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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

    OpenAIRE

    MH Dabbaghmaneh; T. Naderi; Akbarzadeh,M.; HR Tabatabaee; Z Zareh

    2012-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    MH Dabbaghmaneh

    2012-05-01

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

  3. 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.

  4. Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

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    Joseph Loscalzo

    2013-01-01

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

  5. Identification of genes and networks driving cardiovascular and metabolic phenotypes in a mouse F2 intercross.

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    Jonathan M J Derry

    Full Text Available To identify the genes and pathways that underlie cardiovascular and metabolic phenotypes we performed an integrated analysis of a mouse C57BL/6JxA/J F2 (B6AF2 cross by relating genome-wide gene expression data from adipose, kidney, and liver tissues to physiological endpoints measured in the population. We have identified a large number of trait QTLs including loci driving variation in cardiac function on chromosomes 2 and 6 and a hotspot for adiposity, energy metabolism, and glucose traits on chromosome 8. Integration of adipose gene expression data identified a core set of genes that drive the chromosome 8 adiposity QTL. This chromosome 8 trans eQTL signature contains genes associated with mitochondrial function and oxidative phosphorylation and maps to a subnetwork with conserved function in humans that was previously implicated in human obesity. In addition, human eSNPs corresponding to orthologous genes from the signature show enrichment for association to type II diabetes in the DIAGRAM cohort, supporting the idea that the chromosome 8 locus perturbs a molecular network that in humans senses variations in DNA and in turn affects metabolic disease risk. We functionally validate predictions from this approach by demonstrating metabolic phenotypes in knockout mice for three genes from the trans eQTL signature, Akr1b8, Emr1, and Rgs2. In addition we show that the transcriptional signatures for knockout of two of these genes, Akr1b8 and Rgs2, map to the F2 network modules associated with the chromosome 8 trans eQTL signature and that these modules are in turn very significantly correlated with adiposity in the F2 population. Overall this study demonstrates how integrating gene expression data with QTL analysis in a network-based framework can aid in the elucidation of the molecular drivers of disease that can be translated from mice to humans.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. Heliconia phenotypic diversity based on qualitative descriptors.

    Science.gov (United States)

    Guimarães, W N R; Martins, L S S; Castro, C E F; Carvalho Filho, J L S; Loges, V

    2014-04-17

    The aim of this study was to characterize Heliconia genotypes phenotypically using 26 qualitative descriptors. The evaluations were conducted in five flowering stems per clump in three replicates of 22 Heliconia genotypes. Data were subjected to multivariate analysis, the Mahalanobis dissimilarity measure was estimated, and the dendrogram was generated using the nearest neighbor method. From the values generated by the dissimilarity matrix and the clusters formed among the Heliconia genotypes studied, the phenotypic characterizations that best differentiated the genotypes were: pseudostem and wax green tone (light or dark green), leaf-wax petiole, the petiole hair, cleft margin at the base of the petiole, midrib underside shade of green, wax midrib underside, color sheet (light or dark green), unequal lamina base, torn limb, inflorescence-wax, position of inflorescence, bract leaf in apex, twisting of the rachis, and type of bloom. These results will be applied in the preparation of a catalog for Heliconia descriptors, in the selection of different genotypes with most promising characteristics for crosses, and for the characterization of new genotypes to be introduced in germplasm collections.

  11. 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.

  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. Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction

    Science.gov (United States)

    Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOV...

  14. cardiovasculares

    Directory of Open Access Journals (Sweden)

    Cristina Guerrero

    2006-01-01

    Full Text Available Uno de los aspectos que más discusión ha suscitado en los últimos tiempos entre quienes nos dedicamos al estudio de la emoción tiene que ver con la eventual asociación entre percepción, valoración y respuesta fisiológica. Esto es, siguiendo la máxima aristotélica, cabría cuestionar si las cosas son como son o son como cada quien las percibe. El objetivo de este experimento ha sido establecer la existencia de una conexión entre percepción de control y responsividad cardiovascular. La muestra estudiada ha estado conformada por estudiantes de la Universidad de Castellón; todos ellos han participado de forma voluntaria. La prueba de estrés ha consistido en un examen real de una asignatura troncal de la titulación que cursaban los participantes. Así pues, utilizando una situación de estrés real, hipotetizamos que las respuestas cardiovasculares (medidas a través de la tasa cardiaca, la presión sanguínea sistólica y la presión sanguínea diastólica dependen de la percepción de control que el individuo tiene, o cree tener, sobre la situación.

  15. Kinect system in home-based cardiovascular rehabilitation.

    Science.gov (United States)

    Vieira, Ágata; Gabriel, Joaquim; Melo, Cristina; Machado, Jorge

    2017-01-01

    Cardiovascular diseases lead to a high consumption of financial resources. An important part of the recovery process is the cardiovascular rehabilitation. This study aimed to present a new cardiovascular rehabilitation system to 11 outpatients with coronary artery disease from a Hospital in Porto, Portugal, later collecting their opinions. This system is based on a virtual reality game system, using the Kinect sensor while performing an exercise protocol which is integrated in a home-based cardiovascular rehabilitation programme, with a duration of 6 months and at the maintenance phase. The participants responded to a questionnaire asking for their opinion about the system. The results demonstrated that 91% of the participants (n = 10) enjoyed the artwork, while 100% (n = 11) agreed on the importance and usefulness of the automatic counting of the number of repetitions, moreover 64% (n = 7) reported motivation to continue performing the programme after the end of the study, and 100% (n = 11) recognized Kinect as an instrument with potential to be an asset in cardiovascular rehabilitation. Criticisms included limitations in motion capture and gesture recognition, 91% (n = 10), and the lack of home space, 27% (n = 3). According to the participants' opinions, the Kinect has the potential to be used in cardiovascular rehabilitation; however, several technical details require improvement, particularly regarding the motion capture and gesture recognition.

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

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    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.

  17. 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.

  18. 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

    risk groups when the QTc interval was added to a conventional risk model for CVD. CONCLUSION: Important differences were observed across subgroups when the absolute long-term risk of CVD was estimated based on QTc interval duration. The accuracy of the personalized CVD prognosis can be improved when.......1 years, 6647 persons died from cardiovascular causes. Long-term risks of CVD were estimated for subgroups defined by age, gender, cardiovascular disease, and QTc interval categories. In general, we observed an increased risk of CVD for both very short and long QTc intervals. Prolongation of the QTc...

  19. [Systemic cardiovascular risk assessment. Conventional or eye fundus-based?].

    Science.gov (United States)

    Wolf, A; Kernt, M; Kampik, A; Neubauer, A S

    2010-09-01

    Several systemic cardiovascular (CV) risk assessment algorithms exist, of which the ESC HeartScore, Framingham and PROCAM are the most frequently applied in Germany. The risk estimates generated differ and take a number of different risk factors into consideration. Due to existing homology of retinal vessels and brain vessels, eye fundus examination is a promising approach to improving risk prediction. Large cohort studies investigated retinal vascular changes, including arteriovenous ratio, as well as signs of retinopathy such as cotton-wool spots, microaneurysms, or retinal hemorrhages for their ability to predict systemic cardiovascular events. While signs of retinopathy proved to have high predictive power (but are rarely diagnosed,) the retinal vascular changes investigated could contribute little to enhancing systemic CV risk prediction. A number of new and promising approaches based on static and dynamic retinal analysis exist, but still need to be validated prospectively.

  20. Cardiovascular actions of GLP-1 and incretin-based pharmacotherapy.

    Science.gov (United States)

    Avogaro, Angelo; Vigili de Kreutzenberg, Saula; Fadini, Gian Paolo

    2014-01-01

    Incretin-based therapy became recently available as antihyperglycemic treatment for patients with type 2 diabetes (T2DM). Incretin therapy comprises glucagon-like peptide receptor agonists (GLP-1RA) and dipeptidyl-peptidase 4 inhibitors (DPP4-I): these classes of drugs not only have the ability to reduce blood glucose, but also can exert several cardioprotective effects. They have been shown to positively influence some risk factors for cardiovascular disease (CVD), to improve endothelial function, and to directly affect cardiac function. For these reasons incretins are considered not only antidiabetic drugs, but also cardiovascular effective. The first clinical trials aimed to demonstrate the safety of DPP4 inhibitors have been recently published: their clinical significance will be discussed in light of the prior experimental findings.

  1. Novel blood protein based scaffolds for cardiovascular tissue engineering

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    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.

  2. Novel epigenetic-based therapies useful in cardiovascular medicine

    Institute of Scientific and Technical Information of China (English)

    Claudio Napoli; Vincenzo Grimaldi; Maria Rosaria De Pascale; Linda Sommese; Teresa Infante; Andrea Soricelli

    2016-01-01

    Epigenetic modifications include DNA methylation, his-tone modifications, and micro RNA. Gene alterations have been found to be associated with cardiovascular diseases, and epigenetic mechanisms are continuously being studied to find new useful strategies for the clinical management of afflicted patients. Numerous cardiovascular disorders are characterized by the abnormal methylation of Cp G islands and so specific drugs that could inhibit DNA methyltransferase directly or by reducing its gene expression(e.g., hydralazine and procainamide) are currently under investigation. The anti-proliferative and anti-inflammatory properties of histone deacetylase inhibitors and their cardio-protective effects have been confirmed in preclinical studies. Furthermore, the regulation of the expression of micro RNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense micro RNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of eme-rging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols.

  3. UAV-based high-throughput phenotyping in legume crops

    Science.gov (United States)

    Sankaran, Sindhuja; Khot, Lav R.; Quirós, Juan; Vandemark, George J.; McGee, Rebecca J.

    2016-05-01

    In plant breeding, one of the biggest obstacles in genetic improvement is the lack of proven rapid methods for measuring plant responses in field conditions. Therefore, the major objective of this research was to evaluate the feasibility of utilizing high-throughput remote sensing technology for rapid measurement of phenotyping traits in legume crops. The plant responses of several chickpea and peas varieties to the environment were assessed with an unmanned aerial vehicle (UAV) integrated with multispectral imaging sensors. Our preliminary assessment showed that the vegetation indices are strongly correlated (p<0.05) with seed yield of legume crops. Results endorse the potential of UAS-based sensing technology to rapidly measure those phenotyping traits.

  4. CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases.

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    Alexandar V

    Full Text Available Cardiovascular diseases (CVDs account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD, hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies.

  5. Towards microRNA-based therapeutics for cardiovascular diseases

    NARCIS (Netherlands)

    Lei, Z.

    2015-01-01

    Cardiovascular diseases are still one of the leading causes of morbidity and mortality worldwide. The major risk factors currently associated with cardiovascular diseases will continuously increase these numbers, especially in developing countries, which will lead to a steep increase in mortality ra

  6. 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.

  7. Antibody-Based Assays for Phenotyping of Extracellular Vesicles

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    Lotte Hatting Pugholm

    2015-01-01

    Full Text Available Extracellular vesicles (EVs are a heterogeneous population of membrane-enclosed vesicles. EVs are recognized as important players in cell-to-cell communication and are described to be involved in numerous biological and pathological processes. The fact that EVs are involved in the development and progression of several diseases has formed the basis for the use of EV analysis in a clinical setting. As the interest in EVs has increased immensely, multiple techniques have been developed aiming at characterizing these vesicles. These techniques characterize different features of EVs, like the size distribution, enumeration, protein composition, and the intravesicular cargo (e.g., RNA. This review focuses on techniques that exploit the specificity and sensitivity associated with antibody-based assays to characterize the protein phenotype of EVs. The protein phenotype of EVs can provide information on the functionality of the vesicles and may be used for identification of disease-related biomarkers. Thus, protein profiling of EVs holds great diagnostic and prognostic potential.

  8. Imaging-based characterization of cardiometabolic phenotypes focusing on whole-body MRI--an approach to disease prevention and personalized treatment.

    Science.gov (United States)

    Gatidis, Sergios; Schlett, Christopher L; Notohamiprodjo, Mike; Bamberg, Fabian

    2016-01-01

    Metabolic syndrome and cardiovascular disorders pose a challenge to global healthcare systems. Too often, patients with metabolic syndrome are diagnosed in advanced disease stages, where disease-associated damage is irreversible and treatment options are limited. Thus, prevention plays an increasingly important role in the management of cardiometabolic disorders. The main challenge of prevention is to identify patient groups who are at risk for developing overt disease and who might benefit from early therapeutic intervention. In this context, imaging-based phenotyping can add significant information to clinical evaluations, revealing anatomical and physiological changes that reflect intrinsic and extrinsic risk factors. The purpose of this review article was to provide an overview of the current state of imaging-based phenotyping of metabolic syndrome and cardiovascular disorders and to discuss current and potential developments in this field.

  9. Frailty phenotypes in the elderly based on cluster analysis

    DEFF Research Database (Denmark)

    Dato, Serena; Montesanto, Alberto; Lagani, Vincenzo

    2012-01-01

    genetic background on the frailty status is still questioned. We investigated the applicability of a cluster analysis approach based on specific geriatric parameters, previously set up and validated in a southern Italian population, to two large longitudinal Danish samples. In both cohorts, we identified...... groups of subjects homogeneous for their frailty status and characterized by different survival patterns. A subsequent survival analysis availing of Accelerated Failure Time models allowed us to formulate an operative index able to correlate classification variables with survival probability. From...... these models, we quantified the differential effect of various parameters on survival, and we estimated the heritability of the frailty phenotype by exploiting the twin pairs in our sample. These data suggest the presence of a genetic influence on the frailty variability and indicate that cluster analysis can...

  10. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age.

    Directory of Open Access Journals (Sweden)

    Adam J Watkins

    Full Text Available Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein or normal protein diet (18% casein; NPD was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively, throughout gestation (LPD, NPD or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD. LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD. LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr and insulin-like growth factor I receptor (Igf1r in retroperitoneal fat was significantly elevated in Emb-LPD females (P<0.05, whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1 gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring

  11. Association of chromosome 9p21 SNPs with cardiovascular phenotypes in morbid obesity using electronic health record data

    OpenAIRE

    Wood, G. Craig; Still, Christopher D.; Chu, Xin; Susek, Meghan; Erdman, Robert; Hartman, Christina; Yeager, Stephanie; Blosky, Mary Ann; Krum, Wanda; Carey, David J.; Skelding, Kimberly A; Benotti, Peter; Stewart, Walter F.; Gerhard, Glenn S.

    2008-01-01

    Genomic medicine research requires substantial time and resources to obtain phenotype data. The electronic health record offers potential efficiencies in addressing these temporal and economic challenges, but few studies have explored the feasibility of using such data for genetics research. The main objective of this study was to determine the association of two genetic variants located on chromosome 9p21 conferring susceptibility to coronary heart disease and type 2 diabetes with a variety ...

  12. [Phenotype-based genetic association studies (PGAS): a new approach to understanding the genotype contribution to schizophrenic phenotypes].

    Science.gov (United States)

    Ehrenreich, H

    2013-05-01

    Schizophrenias are diagnosed purely clinically. The biological basis for this clinical entity is still fully unknown. Genetic studies have revealed some interesting hints but have not led to the identification of actual disease genotypes. On the contrary, it has become more and more probable that widely differing genotype constellations together with manifold environmental factors can trigger schizophrenia according to the motto "many roads lead to Rome...". Thus, new strategies that allow a better insight into complex genotype-phenotype relationships, e. g. PGAS (phenotype-based genetic associations studies) are urgently needed. PGAS became possible on the basis of the GRAS data collection, the as yet largest worldwide phenotypical databank of schizophrenic patients. First PGAS proof-of-concept results on cognition or development-relevant genes are already available.

  13. VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study.

    Science.gov (United States)

    Calderón, Juan Francisco; Puga, Alonso R; Guzmán, M Luisa; Astete, Carmen Paz; Arriaza, Marta; Aracena, Mariana; Aravena, Teresa; Sanz, Patricia; Repetto, Gabriela M

    2009-01-01

    Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80% of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

  14. Cardiovascular Considerations in Antidepressant Therapy: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Habibeh Yekehtaz

    2015-10-01

    Full Text Available There is a definite correlation between cardiovascular diseases and depressive disorders. Nevertheless, many aspects of this association have yet to be fully elucidated. Up to half of coronary artery disease patients are liable to suffer from some depressive symptoms, with approximately 20% receiving a diagnosis of major depressive disorders. Pharmacotherapy is a key factor in the management of major depression, not least in patients with chronic diseases who are likely to fail to show proper compliance and response to non-pharmacological interventions. Antidepressants are not deemed completely safe. Indeed, numerous side effects have been reported with the administration of antidepressants, among which cardiovascular adverse events are of paramount importance owing to their disabling and life-threatening nature. We aimed to re-examine some of the salient issues in antidepressant therapy vis-à-vis cardiovascular considerations, which should be taken into account when prescribing such medications.

  15. [Brief lecture on cardiovascular biomarkers based on the pathophysiology].

    Science.gov (United States)

    Shimada, Toshio

    2011-10-01

    Living organisms on the earth live dependent on the sun. Human beings are unexceptional. Plants with chlorophyll on the earth capture energy radiated from the sun and produce carbohydrate and oxygen from carbon dioxide and water using the energy from the sun. Herbivorous animals eat plants, carnivorous ones eat herbivorous ones and human beings eat both with a small amount of vitamins and minerals. Food including carbohydrate, protein and lipid which is digested by the gastroenteric system and mainly absorbed through the small intestine. Finally, nutrients from the digestive system and oxygen from the lungs are brought to the cells or the tissue through the cardiovascular system. Acetyl-CoA from food and oxygen from the lungs are chemically burned in the mitochondria to produce a lot of ATP. On the way of ATP production, unfavorable free radicals are inevitably produced to result in cancer and/or atherosclerosis. Cardiovascular system delivers oxygen and nutrients to the tissue or the cells. Literally, it is a pipe line for life support and then we must maintain cardiovascular system well to live long in good health. And therefore, it is essential to find cardiovascular abnormality as early as possible. Cardiovascular biomarkers such as BNP and NT-proBNP for screening for heart failure, RemL-C for screening for metabolic syndrome, cystatin C for screening for renal impairment and high sensitive troponin I, T for screening for ischemic myocardial damage have been greatly expected as tools to find early cardiovascular disorders for long survival in health examination and clinical practice.

  16. Cardiovascular Effects of Saffron: An Evidence-Based Review

    OpenAIRE

    Shahin Akhondzadeh; Maryam Kamalipour

    2011-01-01

    Herbal medicine can be a valuable source of assistance for traditional medicine. There are a number of herbs that can be used in conjunction with modern medicine. Herbs can also be taken to aid recovery from serious diseases. Although one should never aim to treat diseases such as cardiovascular disease solely with herbal medicine, the value of herbs used in tandem with modern medicine cannot be ignored. Saffron has been reported to help lower cholesterol and keep cholesterol levels healthy. ...

  17. Cardiovascular Effects of Saffron: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2011-05-01

    Full Text Available Herbal medicine can be a valuable source of assistance for traditional medicine. There are a number of herbs that can beused in conjunction with modern medicine. Herbs can also be taken to aid recovery from serious diseases. Although one should never aim to treat diseases such as cardiovascular disease solely with herbal medicine, the value of herbs used in tandem with modern medicine cannot be ignored. Saffron has been reported to help lower cholesterol and keep cholesterol levels healthy.Animal studies have shown saffron to lower cholesterol by as much as 50%. Saffron has antioxidant properties; it is, therefore,helpful in maintaining healthy arteries and blood vessels. Saffron is also known to have anti-inflammatory properties, which are beneficial to cardiovascular health. The people of Mediterranean countries, where saffron use is common, have lower than normal incidence of heart diseases. From saffron's cholesterol lowering benefits to its anti inflammatory properties,saffron may be one of the best supplements for cardiac health. This paper reviews the studies regarding the beneficial effects of saffron in cardiovascular health.

  18. A forward model-based validation of cardiovascular system identification

    Science.gov (United States)

    Mukkamala, R.; Cohen, R. J.

    2001-01-01

    We present a theoretical evaluation of a cardiovascular system identification method that we previously developed for the analysis of beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure, and instantaneous lung volume. The method provides a dynamical characterization of the important autonomic and mechanical mechanisms responsible for coupling the fluctuations (inverse modeling). To carry out the evaluation, we developed a computational model of the cardiovascular system capable of generating realistic beat-to-beat variability (forward modeling). We applied the method to data generated from the forward model and compared the resulting estimated dynamics with the actual dynamics of the forward model, which were either precisely known or easily determined. We found that the estimated dynamics corresponded to the actual dynamics and that this correspondence was robust to forward model uncertainty. We also demonstrated the sensitivity of the method in detecting small changes in parameters characterizing autonomic function in the forward model. These results provide confidence in the performance of the cardiovascular system identification method when applied to experimental data.

  19. Image-based plant phenotyping with incremental learning and active contours

    OpenAIRE

    Minervini, Massimo; Mohammed M. Abdelsamea; Tsaftaris, Sotirios A

    2014-01-01

    Plant phenotyping investigates how a plant's genome, interacting with the environment, affects the observable traits of a plant (phenome). It is becoming increasingly important in our quest towards efficient and sustainable agriculture. While sequencing the genome is becoming increasingly efficient, acquiring phenotype information has remained largely of low throughput. Current solutions for automated image-based plant phenotyping, rely either on semi-automated or manual analysis of the imagi...

  20. 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

    show that carefully designed conditions enable cultivation of a representative proportion of human gut bacteria, enabling rapid multiplex phenotypic profiling. We use this approach to determine the phylogenetic distribution of antibiotic tolerance phenotypes for 16 antibiotics in the human gut...... 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...

  1. Fat and carbohydrate intake over three generations modify growth, metabolism and cardiovascular phenotype in female mice in an age-related manner.

    Directory of Open Access Journals (Sweden)

    Samuel P Hoile

    Full Text Available Environmental challenges such as a high fat diet during pregnancy can induce changes in offspring growth, metabolism and cardiovascular function. However, challenges that are sustained over several generations can induce progressive compensatory metabolic adjustments in young adults. It is not known if such effects persist during ageing. We investigated whether diets with different fat and carbohydrate contents over three generations modifies markers of ageing. Female C57BL/6 F0 mice were fed diets containing 5% or 21% fat (w/w throughout pregnancy and lactation. Female offspring were fed the same diet as their dams until the F3 generation. In each generation, body weight, 24-hour food intake were recorded weekly, and plasma metabolites were measured by colorimetric assays, blood pressure by tail cuff plethysmography and vasoconstriction by myography on postnatal day 90 or 456. There was little effect of diet or generation on phenotypic markers in day 90 adults. There was a significant increase in whole body, liver and heart weight with ageing (d456 in the F3 21% fat group compared to the F1 and F3 5% groups. Fasting plasma glucose concentration was significantly increased with ageing in the 5% group in the F3 generation and in the 21% group in both generations. There was a significant effect of diet and generation on ex-vivo vasoconstriction in ageing females. Differences in dietary fat may induce metabolic compensation in young adults that persist over three generations. However, such compensatory effects decline during ageing.

  2. 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.

  3. 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

  4. Cardiovascular Deconditioning

    Science.gov (United States)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William

    1999-01-01

    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

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

    NARCIS (Netherlands)

    Boekel, N.B.; Schaapveld, M.; Gietema, J.A.; Russell, N.S.; Poortmans, P.; Theuws, J.C.; Schinagl, D.A.; Rietveld, D.H.; Versteegh, M.I.; Visser, O; Rutgers, E.J.; Aleman, B.M.; Leeuwen, F.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

  6. Progress in Chimeric Vector and Chimeric Gene Based Cardiovascular Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    HU Chun-Song; YOON Young-sup; ISNER Jeffrey M.; LOSORDO Douglas W.

    2003-01-01

    Gene therapy for cardiovascular diseases has developed from preliminary animal experiments to clinical trials. However, vectors and target genes used currently in gene therapy are mainly focused on viral, nonviral vector and single target gene or monogene. Each vector system has a series of advantages and limitations. Chimeric vectors which combine the advantages of viral and nonviral vector,chimeric target genes which combine two or more target genes and novel gene delivery modes are being developed. In this article, we summarized the progress in chimeric vectors and chimeric genes based cardiovascular gene therapy, which including proliferative or occlusive vascular diseases such as atheroslerosis and restenosis, hypertonic vascular disease such as hypertension and cardiac diseases such as myocardium ischemia, dilated cardiomyopathy and heart failure, even heart transplantation. The development of chimeric vector, chimeric gene and their cardiovascular gene therapy is promising.

  7. Estimating genetic correlations based on phenotypic data: a simulation-based method

    Indian Academy of Sciences (India)

    Elias Zintzaras

    2011-04-01

    Knowledge of genetic correlations is essential to understand the joint evolution of traits through correlated responses to selection, a difficult and seldom, very precise task even with easy-to-breed species. Here, a simulation-based method to estimate genetic correlations and genetic covariances that relies only on phenotypic measurements is proposed. The method does not require any degree of relatedness in the sampled individuals. Extensive numerical results suggest that the propose method may provide relatively efficient estimates regardless of sample sizes and contributions from common environmental effects.

  8. 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

  9. Nocturia, sleep-disordered breathing, and cardiovascular morbidity in a community-based cohort.

    Directory of Open Access Journals (Sweden)

    Sairam Parthasarathy

    Full Text Available BACKGROUND: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB, which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. METHODOLOGY/PRINCIPAL FINDINGS: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women, after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5. After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002, cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02 and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007. Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05. CONCLUSIONS/SIGNIFICANCE: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension.

  10. 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.

  11. GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm

    DEFF Research Database (Denmark)

    Bottolo, Leonardo; Chadeau-Hyam, Marc; Hastie, David I;

    2013-01-01

    -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...

  12. [Web-based interventions targeting cardiovascular risk factors in older people; a systematic review and meta-analysis

    NARCIS (Netherlands)

    Beishuizen, C.R.; Gool, W.A. van; Busschers, W.B.; Peters, R.J.; Moll- van Charante, E.; Richard, E.

    2016-01-01

    OBJECTIVE: To evaluate whether web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people. DESIGN: Systematic review and meta-analysis. METHOD: Embase, Medline, Cochrane Library and CINAHL were systematically searched from January 1995

  13. 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.

  14. Systematic construction of a conceptual minimal model of plasma cholesterol levels based on knockout mouse phenotypes knockout mouse phenotypes

    NARCIS (Netherlands)

    Pas, van de N.; Soffers, A.E.M.F.; Freidig, A.P.; Ommen, van B.; Woutersen, R.A.; Rietjens, I.M.C.M.; Graaf, de A.A.

    2010-01-01

    Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define th

  15. Evaluation of semantic-based information retrieval methods in the autism phenotype domain.

    Science.gov (United States)

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

    2011-01-01

    Biomedical ontologies are increasingly being used to improve information retrieval methods. In this paper, we present a novel information retrieval approach that exploits knowledge specified by the Semantic Web ontology and rule languages OWL and SWRL. We evaluate our approach using an autism ontology that has 156 SWRL rules defining 145 autism phenotypes. Our approach uses a vector space model to correlate how well these phenotypes relate to the publications used to define them. We compare a vector space phenotype representation using class hierarchies with one that extends this method to incorporate additional semantics encoded in SWRL rules. From a PubMed-extracted corpus of 75 articles, we show that average rank of a related paper using the class hierarchy method is 4.6 whereas the average rank using the extended rule-based method is 3.3. Our results indicate that incorporating rule-based definitions in information retrieval methods can improve search for relevant publications.

  16. Proximal Remote Sensing Buggies and Potential Applications for Field-Based Phenotyping

    Directory of Open Access Journals (Sweden)

    David Deery

    2014-07-01

    Full Text Available The achievements made in genomic technology in recent decades are yet to be matched by fast and accurate crop phenotyping methods. Such crop phenotyping methods are required for crop improvement efforts to meet expected demand for food and fibre in the future. This review evaluates the role of proximal remote sensing buggies for field-based phenotyping with a particular focus on the application of currently available sensor technology for large-scale field phenotyping. To illustrate the potential for the development of high throughput phenotyping techniques, a case study is presented with sample data sets obtained from a ground-based proximal remote sensing buggy mounted with the following sensors: LiDAR, RGB camera, thermal infra-red camera and imaging spectroradiometer. The development of such techniques for routine deployment in commercial-scale breeding and pre-breeding operations will require a multidisciplinary approach to leverage the recent technological advances realised in computer science, image analysis, proximal remote sensing and robotics.

  17. 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...

  18. 1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumatoid arthritis patients

    DEFF Research Database (Denmark)

    Lauridsen, Michael Brændgaard; Bliddal, Henning; Christensen, Robin Daniel Kjersgaard;

    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...

  19. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression.

    Science.gov (United States)

    Galbán, Craig J; Han, Meilan K; Boes, Jennifer L; Chughtai, Komal A; Meyer, Charles R; Johnson, Timothy D; Galbán, Stefanie; Rehemtulla, Alnawaz; Kazerooni, Ella A; Martinez, Fernando J; Ross, Brian D

    2012-11-01

    Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a highly heterogeneous disorder, composed of varying pathobiology. Accurate detection of COPD subtypes by image biomarkers is urgently needed to enable individualized treatment, thus improving patient outcome. We adapted the parametric response map (PRM), a voxel-wise image analysis technique, for assessing COPD phenotype. We analyzed whole-lung computed tomography (CT) scans acquired at inspiration and expiration of 194 individuals with COPD from the COPDGene study. PRM identified the extent of functional small airways disease (fSAD) and emphysema as well as provided CT-based evidence that supports the concept that fSAD precedes emphysema with increasing COPD severity. PRM is a versatile imaging biomarker capable of diagnosing disease extent and phenotype while providing detailed spatial information of disease distribution and location. PRM's ability to differentiate between specific COPD phenotypes will allow for more accurate diagnosis of individual patients, complementing standard clinical techniques.

  20. microRNA-based diagnostics and therapy in cardiovascular disease-Summing up the facts.

    Science.gov (United States)

    Schulte, Christian; Zeller, Tanja

    2015-02-01

    Circulating microRNAs (miRNAs) are discussed as potential disease-specific biomarkers in cardiovascular disease. Their diagnostic value has been examined in numerous studies and animal models with respect to coronary artery disease (CAD) and myocardial infarction (MI) and the prognostic abilities of circulating miRNAs in risk stratification of future disease have been evaluated. Various miRNAs are described to complement protein-based biomarkers or classical risk factors in the diagnosis of CAD or MI and even represent potential new biomarkers in the discrimination of unstable angina pectoris (UAP). Signatures consisting of sets of multiple miRNAs seem to improve the predictive power compared to single miRNAs. Furthermore, the emerging field of miRNA-based therapeutics has reached cardiovascular research. The first promising in vitro results are raising hope for future clinical application. However, methods and material used for RNA isolation, miRNA detection and normalization steps still lack ways of standardization and need to be considered carefully. This article reviews the current knowledge of miRNAs in cardiovascular disease focusing on CAD and MI and will provide an overview regarding the use of circulating miRNAs as biomarkers and potential therapeutic targets in the field of CAD.

  1. Ultrasound-based lectures on cardiovascular physiology and reflexes for medical students.

    Science.gov (United States)

    Paganini, M; Rubini, A

    2016-06-01

    Ultrasound has become a widely used diagnostic technique. While its role in patient evaluation is well known, its utility during preclinical courses such as anatomy and physiology is becoming increasingly recognized. The aim of the present study was to assess the feasibility/utility of integrating ultrasound-based sessions into conventional undergraduate medical school programs of physiology of the cardiovascular system and cardiovascular reflexes and to evaluate student perceptions of an ultrasound-based didactic session. Second-year medical students enrolled in the University of Padova attended a didactic session during which basic concepts regarding ultrasound instrumentation, image production, and spatial orientation were presented. Five anatomic sectors (the heart, aorta, neck vessels, inferior vena cava, and femoral veins) were then examined on a volunteer. Student perceptions of the images that were projected, the usefulness of the presentation, and the reproducibility of the experience were assessed at the end of the lecture with an anonymous questionnaire consisting of positive and negative items that were rated using a 5-point Likert scale and with two questions. One hundred eleven students attended the lecture; 99% of them found it very interesting, and none considered it boring or a waste of time. More than 96% thought it helped them to gain a better comprehension of the subject and would recommend it to a colleague. In conclusion, as ultrasound has been found to be a valuable resource for the teaching of physiology of the cardiovascular system and cardiovascular reflexes, efforts should be made to integrate ultrasound sessions into the traditional human physiology curriculum.

  2. [Para-Bombay phenotype caused by combined heterozygote of two bases deletion on fut1 alleles].

    Science.gov (United States)

    Ma, Kan-Rong; Tao, Shu-Dan; Lan, Xiao-Fei; Hong, Xiao-Zhen; Xu, Xian-Guo; Zhu, Fa-Ming; Lü, Hang-Jun; Yan, Li-Xing

    2011-02-01

    This study was purposed to investigate the molecular basis of a para-Bombay phenotype for screening and identification of rare blood group. ABO and H phenotypes of the proband were identified by serological techniques. The exon 6 to exon 7 of ABO gene and full coding region of α-1,2-fucosyltransferase (fut1) gene of the proband were analyzed by polymerase chain reaction and direct sequencing of the amplified fragments. The haplotype of compound heterozygote of fut1 was also identified by cloning sequencing. The results indicated that a rare para-Bombay phenotype was confirmed by serological techniques. Two deletion or insertion variant sites near nucleotide 547 and 880 were detected in fut1 gene. The results of cloning sequence showed that one haplotype of fut1 gene was two bases deletion at 547-552 (AGAGAG→AGAG), and another one was two bases deletion at position 880-882 (TTT→T). Both two variants caused a reading frame shift and a premature stop codon. It is concluded that a rare para-Bombay phenotype is found and confirmed in blood donor population. The molecular basis of this individual is compound heterozygote of two bases deletion on fut1 gene which weaken the activity of α-1, 2-fucosyltransferase.

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

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    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.

  4. A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases.

    Science.gov (United States)

    Karakikes, Ioannis; Termglinchan, Vittavat; Cepeda, Diana A; Lee, Jaecheol; Diecke, Sebastian; Hendel, Ayal; Itzhaki, Ilanit; Ameen, Mohamed; Shrestha, Rajani; Wu, Haodi; Ma, Ning; Shao, Ning-Yi; Seeger, Timon; Woo, Nicole A; Wilson, Kitchener D; Matsa, Elena; Porteus, Matthew H; Sebastiano, Vittorio; Wu, Joseph C

    2017-02-28

    Rationale: Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective: The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results: By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusions: Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular

  5. Thresholds for Diagnosing Hypertension Based on Automated Office Blood Pressure Measurements and Cardiovascular Risk.

    Science.gov (United States)

    Myers, Martin G; Kaczorowski, Janusz; Paterson, J Michael; Dolovich, Lisa; Tu, Karen

    2015-09-01

    The risk of cardiovascular events in relation to blood pressure is largely based on readings taken with a mercury sphygmomanometer in populations which differ from those of today in terms of hypertension severity and drug therapy. Given replacement of the mercury sphygmomanometer with electronic devices, we sought to determine the blood pressure threshold for a significant increase in cardiovascular risk using a fully automated device, which takes multiple readings with the subject resting quietly alone. Participants were 3627 community-dwelling residents aged >65 years untreated for hypertension. Automated office blood pressure readings were obtained in a community pharmacy with subjects seated and undisturbed. This method for recording blood pressure produces similar readings in different settings, including a pharmacy and family doctor's office providing the above procedures are followed. Subjects were followed for a mean (SD) of 4.9 (1.0) years for fatal and nonfatal cardiovascular events. Adjusted hazard ratios (95% confidence intervals) were computed for 10 mm Hg increments in blood pressure (mm Hg) using Cox proportional hazards regression and the blood pressure category with the lowest event rate as the reference category. A total of 271 subjects experienced a cardiovascular event. There was a significant (P=0.02) increase in the hazard ratio of 1.66 (1.09, 2.54) at a systolic blood pressure of 135 to 144 and 1.72 (1.21, 2.45; P=0.003) at a diastolic blood pressure of 80 to 89. A significant (P=0.03) increase in hazard ratio of 1.73 (1.04, 2.86) occurred with a pulse pressure of 80 to 89. These findings are consistent with a threshold of 135/85 for diagnosing hypertension in older subjects using automated office blood pressure.

  6. Risk of cardiovascular disease in a traditional African population with a high infectious load: a population-based study.

    Directory of Open Access Journals (Sweden)

    Jacob J E Koopman

    Full Text Available BACKGROUND: To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. METHODOLOGY/PRINCIPAL FINDINGS: Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%. Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%. CONCLUSIONS/SIGNIFICANCE: Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    Dalleck LC

    2014-08-01

    Full Text Available Lance C Dalleck,1,3 Gary P Van Guilder,2,3 Tara B Richardson,1 Donald L Bredle,3 Jeffrey M Janot31Recreation, Exercise, and Sport Science Department, Western State Colorado University, Gunnison, CO, USA; 2Department of Health and Nutritional Sciences, South Dakota State University, Brookings, SD, USA; 3Department of Kinesiology, University of Wisconsin-Eau Claire, Eau Claire, WI, USABackground: 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 (P<0.05 transitioned to metabolically 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; P<0.05 and 7.5 (95% confidence interval: 1.5–37.5; P<0.05 times more likely to transition from MAO to MHO, respectively.Conclusion: Community-based exercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the

  9. 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.

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

    Science.gov (United States)

    Ispolatov, Iaroslav; Madhok, Vaibhav; Doebeli, Michael

    2016-02-01

    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.

  11. 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.

  12. Population-based resequencing of APOA1 in 10,330 individuals: spectrum of genetic variation, phenotype, and comparison with extreme phenotype approach.

    Science.gov (United States)

    Haase, Christiane L; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2012-01-01

    Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. We used the apolipoprotein A-I gene (APOA1), a major high-density lipoprotein (HDL) gene, and population-based resequencing to determine the spectrum of genetic variants, the phenotypic characteristics of these variants, and how these results compared with results based on resequencing only the extremes of the apolipoprotein A-I (apoA-I) distribution. First, we resequenced APOA1 in 10,330 population-based participants in the Copenhagen City Heart Study. The spectrum and distribution of genetic variants was determined as a function of the number of individuals resequenced. Second, apoA-I and HDL cholesterol phenotypes were determined for nonsynonymous (NS) and synonymous (S) variants and were validated in the Copenhagen General Population Study (n = 45,239). Third, observed phenotypes were compared with those predicted using an extreme phenotype approach based on the apoA-I distribution. Our results are as follows: First, population-based resequencing of APOA1 identified 40 variants of which only 7 (18%) had minor allele frequencies >1%, and most were exceedingly rare. Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis. NS variants associated with a hazard ratio of 1.72 (1.09-2.70) for myocardial infarction (MI), largely driven by A164S, a variant not associated with apoA-I or HDL cholesterol levels. Third, using the extreme apoA-I phenotype approach, NS variants correctly predicted the apoA-I phenotype observed in the population-based resequencing. However, using the extreme approach, between 79% (screening 0-1(st) percentile) and 21% (screening 0-20(th) percentile) of all variants were not identified; among these were variants

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Hrabě de Angelis, Martin; Nicholson, George; Selloum, Mohammed; White, Jacqueline K; 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, Michael R; 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; Fertak, Lahcen El; 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 M J; 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, Edward; 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; Wattenhofer-Donze, Marie; 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 D M

    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.

  16. 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.

  17. 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.

  18. Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

    Science.gov (United States)

    Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

    2017-01-01

    To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

  19. 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.......1(0.0, 0.1) mmol/L). CONCLUSION: Completion of this four-month, pedometer-based, physical activity, workplace programme was associated with improvements in behavioural and anthropometric risk factors for diabetes and cardiovascular disease. Long-term evaluation is required to evaluate the potential...

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

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    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.

  1. Allopurinol therapy in gout patients does not associate with beneficial cardiovascular outcomes: a population-based matched-cohort study.

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    Victor C Kok

    Full Text Available Previous studies have shown an association between gout and/or hyperuricemia and a subsequent increase in cardiovascular disease (CVD outcomes. Allopurinol reduces vascular oxidative stress, ameliorates inflammatory state, improves endothelial function, and prevents atherosclerosis progression. Accordingly, we tested the hypothesis that a positive association between allopurinol therapy in gout patients and future cardiovascular outcomes is present using a population-based matched-cohort study design.Patients aged ≥40 years with newly diagnosed gout having no pre-existing severe form of CVD were separated into allopurinol (n = 2483 and non-allopurinol (n = 2483 groups after matching for age, gender, index date, diabetes mellitus, hypertension, hyperlipidemia, and atrial fibrillation. The two groups were also balanced in terms of uric acid nephrolithiasis, acute kidney injury, hepatitis, and Charlson comorbidity index.With a median follow-up time of 5.25 years, the allopurinol group had a modest increase in cardiovascular risk [relative risk, 1.20; 95% confidence interval (CI, 1.08-1.34]. A Cox proportional hazard model adjusted for chronic kidney disease, uremia, and gastric ulcer gave a hazard ratio (HR for cardiovascular outcomes of 1.25 (95% CI, 1.10-1.41 in gout patients receiving allopurinol compared with the non-allopurinol group. In further analysis of patients receiving urate-lowering therapy, the uricosuric agent group (n = 1713 had an adjusted HR of 0.83 (0.73-0.95 for cardiovascular events compared with the allopurinol group.The current population-based matched-cohort study did not support the association between allopurinol therapy in gout patients with normal risk for cardiovascular sequels and beneficial future cardiovascular outcomes. Several important risk factors for cardiovascular disease, such as smoking, alcohol consumption, body mass index, blood pressure were not obtainable in the current retrospective cohort

  2. Gestational diabetes mellitus and later cardiovascular disease: a Swedish population based case–control study

    Science.gov (United States)

    Fadl, H; Magnuson, A; Östlund, I; Montgomery, S; Hanson, U; Schwarcz, E

    2014-01-01

    Objective To identify if gestational diabetes mellitus (GDM) is a clinically useful marker of future cardiovascular disease (CVD) risk and if GDM combined with other risks (smoking, hypertension or body mass) identifies high-risk groups. Design Population-based matched case–control study. Setting National Swedish register data from 1991 to 2008. Population A total of 2639 women with a cardiovascular event and matched controls. Methods Conditional logistic regression examined associations with CVD before and after adjustment for conventional risk factors and confounders. Effect modification for the association of GDM with CVD by body mass index (BMI), smoking and chronic hypertension was assessed by stratification and interaction testing. Adjustment for diabetes post-pregnancy evaluated its mediating role. Main outcome measures Inpatient diagnoses or causes of death identifying ischemic heart disease, ischemic stroke, atherosclerosis or peripheral vascular disease. Results The adjusted odds ratios (and 95% confidence intervals) for the association of CVD with GDM are 1.51 (1.07–2.14), 2.23 (2.01–2.48) for smoking, 1.98 (1.71–2.29) for obesity and 5.10 (3.18–8.18) for chronic hypertension. In stratified analysis the association of CVD with GDM was only seen among women with BMI ≥25, with an odds ratio of 2.39 (1.39–4.10), but only women with a BMI <30 accounted for this increased risk. Adjustment for post-pregnancy diabetes attenuated it somewhat to 1.99 (1.13–3.52). Conclusions In the absence of other recognised cardiovascular risk factors, such as smoking, obesity or chronic hypertension, GDM is a useful marker of raised CVD risk among women with BMI between 25 and 29. PMID:24762194

  3. 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.

  4. Cardiovascular disease risk reduction for tenth graders. A multiple-factor school-based approach.

    Science.gov (United States)

    Killen, J D; Telch, M J; Robinson, T N; Maccoby, N; Taylor, C B; Farquhar, J W

    All tenth graders in four senior high schools (N = 1447) from two school districts participated in a cardiovascular disease risk-reduction trial. Within each district, one school was assigned at random to receive a special 20-session risk-reduction intervention and one school served as a control. At a two-month follow-up, risk factor knowledge scores were significantly greater for students in the treatment group. Compared with controls, a higher proportion of those in the treatment group who were not exercising regularly at baseline reported regular exercise at follow-up. Almost twice as many baseline experimental smokers in the treatment group reported quitting at follow-up, while only 5.6% of baseline experimental smokers in the treatment group graduated to regular smoking compared with 10.3% in the control group. Students in the treatment group were more likely to report that they would choose "heart-healthy" snack items. Beneficial treatment effects were observed for resting heart rate, body mass index, triceps skin fold thickness, and subscapular skin fold thickness. The results suggest that it is feasible to provide cardiovascular disease risk-reduction training to a large segment of the population through school-based primary prevention approaches.

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

    Science.gov (United States)

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

    2014-01-01

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

  6. Community-Based ECG Monitoring System for Patients with Cardiovascular Diseases.

    Science.gov (United States)

    Lin, Bor-Shyh; Wong, Alice M; Tseng, Kevin C

    2016-04-01

    This study aims to develop a community-based electrocardiogram (ECG) monitoring system for cardiac outpatients to wirelessly detect heart rate, provide personalized healthcare, and enhance interactive social contact because of the prevalence of deaths from cardiovascular disease and the growing problem of aging in the world. The system not only strengthens the performance of the ECG monitoring system but also emphasizes the ergonomic design of wearable devices and user interfaces. In addition, it enables medical professionals to diagnose cardiac symptoms remotely and electronically manage medical reports and suggestions. The experimental result shows high performance of the dry electrode, even in dynamic conditions. The comparison result with different ECG healthcare systems shows the essential factors that the system should possess and the capability of the proposed system. Finally, a user survey was conducted based on the unified theory of acceptance and users of technology (UTAUT) model.

  7. Relationship Between Hypertriglyceridemic-waist Phenotype and Clustering of Cardiovascular Risk Factors in Middle and Aged Population%中老年人群高甘油三酯血症-腰围表型与心血管危险因素聚集关系探讨

    Institute of Scientific and Technical Information of China (English)

    袁宁; 黄晓波; 刘雅; 欧阳凌云; 张廷杰; 陈祥吉

    2016-01-01

    目的:探讨40~79岁中老年人群高甘油三酯(TG)血症-腰围(HTWC)表型与心血管危险因素聚集的关系。  方法:利用2013年成都市4个社区横断面流行病学调查的1004例40~79岁中老年人群数据,将HTWC定义为TG≥2.0 mmol/L,男性腰围≥90 cm,女性腰围≥85 cm。分为(1)TG和腰围正常组(492例)即血TG  结果:40~79岁中老年人群HTWC表型的检出率为13.15%(男性12.69%,女性13.37%),40~79岁人群中HTWC组心血管危险因素聚集检出率为41.67%,而TG和腰围正常组心血管危险因素聚集检出率为13.21%。多因素Logistic逐步回归分析显示,经校正年龄、性别、体重指数、吸烟史、糖尿病家族史及高血压家族史后,HTWC组发生心血管危险因素聚集的检出率仍为TG和腰围正常组的4.50倍(比值比:4.50,95%可信区间:2.84~7.12,P  结论:中老年人群HTWC与心血管危险因素聚集密切相关,可作为筛查心血管危险因素聚集的指标。%Objective: To explore the relationship between hypertriglyceridemic-waist (HTWC) phenotype and clustering of cardiovascular risk factors in middle and aged population. Methods: A community-based cross-sectional survey was conducted in 5 communities of Chengdu city from 2013-10 to 2014-05 and 1004 subjects from (40-79) years of age were investigated. HTWC was defined by TG≥2.0 mmol/L and waist circumference≥90 cm in male, ≥85 cm in female. The subjects were divided into 4 groups:①Normal group, the subjects with TG Results: The prevalence of HTWC phenotype was 13.15% (12.69% in male and 13.37% in female). In HTWC group, the detection rate of clustering of cardiovascular risk factors was 41.67% (13.21% in both Simple abdominal obesity group and Simple hipertrigliceridemia group). Multi Logistic regression analysis indicated that with adjusted age, gender, body mass index, smoking history and family history of diabetes and

  8. Shape based assignment tests suggest transgressive phenotypes in natural sculpin hybrids (Teleostei, Scorpaeniformes, Cottidae

    Directory of Open Access Journals (Sweden)

    Sheets H David

    2005-06-01

    Full Text Available Abstract Background Hybridization receives attention because of the potential role that it may play in generating evolutionary novelty. An explanation for the emergence of novel phenotypes is given by transgressive segregation, which, if frequent, would imply an important evolutionary role for hybridization. This process is still rarely studied in natural populations as samples of recent hybrids and their parental populations are needed. Further, the detection of transgressive segregation requires phenotypes that can be easily quantified and analysed. We analyse variability in body shape of divergent populations of European sculpins (Cottus gobio complex as well as natural hybrids among them. Results A distance-based method is developed to assign unknown specimens to known groups based on morphometric data. Apparently, body shape represents a highly informative set of characters that parallels the discriminatory power of microsatellite markers in our study system. Populations of sculpins are distinct and "unknown" specimens can be correctly assigned to their source population based on body shape. Recent hybrids are intermediate along the axes separating their parental groups but display additional differentiation that is unique and coupled with the hybrid genetic background. Conclusion There is a specific hybrid shape component in natural sculpin hybrids that can be best explained by transgressive segregation. This inference of how hybrids differ from their ancestors provides basic information for future evolutionary studies. Furthermore, our approach may serve to assign candidate specimens to their source populations based on morphometric data and help in the interpretation of population differentiation.

