration System, we randomly selected a comparison cohort of the same age and sex. Subjects were linked to the Danish Patient Register, and observed numbers of first hospitalizations for cardiovascular disease (International......-sided. RESULTS: During follow-up, 10591 survivors (24.5%) were discharged from the hospital with cardiovascular disease, whereas 8124 were expected (RR = 1.30; 95% confidence interval [CI)] = 1.28 to 1.33; P cardiovascular disease per 100000...

  18. Calcium as a cardiovascular toxin in CKD-MBD.

    Science.gov (United States)

    Moe, Sharon M

    2017-07-01

    Disordered calcium balance and homeostasis are common in patients with chronic kidney disease. Such alterations are commonly associated with abnormal bone remodeling, directly and indirectly. Similarly, positive calcium balance may also be a factor in the pathogenesis of extra skeletal soft tissue and arterial calcification. Calcium may directly affect cardiac structure and function through direct effects to alter cell signaling due to abnormal intracellular calcium homeostasis 2) extra-skeletal deposition of calcium and phosphate in the myocardium and small cardiac arterioles, 3) inducing cardiomyocyte hypertrophy through calcium and hormone activation of NFAT signaling mechanisms, and 4) increased aorta calcification resulting in chronic increased afterload leading to hypertrophy. Similarly, calcium may alter vascular smooth muscle cell function and affect cell signaling which may predispose to a proliferative phenotype important in arteriosclerosis and arterial calcification. Thus, disorders of calcium balance and homeostasis due to CKD-MBD may play a role in the high cardiovascular burden observed in patients with CKD. Published by Elsevier Inc.

  19. Asian & Pacific Islanders and Cardiovascular Diseases

    Science.gov (United States)

    ... Fact Sheet 2016 Update Asian & Pacific Islanders and Cardiovascular Diseases Cardiovascular Disease (CVD) (ICD 10 codes I00-I99, Q20- ... of na- tive Hawaiians or oth- A indicates cardiovascular disease plus congenital cardiovascular disease (ICD-10 I00- ...

  20. Genetic Regulation of Phenotypic Plasticity and Canalisation in Yeast Growth.

    Directory of Open Access Journals (Sweden)

    Anupama Yadav

    Full Text Available The ability of a genotype to show diverse phenotypes in different environments is called phenotypic plasticity. Phenotypic plasticity helps populations to evade extinctions in novel environments, facilitates adaptation and fuels evolution. However, most studies focus on understanding the genetic basis of phenotypic regulation in specific environments. As a result, while it's evolutionary relevance is well established, genetic mechanisms regulating phenotypic plasticity and their overlap with the environment specific regulators is not well understood. Saccharomyces cerevisiae is highly sensitive to the environment, which acts as not just external stimulus but also as signalling cue for this unicellular, sessile organism. We used a previously published dataset of a biparental yeast population grown in 34 diverse environments and mapped genetic loci regulating variation in phenotypic plasticity, plasticity QTL, and compared them with environment-specific QTL. Plasticity QTL is one whose one allele exhibits high plasticity whereas the other shows a relatively canalised behaviour. We mapped phenotypic plasticity using two parameters-environmental variance, an environmental order-independent parameter and reaction norm (slope, an environmental order-dependent parameter. Our results show a partial overlap between pleiotropic QTL and plasticity QTL such that while some plasticity QTL are also pleiotropic, others have a significant effect on phenotypic plasticity without being significant in any environment independently. Furthermore, while some plasticity QTL are revealed only in specific environmental orders, we identify large effect plasticity QTL, which are order-independent such that whatever the order of the environments, one allele is always plastic and the other is canalised. Finally, we show that the environments can be divided into two categories based on the phenotypic diversity of the population within them and the two categories have

  1. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou

    2015-12-01

    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  2. Projections of Demand for Cardiovascular Surgery and Supply of Surgeons

    Directory of Open Access Journals (Sweden)

    Jung Jeung Lee

    2016-12-01

    Full Text Available Background: While demand for cardiovascular surgery is expected to increase gradually along with the rapid increase in cardiovascular diseases with respect to the aging population, the supply of thoracic and cardiovascular surgeons has been continuously decreasing over the past 10 years. Consequently, this study aims to achieve guidance in establishing health care policy by analyzing the supply and demand for cardiovascular surgeries in the medical service area of Korea. Methods: After investigating the actual number of cardiovascular surgeries performed using the National Health Insurance claim data of the Health Insurance Review and Assessment Service, as well as drawing from national statistics concerning the elderly population aged 65 and over, this study estimated the number of future cardiovascular surgeries by using a cell-based model. To be able to analyze the supply and demand of surgeons, the recent status of new surgeons specializing in thoracic and cardiovascular surgeries and the ratio of their subspecialties in cardiovascular surgeries were investigated. Then, while taking three different scenarios into account, the number of cardiovascular surgeons expected be working in 5-year periods was projected. Results: The number of cardiovascular surgeries, which was recorded at 10,581 cases in 2014, is predicted to increase consistently to reach a demand of 15,501 cases in 2040—an increase of 46.5%. There was a total of 245 cardiovascular surgeons at work in 2014. Looking at 5 year spans in the future, the number of surgeons expected to be supplied in 2040 is 184, to retire is 249, and expected to be working is 309—an increase of -24.9%, 1.6%, and 26.1%, respectively compared to those in 2014. This forecasts a demand-supply imbalance in every scenario. Conclusion: Cardiovascular surgeons are the most central resource in the medical service of highly specialized cardiovascular surgeries, and fostering the surgeons requires much time

  3. Deep Phenotyping: Deep Learning For Temporal Phenotype/Genotype Classification

    OpenAIRE

    Najafi, Mohammad; Namin, Sarah; Esmaeilzadeh, Mohammad; Brown, Tim; Borevitz, Justin

    2017-01-01

    High resolution and high throughput, genotype to phenotype studies in plants are underway to accelerate breeding of climate ready crops. Complex developmental phenotypes are observed by imaging a variety of accessions in different environment conditions, however extracting the genetically heritable traits is challenging. In the recent years, deep learning techniques and in particular Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs) and Long-Short Term Memories (LSTMs), h...