  9. Cardiovascular age of aviation personnel:based on the principal component analysis of heart rate and blood pressure variability

    Institute of Scientific and Technical Information of China (English)

    牛有国; 王守岩; 张玉海; 王兴邦; 张立藩

    2004-01-01

    Objective: To introduce a method to calculate cardiovascular age, a new, accurate and much simpler index for assessing cardiovascular autonomic regulatory function, based on statistical analysis of heart rate and blood pressure variability (HRV and BPV) and baroreflex sensitivity (BRS) data. Methods: Firstly, HRV and BPV of 89 healthy aviation personnel were analyzed by the conventional autoregressive (AR) spectral analysis and their spontaneous BRS was obtained by the sequence method. Secondly, principal component analysis was conducted over original and derived indices of HRV, BPV and BRS data and the relevant principal components, Pciorig and Pcideri (I=1, 2, 3,...) were obtained. Finally, the equation for calculating cardiovascular age was obtained by multiple regression with the chronological age being assigned as the dependent variable and the principal components significantly related to age as the regressors. Results: The first four principal components of original indices accounted for over 90% of total variance of the indices, so did the first three principal components of derived indices. So, these seven principal components could reflect the information of cardiovascular autonomic regulation which was embodied in the 17 indices of HRV, BPV and BRS exactly with a minimal loss of information. Of the seven principal components, PC2orig, PC4orig and PC2deri were negatively correlated with the chronological age (P<0.05), whereas the PC3orig was positively correlated with the chronological age (P<0.01). The cardiovascular age thus calculated from the regression equation was significantly correlated with the chronological age among the 89 aviation personnel (r=0.73, P<0.01). Conclusion: The cardiovascular age calculated based on a multi-variate analysis of HRV, BPV and BRS could be regarded as a comprehensive indicator reflecting the age dependency of autonomic regulation of cardiovascular system in healthy aviation personnel.

  10. TO STUDY THE RISK OF CARDIOVASCULAR MORBIDITY & MORTALITY IN STABLE COPD PATIENTS BASED ON ESTABLISHED CARDIOVASCULAR RISK FACTORS IN CENTRAL INDIA

    Directory of Open Access Journals (Sweden)

    Ravindra

    2014-03-01

    Full Text Available The epidemiologic evidence linking COPD and cardiovascular morbidity and mortality is strong. Even after adjustments for traditional cardiovascular risk factors such as serum total cholesterol hypertension, obesity and smoking, patients with COPD have a two- to threefold increase in the risk of cardiovascular events including death. Age >60 yrs., Male sex, Significant Smoking History, T2 Diabetes Mellitus, Body Mass Index >30 Kg/M2, Left Ventricular Hypertrophy have a statistically significant correlation to cardiovascular mortality & morbidity. Significant relations were demonstrated between the treatment that patient requires for stability & cardiovascular morbidity & mortality in Central India.

  11. An expanded model of HIV cell entry phenotype based on multi-parameter single-cell data

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    Bozek Katarzyna

    2012-07-01

    Full Text Available Abstract Background Entry of human immunodeficiency virus type 1 (HIV-1 into the host cell involves interactions between the viral envelope glycoproteins (Env and the cellular receptor CD4 as well as a coreceptor molecule (most importantly CCR5 or CXCR4. Viral preference for a specific coreceptor (tropism is in particular determined by the third variable loop (V3 of the Env glycoprotein gp120. The approval and use of a coreceptor antagonist for antiretroviral therapy make detailed understanding of tropism and its accurate prediction from patient derived virus isolates essential. The aim of the present study is the development of an extended description of the HIV entry phenotype reflecting its co-dependence on several key determinants as the basis for a more accurate prediction of HIV-1 entry phenotype from genotypic data. Results Here, we established a new protocol of quantitation and computational analysis of the dependence of HIV entry efficiency on receptor and coreceptor cell surface levels as well as viral V3 loop sequence and the presence of two prototypic coreceptor antagonists in varying concentrations. Based on data collected at the single-cell level, we constructed regression models of the HIV-1 entry phenotype integrating the measured determinants. We developed a multivariate phenotype descriptor, termed phenotype vector, which facilitates a more detailed characterization of HIV entry phenotypes than currently used binary tropism classifications. For some of the tested virus variants, the multivariant phenotype vector revealed substantial divergences from existing tropism predictions. We also developed methods for computational prediction of the entry phenotypes based on the V3 sequence and performed an extrapolating calculation of the effectiveness of this computational procedure. Conclusions Our study of the HIV cell entry phenotype and the novel multivariate representation developed here contributes to a more detailed

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    ischaemic heart disease and nonfatal stroke, amounted to 222 cases. In Cox proportional-hazard models, adjusted for age, sex, smoking habit, total cholesterol, waist circumference, levels of triglycerides and high-density lipoprotein-cholesterol, systolic and diastolic blood pressures, physical activity......BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors....... It is not clear whether CRP predicts CVD independent of IR. DESIGN: Prospective population-based study. METHODS: Two thousand three hundred and fifty-seven Danish men and women, recruited from the general population, aged 41-72 years, without major CVD at baseline were studied. Traditional and new risk factors...

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

    Science.gov (United States)

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

    2015-01-01

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

  14. New Cardiovascular Indices Based on a Nonlinear Spectral Analysis of Arterial Blood Pressure Waveforms

    CERN Document Server

    Laleg, Taous-Meriem; Papelier, Yves; Crépeau, Emmanuelle; Sorine, Michel

    2007-01-01

    A new method for analyzing arterial blood pressure is presented in this report. The technique is based on the scattering transform and consists in solving the spectral problem associated to a one-dimensional Schr\\"odinger operator with a potential depending linearly upon the pressure. This potential is then expressed with the discrete spectrum which includes negative eigenvalues and corresponds to the interacting components of an N-soliton. The approach is similar to a nonlinear Fourier transform where the solitons play the role of sine and cosine components. The method provides new cardiovascular indices that seem to contain relevant physiological information. We first show how to use this approach to decompose the arterial blood pressure pulse into elementary waves and to reconstruct it or to separate its systolic and diastolic phases. Then we analyse the parameters computed from this technique in two physiological conditions, the head-up 60 degrees tilt test and the isometric handgrip test, widely used for...

  15. Swedish snuff and incidence of cardiovascular disease. A population-based cohort study

    Directory of Open Access Journals (Sweden)

    Hedblad Bo

    2009-05-01

    Full Text Available Abstract Background The relationship between smoking and an increased incidence of cardiovascular diseases is well known. Whether smokeless tobacco (snuff is related to myocardial infarction (MI or stroke is still controversial. Aim of this study was to explore whether snuff users have an increased incidence of MI or stroke. Methods A total of 16 754 women and 10 473 men (aged 45–73 years, without history of cardiovascular disease (CVD, belonging to the population-based "Malmö Diet and Cancer" study were examined. Incidence of MI and stroke were monitored over 10.3 years. Results Snuff was used by 737 (7.0% men and 75 (0.4% women, respectively. Among men, snuff was significantly associated with low occupation level, single civil status, high BMI and with current and former smoking. In women, snuff was associated with lower systolic blood pressure. A total of 964 individuals (3.5%, i.e.544 men (5.3% and 420 (2.5% women suffered a MI during the follow-up period. The corresponding numbers of incident stroke cases were 1048, i.e. 553 men (5.3% and 495 (3.0% women, respectively. Snuff was not associated with any statistically significant increased risk of MI or stroke in men or women. The relative risks (RR in male snuff users compared to non-users were 1.05 (95% confidence interval (CI: 0.8–1.4, p = 0.740 for incident MI and 0.97 (0.7–1.4, p = 0.878 for stroke, after taking age and potential confounders into account. In women none of the 420 (2.5% women who were snuff users had a MI and only one suffered a stroke during the follow-up. Conclusion Several life-style risk factors were more prevalent in snuff-users than in non-users. However, the present study does not support any relationship between snuff and incidence of cardiovascular disease in men.

  16. Framingham Risk Score for Prediction of Cardiovascular Diseases: A Population-Based Study from Southern Europe

    Science.gov (United States)

    Artigao-Rodenas, Luis M.; Carbayo-Herencia, Julio A.; Divisón-Garrote, Juan A.; Gil-Guillén, Vicente F.; Massó-Orozco, Javier; Simarro-Rueda, Marta; Molina-Escribano, Francisca; Sanchis, Carlos; Carrión-Valero, Lucinio; López de Coca, Enrique; Caldevilla, David; López-Abril, Juan; Carratalá-Munuera, Concepción; Lopez-Pineda, Adriana

    2013-01-01

    Background The question about what risk function should be used in primary prevention remains unanswered. The Framingham Study proposed a new algorithm based on three key ideas: use of the four risk factors with the most weight (cholesterol, blood pressure, diabetes and smoking), prediction of overall cardiovascular diseases and incorporating the concept of vascular age. The objective of this study was to apply this new function in a cohort of the general non Anglo-Saxon population, with a 10-year follow-up to determine its validity. Methods The cohort was studied in 1992-94 and again in 2004-06. The sample comprised 959 randomly-selected persons, aged 30-74 years, who were representative of the population of Albacete, Spain. At the first examination cycle, needed data for the new function were collected and at the second examination, data on all events were recorded during the follow-up period. Discrimination was studied with ROC curves. Comparisons of prediction models and reality in tertiles (Hosmer-Lemeshow) were performed, and the individual survival functions were calculated. Results The mean risks for women and men, respectively, were 11.3% and 19.7% and the areas under the ROC curve were 0.789 (95%CI, 0.716-0.863) and 0.780 (95%CI, 0.713-0.847) (P<0.001, both). Cardiovascular disease events occurred in the top risk tertiles. Of note were the negative predictive values in both sexes, and a good specificity in women (85.6%) and sensitivity in men (79.1%) when their risk for cardiovascular disease was high. This model overestimates the risk in older women and in middle-aged men. The cumulative probability of individual survival by tertiles was significant in both sexes (P<0.001). Conclusions The results support the proposal for “reclassification” of Framingham. This study, with a few exceptions, passed the test of discrimination and calibration in a random sample of the general population from southern Europe. PMID:24039972

  17. Linking trait-based phenotypes to prefrontal cortex activation during inhibitory control.

    Science.gov (United States)

    Rodrigo, Achala H; Di Domenico, Stefano I; Graves, Bryanna; Lam, Jaeger; Ayaz, Hasan; Bagby, R Michael; Ruocco, Anthony C

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control.

  18. Psoriasis, cardiovascular events, cancer risk and alcohol use: evidence-based recommendations based on systematic review and expert opinion.

    Science.gov (United States)

    Richard, M-A; Barnetche, T; Horreau, C; Brenaut, E; Pouplard, C; Aractingi, S; Aubin, F; Cribier, B; Joly, P; Jullien, D; Le Maître, M; Misery, L; Ortonne, J-P; Paul, C

    2013-08-01

    The relationship between psoriasis, chronic inflammation, cardiovascular risk and risk of cancer has long been debated. In addition, it has been suggested that alcohol consumption may be a risk factor for psoriasis onset and severity. The aim of this study was to develop evidence-based recommendations on the risk of comorbidities and its management for daily clinical use, focusing on cardiovascular risk, risk of cancer and alcohol use in psoriasis. A scientific committee identified and selected through the Delphi method clinically relevant questions about cardiovascular risk, risk of cancer and alcohol use in psoriasis. To address these questions, a systematic literature search was performed in Medline, Embase and the Cochrane Library databases. Systematic literature reviews including meta-analysis whenever possible were performed. Subsequently, an Expert board meeting involving 39 dermatologists took place to analyse the evidence and to elaborate recommendations on the selected questions. Recommendations were graded according to the Oxford level of evidence grading system. The degree of agreement of these recommendations was assessed on a 10-point scale, as well as their potential impact on daily clinical practice. A total of 3242 articles were identified through the systematic literature searches, among which 110 were included in the systematic reviews. Overall, 12 recommendations were elaborated regarding comorbidities management in psoriasis patients. A moderate increased risk of cardiovascular diseases (CVD), mainly myocardial infarction (MI) [meta-analysis of cohort studies: OR = 1.25 (95% CI 1.03-1.52) and of cross-sectional studies: OR = 1.57 (95% CI 1.08-2.27)], and coronary artery disease (CAD) [meta-analysis of cross-sectional: OR = 1.19 (95% CI 1.14-1.24), of cohort studies: OR = 1.20 (95% CI 1.13-1.27) and of case-control studies: OR = 1.84 (95% CI 1.09-3.09)] was acknowledged. This increased cardiovascular risk requires appropriate prevention

  19. Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality Improvement Cardiovascular care Kwara-I (QUICK-I

    Directory of Open Access Journals (Sweden)

    Alli Shade

    2011-03-01

    Full Text Available Abstract Background Cardiovascular diseases (CVD are a leading contributor to the burden of disease in low- and middle-income countries. Guidelines for CVD prevention care in low resource settings have been developed but little information is available on strategies to implement this care. A community health insurance program might be used to improve patients' access to care. The operational research project "QUality Improvement Cardiovascular care Kwara - I (QUICK-I" aims to assess the feasibility of CVD prevention care in rural Nigeria, according to international guidelines, in the context of a community based health insurance scheme. Methods/Design Design: prospective observational hospital based cohort study. Setting: a primary health care centre in rural Nigeria. Study population: 300 patients at risk for development of CVD (patients with hypertension, diabetes, renal disease or established CVD who are enrolled in the Hygeia Community Health Plan. Measurements: demographic and socio- economic data, physical and laboratory examination, CVD risk profile including screening for target organ damage. Measurements will be done at 3 month intervals during 1 year. Direct and indirect costs of CVD prevention care will be estimated. Outcomes: 1 The adjusted cardiovascular quality of care indicator scores based on the "United Kingdom National Health Services Quality and Outcome Framework". 2 The average costs of CVD prevention and treatment per patient per year for patients, the clinic and the insurance company. 3 The estimated net health care costs of standard CVD prevention care per quality-adjusted life year gained. Analysis: The primary outcomes, the score on CVD quality indicators and cost data will be descriptive. The quality scores and cost data will be used to describe the feasibility of CVD prevention care according to international guidelines. A cost-effectiveness analysis will be done using a Markov model. Discussion Results of QUICK-I can

  20. Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease.

    Science.gov (United States)

    Netherton, Stuart J; Jimmo, Sandra L; Palmer, Daniel; Tilley, Douglas G; Dunkerley, Heather A; Raymond, Daniel R; Russell, James C; Absher, P Marlene; Sage, E Helene; Vernon, Robert B; Maurice, Donald H

    2002-04-01

    Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aortic VSMCs, levels of expression of cytosolic PDE3 (PDE3A) and PDE3B in +/? and cp/cp VSMCs, as well as activation of these enzymes following activation of the cAMP-protein kinase A signaling cascade, were not different. Our data are consistent with an increased role for PDE3 in regulating cAMP-dependent signaling in cp/cp VSMCs and identify PDE3 as a cellular activity potentially responsible for the phenotype of cp/cp VSMCs.

  1. 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

  2. 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

  3. 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.

  4. Effects of Incretin-Based Therapies on Neuro-Cardiovascular Dynamic Changes Induced by High Fat Diet in Rats.

    Directory of Open Access Journals (Sweden)

    Silvio Rodrigues Marques-Neto

    Full Text Available Obesity promotes cardiac and cerebral microcirculatory dysfunction that could be improved by incretin-based therapies. However, the effects of this class of compounds on neuro-cardiovascular system damage induced by high fat diet remain unclear. The aim of this study was to investigate the effects of incretin-based therapies on neuro-cardiovascular dysfunction induced by high fat diet in Wistar rats.We have evaluated fasting glucose levels and insulin resistance, heart rate variability quantified on time and frequency domains, cerebral microcirculation by intravital microscopy, mean arterial blood pressure, ventricular function and mitochondrial swelling. High fat diet worsened biometric and metabolic parameters and promoted deleterious effects on autonomic, myocardial and haemodynamic parameters, decreased capillary diameters and increased functional capillary density in the brain. Biometric and metabolic parameters were better improved by glucagon like peptide-1 (GLP-1 compared with dipeptdyl peptidase-4 (DPP-4 inhibitor. On the other hand, both GLP-1 agonist and DPP-4 inhibitor reversed the deleterious effects of high fat diet on autonomic, myocardial, haemodynamic and cerebral microvascular parameters. GLP-1 agonist and DPP-4 inhibitor therapy also increased mitochondrial permeability transition pore resistance in brain and heart tissues of rats subjected to high fat diet.Incretin-based therapies improve deleterious cardiovascular effects induced by high fat diet and may have important contributions on the interplay between neuro-cardiovascular dynamic controls through mitochondrial dysfunction associated to metabolic disorders.

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

    Directory of Open Access Journals (Sweden)

    Nunes ADC

    2014-07-01

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

  6. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    profiling of mammalian neural cells using direct analysis by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). MALDI-MS analysis is rapid, sensitive, robust, and specific for large biomolecules in complex matrices. Here, we describe a newly developed...... and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different....... Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular...

  7. 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 dis

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

    Directory of Open Access Journals (Sweden)

    Ricci NA

    2014-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Om Prakash Singh

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    This paper leads to developing a Labview based ECG patient monitoring system for cardiovascular patient using Simple Mail Transfer Protocol technology. The designed device has been divided into three parts. First part is ECG amplifier circuit, built using instrumentation amplifier (AD620) followed by signal conditioning circuit with the operation amplifier (lm741). Secondly, the DAQ card is used to convert the analog signal into digital form for the further process. Furthermore, the data has been processed in Labview where the digital filter techniques have been implemented to remove the noise from the acquired signal. After processing, the algorithm was developed to calculate the heart rate and to analyze the arrhythmia condition. Finally, SMTP technology has been added in our work to make device more communicative and much more cost-effective solution in telemedicine technology which has been key-problem to realize the telediagnosis and monitoring of ECG signals. The technology also can be easily implemented over already existing Internet. PMID:27006940

  11. Effect of goal attainment theory based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: Randomized study.

    Science.gov (United States)

    Park, Moonkyoung; Song, Rhayun; Jeong, Jin-Ok

    2017-02-24

    Effect of goal-attainment-theory-based education program on cardiovascular risks, behavioral modification, and quality of life among patients with first episode of acute myocardial infarction: randomized study BACKGROUND: The behavioral modification strategies should be explored at the time of admission to lead the maximum effect of cardiovascular risk management.

  12. 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 (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.

  13. Risk of hospitalization for acute cardiovascular events among subjects with lower urinary tract symptoms: a nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Huey-Juan Lin

    Full Text Available BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS have been reported to be associated with metabolic syndrome and may predispose subjects to cardiovascular disease. The magnitude of the impact on the medical care remains to be elucidated. Based on a population-based claims dataset in Taiwan, we explored the association between LUTS and the risk of subsequent hospitalization for acute cardiovascular events. MATERIALS AND METHODS: Among a representative sample of one million subjects from nationwide health insurance enrollees, subjects with codes of LUTS in service claims and without previous cardiovascular diseases including stroke were compared with age- and sex-matched non-LUTS subjects in subsequent hospitalization for acute coronary syndrome or stroke from the recruited date (between 2001-2004 to 2009. The risk of outcomes was assessed with Kaplan-Meier curves and the impact of LUTS was estimated with Poison regression analysis and Cox proportional hazards models. RESULTS: We included 4,553 LUTS subjects and 22,765 matched non-LUTS subjects, with a mean age of 47 years and 43% of men. Hypertension, diabetes, and hyperlipidemia were more prevalent in the LUTS group. The incidence rate of the composite endpoint was significantly higher in the LUTS group than in the non-LUTS group (5.4/1000 vs. 4.0/1000 person-years. The difference mainly derived from stroke rather than acute coronary syndrome. After adjusting for age, sex, diabetes, hypertension, and hyperlipidemia in multivariable analysis, LUTS remained a significant predictor (hazard ratio, 1.29; 95% confidence incidence, 1.06-1.50. CONCLUSION: Subjects free of cardiovascular disease and presenting with LUTS are at risk of subsequent hospitalization for acute cardiovascular events, mainly stroke. The information might prompt practitioners encountering such patients to undergo appropriate diagnostic and preventive measures.

  14. 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.

  15. An ImageJ based measurement setup for automated phenotyping of plants

    NARCIS (Netherlands)

    Kokorian, J.; Polder, G.; Keurentjes, J.J.B.; Vreugdenhil, D.; Olortegui Guzman, M.C.

    2010-01-01

    The objective of plant phenotyping studies is to understand the relationship between a plant’s genotype and phenotype. In our study we focus on the leaf morphology of Arabidopsis seedlings. Our experimental setup consists of a table of 0.9 m × 3.8 m with a matrix of about 1500 small cubes of rockwoo

  16. Increased risk of cardiovascular events in patients with herpes zoster: a population-based study.

    Science.gov (United States)

    Wu, Po-yuan; Lin, Cheng-Li; Sung, Fung-Chang; Chou, Tzu-Chieh; Lee, Yuan-Teh

    2014-05-01

    The association between herpes zoster and cardiovascular complications remains vague with limited study on the association between these two disorders. This study evaluated the risk of cardiovascular diseases in patients with herpes zoster. From insurance claims data of Taiwan, 19,483 patients with herpes zoster diagnosed in 1998-2008 and 77,932 subjects without herpes zoster were identified in this study. Both cohorts were followed up until the end of 2010 to measure the incidence of arrhythmia and coronary artery disease. The incidence rate ratio and adjusted hazard ratio (HR) of the cardiovascular complications with 95% confidence interval (CI) were estimated. The incidence of arrhythmia was 1.17-fold greater in the herpes zoster cohort than in the non-herpes zoster cohort (13.2 vs. 11.3 per 1,000 person-years), with an adjusted HR of 1.16 (P herpes zoster cohort was 1.16-fold higher than that in the non-herpes zoster cohort (9.02 vs. 7.83 per 1,000 person-years), with an adjusted HR of 1.11 (P herpes zoster diagnosis. The risk measured for these disorders declined over time. Comorbidities of hypertension, diabetes, and hyperlipidemia also contributed to these cardiovascular disorders with greater extent. It is concluded that the contribution of herpes zoster to the risk of arrhythmia and cardiovascular diseases is less strong than that of hypertension, diabetes, and hyperlipidemia.

  17. Herb-drug Interactions: An insight into cardiovascular diseases based on case reports.

    Science.gov (United States)

    Campos, Maria; Batista, C; Jesus, N R; Silva, C M; Silva, T P

    2016-10-07

    Cardiovascular patients frequently use herbal medicinal products, in order to contribute to the improvement of their chronic condition without medical intervention. However, they are likely to suffer from adverse effects from natural products and herb-drug interactions. This work aimed to alert cardiovascular patients and healthcare providers of the potential of occurrence of herb-drug interactions with cardiovascular therapy. Information obtained from the campaign "Aprender Saúde Entre as Plantas e os Medicamentos", carried out by the Observatory of Herb-Drug Interactions (www.oipm.uc.pt), was accessed in order to exemplify some selected interactions. From data received during the campaign, it was highlighted the prevalence of certain natural products particularly goji berries, green tea, mangosteen and rooibos that have significant cardiovascular effects. For this reason their intake should be carefully monitored in cardiovascular patients. This prevalence of use suggests a pattern in their use in Portugal. The ending results also indicate that there is still a lack of knowledge about the possible risks of herbal products, which may adversely affect the health of any patient. Thus becomes clear the value of the role of health professionals in the screening of such interactions.

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

    Science.gov (United States)

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

    2016-05-01

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

  19. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.

    Directory of Open Access Journals (Sweden)

    Kjell Petersen

    Full Text Available A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.

  20. ECG-based gating in ultra high field cardiovascular magnetic resonance using an independent component analysis approach

    OpenAIRE

    Krug, Johannes W; Rose, Georg; Clifford, Gari D.; Oster, Julien

    2013-01-01

    Background In Cardiovascular Magnetic Resonance (CMR), the synchronization of image acquisition with heart motion is performed in clinical practice by processing the electrocardiogram (ECG). The ECG-based synchronization is well established for MR scanners with magnetic fields up to 3 T. However, this technique is prone to errors in ultra high field environments, e.g. in 7 T MR scanners as used in research applications. The high magnetic fields cause severe magnetohydrodynamic (MHD) effects w...

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

    Directory of Open Access Journals (Sweden)

    Julio C. Acosta Navarro

    2010-01-01

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

  2. AFM study of the thrombogenicity of carbon-based coatings for cardiovascular applications

    Energy Technology Data Exchange (ETDEWEB)

    Karagkiozaki, V. [Department of Physics, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece); AHEPA Hospital, 1st Cardiology Department, Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece); Logothetidis, S. [Department of Physics, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece)], E-mail: logot@auth.gr; Laskarakis, A. [Department of Physics, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece); Giannoglou, G. [AHEPA Hospital, 1st Cardiology Department, Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece); Lousinian, S. [Department of Physics, Laboratory for Thin Films-Nanosystems and Nanometrology (LTFN), Aristotle University of Thessaloniki, Thessaloniki GR-54124 (Greece)

    2008-08-25

    The new nanotechnologies in biomaterials for cardiovascular applications target at surface alterations for prevention of platelets aggregation and subsequent clotting as their usual failure arises from thrombogenicity. Knowledge of structural properties of platelets during their adhesion on nanostructure materials is required to obtain a comprehensive understanding of their activation and the conventional imaging tools require special preparation of the samples and does not guarantee the viability of the cells. Thus, in this study, the atomic force microscope (AFM) which is a non-destructive and nanoscale precision technique is implemented for the study of platelets' adhesion onto amorphous hydrogenated carbon (a-C:H) thin films and a methodology is developed. Carbon-based thin films grown by magnetron sputtering under different deposition conditions are considered to meet the requirements for biomedical applications and were selected as well-characterized, case study materials. Platelet rich plasma drawn from healthy donors was used for the study of platelets adhesion onto the a-C:H films. The fourier transform IR phase modulated spectroscopic ellipsometry (FTIRSE) (900-3500 cm{sup -1}) being a powerful, non-destructive, optical technique was used for the investigation of bonding structure of the adherent platelets onto the a-C:H materials and the contribution of the different vibration bands of the platelet bonding groups was shown and discussed. The effect of nanostructure, surface properties and wettability of the carbon thin films on their thrombogenic potential was verified and it was found that the different deposition conditions determine their structural, surface and biological properties. Thus, the tailoring of surface properties of biomaterials and the informative study of platelets-nanomaterials interactions with AFM and FTIRSE will revolutionize the development of less thrombogenic biomaterials.

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

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    Wen-Hsien Lee

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

  4. Evaluation of cardiovascular biomarkers In HIV-infected patients switching to abacavir or tenofovir based therapy

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    Langdahl Bente L

    2011-10-01

    Full Text Available Abstract Background Our objective was to evaluate and compare the effect of abacavir on levels of biomarkers associated with cardiovascular risk. Methods In an open-label randomized trial, HIV-infected patients were randomized 1:1 to switch from zidovudine/lamivudine to abacavir/lamivudine or tenofovir/emtricitabine. In the present analysis, we measured levels of interleukin-6 (IL-6, high-sensitivity C-reactive protein (hs-CRP, soluble intercellular adhesion molecule-1 (sICAM-1, soluble vascular adhesion molecule-1 (sVCAM-1, E-selectin, and myeloperoxidase (MPO at baseline and 4, 12, and 48 weeks after randomization. D-dimer and fasting lipids were measured at baseline and weeks 12 and 48. Levels of biomarkers at all time points and changes from baseline were compared across study arms using Wilcoxon rank sum test. Results Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. Levels of E-selectin (P = 0.004 and sVCAM-1 (P = 0.041 increased transiently from baseline to week 4 in the abacavir arm compared with the tenofovir arm, but no long-term increases were detected. We found no significant differences between study arms in the levels or changes in the levels of sICAM-1, MPO, d-dimer, IL-6, or hs-CRP. Levels of total cholesterol and high density lipoprotein (HDL increased in the abacavir arm relative to the tenofovir arm, but no difference was found in total cholesterol/HDL ratio. Conclusion In patients randomized to abacavir-based HIV-treatment transient increases were seen in the plasma levels of E-selectin and sVCAM-1 compared with treatment with tenofovir, but no difference between study arms was found in other biomarkers associated with endothelial dysfunction, inflammation, or coagulation. The clinical significance of these findings is uncertain. Trial Regestration Clinicaltrials.gov identifier: NCT00647244.

  5. 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…

  6. Risk of cardiovascular events after initiation of long-acting bronchodilators in patients with chronic obstructive lung disease: A population-based study

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    Almotasembellah Aljaafareh

    2016-09-01

    Full Text Available Objectives: Long-acting bronchodilators are mainstay treatment for moderate to severe chronic obstructive pulmonary disease. A growing body of evidence indicates an increased risk of cardiovascular events upon initiation of these medications. We hypothesize that this risk is higher in patients with chronic obstructive pulmonary disease who had a preexisting cardiovascular disease regardless of receipt of any cardiovascular medication. Methods: A retrospective cohort of patients with a diagnosis of chronic obstructive pulmonary disease based on two outpatient visits or one inpatient visit for chronic obstructive pulmonary disease (International Classification of Diseases, 9th Edition, Clinical Modification codes 491.x, 492.x, 496 in any year between 2001 and 2012 from a commercial insurance database. We then selected those initiating long-acting bronchodilator treatments between April 2001 and September 2012. Each patient had a 1 year look back period to determine history of cardiovascular disease or cardiovascular disease treatment from the time of first prescription of long-acting beta agonist, long-acting muscarinic antagonist, or long-acting beta agonist combined with inhaled corticosteroids. Patients were followed for 90 days for hospitalizations or emergency department visits for cardiovascular event. The cohort was divided into four groups based on the presence of cardiovascular disease (including ischemic heart disease, hypertension, ischemic stroke, heart failure, tachyarrhythmias and artery disease based on International Classification of Diseases, 9th Edition, Clinical Modification codes and cardiovascular disease treatment defined as acetylsalicylic acid, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, antiplatelet, anticoagulants, calcium channel blockers, nitrate, digoxin, diuretics, antiarrhythmics or statins. Odds of emergency department visit or hospitalization in the 90 days after

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

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    Julio Fernandez-Mendoza

    2016-12-01

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

  8. Phenotyping chronic pelvic pain based on latent class modeling of physical examination.

    Science.gov (United States)

    Fenton, B W; Grey, S F; Reichenbach, M; McCarroll, M; Von Gruenigen, V

    2013-01-01

    Introduction. Defining clinical phenotypes based on physical examination is required for clarifying heterogeneous disorders such as chronic pelvic pain (CPP). The objective of this study was to determine the number of classes within 4 examinable regions and then establish threshold and optimal exam criteria for the classes discovered. Methods. A total of 476 patients meeting the criteria for CPP were examined using pain pressure threshold (PPT) algometry and standardized numeric scale (NRS) pain ratings at 30 distinct sites over 4 pelvic regions. Exploratory factor analysis, latent profile analysis, and ROC curves were then used to identify classes, optimal examination points, and threshold scores. Results. Latent profile analysis produced two classes for each region: high and low pain groups. The optimal examination sites (and high pain minimum thresholds) were for the abdominal wall region: the pair at the midabdomen (PPT threshold depression of > 2); vulvar vestibule region: 10:00 position (NRS > 2); pelvic floor region: puborectalis (combined NRS > 6); vaginal apex region: uterosacral ligaments (combined NRS > 8). Conclusion. Physical examination scores of patients with CPP are best categorized into two classes: high pain and low pain. Standardization of the physical examination in CPP provides both researchers and general gynecologists with a validated technique.

  9. Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae.

    Science.gov (United States)

    Chea, Nora; Bulens, Sandra N; Kongphet-Tran, Thiphasone; Lynfield, Ruth; Shaw, Kristin M; Vagnone, Paula Snippes; Kainer, Marion A; Muleta, Daniel B; Wilson, Lucy; Vaeth, Elisabeth; Dumyati, Ghinwa; Concannon, Cathleen; Phipps, Erin C; Culbreath, Karissa; Janelle, Sarah J; Bamberg, Wendy M; Guh, Alice Y; Limbago, Brandi; Kallen, Alexander J

    2015-09-01

    Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non-CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase-producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

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

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    Tözeren Aydın

    2007-09-01

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

  11. Development of a rapid cell-fusion-based phenotypic HIV-1 tropism assay

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    Phairote Teeranaipong

    2013-09-01

    Full Text Available Introduction: A dual split reporter protein system (DSP, recombining Renilla luciferase (RL and green fluorescent protein (GFP split into two different constructs (DSP1–7 and DSP8–11, was adapted to create a novel rapid phenotypic tropism assay (PTA for HIV-1 infection (DSP-Pheno. Methods: DSP1–7 was stably expressed in the glioma-derived NP-2 cell lines, which expressed CD4/CXCR4 (N4X4 or CD4/CCR5 (N4R5, respectively. An expression vector with DSP8–11 (pRE11 was constructed. The HIV-1 envelope genes were subcloned in pRE11 (pRE11-env and transfected into 293FT cells. Transfected 293FT cells were incubated with the indicator cell lines independently. In developing the assay, we selected the DSP1–7-positive clones that showed the highest GFP activity after complementation with DSP8–11. These cell lines, designated N4R5-DSP1–7, N4X4-DSP1–7 were used for subsequent assays. Results: The env gene from the reference strains (BaL for R5 virus, NL4-3 for X4 virus, SF2 for dual tropic virus subcloned in pRE11 and tested, was concordant with the expected co-receptor usage. Assay results were available in two ways (RL or GFP. The assay sensitivity by RL activity was comparable with those of the published phenotypic assays using pseudovirus. The shortest turnaround time was 5 days after obtaining the patient's plasma. All clinical samples gave positive RL signals on R5 indicator cells in the fusion assay. Median RLU value of the low CD4 group was significantly higher on X4 indicator cells and suggested the presence of more dual or X4 tropic viruses in this group of patients. Comparison of representative samples with Geno2Pheno [co-receptor] assay was concordant. Conclusions: A new cell-fusion-based, high-throughput PTA for HIV-1, which would be suitable for in-house studies, was developed. Equipped with two-way reporter system, RL and GFP, DSP-Pheno is a sensitive test with short turnaround time. Although maintenance of cell lines and

  12. Cardiovascular disease risk factors in a population-based sample of Norwegian children and adolescents

    DEFF Research Database (Denmark)

    Steene-Johannessen, Jostein; Kolle, Elin; Anderssen, Sigmund Alfred

    2009-01-01

    Objective. The objective of the study was to describe the distribution of cardiovascular disease (CVD) risk factors, and to evaluate the extent of clustering of CVD risk factors in Norwegian children and adolescents. Material and methods. A randomly selected cohort of 9-year-olds and 15-year...

  13. Measures of overweight and obesity and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Sehestedt, Thomas Berend; Hansen, Tine W; Olsen, Michael H

    2010-01-01

    Although overweight and obesity are associated with cardiovascular disease (CVD), it is unclear which clinical measure of overweight and obesity is the strongest predictor of CVD, and it is unclear whether the various measures of overweight and obesity are indeed independent predictors of CVD....

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    Parvizi, Mojtaba

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  18. 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

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

    Science.gov (United States)

    Miranda, Andreia Machado; Steluti, Josiane; Fisberg, Regina Mara; Marchioni, Dirce Maria

    2017-01-01

    Epidemiological studies have examined the effect of coffee intake on cardiovascular disease, but the benefits and risks for the cardiovascular system remain controversial. Our objective was to evaluate the association between coffee consumption and its polyphenols on cardiovascular risk factors. Data came from the “Health Survey of São Paulo (ISA-Capital)” among 557 individuals, in São Paulo, Brazil. Diet was assessed by two 24-h dietary recalls. Coffee consumption was categorized into food consumption data with the Phenol-Explorer database. Multiple logistic regression models were used to assess the associations between cardiovascular risk factors (blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, fasting glucose, and homocysteine) and usual coffee intake. The odds were lower among individuals who drank 1–3 cups of coffee/day to elevated systolic blood pressure (SBP) (Odds Ratio (OR) = 0.45; 95% Confidence Interval (95% CI): 0.26, 0.78), elevated diastolic blood pressure (DBP) (OR = 0.44; 95% CI: 0.20, 0.98), and hyperhomocysteinemia (OR = 0.32; 95% CI: 0.11, 0.93). Furthermore, significant inverse associations were also observed between moderate intake of coffee polyphenols and elevated SBP (OR = 0.46; 95% CI: 0.24, 0.87), elevated DBP (OR = 0.51; 95% CI: 0.26, 0.98), and hyperhomocysteinemia (OR = 0.29; 95% CI: 0.11, 0.78). In conclusion, coffee intake of 1–3 cups/day and its polyphenols were associated with lower odds of elevated SBP, DBP, and hyperhomocysteinemia. Thus, the moderate consumption of coffee, a polyphenol-rich beverage, could exert a protective effect against some cardiovascular risk factors. PMID:28335422

  20. Adipocytokines, C-reactive protein, and cardiovascular disease: a population-based prospective study.

    Directory of Open Access Journals (Sweden)

    Ekim Seven

    Full Text Available Being overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD is still unclear.To investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP was used as a proxy for interleukin-6.Prospective population-based study of 6.502 participants, 51.9% women, aged 30-60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke.During the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI, total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87-1.08] per SD increase, P = 0.60 nor leptin (0.97 [0.85-1.12] per SD increase, P = 0.70 predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07-1.35] per SD increase, P = 0.002. Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29-72.In this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their

  1. Systematic construction of a conceptual minimal model of plasma cholesterol levels based on knockout mouse phenotypes

    NARCIS (Netherlands)

    Pas, N.C.A. van de; Soffers, A.E.M.F.; Freidig, A.P.; Ommen, B. van; Woutersen, R.A.; Rietjens, I.M.C.M.; Graaf, A.A. de

    2010-01-01

    Elevated plasma cholesterol, a well-known risk factor for cardiovascular diseases, is the result of the activity of many genes and their encoded proteins in a complex physiological network. We aim to develop a minimal kinetic computational model for predicting plasma cholesterol levels. To define th

  2. Increased Risk of Chronic Kidney Disease in Rheumatoid Arthritis Associated with Cardiovascular Complications - A National Population-Based Cohort Study.

    Directory of Open Access Journals (Sweden)

    Hsien-Yi Chiu

    Full Text Available There have been few large population-based studies of the association between rheumatoid arthritis (RA and chronic kidney disease (CKD and glomerulonephritis. This nationwide cohort study investigated the risks of developing CKD and glomerulonephritis in patients with RA, and the associated risks for cardiovascular complications.From the Taiwan National Health Insurance Research Database, we identified a study cohort of 12,579 patients with RA and randomly selected 37,737 subjects without RA as a control cohort. Each subject was individually followed for up for 5 years, and the risk of CKD was analyzed using Cox proportional hazards regression models.During the follow-up period, after adjusting for traditional cardiovascular risk factors RA was independently associated with a significantly increased risk of CKD (adjusted hazard ratio [aHR] 1.31; 95% confidence interval [CI] 1.23-1.40 and glomerulonephritis (aHR 1.55; 95% CI 1.37-1.76. Increased risk of CKD was also associated with the use of non-steroidal anti-inflammatory drugs, cyclosporine, glucocorticoids, mycophenolate mofetil, and cyclophosphamide. Patients with comorbidities had even greater increased risk of CKD. Moreover, RA patients with concurrent CKD had significantly higher likelihood of developing ischemic heart disease and stroke.RA patients had higher risk of developing CKD and glomerulonephritis, independent of traditional cardiovascular risk factors. Their increased risk of CKD may be attributed to glomerulonephritis, chronic inflammation, comorbidities, and renal toxicity of antirheumatic drugs. Careful monitoring of renal function in RA patients and tight control of their comorbid diseases and cardiovascular risk factors are warranted.

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

    Science.gov (United States)

    Green, Jason M; Harnsomburana, Jaturon; Schaeffer, Mary L; Lawrence, Carolyn J; Shyu, Chi-Ren

    2011-01-01

    Model Organism Databases, including the various plant genome databases, collect and enable access to 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 a variety of basic browsing and search capabilities are available to allow researchers to query and peruse the names and attributes of phenotypic data, next-generation search mechanisms that allow querying and ranking of text descriptions are much less common. In addition, the plant community needs an innovative way to leverage the existing links in these databases to search groups of text descriptions simultaneously. Furthermore, though much time and effort have been afforded to the development of plant-related ontologies, the knowledge embedded in these ontologies remains largely unused in available plant search mechanisms. Addressing these issues, we have developed a unique search engine for mutant phenotypes from MaizeGDB. This advanced search mechanism integrates various text description sources in MaizeGDB to aid a user in retrieving desired mutant phenotype information. Currently, descriptions of mutant phenotypes, loci and gene products are utilized collectively for each search, though expansion of the search mechanism to include other sources is straightforward. The retrieval engine, to our knowledge, is the first engine to exploit the content and structure of available domain ontologies, currently the Plant and Gene Ontologies, to expand and enrich retrieval results in major plant genomic databases. Database URL: http:www.PhenomicsWorld.org/QBTA.php.

  4. Neuroanatomical phenotype of Klinefelter syndrome in childhood: a voxel-based morphometry study.

    Science.gov (United States)

    Bryant, Daniel M; Hoeft, Fumiko; Lai, Song; Lackey, John; Roeltgen, David; Ross, Judith; Reiss, Allan L

    2011-05-04

    Klinefelter syndrome (KS) is a genetic disorder characterized by a supernumerary X chromosome. As such, KS offers a naturally occurring human model for the study of both X-chromosome gene expression and androgen on brain development. Previous neuroimaging studies have revealed neuroanatomical variations associated with KS, but have differed widely with respect to subject inclusion criteria, including mosaicism, pubertal status, and history of testosterone replacement therapy (TRT), all factors likely to influence neurodevelopment. We conducted a voxel-based morphometry study of regional gray and white matter (GM and WM, respectively) volumes in 31 KS males (mean age, 9.69 ± 1.70 years) and 36 typically developing (TD) male controls (10.99 ± 1.72 years). None of the participants with KS had received TRT, and all were prepubertal and had nonmosaic 47,XXY karyotypes. After controlling for age, males with KS showed trends (0.05 < p < 0.10) for significantly reduced total gray matter volume (TGMV) and total white matter volume (TWMV), relative to TD males. After controlling for TGMV and age, the KS group had significantly increased sensorimotor and parietal-occipital GM and significantly reduced amygdalar, hippocampal, insular, temporal, and inferior frontal GM relative to TD controls. After controlling for TWMV and age, the KS group had significantly increased left parietal WM as well as significantly reduced frontal and temporal WM. These findings are indicative of a characteristic prepubertal neuroanatomical phenotype that may be associated with cognitive-behavioral features of KS. This work offers new insight into the relationships among X-chromosome gene expression, neuroanatomy, and cognitive-behavioral functions impaired in KS, including language and attention.

  5. Cardiovascular Endocrinology : The impact of the growth hormone (GH) axis / insulin-like growth factor (IGF) system on the expression of an atherogenic lipid and pro-diabetic phenotype

    NARCIS (Netherlands)

    Twickler, Theodorus Bartholomeus

    2003-01-01

    Cardiovascular disease due to premature atherosclerotic disease is the major cause of death in Western Societies. Key factors in the origin of premature atherosclerotic disease are lipid disturbances. Although classic lipid parameters predict cardiovascular disease in a huge amount, novel factors in

  6. Family-Based Rare Variant Association Analysis: A Fast and Efficient Method of Multivariate Phenotype Association Analysis.

    Science.gov (United States)

    Wang, Longfei; Lee, Sungyoung; Gim, Jungsoo; Qiao, Dandi; Cho, Michael; Elston, Robert C; Silverman, Edwin K; Won, Sungho

    2016-09-01

    Family-based designs have been repeatedly shown to be powerful in detecting the significant rare variants associated with human diseases. Furthermore, human diseases are often defined by the outcomes of multiple phenotypes, and thus we expect multivariate family-based analyses may be very efficient in detecting associations with rare variants. However, few statistical methods implementing this strategy have been developed for family-based designs. In this report, we describe one such implementation: the multivariate family-based rare variant association tool (mFARVAT). mFARVAT is a quasi-likelihood-based score test for rare variant association analysis with multiple phenotypes, and tests both homogeneous and heterogeneous effects of each variant on multiple phenotypes. Simulation results show that the proposed method is generally robust and efficient for various disease models, and we identify some promising candidate genes associated with chronic obstructive pulmonary disease. The software of mFARVAT is freely available at http://healthstat.snu.ac.kr/software/mfarvat/, implemented in C++ and supported on Linux and MS Windows.

  7. 5 Long-term acromegaly and associated cardiovascular complications: a case-based review.

    Science.gov (United States)

    Colao, Annamaria

    2009-12-01

    Because growth hormone and IGF-1 both have regulatory roles in the cardiovascular system, patients with acromegaly often present with abnormalities of heart structure and function and the vascular system, which if left unmanaged can reduce life expectancy. Early symptoms of acromegalic cardiomyopathy (hyperkinetic syndrome) can be characterized by cardiac hypertrophy, increased heart rate, and increased systolic output. When left untreated, more pronounced hypertrophy, signs of diastolic dysfunction and insufficient systolic function on exertion arise, and can lead to systolic dysfunction at rest, and eventually heart failure with signs of dilative cardiomyopathy. Increasingly, evidence suggests that early diagnosis and treatment of acromegaly (before the age of 40 years) can help prevent the progression of cardiovascular disease, improve quality of life, and reduce the risk of premature mortality. This review focuses on management strategies for newly diagnosed patients with acromegaly and evidence of cardiovascular disease. The roles of surgery and medical treatment are discussed in the context of using optimal treatment strategies to help reverse cardiac hypertrophy and normalize other cardiac risk factors.

  8. Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases.

    Science.gov (United States)

    Gormaz, Juan Guillermo; Valls, Nicolas; Sotomayor, Camilo; Turner, Thomas; Rodrigo, Ramón

    2016-01-01

    Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. It is widely accepted that oxidative stress plays a key role in their development and progression; hence oxidative damage might be abrogated by antioxidants. Polyphenols are phytochemicals showing extensively studied antioxidant properties in-vivo. Most representative sources of these compounds include fruits, greens, nuts, herbs, cocoa, tea and coffee. Epidemiological evidence suggests an association between the consumption of polyphenol-rich vegetables and the reduction of cardiovascular disease prevalence. This fact could be related to the anti-inflammatory, antithrombotic and vasodilatory effects of polyphenols. Even though these biological effects could be mainly attributed to the antioxidant activity of polyphenols, other pharmacological mechanisms should also be considered. The latter could comprise direct anti-inflammatory effects, modulation of intracellular signaling and gene expression, improvement of nitric oxide homeostasis, as well as platelet antiaggregation. However, it is noticeable that protocols of interventions to evaluate the properties of polyphenols have failed to show the same positive results reported from observational studies. At present, a controversy exists regarding the actual effectiveness of polyphenols in preventing cardiovascular diseases. Therefore, an improvement of the available knowledge about polyphenol pharmacokinetics, together with a better understanding of the mechanisms of action of these compounds, could be of great benefit. Thus, a rational support for the development of interventional designs could provide reliable evidence on the actual role of polyphenols in CVD prevention.