  4. Current European guidelines for management of cardiovascular disease

    DEFF Research Database (Denmark)

    Vinther, Johan L; Jacobsen, Rikke K; Jørgensen, Torben

    2018-01-01

    Background Health checks of the general population are widely used to prevent cardiovascular diseases, but are the current clinical guidelines from the European Society of Cardiology (ESC) suitable for screening the general population? Design A cross-sectional, population-based study of 978 men...... and women aged 40-65 years examined in 2010-2011 was used to estimate the proportion of the general Danish population fulfilling the criteria from the clinical guidelines from the ESC on medical treatment and lifestyle intervention to prevent cardiovascular disease. Methods The ESC criteria for medical...... treatment and lifestyle intervention were applied to a general population using information on previous cardiovascular diseases, known diabetes, urinalbumin, smoking, total cholesterol, systolic and diabolic blood pressure, low-density lipoprotein cholesterol and a multifactor risk score (SCORE). Results...

  5. Supplementary Material for: The flora phenotype ontology (FLOPO): tool for integrating morphological traits and phenotypes of vascular plants

    KAUST Repository

    Hoehndorf, Robert; AlShahrani, Mona; Gkoutos, Georgios; Gosline, George; Groom, Quentin; Hamann, Thomas; Kattge, Jens; Oliveira, Sylvia de; Schmidt, Marco; Sierra, Soraya; Smets, Erik; Vos, Rutger; Weiland, Claus

    2016-01-01

    traits of plant species found in Floras. We used the Plant Ontology (PO) and the Phenotype And Trait Ontology (PATO) to extract entity-quality relationships from digitized taxon descriptions in Floras, and used a formal ontological approach based

  6. The Human Phenotype Ontology in 2017

    International Nuclear Information System (INIS)

    Köhler, Sebastian; Vasilevsky, Nicole A.; Engelstad, Mark; Foster, Erin; McMurry, Julie

    2016-01-01

    Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human PhenotypeOntology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

  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. Wine Expertise Predicts Taste Phenotype.

    Science.gov (United States)

    Hayes, John E; Pickering, Gary J

    2012-03-01

    Taste phenotypes have long been studied in relation to alcohol intake, dependence, and family history, with contradictory findings. However, on balance - with appropriate caveats about populations tested, outcomes measured and psychophysical methods used - an association between variation in taste responsiveness and some alcohol behaviors is supported. Recent work suggests super-tasting (operationalized via propylthiouracil (PROP) bitterness) not only associates with heightened response but also with more acute discrimination between stimuli. Here, we explore relationships between food and beverage adventurousness and taste phenotype. A convenience sample of wine drinkers (n=330) were recruited in Ontario and phenotyped for PROP bitterness via filter paper disk. They also filled out a short questionnaire regarding willingness to try new foods, alcoholic beverages and wines as well as level of wine involvement, which was used to classify them as a wine expert (n=110) or wine consumer (n=220). In univariate logisitic models, food adventurousness predicted trying new wines and beverages but not expertise. Likewise, wine expertise predicted willingness to try new wines and beverages but not foods. In separate multivariate logistic models, willingness to try new wines and beverages was predicted by expertise and food adventurousness but not PROP. However, mean PROP bitterness was higher among wine experts than wine consumers, and the conditional distribution functions differed between experts and consumers. In contrast, PROP means and distributions did not differ with food adventurousness. These data suggest individuals may self-select for specific professions based on sensory ability (i.e., an active gene-environment correlation) but phenotype does not explain willingness to try new stimuli.

  10. Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP).

    Science.gov (United States)

    Megale, Rodrigo Z; Ferreira, Manuela L; Ferreira, Paulo H; Naganathan, Vasi; Cumming, Robert; Hirani, Vasant; Waite, Louise M; Seibel, Markus J; Le Couteur, David G; Handelsman, David J; Blyth, Fiona M

    2018-05-01

    to determine whether pain increases the risk of developing the frailty phenotype and whether frailty increases the risk of developing chronic or intrusive pain, using longitudinal data. longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study. a total of 1,705 men aged 70 years or older, living in an urban area of New South Wales, Australia. data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study (CHS) frailty phenotype were collected in three waves, from January 2005 to October 2013. Data on age, living arrangements, education, smoking status, alcohol consumption, body mass index, comorbidities, cognitive function, depressive symptoms and history of vertebral or hip fracture were also collected and included as covariates in the analyses. a total of 1,705 participants were included at baseline, of whom 1,332 provided data at the 2-year follow-up and 940 at the 5-year follow-up. Non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02-2.51, P = 0.039) times more likely to develop frailty at follow-up, compared to those with no pain. Intrusive pain did not significantly increase the risk of future frailty. Likewise, the frailty status was not associated with future chronic or intrusive pain in the adjusted analysis. the presence of chronic pain increases the risk of developing the frailty phenotype in community-dwelling older men.

  11. Consequências cardiovasculares na SAOS Cardiovascular consequences of obstructive sleep apnea syndrome

    Directory of Open Access Journals (Sweden)

    Geraldo Lorenzi Filho

    2010-06-01

    Full Text Available Uma condição clínica muito comum é SAOS, que está associada a várias doenças cardiovasculares, incluindo hipertensão arterial sistêmica, fibrilação atrial e aterosclerose. A associação entre SAOS e doença cardiovascular não é somente uma consequência da sobreposição de fatores de risco, incluindo obesidade, sedentarismo, ser do sexo masculino e ter idade maior. Existem evidências crescentes de que SAOS contribui de forma independente para o aparecimento e a progressão de várias doenças cardiovasculares. Os mecanismos pelos quais SAOS pode afetar o sistema cardiovascular são múltiplos e incluem a ativação do sistema nervoso simpático, inflamação sistêmica, resistência a insulina e geração de estresse oxidativo. Existem evidências que o tratamento de SAOS com CPAP pode reduzir a pressão arterial, sinais precoces de aterosclerose, risco de recorrência de fibrilação atrial e mortalidade, principalmente por acidente vascular cerebral e infarto agudo do miocárdio, em pacientes com SAOS grave.Obstructive sleep apnea syndrome (OSAS is a common condition associated with various cardiovascular diseases, including systemic arterial hypertension, atrial fibrillation, and atherosclerosis. The association between OSAS and cardiovascular disease has been related to the overlapping of risk factors, including obesity, having a sedentary lifestyle, being male, and being older. However, there is mounting evidence that OSAS can also independently contribute to the development and progression of various cardiovascular diseases. The mechanisms by which OSAS can affect the cardiovascular system are multiple, including the activation of the sympathetic nervous system, systemic inflammation, insulin resistance, and oxidative stress. There is also evidence that the treatment of OSAS with CPAP can reduce arterial blood pressure, early signs of atherosclerosis, the risk of atrial fibrillation recurrence, and mortality (principally

  12. A point-to-point simple telehealth application for cardiovascular prevention: the ESINO LARIO experience. Cardiovascular prevention at point of care.

    Science.gov (United States)

    Malacarne, Mara; Gobbi, Giorgio; Pizzinelli, Paolo; Lesma, Alessandro; Castelli, Alberto; Lucini, Daniela; Pagani, Massimo

    2009-01-01

    Recent epidemiological evidence indicates that chronic degenerative diseases, notably cardiovascular, represent the major toll in terms of death and of impaired quality of life. Recent estimates indicate that a small increase in financial resources in a number of clinical cases may be sufficient to minimize the consequences of elevated cardiovascular risk per individual. The observation that lifestyle choices, and in particular increased physical exercise, might strongly impact cardiovascular risk, suggests a redesign of preventive strategies, based on the combination of pharmacological and behavioral interventions. Following our recent experience with the INteractive teleConsultation network for worldwide healthcAre Services (INCAS) system, we designed a simpler point-to-point telehealth infrastructure, to be employed in cardiovascular risk reduction programs, predicting a high level of acceptance from the population, at the cost of very limited investment. This model was tested on 181 subjects (ages 18-80 years) in the Italian mountain village of Esino Lario. These subjects underwent a screening test to evaluate arrhythmia and cardiometabolic risks (arrhythmias were found in 14% of subjects, systolic arterial pressure was observed in 43% of subjects above 140 mm Hg, diastolic arterial pressure in 31% above 90 mm Hg). This study demonstrates the feasibility of a scaled-down telehealth application particularly suited to cardiovascular prevention in remote areas, such as in mountain villages.

  13. Supply and consumption of cardiovascular food supplements in lithuania

    OpenAIRE

    Liubartaitė, Elvyra

    2017-01-01

    Supply and Consumption of Cardiovascular Food Supplements in Lithuania. The aim - to evaluate supply and consumption of cardiovascular food supplements in Lithuania. Work tasks: • To collect information on food supplements for heart health. • To rate the range of food supplements for heart health sold in Lithuania. • To analyze the consumption of food supplements for heart health. Research data were collected through questionnaire data collection method based on January-February, 2017 data. 4...

  14. 14 CFR 67.111 - Cardiovascular.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.111 Section 67.111 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.111 Cardiovascular. Cardiovascular...

  15. 14 CFR 67.311 - Cardiovascular.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.311 Section 67.311 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.311 Cardiovascular. Cardiovascular...

  16. 14 CFR 67.211 - Cardiovascular.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Cardiovascular. 67.211 Section 67.211 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.211 Cardiovascular. Cardiovascular...

  17. 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...

  18. Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype.

    Science.gov (United States)

    Bil, Enes; Dilbaz, Berna; Cirik, Derya Akdag; Ozelci, Runa; Ozkaya, Enis; Dilbaz, Serdar

    2016-07-01

    It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes. A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups. Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P 3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women. © 2016 Japan Society of Obstetrics and Gynecology.

  19. Socioeconomic status and parenting during adolescence in relation to ideal cardiovascular health in Black and White men.