  9. Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality improvement cardiovascular care Kwara-I (QUICK-I)

    NARCIS (Netherlands)

    M. Hendriks (Maaike); L.M. Brewster (Lizzy); F.W.N.M. Wit (Ferdinand); O.A. Bolarinwa (Oladimeji Akeem); A.O. Odusola (Aina Olufemi); E. Orlewska (William Ken); N. Bindraban (Navin); A. Vollaard (Albert); S. Alli (Shade); P. Adenusi (Peju); K. Agbede (Kayode); T.M. Akande (Tanimola); J. Lange (Joep); C. Schultsz (Constance)

    2011-01-01

    textabstractBackground: Cardiovascular diseases (CVD) are a leading contributor to the burden of disease in low- and middle-income countries. Guidelines for CVD prevention care in low resource settings have been developed but little information is available on strategies to implement this care. A co

  10. Cardiovascular disease prevention in rural Nigeria in the context of a community based health insurance scheme: QUality Improvement Cardiovascular care Kwara-I (QUICK-I)

    NARCIS (Netherlands)

    M. Hendriks; L. Brewster; F. Wit; O.A. Bolarinwa; A.O. Odusola; W. Redekop; N. Bindraban; A. Vollaard; S. Alli; P. Adenusi; K. Agbede; T. Akande; J. de Lange; C. Schultsz

    2011-01-01

    Background: Cardiovascular diseases (CVD) are a leading contributor to the burden of disease in low- and middle-income countries. Guidelines for CVD prevention care in low resource settings have been developed but little information is available on strategies to implement this care. A community heal

  11. 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.

  12. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  14. Characterization of Lactobacillus from Algerian goat's milk based on phenotypic, 16S rDNA sequencing and their technological properties

    Directory of Open Access Journals (Sweden)

    Ahmed Marroki

    2011-03-01

    Full Text Available Nineteen strains of Lactobacillus isolated from goat's milk from farms in north-west of Algeria were characterized. Isolates were identified by phenotypic, physiological and genotypic methods and some of their important technological properties were studied. Phenotypic characterization was carried out by studying physiological, morphological characteristics and carbohydrate fermentation patterns using API 50 CHL system. Isolates were also characterized by partial 16S rDNA sequencing. Results obtained with phenotypic methods were correlated with the genotypic characterization and 13 isolates were identified as L. plantarum, two isolates as L. rhamnosus and one isolate as L. fermentum. Three isolates identified as L. plantarum by phenotypic characterization were found to be L. pentosus by the genotypic method. A large diversity in technological properties (acid production in skim milk, exopolysaccharide production, aminopeptidase activity, antibacterial activity and antibiotic susceptibility was observed. Based on these results, two strains of L. plantarum (LbMS16 and LbMS21 and one strain of L. rhamnosus (LbMF25 have been tentatively selected for use as starter cultures in the manufacture of artisanal fermented dairy products in Algeria.

  15. Introduction: Cardiovascular physics.

    Science.gov (United States)

    Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert

    2007-03-01

    The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

  16. 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...

  17. Cardiovascular Disease Mortality and Its Association With Socioeconomic Status: Findings From a Population-based Cohort Study in Rural Vietnam, 1999–2003

    OpenAIRE

    Van Minh, Hoang; Lan Huong, Dao; Wall, Stig; Byass, Peter; Thi Kim Chuc, Nguyen

    2006-01-01

    Introduction Cardiovascular disease is an emerging epidemic in Vietnam, but because cause of death and other routine data are not widely available, it is difficult to characterize community-based disease patterns. Using 5-year data from an ongoing cause-specific mortality study conducted within a demographic surveillance system in Vietnam's Bavi district, this article estimates the rates of adult cardiovascular disease mortality in relation to the mortality rates of other noncommunicable dise...

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Anida Sarajlić

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    ischaemic heart disease and nonfatal stroke, amounted to 222 cases. In Cox proportional-hazard models, adjusted for age, sex, smoking habit, total cholesterol, waist circumference, levels of triglycerides and high-density lipoprotein-cholesterol, systolic and diastolic blood pressures, physical activity......BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  2. 青少年高甘油三酯血症-腰围表型与心血管危险因素聚集相关%Relationship between hypertriglyceridemic-waist phenotype and clustering of cardiovascular risk factors in adolescents

    Institute of Scientific and Technical Information of China (English)

    马春明; 陆强; 刘晓丽; 高国芹; 王锐; 尹福在; 刘悦; 韩改玲; 王翠娟; 鲁娜

    2015-01-01

    Objective The aim of the study was to explore the relationship between hypertriglyceridemic-waist(HTWC) phenotype and clustering of cardiovascular risk factors in adolescents. Methods A cross-sectional study was conducted in 3 136 Han adolescents aged 13-17 years in Qinhuangdao. The HTWC phenotype was defined as serum triglyceride concentrations ≥1. 47 mmol/ L and waist circumference ≥90 th percentile for age and sex. Results The prevalence of HTWC phenotype was 3. 3% . The prevalence of clustering of cardiovascular risk factors was 0. 4%in adolescents with normal waist circumference and serum triglyceride and 14. 7% in adolescents with HTWC phenotype. After adjustment for sex, age, body mass index, and family history of diabetes and hypertension, the prevalence of clustering of cardiovascular risk factors in adolescents with HTWC phenotype was 9. 286 fold(95% CI 3. 161-27. 282, P<0. 01) of that in adolescents with normal waist circumference and triglyceride. Conclusion There was a significant correlation between HTWC phenotype and clustering of cardiovascular risk factors, suggesting that this phenotype may be applied as a simple marker for identifying adolescents with clustering of cardiovascular risk factors.%目的:探讨高甘油三酯血症-腰围表型(HTWC)与心血管危险因素聚集的相关性。方法对秦皇岛地区一项3136名13~17岁汉族青少年作横断面调查。 HTWC 定义为腰围≥同年龄同性别青少年腰围的90百分位值且血甘油三酯≥1.47 mmol/ L 者。结果本调查人群中 HTWC 表型检出率为3.3%。甘油三酯和腰围正常组青少年心血管危险因素聚集者检出率为0.4%,而 HTWC 组青少年检出率为14.7%。校正性别、年龄、体重指数、糖尿病家族史和高血压家族史后,HTWC 组青少年心血管危险因素聚集检出率是甘油三酯和腰围正常组青少年的9.286(95% CI 3.161~27.282,P<0.01)倍。结论 HTWC 表型与青少年心血管危险因素聚集密切相

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

    Science.gov (United States)

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

    2015-01-01

    The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20–84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60–1.78; CVD: IRR = 1.61; 95%CI 1.47–1.76; AMI: IRR = 1.59; 95%CI 1.27–1.99; renal causes: IRR = 1.71; 95%CI 1.22–2.38). The impact of diabetes is greater in females than males for all causes (P = 0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males. PMID:25873959

  4. Multi-Parametric Profiling Network Based on Gene Expression and Phenotype Data: A Novel Approach to Developmental Neurotoxicity Testing

    Directory of Open Access Journals (Sweden)

    Hideko Sone

    2011-12-01

    Full Text Available The establishment of more efficient approaches for developmental neurotoxicity testing (DNT has been an emerging issue for children’s environmental health. Here we describe a systematic approach for DNT using the neuronal differentiation of mouse embryonic stem cells (mESCs as a model of fetal programming. During embryoid body (EB formation, mESCs were exposed to 12 chemicals for 24 h and then global gene expression profiling was performed using whole genome microarray analysis. Gene expression signatures for seven kinds of gene sets related to neuronal development and neuronal diseases were selected for further analysis. At the later stages of neuronal cell differentiation from EBs, neuronal phenotypic parameters were determined using a high-content image analyzer. Bayesian network analysis was then performed based on global gene expression and neuronal phenotypic data to generate comprehensive networks with a linkage between early events and later effects. Furthermore, the probability distribution values for the strength of the linkage between parameters in each network was calculated and then used in principal component analysis. The characterization of chemicals according to their neurotoxic potential reveals that the multi-parametric analysis based on phenotype and gene expression profiling during neuronal differentiation of mESCs can provide a useful tool to monitor fetal programming and to predict developmentally neurotoxic compounds.

  5. A Clustered Multiclass Likelihood-Ratio Ensemble Method for Family-Based Association Analysis Accounting for Phenotypic Heterogeneity.

    Science.gov (United States)

    Wen, Yalu; Lu, Qing

    2016-09-01

    Although compelling evidence suggests that the genetic etiology of complex diseases could be heterogeneous in subphenotype groups, little attention has been paid to phenotypic heterogeneity in genetic association analysis of complex diseases. Simply ignoring phenotypic heterogeneity in association analysis could result in attenuated estimates of genetic effects and low power of association tests if subphenotypes with similar clinical manifestations have heterogeneous underlying genetic etiologies. To facilitate the family-based association analysis allowing for phenotypic heterogeneity, we propose a clustered multiclass likelihood-ratio ensemble (CMLRE) method. The proposed method provides an alternative way to model the complex relationship between disease outcomes and genetic variants. It allows for heterogeneous genetic causes of disease subphenotypes and can be applied to various pedigree structures. Through simulations, we found CMLRE outperformed the commonly adopted strategies in a variety of underlying disease scenarios. We further applied CMLRE to a family-based dataset from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOC) to investigate the genetic variants and interactions predisposing to subphenotypes of oral clefts. The analysis suggested that two subphenotypes, nonsyndromic cleft lip without palate (CL) and cleft lip with palate (CLP), shared similar genetic etiologies, while cleft palate only (CP) had its own genetic mechanism. The analysis further revealed that rs10863790 (IRF6), rs7017252 (8q24), and rs7078160 (VAX1) were jointly associated with CL/CLP, while rs7969932 (TBK1), rs227731 (17q22), and rs2141765 (TBK1) jointly contributed to CP.

  6. Balancing benefits and risks in patients receiving incretin-based therapies: focus on cardiovascular and pancreatic side effects.

    Science.gov (United States)

    Haluzík, Martin; Mráz, Miloš; Svačina, Štěpán

    2014-12-01

    Incretin-based therapies either increase endogenous levels of glucagon-like peptide-1 by prolonging its half-life (DPP-4 inhibitors) or directly stimulate its receptor (glucagon-like peptide-1 analogues; GLP-1 RA). They are currently widely used for the treatment of patients with type 2 diabetes mellitus owing to good antidiabetic efficacy, low risk of hypoglycemia, and relatively few other side effects. They also offer potential additional benefits such as weight neutrality or weight loss, positive effects on blood pressure and lipid levels, and potential cardio- and neuroprotectivity. Some experimental and clinical studies have raised concerns with respect to potential cardiovascular and pancreatic side effects of these therapies such as increased risk of heart failure with DPP-4 inhibitors as well as acute pancreatitis and pancreatic cancer with both classes. The available data are at present not robust enough to enable firm conclusions regarding these potential associations. Nevertheless, some recent data suggest a possibility of slightly increased risk of acute pancreatitis with GLP-1 RAs while they do not indicate increased risk of pancreatic cancer. Ongoing cardiovascular outcome trials will shed more light on the possible cardioprotective effects of incretin-based therapies as well as on the possible interconnection of DPP-4 inhibitors and heart failure.

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

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    Thao T. Vo

    2012-01-01

    Full Text Available 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.

  8. Cardiovascular magnetic resonance imaging assessment of diastolic dysfunction in a population without heart disease: a gender-based study

    Energy Technology Data Exchange (ETDEWEB)

    Graca, Bruno; Donato, Paulo; Caseiro-Alves, Filipe [University of Coimbra, Medical Imaging Department, University Centre Hospitals of Coimbra, Faculty of Medicine, Coimbra (Portugal); Ferreira, Maria Joao [University of Coimbra, Cardiology Department, University Centre Hospitals of Coimbra, Faculty of Medicine, Coimbra (Portugal); Castelo-Branco, Miguel [University of Coimbra, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, Coimbra (Portugal)

    2014-01-15

    Asymptomatic left ventricular (LV) diastolic dysfunction is increasingly recognised as an important diagnosis. Our goal was to study the prevalence and gender differences in subclinical LV diastolic dysfunction, using cardiovascular magnetic resonance imaging (CMR) at 3 T. We prospectively studied 48 volunteers (19 male and 29 female, mean age 49 ± 7 years) with no evidence of cardiovascular disease. We used CMR to measure left atrium (LA) and LV volumes, LV peak filling rate and transmitral flow. The overall prevalence of LV diastolic dysfunction in our cohort varied between 20 % (based on evaluation of LV filing profiles) and 24 % (based on the evaluation of the transmitral flow). The prevalence of diastolic dysfunction was higher in men than in women, independently of the criteria used (P between 0.004 and 0.022). Indexed LV end-diastolic volume, indexed LV stroke volume, indexed LV mass, indexed LA minimum volume and indexed LA maximum volume were significantly greater in men than in women (P < 0.05). All the subjects had LV ejection fractions within the normal range. It is clinically feasible to study diastolic flow and LV filling with CMR. CMR detected diastolic dysfunction in asymptomatic men and women. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Silvia A. Marteau

    2001-02-01

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

  10. Phenotype-Based Genetic Association Studies (PGAS—Towards Understanding the Contribution of Common Genetic Variants to Schizophrenia Subphenotypes

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    Hannelore Ehrenreich

    2014-02-01

    Full Text Available Neuropsychiatric diseases ranging from schizophrenia to affective disorders and autism are heritable, highly complex and heterogeneous conditions, diagnosed purely clinically, with no supporting biomarkers or neuroimaging criteria. Relying on these “umbrella diagnoses”, genetic analyses, including genome-wide association studies (GWAS, were undertaken but failed to provide insight into the biological basis of these disorders. “Risk genotypes” of unknown significance with low odds ratios of mostly <1.2 were extracted and confirmed by including ever increasing numbers of individuals in large multicenter efforts. Facing these results, we have to hypothesize that thousands of genetic constellations in highly variable combinations with environmental co-factors can cause the individual disorder in the sense of a final common pathway. This would explain why the prevalence of mental diseases is so high and why mutations, including copy number variations, with a higher effect size than SNPs, constitute only a small part of variance. Elucidating the contribution of normal genetic variation to (disease phenotypes, and so re-defining disease entities, will be extremely labor-intense but crucial. We have termed this approach PGAS (“phenotype-based genetic association studies”. Ultimate goal is the definition of biological subgroups of mental diseases. For that purpose, the GRAS (Göttingen Research Association for Schizophrenia data collection was initiated in 2005. With >3000 phenotypical data points per patient, it comprises the world-wide largest currently available schizophrenia database (N > 1200, combining genome-wide SNP coverage and deep phenotyping under highly standardized conditions. First PGAS results on normal genetic variants, relevant for e.g., cognition or catatonia, demonstrated proof-of-concept. Presently, an autistic subphenotype of schizophrenia is being defined where an unfortunate accumulation of normal genotypes, so

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

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    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

  12. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine W; Rasmussen, Susanne

    2007-01-01

    OBJECTIVES: The goal was to clarify if insulin resistance (IR) would predict cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn). BACKGROUND: Although the cause of MetSyn is not well defined, IR has been proposed to be an important cause. Only a small number of population......, smoking, and low-density lipoprotein cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to 2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The corresponding figures for NCEP...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. DESIGN: Retrospective nationwide cohort study. SETTING: Danish nationwide national registers....... PARTICIPANTS: All individuals in Denmark ≥65 years who used specified CVD-drugs in the study period between 1999 and 2012. MAIN OUTCOMES MEASURES: Time-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, β-blockers, calcium antagonists...... and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. RESULTS: Overall, 1 586 554 persons were included...

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

    Science.gov (United States)

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

    2013-05-01

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

  15. Association of cardiovascular burden with mobility limitation among elderly people: a population-based study.

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    Anna-Karin Welmer

    Full Text Available BACKGROUND: Cardiovascular risk factors (CRFs such as smoking and diabetes have been associated with mobility limitations among older adults. We seek to examine to what extent individual and aggregated CRFs and cardiovascular diseases (CVDs are associated with mobility limitation. METHODS: The study sample included 2725 participants (age ≥60 years, mean age 72.7 years, 62% women in the Swedish National Study on Aging and Care in the Kungsholmen district of central Stockholm, Sweden, who were living either at their own home or in institutions. Data on demographic features, CRFs, and CVDs were collected through interview, clinical examination, self-reported history, laboratory tests, and inpatient register. Mobility limitation was defined as walking speed <0.8 m/s. Data were analyzed using multiple logistic models controlling for potential confounders. RESULTS: Of the 2725 participants, 581 (21.3% had mobility limitation. The likelihood of mobility limitation increased linearly with the increasing number of CRFs (i.e., hypertension, high C-reactive protein, obesity, diabetes and smoking (p for linear trend<0.010 and of CVDs (i.e., ischemic heart disease, atrial fibrillation, heart failure and stroke (p for linear trend<0.001. There were statistical interactions of aggregated CRFs with age and APOE ε4 allele on mobility limitation (p interaction<0.05, such that the association of mobility limitation with aggregated CRFs was statistically evident only among people aged <80 years and among carriers of the APOE ε4 allele. CONCLUSION: Aggregations of multiple CRFs and CVDs are associated with an increased likelihood of mobility limitation among older adults; however the associations of CRFs with mobility limitation vary by age and genetic susceptibility.

  16. Low Physical Activity and Its Association with Diabetes and Other Cardiovascular Risk Factors: A Nationwide, Population-Based Study

    Science.gov (United States)

    Brugnara, Laura; Murillo, Serafín; Novials, Anna; Rojo-Martínez, Gemma; Soriguer, Federico; Goday, Albert; Calle-Pascual, Alfonso; Castaño, Luis; Gaztambide, Sonia; Valdés, Sergio; Franch, Josep; Castell, Conxa; Vendrell, Joan; Casamitjana, Roser; Bosch-Comas, Anna; Bordiú, Elena; Carmena, Rafael; Catalá, Miguel; Delgado, Elias; Girbés, Juan; López-Alba, Alfonso; Martínez-Larrad, Maria Teresa; Menéndez, Edelmiro; Mora-Peces, Inmaculada; Pascual-Manich, Gemma; Serrano-Ríos, Manuel; Gomis, Ramon; Ortega, Emilio

    2016-01-01

    Low physical activity (PA), or sedentary lifestyle, is associated with the development of several chronic diseases. We aimed to investigate current prevalence of sedentariness and its association with diabetes and other cardiovascular risk factors. PA was evaluated in a population-based, cross-sectional, randomly sampled study conducted in 2009–2010 in Spain. International Physical Activity Questionnaire (SF-IPAQ) was used to assess PA. 4991 individuals (median age 50 years, 57% women) were studied. Prevalence of sedentariness was 32.3% for men and 39% for women (p < 0.0001). Sex differences were particularly notable (age*sex interaction, p = 0.0024) at early and older ages. Sedentary individuals had higher BMI (28 vs. 27 kg/m2) and obesity prevalence (37 vs. 26%). Low PA was present in 44, 43, and 38% of individuals with known diabetes (KDM), prediabetes/unknown-diabetes (PREDM/UKDM), and normal glucose regulation (p = 0.0014), respectively. No difference between KDM and PREDM/UKDM (p = 0.72) was found. Variables independently associated (p < 0.05) with sedentariness were age, sex, BMI, central obesity, Mediterranean diet adherence, smoking habit, HDL-cholesterol, triglycerides and dyslipidemia. Low PA is on the rise in Spain, especially among women. Sedentariness is associated with several cardiovascular risk factors and may be responsible for the increasing prevalence of obesity and diabetes in this country. PMID:27532610

  17. Cardiovascular pharmacogenetics.

    Science.gov (United States)

    Myburgh, Renier; Hochfeld, Warren E; Dodgen, Tyren M; Ker, James; Pepper, Michael S

    2012-03-01

    Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.

  18. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.

    Science.gov (United States)

    Aschbacher, Kirstin; Adam, Emma K; Crofford, Leslie J; Kemeny, Margaret E; Demitrack, Mark A; Ben-Zvi, Amos

    2012-10-01

    A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was "personalized" by estimating an individualized set of parameters from each participant's data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups ("fatigue-predominant" patients with CFS only versus "pain-predominant" patients with FM and comorbid chronic fatigue) from controls (all p'sdecreased when more cortisol was produced per unit ACTH, is consistent with cortisol's anti-inflammatory and sleep-modulatory effects. Patients' HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping "behavioral phenotypes" of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.

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

    Directory of Open Access Journals (Sweden)

    Tina Karwalajtys

    2010-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 3D plant phenotyping in sunflower using architecture-based organ segmentation from 3D point clouds

    OpenAIRE

    Gélard, William; Burger, Philippe; Casadebaig, Pierre; Langlade, Nicolas; Debaeke, Philippe; Devy, Michel; Herbulot, Ariane

    2016-01-01

    International audience; This paper presents a 3D phenotyping method applied to sunflower, allowing to compute the leaf area of an isolated plant. This is a preliminary step towards the automated monitoring of leaf area and plant growth through the plant life cycle. First, a model-based segmentation method is applied to 3D data derived from RGB images acquired on sunflower plants grown in pots. The RGB image acquisitions are made all around the isolated plant with a single hand-held standard c...

  2. Skin-Based DNA Repair Phenotype for Cancer Risk from GCR in Genetically Diverse Populations

    Science.gov (United States)

    Guiet, Elodie; Viger, Louise; Snijders, Antoine; Costes, Sylvian V.

    2017-01-01

    Predicting cancer risk associated with cosmic radiation remains a mission-critical challenge for NASA radiation health scientists and mission planners. Epidemiological data are lacking and risk methods do not take individual radiation sensitivity into account. In our approach we hypothesize that genetic factors strongly influence risk of cancer from space radiation and that biomarkers reflecting DNA damage and cell death are ideal tools to predict risk and monitor potential health effects post-flight. At this workshop, we will be reporting the work we have done over the first 9 months of this proposal. Skin cells from 15 different strains of mice already characterized for radiation-induced cancer sensitivity (B6C3F; BALB/cByJ, C57BL/6J, CBA/CaJ, C3H/HeMsNrsf), and 10 strains from the DOE collaborative cross-mouse model were expanded from ear biopsy and cultivated until Passage 3. On average, 3 males and 3 females for each strain were expanded and frozen for further characterization at the NSRL beam line during the NSRL16C run for three LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and two ion fluences (1 and 3 particles per cell). The mice work has established new metrics for the usage of Radiation Induced Foci as a marker for various aspect of DNA repair deficiencies. In year 2, we propose to continue characterization of the mouse lines with low LET to identify loci specific to high- versus low- LET and establish genetic linkage for the various DNA repair biomarkers. Correlation with cancer risk from each animals strain and gender will also be investigated. On the human side, we will start characterizing the DNA damage response induced ex-vivo in 200 human's blood donors for radiation sensitivity with a tentative 500 donors by the end of this project. All ex-vivo phenotypic data will be correlated to genetic characterization of each individual human donors using SNP arrays characterization as done for mice. Similarly, ex-vivo phenotypic features from mice will

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

    Directory of Open Access Journals (Sweden)

    Ceriello A

    2014-06-01

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

  4. LAMA/LABA vs ICS/LABA in the treatment of COPD in Japan based on the disease phenotypes

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    Hizawa N

    2015-06-01

    benefits from ICSs. In this review, I propose one plausible approach to position ICSs and LABAs/LAMAs in clinical practice, based on both the extent of airflow obstruction and the presence of an asthma component or airway eosinophilic inflammation. This approach is a tentative move toward personalized treatment for COPD patients, and with progress in knowledge and developments in physiology, lung imaging, medical biology, and genetics, identification of COPD phenotypes that provide prognostic and therapeutic information that can affect clinically meaningful outcomes is an urgent medical need. Keywords: COPD phenotype, LAMA/LABA combination, ICS

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

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    Bullano Michael F

    2009-09-01

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

  6. Cardiovascular Effects of Allium Sativum (Garlic: An Evidence-Based Review

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    Shahin Akhondzadeh

    2008-07-01

    Full Text Available Garlic has been used since time immemorial as a culinary spice and medicinal herb. Garlic has been cultivated in the Middle East for more than 5,000 years and has been an important part of traditional Chinese medicine. The region with the largest commercial garlic production is central California. China is also a supplier of commercial garlic. The bulb is used medicinally. Garlic has been touted as an herb with numerous health benefits, from treating the common cold to serving as an anticancer agent. Research has proven that garlic is beneficial for those with hypertension. By thinning the blood garlic can lower blood pressure by 5 to 10 percent. It can also lower cholesterol and discourage clot formation. The sulfur compound allicin, produced by crushing or chewing fresh garlic or by taking powdered garlic products with allicin potential, in turn produces other sulfur compounds: ajoene, allyl sulfides, and vinyldithiins. Aged garlic products lack allicin, but may have activity due to the presence of S-allylcysteine. In this review, we focused on the cardiovascular effects of garlic.

  7. Verification of Geometric Model-Based Plant Phenotyping Methods for Studies of Xerophytic Plants

    Directory of Open Access Journals (Sweden)

    Paweł Drapikowski

    2016-06-01

    Full Text Available This paper presents the results of verification of certain non-contact measurement methods of plant scanning to estimate morphological parameters such as length, width, area, volume of leaves and/or stems on the basis of computer models. The best results in reproducing the shape of scanned objects up to 50 cm in height were obtained with the structured-light DAVID Laserscanner. The optimal triangle mesh resolution for scanned surfaces was determined with the measurement error taken into account. The research suggests that measuring morphological parameters from computer models can supplement or even replace phenotyping with classic methods. Calculating precise values of area and volume makes determination of the S/V (surface/volume ratio for cacti and other succulents possible, whereas for classic methods the result is an approximation only. In addition, the possibility of scanning and measuring plant species which differ in morphology was investigated.

  8. A revision of Evaniscus (Hymenoptera, Evaniidae using ontology-based semantic phenotype annotation

    Directory of Open Access Journals (Sweden)

    Patricia Mullins

    2012-09-01

    Full Text Available The Neotropical evaniid genus Evaniscus Szépligeti currently includes six species. Two new species are described, Evaniscus lansdownei Mullins, sp. n. from Colombia and Brazil and E. rafaeli Kawada, sp. n. from Brazil. Evaniscus sulcigenis Roman, syn. n., is synonymized under E. rufithorax Enderlein. An identification key to species of Evaniscus is provided. Thirty-five parsimony informative morphological characters are analyzed for six ingroup and four outgroup taxa. A topology resulting in a monophyletic Evaniscus is presented with E. tibialis and E. rafaeli as sister to the remaining Evaniscus species. The Hymenoptera Anatomy Ontology and other relevant biomedical ontologies are employed to create semantic phenotype statements in Entity-Quality (EQ format for species descriptions. This approach is an early effort to formalize species descriptions and to make descriptive data available to other domains.

  9. A revision of Evaniscus (Hymenoptera, Evaniidae) using ontology-based semantic phenotype annotation.

    Science.gov (United States)

    Mullins, Patricia L; Kawada, Ricardo; Balhoff, James P; Deans, Andrew R

    2012-01-01

    The Neotropical evaniid genus Evaniscus Szépligeti currently includes six species. Two new species are described, Evaniscus lansdownei Mullins, sp. n. from Colombia and Brazil and Evaniscus rafaeli Kawada, sp. n. from Brazil. Evaniscus sulcigenis Roman, syn. n., is synonymized under Evaniscus rufithorax Enderlein. An identification key to species of Evaniscus is provided. Thirty-five parsimony informative morphological characters are analyzed for six ingroup and four outgroup taxa. A topology resulting in a monophyletic Evaniscus is presented with Evaniscus tibialis and Evaniscus rafaeli as sister to the remaining Evaniscus species. The Hymenoptera Anatomy Ontology and other relevant biomedical ontologies are employed to create semantic phenotype statements in Entity-Quality (EQ) format for species descriptions. This approach is an early effort to formalize species descriptions and to make descriptive data available to other domains.

  10. Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

    Directory of Open Access Journals (Sweden)

    Kevin C. O’Connor

    2006-01-01

    Full Text Available Currently, there is no single test for multiple sclerosis (MS. Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI, and analysis of cerebrospinal fluid (CSF chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

  12. Quantitative, Image-Based Phenotyping Methods Provide Insight into Spatial and Temporal Dimensions of Plant Disease1[OPEN

    Science.gov (United States)

    Fentress, Sarah J.; Sher, Joel W.; Berry, Jeffrey C.; Pretz, Chelsea

    2016-01-01

    Plant disease symptoms exhibit complex spatial and temporal patterns that are challenging to quantify. Image-based phenotyping approaches enable multidimensional characterization of host-microbe interactions and are well suited to capture spatial and temporal data that are key to understanding disease progression. We applied image-based methods to investigate cassava bacterial blight, which is caused by the pathogen Xanthomonas axonopodis pv. manihotis (Xam). We generated Xam strains in which individual predicted type III effector (T3E) genes were mutated and applied multiple imaging approaches to investigate the role of these proteins in bacterial virulence. Specifically, we quantified bacterial populations, water-soaking disease symptoms, and pathogen spread from the site of inoculation over time for strains with mutations in avrBs2, xopX, and xopK as compared to wild-type Xam. ∆avrBs2 and ∆xopX both showed reduced growth in planta and delayed spread through the vasculature system of cassava. ∆avrBs2 exhibited reduced water-soaking symptoms at the site of inoculation. In contrast, ∆xopK exhibited enhanced induction of disease symptoms at the site of inoculation but reduced spread through the vasculature. Our results highlight the importance of adopting a multipronged approach to plant disease phenotyping to more fully understand the roles of T3Es in virulence. Finally, we demonstrate that the approaches used in this study can be extended to many host-microbe systems and increase the dimensions of phenotype that can be explored. PMID:27443602

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

    Directory of Open Access Journals (Sweden)

    Zahra Jahangard-Rafsanjani

    2015-10-01

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

  14. A SCHOOL-BASED INTERVENTION PROGRAM FOR IMPROVING THE RISK FACTORS FOR CARDIOVASCULAR DISEASE AT AGES 12 TO 16.

    Directory of Open Access Journals (Sweden)

    Konstantinos Laparidis

    2010-06-01

    Full Text Available Background. Cardiovascular disease begins in childhood and this can be correlated with the presence of risk factors in adults. It is reasonable to initiate healthful lifestyle training in childhood to promote improved cardiovascular health in adult life. The purpose of the study was to evaluate the effectiveness of a school-basedprogram designed to reduce specific modifiable risk factors for preventing cardiovascular diseases.Methods. The sample was 343 students (160 boys, 183 girls aged 12–16 years from the prefecture of Larissa, Greece. The duration of intervention was 1 school year. The practical part of intervention took place during the class of physical education, while the theoretical part took place in the classroom. Measurements weretaken at the beginning, in the middle and at the end of the intervention. The following parameters were measured: weight, height, blood pressure, heart rate, components of the Healthy Eating Index, VO2max,Fitnessgram test battery (1 mile run-walk, trunk lift, push up, curl up, back saver sit and reach.Results. There were significant differences between the school-groups in the 1 mile run walk (p<0,001,90o push up test (p<0,001, Healthy Eating Index (p<0,001, fruit component (p<0,001, saturated fat intake(p<0,05 and variety component (p<0,001. In the intervention group there was significant increase in VO2max(p<0,05, in the weight (p<0,001, in the Healthy Eating Index (p<0,05, in the trunk lift test (p<0,001, in the push up test (p<0,05, in the sit and reach test (p<0,001 and in the component of fruits (p<0,001, while there was significant reduction in the 1 mile run walk test (p<0,001, in the body mass index (p<0,05 and in the component of saturated fat (p<0,05.Conclusion. The intervention program was successfully implemented in schools and there were many significant and positive effects. These results highlight the importance of multicomponent programs for theprevention of CVD in schools. Additional

  15. Quantitative Phenotyping-Based In Vivo Chemical Screening in a Zebrafish Model of Leukemia Stem Cell Xenotransplantation

    Science.gov (United States)

    Zhang, Beibei; Shimada, Yasuhito; Kuroyanagi, Junya; Umemoto, Noriko; Nishimura, Yuhei; Tanaka, Toshio

    2014-01-01

    Zebrafish-based chemical screening has recently emerged as a rapid and efficient method to identify important compounds that modulate specific biological processes and to test the therapeutic efficacy in disease models, including cancer. In leukemia, the ablation of leukemia stem cells (LSCs) is necessary to permanently eradicate the leukemia cell population. However, because of the very small number of LSCs in leukemia cell populations, their use in xenotransplantation studies (in vivo) and the difficulties in functionally and pathophysiologically replicating clinical conditions in cell culture experiments (in vitro), the progress of drug discovery for LSC inhibitors has been painfully slow. In this study, we developed a novel phenotype-based in vivo screening method using LSCs xenotransplanted into zebrafish. Aldehyde dehydrogenase-positive (ALDH+) cells were purified from chronic myelogenous leukemia K562 cells tagged with a fluorescent protein (Kusabira-orange) and then implanted in young zebrafish at 48 hours post-fertilization. Twenty-four hours after transplantation, the animals were treated with one of eight different therapeutic agents (imatinib, dasatinib, parthenolide, TDZD-8, arsenic trioxide, niclosamide, salinomycin, and thioridazine). Cancer cell proliferation, and cell migration were determined by high-content imaging. Of the eight compounds that were tested, all except imatinib and dasatinib selectively inhibited ALDH+ cell proliferation in zebrafish. In addition, these anti-LSC agents suppressed tumor cell migration in LSC-xenotransplants. Our approach offers a simple, rapid, and reliable in vivo screening system that facilitates the phenotype-driven discovery of drugs effective in suppressing LSCs. PMID:24454867

  16. Prescrição de terapias baseadas em evidências para pacientes de alto risco cardiovascular: estudo REACT Evidence-based therapy prescription in high-cardiovascular risk patients: the REACT study

    Directory of Open Access Journals (Sweden)

    Otávio Berwanger

    2013-03-01

    practice of outpatient care in patients at high cardiovascular risk in Brazil, regarding the prescription of evidence-based therapies. METHODS: Prospective registry that documented the ambulatory clinical practice in individuals at high cardiovascular risk, which was defined as the presence of the following factors: coronary artery disease, cerebrovascular and peripheral vascular diseases, diabetes, or those with at least three of the following factors: hypertension, smoking, dyslipidemia, age > 70 years, family history of coronary artery disease, chronic kidney disease or asymptomatic carotid artery disease. Basal characteristics were assessed and the rate of prescription of pharmacological and non-pharmacological interventions was analyzed. RESULTS: A total of 2364 consecutive patients were included, of which 52.2% were males, with a mean age of 66.0 years (± 10.1. Of these, 78.3% used antiplatelet agents, 77.0% used statins and of patients with a history of myocardial infarction, 58.0% received beta-blockers. Concomitant use of these three classes of drugs was 34%; 50.9% of hypertensive, 67% of diabetic and 25.7% of dyslipidemic patients did not achieve the goals recommended by guidelines. The main predictors of prescription therapies with proven benefit were centers with a cardiologist and history of coronary artery disease. CONCLUSION: This national and representative registry identified important gaps in the incorporation of therapies with proven benefit, offering a realistic outlook of patients at high cardiovascular risk.

  17. Mobile Phone-Based Lifestyle Intervention for Reducing Overall Cardiovascular Disease Risk in Guangzhou, China: A Pilot Study.

    Science.gov (United States)

    Liu, Zhiting; Chen, Songting; Zhang, Guanrong; Lin, Aihua

    2015-12-17

    With the rapid and widespread adoption of mobile devices, mobile phones offer an opportunity to deliver cardiovascular disease (CVD) interventions. This study evaluated the efficacy of a mobile phone-based lifestyle intervention aimed at reducing the overall CVD risk at a health management center in Guangzhou, China. We recruited 589 workers from eight work units. Based on a group-randomized design, work units were randomly assigned either to receive the mobile phone-based lifestyle interventions or usual care. The reduction in 10-year CVD risk at 1-year follow-up for the intervention group was not statistically significant (-1.05%, p = 0.096). However, the mean risk increased significantly by 1.77% (p = 0.047) for the control group. The difference of the changes between treatment arms in CVD risk was -2.83% (p = 0.001). In addition, there were statistically significant changes for the intervention group relative to the controls, from baseline to year 1, in systolic blood pressure (-5.55 vs. 6.89 mmHg; p Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China.

  18. Cardiovascular risk management after reproductive and pregnancy-related disorders : A Dutch multidisciplinary evidence-based guideline

    NARCIS (Netherlands)

    Heida, Karst Y.; Bots, Michiel L.; De Groot, Christianne J M; Van Dunné, Frederique M.; Hammoud, Nurah M.; Hoek, Annemiek; Laven, Joop S E; Maas, Angela H E M; Roeters Van Lennep, Jeanine E.; Velthuis, Birgitta K.; Franx, Arie

    2016-01-01

    Background In the past decades evidence has accumulated that women with reproductive and pregnancy-related disorders are at increased risk of developing cardiovascular disease (CVD) in the future. Up to now there is no standardised follow-up of these women becausee guidelines on cardiovascular risk

  19. Computed Tomography Coronary Artery Calcium Scoring Review of Evidence Base and Cost-effectiveness in Cardiovascular Risk Prediction

    NARCIS (Netherlands)

    Vliegenthart, Rozemarijn; Morris, Pamela B.

    2012-01-01

    Cardiovascular risk factor-scoring algorithms may fall short in identifying asymptomatic individuals who will subsequently suffer a coronary event. It is generally thought that evaluation of the extent of the atherosclerotic plaque and total plaque burden can improve cardiovascular risk stratificati

  20. Research in cardiovascular care

    DEFF Research Database (Denmark)

    Jaarsma, Tiny; Deaton, Christi; Fitzsimmons, Donna

    2014-01-01

    To deliver optimal patient care, evidence-based care is advocated and research is needed to support health care staff of all disciplines in deciding which options to use in their daily practice. Due to the increasing complexity of cardiac care across the life span of patients combined...... 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....

  1. Effects of a 2-year school-based daily physical activity intervention on cardiovascular disease risk factors: the Sogndal school-intervention study

    DEFF Research Database (Denmark)

    Resaland, G K; Anderssen, S A; Holme, I M

    2011-01-01

    The aim of this study was to investigate the effect of a 2-year school-based physical activity (PA) intervention in 9-year-old children on cardiovascular disease (CVD) risk factors. One intervention school (I-school) (n=125) and one control school (C-school) (n=131) were included. The children...

  2. Effects on cardiovascular disease risk of a web-based health risk assessment with tailored health advice: A follow-up study

    NARCIS (Netherlands)

    E.B. Colkesen (Ersen); B.S. Ferket (Bart); J.G.P. Tijssen (Jan); R.A. Kraaijenhagen (Roderik); C.K. Kalken (Coenraad); R.J. Peters (Ron)

    2011-01-01

    textabstractIntroduction: A large proportion of the cardiovascular disease (CVD) burden can potentially be prevented by primary prevention programs addressing major causal risk factors. A Web- based health risk assessment (HRA) with tailored feedback for individual health promotion is a promising st

  3. National dissemination of StrongWomen – Healthy Hearts: A community-based program to reduce risk of cardiovascular disease among midlife and older women

    Science.gov (United States)

    Objective: We describe the national dissemination of an evidence-based community cardiovascular disease prevention program for midlife and older women using the RE-AIM (reach effectiveness adoption implementation maintenance) framework and share key lessons learned during translation. Methods: In a ...

  4. LAMA/LABA vs ICS/LABA in the treatment of COPD in Japan based on the disease phenotypes.

    Science.gov (United States)

    Hizawa, Nobuyuki

    2015-01-01

    In the combined use of bronchodilators of different classes, ie, long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), bronchodilation is obtained both directly, through LABA-mediated stimulation of β2-adrenergic receptors, and indirectly, through LAMA-mediated inhibition of acetylcholine action at muscarinic receptors. The clinical trial data for LABAs/LAMAs in the treatment of chronic obstructive pulmonary disease (COPD) continue to be promising, and these combinations will provide the convenience of delivering the two major bronchodilator classes, recommended as first-line maintenance options in COPD treatment guidelines. COPD is a complex condition that has pulmonary and extrapulmonary manifestations. These clinical manifestations are highly variable, and several are associated with different responses to currently available therapies. The concept of a COPD phenotype is rapidly evolving from one focusing on the clinical characteristics to one linking the underlying biology to the phenotype of the disease. Identification of the peculiarities of the different COPD phenotypes will permit us to implement a more personalized treatment in which the patient's characteristics, together with his or her genotype, will be key to choosing the best treatment option. At present in Japan, fixed combinations of inhaled corticosteroids (ICSs) and LABAs are frequently prescribed in the earlier stages of COPD. However, ICSs increase the risk of pneumonia. Notably, 10%-30% of patients with COPD with or without a history of asthma have persistent circulating and airway eosinophilia associated with an increased risk of exacerbations and sensitivity to steroids. Thus, sputum or blood eosinophil counts might identify a subpopulation in which ICSs could have potentially deleterious effects as well as a subpopulation that benefits from ICSs. In this review, I propose one plausible approach to position ICSs and LABAs/LAMAs in clinical practice, based on both

  5. A Systematic Phenotypic Screen of F-box Genes Through a Tissue-specific RNAi-based Approach in Drosophila

    Institute of Scientific and Technical Information of China (English)

    Wen Dui; Wei Lu; Jun Ma; Renjie Jiao

    2012-01-01

    F-box proteins are components of the SCF (SkpA-Cullin 1-F-box) E3 ligase complexes,acting as the specificity-determinants in targeting substrate proteins for ubiquitination and degradation.In humans,at least 22 out of 75 F-box proteins have experimentally documented substrates,whereas in Drosophila 12 F-box proteins have been characterized with known substrates.To systematically investigate the genetic and molecular functions of F-box proteins in Drosophila,we performed a survey of the literature and databases.We identified 45 Drosophila genes that encode proteins containing at least one F-box domain.We collected publically available RNAi lines against these genes and used them in a tissue-specific RNAi-based phenotypic screen.Here,we present our systematic phenotypic dataset from the eye,the wing and the notum.This dataset is the first of its kind and represents a useful resource for future studies of the molecular and genetic functions of F-box genes in Drosophila.Our results show that,as expected,F-box genes in Drosophila have regulatory roles in a diverse array of processes including cell proliferation,cell growth,signal transduction,and cellular and animal survival.

  6. Integrating clinical and laboratory data in genetic studies of complex phenotypes: a network-based data management system.

    Science.gov (United States)

    McMahon, F J; Thomas, C J; Koskela, R J; Breschel, T S; Hightower, T C; Rohrer, N; Savino, C; McInnis, M G; Simpson, S G; DePaulo, J R

    1998-05-01

    The identification of genes underlying a complex phenotype can be a massive undertaking, and may require a much larger sample size than thought previously. The integration of such large volumes of clinical and laboratory data has become a major challenge. In this paper we describe a network-based data management system designed to address this challenge. Our system offers several advantages. Since the system uses commercial software, it obviates the acquisition, installation, and debugging of privately-available software, and is fully compatible with Windows and other commercial software. The system uses relational database architecture, which offers exceptional flexibility, facilitates complex data queries, and expedites extensive data quality control. The system is particularly designed to integrate clinical and laboratory data efficiently, producing summary reports, pedigrees, and exported files containing both phenotype and genotype data in a virtually unlimited range of formats. We describe a comprehensive system that manages clinical, DNA, cell line, and genotype data, but since the system is modular, researchers can set up only those elements which they need immediately, expanding later as needed.

  7. Comparing partial least square approaches in a gene- or region-based association study for multiple quantitative phenotypes.

    Science.gov (United States)

    Yuan, Zhongshang; Zhang, Xiaoshuai; Li, Fangyu; Zhao, Jinghua; Xue, Fuzhong

    2014-01-01

    On thinking quantitatively of complex diseases, there are at least three statistical strategies for association studies: one single-nucleotide polymorphism (SNP) on a single trait, gene or region (with multiple SNPs) on a single trait, and gene or region on multiple traits. The third approach is the most general in dissecting genetic mechanisms underlying complex diseases underpinning multiple quantitative traits. Gene or region association methods based on partial least square (PLS) approaches have been shown to have apparent power advantage. However, few approaches have been developed for multiple quantitative phenotypes or traits underlying a condition or disease, and the performance of various PLS approaches used in association studies for multiple quantitative traits have not been assessed. Here we exploit association between multiple SNPs and multiple phenotypes or traits, from a regression perspective, through exhaustive scan statistics (sliding window) using PLS and sparse PLS regressions. Simulations were conducted to assess the performance of the proposed scan statistics and compare them with existing methods. The proposed methods were applied to 12 regions of genome-wide association study data from the European Prospective Investigation of Cancer-Norfolk study.

  8. Molecular and phenotypic profiling from the base to the crown in maritime pine wood-forming tissue.

    Science.gov (United States)

    Paiva, Jorge A P; Garcés, Marcelo; Alves, Ana; Garnier-Géré, Pauline; Rodrigues, José Carlos; Lalanne, Céline; Porcon, Stéphane; Le Provost, Grégoire; Perez, Denilson da Silva; Brach, Jean; Frigerio, Jean-Marc; Claverol, Stéphane; Barré, Aurélien; Fevereiro, Pedro; Plomion, Christophe

    2008-01-01

    Environmental, developmental and genetic factors affect variation in wood properties at the chemical, anatomical and physical levels. Here, the phenotypic variation observed along the tree stem was explored and the hypothesis tested that this variation could be the result of the differential expression of genes/proteins during wood formation. Differentiating xylem samples of maritime pine (Pinus pinaster) were collected from the top (crown wood, CW) to the bottom (base wood, BW) of adult trees. These samples were characterized by Fourier transform infrared spectroscopy (FTIR) and analytical pyrolysis. Two main groups of samples, corresponding to CW and BW, could be distinguished from cell wall chemical composition. A genomic approach, combining large-scale production of expressed sequence tags (ESTs), gene expression profiling and quantitative proteomics analysis, allowed identification of 262 unigenes (out of 3512) and 231 proteins (out of 1372 spots) that were differentially expressed along the stem. A good relationship was found between functional categories from transcriptomic and proteomic data. A good fit between the molecular mechanisms involved in CW-BW formation and these two types of wood phenotypic differences was also observed. This work provides a list of candidate genes for wood properties that will be tested in forward genetics.

  9. Phenotypic correction of murine hemophilia A using an iPS cell-based therapy.

    Science.gov (United States)

    Xu, Dan; Alipio, Zaida; Fink, Louis M; Adcock, Dorothy M; Yang, Jianchang; Ward, David C; Ma, Yupo

    2009-01-20

    Hemophilia A is caused by mutations within the Factor VIII (FVIII) gene that lead to depleted protein production and inefficient blood clotting. Several attempts at gene therapy have failed for various reasons-including immune rejection. The recent generation of induced pluripotent stem (iPS) cells from somatic cells by the ectopic expression of 3 transcription factors, Oct4, Sox2, and Klf4, provides a means of circumventing the immune rejection barrier. To date, iPS cells appear to be indistinguishable from ES cells and thus provide tremendous therapeutic potential. Here we prepared murine iPS cells from tail-tip fibroblasts and differentiated them to both endothelial cells and endothelial progenitor cells by using the embryoid body differentiation method. These iPS cells express major ES cell markers such as Oct4, Nanog, SSEA-1, alkaline phosphatase, and SALL4. Endothelial/endothelial progenitor cells derived from iPS cells expressed cell-specific markers such as CD31, CD34, and Flk1 and secreted FVIII protein. These iPS-derived cells were injected directly into the liver of irradiated hemophilia A mice. At various times after transplantation (7-90 days) hemophilia A mice and their control mice counterparts were challenged by a tail-clip bleeding assay. Nontransplanted hemophilia A mice died within a few hours, whereas transplanted mice survived for more than 3 months. Plasma FVIII levels increased in transplanted hemophilia A mice during this period to 8% to 12% of wild type and corrected the hemophilia A phenotype. Our studies provide additional evidence that iPS cell therapy may be able to treat human monogenetic disorders in the future.

  10. Losartan versus atenolol-based antihypertensive treatment reduces cardiovascular events especially well in elderly patients

    DEFF Research Database (Denmark)

    Ruwald, Anne Christine H; Westergaard, Bo; Sehestedt, Thomas;

    2012-01-01

    The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study has previously demonstrated a beneficial effect of losartan compared to atenolol-based antihypertensive treatment in patients with essential hypertension and left-ventricular hypertrophy (LVH). However, patient age often...... influences the choice of antihypertensive drugs. Therefore, we investigated the influence of age on the effects of losartan versus atenolol-based antihypertensive treatment....