    Science.gov (United States)

    Matthews, Karen A; Boylan, Jennifer M; Jakubowski, Karen P; Cundiff, Jenny M; Lee, Laisze; Pardini, Dustin A; Jennings, J Richard

    2017-07-01

    American Heart Association (AHA) developed a new metric to evaluate ideal cardiovascular health based on optimal levels of 7 cardiovascular risk factors and health behaviors. We evaluated the relationships of parenting characteristics and academic achievement in adolescence in relation to ideal cardiovascular health in midlife men. We measured cardiovascular risk factors in 171 Black and 136 White men and their ideal cardiovascular health score was constructed based on AHA guidelines. When the participants were 13-16 years old, annual measures of parent-child communication, positive relationship, parental monitoring, family cohesion, boys' involvement in family activities, and academic achievement were recorded and averaged. Confirmatory factor analysis of adolescent parenting measures revealed a single Parenting Composite. Multiple linear regressions showed a significant Race by Parenting Composite interaction term, β = -.19, p = .03; better parenting was significantly related to more ideal cardiovascular health in Blacks only, β = -.23, p = .004, which remained after adjustments for adolescent and adult socioeconomic status (SES). Academic achievement was related to ideal cardiovascular health, β = -.13, but was no longer significant after controls for adult SES. Adult SES was a strong correlate of ideal cardiovascular health in Black and White men. Black men exposed to positive parenting during adolescence had more ideal cardiovascular health based on AHA guidelines. Improving academic achievement in adolescence may indirectly benefit adult cardiovascular health through improving adult SES. This is the first study of adolescent family predictors of the extent of ideal cardiovascular health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Genetic and environmental contributions to cardiovascular disease risk in American Indians: the strong heart family study.

    Science.gov (United States)

    North, Kari E; Howard, Barbara V; Welty, Thomas K; Best, Lyle G; Lee, Elisa T; Yeh, J L; Fabsitz, Richard R; Roman, Mary J; MacCluer, Jean W

    2003-02-15

    The aims of the Strong Heart Family Study are to clarify the genetic determinants of cardiovascular disease (CVD) risk in American Indians and to map and identify genes for CVD susceptibility. The authors describe the design of the Strong Heart Family Study (conducted between 1998 and 1999) and evaluate the heritabilities of CVD risk factors in American Indians from this study. In the first phase of the study, approximately 950 individuals, aged 18 years or more, in 32 extended families, were examined. The examination consisted of a personal interview, physical examination, laboratory tests, and an ultrasound examination of the carotid arteries. The phenotypes measured during the physical examination included anthropometry, lipoproteins, blood pressure, glycemic status, and clotting factors. Heritabilities for CVD risk factor phenotypes were estimated using a variance component approach and the program SOLAR. After accounting for the effects of covariates, the authors detected significant heritabilities for many CVD risk factor phenotypes (e.g., high density lipoprotein cholesterol (heritability = 0.50) and diastolic blood pressure (heritability = 0.34)). These results suggest that heredity explains a substantial proportion of the variability of CVD risk factors and that these heritabilities are large enough to warrant a search for major risk factor genes.

  1. 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.

  2. 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...

  3. GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations

    Directory of Open Access Journals (Sweden)

    Eva Y. G. De Vilder

    2017-01-01

    Full Text Available Gamma-carboxylation, performed by gamma-glutamyl carboxylase (GGCX, is an enzymatic process essential for activating vitamin K-dependent proteins (VKDP with important functions in various biological processes. Mutations in the encoding GGCX gene are associated with multiple phenotypes, amongst which vitamin K-dependent coagulation factor deficiency (VKCFD1 is best known. Other patients have skin, eye, heart or bone manifestations. As genotype–phenotype correlations were never described, literature was systematically reviewed in search of patients with at least one GGCX mutation with a phenotypic description, resulting in a case series of 47 patients. Though this number was too low for statistically valid correlations—a frequent problem in orphan diseases—we demonstrate the crucial role of the horizontally transferred transmembrane domain in developing cardiac and bone manifestations. Moreover, natural history suggests ageing as the principal determinant to develop skin and eye symptoms. VKCFD1 symptoms seemed more severe in patients with both mutations in the same protein domain, though this could not be linked to a more perturbed coagulation factor function. Finally, distinct GGCX functional domains might be dedicated to carboxylation of very specific VKDP. In conclusion, this systematic review suggests that there indeed may be genotype–phenotype correlations for GGCX-related phenotypes, which can guide patient counseling and management.

  4. A four-year cardiovascular risk score for type 2 diabetic inpatients

    Directory of Open Access Journals (Sweden)

    Dolores Ramírez-Prado

    2015-06-01

    Full Text Available As cardiovascular risk tables currently in use were constructed using data from the general population, the cardiovascular risk of patients admitted via the hospital emergency department may be underestimated. Accordingly, we constructed a predictive model for the appearance of cardiovascular diseases in patients with type 2 diabetes admitted via the emergency department. We undertook a four-year follow-up of a cohort of 112 adult patients with type 2 diabetes admitted via the emergency department for any cause except patients admitted with acute myocardial infarction, stroke, cancer, or a palliative status. The sample was selected randomly between 2010 and 2012. The primary outcome was time to cardiovascular disease. Other variables (at baseline were gender, age, heart failure, renal failure, depression, asthma/chronic obstructive pulmonary disease, hypertension, dyslipidaemia, insulin, smoking, admission for cardiovascular causes, pills per day, walking habit, fasting blood glucose and creatinine. A cardiovascular risk table was constructed based on the score to estimate the likelihood of cardiovascular disease. Risk groups were established and the c-statistic was calculated. Over a mean follow-up of 2.31 years, 39 patients had cardiovascular disease (34.8%, 95% CI [26.0–43.6%]. Predictive factors were gender, age, hypertension, renal failure, insulin, admission due to cardiovascular reasons and walking habit. The c-statistic was 0.734 (standard error: 0.049. After validation, this study will provide a tool for the primary health care services to enable the short-term prediction of cardiovascular disease after hospital discharge in patients with type 2 diabetes admitted via the emergency department.

  5. Yoga, Anxiety, and Some Cardiovascular Risk Factors in Women

    Directory of Open Access Journals (Sweden)

    Asim CENGIZ

    2015-06-01

    Full Text Available This study aimed to examine the effects of a yoga program on anxiety, and some cardiovascular risk factors. Forty - six elderly participants aged 40 – 51 years women. The yoga program was based on 3 times/week for 10 weeks a set of yoga techniques, in the form of asana (postures and deep relaxation technique, pranayama (breathing techniques and meditation three for 60 minutes three times a week. The level of anxiety and decreased the risk factors for cardiovascular disease risk factors (CVD. The yoga program reduced the level of anxiety and decreased the risk factors for cardiovascular disease risk factors (CVD in the experimental group. After 8 weeks of the yoga program. SBP, DBP, B MI, HR and WC values were improved. It is likely that the yoga practices of controlling body, mind, and spirit combine to provide useful physiological effects for healthy people and for people compromised by cardiovascular disease.

  6. TH-B-207B-02: Optimizing Pediatic Cardiovascular MRI

    International Nuclear Information System (INIS)

    Deng, J.

    2016-01-01

    This imaging educational program will focus on solutions to common pediatric image quality optimization challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children’s hospitals. One of the most commonly encountered pediatric imaging requirements for the non-specialist hospital is pediatric CT in the emergency room setting. Thus, this educational program will begin with optimization of pediatric CT in the emergency department. Though pediatric cardiovascular MRI may be less common in the non-specialist hospitals, low pediatric volumes and unique cardiovascular anatomy make optimization of these techniques difficult. Therefore, our second speaker will review best practices in pediatric cardiovascular MRI based on experiences from a children’s hospital with a large volume of cardiac patients. Learning Objectives: To learn techniques for optimizing radiation dose and image quality for CT of children in the emergency room setting. To learn solutions for consistently high quality cardiovascular MRI of children

  7. TH-B-207B-02: Optimizing Pediatic Cardiovascular MRI

    Energy Technology Data Exchange (ETDEWEB)

    Deng, J. [Ann & Robert H. Lurie Childrens Hospital, Chicago, IL (United States)

    2016-06-15

    This imaging educational program will focus on solutions to common pediatric image quality optimization challenges. The speakers will present collective knowledge on best practices in pediatric imaging from their experience at dedicated children’s hospitals. One of the most commonly encountered pediatric imaging requirements for the non-specialist hospital is pediatric CT in the emergency room setting. Thus, this educational program will begin with optimization of pediatric CT in the emergency department. Though pediatric cardiovascular MRI may be less common in the non-specialist hospitals, low pediatric volumes and unique cardiovascular anatomy make optimization of these techniques difficult. Therefore, our second speaker will review best practices in pediatric cardiovascular MRI based on experiences from a children’s hospital with a large volume of cardiac patients. Learning Objectives: To learn techniques for optimizing radiation dose and image quality for CT of children in the emergency room setting. To learn solutions for consistently high quality cardiovascular MRI of children.

  8. 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

  9. Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

    Science.gov (United States)

    Caterson, I D; Finer, N; Coutinho, W; Van Gaal, L F; Maggioni, A P; Torp-Pedersen, C; Sharma, A M; Legler, U F; Shepherd, G M; Rode, R A; Perdok, R J; Renz, C L; James, W P T

    2012-06-01

    The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups. © 2011 Blackwell Publishing Ltd.

  10. Estudio del riesgo cardiovascular en la infancia a través de un modelo clínico-investigativo Study of cardiovascular risk in infancy through a clinical-investigative model

    Directory of Open Access Journals (Sweden)

    Álvaro E Durán

    2006-10-01

    Full Text Available Antecedentes: desde el 2004, el Área de Investigación en Pediatría de la Fundación Cardiovascular de Colombia, ha desarrollado la línea de investigación: factores de riesgo cardiovascular en la infancia, a través del planteamiento de un modelo clínico investigativo. Objetivo: describir la experiencia de la Fundación Cardiovascular de Colombia en el desarrollo de actividades clínico-investigativas orientadas al estudio y la prevención primaria de las enfermedades cardiovasculares. Método: no aplica. Resultados: no aplican. Conclusiones: a partir de este modelo se han desarrollado diversas actividades de investigación encaminadas a la cuantificación de la magnitud del problema que representan estos factores de riesgo en la población pediátrica de Bucaramanga, pasando de estudios de tamizaje a estudios de carácter poblacional, y derivando de sus resultados la creación de programas clínicos y comunitarios enfocados a la sensibilización de la población general y a la prevención e intervención oportuna de las enfermedades cardiovasculares.Antecedents: since 2004, the Pediatric Area of Research from the Colombian Cardiovascular Foundation has developed the investigation line: cardiovascular risk factors in infancy, through a clinical-investigative model. Objective: to describe the Colombian Cardiovascular Foundation experience in the development of clinical-investigative activities oriented to the study and primary prevention of cardiovascular diseases. Method: does not apply. Results: do not apply. Conclusions: several investigative activities have been developed based on this model, tending to quantify the magnitude of the problem represented by these risk factors in the pediatric population of Bucaramanga, passing from screening studies to population-based studies, allowing by its results the creation of clinical and communitarian programs focused in the awareness of the general population and the prevention and opportune

  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. 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

  13. 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...