  11. Predicting 10-Year Risk of Fatal Cardiovascular Disease in Germany: An Update Based on the SCORE-Deutschland Risk Charts

    Science.gov (United States)

    Rücker, Viktoria; Keil, Ulrich; Fitzgerald, Anthony P; Malzahn, Uwe; Prugger, Christof; Ertl, Georg; Heuschmann, Peter U; Neuhauser, Hannelore

    2016-01-01

    Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40–65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk. PMID:27612145

  12. 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

    Genome-scale metabolic reconstructions are currently available for hundreds of organisms. Constraint-based modeling enables the analysis of the phenotypic landscape of these organisms, predicting the response to genetic and environmental perturbations. However, since constraint-based models can...... level by explicitly accounting for the individual fluxes of enzymes (and subunits) encoded by each gene. We show how this can be applied to different kinds of constraint-based analysis: flux distribution prediction, gene essentiality analysis, random flux sampling, elementary mode analysis...... 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...

  13. Endothelial progenitor cells, cardiovascular risk factors, cytokine levels and atherosclerosis--results from a large population-based study.

    Directory of Open Access Journals (Sweden)

    Qingzhong Xiao

    Full Text Available BACKGROUND: EPC number and functionality are assumed to reflect the endogenous vascular repair capacity with the EPC pool declining in higher ages and being exhausted by unfavorable life-style and risk factors. This intriguing and clinically highly relevant concept, however, has so far been derived from small case-control studies and patient series. METHODOLOGY AND PRINCIPLE FINDINGS: In the population-based Bruneck Study EPC number and EPC-colony forming units (EPC-CFU were assessed as part of the fourth follow-up evaluation (2005 in 571 and 542 subjects, respectively. EPC number declined with age (p = 0.013, was significantly lower in women (p = 0.006 and higher in subjects on statin, hormone replacement or ACE inhibitor/angiotensin-receptor blockers, and correlated positively with moderate alcohol consumption. Unexpectedly, a positive relation between EPC number and several vascular risk factors emerged. In a step forward multivariate linear regression analysis EPC number was independently related with SDF1alpha, MMP-9, triglycerides, alcohol consumption, and Hba1c. EPC-CFU in turn was related to SDF1alpha and diastolic blood pressure. Moreover, EPC number showed a significant positive association with the Framingham risk score (P = 0.001. Finally, there was an inverse association between EPC number and common carotid artery intima-media thickness (p = 0.02 and the carotid artery atherosclerosis score (p = 0.059. CONCLUSIONS: Our population-based data confirm the decline of EPC number with advancing age and lend first epidemiological support to a role of SDF-1alpha and MMP9 in EPC differentiation, mobilization and homing, but are conflict with the view that EPC number is unfavorably affected by cardiovascular risk factors. EPC number increases with the cardiovascular risk estimated by the Framingham risk score (FRS, which in the absence of similar changes for EPC-CFU. Finally, we demonstrate a significant inverse association between EPC

  14. Changes in body composition and cardiovascular risk indicators in healthy Spanish adolescents after lamb- (Ternasco de Aragón or chicken-based diets

    Directory of Open Access Journals (Sweden)

    María Isabel Mesana Graffe

    2013-06-01

    Full Text Available Objective: To assess the effect of lamb consumption (Protected Geographical Indication (PGI, Ternasco de Aragón on health indicators including body composition and cardiovascular risk indicators of healthy young Spanish students living in the area of Aragón, Spain. Methodology: A randomized-controlled and cross-over trial (two periods of 8 weeks duration assessing changes on body composition (body mass index and skinfold thicknesses and cardiovascular risk indicators of 50 participants randomly assigned to follow a normocaloric diet with lamb (Ternasco de Aragón or chicken. Body composition and serum cardiovascular risk profiles were measured both at baseline and follow-up. Results: Healthy men (n = 22 and women (n = 28, aged 19.43 ± 0.85 years were studied. Suprailiac skinfold thickness and waist circumference significantly decreased (p < 0.05 in the lamb-consumption group compared to the chicken based diet group. No significant changes were observed in the rest of the variables in either group. Tryacilglicerol and insulin serum concentrations significantly decreased (p < 0.05 in the lamb-consumption group compared to the chicken based diet group. Conclusions: The results suggest that regular consumption of lamb (Ternasco de Aragón can be integrated into a healthy, varied and well-balanced diet, as body composition and cardiovascular risk profile changes are similar or even healthier to those observed following chicken consumption.

  15. Quantitative phenotyping-based in vivo chemical screening in a zebrafish model of leukemia stem cell xenotransplantation.

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    Beibei Zhang

    Full Text Available Zebrafish-based chemical screening has recently emerged as a rapid and efficient method to identify important compounds that modulate specific biological processes and to test the therapeutic efficacy in disease models, including cancer. In leukemia, the ablation of leukemia stem cells (LSCs is necessary to permanently eradicate the leukemia cell population. However, because of the very small number of LSCs in leukemia cell populations, their use in xenotransplantation studies (in vivo and the difficulties in functionally and pathophysiologically replicating clinical conditions in cell culture experiments (in vitro, the progress of drug discovery for LSC inhibitors has been painfully slow. In this study, we developed a novel phenotype-based in vivo screening method using LSCs xenotransplanted into zebrafish. Aldehyde dehydrogenase-positive (ALDH+ cells were purified from chronic myelogenous leukemia K562 cells tagged with a fluorescent protein (Kusabira-orange and then implanted in young zebrafish at 48 hours post-fertilization. Twenty-four hours after transplantation, the animals were treated with one of eight different therapeutic agents (imatinib, dasatinib, parthenolide, TDZD-8, arsenic trioxide, niclosamide, salinomycin, and thioridazine. Cancer cell proliferation, and cell migration were determined by high-content imaging. Of the eight compounds that were tested, all except imatinib and dasatinib selectively inhibited ALDH+ cell proliferation in zebrafish. In addition, these anti-LSC agents suppressed tumor cell migration in LSC-xenotransplants. Our approach offers a simple, rapid, and reliable in vivo screening system that facilitates the phenotype-driven discovery of drugs effective in suppressing LSCs.

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

    Science.gov (United States)

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

    2015-12-01

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

  17. A hospital based study to assess the prevalence of cardiovascular risk factors among patients of chronic plaque psoriasis

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    Bela Bhat

    2016-11-01

    Conclusions: Psoriasis patients have a unfavourable cardiovascular risk profile. Therefore these patients should undergo screening and treatment of various modifiable risk factors to reduce morbidity and mortality. [Int J Res Med Sci 2016; 4(11.000: 4974-4978

  18. Effectiveness of a Web-Based Computer-Tailored Multiple-Lifestyle Intervention for People Interested in Reducing their Cardiovascular Risk: A Randomized Controlled Trial

    OpenAIRE

    Storm, Vera; Dörenkämper, Julia; Reinwand, Dominique A; Wienert, Julian; de Vries, Hein; Lippke, Sonia

    2016-01-01

    Background Web-based computer-tailored interventions for multiple health behaviors can improve the strength of behavior habits in people who want to reduce their cardiovascular risk. Nonetheless, few randomized controlled trials have tested this assumption to date. Objective The study aim was to test an 8-week Web-based computer-tailored intervention designed to improve habit strength for physical activity and fruit and vegetable consumption among people who want to reduce their cardiovascula...

  19. Microalbuminuria and its relation to cardiovascular disease and risk factors. A population-based study of 1254 hypertensive individuals

    DEFF Research Database (Denmark)

    Jensen, J S; Feldt-Rasmussen, B; Borch-Johnsen, K;

    1997-01-01

    , and reversely related to the use of antihypertensive drugs. In a major health screening at the State University Hospital in Copenhagen, including urinary albumin excretion, glomerular filtration rate, blood pressure (BP), electrocardiogram, body mass index, plasma lipoproteins, fibrinogen, and albumin...... subjects. The frequency of cardiovascular disease was similar in the two groups. In contrast, when analysed as a continuous variable, a one unit increase in the logarithmically transformed urinary albumin excretion significantly increased the likelihood of cardiovascular disease (odds ratio [95% confidence...

  20. Association of socioeconomic status measured by education, and cardiovascular health: a population-based cross-sectional study

    Science.gov (United States)

    Janković, Slavenka; Stojisavljević, Dragana; Janković, Janko; Erić, Miloš; Marinković, Jelena

    2014-01-01

    Objective Cardiovascular health (CVH) is a relatively new concept defined by the American Heart Association (AHA). The aim of the present study was to assess whether the indices of CVH were discriminators of socioeconomic status (SES) in the adult population of the Republic of Srpska (RS). Design Population-based cross-sectional study. Setting RS, Bosnia and Herzegovina. Participants The study involved 4165 adults aged ≥18 years (mean age 50.2; 54% women) who participated in the National Health Survey performed from September to November 2010 in the RS. Study variables Participant's education was a proxy for SES. Potential discriminators of SES were indices of CVH presented according to AHA as: ideal health behaviours index (non-smoking, body mass index <25 kg/m2, physical activity at goal level and healthy diet); ideal health factors index (untreated total cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, untreated fasting glucose <100 mg/dL and non-smoking); and ideal CVH status (defined as all seven ideal health metrics present) versus intermediate and poor CVH status. Results Participants with high educational levels had a significantly greater number of ideal CVH metrics, and ideal health factor metrics compared with those with low or medium educational level (OR 0.88 95% CI 0.77 to 0.99 and OR 0.88 95% CI 0.80 to 0.96; OR 0.81 95% CI 0.69 to 0.96 and OR 0.77 95% CI 0.68 to 0.87; respectively). The number of ideal behaviour metrics was not a discriminator of educational groups. Concerning the categories of CVH status the poor CVH was a discriminator for low and medium education compared with those with high education (OR 1.93 95% CI 1.24 to 3.01 and OR 1.54 95% CI 1.08 to 2.19, respectively). Conclusions Our findings emphasise the large potential for preventing cardiovascular disease, showing a low proportion with a favourable CVH profile, especially among low-educated people. It is necessary to consider prevention strategies aimed

  1. Urbanization, ethnicity and cardiovascular risk in a population in transition in Nakuru, Kenya: a population-based survey

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    Foster Allen

    2010-09-01

    Full Text Available Abstract Background Cardiovascular disease (CVD is the leading cause of death among older people in Africa. This study aimed to investigate the relationship of urbanization and ethnicity with CVD risk markers in Kenya. Methods A cross-sectional population-based survey was carried out in Nakuru Kenya in 2007-2008. 100 clusters of 50 people aged ≥50 years were selected by probability proportionate to size sampling. Households within clusters were selected through compact segment sampling. Participants were interviewed by nurses to collect socio-demographic and lifestyle information. Nurses measured blood pressure, height, weight and waist and hip circumference. A random finger-prick blood sample was taken to measure glucose and cholesterol levels. Hypertension was defined as systolic blood pressure (SBP ≥140 mm Hg, or diastolic blood pressure (DBP ≥90 mm Hg or current use of antihypertensive medication; Diabetes as reported current medication or diet control for diabetes or random blood glucose level ≥11.1 mmol/L; High cholesterol as random blood cholesterol level ≥5.2 mmol/L; and Obesity as Body Mass Index (BMI≥30 kg/m2. Results 5010 eligible subjects were selected, of whom 4396 (88% were examined. There was a high prevalence of hypertension (50.1%, 47.5-52.6%, obesity (13.0%, 11.7-14.5%, diabetes (6.6%, 5.6-7.7% and high cholesterol (21.1%, 18.6-23.9. Hypertension, diabetes and obesity were more common in urban compared to rural groups and the elevated prevalence generally persisted after adjustment for socio-demographic, lifestyle, obesity and cardiovascular risk markers. There was also a higher prevalence of hypertension, obesity, diabetes and high cholesterol among Kikuyus compared to Kalenjins, even after multivariate adjustment. CVD risk markers were clustered both across the district and within individuals. Few people received treatment for hypertension (15%, while the majority of cases with diabetes received treatment (68

  2. Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.

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    Maxime Levert

    Full Text Available Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients or by members of a single clone that exhibit micro-heterogeneity (11 patients; both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC. We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious

  3. Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases.

    Science.gov (United States)

    Booij, Tijmen H; Klop, Maarten J D; Yan, Kuan; Szántai-Kis, Csaba; Szokol, Balint; Orfi, Laszlo; van de Water, Bob; Keri, Gyorgy; Price, Leo S

    2016-10-01

    3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools were developed to process 3D image data to measure over 800 phenotypic parameters. Multiparametric analysis was used to evaluate the effect of compounds on tissue morphology. We applied this screening platform to measure the activity and selectivity of inhibitors of the c-Met and epidermal growth factor (EGF) receptor (EGFR) tyrosine kinases in 3D cultured prostate carcinoma cells. c-Met and EGFR activity was quantified based on the phenotypic profiles induced by their respective ligands, hepatocyte growth factor and EGF. The screening method was applied to a novel collection of 80 putative inhibitors of c-Met and EGFR. Compounds were identified that induced phenotypic profiles indicative of selective inhibition of c-Met, EGFR, or bispecific inhibition of both targets. In conclusion, we describe a fully scalable high-content screening platform that uses phenotypic profiling to discriminate selective and nonselective (off-target) inhibitors in a physiologically relevant 3D cell culture setting.

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

    Science.gov (United States)

    Vázquez-Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez, Miguel Ángel; Vinaixa, Maria; Chiva-Blanch, Gemma; Estruch, Ramon; Correig, Xavier; Andrés-Lacueva, Cristina

    2012-08-01

    Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100mL/day, alcohol control). After each period, 24-h urine samples were collected and analyzed by (1) H-NMR. According to the results of a one-way ANOVA, significant markers were grouped in four categories: alcohol-related markers (ethanol); gin-related markers; wine-related markers; and gut microbiota markers (hippurate and 4-hydroxphenylacetic acid). Wine metabolites were classified into two groups; first, metabolites of food metabolome: tartrate (RWA and RWD), ethanol, and mannitol (RWA); and second, biomarkers that relates to endogenous modifications after wine consumption, comprising branched-chain amino acid (BCAA) metabolite (3-methyl-oxovalerate). Additionally, a possible interaction between alcohol and gut-related biomarkers has been identified. To our knowledge, this is the first time that this approach has been applied in a nutritional intervention with red wine. The results show the capacity of this approach to obtain a comprehensive metabolome picture including food metabolome and endogenous biomarkers of moderate wine intake.

  5. Epidemiology of cardiovascular malformations among newborns in Monchegorsk (north-west Russia: a register-based study

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    Vitaly A. Postoev

    2014-08-01

    Full Text Available Background. Cardiovascular malformations (CVM are one of the most prevalent groups of birth defects. Knowledge about the prevalence, distribution and survival in Russia has been limited. The aim of our study was to assess the perinatal prevalence, structure and risk factors for CVM among newborns in Monchegorsk (Murmansk Oblast, Russia and the mortality among the affected newborns in the period 1973-2008. Design and methods. A register-based study on data from the Kola and Murmansk County Birth Registers. The study included 28,511 births. Results. The registered perinatal prevalence was 3.0 per 1000 newborns, with septal defects as the most prevalent. CVM was twenty times more prevalent among stillborn than live born, and one-third of the live born with a CVM died during the first week of life. The perinatal mortality rate with CVM was 442 per 1000 newborns. This indicator decreased over time. The mothers of newborns with a CVM were ten times more likely to have stillbirth in their anamnesis. The adjusted odds ratio between maternal smoking during pregnancy and CVM was 4.09 [95% confidence interval: 1.75-9.53]. Conclusions. The diagnosed perinatal prevalence was relatively low. A previous stillbirth by the mother was highly associated with being born with a CVM. An adjusted elevated risk was also observed among smoking mothers. Perinatal survival increased over time, but varied to a large extent between the different types of CVM.

  6. Association of oral health and cardiovascular disease risk factors "results from a community based study on 5900 adult subjects".

    Science.gov (United States)

    Najafipour, Hamid; Malek Mohammadi, Tayebeh; Rahim, Foad; Haghdoost, Ali Akbar; Shadkam, Mitra; Afshari, Mahdi

    2013-01-01

    Objectives. This study aimed to determine the association between some oral health status as a risk factor for cardiac diseases and other cardiovascular disease (CVD) risk factors in a sample of Iranian population in 2011. Methods. The study recruited 5900 inhabitants who aged 15-75 years old of Kerman city through a population based cluster sampling. Having collected informed consent, participants were interviewed for CVD risk factors. Some oral health indicators such as DMFT, Gingival Inflammation index, and Community Periodontal Index were assessed. The association between oral health indices and CVD risk factors was tested using multivariate regression models. Results. The mean age of participants was 33.5 years, and 45.1% were male. Moderate gingival inflammation was observed in 67.6% of participants. Presence of sub- or supragingival calculus was more common (90%) in participants. Older age (RR from 2.7 to 3.88), cigarette smoking (RR = 1.49), and high blood glucose (RR = 1.41) showed an increased risk for oral diseases after adjustment for different covariates including established CVD risk factors. Conclusion. The study results showed an increase in periodontal diseases in the presence of some CVD risk factors. Therefore there may be a bilateral but independent association for both conditions and common risk factor approach preventive program is highly recommended.

  7. The Prevalence of Metabolic Syndrome and Cardiovascular Risk Factors in Obese Children and Adolescents in Dalmatia: A Hospital Based Study

    Science.gov (United States)

    Milić, Lukrecija; Unić, Ivana; Škrabić, Veselin

    2016-01-01

    Obesity and metabolic syndrome (MS) are one of the biggest public health issues in child and adolescent population. To the best of the authors' knowledge, this hospital based study is the first report on the prevalence of MS in obese children and adolescents in Dalmatia, the Mediterranean part of Croatia. The objectives of this study were to determine the prevalence of individual cardiovascular risk factors and MS. Between January 2009 and June 2014, 201 obese subjects aged 6 to 18 were analyzed retrospectively from our Pediatric Endocrine Unit database. The subjects were then classified in two groups of obesity; subjects with BMI z score 2.0–3.0 were classified as moderately obese and subjects with BMI z score > 3.0 were classified as severely obese. The overall prevalence of MS using the modified IDF criteria was 30.3%. The most common component of MS in both groups was arterial hypertension, while impaired fasting glucose was the least common component of MS. Our finding of high prevalence of MS underlines the importance of early childhood obesity treatment.

  8. Assessment of cardiovascular risk based on a data-driven knowledge discovery approach.

    Science.gov (United States)

    Mendes, D; Paredes, S; Rocha, T; Carvalho, P; Henriques, J; Cabiddu, R; Morais, J

    2015-01-01

    The cardioRisk project addresses the development of personalized risk assessment tools for patients who have been admitted to the hospital with acute myocardial infarction. Although there are models available that assess the short-term risk of death/new events for such patients, these models were established in circumstances that do not take into account the present clinical interventions and, in some cases, the risk factors used by such models are not easily available in clinical practice. The integration of the existing risk tools (applied in the clinician's daily practice) with data-driven knowledge discovery mechanisms based on data routinely collected during hospitalizations, will be a breakthrough in overcoming some of these difficulties. In this context, the development of simple and interpretable models (based on recent datasets), unquestionably will facilitate and will introduce confidence in this integration process. In this work, a simple and interpretable model based on a real dataset is proposed. It consists of a decision tree model structure that uses a reduced set of six binary risk factors. The validation is performed using a recent dataset provided by the Portuguese Society of Cardiology (11113 patients), which originally comprised 77 risk factors. A sensitivity, specificity and accuracy of, respectively, 80.42%, 77.25% and 78.80% were achieved showing the effectiveness of the approach.

  9. Molecular identification of four phenotypes of human Demodex mites (Acari: Demodicidae) based on mitochondrial 16S rDNA.

    Science.gov (United States)

    Zhao, Ya-E; Hu, Li; Ma, Jun-Xian

    2013-11-01

    Classification of Demodex mites has long depended on hosts and morphological characteristics. However, the fact that two species coexist in the same host and phenotype is easily influenced by environment causes difficulty and indeterminacy in traditional classification. Genotype, which directly reflects the molecular structure characteristics, is relatively stable. In this study, species identification of four phenotypes of human Demodex mites was conducted. Mites were morphologically classified into four phenotypes: long- and short-bodied Demodex folliculorum with finger-like terminus and Demodex brevis with finger- or cone-like terminus. The mitochondrial 16S ribosomal DNA (rDNA) fragment of individual mite was amplified, cloned, sequenced, and aligned. Sequence divergences, genetic distances, transition/transversion rates, and phylogenetic trees were analyzed. The results demonstrated that the 16S rDNA sequence of three phenotypes with finger-like terminus was 337 bp, and that of phenotype with cone-like terminus was 342 bp. The divergences, genetic distances, and transition/transversion rates among the three phenotypes with finger-like terminus were 0.0-2.7%, 0.000-0.029, and 5.0-7/0 (5/1-7/0), respectively, indicating an intraspecific variation. Yet, those between these three phenotypes and the one with cone-like terminus were 21.6-22.8%, 2.510-2.589, and 0.47-0.59 (22/47-27/46), respectively, suggesting an interspecific variation. The five phylogenetic trees showed that the three phenotypes with finger-like terminus clustered into one branch, while the phenotype with cone-like terminus clustered into another. In conclusion, terminus is a major morphological characteristic for the identification of human Demodex species. The three phenotypes with finger-like terminus belong to D. folliculorum, while the phenotype with cone-like terminus belongs to D. brevis. Molecular identification can verify and replenish morphological identification.

  10. Pharmacogenetics of cardiovascular drugs.

    Science.gov (United States)

    Johnson, Julie A; Humma, Larisa M

    2002-02-01

    Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.

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

    Directory of Open Access Journals (Sweden)

    Jesús eFernández

    2014-11-01

    Full Text Available 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 those 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 ten generations of phenotypic selection applied in the subsequent breeding program.

  12. 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.

  13. Optimization of cardiovascular stent against restenosis: factorial design-based statistical analysis of polymer coating conditions.

    Directory of Open Access Journals (Sweden)

    Gayathri Acharya

    Full Text Available The objective of this study was to optimize the physicodynamic conditions of polymeric system as a coating substrate for drug eluting stents against restenosis. As Nitric Oxide (NO has multifunctional activities, such as regulating blood flow and pressure, and influencing thrombus formation, a continuous and spatiotemporal delivery of NO loaded in the polymer based nanoparticles could be a viable option to reduce and prevent restenosis. To identify the most suitable carrier for S-Nitrosoglutathione (GSNO, a NO prodrug, stents were coated with various polymers, such as poly (lactic-co-glycolic acid (PLGA, polyethylene glycol (PEG and polycaprolactone (PCL, using solvent evaporation technique. Full factorial design was used to evaluate the effects of the formulation variables in polymer-based stent coatings on the GSNO release rate and weight loss rate. The least square regression model was used for data analysis in the optimization process. The polymer-coated stents were further assessed with Differential scanning calorimetry (DSC, Fourier transform infrared spectroscopy analysis (FTIR, Scanning electron microscopy (SEM images and platelet adhesion studies. Stents coated with PCL matrix displayed more sustained and controlled drug release profiles than those coated with PLGA and PEG. Stents coated with PCL matrix showed the least platelet adhesion rate. Subsequently, stents coated with PCL matrix were subjected to the further optimization processes for improvement of surface morphology and enhancement of the drug release duration. The results of this study demonstrated that PCL matrix containing GSNO is a promising system for stent surface coating against restenosis.

  14. Liquid pressure wireless sensor based on magnetostrictive microwires for applications in cardiovascular localized diagnostic

    Directory of Open Access Journals (Sweden)

    A. M. Aragón

    2015-08-01

    Full Text Available In this letter, we report a method to measure changes in a fluid pressure, flowing through a flexible pipeline, by means of a ring of magnetic microwire concentric to the pipeline. The detection is based on the modulated scattering of electromagnetic waves by the magnetoelastic ring. This modulation is driven by applying a low frequency bias magnetic field able to tune the magnetic permeability of the ferromagnetic microwire. Pressure detection, by means of magnetic permeability changes, is possible due to the magnetostrictive character of the sample. The experimental work developed has, also, allowed fluid pressure detection in a hydraulic circuit connected to ventricular assist system where a fluid with a viscosity close to blood flows.

  15. Phenotypic and Genetic Associations between Reading Comprehension, Decoding Skills, and ADHD Dimensions: Evidence from Two Population-Based Studies

    Science.gov (United States)

    Plourde, Vickie; Boivin, Michel; Forget-Dubois, Nadine; Brendgen, Mara; Vitaro, Frank; Marino, Cecilia; Tremblay, Richard T.; Dionne, Ginette

    2015-01-01

    Background: The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and…

  16. Variaciones en la prevención del riesgo cardiovascular: estudio poblacional Variation in the prevention of cardiovascular risk factors. A population-based study

    Directory of Open Access Journals (Sweden)

    I. Ruiz Pérez

    2003-02-01

    until they are performed with the same frequency as among physicians and nurses. Efforts should be directed to increasing cardiovascular prevention programs in health centers.

  17. Effects of Music on Cardiovascular Responses in Men with Essential Hypertension Compared with Healthy Men Based on Introversion and Extraversion

    Directory of Open Access Journals (Sweden)

    Hossein Namdar

    2014-10-01

    Full Text Available Introduction: The present research investigated the effects of two different types of music on cardiovascular responses in essential hypertensive men in comparison with healthy men based on introversion and extraversion. Methods: One hundred and thirteen hypertensive men referred to Madani Heart Hospital in Tabriz completed the NEO-FFI Questionnaire and after obtaining acceptable scores were classified in four groups: introvert patients, extravert patients, introvert healthy subjects, and extravert healthy subjects (each group with 25 samples with age range 31-50. Baseline blood pressure and heart rate of each subject was recorded without any stimulus. Then subjects were exposed to slow-beat music and blood pressure and heart rate were recorded. After15 minute break, and a little cognitive task for distraction, subjects were exposed to fast-beat music and blood pressure and heart rate were recorded again. Results: Multivariate analysis of covariance (MANCOVA test showed that extravert patient subjects obtained greater reduction in systolic blood pressure and heart rate after presenting slow-beat music compared with introvert patients (P= 0.035, and P= 0.033 respectively. And extravert healthy subjects obtained greater reduction in heart rate after presenting slow-beat music compared with introvert healthy subjects (P= 0.036. However, there are no significant differences between introvert and extravert groups in systolic and diastolic blood pressure and heart rate after presenting fast-beat music. Conclusion: Based on our results, introvert subjects experience negative emotions more than extravert subjects and negative emotions cause less change in blood pressure in these subjects compared with extravert subjects.

  18. Prevalence of arterial stiffness in North China, and associations with risk factors of cardiovascular disease: a community-based study

    Directory of Open Access Journals (Sweden)

    Wang Jin-Wen

    2012-12-01

    Full Text Available Abstract Background Brachial-ankle pulse wave velocity (baPWV, which reflects the stiffness of both central and peripheral muscular arteries, has been frequently used as a simple index for assessing arterial stiffness. The aim of the present study was to investigate the prevalence of arterial stiffness in North China based on baPWV measurements, and explore the associations between increased arterial stiffness and risk factors of cardiovascular diseases (CVD. Methods Twenty-three community populations were established in North China. For each participant, parameters for calculating baPWV, including blood pressures and pressure waveforms, were measured using a non-invasive automatic device. All participants were required to respond to an interviewer-led questionnaire including medical histories and demographic data, and to receive blood tests on biochemical indictors. Results A total of 2,852 participants were finally investigated. Among them, 1,201 people with low burden of CVD risk factors were chosen to be the healthy reference sample. The cut-off point of high baPWV was defined as age-specific 90th percentile of the reference sample. Thus, the prevalence of high baPWV was found to be 22.3% and 26.4% in men and women respectively. After adjusted for age, heart rate (HR, systolic blood pressure (SBP, fasting glucose level, and smoking were significantly associated with high baPWV in men; while level of serum total cholesterol (TC, HR, SBP, and diabetes were significantly associated with high baPWV in women. Conclusions Based on the age-specific cut-off points, the middle-aged population has a higher prevalence of high baPWV in North China. There exists a difference between men and women in terms of the potential risk factors associated with arterial stiffness.

  19. A Device for Fetal Monitoring by Means of Control Over Cardiovascular Parameters Based on Acoustic Data

    Science.gov (United States)

    Khokhlova, L. A.; Seleznev, A. I.; Zhdanov, D. S.; Zemlyakov, I. Yu; Kiseleva, E. Yu

    2016-01-01

    The problem of monitoring fetal health is topical at the moment taking into account a reduction in the level of fertile-age women's health and changes in the concept of perinatal medicine with reconsideration of live birth criteria. Fetal heart rate monitoring is a valuable means of assessing fetal health during pregnancy. The routine clinical measurements are usually carried out by the means of ultrasound cardiotocography. Although the cardiotocography monitoring provides valuable information on the fetal health status, the high quality ultrasound devices are expensive, they are not available for home care use. The recommended number of measurement is also limited. The passive and fully non-invasive acoustic recording provides an alternative low-cost measurement method. The article describes a device for fetal and maternal health monitoring by analyzing the frequency and periodicity of heart beats by means of acoustic signal received on the maternal abdomen. Based on the usage of this device a phonocardiographic fetal telemedicine system, which will allow to reduce the antenatal fetal mortality rate significantly due to continuous monitoring over the state of fetus regardless of mother's location, can be built.

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

    Science.gov (United States)

    Cosio, Borja G.; Soriano, Joan B.; López-Campos, Jose Luis; Calle, Myriam; Soler, Juan José; de-Torres, Juan Pablo; Marín, Jose Maria; Martínez, Cristina; de Lucas, Pilar; Mir, Isabel; Peces-Barba, Germán; Feu-Collado, Nuria; Solanes, Ingrid; Alfageme, Inmaculada

    2016-01-01

    Rationale 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. Objective We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. Methods 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. Results 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. Conclusions 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. PMID:27684372

  1. Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases.

    Directory of Open Access Journals (Sweden)

    Ronan Roussel

    Full Text Available According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk.Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09 with a follow-up of up to 30 months.Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and > 50 (men or 60 (women, but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death.Of the 31,652 patients enrolled, 4,058 (12.8% received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates and 2.21% (statins. The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR 540 of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR 540 = 1.73 (1.28-2.32.Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.

  2. Cardiovascular Outcomes of Sitagliptin in Type 2 Diabetic Patients with Acute Myocardial Infarction, a Population-Based Cohort Study in Taiwan.

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    Szu-Heng Wang

    Full Text Available The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4 inhibitor, in type 2 diabetic patients after acute myocardial infarction (AMI has so far remained uncertain.We analyzed data from the National Health Insurance Research Database (NHIRD, a government-operated, population-based database, from March 1st, 2009 to December 31st, 2011. Type 2 diabetic patients hospitalized for AMI were included in our study. We compared subjects using sitagliptin with comparison group to evaluate its cardiovascular safety and efficacy. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and ischemic stroke.We identified a total of 3,282 type 2 diabetic patients hospitalized for AMI (mean follow-up 1.15 years. Of these patients, 547 (16.7% who were exposed to sitagliptin were defined as the sitagliptin group and 2,735 (83.3 % who did not use sitagliptin were the comparison group. The incidence of primary composite cardiovascular outcomes was 9.50 per 100 person-years in the sitagliptin group and was 9.70 per 100 person-years in the comparison group (hazard ratio (HR, 0.97; 95% CI, 0.73-1.29, P=0.849. Compared to the non-sitagliptin group, the sitagliptin group had similar risks of all-cause mortality, hospitalization for heart failure (HF or percutaneous coronary intervention (PCI with a HR of 0.82 (95% CI, 0.61-1.11, P=0.195, 0.93 (95% CI, 0.67-1.29, P=0.660, and 0.93 (95% CI, 0.75-1.14, P=0.473, respectively.The use of sitagliptin in type 2 diabetic patients with recent AMI was not associated with increased risk of adverse cardiovascular events.

  3. Enabling Metabolomics Based Biomarker Discovery Studies Using Molecular Phenotyping of Exosome-Like Vesicles.

    Directory of Open Access Journals (Sweden)

    Tatiana Altadill

    Full Text Available Identification of sensitive and specific biomarkers with clinical and translational utility will require smart experimental strategies that would augment expanding the breadth and depth of molecular measurements within the constraints of currently available technologies. Exosomes represent an information rich matrix to discern novel disease mechanisms that are thought to contribute to pathologies such as dementia and cancer. Although proteomics and transcriptomic studies have been reported using Exosomes-Like Vesicles (ELVs from different sources, exosomal metabolome characterization and its modulation in health and disease remains to be elucidated. Here we describe methodologies for UPLC-ESI-MS based small molecule profiling of ELVs from human plasma and cell culture media. In this study, we present evidence that indeed ELVs carry a rich metabolome that could not only augment the discovery of low abundance biomarkers but may also help explain the molecular basis of disease progression. This approach could be easily translated to other studies seeking to develop predictive biomarkers that can subsequently be used with simplified targeted approaches.

  4. Cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Graversen, Peter; Abildstrøm, Steen Z; Jespersen, Lasse

    2016-01-01

    (ECG) abnormalities, heart rate, family history (of ischaemic heart disease), body mass index (BMI), waist-hip ratio, walking duration and pace, leisure time physical activity, forced expiratory volume (FEV)1%pred, household income, education, vital exhaustion, high-density lipoprotein (HDL......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...

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

    Directory of Open Access Journals (Sweden)

    Eils Roland

    2005-11-01

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

  6. Fabrication of polyurethane and polyurethane based composite fibres by the electrospinning technique for soft tissue engineering of cardiovascular system.

    Science.gov (United States)

    Kucinska-Lipka, J; Gubanska, I; Janik, H; Sienkiewicz, M

    2015-01-01

    Electrospinning is a unique technique, which provides forming of polymeric scaffolds for soft tissue engineering, which include tissue scaffolds for soft tissues of the cardiovascular system. Such artificial soft tissues of the cardiovascular system may possess mechanical properties comparable to native vascular tissues. Electrospinning technique gives the opportunity to form fibres with nm- to μm-scale in diameter. The arrangement of obtained fibres and their surface determine the biocompatibility of the scaffolds. Polyurethanes (PUs) are being commonly used as a prosthesis of cardiovascular soft tissues due to their excellent biocompatibility, non-toxicity, elasticity and mechanical properties. PUs also possess fine spinning properties. The combination of a variety of PU properties with an electrospinning technique, conducted at the well tailored conditions, gives unlimited possibilities of forming novel polyurethane materials suitable for soft tissue scaffolds applied in cardiovascular tissue engineering. This paper can help researches to gain more widespread and deeper understanding of designing electrospinable PU materials, which may be used as cardiovascular soft tissue scaffolds. In this paper we focus on reagents used in PU synthesis designed to increase PU biocompatibility (polyols) and biodegradability (isocyanates). We also describe suggested surface modifications of electrospun PUs, and the direct influence of surface wettability on providing enhanced biocompatibility of scaffolds. We indicate a great influence of electrospinning parameters (voltage, flow rate, working distance) and used solvents (mostly DMF, THF and HFIP) on fibre alignment and diameter - what impacts the biocompatibility and hemocompatibility of such electrospun PU scaffolds. Moreover, we present PU modifications with natural polymers with novel approach applied in electrospinning of PU scaffolds. This work may contribute with further developing of novel electrospun PUs, which may be

  7. 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 Jr, Kenneth L; Mitchell, Valerie; Saygbe, Johnetta N; Johnson, Twanda D; Curry, Rev. Kendrick E; Johnson, Allan A; Graham, Avis P; Graham, Lennox A

    2016-01-01

    Background 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. Objective 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. Methods 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. Results Study participants (5 males, 3 females) were African American and age 28-70 years

  8. Caracterización mecánica de materiales de base colágeno para aplicaciones cardiovasculares

    OpenAIRE

    Tobaruela Arnedo, María de la Almudena

    2016-01-01

    Las enfermedades cardiovasculares son una de las principales causas de muerte en el mundo. Este hecho ha propiciado que numerosas investigaciones se hayan centrado en la mejora de las prótesis cardiovasculares ya existentes así como en la búsqueda de nuevos materiales más resistentes, duraderos y biocompatibles. Actualmente, existen dos tipos principales de prótesis valvulares: las mecánicas y las biológicas. En muchos países cada vez es más frecuente el uso de estas últimas. Las válvulas bio...

  9. [Research on distribution of patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular based on cluster analysis].

    Science.gov (United States)

    YANG, Xu-Jie; XIAO, Shi-Ying

    2015-09-01

    To discuss the distribution of patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular, the patents' holders for Chinese herbal compounds in treating cardiovascular and cerebrovascular were cluster analyzed by means of simple statistics and cluster analysis. Clustering variables were composed of patent applications, patent maintained number, related papers' quantity, etc. Chinese herbal compound patents' holders were divided into four categories according to their different scientific research and patent strength. It is the magic weapon for Chinese herbal compound patents' holders that have scientific research patents' transforming and make coordination of patent protection and scientific innovation.

  10. A new versatile database created for geneticists and breeders to link molecular and phenotypic data in perennial crops: the AppleBreed DataBase

    NARCIS (Netherlands)

    Antofie, A.; Lateur, M.; Oger, R.; Patocchi, A.; Durel, C.E.; Weg, van de W.E.

    2007-01-01

    Objective: AppleBreed DataBase (DB) aims to store genotypic and phenotypic data from multiple pedigree verified plant populations (crosses, breeding selections and commercial cultivars) so that they are easily accessible for geneticists and breeders. It will help in elucidating the genetics of econo

  11. 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.

  12. COPD: Definition and Phenotypes

    DEFF Research Database (Denmark)

    Vestbo, J.

    2014-01-01

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

  13. The DFNA10 phenotype.

    NARCIS (Netherlands)

    Leenheer, E. de; Huygen, P.L.M.; Wayne, S.; Smith, R.J.H.; Cremers, C.W.R.J.

    2001-01-01

    We present a detailed analysis of the DFNA10 phenotype based on data from 25 hearing-impaired persons coming from a large American pedigree segregating for deafness at the DFNA10 locus (chromosome 6q22.3-23.2). Cross-sectional analysis of air conduction threshold-on-age data from all available last-

  14. Effect of eprosartan-based therapy on systolic blood pressure and total cardiovascular risk in a large international population: preliminary report of the observational POWER study

    Directory of Open Access Journals (Sweden)

    Goudev A

    2012-09-01

    Full Text Available Assen Goudev,1 Jean-Pascal Berrou,2 Atul Pathak3 On behalf of the POWER Investigators1Department of Cardiology, Queen Giovanna University Hospital, Sofia, Bulgaria; 2Strategic Medical Affairs, CardioMetabolic Established Products, Abbott Products Operations AG, Allschwil, Switzerland; 3Faculte´ de Médecine et CHU Toulouse, Unité de Pharmacologie Cardiovasculaire et Autonome, Service de Pharmacologie et Cardiologie, INSERM U 1048, Université Paul Sabatier, Toulouse, FranceBackground: Estimation of total cardiovascular risk is useful for developing preventive strategies for individual patients. The POWER (Physicians' Observational Work on Patient Education According to their Vascular Risk survey, a 6-month, open-label, multinational, post-marketing observational evaluation of eprosartan, an angiotensin II receptor blocker, was undertaken to assess the efficacy and safety of eprosartan-based therapy in the treatment of high arterial blood pressure in a large population recruited from 16 countries with varying degrees of baseline cardiovascular risk, and the effect of eprosartan-based therapy on total cardiovascular risk, as represented by the SCORE® (Systematic Coronary Risk Assessment or Framingham risk equations.Methods: Participating physicians recruited > 29,000 hypertensive patients whom they considered to be candidates (according to specified criteria for treatment with eprosartan 600 mg/day, with other drugs added at the discretion of the physician.Results: During treatment, systolic blood pressure decreased by 25.8 ± 14.4 mmHg to 134.6 ± 11.4 mmHg (P < 0.001, mean diastolic blood pressure fell by 12.6 ± 9.5 mmHg to 81.1 ± 7.6 mmHg, and pulse pressure fell by 13.2 ± 13.5 mmHg to 53.6 ± 11.4 mmHg (both P < 0.01. Calculated total cardiovascular risk declined in parallel with the reduction in blood pressure.Conclusion: The POWER study has demonstrated, in a large and nonselected population, the feasibility and practicability of

  15. Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis.

    Science.gov (United States)

    Schulz, Martin Michael Peter; Reisen, Felix; Zgraggen, Silvana; Fischer, Stephanie; Yuen, Don; Kang, Gyeong Jin; Chen, Lu; Schneider, Gisbert; Detmar, Michael

    2012-10-02

    Lymphangiogenesis plays an important role in promoting cancer metastasis to sentinel lymph nodes and beyond and also promotes organ transplant rejection. We used human lymphatic endothelial cells to establish a reliable three-dimensional lymphangiogenic sprouting assay with automated image acquisition and analysis for inhibitor screening. This high-content phenotype-based assay quantifies sprouts by automated fluorescence microscopy and newly developed analysis software. We identified signaling pathways involved in lymphangiogenic sprouting by screening the Library of Pharmacologically Active Compounds (LOPAC)(1280) collection of pharmacologically relevant compounds. Hit characterization revealed that mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors substantially block lymphangiogenesis in vitro and in vivo. Importantly, the drug class of statins, for the first time, emerged as potent inhibitors of lymphangiogenic sprouting in vitro and of corneal and cutaneous lymphangiogenesis in vivo. This effect was mediated by inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and subsequently the isoprenylation of Rac1. Supplementation with the enzymatic products of HMG-CoA reductase functionally rescued lymphangiogenic sprouting and the recruitment of Rac1 to the plasma membrane.

  16. Detection of overlapping protein complexes in gene expression, phenotype and pathways of Saccharomyces cerevisiae using Prorank based Fuzzy algorithm.

    Science.gov (United States)

    Manikandan, P; Ramyachitra, D; Banupriya, D

    2016-04-15

    Proteins show their functional activity by interacting with other proteins and forms protein complexes since it is playing an important role in cellular organization and function. To understand the higher order protein organization, overlapping is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Most of the clustering algorithms do not consider the weighted as well as overlapping complexes. In this research, Prorank based Fuzzy algorithm has been proposed to find the overlapping protein complexes. The Fuzzy detection algorithm is incorporated in the Prorank algorithm after ranking step to find the overlapping community. The proposed algorithm executes in an iterative manner to compute the probability of robust clusters. The proposed and the existing algorithms were tested on different datasets such as PPI-D1, PPI-D2, Collins, DIP, Krogan Core and Krogan-Extended, gene expression such as GSE7645, GSE22269, GSE26923, pathways such as Meiosis, MAPK, Cell Cycle, phenotypes such as Yeast Heterogeneous and Yeast Homogeneous datasets. The experimental results show that the proposed algorithm predicts protein complexes with better accuracy compared to other state of art algorithms.

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

    Directory of Open Access Journals (Sweden)

    Stephen C Collins

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

  18. SORTA: a system for ontology-based re-coding and technical annotation of biomedical phenotype data.

    Science.gov (United States)

    Pang, Chao; Sollie, Annet; Sijtsma, Anna; Hendriksen, Dennis; Charbon, Bart; de Haan, Mark; de Boer, Tommy; Kelpin, Fleur; Jetten, Jonathan; van der Velde, Joeri K; Smidt, Nynke; Sijmons, Rolf; Hillege, Hans; Swertz, Morris A

    2015-01-01

    There is an urgent need to standardize the semantics of biomedical data values, such as phenotypes, to enable comparative and integrative analyses. However, it is unlikely that all studies will use the same data collection protocols. As a result, retrospective standardization is often required, which involves matching of original (unstructured or locally coded) data to widely used coding or ontology systems such as SNOMED CT (clinical terms), ICD-10 (International Classification of Disease) and HPO (Human Phenotype Ontology). This data curation process is usually a time-consuming process performed by a human expert. To help mechanize this process, we have developed SORTA, a computer-aided system for rapidly encoding free text or locally coded values to a formal coding system or ontology. SORTA matches original data values (uploaded in semicolon delimited format) to a target coding system (uploaded in Excel spreadsheet, OWL ontology web language or OBO open biomedical ontologies format). It then semi- automatically shortlists candidate codes for each data value using Lucene and n-gram based matching algorithms, and can also learn from matches chosen by human experts. We evaluated SORTA's applicability in two use cases. For the LifeLines biobank, we used SORTA to recode 90 000 free text values (including 5211 unique values) about physical exercise to MET (Metabolic Equivalent of Task) codes. For the CINEAS clinical symptom coding system, we used SORTA to map to HPO, enriching HPO when necessary (315 terms matched so far). Out of the shortlists at rank 1, we found a precision/recall of 0.97/0.98 in LifeLines and of 0.58/0.45 in CINEAS. More importantly, users found the tool both a major time saver and a quality improvement because SORTA reduced the chances of human mistakes. Thus, SORTA can dramatically ease data (re)coding tasks and we believe it will prove useful for many more projects. Database URL: http://molgenis.org/sorta or as an open source download from

  19. Stress and atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Inoue, Nobutaka

    2014-01-01

    Recent major advances in medical science have introduced a wide variety of treatments against atherosclerosis-based cardiovascular diseases, which has led to a significant reduction in mortality associated with these diseases. However, atherosclerosis-based cardiovascular disease remains a leading cause of death. Furthermore, progress in medical science has demonstrated the pathogenesis of cardiovascular disease to be complicated, with a wide variety of underlying factors. Among these factors, stress is thought to be pivotal. Several types of stress are involved in the development of cardiovascular disease, including oxidative stress, mental stress, hemodynamic stress and social stress. Accumulating evidence indicates that traditional risk factors for atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking, induce oxidative stress in the vasculature. Oxidative stress is implicated in the pathogenesis of endothelial dysfunction, atherogenesis, hypertension and remodeling of blood vessels. Meanwhile, mental stress is a well-known major contributor to the development of cardiovascular disease. The cardiovascular system is constantly exposed to hemodynamic stress by the blood flow and/or pulsation, and hemodynamic stress exerts profound effects on the biology of vascular cells and cardiomyocytes. In addition, social stress, such as that due to a lack of social support, poverty or living alone, has a negative impact on the incidence of cardiovascular disease. Furthermore, there are interactions between mental, oxidative and hemodynamic stress. The production of reactive oxygen species is increased under high levels of mental stress in close association with oxidative stress. These stress responses and their interactions play central roles in the pathogenesis of atherosclerosis-based cardiovascular disease. Accordingly, the pathophysiological and clinical implications of stress are discussed in this article.

  20. Literature-based genetic risk scores for coronary heart disease : the Cardiovascular Registry Maastricht (CAREMA) Prospective Cohort Study

    NARCIS (Netherlands)

    Vaathorst, A.A.; Lu Yingchang (Kevin), Y.; Heijmans, B.T.; Dolle, M.E.; Bohringer, S.; Putter, de H.; Imholz, S.; Merry, A.H.; Greevenbroek, M.M.; Jukema, J.W.; Gorgels, A.P.; Brandt, van den P.A.; Muller, M.R.; Schouten, L.J.; Feskens, E.J.M.; Boer, J.M.A.; Slagboom, P.E.

    2012-01-01

    Background-Genome-wide association studies (GWAS) have identified many single-nucleotide polymorphisms (SNPs) associated with coronary heart disease (CHD) or CHD risk factors (RF). Using a case-cohort study within the prospective Cardiovascular Registry Maastricht (CAREMA) cohort, we tested if genet

  1. Susceptibility of the aging Brown Norway rat to carbaryl, an anti-cholinesterase-based insecticide: Thermoregulatory and cardiovascular responses.

    Science.gov (United States)

    The proportion of aged in the United States is projected to expand markedly for the next several decades. Hence, the U.S.EPA is assessing if the aged are more susceptible to environmental toxicants. The thermoregulatory and cardiovascular responses of young adult, mature adult, a...

  2. Blood pressure-lowering treatment based on cardiovascular risk : a meta-analysis of individual patient data

    NARCIS (Netherlands)

    Sundström, Johan; Arima, Hisatomi; Woodward, Mark; Jackson, Rod; Karmali, Kunal; Lloyd-Jones, Donald; Baigent, Colin; Emberson, Jonathan; Rahimi, Kazem; MacMahon, Stephen; Patel, Anushka; Perkovic, Vlado; Turnbull, Fiona; Neal, Bruce; de Zeeuw, Dick

    2014-01-01

    BACKGROUND: We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy

  3. 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

    2015-01-01

    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 (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) 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. PMID:25758824

  4. FGFR2 mutation in a patient without typical features of Pfeiffer syndrome--The emerging role of combined NGS and phenotype based strategies.