  14. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  15. 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

  16. Computer vision and machine learning for robust phenotyping in genome-wide studies.

    Science.gov (United States)

    Zhang, Jiaoping; Naik, Hsiang Sing; Assefa, Teshale; Sarkar, Soumik; Reddy, R V Chowda; Singh, Arti; Ganapathysubramanian, Baskar; Singh, Asheesh K

    2017-03-08

    Traditional evaluation of crop biotic and abiotic stresses are time-consuming and labor-intensive limiting the ability to dissect the genetic basis of quantitative traits. A machine learning (ML)-enabled image-phenotyping pipeline for the genetic studies of abiotic stress iron deficiency chlorosis (IDC) of soybean is reported. IDC classification and severity for an association panel of 461 diverse plant-introduction accessions was evaluated using an end-to-end phenotyping workflow. The workflow consisted of a multi-stage procedure including: (1) optimized protocols for consistent image capture across plant canopies, (2) canopy identification and registration from cluttered backgrounds, (3) extraction of domain expert informed features from the processed images to accurately represent IDC expression, and (4) supervised ML-based classifiers that linked the automatically extracted features with expert-rating equivalent IDC scores. ML-generated phenotypic data were subsequently utilized for the genome-wide association study and genomic prediction. The results illustrate the reliability and advantage of ML-enabled image-phenotyping pipeline by identifying previously reported locus and a novel locus harboring a gene homolog involved in iron acquisition. This study demonstrates a promising path for integrating the phenotyping pipeline into genomic prediction, and provides a systematic framework enabling robust and quicker phenotyping through ground-based systems.

  17. Nonfasting hyperlipidemia and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, B G; Langsted, A; Freiberg, J J

    2009-01-01

    , total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A1 all associate with increased risk of cardiovascular disease. These new data open the possibility that nonfasting rather than fasting lipid profiles can be used for cardiovascular risk prediction. If implemented, this would...... of cardiovascular disease and early death....

  18. Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease.

    Science.gov (United States)

    Krentz, Andrew J; von Mühlen, Denise; Barrett-Connor, Elizabeth

    2007-01-01

    To test the hypothesis that polycystic ovary syndrome (PCOS) is associated with an increased risk of atherosclerotic cardiovascular disease (CVD) in older postmenopausal women. Cross-sectional study of community-dwelling non-estrogen-using postmenopausal-white women (N=713; mean+/-SD age, 73.8+/-7.9 years; mean body mass index, 24.0+/-3.5 kg/m) participating in the Rancho Bernardo Study. A putative PCOS phenotype was defined as the presence of three or more of the following features: (1) recalled history of irregular menses, (2) symptomatic premenopausal hyperandrogenism or biochemical evidence of current biochemical hyperandrogenism, (3) history of infertility or miscarriage, (4) central obesity, or (5) insulin resistance. Atherosclerotic CVD was determined from clinical history, electrocardiography, and structured interviews using validated techniques. The analysis was stratified by diabetes status, ascertained from medical history or 75-g oral glucose tolerance tests. The PCOS phenotype was present in 9.3% of the entire cohort and 5.8% of nondiabetic women. The prevalence of CVD was similar between women with the phenotype and unaffected women (27.3% vs 24.4%). Among women with intact ovaries and no diabetes, there was a stepwise graded association between an increasing number of features of the PCOS phenotype (ie, none to three or more) and prevalent CVD (P=0.02). A similar association was also observed for coronary heart disease alone (P=0.03). Among nondiabetic postmenopausal women with intact ovaries, prevalent atherosclerotic CVD is associated with features of a putative PCOS phenotype. This finding supports the thesis that PCOS increases the risk of atherosclerotic CVD after menopause.

  19. 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.

  20. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout.

    Science.gov (United States)

    White, William B; Saag, Kenneth G; Becker, Michael A; Borer, Jeffrey S; Gorelick, Philip B; Whelton, Andrew; Hunt, Barbara; Castillo, Majin; Gunawardhana, Lhanoo

    2018-03-29

    Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease. We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization). In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis. In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and

  1. 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.

  2. Estimating rice yield related traits and quantitative trait loci analysis under different nitrogen treatments using a simple tower-based field phenotyping system with modified single-lens reflex cameras

    Science.gov (United States)

    Naito, Hiroki; Ogawa, Satoshi; Valencia, Milton Orlando; Mohri, Hiroki; Urano, Yutaka; Hosoi, Fumiki; Shimizu, Yo; Chavez, Alba Lucia; Ishitani, Manabu; Selvaraj, Michael Gomez; Omasa, Kenji

    2017-03-01

    Application of field based high-throughput phenotyping (FB-HTP) methods for monitoring plant performance in real field conditions has a high potential to accelerate the breeding process. In this paper, we discuss the use of a simple tower based remote sensing platform using modified single-lens reflex cameras for phenotyping yield traits in rice under different nitrogen (N) treatments over three years. This tower based phenotyping platform has the advantages of simplicity, ease and stability in terms of introduction, maintenance and continual operation under field conditions. Out of six phenological stages of rice analyzed, the flowering stage was the most useful in the estimation of yield performance under field conditions. We found a high correlation between several vegetation indices (simple ratio (SR), normalized difference vegetation index (NDVI), transformed vegetation index (TVI), corrected transformed vegetation index (CTVI), soil-adjusted vegetation index (SAVI) and modified soil-adjusted vegetation index (MSAVI)) and multiple yield traits (panicle number, grain weight and shoot biomass) across a three trials. Among all of the indices studied, SR exhibited the best performance in regards to the estimation of grain weight (R2 = 0.80). Under our tower-based field phenotyping system (TBFPS), we identified quantitative trait loci (QTL) for yield related traits using a mapping population of chromosome segment substitution lines (CSSLs) and a single nucleotide polymorphism data set. Our findings suggest the TBFPS can be useful for the estimation of yield performance during early crop development. This can be a major opportunity for rice breeders whom desire high throughput phenotypic selection for yield performance traits.

  3. The role of the apelinergic and vasopressinergic systems in the regulation of the cardiovascular system and the pathogenesis of cardiovascular disease.

    Science.gov (United States)

    Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka

    2014-01-01

    Research studies indicate a role of the apelinergic and vasopressinergic systems both in the regulation of the cardiovascular system and the pathogenesis of CVD, including in such settings as obesity and stress. Based on these data, it may be suggested that interactions between these systems underlie numerous physiological and pathophysiological processes, some of them related to the cardiovascular system. Better understanding of the role of these systems and their interactions, both physiological and related to the pathogenesis of CVD, will allow further advances in prevention and drug therapy.

  4. Haptoglobin phenotype, preeclampsia risk and the efficacy of vitamin C and E supplementation to prevent preeclampsia in a racially diverse population.

    Directory of Open Access Journals (Sweden)

    Tracey L Weissgerber

    Full Text Available Haptoglobin's (Hp antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH. This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393 and a case-control cohort (703 cases, 1,406 controls. The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01 in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia.

  5. A refined model of the genomic basis for phenotypic variation in vertebrate hemostasis.

    Science.gov (United States)

    Ribeiro, Ângela M; Zepeda-Mendoza, M Lisandra; Bertelsen, Mads F; Kristensen, Annemarie T; Jarvis, Erich D; Gilbert, M Thomas P; da Fonseca, Rute R

    2015-06-30

    Hemostasis is a defense mechanism that enhances an organism's survival by minimizing blood loss upon vascular injury. In vertebrates, hemostasis has been evolving with the cardio-vascular and hemodynamic systems over the last 450 million years. Birds and mammals have very similar vascular and hemodynamic systems, thus the mechanism that blocks ruptures in the vasculature is expected to be the same. However, the speed of the process varies across vertebrates, and is particularly slow for birds. Understanding the differences in the hemostasis pathway between birds and mammals, and placing them in perspective to other vertebrates may provide clues to the genetic contribution to variation in blood clotting phenotype in vertebrates. We compiled genomic data corresponding to key elements involved in hemostasis across vertebrates to investigate its genetic basis and understand how it affects fitness. We found that: i) fewer genes are involved in hemostasis in birds compared to mammals; and ii) the largest differences concern platelet membrane receptors and components from the kallikrein-kinin system. We propose that lack of the cytoplasmic domain of the GPIb receptor subunit alpha could be a strong contributor to the prolonged bleeding phenotype in birds. Combined analysis of laboratory assessments of avian hemostasis with the first avian phylogeny based on genomic-scale data revealed that differences in hemostasis within birds are not explained by phylogenetic relationships, but more so by genetic variation underlying components of the hemostatic process, suggestive of natural selection. This work adds to our understanding of the evolution of hemostasis in vertebrates. The overlap with the inflammation, complement and renin-angiotensin (blood pressure regulation) pathways is a potential driver of rapid molecular evolution in the hemostasis network. Comparisons between avian species and mammals allowed us to hypothesize that the observed mammalian innovations might have

  6. Sex hormone binding globulin phenotypes

    DEFF Research Database (Denmark)

    Cornelisse, M M; Bennett, Patrick; Christiansen, M

    1994-01-01

    Human sex hormone binding globulin (SHBG) is encoded by a normal and a variant allele. The resulting SHBG phenotypes (the homozygous normal SHBG, the heterozygous SHBG and the homozygous variant SHBG phenotype) can be distinguished by their electrophoretic patterns. We developed a novel detection....... This method of detection was used to determine the distribution of SHBG phenotypes in healthy controls of both sexes and in five different pathological conditions characterized by changes in the SHBG level or endocrine disturbances (malignant and benign ovarian neoplasms, hirsutism, liver cirrhosis...... on the experimental values. Differences in SHBG phenotypes do not appear to have any clinical significance and no sex difference was found in the SHBG phenotype distribution....

  7. Research in cardiovascular care

    DEFF Research Database (Denmark)

    Jaarsma, Tiny; Deaton, Christi; Fitzsimmons, Donna

    2014-01-01

    with the increasing opportunities and challenges in multidisciplinary research, the Science Committee of the Council on Cardiovascular Nursing and Allied Professionals (CCNAP) recognised the need for a position statement to guide researchers, policymakers and funding bodies to contribute to the advancement...... of the body of knowledge that is needed to further improve cardiovascular care. In this paper, knowledge gaps in current research related to cardiovascular patient care are identified, upcoming challenges are explored and recommendations for future research are given....

  8. Cardiovascular consequences of hormone therapy in postmenopausal women: Messages to clinicians.

    Science.gov (United States)

    Ylikorkala, O; Mikkola, T

    2005-03-01

    Results from the recent randomized clinical trials indicating that hormone therapy (HT) does not provide cardiovascular protection, but potentially harm are in profound disagreement with the sound evidence from numerous observational and experimental studies. While the observational studies have mainly assessed symptomatic recently menopausal women, the randomized trials have studied symptomless elderly postmenopausal women with established coronary heart disease or various risk factors for cardiovascular disease. Therefore, the recent trials have only revealed that HT does not provide secondary cardiovascular benefits. Since primary cardiovascular benefits of HT are rational but not yet proven in clinical trials, new studies are in demand. Until more data from recently menopausal symptomatic women are available, we need to base our decisions on existing evidence and good clinical practice. Although the potential of HT to provide cardiovascular benefits is decreased by advancing age and time since menopause, this should not preclude the use of individualized HT in younger postmenopausal women. (Reprod Med Biol 2005; 4 : 1- 6).