    Science.gov (United States)

    Flöttmann, Ricarda; Knaus, Alexej; Zemojtel, Tomasz; Robinson, Peter N; Mundlos, Stefan; Horn, Denise; Spielmann, Malte

    2015-08-01

    Pfeiffer syndrome (MIM: #101600) is a rare autosomal dominant disorder classically characterized by limb and craniofacial anomalies. It is caused by heterozygous mutations in the fibroblast growth factor receptors types 1 and 2 (FGFR1 and FGFR2). We applied a next generation sequencing (NGS) panel approach comprising all 2877 genes currently known to be causative for one or more Mendelian diseases combined with the phenotype based computational tool PhenIX (Phenotypic Interpretation of eXomes). We report on a patient presenting with multiple anomalies of hands and feet including brachydactyly and symphalangism. No clinical diagnosis could be established based on the clinical findings and testing of several genes associated with brachydactyly and symphalangism failed to identify mutations. Via next generation sequencing (NGS) panel approach we then identified a novel de novo missense FGFR2 mutation affecting an amino acid reported to be mutated in Pfeiffer syndrome. Since our patient shows typical radiological findings of Pfeiffer syndrome in hands and feet but at the same time lacks several characteristic features such as clinical signs of craniosynostosis and prominent eyes we suggest introducing the term "FGFR2 associated phenotypes" for similar cases. Our results highlight the emerging role of combined NGS and phenotype based bioinformatics strategies to establish clinical diagnoses.

  5. The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases.

    Science.gov (United States)

    Laakso, Markku; Kuusisto, Johanna; Stančáková, Alena; Kuulasmaa, Teemu; Pajukanta, Päivi; Lusis, Aldons J; Collins, Francis S; Mohlke, Karen L; Boehnke, Michael

    2017-03-01

    The Metabolic Syndrome in Men (METSIM) study is a population-based study including 10,197 Finnish men examined in 2005-2010. The aim of the study is to investigate nongenetic and genetic factors associated with the risk of T2D and CVD, and with cardiovascular risk factors. The protocol includes a detailed phenotyping of the participants, an oral glucose tolerance test, fasting laboratory measurements including proton NMR measurements, mass spectometry metabolomics, adipose tissue biopsies from 1,400 participants, and a stool sample. In our ongoing follow-up study, we have, to date, reexamined 6,496 participants. Extensive genotyping and exome sequencing have been performed for essentially all METSIM participants, and >2,000 METSIM participants have been whole-genome sequenced. We have identified several nongenetic markers associated with the development of diabetes and cardiovascular events, and participated in several genetic association studies to identify gene variants associated with diabetes, hyperglycemia, and cardiovascular risk factors. The generation of a phenotype and genotype resource in the METSIM study allows us to proceed toward a "systems genetics" approach, which includes statistical methods to quantitate and integrate intermediate phenotypes, such as transcript, protein, or metabolite levels, to provide a global view of the molecular architecture of complex traits.

  6. Phenotypic transition maps of 3D breast acini obtained by imaging-guided agent-based modeling

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jonathan; Enderling, Heiko; Becker-Weimann, Sabine; Pham, Christopher; Polyzos, Aris; Chen, Chen-Yi; Costes, Sylvain V

    2011-02-18

    We introduce an agent-based model of epithelial cell morphogenesis to explore the complex interplay between apoptosis, proliferation, and polarization. By varying the activity levels of these mechanisms we derived phenotypic transition maps of normal and aberrant morphogenesis. These maps identify homeostatic ranges and morphologic stability conditions. The agent-based model was parameterized and validated using novel high-content image analysis of mammary acini morphogenesis in vitro with focus on time-dependent cell densities, proliferation and death rates, as well as acini morphologies. Model simulations reveal apoptosis being necessary and sufficient for initiating lumen formation, but cell polarization being the pivotal mechanism for maintaining physiological epithelium morphology and acini sphericity. Furthermore, simulations highlight that acinus growth arrest in normal acini can be achieved by controlling the fraction of proliferating cells. Interestingly, our simulations reveal a synergism between polarization and apoptosis in enhancing growth arrest. After validating the model with experimental data from a normal human breast line (MCF10A), the system was challenged to predict the growth of MCF10A where AKT-1 was overexpressed, leading to reduced apoptosis. As previously reported, this led to non growth-arrested acini, with very large sizes and partially filled lumen. However, surprisingly, image analysis revealed a much lower nuclear density than observed for normal acini. The growth kinetics indicates that these acini grew faster than the cells comprising it. The in silico model could not replicate this behavior, contradicting the classic paradigm that ductal carcinoma in situ is only the result of high proliferation and low apoptosis. Our simulations suggest that overexpression of AKT-1 must also perturb cell-cell and cell-ECM communication, reminding us that extracellular context can dictate cellular behavior.

  7. O perfil de saúde cardiovascular dos idosos brasileiros precisa melhorar: estudo de base populacional The profile of cardiovascular health of elderly brazilian people needs to improve: a population-based study

    Directory of Open Access Journals (Sweden)

    Janaina Caldeira Pereira

    2008-07-01

    Full Text Available FUNDAMENTO: No Brasil, existe pouca informação de base populacional sobre a aglomeração de fatores de risco e sua relação com doenças cardiovasculares em idosos. OBJETIVO: Estimar prevalência e aglomeração de fatores de risco e investigar associação com doença isquêmica do coração (DIC em idosos. MÉTODOS: Foram incluídos todos os participantes > 60 anos do "Inquérito domiciliar sobre comportamentos de risco e morbidade referida de doenças e agravos não-transmissíveis", realizado pelo Ministério da Saúde em 2002/2003, em quinze capitais e no Distrito Federal. Investigou-se a prevalência de fatores de risco (tabagismo, consumo de álcool, inatividade física, dieta inadequada e obesidade e de morbidade referida (hipertensão, hipercolesterolemia e diabete, além da associação entre DIC e aglomeração desses fatores pela regressão de Poisson. RESULTADOS: Os idosos representaram 13,4% (3.142/23.457, 59,4% mulheres e 40,6% homens. A idade média foi de 69,5 anos. Prevalências de dieta inadequada, inatividade física, obesidade, tabagismo e consumo de risco de álcool foram 94,4%, 40%, 17%, 12,7%e 3,2%, respectivamente. Cerca de 50% referiram hipertensão; 33% hipercolesterolemia e 18%, diabete. Tabagismo e hipercolesterolemia reduziram significativamente com a idade. Hipertensão, inatividade física, obesidade e hipercolesterolemia foram mais prevalentes em mulheres. Aglomeração de dois ou mais fatores foi observada em 71,3% dos idosos e reduziu com o avançar da idade. Idosos com DIC apresentaram uma prevalência quatro vezes maior de aglomeração de quatro ou mais fatores (RP = 4,1; IC_95%: 2,6-6,4. CONCLUSÃO: A associação entre DIC e maior aglomeração de fatores de risco expressa, provavelmente, maior risco acumulado ao longo da vida, mas indica também a necessidade de melhorar o perfil de risco desses idosos.BACKGROUND: In Brazil, population-based information on risk factors and their relationship with

  8. Cytokines and hs-CRP levels in individuals treated with low-dose aspirin for cardiovascular prevention: a population-based study (CoLaus Study).

    Science.gov (United States)

    Vaucher, Julien; Marques-Vidal, Pedro; Waeber, Gérard; Vollenweider, Peter

    2014-04-01

    Pro-inflammatory cytokines and high-sensitive C-reactive protein (hs-CRP) are associated with increased risk for cardiovascular disease. Low-dose aspirin for CV prevention is reported to have anti-inflammatory effects. The aim of this study was to determine the association between pro-inflammatory cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention in a population-based cohort (CoLaus Study). We assessed blood samples in 6085 participants (3201 women) aged 35-75years. Medications' use and indications were recorded. Among aspirin users (n=1'034; 17%), overall low-dose users (351; 5.8%) and low-dose for cardiovascular prevention users (324; 5.3%) were selected for analysis. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α were assessed by a multiplex particle-based flow cytometric assay and hs-CRP by an immunometric assay. Cytokines and hs-CRP were presented in quartiles. Multivariate analysis adjusting for sex, age, smoking status, body mass index, diabetes mellitus and immunomodulatory drugs showed no association between cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention, either comparing the topmost vs. the three other quartiles (OR 95% CI, 0.84 (0.59-1.18), 1.03 (0.78-1.32), 1.10 (0.83-1.46), 1.00 (0.67-1.69) for IL-1β, IL-6, TNF-α and hs-CRP, respectively), or comparing the topmost quartile vs. the first one (OR 95% CI, 0.87 (0.60-1.26), 1.19 (0.79-1.79), 1.26 (0.86-1.84), 1.06 (0.67-1.69)). Low-dose aspirin use for cardiovascular prevention does not impact plasma pro-inflammatory cytokine and hs-CRP levels in a population-based cohort.

  9. Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness.

    Science.gov (United States)

    Polak, Emil; Ficek, Andrej; Radvanszky, Jan; Soltysova, Andrea; Urge, Otto; Cmelova, Eleonora; Kantarska, Dana; Kadasi, Ludevit

    2013-09-10

    We investigated the mutation spectrum of the phenylalanine hydroxylase gene (PAH) in a cohort of patients from 135 Slovak PKU families. Mutational screening of the known coding region, including conventional intron splice sites, was performed using high-resolution melting analysis, with subsequent sequencing analysis of the samples showing deviated melting profiles compared to control samples. The PAH gene was also screened for deletions and duplications using MLPA analysis. Forty-eight different disease causing mutations were identified in our patient group, including 30 missense, 8 splicing, 7 nonsense, 2 large deletions and 1 small deletion with frameshift; giving a detection rate of 97.6%. The most prevalent mutation was the p.R408W, occurring in 47% of all alleles, which concurs with results from neighboring and other Slavic countries. Other frequent mutations were: p.R158Q (5.3%), IVS12+1G>A (5.3%), p.R252W (5.1%), p.R261Q (3.9%) and p.A403V (3.6%). We also identified three novel missense mutations: p.F233I, p.R270I, p.F331S and one novel variant: c.-30A>T in the proximal part of the PAH gene promoter. A spectrum of 84 different genotypes was observed and a genotype based predictions of BH4-responsiveness were assessed. Among all genotypes, 36 were predicted to be BH4-responsive represented by 51 PKU families. In addition, genotype-phenotype correlations were performed.

  10. Genotyping using whole-genome sequencing is a realistic alternative to surveillance based on phenotypic antimicrobial susceptibility testing

    DEFF Research Database (Denmark)

    Zankari, Ea; Hasman, Henrik; Kaas, Rolf Sommer;

    2013-01-01

    genes and MLST types (where MLST stands for multilocus sequence typing). ResFinder results were compared with phenotypic antimicrobial susceptibility testing results using EUCAST epidemiological cut-off values and MLST types. Results: A total of 3051 different phenotypic tests were performed; 482 led......-genome sequencing (WGS) may soon be within reach even for routine surveillance and clinical diagnostics. The aim of this study was to evaluate WGS as a routine tool for surveillance of antimicrobial resistance compared with current phenotypic procedures. Methods: Antimicrobial susceptibility tests were performed...... on 200 isolates originating from Danish pigs, covering four bacterial species. Genomic DNA was purified from all isolates and sequenced as paired-end reads on the Illumina platform. The web servers ResFinder and MLST (www.genomicepidemiology.org) were used to identify acquired antimicrobial resistance...

  11. The "lipid accumulation product" performs better than the body mass index for recognizing cardiovascular risk: a population-based comparison

    Directory of Open Access Journals (Sweden)

    Kahn Henry S

    2005-09-01

    Full Text Available Abstract Background Body mass index (BMI, kg/m2 may not be the best marker for estimating the risk of obesity-related disease. Consistent with physiologic observations, an alternative index uses waist circumference (WC and fasting triglycerides (TG concentration to describe lipid overaccumulation. Methods The WC (estimated population minimum 65 cm for men and 58 cm for women and TG concentration from the third National Health and Nutrition Examination Survey (N = 9,180, statistically weighted to represent 100.05 million US adults were used to compute a "lipid accumulation product" [LAP = (WC-65 × TG for men and (WC-58 × TG for women] and to describe the population distribution of LAP. LAP and BMI were compared as categorical variables and as log-transformed continuous variables for their ability to identify adverse levels of 11 cardiovascular risk factors. Results Nearly half of the represented population was discordant for their quartile assignments to LAP and BMI. When 23.54 million with ordinal LAP quartile > BMI quartile were compared with 25.36 million with ordinal BMI quartile > LAP quartile (regression models adjusted for race-ethnicity and sex the former had more adverse risk levels than the latter (p 0.1. As continuous variables, LAP provided a consistently more adverse beta coefficient (slope than BMI for nine cardiovascular risk variables (p 0.2. Conclusion LAP (describing lipid overaccumulation performed better than BMI (describing weight overaccumulation for identifying US adults at cardiovascular risk. Compared to BMI, LAP might better predict the incidence of cardiovascular disease, but this hypothesis needs prospective testing.

  12. Medication effectiveness may not be the major reason for accepting cardiovascular preventive medication: A population-based survey

    Directory of Open Access Journals (Sweden)

    Harmsen Charlotte

    2012-08-01

    Full Text Available Abstract Background Shared decision-making and patients’ choice of interventions are areas of increasing importance, not least seen in the light of the fact that chronic conditions are increasing, interventions considered important for public health, and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases (CVD is prevalent. A better understanding of patients’ medication-taking behavior is needed and may be reached by studying the reasons why people accept or decline medication recommendations. The aim of this paper was to identify factors that may influence people’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer. Methods From a random sample of 4,000 people aged 40–59 years in a Danish population, 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication. After receiving ‘complete’ information about effectiveness of the medication they were asked whether they would accept medication. Finally, they were asked about reasons for the decision. Results A total of 725 (67% of 1,082 participants accepted the medication offer. Even quite large effects of medication (up to 8 percentage points absolute risk reduction had a smaller impact on acceptance to medication than personal experience with cardiovascular disease. Furthermore, increasing age of the participant and living with a partner were significantly associated with acceptance. Some 45% of the respondents accepting justified their choice as being for health reasons, and they were more likely to be women, live alone, have higher income and higher education levels. Among those who did not accept the medication offer, 56% indicated that they would rather prefer to change lifestyle. Conclusions Medication effectiveness seems to have a moderate influence on people’s decisions to accept preventive medication, while factors such as

  13. Increased cardiovascular mortality more than fifteen years after radiotherapy for breast cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Darby Sarah

    2007-01-01

    Full Text Available Abstract Background Breast radiotherapy as practised in the 1970s and 1980s resulted in significant myocardial exposure, and this was higher when the left breast was treated. It has been proposed that this difference might result in greater cardiovascular mortality following irradiation of the left breast when compared with the right. Methods All cases of female breast cancer diagnosed between 1971 and 1988 and recorded on the Thames Cancer Registry database were followed up to the end of 2003 to identify cases who had died from ischaemic heart disease (IHD or any cardiovascular disease (CVD. A proportional hazards regression analysis was performed, stratified by time since diagnosis, using as the baseline group those women with right-sided disease who did not receive radiotherapy, and adjusting for age at diagnosis. Results A total of 20,871 women with breast cancer were included in the analysis, of which 51% had left-sided disease. Mortality at 15+ years after diagnosis was increased in recipients of left-breast radiotherapy compared to non-irradiated women with right-sided breast cancer, both for IHD (hazard ratio 1.59; 95% confidence interval 1.21–2.08; p = 0.001 and all CVD (hazard ratio 1.27; 95% confidence interval 1.07–1.51; p = 0.006. When irradiated women with left-sided breast cancer were compared with irradiated women with right-sided breast cancer, cardiovascular mortality at 15+ years after diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence interval 0.95–1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval 1.05–1.49; p = 0.014. Conclusion We have found an elevation in cardiovascular mortality more than 15 years after breast radiotherapy in women diagnosed with breast cancer between 1971 and 1988. The risk was greater following irradiation of the left breast compared with the right. This confirms that radiotherapy as practised in the 1970s and 1980s has resulted in significant long

  14. Cardiovascular physiology and diseases of the rabbit.

    Science.gov (United States)

    Pariaut, Romain

    2009-01-01

    This article reviews what is known about the diagnosis and management of cardiovascular diseases in the pet rabbit. Current knowledge is based on anecdotal reports, derived from research data using the rabbit as an animal model of human cardiovascular diseases, but most importantly canine and feline cardiology. It is likely that, as cardiovascular diseases are more often recognized, more specific information will soon become available for the treatment of the pet rabbit with cardiac disease.

  15. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

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

    DEFF Research Database (Denmark)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for th...

  17. Adapting Phonological Awareness Interventions for Children with Down Syndrome Based on the Behavioral Phenotype: A Promising Approach?

    Science.gov (United States)

    Lemons, Christopher J.; King, Seth A.; Davidson, Kimberly A.; Puranik, Cynthia S.; Fulmer, Deborah; Mrachko, Alicia A.; Partanen, Jane; Al Otaiba, Stephanie; Fidler, Deborah J.

    2015-01-01

    Many children with Down syndrome demonstrate deficits in phonological awareness, a prerequisite to learning to read in an alphabetic language. The purpose of this study was to determine whether adapting a commercially available phonological awareness program to better align with characteristics associated with the behavioral phenotype of Down…

  18. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  19. Evolution of Framingham cardiovascular risk score in HIV-infected patients initiating EFV- and LPV/r-based HAART in a Latin American cohort

    Directory of Open Access Journals (Sweden)

    Diego Cecchini

    2014-11-01

    Full Text Available Introduction: Epidemiological studies suggest that some antiretroviral drugs may contribute to increase cardiovascular risk in HIV-infected patients. However, data from Latin American countries are limited, as impact of HAART on cardiovascular risk remains understudied. In this context, we aimed to evaluate if 10-year Framingham Cardiovascular Risk Score (FCRS increases in patients following exposure to EFV- and LPV/r-based HAART in a Latin American cohort. Materials and Methods: Retrospective 48-week cohort study. We reviewed clinical charts of randomly selected samples of patients initiating (according to national guidelines EFV first-line HAART and LPV/r first- or second-line (but first PI-based HAART assisted at a reference HIV centre in Buenos Aires, Argentina (period 2004–2012. Each patient could only be included in one arm. FCRS was calculated according to National Institutes of Health risk assessment tool (http://cvdrisk.nhlbi.nih.gov/. Results: A total of 357 patients were included: 249 in EFV arm and 108 in LPV/r arm (80 as first line and 28 as second line, but first PI-based HAART. Baseline characteristics (median, interquartile range: age, 38 (33–45 years; male, 247 (69%; viral load, 98200 (20550–306000 copies/mL; CD4 T-cell count, 115 (60–175 cel/µL; total cholesterol, 159 (135–194 mg/dL; HDL: 39 (31–41 mg/dL; LDL: 94 (72–123 mg/dL; current smoker, 29%; on antihypertensive drugs: 14 (4%, diabetic: 4 (1%. Most frequent accompanying nucleoside reverse transcriptase inhibitors (NRTIs were 3TC (92% and zidovudine (AZT; 76%. Baseline FCRS was low, moderate and high for 93%, 7% and 0% of patients on EFV arm and 96.7%, 1.7% and 1.7% on LPV/r arm. On EFV arm, an increase in FCRS category (low to moderate or moderate to high was observed in 1 patient (0.9% at 24 weeks and 6 (5,6% at 48 weeks; 5 (4.7% decreased category. On LPV/r arm no one varied FCRS category at 24 weeks and 2 (3.4% increased from low to moderate at 48 weeks

  20. The relation of metabolic syndrome according to five definitions to cardiovascular risk factors - a population-based study

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    Lai Ming-May

    2009-12-01

    Full Text Available Abstract Background Although National Cholesterol Education Program (NCEP, International Diabetes Federation (IDF, American Heart Association and National Heart, Lung and Blood Institute (AHA/NHLBI, World Health Organization (WHO, and the European Group for the Study of Insulin Resistance (EGIR definitions of metabolic syndrome (MetS have been commonly used by studies, little is known about agreement among these five definitions. We examined the agreement among these five definitions and explored their relationship with risk factors of cardiovascular disease in a Taiwan population. Methods A total of 1305 subjects aged 40 years and over in Taiwan were analyzed. Biomedical markers and anthropometric indices were measured. Agreement among definitions was determined by the kappa statistic. Logistic regression models were fit to estimate the odds of a high cardiovascular risk group for five definitions of MetS. Results The agreement among the NCEP, IDF, and AHA/NHLBI definitions was from substantial to very good, and agreement between the WHO and EGIR definitions was also substantial. All MetS definitions were significantly associated prevalence of microalbuminuria, elevated highly sensitive CRP (hs-CRP, and arterial stiffness only in women. In men, MetS by NCEP and AHA/NHLBI was associated with elevated level of hs-CRP and arterial stiffness. MetS by WHO and EGIR were significantly associated with microalbuminuria. And MetS by WHO was the only MetS definition that significantly associated with prevalence of arterial stiffness (OR: 2.75, 95% CI: 1.22-6.19. Conclusions The associations of these five definitions with cardiovascular risk factors were similar in women, and it was evident that the five definitions performed better in women than in men, with higher ORs observed in relation to arterial stiffness, elevated hs-CRP, and higher Framingham risk scores.

  1. Image-Based Computational Fluid Dynamics in Blood Vessel Models: Toward Developing a Prognostic Tool to Assess Cardiovascular Function Changes in Prolonged Space Flights

    Science.gov (United States)

    Chatzimavroudis, George P.; Spirka, Thomas A.; Setser, Randolph M.; Myers, Jerry G.

    2004-01-01

    One of NASA's objectives is to be able to perform a complete, pre-flight, evaluation of cardiovascular changes in astronauts scheduled for prolonged space missions. Computational fluid dynamics (CFD) has shown promise as a method for estimating cardiovascular function during reduced gravity conditions. For this purpose, MRI can provide geometrical information, to reconstruct vessel geometries, and measure all spatial velocity components, providing location specific boundary conditions. The objective of this study was to investigate the reliability of MRI-based model reconstruction and measured boundary conditions for CFD simulations. An aortic arch model and a carotid bifurcation model were scanned in a 1.5T Siemens MRI scanner. Axial MRI acquisitions provided images for geometry reconstruction (slice thickness 3 and 5 mm; pixel size 1x1 and 0.5x0.5 square millimeters). Velocity acquisitions provided measured inlet boundary conditions and localized three-directional steady-flow velocity data (0.7-3.0 L/min). The vessel walls were isolated using NIH provided software (ImageJ) and lofted to form the geometric surface. Constructed and idealized geometries were imported into a commercial CFD code for meshing and simulation. Contour and vector plots of the velocity showed identical features between the MRI velocity data, the MRI-based CFD data, and the idealized-geometry CFD data, with less than 10% differences in the local velocity values. CFD results on models reconstructed from different MRI resolution settings showed insignificant differences (less than 5%). This study illustrated, quantitatively, that reliable CFD simulations can be performed with MRI reconstructed models and gives evidence that a future, subject-specific, computational evaluation of the cardiovascular system alteration during space travel is feasible.

  2. Social factors and cardiovascular morbidity.

    Science.gov (United States)

    Brunner, Eric John

    2017-03-01

    Recent progress in population health at aggregate level, measured by life expectancy, has been accompanied by lack of progress in reducing the difference in health prospects between groups defined by social status. Cardiovascular disease is an important contributor to this undesirable situation. The stepwise gradient of higher risk with lower status is accounted for partly by social gradients in health behaviors. The psychosocial hypothesis provides a stronger explanation, based on social patterning of living and working environments and psychological assets that individuals develop during childhood. Three decades of research based on Whitehall II and other cohort studies provide evidence for psychosocial pathways leading to cardiovascular morbidity and mortality. Job stress is a useful paradigm because exposure is long term and depends on occupational status. Studies of social-biological translation implicate autonomic and neuroendocrine function among the biological systems that mediate between chronic adverse psychosocial exposures and increased cardiometabolic risk and cardiovascular disease incidence.

  3. Cardiovascular Disease and Diabetes

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Nov 4,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  4. Cardiovascular manifestations of phaeochromocytoma

    NARCIS (Netherlands)

    Prejbisz, A.; Lenders, J.W.M.; Eisenhofer, G.; Januszewicz, A.

    2011-01-01

    Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma,

  5. 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 ...

  6. APOE Genotyping, Cardiovascular Disease

    Science.gov (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...

  7. Cardiovascular comorbiditiy in psoriasis

    OpenAIRE

    Gurcharan Singh; Simran Pal Singh Aneja

    2011-01-01

    The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite) disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatolog...

  8. Distribuição por gênero de ácido úrico sérico e fatores de risco cardiovascular: estudo populacional Distribución por género del ácido úrico sérico y factores de riesgo cardiovascular: estudio poblacional Gender distribution of serum uric acid and cardiovascular risk factors: population based study

    Directory of Open Access Journals (Sweden)

    Sérgio Lamego Rodrigues

    2012-01-01

    Full Text Available FUNDAMENTO: Não há dados relativos à epidemiologia da hiperuricemia em estudos brasileiros de base populacional. OBJETIVO: Investigar a distribuição de ácido úrico sérico e sua relação com variáveis demográficas e cardiovasculares. MÉTODOS: Estudamos 1.346 indivíduos. A hiperuricemia foi definida como > 6,8 e > 5,4 mg/dL para homens e mulheres, respectivamente. A síndrome metabólica (SM foi definida utilizando-se os critérios NCEP ATP III. RESULTADOS: A prevalência de hiperuricemia foi de 13,2%. A associação de ácido úrico sérico (AUS com fatores de risco cardiovasculares foi específica para o gênero: em mulheres, maiores níveis de AUS estiveram associados com IMC elevado, mesmo após ajustes da pressão arterial sistólica para idade (PAS. Em homens, a relação do AUS com o colesterol HDL esteve mediada pelo IMC, enquanto em mulheres, o AUS mostrou-se semelhante e dependente do IMC, independentemente dos níveis glicose e presença de hipertensão. Nos homens, os triglicerídeos, a circunferência abdominal (CA e a PAS explicaram 11%, 4% e 1% da variabilidade do AUS, respectivamente. Nas mulheres, a circunferência abdominal e os triglicerídeos explicaram 9% e 1% da variabilidade de AUS, respectivamente. Em comparação com o primeiro quartil, homens e mulheres no quarto quartil apresentavam 3,29 e 4,18 vezes mais de aumento de risco de SM, respectivamente. As mulheres apresentaram uma prevalência quase três vezes maior de diabetes melito. Homens normotensos com MS apresentaram maiores níveis de AUS, independente do IMC. CONCLUSÃO: Nossos resultados parecem justificar a necessidade de uma avaliação baseada no gênero em relação à associação do AUS com fatores de risco cardiovasculares, que se mostraram mais acentuados em mulheres. A SM esteve positivamente associada com AUS elevado, independentemente do gênero. A obesidade abdominal e a hipertrigliceridemia foram os principais fatores associados com a

  9. 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 3.07

  10. 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.

  11. Kernel-based variance component estimation and whole-genome prediction of pre-corrected phenotypes and progeny tests for dairy cow health traits

    Science.gov (United States)

    Morota, Gota; Boddhireddy, Prashanth; Vukasinovic, Natascha; Gianola, Daniel; DeNise, Sue

    2014-01-01

    Prediction of complex trait phenotypes in the presence of unknown gene action is an ongoing challenge in animals, plants, and humans. Development of flexible predictive models that perform well irrespective of genetic and environmental architectures is desirable. Methods that can address non-additive variation in a non-explicit manner are gaining attention for this purpose and, in particular, semi-parametric kernel-based methods have been applied to diverse datasets, mostly providing encouraging results. On the other hand, the gains obtained from these methods have been smaller when smoothed values such as estimated breeding value (EBV) have been used as response variables. However, less emphasis has been placed on the choice of phenotypes to be used in kernel-based whole-genome prediction. This study aimed to evaluate differences between semi-parametric and parametric approaches using two types of response variables and molecular markers as inputs. Pre-corrected phenotypes (PCP) and EBV obtained for dairy cow health traits were used for this comparison. We observed that non-additive genetic variances were major contributors to total genetic variances in PCP, whereas additivity was the largest contributor to variability of EBV, as expected. Within the kernels evaluated, non-parametric methods yielded slightly better predictive performance across traits relative to their additive counterparts regardless of the type of response variable used. This reinforces the view that non-parametric kernels aiming to capture non-linear relationships between a panel of SNPs and phenotypes are appealing for complex trait prediction. However, like past studies, the gain in predictive correlation was not large for either PCP or EBV. We conclude that capturing non-additive genetic variation, especially epistatic variation, in a cross-validation framework remains a significant challenge even when it is important, as seems to be the case for health traits in dairy cows. PMID:24715901

  12. Kernel-based variance component estimation and whole-genome prediction of pre-corrected phenotypes and progeny tests for dairy cow health traits

    Directory of Open Access Journals (Sweden)

    Gota eMorota

    2014-03-01

    Full Text Available Prediction of complex trait phenotypes in the presence of unknown gene action is an ongoing challenge in animals, plants, and humans. Development of flexible predictive models that perform well irrespective of genetic and environmental architectures is desirable. Methods that can address non-additive variation in a non-explicit manner are gaining attention for this purpose and, in particular, semi-parametric kernel-based methods have been applied to diverse datasets, mostly providing encouraging results. On the other hand, the gains obtained from these methods have been smaller when smoothed values such as estimated breeding value (EBV have been used as response variables. However, less emphasis has been placed on the choice of phenotypes to be used in kernel-based whole-genome prediction. This study aimed to evaluate differences between semi-parametric and parametric approaches using two types of response variables and molecular markers as inputs. Pre-corrected phenotypes (PCP and EBV obtained for dairy cow health traits were used for this comparison. We observed that non-additive genetic variances were major contributors to total genetic variances in PCP, whereas additivity was the largest contributor to variability of EBV, as expected. Within the kernels evaluated, non-parametric methods yielded slightly better predictive performance across traits relative to their additive counterparts regardless of the type of response variable used. This reinforces the view that non-parametric kernels aiming to capture non-linear relationships between a panel of SNPs and phenotypes are appealing for complex trait prediction. However, like past studies, the gain in predictive correlation was not large for either PCP or EBV. We conclude that capturing non-additive genetic variation, especially epistatic variation, in a cross-validation framework remains a significant challenge even when it is important, as seems to be the case for health traits in dairy cows.

  13. Assesment of endocrinal and biochemical entities through liquid chromatography–tandem mass spectrometry/mass spectrometer: Inter-relative investigation of the interaction based cardiovascular formulation

    Science.gov (United States)

    Das, Rakesh; Pal, Tapan Kumar

    2015-01-01

    Background: Combinatory oral dosage treatment of atorvastatin (ATVS) and olmesartan (OLM) drugs to cardiovascular patients reflects unpredicted results instead of its individual therapy, which was accessed on quantification of endocrinal and biochemicals of plasma through liquid chromatography–tandem mass spectrometry/mass spectrometer (LCMS/MS). Objective: Mission was to track the remarkable biochemical variation in the plasma after induction of the combined formulation, to evaluate the pharma-market rumor on its efficiency. Methods: To fulfil undergoing research objectives for digging-up of market insult, human patient volunteers were chosen according to the required criteria along with bioethical regulation. A sensitive, rapid and precise method was developed and validated to estimate aldosterone (ALD), angiotensin (ANG-II) and the Mevalonate (MVA) not Mevalonic acid through LCMS/MS over least samples of cardiovascular patients. Level of each endogenous biochemicals were determined in three stages - without drugs, with a single drug (OLM/ATVS) and with their combination that was then correlate with blood pressure of respective volunteers. Result and Discussion: Comparative and correlative studies panaroma among these analytes was detected. The selectivity, specificity, linearity, precision, accuracy, extraction recovery, limit of detection and limit of quantification, stability were the essential points of validation of the developed methodology. And the significance of each endogenous analyte data were based on P ≥ 0.001. Thus, low value of ALD and reciprocally higher in ANG-II on administered single drug than its combination and equal concentration of mevalonate in both stages, was discovered. Conclusion: This concludes that the cardiovascular dosage formulation entrenched in the market are not synergistic and effective compared with a single drug as antihypertensive drug. PMID:25709337

  14. Cardiovascular risk factor profiles for peripheral artery disease and carotid atherosclerosis among Chinese older people: a population-based study.

    Directory of Open Access Journals (Sweden)

    Yajun Liang

    Full Text Available OBJECTIVES: Epidemiological data concerning atherosclerotic disease among older people in rural China are sparse. We seek to determine prevalence and cardiovascular risk factor profiles for peripheral artery disease (PAD and carotid atherosclerosis (CAS among Chinese older people living in a rural community. METHODS: This cross-sectional study included 1499 participants (age ≥60 years, 59.0% women of the Confucius Hometown Aging Project in Shandong, China. From June 2010-July 2011, data were collected through interviews, clinical examinations, and laboratory tests. PAD was defined as an ankle-brachial index ≤0.9. Carotid intima-media thickness (cIMT and carotid artery stenosis were assessed by ultrasonography. We defined moderate stenosis as carotid stenosis ≥50%, and severe stenosis as carotid stenosis ≥70%. cIMT≥1.81 mm was considered as an increased cIMT (a measure of CAS. Data were analyzed with multiple logistic models. RESULTS: The prevalence was 5.7% for PAD, 8.9% for moderate stenosis, 1.8% for severe stenosis, and 11.2% for increased cIMT. After controlling for multiple potential confounders, diabetes, an increased low-density lipoprotein cholesterol (LDL-C/high-density lipoprotein cholesterol (HDL-C ratio, and hypertension were significantly or marginally associated with PAD. Ever smoking, hypertension, and an increased LDL-C/HDL-C ratio were significantly associated with an increased likelihood of increased cIMT. An increasing number of those cardiovascular risk factors were significantly associated with an increasing odds ratio of PAD and increased cIMT, respectively (p for linear trend <0.001. CONCLUSION: Among Chinese older people living in a rural community, PAD, carotid artery stenosis, and an increased cIMT are relatively uncommon. Cardiovascular risk factor profiles for PAD and CAS are slightly different, with hypertension and an increased LDL-C/HDL-C ratio being associated with an increased likelihood of both PAD and

  15. [Cardiovascular manifestations of human toxocariasis].

    Science.gov (United States)

    Bolívar-Mejía, Adrián; Rodríguez-Morales, Alfonso J; Paniz-Mondolfi, Alberto E; Delgado, Olinda

    2013-01-01

    Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.

  16. Framingham Risk Score underestimates cardiovascular disease risk in severe psoriatic patients: implications in cardiovascular risk factors management and primary prevention of cardiovascular disease.

    Science.gov (United States)

    Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Martins da Silva, Berta; Selores, Manuela

    2013-11-01

    Severe psoriasis has been associated with increase cardiovascular mortality, due to a higher prevalence of traditional cardiovascular risk factors and premature atherosclerosis, as a consequence of its systemic inflammation. Recently, it has been estimated that severe psoriasis may confer an increased 6.2% on long-term risk of cardiovascular disease based on Framingham Risk Score, which can have practical implications in the treatment of cardiovascular risk factors and primary prevention of cardiovascular disease, as treatment guidelines account for the risk of cardiovascular disease in treatment goals. The aim of this study was to analyze the influence of the attributable risk of severe psoriasis on long-term risk of cardiovascular disease and its implication on the correct treatment of cardiovascular risk factors and primary prevention of cardiovascular disease on a real-world cohort of patients. One hundred severe psoriasis patients without psoriatic arthritis or previous cardiovascular disease were evaluated and it was found that more than half of the patients were reclassified to a higher cardiovascular risk category with important clinical implications on the correct management of their cardiovascular risk factors and primary prevention of cardiovascular disease, as a considerable proportion of patients with hypertension, hypercholesterolemia and coronary heart disease equivalent risk were not being correctly managed.

  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. Cardiovascular Comorbidity and Mortality in Men With Prostate Cancer Treated With Brachytherapy-Based Radiation With or Without Hormonal Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Nanda, Akash, E-mail: akash.nanda@orlandohealth.com [Department of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, Florida (United States); Chen, Ming-Hui [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Moran, Brian J.; Braccioforte, Michelle H. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-04-01

    Purpose: To assess the impact of coronary artery disease (CAD) risk factors and sequelae on the risk of all-cause mortality (ACM) in men treated for prostate cancer (PC). Methods and Materials: The study cohort comprised 5077 men with PC consecutively treated with curative intent between 1997 and 2006 at the Chicago Prostate Cancer Center. Cox and Fine and Gray's competing risks regression multivariable analyses were performed, assessing whether cardiovascular comorbidity impacted the risk of ACM and PC-specific mortality, respectively, adjusting for CAD risk factors (diabetes mellitus, hypercholesterolemia, or hypertension) and sequelae (congestive heart failure or myocardial infarction), age, year and type of treatment, and known PC prognostic factors. Results: When compared with men with no comorbidity there was a significantly increased risk of ACM in men with congestive heart failure or myocardial infarction (adjusted hazard ratio [AHR] 1.96, P<.001) and in men with diabetes mellitus (AHR 1.60, P=.03) and hypertension (AHR 1.25, P=.04). In contrast, men with hypercholesterolemia had a similar risk of ACM (AHR 0.68, P=.17) when compared with men with no comorbidity. Other factors associated with a significantly increased risk of ACM included age (AHR 1.09, P<.001), prostate-specific antigen level (AHR 1.25, P=.008), and Gleason score 8-10 disease (AHR 1.71, P=.003). Cardiovascular comorbidity did not impact the risk of PC-specific mortality. Conclusions: In addition to age and unfavorable PC prognostic factors, select CAD risk factors and sequelae are associated with an increased risk of ACM in men treated for PC. These comorbidity prognostic factors predict time courses of mortality from competing causes, which may be factored into the decision-making process when considering management options for PC in a given individual.

  19. Chemometric Classification of Different Tree Peony Species Native to China Based on the Assessment of Major Fatty Acids of Seed Oil and Phenotypic Characteristics of the Seeds.

    Science.gov (United States)

    Zhang, Xiao-Xiao; Zhang, Yan-Long; Niu, Li-Xin; Sun, Jia-Yi; Li, Lin-Hao; Zhang, Jing; Li, Jian

    2017-01-01

    In the present study, we quantitatively measured five major fatty acids (FA) in seed oil using gas chromatography/mass spectrometry (GC/MS) and examined four phenotypic characteristics of the seeds from 19 populations from nine wild tree peony species native to China. The results showed that the unsaturated FAs contents were dominant, of which α-linolenic acid (ALA), linoleic acid, and oleic acid (OA) contents ranged from 14.84 to 42.54 g/100 g, 7.33 to 19.66 g/100 g, and 15.07 - 35.31 g/100 g crude oil, respectively. The phenotypic seed characteristics, such as thousand seed weight (244.01 - 1772.91 g), seed volume (91.31 - 1000.79 mm(3) ), weight rate of kernel and coat (1.29 - 3.62) and oil extraction ratio (20.32 - 34.69%), dramatically varied. Based on the contents of the five FAs, the nine species were classified into two groups. The species belonging to subsection Vaginatae were arranged in cluster I and were characterized by high ALA content. Cluster II, consistent with subsection Delavayanae, had a high OA content. From horizontal and vertical perspectives, the natural distribution areas of these two groups were different, reflecting differences in the FA contents and phenotypic seed characteristics. In conclusion, the FAs composition could be used as a chemotaxonomic marker for tree peony species.

  20. Efficient in vitro RNA interference and immunofluorescence-based phenotype analysis in a human parasitic nematode, Brugia malayi

    Directory of Open Access Journals (Sweden)

    Landmann Frédéric

    2012-01-01

    Full Text Available Abstract Background RNA interference (RNAi is an efficient reverse genetics technique for investigating gene function in eukaryotes. The method has been widely used in model organisms, such as the free-living nematode Caenorhabditis elegans, where it has been deployed in genome-wide high throughput screens to identify genes involved in many cellular and developmental processes. However, RNAi techniques have not translated efficiently to animal parasitic nematodes that afflict humans, livestock and companion animals across the globe, creating a dependency on data tentatively inferred from C. elegans. Results We report improved and effective in vitro RNAi procedures we have developed using heterogeneous short interfering RNA (hsiRNA mixtures that when coupled with optimized immunostaining techniques yield detailed analysis of cytological defects in the human parasitic nematode, Brugia malayi. The cellular disorganization observed in B. malayi embryos following RNAi targeting the genes encoding γ-tubulin, and the polarity determinant protein, PAR-1, faithfully phenocopy the known defects associated with gene silencing of their C. elegans orthologs. Targeting the B. malayi cell junction protein, AJM-1 gave a similar but more severe phenotype than that observed in C. elegans. Cellular phenotypes induced by our in vitro RNAi procedure can be observed by immunofluorescence in as little as one week. Conclusions We observed cytological defects following RNAi targeting all seven B. malayi transcripts tested and the phenotypes mirror those documented for orthologous genes in the model organism C. elegans. This highlights the reliability, effectiveness and specificity of our RNAi and immunostaining procedures. We anticipate that these techniques will be widely applicable to other important animal parasitic nematodes, which have hitherto been mostly refractory to such genetic analysis.

  1. Computational modeling as part of alternative testing strategies in the respiratory and cardiovascular systems: inhaled nanoparticle dose modeling based on representative aerosol measurements and corresponding toxicological analysis.

    Science.gov (United States)

    Pilou, Marika; Mavrofrydi, Olga; Housiadas, Christos; Eleftheriadis, Kostas; Papazafiri, Panagiota

    2015-05-01

    The objectives of modeling in this work were (a) the integration of two existing numerical models in order to connect external exposure to nanoparticles (NPs) with internal dose through inhalation, and (b) to use computational fluid-particle dynamics (CFPD) to analyze the behavior of NPs in the respiratory and the cardiovascular system. Regarding the first objective, a lung transport and deposition model was combined with a lung clearance/retention model to estimate NPs dose in the different regions of the human respiratory tract and some adjacent tissues. On the other hand, CFPD was used to estimate particle transport and deposition of particles in a physiologically based bifurcation created by the third and fourth lung generations (respiratory system), as well as to predict the fate of super-paramagnetic particles suspended in a liquid under the influence of an external magnetic field (cardiovascular system). All the above studies showed that, with proper refinement, the developed computational models and methodologies may serve as an alternative testing strategy, replacing transport/deposition experiments that are expensive both in time and resources and contribute to risk assessment.

  2. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    Science.gov (United States)

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  3. Physiologically Based Pharmacokinetic Modeling of Tamoxifen and its Metabolites in Women of Different CYP2D6 Phenotypes Provides New Insight into the Tamoxifen Mass Balance

    Science.gov (United States)

    Dickschen, Kristin; Willmann, Stefan; Thelen, Kirstin; Lippert, Jörg; Hempel, Georg; Eissing, Thomas

    2012-01-01

    Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+) mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6). It is widely accepted that CYP2D6 poor metabolizers exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved. In this study, physiologically based pharmacokinetic (PBPK)-modeling was applied to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy. A PBPK-model of tamoxifen and its pharmacologically important metabolites N-desmethyltamoxifen (NDM-TAM), 4-hydroxytamoxifen (4-OH-TAM), and endoxifen was developed and validated. This model is able to simulate the pharmacokinetics (PK) after single and repeated oral tamoxifen doses in female breast cancer patients in dependence of the CYP2D6 phenotype. A detailed model-based analysis of the mass balance offered support for a recent hypothesis stating a more prominent role for endoxifen formation from 4-OH-TAM. In the future this model provides a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity, or co-treatment with CYP2D6 inhibitors. PMID:22661948

  4. Finding our way through phenotypes.

    Directory of Open Access Journals (Sweden)

    Andrew R Deans

    2015-01-01

    Full Text Available Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  5. Finding our way through phenotypes.

    Science.gov (United States)

    Deans, Andrew R; Lewis, Suzanna E; Huala, Eva; Anzaldo, Salvatore S; Ashburner, Michael; Balhoff, James P; Blackburn, David C; Blake, Judith A; Burleigh, J Gordon; Chanet, Bruno; Cooper, Laurel D; Courtot, Mélanie; Csösz, Sándor; Cui, Hong; Dahdul, Wasila; Das, Sandip; Dececchi, T Alexander; Dettai, Agnes; Diogo, Rui; Druzinsky, Robert E; Dumontier, Michel; Franz, Nico M; Friedrich, Frank; Gkoutos, George V; Haendel, Melissa; Harmon, Luke J; Hayamizu, Terry F; He, Yongqun; Hines, Heather M; Ibrahim, Nizar; Jackson, Laura M; Jaiswal, Pankaj; James-Zorn, Christina; Köhler, Sebastian; Lecointre, Guillaume; Lapp, Hilmar; Lawrence, Carolyn J; Le Novère, Nicolas; Lundberg, John G; Macklin, James; Mast, Austin R; Midford, Peter E; Mikó, István; Mungall, Christopher J; Oellrich, Anika; Osumi-Sutherland, David; Parkinson, Helen; Ramírez, Martín J; Richter, Stefan; Robinson, Peter N; Ruttenberg, Alan; Schulz, Katja S; Segerdell, Erik; Seltmann, Katja C; Sharkey, Michael J; Smith, Aaron D; Smith, Barry; Specht, Chelsea D; Squires, R Burke; Thacker, Robert W; Thessen, Anne; Fernandez-Triana, Jose; Vihinen, Mauno; Vize, Peter D; Vogt, Lars; Wall, Christine E; Walls, Ramona L; Westerfeld, Monte; Wharton, Robert A; Wirkner, Christian S; Woolley, James B; Yoder, Matthew J; Zorn, Aaron M; Mabee, Paula

    2015-01-01

    Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.

  6. Epigenetics in heart failure phenotypes

    Directory of Open Access Journals (Sweden)

    Alexander Berezin

    2016-12-01

    Full Text Available Chronic heart failure (HF is a leading clinical and public problem posing a higher risk of morbidity and mortality in different populations. HF appears to be in both phenotypic forms: HF with reduced left ventricular ejection fraction (HFrEF and HF with preserved left ventricular ejection fraction (HFpEF. Although both HF phenotypes can be distinguished through clinical features, co-morbidity status, prediction score, and treatment, the clinical outcomes in patients with HFrEF and HFpEF are similar. In this context, investigation of various molecular and cellular mechanisms leading to the development and progression of both HF phenotypes is very important. There is emerging evidence that epigenetic regulation may have a clue in the pathogenesis of HF. This review represents current available evidence regarding the implication of epigenetic modifications in the development of different HF phenotypes and perspectives of epigenetic-based therapies of HF.

  7. Cardiovascular Disease Burden: Evolving Knowledge of Risk Factors in Myocardial Infarction and Stroke through Population-Based Research and Perspectives in Global Prevention

    Directory of Open Access Journals (Sweden)

    GUSTAVO B.F. OLIVEIRA

    2015-08-01

    Full Text Available Current knowledge and research perspectives on the top ranking causes of mortality worldwide, i.e., ischemic heart disease and cerebrovascular diseases have developed rapidly. In fact, until recently, it was considered that only half of the myocardial infarctions were due to traditional risk factors such as hypertension, hypercholesterolemia, smoking and diabetes. In addition, most of the available evidence of incidence, risk factors, and clinical outcomes, if not all of it, was derived from studies conducted in developed countries, which included lower proportion of female individuals and with low ethnic diversity. Recent reports by the WHO have provided striking public health information, i.e., the global burden of cardiovascular mortality for the next decades is expected to predominantly occur among developing countries. Therefore, multi-ethnic population-based research including prospective cohorts and, when appropriate, case-control studies, is warranted. These studies should be specifically designed to ascertain key public health measures such as geographic variations in noncommunicable diseases, diagnosis of traditional and potential newly discovered risk factors, causes of death and disability, and gaps for improvement in healthcare prevention (both primary and secondary and specific treatments. As an example, a multinational, multiethnic population-based cohort study is the Prospective Urban and Rural Epidemiology (PURE study, which is the largest global initiative of 150,000 adults aged 35-70 yrs, looking at environmental, societal and biological influences on obesity and chronic health conditions such as ischemic heart disease, stroke and cancer among urban and rural communities in low-, middle-, and high-income countries, with national, community, household and individual-level data. Implementation of population-based strategies is crucial to optimizing limited health system resources while improving care and cardiovascular morbidity

  8. Fruit and vegetable intake and risk of total cancer and cardiovascular disease: Japan Public Health Center-Based Prospective Study.

    Science.gov (United States)

    Takachi, Ribeka; Inoue, Manami; Ishihara, Junko; Kurahashi, Norie; Iwasaki, Motoki; Sasazuki, Shizuka; Iso, Hiroyasu; Tsubono, Yoshitaka; Tsugane, Shoichiro

    2008-01-01

    Few studies have investigated the effects of fruit and vegetables on the risk of both cancer and cardiovascular disease (CVD). The authors examined associations between fruit and vegetable consumption and risk of total cancer and CVD in the same Japanese population. During 1995-1998, a validated food frequency questionnaire was administered in nine areas to 77,891 men and women aged 45-74 years. During as many as 459,320 person-years of follow-up until the end of 2002, 3,230 cancer cases and 1,386 CVD cases were identified. Higher consumption of fruit, but not vegetables, was associated with significantly lower risk of CVD: multivariate hazard ratios for the highest versus lowest quartiles of intake were 0.81 (95% confidence interval (CI): 0.67, 0.97; trend p = 0.01) for fruit and 0.97 (95% CI: 0.82, 1.15; trend p = 0.66) for vegetables. Consumption of fruit or vegetables was not associated with decreased risk of total cancer: corresponding hazard ratios were 1.02 (95% CI: 0.90, 1.14; trend p = 0.95) for fruit and 0.94 (95% CI: 0.84, 1.05; trend p = 0.16) for vegetables. This prospective cohort study demonstrated that, in the Japanese population, consumption of fruit is associated with lower risk of CVD, whereas fruit or vegetables may not be associated with lower risk of total cancer.

  9. Development of a hospital-based cardiovascular risk factor reduction program for the community: Beyond Heart Disease.

    Science.gov (United States)

    Lipon, K R; Carlson, L R

    1994-01-01

    The current and future trend of the health care delivery system is prevention and health promotion. Long-term viability of hospitals depends on meeting community health education needs. With heart disease as the leading cause of death among adults nationwide, hospitals have an opportunity to offer appropriate lifestyle theory and guidance beyond conventional medical and interventional practices. Sequoia Hospital in Redwood City is one of the first hospitals in Northern California to develop a comprehensive outpatient program to complement its world renowned cardiovascular services. This paper details the Beyond Heart Disease (BHD) program designed by nurses. The goal of this program is to effectively help people reduce their risk of coronary events via successful long-term risk factor interventions. BHD, a unique medical and business venture, spans a six-week period. Group members meet in the evening for two hours, twice a week. The program includes lipid testing, a complete program syllabus, didactic lectures, small group discussion, support and goal-setting, nutritional analysis, and experiential stress reduction sessions.

  10. Major Adverse Cardiovascular Events in Treated Periodontitis: A Population-Based Follow-Up Study from Taiwan.

    Directory of Open Access Journals (Sweden)

    Shing-Hsien Chou

    Full Text Available The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE in treated periodontitis patients in Taiwan.From the National Health Insurance Research Database (2001-2010, adult patients (≥ 18 years with treated periodontitis were identified. Comparison was made between patients with mild form and severe form of treated periodontitis after propensity score matching. The primary end point was the incidence of MACE.A total of 32,504 adult patients with treated periodontitis were identified between 2001 and 2010. After propensity score matching, 27,146 patients were preserved for comparison, including 13,573 patients with mild form and 13,573 patients with severe form of treated periodontitis. During follow-up, 728 individuals in mild treated periodontitis group and 1,206 individuals in severe treated periodontitis group had at least 1 MACE event. After adjustment for gender, hyperlipidemia, hypertension and diabetes mellitus, severe treated periodontitis was associated with a mildly but significantly increased risk of MACE among older patients > 60 years of age (incidence rate ratio, 1.26; 95% confidence interval, 1.08-1.46. No association was found among younger patients ≤ 60 years of age.Severe form of treated periodontitis was associated with an increased risk of MACE among older Taiwanese patients, but not among younger Taiwanese patients. We should put more efforts on the improvement of periodontal health to prevent further MACE.

  11. Serum Albumin and Cerebro-cardiovascular Mortality During a 15-year Study in a Community-based Cohort in Tanushimaru, a Cohort of the Seven Countries Study.

    Science.gov (United States)

    Umeki, Yoko; Adachi, Hisashi; Enomoto, Mika; Fukami, Ako; Nakamura, Sachiko; Nohara, Yume; Nakao, Erika; Sakaue, Akiko; Tsuru, Tomoko; Morikawa, Nagisa; Fukumoto, Yoshihiro

    Objective There is little long-term data on the association between the serum albumin levels and mortality in community-based populations. We aimed to determine whether the serum albumin level is an independent risk factor for all-cause and cause-specific death in a community-based cohort study in Japan. Methods In 1999, we performed a periodic epidemiological survey over a 15-year period in a population of 1,905 healthy subjects (783 males, 1,122 females) who were older than 40 years of age and who resided in Tanushimaru, a rural community, in Japan. Over the course of the study, we periodically examined the blood chemistry of the study subjects, including their serum albumin levels. Their baseline serum albumin levels were categorized into quartiles. Results The baseline albumin levels were significantly associated with age (inversely), body mass index (BMI), diastolic blood pressure, lipid profiles [high density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) and triglycerides] and estimated glomerular filtration rate (eGFR). After adjusting for confounders, a Cox proportional hazards regression analysis demonstrated that a low serum albumin level was an independent predictor of all-cause death [hazard ratio (HR): 0.39, 95% confidence interval (CI): 0.24-0.65], cancer death (HR: 0.43, 95% CI: 0.18-0.99), death from infection (HR: 0.21, 95% CI: 0.06-0.73) and cerebro-cardiovascular death (HR: 0.19, 95% CI: 0.06-0.63). The HRs for all-cause and cerebro-cardiovascular death in the highest quartile vs. the lowest quartile of albumin after adjusting for confounders were 0.59 (95%CI:0.39-0.88) and 0.15 (95%CI: 0.03-0.66), respectively. Conclusion The serum albumin level was thus found to be a predictor of all-cause and cerebro-cardiovascular death in a general population.

  12. 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.

  13. Adapting Phonological Awareness Interventions for Children With Down Syndrome Based on the Behavioral Phenotype: A Promising Approach?

    Science.gov (United States)

    Lemons, Christopher J; King, Seth A; Davidson, Kimberly A; Puranik, Cynthia S; Fulmer, Deborah; Mrachko, Alicia A; Partanen, Jane; Al Otaiba, Stephanie; Fidler, Deborah J

    2015-08-01

    Many children with Down syndrome demonstrate deficits in phonological awareness, a prerequisite to learning to read in an alphabetic language. The purpose of this study was to determine whether adapting a commercially available phonological awareness program to better align with characteristics associated with the behavioral phenotype of Down syndrome would increase children's learning of phonological awareness, letter sounds, and words. Five children with Down syndrome, ages 6 to 8 years, participated in a multiple baseline across participants single case design experiment in which response to an adapted phonological awareness intervention was compared with response to the nonadapted program. Results indicate a functional relation between the adapted program and phonological awareness. Suggestions for future research and implications for practice are provided.

  14. 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...... of diabetes has been rather constant at higher level in males (around 16-18%) than in females (around 12-14%) during 2000-2011 (incl.). In contrast, the incidence rate of CVD after having diabetes diagnosis has declined from about 4.5 to less than 3 during the same period, with higher declining level...... for males than for females. Efforts to detect diabetes at an earlier stage have not resulted in a reduced occurrence of CVD at the diagnosis of diabetes in Denmark. However, the risk of developing CVD after the diagnosis of diabetes has been declining, possibly reflecting benefits of intensified treatment...

  15. Physiologically-based pharmacokinetic modeling of tamoxifen and its metabolites in women of different CYP2D6 phenotypes provides new insight into the tamoxifen mass balance

    Directory of Open Access Journals (Sweden)

    Kristin eDickschen

    2012-05-01

    Full Text Available Tamoxifen is a first-line endocrine agent in the mechanism-based treatment of estrogen receptor positive (ER+ mammary carcinoma and applied to breast cancer patients all over the world. Endoxifen is a secondary and highly active metabolite of tamoxifen that is formed among others by the polymorphic cytochrome P450 2D6 (CYP2D6. It is widely accepted that CYP2D6 poor metabolizers (PM exert a pronounced decrease in endoxifen steady-state plasma concentrations compared to CYP2D6 extensive metabolizers (EM. Nevertheless, an in-depth understanding of the chain of cause and effect between CYP2D6 genotype, endoxifen steady-state plasma concentration, and subsequent tamoxifen treatment benefit still remains to be evolved.In this context, physiologically-based pharmacokinetic (PBPK-modeling provides a useful tool to mechanistically investigate the impact of CYP2D6 phenotype on endoxifen formation in female breast cancer patients undergoing tamoxifen therapy.It has long been thought that only a minor percentage of endoxifen is formed via 4-hydroxytamoxifen. However, the current investigation supports very recently published data that postulates a contribution of 4-hydroxytamoxifen above 20 % to total endoxifen formation. The developed PBPK-model describes tamoxifen PK in rats and humans. Moreover, tamoxifen metabolism in dependence of CYP2D6 phenotype in populations of European female individuals is well described, thus providing a good basis to further investigate the linkage of PK, mode of action, and treatment outcome in dependence of factors such as phenotype, ethnicity or co-treatment with CYP2D6 inhibitors.

  16. 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.

  17. Reference values for the incremental shuttle walk test in patients with cardiovascular disease entering exercise-based cardiac rehabilitation.

    Science.gov (United States)

    Cardoso, Fernando M F; Almodhy, Meshal; Pepera, Garyfalia; Stasinopoulos, Dimitrios M; Sandercock, Gavin R H

    2017-01-01

    The incremental shuttle walk test (ISWT) is used to assess functional capacity of patients entering cardiac rehabilitation. Factors such as age and sex account for a proportion of the variance in test performance in healthy individuals but there are no reference values for patients with cardiovascular disease. The aim of this study was to produce reference values for the ISWT. Participants were n = 548 patients referred to outpatient cardiac rehabilitation who underwent a clinical examination and performed the ISWT. We used regression to identify predictors of performance and produced centile values using the generalised additive model for location, scale and shape model. Men walked significantly further than women (395 ± 165 vs. 269 ± 118 m; t = 9.5, P sex. Age (years) was the strongest predictor of performance in men (β = -5.9; 95% CI: -7.1 to -4.6 m) and women (β = -4.8; 95% CI: -6.3 to 3.3). Centile curves demonstrated a broadly linear decrease in expected ISWT values in males (25-85 years) and a more curvilinear trend in females. Patients entering cardiac rehabilitation present with highly heterogeneous ISWT values. Much of the variance in performance can be explained by patients' age and sex. Comparing absolute values with age-and sex-specific reference values may aid interpretation of ISWT performance during initial patient assessment at entry to cardiac rehabilitation.

  18. Impacto econômico dos casos de doença cardiovascular grave no Brasil: uma estimativa baseada em dados secundários Economic burden of severe cardiovascular diseases in Brazil: an estimate based on secondary data

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    Maria Inês Reinert Azambuja

    2008-09-01

    Full Text Available FUNDAMENTO: Há escassez de dados no Brasil para subsidiar a crescente preocupação sobre o impacto econômico das doenças cardiovasculares (DCV. OBJETIVO: Estimar os custos referentes aos casos de DCV grave no Brasil. MÉTODOS: O número de casos de DCV grave foi estimado a partir das taxas de letalidade e mortalidade dos pacientes hospitalizados. Estudos observacionais e bancos de dados nacionais foram utilizados para estimar os custos referentes à hospitalização, atendimento ambulatorial e benefícios pagos pela previdência. A perda da renda foi estimada com base nos dados do estudo de Carga de Doenças no Brasil. RESULTADOS: Aproximadamente dois milhões de casos de DCV grave foram relatados em 2004 no Brasil, representando 5,2% da população acima de 35 anos de idade. O custo anual foi de, pelo menos, R$ 30,8 bilhões (36,4% para a saúde, 8,4% para o seguro social e reembolso por empregadores e 55,2% como resultado da perda de produtividade, correspondendo a R$ 500,00 per capita (para a população de 35 anos e acima e R$ 9.640,00 por paciente. Somente nesse subgrupo, os custos diretos em saúde corresponderam por 8% do gasto total do país com saúde e 0,52% do PIB (R$ 1.767 bilhões = 602 bilhões de dólares, o que corresponde a uma média anual de R$ 182,00 para os custos diretos per capita (R$ 87,00 de recursos públicos e de R$ 3.514,00 por caso de DCV grave. CONCLUSÃO: Os custos anuais totais para cada caso de DCV grave foram significativos. Estima-se que tanto os custos per capita como aqueles correspondentes ao subgrupo de pacientes com DCV grave aumentem significativamente à medida que a população envelhece e a prevalência de casos graves aumente.BACKGROUND: The scarce amount of data available in Brazil on the economic burden of cardiovascular diseases (CVD does not justify the growing concern in regard to the economic burden involved. OBJECTIVE: The present study aims at estimating the costs of severe CVD cases in

  19. 基于ARM的无创心血管功能检测系统%Non-Invasive Cardiovascular Monitoring System Based on ARM

    Institute of Scientific and Technical Information of China (English)

    赵学玲; 陈小红; 刘瑾; 杜振辉; 徐可欣

    2008-01-01

    An intelligent non-invasive cardiovascular monitoring device was developed to measure ten important parame-ters on the basis of arterial windkessel model and hemodynamic theory of pulse wave. By using the technology of advanced RISC machines(ARM) based on embedded platform, some defectiveness of the existing commercial systems was overcome,such as computer-attached, clumsy volume, and singularity of cardiovascular parameters measured, etc. Both the hardware and software design were described in detail. Through a preliminary experiment of 30 persons, it is proved that the system keeps good reliability and stability, which can achieve the correlation of 0.95 with the consulted device, and its repeatability error is less than 2.36%. The acquired parameters can be used to better evaluate the cardiovascular state of a person. The sys-tem is expected to be applied to the clinic and home healthcare.%研发了一种智能化的无创心血管参数诊断系统.该系统应用动脉弹性腔模型和血液动力学理论,可以对10个重要的心血管参数进行测量.采用了基于ARM的嵌入式系统技术,克服了目前其他同类仪器体积大、测量参数单一等缺点.详细介绍了系统的硬件构成与软件流程.为了验证系统的性能,该系统在30个人中进行了初步实验.结果证明,该仪器具有良好的准确性和稳定性,与参考仪器测量结果的相关系数可达到0.95,重复性误差最大为2.36%,所获得的参数能较好地评价心血管功能状况,系统可运用于临床诊断和家庭健康监护.

  20. Microglia phenotype diversity

    NARCIS (Netherlands)

    Olah, M.; Biber, K.; Vinet, J.; Boddeke, H. W. G. M.

    2011-01-01

    Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype

  1. Short- and long-term major cardiovascular adverse events in carotid artery interventions: a nationwide population-based cohort study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Ming-Lung Tsai

    Full Text Available Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI database.2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting.The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively. The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively. Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality.Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.

  2. Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

    Energy Technology Data Exchange (ETDEWEB)

    Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H., E-mail: hans.maurer@uks.eu

    2015-09-03

    LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

  3. Lifestyle in Cardiovascular Disease

    NARCIS (Netherlands)

    J.O. Younge (John)

    2015-01-01

    markdownabstract__Abstract__ Globally, the burden of cardiovascular disease (CVD) is still increasing. However, in recent decades, better treatment modalities have led to less cardiovascular related deaths. After years of research, we now generally accept that lifestyle factors are the most importa

  4. Effectiveness of a Web-Based Computer-Tailored Multiple-Lifestyle Intervention for People Interested in Reducing their Cardiovascular Risk: A Randomized Controlled Trial

    Science.gov (United States)

    Dörenkämper, Julia; Reinwand, Dominique Alexandra; Wienert, Julian; De Vries, Hein; Lippke, Sonia

    2016-01-01

    Background Web-based computer-tailored interventions for multiple health behaviors can improve the strength of behavior habits in people who want to reduce their cardiovascular risk. Nonetheless, few randomized controlled trials have tested this assumption to date. Objective The study aim was to test an 8-week Web-based computer-tailored intervention designed to improve habit strength for physical activity and fruit and vegetable consumption among people who want to reduce their cardiovascular risk. In a randomized controlled design, self-reported changes in perceived habit strength, self-efficacy, and planning across different domains of physical activity as well as fruit and vegetable consumption were evaluated. Methods This study was a randomized controlled trial involving an intervention group (n=403) and a waiting control group (n=387). Web-based data collection was performed in Germany and the Netherlands during 2013-2015. The intervention content was based on the Health Action Process Approach and involved personalized feedback on lifestyle behaviors, which indicated whether participants complied with behavioral guidelines for physical activity and fruit and vegetable consumption. There were three Web-based assessments: baseline (T0, N=790), a posttest 8 weeks after the baseline (T1, n=206), and a follow-up 3 months after the baseline (T2, n=121). Data analysis was conducted by analyzing variances and structural equation analysis. Results Significant group by time interactions revealed superior treatment effects for the intervention group, with substantially higher increases in self-reported habit strength for physical activity (F1,199=7.71, P=.006, Cohen’s d=0.37) and fruit and vegetable consumption (F1,199=7.71, P=.006, Cohen’s d=0.30) at posttest T1 for the intervention group. Mediation analyses yielded behavior-specific sequential mediator effects for T1 planning and T1 self-efficacy between the intervention and habit strength at follow-up T2 (fruit

  5. Effects on cardiovascular disease risk of a web-based health risk assessment with tailored health advice: a follow-up study

    Directory of Open Access Journals (Sweden)

    Colkesen

    2011-02-01

    Full Text Available Ersen B Colkesen1,2, Bart S Ferket2,3, Jan GP Tijssen1, Roderik A Kraaijenhagen2, Coenraad K van Kalken2, Ron JG Peters11Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 2NDDO Institute for Prevention and Early Diagnostics (NIPED, Amsterdam, the Netherlands; 3Department of Epidemiology, Erasmus Medical Center, Rotterdam, the NetherlandsIntroduction: A large proportion of the cardiovascular disease (CVD burden can potentially be prevented by primary prevention programs addressing major causal risk factors. A Web-based health risk assessment (HRA with tailored feedback for individual health promotion is a promising strategy. We evaluated the effect on CVD risk of such a program among employees of a Dutch worksite.Methods: We conducted a prospective follow-up study among 368 employees who voluntarily participated in a Web-based HRA program at a single Dutch worksite in 2008. The program included a multicomponent HRA through a Web-based electronic questionnaire, biometrics, and laboratory evaluation. The results were combined with health behavior change theory to generate tailored motivational and educational health advice. On request, a health counseling session with the program physician was available. Follow-up data on CVD risk were collected 1 year after initial participation. The primary outcome was a change in Framingham CVD risk at 6 months relative to baseline. We checked for a possible background effect of an increased health consciousness as a consequence of program introduction at the worksite by comparing baseline measurements of early program participants with baseline measurements of participants who completed the program 6 months later.Results: A total of 176 employees completed follow-up measurements after a mean of 7 months. There was a graded relation between CVD risk changes and baseline risk, with a relative reduction of 17.9% (P = 0.001 in the high-risk category (baseline

  6. Is an unfavourable cardiovascular risk profile a risk factor for vasomotor menopausal symptoms? Results of a population-based cohort study

    NARCIS (Netherlands)

    Van Den Berg, M. J.; Herber-Gast, G. C M; Van Der Schouw, Y. T.

    2015-01-01

    Objective Evidence suggests an association between vasomotor menopausal symptoms (VMSs), i.e. hot flushes and night sweats, and cardiovascular disease. However, the causal pathway is unclear. We investigated whether an unfavourable cardiovascular risk profile is a risk factor for VMS later in life.

  7. Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system Prevención de la enfermedad cardiovascular basada en tratamiento hipolipemiante: un reto para el sistema de salud de México

    Directory of Open Access Journals (Sweden)

    Francisco J Gómez-Pérez

    2010-01-01

    Full Text Available OBJECTIVE: To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006. MATERIAL AND METHODS: Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. RESULTS: A cardiovascular risk equivalent was found in 13.8% and >2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. CONCLUSIONS: Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%.OBJETIVO: Calcular el porcentaje de adultos que requiere tratamiento hipolipemiante de acuerdo con las recomendaciones del Programa Nacional de Educación en Colesterol-III, usando los datos de la Encuesta Nacional de Salud y Nutrición 2006. MATERIAL Y MÉTODOS: Se incluyeron 4040 individuos con edad entre 20 y 69 años estudiados bajo un ayuno de 9 a 12 horas. RESULTADOS: Un equivalente de enfermedad cardiovascular fue identificado en 13.8% de los participantes. El 31.5% de la población tenía >2 factores de riesgo cardiovascular. La concentración de colesterol LDL estuvo arriba de la meta terapéutica en 70% de los casos con alto riesgo cardiovascular y en el 38.6% de los sujetos con >2 factores de riesgo. Cerca de 12 millones de mexicanos deben modificar su estilo de vida para reducir su concentración de colesterol LDL. Casi 8 millones califican para recibir tratamiento farmacológico. CONCLUSIONES: Una tercera parte de los adultos requiere alguna forma de tratamiento hipolipemiante (cambios en el estilo de vida: 36

  8. Association between Stress Response Genes and Features of Diurnal Cortisol Curves in the Multi-Ethnic Study of Atherosclerosis: A New Multi-Phenotype Approach for Gene-Based Association Tests.

    Science.gov (United States)

    He, Zihuai; Payne, Erin K; Mukherjee, Bhramar; Lee, Seunggeun; Smith, Jennifer A; Ware, Erin B; Sánchez, Brisa N; Seeman, Teresa E; Kardia, Sharon L R; Diez Roux, Ana V

    2015-01-01

    The hormone cortisol is likely to be a key mediator of the stress response that influences multiple physiologic systems that are involved in common chronic disease, including the cardiovascular system, the immune system, and metabolism. In this paper, a candidate gene approach was used to investigate genetic contributions to variability in multiple correlated features of the daily cortisol profile in a sample of European Americans, African Americans, and Hispanic Americans from the Multi-Ethnic Study of Atherosclerosis (MESA). We proposed and applied a new gene-level multiple-phenotype analysis and carried out a meta-analysis to combine the ethnicity specific results. This new analysis, instead of a more routine single marker-single phenotype approach identified a significant association between one gene (ADRB2) and cortisol features (meta-analysis p-value=0.0025), which was not identified by three other commonly used existing analytic strategies: 1. Single marker association tests involving each single cortisol feature separately; 2. Single marker association tests jointly testing for multiple cortisol features; 3. Gene-level association tests separately carried out for each single cortisol feature. The analytic strategies presented consider different hypotheses regarding genotype-phenotype association and imply different costs of multiple testing. The proposed gene-level analysis integrating multiple cortisol features across multiple ethnic groups provides new insights into the gene-cortisol association.

  9. All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study.

    Directory of Open Access Journals (Sweden)

    Gillian A Hawker

    Full Text Available BACKGROUND: Because individuals with osteoarthritis (OA avoid physical activities that exacerbate symptoms, potentially increasing risk for cardiovascular disease (CVD and death, we assessed the relationship between OA disability and these outcomes. METHODS: In a population cohort aged 55+ years with at least moderately severe symptomatic hip and/or knee OA, OA disability (Western Ontario McMaster Universities (WOMAC OA scores; Health Assessment Questionnaire (HAQ walking score; use of walking aids and other covariates were assessed by questionnaire. Survey data were linked to health administrative data to determine the relationship between baseline OA symptom severity to all-cause mortality and occurrence of a composite CVD outcome (acute myocardial infarction, coronary revascularization, heart failure, stroke or transient ischemic attack over a median follow-up of 13.2 and 9.2 years, respectively. RESULTS: Of 2156 participants, 1,236 (57.3% died and 822 (38.1% experienced a CVD outcome during follow-up. Higher (worse baseline WOMAC function scores and walking disability were independently associated with a higher all-cause mortality (adjusted hazard ratio, aHR, per 10-point increase in WOMAC function score 1.04, 95% confidence interval, CI 1.01-1.07, p = 0.004; aHR per unit increase in HAQ walking score 1.30, 95% CI 1.22-1.39, p<0.001; and aHR for those using versus not using a walking aid 1.51, 95% CI 1.34-1.70, p<0.001. In survival analysis, censoring on death, risk of our composite CVD outcome was also significantly and independently associated with greater baseline walking disability ((aHR for use of a walking aid = 1.27, 95% CI 1.10-1.47, p = 0.001; aHR per unit increase in HAQ walking score = 1.17, 95% CI 1.08-1.27, p<0.001. CONCLUSIONS: Among individuals with hip and/or knee OA, severity of OA disability was associated with a significant increase in all-cause mortality and serious CVD events after controlling for multiple confounders

  10. 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...

  11. A Pyramid Breeding of Eight Grain-yield Related Quantitative Trait Loci Based on Marker-assistant and Phenotype Selection in Rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    Guo Zong; Ahong Wang; Lu Wang; Guohua Liang; Minghong Gu; Tao Sang; Bin Han

    2012-01-01

    1000-Grain weight and spikelet number per panicle are two important components for rice grain yield.In our previous study,eight quantitative trait loci (QTLs) conferring spikelet number per panicle and 1000-grain weight were mapped through sequencing-based genotyping of 150 rice recombinant inbred lines (RILs).In this study,we validated the effects of four QTLs from Nipponbare using chromosome segment substitution lines (CSSLs),and pyramided eight grain yield related QTLs.The new lines containing the eight QTLs with positive effects showed increased panicle and spikelet size as compared with the parent variety 93-11.We further proposed a novel pyramid breeding scheme based on marker-assistant and phenotype selection (MAPS).This scheme allowed pyramiding of as many as 24QTLs at a tingle hybridization without massive cross work.This study provided insights into the molecular basis of rice grain yield for direct wealth for high-yielding rice breeding.

  12. Project h[schwa]li?dx[superscript w]/Healthy Hearts across Generations: Development and Evaluation Design of a Tribally Based Cardiovascular Disease Prevention Intervention for American Indian Families

    Science.gov (United States)

    Walters, Karina L.; LaMarr, June; Levy, Rona L.; Pearson, Cynthia; Maresca, Teresa; Mohammed, Selina A.; Simoni, Jane M.; Evans-Campbell, Teresa; Fredriksen-Goldsen, Karen; Fryberg, Sheryl; Jobe, Jared B.

    2012-01-01

    American Indian and Alaska Native (AIAN) populations are disproportionately at risk for cardiovascular disease (CVD), diabetes, and obesity, compared with the general US population. This article describes the h[schwa]li?dx[superscript w]/Healthy Hearts Across Generations project, an AIAN-run, tribally based randomized controlled trial (January…

  13. Phenotypic screens targeting neurodegenerative diseases.

    Science.gov (United States)

    Zhang, Minhua; Luo, Guangrui; Zhou, Yanjiao; Wang, Shaohui; Zhong, Zhong

    2014-01-01

    Neurodegenerative diseases affect millions of people worldwide, and the incidences increase as the population ages. Disease-modifying therapy that prevents or slows disease progression is still lacking, making neurodegenerative diseases an area of high unmet medical need. Target-based drug discovery for disease-modifying agents has been ongoing for many years, without much success due to incomplete understanding of the molecular mechanisms underlying neurodegeneration. Phenotypic screening, starting with a disease-relevant phenotype to screen for compounds that change the outcome of biological pathways rather than activities at certain specific targets, offers an alternative approach to find small molecules or targets that modulate the key characteristics of neurodegeneration. Phenotypic screens that focus on amelioration of disease-specific toxins, protection of neurons from degeneration, or promotion of neuroregeneration could be potential fertile grounds for discovering therapeutic agents for neurodegenerative diseases. In this review, we will summarize the progress of compound screening using these phenotypic-based strategies for this area, with a highlight on unique considerations for disease models, assays, and screening methodologies. We will further provide our perspectives on how best to use phenotypic screening to develop drug leads for neurodegenerative diseases.

  14. A cluster randomised school-based lifestyle intervention programme for the prevention of childhood obesity and related early cardiovascular disease (JuvenTUM 3

    Directory of Open Access Journals (Sweden)

    Haller Bernhard

    2011-04-01

    Full Text Available Abstract Background Childhood obesity is not only associated with adult obesity but also with increased risk of adult onset of type 2 diabetes and subsequent coronary heart disease. The potential effects of school-based health intervention programmes on cardiovascular risk and surrogate markers are unclear, as only few studies have attempted to investigate a complete risk profile including a detailed laboratory analysis or micro- and macrovascular function. In this study a comprehensive school-based randomized intervention programme will be investigated in 10-14-year old children addressing the influence of lifestyle intervention on inactivity, cardiometabolic risk factors and early signs of vascular disease. Methods/Design 15 secondary schools in Southern Germany are randomly assigned to intervention or control schools. Children in the fifth grade (10-11 years will be observed over four years. The study combines a school-based with a home-based approach, aiming at children, teachers and parents. The main components are weekly lifestyle-lessons for children, taught by regular classroom teachers to increase physical activity in- and outside of school, to improve eating patterns at school and at home, to reduce media consumption and to amplify well-being. In 4-6 annual meetings, teachers receive information about health-related topics with worksheets for children and supporting equipment, accounting for school-specific needs and strategies. Parents' trainings are provided on a regular basis. All examinations are performed at the beginning and at the end of every school year. Anthropometry includes measurements of BMI, waist and upper arm circumferences, skinfold thickness as well as peripheral blood pressure. Blood sampling includes lipid parameters, insulin, glucose, hsCRP, adiponectin, and IL-6 as well as testosteron and estrogen to determine maturation status. Vascular function is non-invasively assessed by measuring arterial stiffness in large

  15. 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.

  16. Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model

    Directory of Open Access Journals (Sweden)

    In Young Choi

    2016-06-01

    Full Text Available Duchenne muscular dystrophy (DMD remains an intractable genetic disease. Althogh there are several animal models of DMD, there is no human cell model that carries patient-specific DYSTROPHIN mutations. Here, we present a human DMD model using human induced pluripotent stem cells (hiPSCs. Our model reveals concordant disease-related phenotypes with patient-dependent variation, which are partially reversed by genetic and pharmacological approaches. Our “chemical-compound-based” strategy successfully directs hiPSCs into expandable myoblasts, which exhibit a myogenic transcriptional program, forming striated contractile myofibers and participating in muscle regeneration in vivo. DMD-hiPSC-derived myoblasts show disease-related phenotypes with patient-to-patient variability, including aberrant expression of inflammation or immune-response genes and collagens, increased BMP/TGFβ signaling, and reduced fusion competence. Furthermore, by genetic correction and pharmacological “dual-SMAD” inhibition, the DMD-hiPSC-derived myoblasts and genetically corrected isogenic myoblasts form “rescued” multi-nucleated myotubes. In conclusion, our findings demonstrate the feasibility of establishing a human “DMD-in-a-dish” model using hiPSC-based disease modeling.

  17. Frailty phenotypes in the elderly based on cluster analysis: a longitudinal study of two Danish cohorts. Evidence for a genetic influence on frailty.

    Science.gov (United States)

    Dato, Serena; Montesanto, Alberto; Lagani, Vincenzo; Jeune, Bernard; Christensen, Kaare; Passarino, Giuseppe

    2012-06-01

    Frailty is a physiological state characterized by the deregulation of multiple physiologic systems of an aging organism determining the loss of homeostatic capacity, which exposes the elderly to disability, diseases, and finally death. An operative definition of frailty, useful for the classification of the individual quality of aging, is needed. On the other hand, the documented heterogeneity in the quality of aging among different geographic areas suggests the necessity for a frailty classification approach providing population-specific results. Moreover, the contribution of the individual genetic background on the frailty status is still questioned. We investigated the applicability of a cluster analysis approach based on specific geriatric parameters, previously set up and validated in a southern Italian population, to two large longitudinal Danish samples. In both cohorts, we identified groups of subjects homogeneous for their frailty status and characterized by different survival patterns. A subsequent survival analysis availing of Accelerated Failure Time models allowed us to formulate an operative index able to correlate classification variables with survival probability. From these models, we quantified the differential effect of various parameters on survival, and we estimated the heritability of the frailty phenotype by exploiting the twin pairs in our sample. These data suggest the presence of a genetic influence on the frailty variability and indicate that cluster analysis can define specific frailty phenotypes in each population.

  18. Development and characterization of a replicon-based phenotypic assay for assessing HCV NS4B from clinical isolates.

    Science.gov (United States)

    Rajyaguru, Sonal; Yang, Huiling; Martin, Ross; Miller, Michael D; Mo, Hongmei

    2013-11-01

    The hepatitis C virus (HCV) NS4B inhibitors have shown potent inhibition of HCV replication in vitro. To assess the effect of viral diversity on the susceptibility to NS4B inhibitors, genotype (GT)-specific GT1a and GT1b replicon shuttle vectors were designed and created for cloning HCV NS4B genes from clinical isolates. For the GT1b NS4B shuttle vector, the S2204I adaptive mutation was introduced in NS5A to improve replication due to the replacement of the K1846T adaptive mutation in NS4B with NS4B from the clinical isolates. In addition to the adaptive mutations, a newly identified Huh-7 cell line, Huh-7-1C, which is highly permissive for both GT1a and GT1b replication, was used to further enhance the replication levels. HCV NS4B gene from clinical isolates was amplified and inserted into the corresponding GT1a and GT1b modified lab strain chimeric replicons. GT1a and GT1b chimeric replicons expressing diverse NS4B genes from corresponding subtypes of clinical isolates replicated at highly efficient levels for phenotypic analysis. Due to natural variation in their amino acid residues in NS4B, these isolates displayed varying drug susceptibilities to an NS4B inhibitor. In mixed populations with wild-type, the sensitivity of resistance detection of NS4B resistant mutants H94R and V105M was between 20% and 80%. The chimeric shuttle vectors can be used to characterize the activity of antiviral drugs targeting NS4B from diverse natural clinical isolates and aid in the development of novel compounds against HCV NS4B.

  19. Cocoa, chocolate and cardiovascular disease

    OpenAIRE

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

    2009-01-01

    A significant body of evidence demonstrates that diets rich in fruit and vegetables promote health, and attenuate, or delay, the onset of various diseases, including cardiovascular disease (CVD), 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 the last years based on the health benefits ascribed to selected cocoa components. Specifically, cocoa as a plant a...

  20. Is the Cardiovascular Response Equivalent Between a Supervised Center-Based Setting and a Self-care Home-Based Setting When Rating of Perceived Exertion Is Used to Guide Aerobic Exercise Intensity During a Cardiac Rehabilitation Program?

    DEFF Research Database (Denmark)

    Tang, Lars H.; Zwisler, Ann-Dorthe; Berg, Selina K.

    2016-01-01

    OBJECTIVES: The aim of this study was to investigate if exercise intensity guided by rating of perceived exertion (RPE) results in an equivalent cardiovascular response when applied in either a center-based or a home-based setting. DESIGN: Data from patients with heart disease (post-valve surgery...... and atrial fibrillation post-radiofrequency ablation) participating in exercise-based rehabilitation were included. Patients performed a 12-week program in either a center- or a home-based setting. Using RPE, patients recorded their exercise intensity 3 times during an aerobic training phase. Exercise.......0 difference in RPE; 95% confidence interval, 4.8-7.5 beats/min) compared with the home-based setting (mean of 5.3 beats/min per 1.0 difference in RPE; 95% confidence interval, 4.0-6.5 beats/min). The level of patient familiarization, exercise intensity, and patient characteristics did not affect the level...

  1. 循证医学在心血管教学中的应用研究%Application of evidence-based medicine in cardiovascular teaching

    Institute of Scientific and Technical Information of China (English)

    娜几娜·吾格提; 王坤; 迪力努尔·塔吉; 赵利; 艾力曼·马合木提

    2015-01-01

    Objective:To investigate the effect of Evidence-based medicine teaching practice in the teaching of cardiovascular disease. Methods:Clinical Cardiology selected 97 student interns, EBM were randomly divided into two groups, which EBM group 49, control group 48. EBM group with evidence-based medicine teaching unit group, the control group using traditional teaching methods. Results:EBM group, the average score was (79.45 ± 7.30) points, the average score in the control group (67.92 ± 6.87) points, including clinical skills assessment score in the EBM group (10.73 ± 4.76) points, the score of the control group (9.45 ± 5.78) points, there was a significant difference (P<0.05) between the two. Conclusions:Evidence-based medicine theory in cardiovascular disease teaching has a good effect, with a certain value.%目的:探讨心血管疾病教学中开展循证医学教学的实践效果。方法:选取临床心内科实习学生97名,采用随机分组的原则分为EBM组和对照组,其中EBM组49名,对照组48名。EBM组采用小组单位循证医学教学,对照组采用传统教学方法,比较两组在心血管疾病教学中的成绩和临床技能考核分数。结果:通过实验显示E B M组平均成绩为(79.45±7.30)分,对照组平均成绩(67.92±6.87)分,其中临床技能考核中E B M组成绩为(10.73±4.76)分,对照组成绩为(9.45±5.78)分,通过t检验,两者间存在显著性差异(P<0.05),E B M组成绩要优于对照组。结论:循证医学理论在心血管疾病教学的应用具有很好的效果,具有一定的应用价值。

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

    Directory of Open Access Journals (Sweden)

    Sehnert Scott T

    2008-12-01

    Full Text Available 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-disciplinary team of Michigan State University (MSU faculty, clinicians, and health profession students was formed to "(Spartner" with elementary school physical education (PE teachers and MSU Extension staff to develop and implement a cost-effective, sustainable program aimed at CVD risk factor prevention and management for 5th grade students. This (Spartnership is intended to augment and improve the existing 5th grade PE, health and nutrition curriculum by achieving the following aims: 1 improve the students' knowledge, attitudes and confidence about nutrition, PA and heart health; 2 increase the number of students achieving national recommendations for PA and nutrition; and 3 increase the number of students with a desirable CVD risk factor status based on national pediatric guidelines. Secondary aims include promoting school staff and parental support for heart health to help children achieve their goals and to provide experiential learning and service for MSU health profession students for academic credit. Methods/Design This pilot effectiveness study was approved by the MSU IRB. At the beginning and the end of the school year students undergo a CVD risk factor assessment conducted by MSU medical students and graduate students. Key intervention components include eight lesson plans (conducted bi-monthly designed to promote heart healthy nutrition and PA behaviors conducted by PE teachers with assistance from MSU undergraduate dietetic and kinesiology students

  3. CARDIOVASCULAR DISORDERS IN ADOLESCENTS WITH CHEST PAIN

    Directory of Open Access Journals (Sweden)

    Sri Endah Rahayuningsih

    2014-06-01

    Full Text Available Objective: To detect cardiovascular abnormalities in adolescents with chest pain. Methods: In this cross sectional study, the subjects were 25 adolescents with chest pain who came to the Cardiac Center of Dr. Hasan Sadikin General Hospital, Bandung during the period of January 2008 to January 2011. The presence of established cardiovascular disorders were based on history, physical examination, electrocardiography and echocardiography Results: It was found that 13/25 adolescents with chest pain had cardiovascular abnormalities. Of the 25 teens that came with chest pain, most of which showed normal electrocardiographic results, only 9/25 of those with dysrhythmias experienced sinus tachycardia and 8 had a first degree AV block. Echocardiography examination showed only four patients with abnormal cardiac anatomy. No correlation between nutritional status and chest pain, and cardiovascular abnormalities and chest pain (p=0.206 and p=0.632, respectively. There was a positive correlation between sex and cardiovascular abnormalities in adolescents with chest pain (p=0.007. Chest pain is a prevalent problem that is usually benign and that it frequently signals underlying cardiac disease. Conclusions: Cardiovascular abnormalities in adolescents with symptoms of chest pain are found in some cases. There is no correlation between female and male adolescents with chest pain and cardiovascular abnormalities.

  4. Biomarkers of cardiovascular disease risk in women.

    Science.gov (United States)

    Manson, JoAnn E; Bassuk, Shari S

    2015-03-01

    Cardiovascular disease (CVD), including coronary heart disease and stroke, is the leading cause of death among U.S. women and men. Established cardiovascular risk factors such as smoking, diabetes, hypertension, and elevated total cholesterol, and risk prediction models based on such factors, perform well but do not perfectly predict future risk of CVD. Thus, there has been much recent interest among cardiovascular researchers in identifying novel biomarkers to aid in risk prediction. Such markers include alternative lipids, B-type natriuretic peptides, high-sensitivity troponin, coronary artery calcium, and genetic markers. This article reviews the role of traditional cardiovascular risk factors, risk prediction tools, and selected novel biomarkers and other exposures in predicting risk of developing CVD in women. The predictive role of novel cardiovascular biomarkers for women in primary prevention settings requires additional study, as does the diagnostic and prognostic utility of cardiac troponins for acute coronary syndromes in clinical settings. Sex differences in the clinical expression and physiology of metabolic syndrome may have implications for cardiovascular outcomes. Consideration of exposures that are unique to, or more prevalent in, women may also help to refine cardiovascular risk estimates in this group.

  5. CARDIOVASCULAR DISORDERS IN ADOLESCENTS WITH CHEST PAIN

    OpenAIRE

    Sri Endah Rahayuningsih; Rahmat Budi; Herry Garna

    2014-01-01

    Objective: To detect cardiovascular abnormalities in adolescents with chest pain. Methods: In this cross sectional study, the subjects were 25 adolescents with chest pain who came to the Cardiac Center of Dr. Hasan Sadikin General Hospital, Bandung during the period of January 2008 to January 2011. The presence of established cardiovascular disorders were based on history, physical examination, electrocardiography and echocardiography Results: It was found that 13/25 adolesce...

  6. 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.

  7. 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 cha

  8. Cardiovascular comorbiditiy in psoriasis

    Directory of Open Access Journals (Sweden)

    Gurcharan Singh

    2011-01-01

    Full Text Available The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatologists treating psoriasis need to approach the disease as a potentially multisystem disorder and must alert these patients to the potentially negative effects of their disease.

  9. Urocortin and cardiovascular protection

    Institute of Scientific and Technical Information of China (English)

    Yu HUANG; Xiao-qiang YAO; Chi-wai LAU; Yau-chi CHAN; Suk-ying TSANG; Franky Leung CHAN

    2004-01-01

    Urocortin and other hypothalamus corticotropin-releasing factor (CRF) polypeptides play biologically diverse roles in the stress, cardiovascular and inflammatory responses by acting on central and peripheral CRF receptors.Urocortin shows a significantly high sequence homology to CRF, and the concurrent expression of type-2 CRF (CRF2) receptors with urocortin in the heart suggests that urocortin may play a physiological role in the cardiac function. Urocortin is thought to be the endogenous agonist producing the cardiovascular actions previously attributed to CRF. This review highlights the current novel findings on the molecular and cellular mechanisms by which urocortin may exert its cardiovascular protective action.

  10. Adherence with physical activity monitoring wearable devices in a community-based population: observations from the Washington, D.C., Cardiovascular Health and Needs Assessment.

    Science.gov (United States)

    Yingling, Leah R; Mitchell, Valerie; Ayers, Colby R; Peters-Lawrence, Marlene; Wallen, Gwenyth R; Brooks, Alyssa T; Troendle, James F; Adu-Brimpong, Joel; Thomas, Samantha; Henry, JaWanna; Saygbe, Johnetta N; Sampson, Dana M; Johnson, Allan A; Graham, Avis P; Graham, Lennox A; Wiley, Kenneth L; Powell-Wiley, Tiffany

    2017-01-17

    Wearable mobile health (mHealth) technologies offer approaches for targeting physical activity (PA) in resource-limited, community-based interventions. We sought to explore user characteristics of PA tracking, wearable technology among a community-based population within a health and needs assessment. In 2014-2015, we conducted the Washington, D.C., Cardiovascular Health and Needs Assessment in predominantly African-American churches among communities with higher obesity rates and lower household incomes. Participants received a mHealth PA monitor and wirelessly uploaded PA data weekly to church data collection hubs. Participants (n = 99) were 59 ± 12 years, 79% female, and 99% African-American, with a mean body mass index of 33 ± 7 kg/m(2). Eighty-one percent of participants uploaded PA data to the hub and were termed "PA device users." Though PA device users were more likely to report lower household incomes, no differences existed between device users and non-users for device ownership or technology fluency. Findings suggest that mHealth systems with a wearable device and data collection hub may feasibly target PA in resource-limited communities.

  11. Integrated e-Health approach based on vascular ultrasound and pulse wave analysis for asymptomatic atherosclerosis detection and cardiovascular risk stratification in the community.

    Science.gov (United States)

    Santana, Daniel Bia; Zócalo, Yanina A; Armentano, Ricardo L

    2012-03-01

    New strategies are urgently needed to identify subjects at increased risk of atherosclerotic cardiovascular disease (ACVD) development or complications. A National Public University Center (CUiiDARTE) was created in Uruguay, based on six main pillars: 1) integration of experts in different disciplines and creation of multidisciplinary teams, 2) incidence in public and professional education programs to give training in the use of new technologies and to shift the focus from ACVD treatment to disease prevention, 3) implementation of free vascular studies in the community (distributed rather than centralized healthcare), 4) innovation and application of e-Health and noninvasive technology and approaches, 5) design and development of a biomedical approach to determine the target population and patient workflow, and 6) improvement in individual risk estimation and differentiation between aging and ACVD-related arterial changes using population-based epidemiological and statistical patient-specific models. This work describes main features of CUiiDARTE project implementation, the scientific and technological steps and innovations done for individual risk stratification, and sub-clinical ACVD diagnosis.

  12. Subject-specific cardiovascular system model-based identification and diagnosis of septic shock with a minimally invasive data set: animal experiments and proof of concept.

    Science.gov (United States)

    Chase, J Geoffrey; Lambermont, Bernard; Starfinger, Christina; Hann, Christopher E; Shaw, Geoffrey M; Ghuysen, Alexandre; Kolh, Philippe; Dauby, Pierre C; Desaive, Thomas

    2011-01-01

    A cardiovascular system (CVS) model and parameter identification method have previously been validated for identifying different cardiac and circulatory dysfunctions in simulation and using porcine models of pulmonary embolism, hypovolemia with PEEP titrations and induced endotoxic shock. However, these studies required both left and right heart catheters to collect the data required for subject-specific monitoring and diagnosis-a maximally invasive data set in a critical care setting although it does occur in practice. Hence, use of this model-based diagnostic would require significant additional invasive sensors for some subjects, which is unacceptable in some, if not all, cases. The main goal of this study is to prove the concept of using only measurements from one side of the heart (right) in a 'minimal' data set to identify an effective patient-specific model that can capture key clinical trends in endotoxic shock. This research extends existing methods to a reduced and minimal data set requiring only a single catheter and reducing the risk of infection and other complications-a very common, typical situation in critical care patients, particularly after cardiac surgery. The extended methods and assumptions that found it are developed and presented in a case study for the patient-specific parameter identification of pig-specific parameters in an animal model of induced endotoxic shock. This case study is used to define the impact of this minimal data set on the quality and accuracy of the model application for monitoring, detecting and diagnosing septic shock. Six anesthetized healthy pigs weighing 20-30 kg received a 0.5 mg kg(-1) endotoxin infusion over a period of 30 min from T0 to T30. For this research, only right heart measurements were obtained. Errors for the identified model are within 8% when the model is identified from data, re-simulated and then compared to the experimentally measured data, including measurements not used in the identification

  13. Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.

    Science.gov (United States)

    Yu, Meng; Jia, Hongmei; Zhou, Chao; Yang, Yong; Zhao, Yang; Yang, Maohua; Zou, Zhongmei

    2017-05-10

    As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression.

  14. [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

  15. Phenotypic screening: the future of antibody discovery.

    Science.gov (United States)

    Gonzalez-Munoz, Andrea L; Minter, Ralph R; Rust, Steven J

    2016-01-01

    Most antibody therapeutics have been isolated from high throughput target-based screening. However, as the number of validated targets diminishes and the target space becomes increasingly competitive, alternative strategies, such as phenotypic screening, are gaining momentum. Here, we review successful phenotypic screens, including those used to isolate antibodies against cancer and infectious agents. We also consider exciting advances in the expression and phenotypic screening of antibody repertoires in single cell autocrine systems. As technologies continue to develop, we believe that antibody phenotypic screening will increase further in popularity and has the potential to provide the next generation of therapeutic antibodies.