  9. 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.

  10. 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.

  11. Erectile dysfunction in the cardiovascular patient.

    Science.gov (United States)

    Vlachopoulos, Charalambos; Jackson, Graham; Stefanadis, Christodoulos; Montorsi, Piero

    2013-07-01

    Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

  12. Cardiovascular Disease and Diabetes

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Jan 29,2018 The following ... clear that there is a strong correlation between cardiovascular disease (CVD) and diabetes. At least 68 percent ...

  13. Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

    Science.gov (United States)

    Faber, J; Wingerter, A; Neu, M A; Henninger, N; Eckerle, S; Münzel, T; Lackner, K J; Beutel, M E; Blettner, M; Rathmann, W; Peters, A; Meisinger, C; Linkohr, B; Neuhauser, H; Kaatsch, P; Spix, C; Schneider, A; Merzenich, H; Panova-Noeva, M; Prochaska, J H; Wild, P S

    2018-05-01

    The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. NCT02181049.

  14. Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

    Science.gov (United States)

    Santos, Ana Paula Caires Dos; Couto, Ricardo David

    2018-05-16

    Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

  15. Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model.

    Science.gov (United States)

    Mas-Stachurska, Aleksandra; Siegert, Anna-Maria; Batlle, Monsterrat; Gorbenko Del Blanco, Darya; Meirelles, Thayna; Rubies, Cira; Bonorino, Fabio; Serra-Peinado, Carla; Bijnens, Bart; Baudin, Julio; Sitges, Marta; Mont, Lluís; Guasch, Eduard; Egea, Gustavo

    2017-09-25

    Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype. In a transgenic mouse model of MF ( Fbn1 C1039G/+ ), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis. Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Oral health and cardiovascular care: Perceptions of people with cardiovascular disease

    Science.gov (United States)

    Salamonson, Yenna; Ajwani, Shilpi; Bhole, Sameer; Bishop, Joshua; Lintern, Karen; Nolan, Samantha; Rajaratnam, Rohan; Redfern, Julie; Sheehan, Maria; Skarligos, Fiona; Spencer, Lissa; Srinivas, Ravi

    2017-01-01

    Main objective The aim of this study was to explore the perception of patients with cardiovascular disease towards oral health and the potential for cardiac care clinicians to promote oral health. Method A needs assessment was undertaken with twelve patients with cardiovascular disease attending cardiac rehabilitation between 2015 and 2016, in three metropolitan hospitals in Sydney, Australia. These patients participated in face-to-face semi-structured interviews. Data was analysed using thematic analysis. Results Results suggested that while oral health was considered relevant there was high prevalence of poor oral health among participants, especially those from socioeconomic disadvantaged background. Awareness regarding the importance of oral health care its impact on cardiovascular outcomes was poor among participants. Oral health issues were rarely discussed in the cardiac setting. Main barriers deterring participants from seeking oral health care included lack of awareness, high cost of dental care and difficulties in accessing the public dental service. Findings also revealed that participants were interested in receiving further information about oral health and suggested various mediums for information delivery. The concept of cardiac care clinicians, especially nurses providing education, assessment and referrals to ongoing dental care was well received by participants who felt the post-acute period was the most appropriate time to receive oral health care advice. The issues of oral health training for non-dental clinicians and how to address existing barriers were highlighted by participants. Relevance to clinical practice The lack of oral health education being provided to patients with cardiovascular disease offers an opportunity to improve care and potentially, outcomes. In view of the evidence linking poor oral health with cardiovascular disease, cardiac care clinicians, especially nurses, should be appropriately trained to promote oral health in

  17. Oral health and cardiovascular care: Perceptions of people with cardiovascular disease.

    Directory of Open Access Journals (Sweden)

    Paula Sanchez

    Full Text Available The aim of this study was to explore the perception of patients with cardiovascular disease towards oral health and the potential for cardiac care clinicians to promote oral health.A needs assessment was undertaken with twelve patients with cardiovascular disease attending cardiac rehabilitation between 2015 and 2016, in three metropolitan hospitals in Sydney, Australia. These patients participated in face-to-face semi-structured interviews. Data was analysed using thematic analysis.Results suggested that while oral health was considered relevant there was high prevalence of poor oral health among participants, especially those from socioeconomic disadvantaged background. Awareness regarding the importance of oral health care its impact on cardiovascular outcomes was poor among participants. Oral health issues were rarely discussed in the cardiac setting. Main barriers deterring participants from seeking oral health care included lack of awareness, high cost of dental care and difficulties in accessing the public dental service. Findings also revealed that participants were interested in receiving further information about oral health and suggested various mediums for information delivery. The concept of cardiac care clinicians, especially nurses providing education, assessment and referrals to ongoing dental care was well received by participants who felt the post-acute period was the most appropriate time to receive oral health care advice. The issues of oral health training for non-dental clinicians and how to address existing barriers were highlighted by participants.The lack of oral health education being provided to patients with cardiovascular disease offers an opportunity to improve care and potentially, outcomes. In view of the evidence linking poor oral health with cardiovascular disease, cardiac care clinicians, especially nurses, should be appropriately trained to promote oral health in their practice. Affordable and accessible

  18. Educational inequality in cardiovascular diseases

    DEFF Research Database (Denmark)

    Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas

    2018-01-01

    AIMS: Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases...... educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate...... factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart...

  19. 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

  20. 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.