  16. Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study

    Science.gov (United States)

    Padmanabhan, Sandosh; Porteous, David J.; Burri, Andrea V.; Tanaka, Haruka; Williams, Frances M. K.

    2017-01-01

    Background Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. Methods and findings We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34–2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64–4·82]); those with depression were twice as likely to have angina

  17. Educational differences in cardiovascular mortality

    DEFF Research Database (Denmark)

    Kjøllesdal, M. K. R.; Ariansen, I.; Mortensen, L. H.;

    2016-01-01

    Aims: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Methods: Data from national and regional health surveys in Norway (1974–2003) were linked...... with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants (n=271,310). Data were available on CVD risk factors, including...... weight, height, blood pressure, total cholesterol and smoking. Results: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98–3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors...

  18. Robotic technology in cardiovascular medicine.

    Science.gov (United States)

    Bonatti, Johannes; Vetrovec, George; Riga, Celia; Wazni, Oussama; Stadler, Petr

    2014-05-01

    Robotic technology has been used in cardiovascular medicine since the late 1990s. Interventional cardiology, electrophysiology, endovascular surgery, minimally invasive cardiac surgery, and laparoscopic vascular surgery are all fields of application. Robotic devices enable endoscopic reconstructive surgery in narrow spaces and fast, very precise placement of catheters and devices in catheter-based interventions. In all robotic systems, the operator manipulates the robotic arms from a control station or console. In the field of cardiac surgery, mitral valve repair, CABG surgery, atrial septal defect repair, and myxoma resection can be achieved using robotic technology. Furthermore, vascular surgeons can perform a variety of robotically assisted operations to treat aortic, visceral, and peripheral artery disease. In electrophysiology, ablation procedures for atrial fibrillation can be carried out with robotic support. In the past few years, robotically assisted percutaneous coronary intervention and abdominal aortic endovascular surgery techniques have been developed. The basic feasibility and safety of robotic approaches in cardiovascular medicine has been demonstrated, but learning curves and the high costs associated with this technology have limited its widespread use. Nonetheless, increased procedural speed, accuracy, and reduced exposure to radiation and contrast agent in robotically assisted catheter-based interventions, as well as reduced surgical trauma and shortened patient recovery times after robotic cardiovascular surgery are promising achievements in the field.

  19. Cardiovascular manifestations in hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Vairamani Kandan

    2016-07-01

    Conclusions: This study shows that cardiovascular manifestations are quite common and varied in hyperthyroidism which are to be looked for in the management. [Int J Res Med Sci 2016; 4(7.000: 3032-3038

  20. Cardiovascular modeling and diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T. [Pacific Northwest Lab., Richland, WA (United States)

    1995-12-31

    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  1. Cardiovascular disease markers in type 2 diabetes: the effects of a moderate home-based exercise training programme

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Benee Olsen, David; Reving, Danny

    2009-01-01

    -based exercise training program improves biomarker levels and insulin sensitivity. Patients with T2DM (n=12), IGT (n=4) and healthy control subjects (n=9) were studied before and after eight weeks of exercise training by rowing ergometry at 65-70% of peak oxygen uptake. Conclusions: 1) patients with T2DM have...... elevated plasma concentrations of CVD biomarkers compared to the matched control and IGT groups; 2) a moderate to vigorous intensity home-based training program did not reduce plasma concentrations of these CVD markers; 3) insulin sensitivity improved as a result of exercise training in the control group...

  2. Single cell dynamic phenotyping

    OpenAIRE

    Katherin Patsch; Chi-Li Chiu; Mark Engeln; Agus, David B.; Parag Mallick; Shannon M. Mumenthaler; Daniel Ruderman

    2016-01-01

    Live cell imaging has improved our ability to measure phenotypic heterogeneity. However, bottlenecks in imaging and image processing often make it difficult to differentiate interesting biological behavior from technical artifact. Thus there is a need for new methods that improve data quality without sacrificing throughput. Here we present a 3-step workflow to improve dynamic phenotype measurements of heterogeneous cell populations. We provide guidelines for image acquisition, phenotype track...

  3. Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study

    DEFF Research Database (Denmark)

    Hallas, Jesper; Bjerrum, Lars; Støvring, Henrik;

    2008-01-01

    Ephedrine and herbal ephedra preparations have been shown to induce a small-to-moderate weight loss. Owing to reports on serious cardiovascular events, they were banned from the US market in 2004. There have been no large controlled studies on the possible association between prescribed ephedrine...... risk among naïve users or users with large cumulative doses. Prescribed ephedrine/caffeine was not associated with a substantially increased risk of adverse cardiovascular outcomes in this study....

  4. 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

  5. Gout and subsequent increased risk of cardiovascular mortality in non-diabetics aged 50 and above: a population-based cohort study in Taiwan

    Directory of Open Access Journals (Sweden)

    Kok Victor C

    2012-11-01

    Full Text Available Abstract Background Limited data are available on the risk ratios for fatal cardiovascular disease (CVD outcome from gout and chronic kidney disease (CKD in non-diabetic individuals. Methods Nationwide population-based retrospective prospective study with a 5-year follow-up to investigate the association between physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios (HR of CVD mortality were adjusted for gender, age, smoking- and alcoholism-related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and Charlson’s comorbidity index score. Results A case cohort (n=164,463 having gout and a control cohort (n= 3,694,377 having no gout were formed. The prevalence of gout in this study was 4.26% whereas that of gout plus CKD was 8.17%. Male to female ratio among the individuals with gout was 3.2:1. The relative risk (RR of subsequent cardiovascular mortality between the case and control cohort was 1.71 (95% confidence interval (CI, 1.66-1.75. The presence of CKD in nondiabetic subjects with no gout (control group has a RR of CVD mortality at 3.05 (95% CI, 2.94-3.15. The presence of gout has protective effect on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98. As compared with individuals with no gout, the adjusted HR (aHR for CVD mortality among the individuals with gout was 1.10 (95% CI 1.07-1.13. In a Cox model, when compared with subjects having neither gout nor CKD, the aHR in subjects with no gout but with CKD is 1.76 (95% CI, 1.70-1.82; in subjects with gout but without CKD, 1.10 (1.07-1.13; interestingly, the aHR is attenuated in subjects with concomitant gout plus CKD which is 1.38 (1.29-1.48. Conclusions Among non-diabetic individuals aged 50 years or above who had no preceding serious CVD, those with gout were 1.1 times more likely to die from CVD as were individuals without gout. The presence of gout appears to

  6. Vegetarian Diets and Cardiovascular Health: Evidence-based and Pondering%素食与心血管健康:循证与思考

    Institute of Scientific and Technical Information of China (English)

    陈可冀; 刘玥

    2014-01-01

    The correlation between vegetarian diets and cardiovascular health is always one of the hotspots.Many scholars have performed so many clinical researches all over the world,providing evidence-based medicine (EBM) reference for clarifying their correlation.In this paper,we raise ideas and expectation on the basis of a Meta-analysis about vegetarian diets and blood pressure (published on JAMA Internal Medicine in Feb 2014) in combination of main clinical research literature in this field in recent 20 years.%素食与心血管健康的关系一直是研究热点之一,国内外学者对其进行了较多的临床研究,为其关系的阐明提供了许多循证医学依据.本文基于2014年2月发表在《美国医学会杂志·内科学》上的一篇关于素食与血压的Meta分析,并结合近20年来该领域发表的主要临床研究文献,提出思考与展望.

  7. Hydroxytyrosol ameliorates metabolic, cardiovascular and liver changes in a rat model of diet-induced metabolic syndrome: Pharmacological and metabolism-based investigation.

    Science.gov (United States)

    Poudyal, Hemant; Lemonakis, Nikolaos; Efentakis, Panagiotis; Gikas, Evangelos; Halabalaki, Maria; Andreadou, Ioanna; Skaltsounis, Leandros; Brown, Lindsay

    2017-03-01

    Metabolic syndrome is a clustering of interrelated risk factors for cardiovascular disease and diabetes. The Mediterranean diet has been proposed as an important dietary pattern to confer cardioprotection by attenuating risk factors of metabolic syndrome. Hydroxytyrosol (HT) is present in olive fruit and oil, which are basic constituents of the Mediterranean diet. In this study, we have shown that treatment with HT (20mg/kg/d for 8 weeks) decreased adiposity, improved impaired glucose and insulin tolerance, improved endothelial function with lower systolic blood pressure, decreased left ventricular fibrosis and resultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolic syndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into the heart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study of HT, we have identified 24 HT phase I and II metabolites, six of them being over-produced in high-starch, low-fat diet fed rats treated with HT compared to obese rats on high-carbohydrate, high-fat diet. These results provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolic risk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obese rats warrant further investigation.

  8. A review of ground-based heavy-ion radiobiology relevant to space radiation risk assessment: Part II. Cardiovascular and immunological effects

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, Eleanor A.; Chang, Polly Y.

    2007-02-26

    The future of manned space flight depends on an analysis of the numerous potential risks of travel into deep space. Currently no radiation dose limits have been established for these exploratory missions. To set these standards more information is needed about potential acute and late effects on human physiology from appropriate radiation exposure scenarios, including pertinent radiation types and dose rates. Cancer risks have long been considered the most serious late effect from chronic daily relatively low-dose exposures to the complex space radiation environment. However, other late effects from space radiation exposure scenarios are under study in ground-based accelerator facilities and have revealed some unique particle radiation effects not observed with conventional radiations. A comprehensive review of pertinent literature that considers tissue effects of radiation leading to functional detriments in specific organ systems has recently been published (NCRP National Council on Radiation Protection and Measurements, Information Needed to Make Radiation Protection Recommendations for Space Missions Beyond Low-Earth Orbit, Report 153, Bethesda, MD, 2006). This paper highlights the review of two non-cancer concerns from this report: cardiovascular and immunological effects.

  9. Space radiation and cardiovascular disease risk.

    Science.gov (United States)

    Boerma, Marjan; Nelson, Gregory A; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Koturbash, Igor; Hauer-Jensen, Martin

    2015-12-26

    Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  10. From Phenotype to Genotype: Exploring Middle School Students' Understanding of Genetic Inheritance in a Web-Based Environment

    Science.gov (United States)

    Williams, Michelle; Montgomery, Beronda L.; Manokore, Viola

    2012-01-01

    Research shows that students face challenges as they learn about genetic inheritance. The challenges could emanate from the fact that genetic inheritance involves unseen processes at different organizational levels. We explored students' understanding of heredity and related concepts such as cells and reproduction using a Web-based Science Inquiry…

  11. Evaluation of a Web-Based E-Learning Platform for Brief Motivational Interviewing by Nurses in Cardiovascular Care: A Pilot Study

    Science.gov (United States)

    Cossette, Sylvie; Heppell, Sonia; Boyer, Louise; Mailhot, Tanya; Simard, Marie-Josée; Tanguay, Jean-Francois

    2016-01-01

    Background Brief motivational interviewing (MI) can contribute to reductions in morbidity and mortality related to coronary artery disease, through health behavior change. Brief MI, unlike more intensive interventions, was proposed to meet the needs of clinicians with little spare time. While the provision of face-to-face brief MI training on a large scale is complicated, Web-based e-learning is promising because of the flexibility it offers. Objective The primary objective of this pilot study was to examine the feasibility and acceptability of a Web-based e-learning platform for brief MI (MOTIV@CŒUR), which was evaluated by nurses in cardiovascular care. The secondary objective was to assess the preliminary effect of the training on nurses’ perceived brief MI skills and self-reported clinical use of brief MI. Methods We conducted a single-group, pre-post pilot study involving nurses working in a coronary care unit to evaluate MOTIV@CŒUR, which is a Web-based e-learning platform for brief MI, consisting of two sessions lasting 30 and 20 minutes. MOTIV@CŒUR covers 4 real-life clinical situations through role-modeling videos showing nurse-client interactions. A brief introduction to MI is followed by role playing, during which a nurse practitioner evaluates clients’ motivation to change and intervenes according to the principles of brief MI. The clinical situations target smoking, medication adherence, physical activity, and diet. Nurses were asked to complete both Web-based training sessions asynchronously within 20 days, which allowed assessment of the feasibility of the intervention. Data regarding acceptability and preliminary effects (perceived skills in brief MI, and self-reported clinical use of conviction and confidence interventions) were self-assessed through Web-based questionnaires 30 days (±5 days) after the first session. Results We enrolled 27 women and 4 men (mean age 37, SD 9 years) in March 2016. Of the 31 participants, 24 (77%, 95% CI 63%

  12. Improving teamwork, confidence, and collaboration among members of a pediatric cardiovascular intensive care unit multidisciplinary team using simulation-based team training.

    Science.gov (United States)

    Figueroa, Mayte I; Sepanski, Robert; Goldberg, Steven P; Shah, Samir

    2013-03-01

    Findings show that simulation-based team training (SBTT) is effective at increasing teamwork skills. Postpediatric cardiac surgery cardiac arrest (PPCS-CA) is a high-risk clinical situation with high morbidity and mortality. Whereas adult guidelines managing cardiac arrest after cardiac surgery are available, little exists for pediatric cardiac surgery. The authors developed a post-PPCS-CA algorithm and used SBTT to improve identification and management of PPCS-CA in the pediatric cardiovascular intensive care unit. Their goal was to determine whether participation aids in improving teamwork, confidence, and communication during these events. The authors developed a simulation-based training course using common postcardiac surgical emergency scenarios with specific learning objectives. Simulated scenarios are followed by structured debriefings. Participants were evaluated based on critical performance criteria, key elements in the PPCS-CA algorithm, and Team Strategies and Tools to Enhance Performance and Patient Safety (Team STEPPS) principles. Surveys performed before, immediately after, and 3 months after participation evaluated perception of skill, knowledge, and confidence. The study had 37 participants (23 nurses, 5 cardiology/critical care trainees, 5 respiratory therapists, and 4 noncategorized subjects). Confidence and skill in the roles of team leader, advanced airway management, and cardioversion/defibrillation were increased significantly (p Team STEPPS concepts immediately after training and 3 months later. This study showed SBTT to be effective in improving communication and increasing confidence among members of a multidisciplinary team during crisis scenarios. Thus, SBTT provides an excellent tool for teaching and implementing new processes.

  13. [Vitamin D and cardiovascular risk].

    Science.gov (United States)

    Mayer, Otto

    2012-05-01

    The pathogenesis of cardiovascular disease is without any doubt multifactorial, and it is generally accepted, that conventional risk factors determined only about 80% of cardiovascular risk. There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. This review summarizes recent epidemiological evidence and possible pathophysiological mechanism for a role of low vitamin D in cardiovascular diseases. Moreover, available data concerning vitamin D supplementation are depicted.

  14. ADMA, cardiovascular disease and diabetes.

    Science.gov (United States)

    Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Wolzt, Michael; Schernthaner, Guntram

    2008-12-15

    The endogenous competitive nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk marker for future cardiovascular events. Elevated ADMA concentrations have been described in patients with an adverse cardiovascular risk profile. Recently, various studies investigated the independent role of ADMA as a cardiovascular risk predictor in several patient cohorts. In addition, ADMA might not only be a risk marker but also a causative factor for cardiovascular disease. This review summarizes the literature on the relationship between ADMA, cardiovascular disease and diabetes.

  15. A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict Aggressive Phenotype of Prostate Cancer

    Science.gov (United States)

    2015-10-01

    2009). Thus, a clinical dilemma today in the management of PCa is to distinguish men with aggressive disease who need definitive treatment from men...based biomarker can be used to discern PCa patients with aggressive disease and hence would need definitive treatment from those in whom it is less...FOXP3+ cells are T regulatory cells with immunosuppressive properties. Identifying these populations of T cells in the tumor will be an indication of

  16. 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.

  17. Internet-based treatment for older adults with depression and co-morbid cardiovascular disease: protocol for a randomised, double-blind, placebo controlled trial

    Directory of Open Access Journals (Sweden)

    Christensen Helen

    2011-01-01

    Full Text Available Abstract Background Depression, cardiovascular disease (CVD risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. Methods/Design This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Discussion Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on

  18. Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases.

    NARCIS (Netherlands)

    Booij, T.H.; Klop, M.J.; Yan, K.; Szántai-Kis, C.; Szokol, B.; Orfi, L .; Water, van de B.; Keri, G.; Price, L.S.

    2016-01-01

    3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses

  19. Cloud-Based Smart Health Monitoring System for Automatic Cardiovascular and Fall Risk Assessment in Hypertensive Patients.

    Science.gov (United States)

    Melillo, P; Orrico, A; Scala, P; Crispino, F; Pecchia, L

    2015-10-01

    The aim of this paper is to describe the design and the preliminary validation of a platform developed to collect and automatically analyze biomedical signals for risk assessment of vascular events and falls in hypertensive patients. This m-health platform, based on cloud computing, was designed to be flexible, extensible, and transparent, and to provide proactive remote monitoring via data-mining functionalities. A retrospective study was conducted to train and test the platform. The developed system was able to predict a future vascular event within the next 12 months with an accuracy rate of 84 % and to identify fallers with an accuracy rate of 72 %. In an ongoing prospective trial, almost all the recruited patients accepted favorably the system with a limited rate of inadherences causing data losses (<20 %). The developed platform supported clinical decision by processing tele-monitored data and providing quick and accurate risk assessment of vascular events and falls.

  20. Role of biomarkers in cardiac structure phenotyping in heart failure with preserved ejection fraction: critical appraisal and practical use.

    Science.gov (United States)

    D'Elia, Emilia; Vaduganathan, Muthiah; Gori, Mauro; Gavazzi, Antonello; Butler, Javed; Senni, Michele

    2015-12-01

    Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by cardiovascular, metabolic, and pro-inflammatory diseases associated with advanced age and extracardiac comorbidities. All of these conditions finally lead to impairment of myocardial structure and function. The large phenotypic heterogeneity of HFpEF from pathophysiological underpinnings presents a major hurdle to HFpEF therapy. The new therapeutic approach in HFpEF should be targeted to each HF phenotype, instead of the 'one-size-fits-all' approach, which has not been successful in clinical trials. Unless the structural and biological determinants of the failing heart are deeply understood, it will be impossible to appropriately differentiate HFpEF patients, identify subtle myocardial abnormalities, and finally reverse abnormal cardiac function. Based on evidence from endomyocardial biopsies, some of the specific cardiac structural phenotypes to be targeted in HFpEF may be represented by myocyte hypertrophy, interstitial fibrosis, myocardial inflammation associated with oxidative stress, and coronary disease. Once the diagnosis of HFpEF has been established, a potential approach could be to use a panel of biomarkers to identify the main cardiac structural HFpEF phenotypes, guiding towards more appropriate therapeutic strategies. Accordingly, the purpose of this review is to investigate the potential role of biomarkers in identifying different cardiac structural HFpEF phenotypes and to discuss the merits of a biomarker-guided strategy in HFpEF.

  1. Phenotype definition in epilepsy.

    Science.gov (United States)

    Winawer, Melodie R

    2006-05-01

    Phenotype definition consists of the use of epidemiologic, biological, molecular, or computational methods to systematically select features of a disorder that might result from distinct genetic influences. By carefully defining the target phenotype, or dividing the sample by phenotypic characteristics, we can hope to narrow the range of genes that influence risk for the trait in the study population, thereby increasing the likelihood of finding them. In this article, fundamental issues that arise in phenotyping in epilepsy and other disorders are reviewed, and factors complicating genotype-phenotype correlation are discussed. Methods of data collection, analysis, and interpretation are addressed, focusing on epidemiologic studies. With this foundation in place, the epilepsy subtypes and clinical features that appear to have a genetic basis are described, and the epidemiologic studies that have provided evidence for the heritability of these phenotypic characteristics, supporting their use in future genetic investigations, are reviewed. Finally, several molecular approaches to phenotype definition are discussed, in which the molecular defect, rather than the clinical phenotype, is used as a starting point.

  2. SimVascular 2.0: an Integrated Open Source Pipeline for Image-Based Cardiovascular Modeling and Simulation

    Science.gov (United States)

    Lan, Hongzhi; Merkow, Jameson; Updegrove, Adam; Schiavazzi, Daniele; Wilson, Nathan; Shadden, Shawn; Marsden, Alison

    2015-11-01

    SimVascular (www.simvascular.org) is currently the only fully open source software package that provides a complete pipeline from medical image based modeling to patient specific blood flow simulation and analysis. It was initially released in 2007 and has contributed to numerous advances in fundamental hemodynamics research, surgical planning, and medical device design. However, early versions had several major barriers preventing wider adoption by new users, large-scale application in clinical and research studies, and educational access. In the past years, SimVascular 2.0 has made significant progress by integrating open source alternatives for the expensive commercial libraries previously required for anatomic modeling, mesh generation and the linear solver. In addition, it simplified the across-platform compilation process, improved the graphical user interface and launched a comprehensive documentation website. Many enhancements and new features have been incorporated for the whole pipeline, such as 3-D segmentation, Boolean operation for discrete triangulated surfaces, and multi-scale coupling for closed loop boundary conditions. In this presentation we will briefly overview the modeling/simulation pipeline and advances of the new SimVascular 2.0.

  3. Metabolic and carbohydrate characteristics of different phenotypes of polycystic ovary syndrome

    Science.gov (United States)

    Çelik, Ebru; Türkçüoğlu, Ilgın; Ata, Barış; Karaer, Abdullah; Kırıcı, Pınar; Eraslan, Sevil; Taşkapan, Çağatay; Berker, Bülent

    2016-01-01

    Objective To compare the prevalence of various metabolic and cardiovascular risk factors and insulin resistance between polycystic ovary syndrome (PCOS) patients with or without hyperandrogenism. Material and Methods This is a retrospective cross-sectional study involving women with PCOS as diagnosed according to the Androgen Excess (AE) Society definition (n=504) and women with normoandrogenemic PCOS (n=183). Anthropometrics, lipid profile, glucose, insulin, oral glucose tolerance test (OGTT), and reproductive hormone levels were evaluated. Results Women with PCOS diagnosed according to the AE Society had a significantly higher prevalence of metabolic syndrome compared with the normoandrogenemic PCOS phenotype: odds ratio (OR) 2.95 [95% confidence interval (CI) 1.21–7.21]. There was no significant difference in the prevalence glucose intolerance test between the groups [OR: 2.15, 95% CI 0.71–6.56]. The prevalence of low high density lipoprotein (HDL)-cholesterol in the group under the AE-PCOS Society criteria was higher than that of the normoandrogenemic PCOS group [OR: 2.82, 95%CI 1.29–3.36]. Conclusion The risks of metabolic syndrome and cardiovascular disease may vary among the phenotypes of PCOS based on the Rotterdam criteria. This new data may be of reference in informing women with PCOS, although further prospective studies are needed to validate this proposition. PMID:27990089

  4. Space radiation and cardiovascular disease risk

    Institute of Scientific and Technical Information of China (English)

    Marjan Boerma; Gregory A Nelson; Vijayalakshmi Sridharan; Xiao-Wen Mao; Igor Koturbash; Martin Hauer-Jensen

    2015-01-01

    Future long-distance space missions will be associated with significant exposures to ionizing radiation,and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Groundbased studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses,appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk,and several other studies are ongoing. Moreover,astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation,and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined,the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  5. Vitamin D and cardiovascular diseases: Causality.

    Science.gov (United States)

    Wimalawansa, Sunil J

    2016-12-24

    Vitamin D regulates blood pressure, cardiac functions, and endothelial and smooth muscle cell functions, thus, playing an important role in cardiovascular health. Observational studies report associations between vitamin D deficiency with hypertension and cardiovascular-related deaths. Peer-reviewed papers were examined in several research databases as per the guidelines of the Preferred Reporting Items for Systematic Reviews, using key words that address the relationship between vitamin D and cardiovascular disease. Correlations and interpretations were made considering the risks-benefits, broader evidence, and implications. This review analyzed current knowledge regarding the effects of vitamin D on the cardiovascular system. 1,25(OH)2D and related epigenetic modifications subdue cellular inflammation, improve overall endothelial functions, reduce age-related systolic hypertension and vascular rigidity, and attenuate the actions of the renin-angiotensin-aldosterone system. Most observational and ecological studies support 25(OH)vitamin D having protective effects on the cardiovascular system. However, the association of vitamin D deficiency with cardiovascular diseases is based primarily on observational and ecological studies and thus, is a matter of controversy. Adequately powered, randomized controlled clinical trial data are not available to confirm these associations. Thus, to test the hypothesis that correction of vitamin D deficiency protects the cardiovascular system, well-designed, statistically powered, longer-term clinical trials are needed in persons with vitamin D deficiency. Nevertheless, the available data support that adequate vitamin D supplementation and/or sensible sunlight exposure to achieve optimal vitamin D status are important in the prevention of cardiovascular disease and other chronic diseases.

  6. Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton

    Directory of Open Access Journals (Sweden)

    Bovet P

    2011-06-01

    /L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600.Conclusion: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.Keywords: hypertension, cholesterol, community-based program, evaluation, Switzerland

  7. Concordance of HIV type 1 tropism phenotype to predictions using web-based analysis of V3 sequences: composite algorithms may be needed to properly assess viral tropism.

    Science.gov (United States)

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza; Brígido, Luis Fernando de Macedo

    2012-07-01

    Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications.

  8. 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.

  9. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

    Directory of Open Access Journals (Sweden)

    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  10. Multiple Genetic Analysis System-Based Antibiotic Susceptibility Testing in Helicobacter pylori and High Eradication Rate With Phenotypic Resistance-Guided Quadruple Therapy.

    Science.gov (United States)

    Dong, Fangyuan; Ji, Danian; Huang, Renxiang; Zhang, Fan; Huang, Yiqin; Xiang, Ping; Kong, Mimi; Nan, Li; Zeng, Xianping; Wu, Yong; Bao, Zhijun

    2015-11-01

    Antibiotics resistance in Helicobacter pylori (H. pylori) is the major factor for eradication failure. Molecular tests including fluorescence in situ hybridization, PCR-restriction fragment length polymorphism, and dual priming oligonucleotide-PCR (DPO-PCR) play critical roles in the detection of antibiotic susceptibility; however, limited knowledge is known about application of multiple genetic analysis system (MGAS) in the area of H. pylori identification and antibiotics resistance detection.The aim of this study is to determine the antibiotics resistance using different molecular tests and evaluate the treatment outcomes of E-test-based genotypic resistance.A total of 297 patients with dyspepsia complaint were recruited for gastroscopies. Ninety patients with H. pylori culture positive were randomly divided into 2 groups (test group and control group). E-test, general PCR, and MGAS assay were performed in test group. Patients in control group were treated with empirical therapy (rabeprazole + bismuth potassium citrate + amoxicillin [AMX] + clarithromycin [CLR]), whereas patients in test group received quadruple therapy based on E-test results twice daily for 14 consecutive days. The eradication effect of H. pylori was confirmed by C-urea breath test after at least 4 weeks when treatment was finished.Rapid urease test showed 46.5% (128/297) patients with H. pylori infection, whereas 30.3% (90/297) patients were H. pylori culture positive. E-test showed that H. pylori primary resistance rate to CLR, AMX, metronidazole, tetracycline, and levofloxacin (LVX) was 40.0% (18/45), 4.4% (2/45), 53.3% (24/45), 0% (0/45), and 55.6% (25/45), respectively. In addition, there are many multidrug resistant (MDR) phenotypes, and the MDR strains have higher minimum inhibitory concentration than their single-drug resistant counterparts. Considering E-test as the reference test, the sensitivities of general PCR and MGAS in detecting CLR resistance were 83.3% (15/18) and 94.4% (17

  11. Single base substitution causing the fragrant phenotype and development of a type-specific marker in aromatic coconut (Cocos nucifera).

    Science.gov (United States)

    Vongvanrungruang, A; Mongkolsiriwatana, C; Boonkaew, T; Sawatdichaikul, O; Srikulnath, K; Peyachoknagul, S

    2016-09-19

    The fragrance gene, betaine aldehyde dehydrogenase 2 (Badh2), has been well studied in many plant species. The objectives of this study were to clone Badh2 and compare the sequences between aromatic and non-aromatic coconuts. The complete coding region was cloned from cDNA of both aromatic and non-aromatic coconuts. The nucleotide sequences were highly homologous to Badh2 genes of other plants. Badh2 consisted of a 1512-bp open reading frame encoding 503 amino acids. A single nucleotide difference between aromatic and non-aromatic coconuts resulted in the conversion of alanine (non-aromatic) to proline (aromatic) at position 442, which was the substrate binding site of BADH2. The ring side chain of proline could destabilize the structure leading to a non-functional enzyme. Badh2 genomic DNA was cloned from exon 1 to 4, and from exon 5 to 15 from the two coconut types, except for intron 4 that was very long. The intron sequences of the two coconut groups were highly homologous. No differences in Badh2 expression were found among the tissues of aromatic coconut or between aromatic and non-aromatic coconuts. The amino acid sequences of BADH2 from coconut and other plants were compared and the genetic relationship was analyzed using MEGA 7.0. The phylogenetic tree reconstructed by the Bayesian information criterion consisted of two distinct groups of monocots and dicots. Among the monocots, coconut (Cocos nucifera) and oil palm (Elaeis guineensis) were the most closely related species. A marker for coconut differentiation was developed from one-base substitution site and could be successfully used.

  12. From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study.

    Science.gov (United States)

    Aghakhanyan, Gayane; Bonanni, Paolo; Randazzo, Giovanna; Nappi, Sara; Tessarotto, Federica; De Martin, Lara; Frijia, Francesca; De Marchi, Daniele; De Masi, Francesco; Kuppers, Beate; Lombardo, Francesco; Caramella, Davide; Montanaro, Domenico

    2016-01-01

    Angelman syndrome (AS) is a rare neurogenetic disorder due to loss of expression of maternal ubiquitin-protein ligase E3A (UBE3A) gene. It is characterized by severe developmental delay, speech impairment, movement or balance disorder and typical behavioral uniqueness. Affected individuals show normal magnetic resonance imaging (MRI) findings, although mild dysmyelination may be observed. In this study, we adopted a quantitative MRI analysis with voxel-based morphometry (FSL-VBM) method to investigate disease-related changes in the cortical/subcortical grey matter (GM) structures. Since 2006 to 2013 twenty-six AS patients were assessed by our multidisciplinary team. From those, sixteen AS children with confirmed maternal 15q11-q13 deletions (mean age 7.7 ± 3.6 years) and twenty-one age-matched controls were recruited. The developmental delay and motor dysfunction were assessed using Bayley III and Gross Motor Function Measure (GMFM). Principal component analysis (PCA) was applied to the clinical and neuropsychological datasets. High-resolution T1-weighted images were acquired and FSL-VBM approach was applied to investigate differences in the local GM volume and to correlate clinical and neuropsychological changes in the regional distribution of GM. We found bilateral GM volume loss in AS compared to control children in the striatum, limbic structures, insular and orbitofrontal cortices. Voxel-wise correlation analysis with the principal components of the PCA output revealed a strong relationship with GM volume in the superior parietal lobule and precuneus on the left hemisphere. The anatomical distribution of cortical/subcortical GM changes plausibly related to several clinical features of the disease and may provide an important morphological underpinning for clinical and neurobehavioral symptoms in children with AS.

  13. Clocks and cardiovascular function

    Science.gov (United States)

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.

    2016-01-01

    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  14. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    2008-01-01

    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed....

  15. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2008-01-01

    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.  ...

  16. Envejecimiento del sistema cardiovascular

    OpenAIRE

    2005-01-01

    Las principales características del envejecimiento del sistema cardiovascular reflejan cambios anatómicos y estructurales a nivel de la pared de los vasos, la relajación miocárdica, el llenado ventricular y la respuesta a las catecolaminas . Muchos de los cambios funcionales asociados con la edad están relacionados con estos fenómenos. Esta revisión describe los cambios relacionados con el envejecimiento a nivel estructural y funcional del sistema cardiovascular, sus posibles factores etiológ...

  17. Pharmacogenomics and cardiovascular disease

    DEFF Research Database (Denmark)

    Weeke, Peter; Roden, Dan M

    2013-01-01

    Variability in drug responsiveness is a sine qua non of modern therapeutics, and the contribution of genomic variation is increasingly recognized. Investigating the genomic basis for variable responses to cardiovascular therapies has been a model for pharmacogenomics in general and has established...... resulted in changes to the product labels but also have led to development of initial clinical guidelines that consider how to facilitate incorporating genetic information to the bedside. This review summarizes the state of knowledge in cardiovascular pharmacogenomics and considers how variants described...

  18. Myeloperoxidase and cardiovascular disease.

    Science.gov (United States)

    Nicholls, Stephen J; Hazen, Stanley L

    2005-06-01

    Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.

  19. Incidence of cardiovascular events after kidney transplantation and cardiovascular risk scores: study protocol

    Directory of Open Access Journals (Sweden)

    Lorenzo-Aguiar Dolores

    2011-01-01

    Reduction, RRR (Relative Risk Reduction and NNT (Number Needed to Treat. The ability of different cardiovascular risk scores to predict cardiovascular events will be analyzed by using the c index and the area under ROC curves. Based on the competing risks analysis, a nomogram to predict the probability of cardiovascular events after kidney transplantation will be developed. Discussion This study will make it possible to determine the post-transplant incidence of cardiovascular events in a large cohort of renal transplant recipients in Spain, to confirm the relationship between traditional and transplant-specific cardiovascular risk factors and CVD, and to develop a score to predict the risk of CVD in these patients.

  20. Candidate genes involved in cardiovascular risk factors by a family-based association study on the island of Kosrae, Federated States of Micronesia.

    Science.gov (United States)

    Han, Zhihua; Heath, Simon C; Shmulewitz, Dvora; Li, Wentian; Auerbach, Steve B; Blundell, Maude L; Lehner, Thomas; Ott, Jurg; Stoffel, Markus; Friedman, Jeffrey M; Breslow, Jan L

    2002-07-01

    Altered plasma levels of lipids and lipoproteins, obesity, hypertension, and diabetes are major risk factors for atherosclerotic cardiovascular disease. To identify genes that affect these traits and disorders, we looked for association between markers in candidate genes (apolipoprotein AII (apo AII), apolipoprotein AI-CIII-AIV gene cluster (apo AI-CIII-AIV), apolipoprotein E (apo E), cholesteryl ester transfer protein (CETP), cholesterol 7alpha-hydroxylase (CYP7a), hepatic lipase (HL), and microsomal triglyceride transfer protein (MTP)) and known risk factors (triglycerides (Tg), total cholesterol (TC), apolipoprotein AI (apo AI), apolipoprotein AII (apo AII), apolipoprotein B (apo B), body mass index (BMI), blood pressure (BP), leptin, and fasting blood sugar (FBS) levels.) A total of 1,102 individuals from the Pacific island of Kosrae were genotyped for the following markers: Apo AII/MspI, Apo CIII/SstI, Apo AI/XmnI, Apo E/HhaI, CETP/TaqIB, CYP7a/BsaI, HL/DraI, and MTP/HhpI. After testing for population stratification, family-based association analysis was carried out. Novel associations found were: 1) the apo AII/MspI with apo AI and BP levels, 2) the CYP7a/BsaI with apo AI and BMI levels. We also confirmed the following associations: 1) the apo AII/MspI with Tg level; 2) the apo CIII/SstI with Tg, TC, and apo B levels; 3) the Apo E/HhaI E2, E3, and E4 alleles with TC, apo AI, and apo B levels; and 4) the CETP/TaqIB with apo AI level. We further confirmed the connection between the apo AII gene and Tg level by a nonparametric linkage analysis. We therefore conclude that many of these candidate genes may play a significant role in susceptibility to heart disease.

  1. The mutation p.E113K in the Schiff base counterion of rhodopsin is associated with two distinct retinal phenotypes within the same family

    Science.gov (United States)

    Reiff, Charlotte; Owczarek-Lipska, Marta; Spital, Georg; Röger, Carsten; Hinz, Hebke; Jüschke, Christoph; Thiele, Holger; Altmüller, Janine; Nürnberg, Peter; Da Costa, Romain; Neidhardt, John

    2016-01-01

    The diagnoses of retinitis pigmentosa (RP) and stationary night blindness (CSNB) are two distinct clinical entities belonging to a group of clinically and genetically heterogeneous retinal diseases. The current study focused on the identification of causative mutations in the RP-affected index patient and in several members of the same family that reported a phenotype resembling CSNB. Ophthalmological examinations of the index patient confirmed a typical form of RP. In contrast, clinical characterizations and ERGs of another affected family member showed the Riggs-type CSNB lacking signs of RP. Applying whole exome sequencing we detected the non-synonymous substitution c.337G > A, p.E113 K in the rhodopsin (RHO) gene. The mutation co-segregated with the diseases. The identification of the pathogenic variant p.E113 K is the first description of a naturally-occurring mutation in the Schiff base counterion of RHO in human patients. The heterozygous mutation c.337G > A in exon 1 was confirmed in the index patient as well as in five CSNB-affected relatives. This pathogenic sequence change was excluded in a healthy family member and in 199 ethnically matched controls. Our findings suggest that a mutation in the biochemically well-characterized counterion p.E113 in RHO can be associated with RP or Riggs-type CSNB, even within the same family. PMID:27812022

  2. Hybrid microarray based on double biomolecular markers of DNA and carbohydrate for simultaneous genotypic and phenotypic detection of cholera toxin-producing Vibrio cholerae.

    Science.gov (United States)

    Shin, Hwa Hui; Seo, Jeong Hyun; Kim, Chang Sup; Hwang, Byeong Hee; Cha, Hyung Joon

    2016-05-15

    Life-threatening diarrheal cholera is usually caused by water or food contaminated with cholera toxin-producing Vibrio cholerae. For the prevention and surveillance of cholera, it is crucial to rapidly and precisely detect and identify the etiological causes, such as V. cholerae and/or its toxin. In the present work, we propose the use of a hybrid double biomolecular marker (DBM) microarray containing 16S rRNA-based DNA capture probe to genotypically identify V. cholerae and GM1 pentasaccharide capture probe to phenotypically detect cholera toxin. We employed a simple sample preparation method to directly obtain genomic DNA and secreted cholera toxin as target materials from bacterial cells. By utilizing the constructed DBM microarray and prepared samples, V. cholerae and cholera toxin were detected successfully, selectively, and simultaneously; the DBM microarray was able to analyze the pathogenicity of the identified V. cholerae regardless of whether the bacteria produces toxin. Therefore, our proposed DBM microarray is a new effective platform for identifying bacteria and analyzing bacterial pathogenicity simultaneously.

  3. Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the chinese population: a twin-based heritability study

    DEFF Research Database (Denmark)

    Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng;

    2011-01-01

    contributions. Results: The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for all phenotypes except for triglyceride. Modest to high heritability estimates were obtained in univariate analysis ranging from 0.5 for total cholesterol to 0.78 for weight......Objective: We perform a comprehensive heritability study on multiple phenotypes related to metabolic syndrome using Chinese twins to assess the genetic and environmental effects in determining the variation and covariation of the phenotypes in the Chinese population. Methods: The studied sample...... contains 654 twins collected in the Qingdao municipality. A total of 10 phenotypes covering anthropometric measurements, plasma glucose levels, lipids, blood pressures etc. were examined. Univariate and bivariate structural equation models were fitted for assessing the genetic and environmental...

  4. Hypertriglyceridemic waist phenotype: association with metabolic disorders and visceral fat in adults

    Directory of Open Access Journals (Sweden)

    Carolina Cunha de Oliveira

    2014-07-01

    Full Text Available Objective: To evaluate the association of Hypertriglyceridemic waist with metabolic disorders and visceral fat in adults. Methods: Cross-sectional study with 191 individuals of both sexes. Subjects were grouped according to Waist Circumference (WC ratings (Men: > 90 cm; Women: > 80 cm and triglycerides (TG (> 150 mg/dl in Group 1 (HTW Phenotype: elevated WC and TG; Group 2 (absence of HTW Phenotype: elevated WC and normal TG or normal WC and elevated TG or normal WC and TG. Metabolic alternations, visceral adipose tissue (VAT and visceral/subcutaneous fat index (VF/SF measured by computed tomography were evaluated as cardiovascular risk factors between the groups. Results: Individuals with HTW phenotype, 82% had three or more cardiovascular risk factors. The association between cardiovascular risk factors with HTW phenotype revealed that among men 73.7% had hypercholesterolemia, 94.9% elevated non-HDLc and 78.9% excess of VAT area (p = 0.001. Among women, 65% had elevated Sistolic Blood Plessure, 80% hypercholesterolemia and 90% elevated non-HDLc (p < 0.02. Conclusion: The HTW phenotype associated with the metabolic alternations and VAT excess. Individuals with HTW had higher number of cardiovascular risk factors. The Hypertriglyceridemic waist can be used in clinical practice for investigating cardiovascular risk and visceral adipose tissue in individuals.

  5. Plant Phenotype Characterization System

    Energy Technology Data Exchange (ETDEWEB)

    Daniel W McDonald; Ronald B Michaels

    2005-09-09

    This report is the final scientific report for the DOE Inventions and Innovations Project: Plant Phenotype Characterization System, DE-FG36-04GO14334. The period of performance was September 30, 2004 through July 15, 2005. The project objective is to demonstrate the viability of a new scientific instrument concept for the study of plant root systems. The root systems of plants are thought to be important in plant yield and thus important to DOE goals in renewable energy sources. The scientific study and understanding of plant root systems is hampered by the difficulty in observing root activity and the inadequacy of existing root study instrumentation options. We have demonstrated a high throughput, non-invasive, high resolution technique for visualizing plant root systems in-situ. Our approach is based upon low-energy x-ray radiography and the use of containers and substrates (artificial soil) which are virtually transparent to x-rays. The system allows us to germinate and grow plant specimens in our containers and substrates and to generate x-ray images of the developing root system over time. The same plant can be imaged at different times in its development. The system can be used for root studies in plant physiology, plant morphology, plant breeding, plant functional genomics and plant genotype screening.

  6. Development of a 3D Tissue Culture–Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases

    OpenAIRE

    Booij, T.H.; Klop, M.J.; Yan, K.; Szántai-Kis, C.; Szokol, B.; L. Orfi; Water, de; Keri, G.; Price, L. S.

    2016-01-01

    3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in 3D hydrogels also show complex phenotypes, increasing the scope for phenotypic profiling. Here we describe a high-content screening platform that uses invasive human prostate cancer cells cultured in 3D in standard 384-well assay plates to study the activity of potential therapeutic small molecules and antibody biologics. Image analysis tools wer...

  7. Effects of an evidence-based computerized virtual clinician on low-density lipoprotein and non-high-density lipoprotein cholesterol in adults without cardiovascular disease: The Interactive Cholesterol Advisory Tool.

    Science.gov (United States)

    Block, Robert C; Abdolahi, Amir; Niemiec, Christopher P; Rigby, C Scott; Williams, Geoffrey C

    2016-12-01

    There is a lack of research on the use of electronic tools that guide patients toward reducing their cardiovascular disease risk. We conducted a 9-month clinical trial in which participants who were at low (n = 100) and moderate (n = 23) cardiovascular disease risk-based on the National Cholesterol Education Program III's 10-year risk estimator-were randomized to usual care or to usual care plus use of an Interactive Cholesterol Advisory Tool during the first 8 weeks of the study. In the moderate-risk category, an interaction between treatment condition and Framingham risk estimate on low-density lipoprotein and non-high-density lipoprotein cholesterol was observed, such that participants in the virtual clinician treatment condition had a larger reduction in low-density lipoprotein and non-high-density lipoprotein cholesterol as their Framingham risk estimate increased. Perceptions of the Interactive Cholesterol Advisory Tool were positive. Evidence-based information about cardiovascular disease risk and its management was accessible to participants without major technical challenges.

  8. 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

  9. Cheese and cardiovascular health

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard

    Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. Low-density lipoprotein (LDL) cholesterol is a well-known risk factor of CVD which increases after the intake of saturated fatty acids (SFA). Cheese is a dietary product commonly consumed in Western countries and known...

  10. Cardiovascular effects of gliptins.

    Science.gov (United States)

    Scheen, André J

    2013-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

  11. Neuropeptides in cardiovascular control.

    Science.gov (United States)

    Ganong, W F

    1984-12-01

    Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Epigenetics and cardiovascular disease

    Science.gov (United States)

    Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

  13. Prevalence of thoracic aortic calcification and its relationship to cardiovascular risk factors and coronary calcification in an unselected population-based cohort: the Heinz Nixdorf Recall Study.

    Science.gov (United States)

    Kälsch, Hagen; Lehmann, Nils; Möhlenkamp, Stefan; Hammer, Cornelia; Mahabadi, Amir A; Moebus, Susanne; Schmermund, Axel; Stang, Andreas; Bauer, Marcus; Jöckel, Karl-Heinz; Erbel, Raimund

    2013-01-01

    Thoracic aortic calcification (TAC) and coronary artery calcium (CAC) have been proposed for risk assessment of coronary artery and cardiovascular disease events. The aim of this analysis is to assess the prevalence of TAC and to determine its relationship with cardiovascular risk factors and CAC in a general unselected population. TAC was measured from electron beam computed tomography scans and quantified by Agatston-Score in 4,025 participants aged 45-75 years (mean age 59.4 ± 7.8 years, 53% female) from the Heinz Nixdorf Recall Study. Multivariable generalized linear regression was used to evaluate relationships between TAC and cardiovascular risk factors and CAC. Overall 2,538/4,025 (63.1%) participants revealed TAC. Prevalence of TAC was greater in men than in women (65.2 vs. 61.7%, p = 0.009). TAC was most strongly associated with age, systolic blood pressure, smoking and high levels of LDL-cholesterol. Prevalence of CAC was significantly higher in participants with TAC than without (74.0 vs. 57.6%, p CAC in the presence of TAC (prevalence ratio (PR) 1.29 [95% CI: 1.22-1.35], p TAC has high prevalence and largely shares cardiovascular risk factors with CAD while being independently associated with present CAC.

  14. Self-management support program for patients with cardiovascular diseases: user-centered development of the tailored, web-based program vascular view.

    NARCIS (Netherlands)

    Puijk-Hekman, S.; Gaal, B.G.I. van; Bredie, S.J.; Nijhuis-van der Sanden M.W.G.; Dulmen, S. van

    2017-01-01

    Background: In addition to medical intervention and counseling, patients with cardiovascular disease (CVD) need to manage their disease and its consequences by themselves in daily life. Objective: The aim of this paper is to describe the development of “Vascular View,” a comprehensive, multi-compone

  15. High dietary glycemic load and glycemic index increase risk of cardiovascular disease among middle-aged women : a population-based follow-up study

    NARCIS (Netherlands)

    Beulens, Joline W. J.; de Bruijne, Leonie M.; Stolk, Ronald P.; Peeters, Petra H. M.; Bots, Michiel L.; Grobbee, Diederick E.; van der Schouw, Yvonne T.

    2007-01-01

    Objectives The goal of this work was to assess whether high dietary glycemic load and glycemic index are associated with an increased risk of cardiovascular disease (CVD). Background The associations of dietary glycemic index and glycemic load with risk of CVD are not well established, particularly

  16. High dietary glycemic load and glycemic index increase risk of cardiovascular disease among middle-aged women - A population-based follow-up study

    NARCIS (Netherlands)

    Beulens, Joline W. J.; de Bruijne, Leonie M.; Stolk, Ronald P.; Peeters, Petra H. M.; Bots, Michiel L.; Grobbee, Diederick E.; van der Schouw, Yvonne T.

    2007-01-01

    Objectives The goal of this work was to assess whether high dietary glycemic load and glycemic index are associated with an increased risk of cardiovascular disease (CVD). Background The associations of dietary glycemic index and glycemic load with risk of CVD are not well established, particularly

  17. The Cardiovascular Research Grid (CVRG)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CardioVascular Research Grid (CVRG) project is creating an infrastructure for sharing cardiovascular data and data analysis tools. CVRG tools are developed using...

  18. Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP study: a randomised controlled trial of a polypill-based strategy amongst Indigenous and non Indigenous people at high cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Usherwood Tim

    2010-08-01

    Full Text Available Abstract Background The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels. Methods/Design The study is an open, randomised, controlled, multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practices and Aboriginal Medical Services, followed for an average of 18 months. The participants will be randomised to one of two versions of the polypill, the version chosen by the treating health professional according to clinical features of the patient, or to usual care. The primary study outcomes will be changes, from baseline measures, in serum cholesterol and systolic blood pressure and self-reported current use of aspirin, a statin and at least two blood pressure lowering agents. Secondary study outcomes include cardiovascular events, renal outcomes, self-reported barriers to indicated therapy, prescription of indicated therapy, occurrence of serious adverse events and changes in quality-of-life. The trial will be supplemented by formal economic and process evaluations. Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated. Trial Registration This trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN126080005833347.

  19. Use of vitamin supplements and risk of total cancer and cardiovascular disease among the Japanese general population: A population-based survey

    Directory of Open Access Journals (Sweden)

    Ishihara Junko

    2011-07-01

    Full Text Available Abstract Background Despite the popular use of vitamin supplements and several prospective cohort studies investigating their effect on cancer incidence and cardiovascular disease (CVD, scientific data supporting their benefits remain controversial. Inconsistent results may be partly explained by the fact that use of supplements is an inconsistent behavior in individuals. We examined whether vitamin supplement use patterns affect cancer and CVD risk in a population-based cohort study in Japan. Methods A total of 28,903 men and 33,726 women in the Japan Public Health Center-based Prospective Study cohort, who answered questions about vitamin supplement use in the first survey from 1990-1994 and the second survey from 1995-1998, were categorized into four groups (never use, past use, recent use, and consistent use and followed to the end of 2006 for cancer and 2005 for CVD. Sex-specific hazard ratios (HRs and 95% confidence intervals (95% CIs were used to describe the relative risks of cancer and CVD associated with vitamin supplement use. Results During follow-up, 4501 cancer and 1858 CVD cases were identified. Multivariate adjusted analysis revealed no association of any pattern of vitamin supplement use with the risk of cancer and CVD in men. In women, consistent use was associated with lower risk of CVD (HR 0.60, 95% CI 0.41-0.89, whereas past (HR 1.17, 95% CI 1.02-1.33 and recent use (HR 1.24, 95% CI 1.01-1.52 were associated with higher risk of cancer. Conclusions To our knowledge, this is the first prospective cohort study to examine simultaneously the associations between vitamin supplement use patterns and risk of cancer and CVD. This prospective cohort study demonstrated that vitamin supplement use has little effect on the risk of cancer or CVD in men. In women, however, consistent vitamin supplement use might reduce the risk of CVD. Elevated risk of cancer associated with past and recent use of vitamin supplements in women may be partly

  20. 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....

  1. 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.

  2. Cardiovascular protection in type 2 diabetes: time to ADVANCE management ACCORDing to the evidence

    Directory of Open Access Journals (Sweden)

    Hajhosseiny R

    2013-12-01

    Full Text Available Reza Hajhosseiny,1 Kaivan Khavandi,1 Soudeh Mashayekhi,2 Adam S Greenstein,3 Rayaz A Malik31British Heart Foundation Centre of Cardiovascular Excellence, St Thomas' Hospital, London, UK; 2Department of Primary Care and Public Health, Imperial College London, London, UK; 3Institute of Human Development, University of Manchester, Manchester, UKAbstract: Individuals with type 2 diabetes mellitus are at very substantial risk of cardiovascular disease, and most will succumb to complications from premature coronary artery events. At the same time, the diabetic myocardium undergoes unique phenotypic alterations as a consequence of multiple structural and cellular injuries, which together form "diabetic cardiomyopathy." Attempts to curb risk through intensive modulation of glycemia and blood pressure have proven disappointing in preventing cardiovascular events, and potentially even dangerous. Conversely, prior to development of disease, there appears to be a linear relationship between risk parameters and events. These observations are likely the consequence of widespread vascular damage, which is present at the point that glycemic thresholds meet diagnostic criteria for diabetes. This is particularly true of the microcirculation. Interventions at the prediabetic stage have been consistent with this, where early intensive risk-factor modulation has been successful in preventing events and even regressing existing risk. Upstream, the force driving these pathologies is being overweight and obesity. High-risk individuals can be identified through simple body mass parameters, with confirmation of prediabetes/metabolic syndrome with further assessment of other metabolic parameters such as glucose and lipids. A number of novel pharmacotherapies may prove beneficial at this stage, and incretin-based therapies appear particularly promising in this respect. Similarly, bariatric procedures have shown remarkable improvements in metabolic and cardiovascular

  3. Metabolomic phenotyping of a cloned pig model

    Directory of Open Access Journals (Sweden)

    Callesen Henrik

    2011-08-01

    Full Text Available Abstract Background Pigs are widely used as models for human physiological changes in intervention studies, because of the close resemblance between human and porcine physiology and the high degree of experimental control when using an animal model. Cloned animals have, in principle, identical genotypes and possibly also phenotypes and this offer an extra level of experimental control which could possibly make them a desirable tool for intervention studies. Therefore, in the present study, we address how phenotype and phenotypic variation is affected by cloning, through comparison of cloned pigs and normal outbred pigs. Results The metabolic phenotype of cloned pigs (n = 5 was for the first time elucidated by nuclear magnetic resonance (NMR-based metabolomic analysis of multiple bio-fluids including plasma, bile and urine. The metabolic phenotype of the cloned pigs was compared with normal outbred pigs (n = 6 by multivariate data analysis, which revealed differences in the metabolic phenotypes. Plasma lactate was higher for cloned vs control pigs, while multiple metabolites were altered in the bile. However a lower inter-individual variability for cloned pigs compared with control pigs could not be established. Conclusions From the present study we conclude that cloned and normal outbred pigs are phenotypically different. However, it cannot be concluded that the use of cloned animals will reduce the inter-individual variation in intervention studies, though this is based on a limited number of animals.

  4. 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.

  5. 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.

  6. Effectiveness of community-based comprehensive healthy lifestyle promotion on cardiovascular disease risk factors in a rural Vietnamese population: a quasi-experimental study

    Directory of Open Access Journals (Sweden)

    Nguyen Quang

    2012-07-01

    Full Text Available Abstract Background Health promotion is a key component for primary prevention of cardiovascular disease (CVD. This study evaluated the impact of healthy lifestyle promotion campaigns on CVD risk factors (CVDRF in the general population in the context of a community-based programme on hypertension management. Methods A quasi-experimental intervention study was carried out in two rural communes of Vietnam from 2006 to 2009. In the intervention commune, a hypertensive-targeted management programme integrated with a community-targeted health promotion was initiated, while no new programme, apart from conventional healthcare services, was provided in the reference commune. Health promotion campaigns focused on smoking cessation, reducing alcohol consumption, encouraging physical activity and reducing salty diets. Repeated cross-sectional surveys in local adult population aged 25 years and over were undertaken to assess changes in blood pressure (BP and behavioural CVDRFs (smoking, alcohol consumption, physical inactivity and salty diet in both communes before and after the 3-year intervention. Results Overall 4,650 adults above 25 years old were surveyed, in four randomly independent samples covering both communes at baseline and after the 3-year intervention. Although physical inactivity and obesity increased over time in the intervention commune, there was a significant reduction in systolic and diastolic BP (3.3 and 4.7 mmHg in women versus 3.0 and 4.6 mmHg in men respectively in the general population at the intervention commune. Health promotion reduced levels of salty diets but had insignificant impact on the prevalence of daily smoking or heavy alcohol consumption. Conclusion Community-targeted healthy lifestyle promotion can significantly improve some CVDRFs in the general population in a rural area over a relatively short time span. Limited effects on a context-bound CVDRF like smoking suggested that higher intensity of intervention

  7. PPAR Genomics and Pharmacogenomics: Implications for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sharon Cresci

    2008-03-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs consist of three related transcription factors that serve to regulate a number of cellular processes that are central to cardiovascular health and disease. Numerous pharmacologic studies have assessed the effects of specific PPAR agonists in clinical trials and have provided insight into the clinical effects of these genes while genetic studies have demonstrated clinical associations between PPAR polymorphisms and abnormal cardiovascular phenotypes. With the abundance of data available from these studies as a background, PPAR pharmacogenetics has become a promising and rapidly advancing field. This review focuses on summarizing the current state of understanding of PPAR genetics and pharmacogenetics and the important implications for the individualization of therapy for patients with cardiovascular diseases.

  8. Rho kinases in cardiovascular physiology and pathophysiology.

    Science.gov (United States)

    Loirand, Gervaise; Guérin, Patrice; Pacaud, Pierre

    2006-02-17

    Rho kinases (ROCKs) are the first and the best-characterized effectors of the small G-protein RhoA. In addition to their effect on actin organization, or through this effect, ROCKs have been found to regulate a wide range of fundamental cell functions such as contraction, motility, proliferation, and apoptosis. Abnormal activation of the RhoA/ROCK pathway has been observed in major cardiovascular disorders such as atherosclerosis, restenosis, hypertension, pulmonary hypertension, and cardiac hypertrophy. This review, based on recent molecular, cellular, and animal studies, focuses on the current understanding of ROCK signaling and its roles in cardiovascular physiology and pathophysiology.

  9. The Danish Cardiovascular Screening Trial (DANCAVAS)

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Rasmussen, Lars Melholt; Søgaard, Rikke

    2015-01-01

    /iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for CVD in men aged 65-74. Attendance rate and compliance to initiated preventive actions must be expected to become of major importance. TRIAL REGISTRATION: Current......) a telemetric assessment of the heart rhythm, and (4) a measurement of the cholesterol and plasma glucose levels. Up-to-date cardiovascular preventive treatment is recommended in case of positive findings. OBJECTIVE: To investigate whether advanced cardiovascular screening will prevent death and cardiovascular...... events, and whether the possible health benefits are cost effective. OUTCOME: Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). RANDOMIZATION: Each of the 45,000 individuals is, by EPIDATA, given a random number from 1-100. Those...

  10. [Multiculturalism and cardiovascular diseases].

    Science.gov (United States)

    Gaudio, Carlo; Corsi, Filippo; Esposito, Cosimo; Di Michele, Sara; Nguyen, Bich Lien; Khatibi, Shahrzad; Sciarretta, Tesir; Franchitto, Silvia; Mirabelli, Francesca; Pannarale, Giuseppe

    2004-01-01

    Immigration has increased drastically to the point of becoming an ordinary structure of our society. Once in Italy, the immigrant's health is compromised rapidly due to a series of conditions and illnesses that exist in our country: lack of work, inadequate salary, inappropriate residence, lacking family support, climate changes, nutritional differences. Cardiovascular illnesses represent 7.6% of the diseases of the immigrants, and cause 36.6% of deaths. The risk factors that affect the genesis of cardiovascular diseases include: subjective factors (age, ethnic group), environmental, nutritional and pathological (arterial hypertension, AIDS, tuberculosis, alcohol). The challenge for our time is to design a new solidarity model to promote cultural and social integration in order to meet the multiethnical and multiracial needs of western society. This model should permit reconsideration of doctor-patient relationship in order to build a real intercultural society.

  11. Migraine and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Marcelo E. Bigal

    2011-02-01

    Full Text Available Migraine, especially migraine with aura is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine with and without aura to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication and cardiovascular mortality. The topic is therefore of considerable interest. Accordingly, herein we review the association between migraine and cardiovascular disease. We start by briefly presenting diagnostic criteria for migraine and revising its pathophysiology. We follow by summarizing the evidence on the topic. We then briefly present the results of a recent meta-analysis. We close by highlighting results of a large epidemiological study conducted after the publication of the meta-analysis.

  12. Prodrugs in Cardiovascular Therapy

    Directory of Open Access Journals (Sweden)

    Maryam Tabrizian

    2008-05-01

    Full Text Available Prodrugs are biologically inactive derivatives of an active drug intended to solve certain problems of the parent drug such as toxicity, instability, minimal solubility and non-targeting capabilities. The majority of drugs for cardiovascular diseases undergo firstpass metabolism, resulting in drug inactivation and generation of toxic metabolites, which makes them appealing targets for prodrug design. Since prodrugs undergo a chemical reaction to form the parent drug once inside the body, this makes them very effective in controlling the release of a variety of compounds to the targeted site. This review will provide the reader with an insight on the latest developments of prodrugs that are available for treating a variety of cardiovascular diseases. In addition, we will focus on several drug delivery methodologies that have merged with the prodrug approach to provide enhanced target specificity and controlled drug release with minimal side effects.

  13. 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.

  14. Slow breathing and cardiovascular disease.

    Science.gov (United States)

    Chaddha, Ashish

    2015-01-01

    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.

  15. Teaching Cardiovascular Integrations with Computer Laboratories.

    Science.gov (United States)

    Peterson, Nils S.; Campbell, Kenneth B.

    1985-01-01

    Describes a computer-based instructional unit in cardiovascular physiology. The program (which employs simulated laboratory experimental techniques with a problem-solving format is designed to supplement an animal laboratory and to offer students an integrative approach to physiology through use of microcomputers. Also presents an overview of the…

  16. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Energy Technology Data Exchange (ETDEWEB)

    Farzan, Shohreh F. [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Chen, Yu [Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY (United States); Rees, Judy R.; Zens, M. Scot [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States); Karagas, Margaret R., E-mail: margaret.r.karagas@dartmouth.edu [Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH (United States)

    2015-09-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic's effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. - Highlights: • Arsenic (As) has been associated with increased cardiovascular disease (CVD) risk. • Little is known about CVD effects at lower levels of As exposure common in the US. • Few have investigated the joint effects of As and smoking on CVD in US adults. • We examine chronic low-level As exposure and smoking in relation to CVD mortality. • Arsenic exposure may increase ischemic heart disease mortality among smokers in US.

  17. 基于肠促胰素的治疗药物在心血管系统中作用的研究进展%Advances in Studies on the Effect of Incretin-Based Therapy on Cardiovascular System

    Institute of Scientific and Technical Information of China (English)

    于倩; 于德民

    2014-01-01

    心血管疾病(CVD)是糖尿病的大血管并发症之一,也是致患者死亡的主要原因。新型药物的心血管安全性是广受关注的问题,胰高血糖素样肽-1受体激动剂(GLP-1RA)和二肽基肽酶-4抑制剂(DPP-4I)是两类通过提高肠促胰素活性治疗2型糖尿病(T2DM)的新型药物。GLP-1RA和DPP-4I对心血管功能异常的动物模型及缺血性心脏病患者的心功能都具有保护作用。但其对已合并心脏疾病的糖尿病患者心血管系统的作用尚不确定。本文将近年来关于GLP-1RA和DPP-4I对心血管系统影响的研究进行综述,为临床治疗糖尿病及其并发症提供依据。%Cardiovascular disease (CVD) is one of the major complications of type 2 diabetes mellitus (T2DM), which results in a high risk of mortality. Thus, the cardiovascular safety of new anti-diabetic agents has become an important prob⁃lem with wide concern. There are two classes of incretine-based medications: glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitor (DPP-4I). It has been demonstrated that GLP-1RA and DPP-4I possesse beneficial actions in both animal models of cardiovascular dysfunction and patients with ischemic heart diseases. However, their effects on the cardiovascular system in diabetic patients with heart diseases are still uncertain. Here, we sys⁃tematically reviewed the effects of GLP-1RA and DPP-4I on cardiovascular system to provide more evidence of incretin-based therapy application for diabetes and complications.

  18. Adaptive evolution of molecular phenotypes

    Science.gov (United States)

    Held, Torsten; Nourmohammad, Armita; Lässig, Michael

    2014-09-01

    Molecular phenotypes link genomic information with organismic functions, fitness, and evolution. Quantitative traits are complex phenotypes that depend on multiple genomic loci. In this paper, we study the adaptive evolution of a quantitative trait under time-dependent selection, which arises from environmental changes or through fitness interactions with other co-evolving phenotypes. We analyze a model of trait evolution under mutations and genetic drift in a single-peak fitness seascape. The fitness peak performs a constrained random walk in the trait amplitude, which determines the time-dependent trait optimum in a given population. We derive analytical expressions for the distribution of the time-dependent trait divergence between populations and of the trait diversity within populations. Based on this solution, we develop a method to infer adaptive evolution of quantitative traits. Specifically, we show that the ratio of the average trait divergence and the diversity is a universal function of evolutionary time, which predicts the stabilizing strength and the driving rate of the fitness seascape. From an information-theoretic point of view, this function measures the macro-evolutionary entropy in a population ensemble, which determines the predictability of the evolutionary process. Our solution also quantifies two key characteristics of adapting populations: the cumulative fitness flux, which measures the total amount of adaptation, and the adaptive load, which is the fitness cost due to a population's lag behind the fitness peak.

  19. 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.

  20. Risk of death from cardiovascular disease associated with low-level arsenic exposure among long-term smokers in a US population-based study

    Science.gov (United States)

    Farzan, Shohreh F.; Chen, Yu; Rees, Judy R.; Zens, M. Scot; Karagas, Margaret R.

    2015-01-01

    High levels of arsenic exposure have been associated with increases in cardiovascular disease risk. However, studies of arsenic’s effects at lower exposure levels are limited and few prospective studies exist in the United States using long-term arsenic exposure biomarkers. We conducted a prospective analysis of the association between toenail arsenic and cardiovascular disease mortality using longitudinal data collected on 3939 participants in the New Hampshire Skin Cancer Study. Using Cox proportional hazard models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals associated with the risk of death from any cardiovascular disease, ischemic heart disease, and stroke, in relation to natural-log transformed toenail arsenic concentrations. In this US population, although we observed no overall association, arsenic exposure measured from toenail clipping samples was related to an increased risk of ischemic heart disease mortality among long-term smokers (as reported at baseline), with increased hazard ratios among individuals with ≥ 31 total smoking years (HR: 1.52, 95% CI: 1.02, 2.27), ≥ 30 pack-years (HR: 1.66, 95% CI: 1.12, 2.45), and among current smokers (HR: 1.69, 95% CI: 1.04, 2.75). These results are consistent with evidence from more highly exposed populations suggesting a synergistic relationship between arsenic exposure and smoking on health outcomes and support a role for lower-level arsenic exposure in ischemic heart disease mortality. PMID:26048586

  1. Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular Diseases: Results from a Population-Based Study in Italy

    Science.gov (United States)

    Greci, Marina; Manicardi, Valeria

    2017-01-01

    The aim of the study is to assess sex difference in association between type 2 diabetes and incidence of major cardiovascular events, that is, myocardial infarction, stroke, and heart failure, using information retrieved by diabetes register. The inhabitants of Reggio Emilia (Italy) aged 30–84 were followed during 2012–2014. Incidence rate ratios and 95% confidence intervals were calculated using multivariate Poisson model. The age- and sex-specific event rates were graphed. Subjects with type 2 diabetes had an excess risk compared to their counterparts without diabetes for all the three major cardiovascular events. The excess risk is similar in women and men for stroke (1.8 times) and heart failure (2.7 times), while for myocardial infarction, the excess risk in women is greater than the one observed in men (IRR 2.58, 95% CI 2.22–3.00 and IRR 1.78, 95% CI 1.60–2.00, resp.; P of interaction diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95% CI 0.53–0.72 and IRR 0.36, 95% CI 0.33–0.39, resp.). In women with type 2 diabetes, the risk of major cardiovascular events is anticipated by 20–30 years, while in men it is by 15–20.

  2. Assessment of Medication Adherence in Elderly Patients With Cardiovascular Diseases Based on Demographic Factors in Bushehr City in the Year 2013

    Directory of Open Access Journals (Sweden)

    Jahanpour

    2015-07-01

    Full Text Available Background The growing global elderly population is in need of more prescription medications. Objectives The present study assessed medication adherence with respect to demographic factors among elderly patients with cardiovascular disease who were admitted to a teaching hospital as well as outpatients referred to treatment centers in Bushehr, Iran. Patients and Methods The present study was a descriptive-analytic cross-sectional study using a simple random sampling method that investigated 125 elderly patients with cardiovascular disease. Data were collected through the Medication Adherence Questionnaire. Data were analyzed by using descriptive statistics, and Pearson and Cramer’s V correlation analyses, using SPSS version 18. Results Among the patients, 57.6% and 42.4% were female and male, respectively. Moreover, 62.4% had high adherence to their prescribed medications. Frequency of medication use, history of previous hospitalization, and sex were significantly associated with adherence to medication (P < 0.05. Conclusions More than half of elderly patients with cardiovascular disease had high adherence to their medications. Demographic factors including the frequency of daily medication use, history of hospitalization, and female sex were associated with adherence to medication. By considering these factors, doctors and nurses increase medication adherence, especially for older adults.

  3. Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study.

    Science.gov (United States)

    Hallas, Jesper; Bjerrum, Lars; Støvring, Henrik; Andersen, Morten

    2008-10-15

    Ephedrine and herbal ephedra preparations have been shown to induce a small-to-moderate weight loss. Owing to reports on serious cardiovascular events, they were banned from the US market in 2004. There have been no large controlled studies on the possible association between prescribed ephedrine/caffeine and cardiovascular events in general. The authors linked data from four different sources within Statistics Denmark, using data on 257,364 users of prescribed ephedrine/caffeine for the period 1995-2002. The data were analyzed using a case-crossover technique with a composite endpoint: death outside of a hospital, myocardial infarction, or stroke. To account for effects of chronic exposure and effects in naïve users, the authors performed a secondary case-control study nested within the cohort of ephedrine/caffeine ever users. Among 2,316 case subjects, 282 (12.2%) were current users of ephedrine/caffeine. The case-crossover analysis yielded an odds ratio of 0.84 (95% confidence interval: 0.71, 1.00); after adjustment for trends in ephedrine/caffeine use, it was 0.95 (95% confidence interval: 0.79, 1.16). Subgroup analyses revealed no strata with significantly elevated risk. In the case-control substudy, there was no increased risk among naïve users or users with large cumulative doses. Prescribed ephedrine/caffeine was not associated with a substantially increased risk of adverse cardiovascular outcomes in this study.

  4. Cocaine-induced cardiovascular effects: lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide.

    Science.gov (United States)

    Dickerson, L W; Rodak, D J; Kuhn, F E; Wahlstrom, S K; Tessel, R E; Visner, M S; Schaer, G L; Gillis, R A

    1999-01-01

    It has been suggested that cocaine acts directly in the brain to enhance central sympathetic outflow. However, some studies suggested that the cardiovascular effects of cocaine are related to a peripheral action. To characterize further the site of cocaine's cardiovascular effect, we compared the hemodynamic effects of cocaine (2 mg/kg, i.v. bolus) with those observed after administration of an equimolar dose (2.62 mg/kg, i.v. bolus) of cocaine methiodide, a quaternary derivative of cocaine that does not penetrate the blood-brain barrier, by using sufentanil-sedated dogs. Cocaine produced significant (p < 0.05) increases in heart rate (+37+/-11 beats/min), mean arterial pressure (+55+/-11 mm Hg), left ventricular end-diastolic pressure (+5.3+/-1.0 mm Hg), and cardiac output (+2.4+/-0.9 L/min). Cocaine methiodide produced increases in heart rate (+57+/-11 beats/min), mean arterial pressure (+45+/-11 mm Hg), left ventricular end-diastolic pressure (+3.4+/-1.0 mm Hg), and cardiac output (1.1+/-0.9 L/min), which were not significantly different from those observed with cocaine. Because opiate sedation potentially might have attenuated central sympathetic outflow, we further confirmed the qualitative similarity of the actions of cocaine and cocaine methiodide on heart rate and blood pressure in unsedated, conscious dogs. Our data suggest that the cardiovascular effects of cocaine result primarily from a peripheral site of action.

  5. 30. Cardiovascular risk factors burden in Saudi Arabia: The africa middle east cardiovascular epidemiological (ace study

    Directory of Open Access Journals (Sweden)

    A. Ahmed

    2016-07-01

    Full Text Available Limited data exit on the epidemiology of cardiovascular risk factors in Saudi Arabia particularly in relation to the differences between local citizens and expatriates. The aim of this analysis is to describe the current prevalence of cardiovascular risk factors among patients attending general practice clinics in Saudi Arabia. In a cross- sectional epidemiological study, the presence of cardiovascular risk factors (hypertension, diabetes, dyslipidaemia, obesity, smoking, and abdominal obesity was evaluated in stable adult outpatients attending primary care clinics in Saudi Arabia. Groups comparison were made between local Saudi patients and expatriates. A total of 550 participant were enrolled form different clinics in Saudi Arabia (71% were male, mean age was 43 ± 10 years. Nearly half of the study cohort had more than two cardiovascular risk factors (49.6%. Dyslipidemia had the highest prevalence (68.4%. Furthermore, prevalence of hypertension (47.5% vs. 31.4%, dyslipidaemia (75.2% vs. 55.1% and abdominal obesity (63.9% vs. 52.2% were higher among expatriates compare to Saudis (p-value < 0.001. This analysis clearly shows that there is a high prevalence of cardiovascular risk factors prevalence in Saudi population. In addition, a significant proportion of patients with risk factors have poor overall control. Programmed community based screening is needed for all cardiovascular risk factors in Saudi Arabia. Increased awareness and improved primary care services may decrease incidence of coronary artery disease and improve overall quality of life.

  6. Personalized medicine in cardiovascular diseases.

    Science.gov (United States)

    Lee, Moo-Sik; Flammer, Andreas J; Lerman, Lilach O; Lerman, Amir

    2012-09-01

    Personalized medicine is a novel medical model with all decisions and practices being tailored to individual patients in whatever ways possible. In the era of genomics, personalized medicine combines the genetic information for additional benefit in preventive and therapeutic strategies. Personalized medicine may allow the physician to provide a better therapy for patients in terms of efficiency, safety and treatment length to reduce the associated costs. There was a remarkable growth in scientific publication on personalized medicine within the past few years in the cardiovascular field. However, so far, only very few cardiologists in the USA are incorporating personalized medicine into clinical treatment. We review the concepts, strengths, limitations and challenges of personalized medicine with a particular focus on cardiovascular diseases (CVDs). There are many challenges from both scientific and policy perspectives to personalized medicine, which can overcome them by comprehensive concept and understanding, clinical application, and evidence based practices. Individualized medicine serves a pivotal role in the evolution of national and global healthcare reform, especially, in the CVDs fields. Ultimately, personalized medicine will affect the entire landscape of health care system in the near future.

  7. 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.

  8. Mammalian Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

    Science.gov (United States)

    Anderson, Gregory Arthur

    Cardiovascular development is a process that involves the timing of multiple molecular events, and numerous subtle three-dimensional conformational changes. Traditional developmental biology techniques have provided large quantities of information as to how these complex organ systems develop. However, the major drawback of the majority of current developmental biological imaging is that they are two-dimensional in nature. It is now well recognized that circulation of blood is required for normal patterning and remodeling of blood vessels. Normal blood vessel formation is dependent upon a complex network of signaling pathways, and genetic mutations in these pathways leads to impaired vascular development, heart failure, and lethality. As such, it is not surprising that mutant mice with aberrant cardiovascular patterning are so common, since normal development requires proper coordination between three systems: the heart, the blood, and the vasculature. This thesis describes the implementation of a three-dimensional imaging technique, optical projection tomography (OPT), in conjunction with a computer-based registration algorithm to statistically analyze developmental differences in groups of wild-type mouse embryos. Embryos that differ by only a few hours' gestational time are shown to have developmental differences in blood vessel formation and heart development progression that can be discerned. This thesis describes how we analyzed mouse models of cardiovascular perturbation by OPT to detect morphological differences in embryonic development in both qualitative and quantitative ways. Both a blood vessel specific mutation and a cardiac specific mutation were analyzed, providing evidence that developmental defects of these types can be quantified. Finally, we describe the implementation of OPT imaging to identify statistically significant phenotypes from three different mouse models of cardiovascular perturbation across a range of developmental time points. Image

  9. The effect of different cardiovascular risk presentation formats on intentions, understanding and emotional affect: a randomised controlled trial using a web-based risk formatter (protocol

    Directory of Open Access Journals (Sweden)

    Newcombe Robert

    2010-07-01

    Full Text Available Abstract Background The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect. Methods/design A randomised controlled trial comprising four arms, with a between subjects design will be performed. There will be two intervention groups and two control groups. The first control comprises a pre-intervention questionnaire and presents risk in a bar graph format. The second control presents risk in a bar graph format without pre-intervention questionnaire. These two control groups are to account for the potential Hawthorne effect of thinking about cardiovascular risk before viewing actual risk. The two intervention groups comprise presenting risk in either a pictogram or metonym format (image depicting seriousness of having a myocardial infarction. 800 individuals' aged between 45 and 64 years, who have not been previously diagnosed with heart disease and have access to a computer with internet, will be given a link to a website comprising a risk calculator and electronic questionnaires. 10-year risk of having a coronary heart disease event will be assessed and presented in one of the three formats. A post-intervention questionnaire will be completed after viewing the risk format. Main outcome measures are (i intention to change behaviour, (ii understanding of risk information, (iii emotional affect and (iv worry about future heart disease. Secondary outcomes are the sub-components of the theory of planned behaviour: attitudes, perceived behavioural control and subjective norms. Discussion Having reviewed the literature, we are not aware of any other studies which have used the assessment of actual risk, in a trial to compare different

  10. Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype

    NARCIS (Netherlands)

    Hubert, Francois-Xavier; Kinkel, Sarah A.; Crewther, Pauline E.; Cannon, Ping Z. F.; Webster, Kylie E.; Link, Maire; Uibo, Raivo; O'Bryan, Moira K.; Meager, Anthony; Forehan, Simon P.; Smyth, Gordon K.; Mittaz, Laureane; Antonarakis, Stylianos E.; Peterson, Paert; Heath, William R.; Scott, Hamish S.

    2009-01-01

    Autoimmune regulator (AIRE) is an important transcription regulator that mediates a role in central tolerance via promoting the "promiscuous" expression of tissue-specific Ags in the thymus. Although several mouse models of Aire deficiency have been described, none has analyzed the phenotype induced

  11. PhenoBlocks: Phenotype Comparison Visualizations.

    Science.gov (United States)

    Glueck, Michael; Hamilton, Peter; Chevalier, Fanny; Breslav, Simon; Khan, Azam; Wigdor, Daniel; Brudno, Michael

    2016-01-01

    The differential diagnosis of hereditary disorders is a challenging task for clinicians due to the heterogeneity of phenotypes that can be observed in patients. Existing clinical tools are often text-based and do not emphasize consistency, completeness, or granularity of phenotype reporting. This can impede clinical diagnosis and limit their utility to genetics researchers. Herein, we present PhenoBlocks, a novel visual analytics tool that supports the comparison of phenotypes between patients, or between a patient and the hallmark features of a disorder. An informal evaluation of PhenoBlocks with expert clinicians suggested that the visualization effectively guides the process of differential diagnosis and could reinforce the importance of complete, granular phenotypic reporting.

  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 physiology and sleep.

    Science.gov (United States)

    Murali, Narayana S; Svatikova, Anna; Somers, Virend K

    2003-05-01

    Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the

  14. Osteoporosis y enfermedad cardiovascular

    OpenAIRE

    Sarahí Mendoza; Miriam Noa; Rosa Más

    2007-01-01

    Las enfermedades cardiovasculares (ECV) y la osteoporosis son causas frecuentes de morbilidad en la población adulta, cuya frecuencia aumenta con la edad, por lo que al aumentar la expectativa de vida, constituyen importantes problemas de salud. El riesgo a padecer ambas patologías depende de factores de riesgo, y la prevención consiste en controlar los modificables. Las ECV y la osteoporosis presentan factores etiológicos comunes que involucran la biosíntesis del colesterol y la oxidación li...

  15. Postnatal Cardiovascular Adaptation

    Directory of Open Access Journals (Sweden)

    Ferda Ozlu

    2016-06-01

    Full Text Available Fetus depends on placental circulation in utero. A successful transition from intrauterin to extrauterine life depends on succesful physiological changes during labor. During delivery, fetus transfers from a liquid environment where oxygen comes via umbilical vein to air environement where oxygenation is supported via air breathing. Endocrinological changes are important for fetus to adapt to extrauterine life. In addition to these, cord clemping plays a crucial role in postnatal adaptation. Establishment of neonatal postnatal life and succesful overcome, the fetal cardiovascular transition period are important to stay on. [Archives Medical Review Journal 2016; 25(2.000: 181-190

  16. Cardiovascular hypertensive emergencies.

    Science.gov (United States)

    Papadopoulos, D P; Sanidas, E A; Viniou, N A; Gennimata, V; Chantziara, V; Barbetseas, I; Makris, T K

    2015-02-01

    Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

  17. Fetal cardiovascular physiology.

    Science.gov (United States)

    Rychik, J

    2004-01-01

    The cardiovascular system of the fetus is physiologically different than the adult, mature system. Unique characteristics of the myocardium and specific channels of blood flow differentitate the physiology of the fetus from the newborn. Conditions of increased preload and afterload in the fetus, such as sacrococcygeal teratoma and twin-twin transfusion syndrome, result in unique and complex pathophysiological states. Echocardiography has improved our understanding of human fetal cadiovasvular physiology in the normal and diseased states, and has expanded our capability to more effectively treat these disease processes.

  18. Antioxidantes y enfermedad cardiovascular

    OpenAIRE

    Vázquez, Clotilde

    2004-01-01

    La enfermedad cardiovascular se mantiene como la más importante causa de morbi y mortalidad en la mayoría de los países desarrollados, siendo cada vez más frecuente en los países en vías de desarrollo. La orteroesclerosis es un enfermedad crónica de las arterias de mediano y gran calibre, caracterizadas por el endurecimiento y pérdida de elasticidad de su pared, que se acompaña de estrechamiento de su luz. En general, la lesión arteriosclerótica se desarrolla en tres fases: a) inici...

  19. A Speedy Cardiovascular Diseases Classifier Using Multiple Criteria Decision Analysis

    Directory of Open Access Journals (Sweden)

    Wah Ching Lee

    2015-01-01

    Full Text Available Each year, some 30 percent of global deaths are caused by cardiovascular diseases. This figure is worsening due to both the increasing elderly population and severe shortages of medical personnel. The development of a cardiovascular diseases classifier (CDC for auto-diagnosis will help address solve the problem. Former CDCs did not achieve quick evaluation of cardiovascular diseases. In this letter, a new CDC to achieve speedy detection is investigated. This investigation incorporates the analytic hierarchy process (AHP-based multiple criteria decision analysis (MCDA to develop feature vectors using a Support Vector Machine. The MCDA facilitates the efficient assignment of appropriate weightings to potential patients, thus scaling down the number of features. Since the new CDC will only adopt the most meaningful features for discrimination between healthy persons versus cardiovascular disease patients, a speedy detection of cardiovascular diseases has been successfully implemented.

  20. Pharmacogenetics of cardiovascular drug therapy

    OpenAIRE

    Peters, Bas J.M.; Olaf H Klungel; de Boer, Anthonius; Ch Stricker, Bruno H; Maitland-van der Zee, Anke-Hilse

    2009-01-01

    In developed countries cardiovascular disease is one of the leading causes of death. Cardiovascular drugs such as platelet aggregation inhibitors, oral anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly prescribed to reduce risk of cardiovascular disease. Notable interindividual variation exists in the response to these pharmacotherapeutic interventions, which can be partially explained by factors such as gender, age, diet, concomitant drug use and environmental f...

  1. Understanding changes in cardiovascular pathophysiology.

    Science.gov (United States)

    Chummun, Harry

    Cardiovascular pathophysiological changes, such as hypertension and enlarged ventricles, reflect the altered functions of the heart and its circulation during ill-health. This article examines the normal and altered anatomy of the cardiac valves, the contractile elements and enzymes of the myocardium, the significance of the different factors associated with cardiac output, and the role of the autonomic nervous system in the heart beat. It also explores how certain diseases alter these functions and result in cardiac symptoms. Nurses can benefit from knowledge of these specific changes, for example, by being able to ask relevant questions in order to ascertain the nature of a patients condition, by being able to take an effective patient history and by being able to read diagnostic results, such as electrocardiograms and cardiac enzyme results. All this will help nurses to promote sound cardiac care based on a physiological rationale.

  2. Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gábor Csányi

    2014-04-01

    Full Text Available In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine.

  3. Cardiovascular benefits of exercise

    Directory of Open Access Journals (Sweden)

    Agarwal SK

    2012-06-01

    Full Text Available Shashi K AgarwalMedical Director, Agarwal Health Center, NJ, USAAbstract: Regular physical activity during leisure time has been shown to be associated with better health outcomes. The American Heart Association, the Centers for Disease Control and Prevention and the American College of Sports Medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases. The therapeutic role of exercise in maintaining good health and treating diseases is not new. The benefits of physical activity date back to Susruta, a 600 BC physician in India, who prescribed exercise to patients. Hippocrates (460–377 BC wrote “in order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one's strength and staying healthy, and the best way to do so is through physical exercise.” Plato (427–347 BC referred to medicine as a sister art to physical exercise while the noted ancient Greek physician Galen (129–217 AD penned several essays on aerobic fitness and strengthening muscles. This article briefly reviews the beneficial effects of physical activity on cardiovascular diseases.Keywords: exercise, cardiovascular disease, lifestyle changes, physical activity, good health

  4. Resveratrol and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Dominique Bonnefont-Rousselot

    2016-05-01

    Full Text Available The increased incidence of cardiovascular diseases (CVDs has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES, a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS. RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH, an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA. Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…; however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure should compare the results of preclinical studies with those of clinical trials.

  5. Cardiovascular Complications of Pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Carolina Gongora

    2015-10-01

    Full Text Available Pregnancy causes significant metabolic and hemodynamic changes in a woman’s physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia, gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  6. Cardiovascular Complications of Pregnancy.

    Science.gov (United States)

    Gongora, Maria Carolina; Wenger, Nanette K

    2015-10-09

    Pregnancy causes significant metabolic and hemodynamic changes in a woman's physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  7. [Comparison of treatment principles of elderly hypertensive patients with different cardiovascular risks based on Hungarian and international guidelines (2001-2015)].

    Science.gov (United States)

    Bödör, Anikó; Kiss, István

    2016-02-14

    The aim of this review is to present recommendations of the currently valid Hungarian practice guidelines regarding antihypertensive therapy of the elderly and very elderly with different cardiovascular risk profiles, compare and contrast these with international guidelines, describe changes brought about by the past 15 years, and review the evidence behind. Hypertension treatment guidelines and relevant statements of the Hungarian and European Societies of Hypertension, of the Joint National Committee and American Heart Association were processed. The use of age-independent treatment threshold, goal blood pressure values, and the tendency towards more intensive control in co-morbidities conferring high cardiovascular risk were overcome by the upsurge of new evidence and the re-evaluation of previous clinical trial data. These lead to the introduction of age-specific and generally less stringent blood pressure targets in all regions compared. However, the guidelines currently in force still differ in terms of the attainable values in concomitant diabetes, chronic kidney disease or albuminuria, use of beta-blockers and the definition of elderly. Nevertheless, there is unanimous agreement that benefit from lowering of blood pressure under systolic 140 mmHg is not supported by evidence and further investigation is warranted to determine optimal treatment targets in the elderly, in the aged over 80 and specific elderly risk groups.

  8. The Genetics of Phenotypic Plasticity. XIV. Coevolution.

    Science.gov (United States)

    Scheiner, Samuel M; Gomulkiewicz, Richard; Holt, Robert D

    2015-05-01

    Plastic changes in organisms' phenotypes can result from either abiotic or biotic effectors. Biotic effectors create the potential for a coevolutionary dynamic. Through the use of individual-based simulations, we examined the coevolutionary dynamic of two species that are phenotypically plastic. We explored two modes of biotic and abiotic interactions: ecological interactions that determine the form of natural selection and developmental interactions that determine phenotypes. Overall, coevolution had a larger effect on the evolution of phenotypic plasticity than plasticity had on the outcome of coevolution. Effects on the evolution of plasticity were greater when the fitness-maximizing coevolutionary outcomes were antagonistic between the species pair (predator-prey interactions) than when those outcomes were augmenting (competitive or mutualistic). Overall, evolution in the context of biotic interactions reduced selection for plasticity even when trait development was responding to just the abiotic environment. Thus, the evolution of phenotypic plasticity must always be interpreted in the full context of a species' ecology. Our results show how the merging of two theory domains--coevolution and phenotypic plasticity--can deepen our understanding of both and point to new empirical research.

  9. The Phenotype of Spontaneous Preterm Birth: Application of a Clinical Phenotyping Tool

    Science.gov (United States)

    Manuck, Tracy A.; Esplin, M. Sean; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Varner, Michael W.; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

    2015-01-01

    Objective Spontaneous preterm birth (SPTB) is a complex condition that is likely a final common pathway with multiple possible etiologies. We hypothesized that a comprehensive classification system could appropriately group women with similar STPB etiologies, and provide an explanation, at least in part, for the disparities in SPTB associated with race and gestational age at delivery. Study Design Planned analysis of a multicenter, prospective study of singleton SPTB. Women with SPTB < 34 weeks were included. We defined 9 potential SPTB phenotypes based on clinical data, including infection/inflammation, maternal stress, decidual hemorrhage, uterine distention, cervical insufficiency, placental dysfunction, premature rupture of the membranes, maternal comorbidities, and familial factors. Each woman was evaluated for each phenotype. Delivery gestational age was compared between those with and without each phenotype. Phenotype profiles were also compared between women with very early (20.0–27.9 weeks) SPTB vs. those with early SPTB (28.0–34.0 weeks), and between African-American and Caucasian women. Statistical analysis was by t-test and chi-square as appropriate. Results The phenotyping tool was applied to 1025 women with SPTB who delivered at a mean 30.0 (+/− 3.2) weeks gestation. Of these, 800 (78%) had ≥2 phenotypes. Only 43 (4.2%) had no phenotypes. The 281 women with early SPTB were more likely to have infection/inflammation, decidual hemorrhage, and cervical insufficiency phenotypes (all p≤0.001). African-American women had more maternal stress and cervical insufficiency but less decidual hemorrhage and placental dysfunction compared to Caucasian women (all p<0.05). Gestational age at delivery decreased as the number of phenotypes present increased. Conclusions Precise SPTB phenotyping classifies women with SPTB and identifies specific differences between very early and early SPTB and between African-Americans and Caucasians. PMID:25687564

  10. Artificial neural interfaces for bionic cardiovascular treatments.

    Science.gov (United States)

    Kawada, Toru; Sugimachi, Masaru

    2009-01-01

    An artificial nerve, in the broad sense, may be conceptualized as a physical and logical interface system that reestablishes the information traffic between the central nervous system and peripheral organs. Studies on artificial nerves targeting the autonomic nervous system are in progress to explore new treatment strategies for several cardiovascular diseases. In this article, we will review our research targeting the autonomic nervous system to treat cardiovascular diseases. First, we identified the rule for decoding native sympathetic nerve activity into a heart rate using transfer function analysis, and established a framework for a neurally regulated cardiac pacemaker. Second, we designed a bionic baroreflex system to restore the baroreflex buffering function using electrical stimulation of the celiac ganglion in a rat model of orthostatic hypotension. Third, based on the hypothesis that autonomic imbalance aggravates chronic heart failure, we implanted a neural interface into the right vagal nerve and demonstrated that intermittent vagal stimulation significantly improved the survival rate in rats with chronic heart failure following myocardial infarction. Although several practical problems need to be resolved, such as those relating to the development of electrodes feasible for long-term nerve activity recording, studies of artificial neural interfaces with the autonomic nervous system have great possibilities in the field of cardiovascular treatment. We expect further development of artificial neural interfaces as novel strategies to cope with cardiovascular diseases resistant to conventional therapeutics.

  11. Prevalence of cardiovascular disease and risk factors in a rural district of Beijing, China: a population-based survey of 58,308 residents

    Directory of Open Access Journals (Sweden)

    He Liu

    2012-01-01

    Full Text Available Abstract Background Cardiovascular disease (CVD is the leading cause of global disease burden. Although stroke was thought to be more prevalent than coronary heart disease (CHD in Chinese, the epidemic pattern might have been changed in some rural areas nowadays. This study was to estimate up-to-date prevalence of CVD and its risk factors in rural communities of Fangshan District, Beijing, China. Methods A cross-sectional population survey was carried out by stratified cluster sampling. A total of 58,308 rural residents aged over 40 years were surveyed by face-to-face interview and physical examination during 2008 and 2010. The standardized prevalence was calculated according to adult sample data of China's 5th Population Census in 2000, and the adjusted prevalence odds ratio (POR was calculated for the association of CHD/stroke with its cardiovascular risk factors in multivariate logistic regression models. Results Age- and sex-standardized prevalence was 5.6% for CHD (5.2% in males and 5.9% in females, higher than the counterpart of 3.7% (4.7% in males and 2.6% in females for stroke. Compared with previous studies, higher prevalence of 7.7%, 47.2%, 53.3% in males and 8.2%, 44.8%, 60.7% in females for diabetes, hypertension and overweight/obesity were presented accordingly. Moreover, adjusted POR (95% confidence interval of diabetes, obesity, stage 1 and stage 2 hypertension for CHD as 2.51 (2.29 to 2.75, 1.53 (1.38 to 1.70, 1.13 (1.02 to 1.26 and 1.35 (1.20 to 1.52, and for stroke as 2.24 (1.98 to 2.52, 1.25 (1.09 to 1.44, 1.44 (1.25 to 1.66 and 1.70 (1.46 to 1.98 were shown respectively in the multivariate logistic regression models. Conclusions High prevalence of CVD and probably changed epidemic pattern in rural communities of Beijing, together with the prevalent cardiovascular risk factors and population aging, might cause public health challenges in rural Chinese population.

  12. Cheese and cardiovascular disease risk

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Tholstrup, Tine

    2016-01-01

    Abstract Currently, the effect of dairy products on cardiovascular risk is a topic with much debate and conflicting results. The purpose of this review is to give an overview of the existing literature regarding the effect of cheese intake and risk of cardiovascular disease (CVD). Studies included...

  13. 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.

  14. Arterial hypertension and cardiovascular risk in HIV-infected patients.

    Science.gov (United States)

    Calò, Lorenzo A; Caielli, Paola; Maiolino, Giuseppe; Rossi, Gianpaolo

    2013-08-01

    The dramatic change of the natural history of HIV-infected patients by highly active antiretroviral therapy (HAART) has exposed these patients to cardiovascular risk, including cardiovascular disease and hypertension. In HIV-infected patients, the development of arterial hypertension, at least in the medium-long term is an established feature, although recognized predictors of its development have not been clearly identified. In addition, conflicting data regarding the influence of antiretroviral therapy (ART) are reported. The presence of a proinflammatory state and oxidative stress-mediated endothelial dysfunction seem, however, to play a pathophysiologic role. In this review, we examine and provide a comprehensive, literature based, consideration of the pathophysiologic aspects of hypertension in these patients. HIV-infected patients, independently of the presence of hypertension, remain at very high cardiovascular risk due to the presence of the same cardiovascular risk factors recognized for the general population with, in addition, the indirect influence of the ART, essentially via its effect on lipid metabolism. This review based on the evidence from the literature, concludes that the management of HIV-infected patients in terms of cardiovascular prevention emerges as a priority. The consideration of cardiovascular risk in these patients should receive the same emphasis given for the general population at high cardiovascular risk, including adequate blood pressure control according to international guidelines.

  15. Indian poverty and cardiovascular disease.

    Science.gov (United States)

    Ramaraj, Radhakrishnan; Alpert, Joseph Stephen

    2008-07-01

    Cardiovascular disease is among the world's leading causes of death, and nearly 80% of deaths occur in developing countries. Cardiovascular disease is becoming a major health problem in India, where life expectancy has increased with decreases in infectious disease and childhood mortality. It is well established that this population experiences coronary artery disease at a younger age than other populations. With infectious diseases still endemic, noncommunicable diseases are a lower priority for the governments of developing countries. There is a clear progression to degenerative and lifestyle-related diseases such as cardiovascular disease as a result of current social and economic change. The lack of a public response to the increasing risk for cardiovascular disease thus far is due mostly to a perception among policy makers and the public that cardiovascular disease is largely a problem of the urban rich. In conclusion, this review addresses the imminent threats and ways to tackle the epidemic in India.

  16. Assessment of cardiovascular risk.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2010-10-01

    Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

  17. Cardiovascular complications in acromegaly.

    Science.gov (United States)

    Vitale, G; Pivonello, R; Lombardi, G; Colao, A

    2004-09-01

    Cardiovascular morbidity and mortality are increas