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Sample records for cardiovascular phenotypes based

  1. Metabolic and Cardiovascular Implications of a Metabolically Healthy Obesity Phenotype

    PubMed Central

    Seo, Mi Hae

    2014-01-01

    Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases. PMID:25559571

  2. Identification of Loci Modulating the Cardiovascular and Skeletal Phenotypes of Marfan Syndrome in Mice

    PubMed Central

    Fernandes, Gustavo R.; Massironi, Silvia M. G.; Pereira, Lygia V.

    2016-01-01

    Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue, affecting mostly the skeletal, ocular and cardiovascular systems, caused by mutations in the FBN1 gene. The existence of modifier genes has been postulated based on the wide clinical variability of manifestations in patients, even among those with the same FBN1 mutation. Although isogenic mouse models of the disease were fundamental in dissecting the molecular mechanism of pathogenesis, they do not address the effect of genetic background on the disease phenotype. Here, we use a new mouse model, mgΔloxPneo, which presents different phenotype severity dependent on the genetic backgrounds, to identify genes involved in modulating MFS phenotype. F2 heterozygotes showed wide phenotypic variability, with no correlations between phenotypic severities of the different affected systems, indicating that each has its specific set of modifier genes. Individual analysis of the phenotypes, with SNP microarrays, identified two suggestive QTL each to the cardiovascular and skeletal, and one significant QTL to the skeletal phenotype. Epistatic interactions between the QTL account for 47.4% and 53.5% of variation in the skeletal and cardiovascular phenotypes, respectively. This is the first study that maps modifier loci for MFS, showing the complex genetic architecture underlying the disease. PMID:26927851

  3. Pharmacogenomics and cardiovascular drugs: need for integrated biological system with phenotypes and proteomic markers.

    PubMed

    Siest, Gérard; Marteau, Jean-Brice; Maumus, Sandy; Berrahmoune, Hind; Jeannesson, Elise; Samara, Anastasia; Batt, Anne-Marie; Visvikis-Siest, Sophie

    2005-12-19

    Personalized medicine is based on a better knowledge of biological variability, considering the important part due to genetics. When trying to identify involved genes and their products in differential cardiovascular drug responses, a five-step strategy is to be followed: 1) Pharmacokinetic-related genes and phenotypes (2) Pharmacodynamic targets, genes and products (3) Cardiovascular diseases and risks depending on specific or large metabolic cycles (4) Physiological variations of previously identified genes and proteins (5) Environment influences on them. After summarizing the most well-known genes involved in drug metabolism, we will take as example of drugs, the statins, considered as very important drugs from a Public-Health standpoint, but also for economical reasons. These drugs respond differently in human depending on multiple polymorphisms. We will give examples with common ApoE polymorphisms influencing the hypolipemic effects of statins. These drugs also have pleiotropic effects and decrease inflammatory markers. This illustrates the need to separate clinical diseases phenotypes in specific metabolic pathways, which could propose other classifications, of diseases and related genes. Hypertension is also a good example of clinical phenotype which should be followed after various therapeutic approaches by genes polymorphisms and proteins markers. Gene products are under clear environmental expression variations such as age, body mass index and obesity, alcohol, tobacco and dietary interventions which are the first therapeutical actions taken in cardiovascular diseases. But at each of the five steps, within a pharmacoproteomic strategy, we also need to use available information from peptides, proteins and metabolites, which usually are the gene products. A profiling approach, i.e., dealing with genomics, but now also with proteomics, is to be used. In conclusion, the profiling, as well as the large amount of data, will more than before render necessary an

  4. GENETIC VARIATION IN THE β2-ADRENERGIC RECEPTOR: IMPACT ON INTERMEDIATE CARDIOVASCULAR PHENOTYPES

    PubMed Central

    Hesse, C.; Eisenach, J.H.

    2009-01-01

    Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient. PMID:19727431

  5. Integromic Analysis of Genetic Variation and Gene Expression Identifies Networks for Cardiovascular Disease Phenotypes

    PubMed Central

    Yao, Chen; Chen, Brian H.; Joehanes, Roby; Otlu, Burcak; Zhang, Xiaoling; Liu, Chunyu; Huan, Tianxiao; Tastan, Oznur; Cupples, L. Adrienne; Meigs, James B.; Fox, Caroline S.; Freedman, Jane E.; Courchesne, Paul; O’Donnell, Christopher J.; Munson, Peter J.; Keles, Sunduz; Levy, Daniel

    2015-01-01

    Background Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. Methods and Results We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10−8) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes. Conclusions Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD. PMID:25533967

  6. Treating mixed hyperlipidemia and the atherogenic lipid phenotype for prevention of cardiovascular events.

    PubMed

    Rubenfire, Melvyn; Brook, Robert D; Rosenson, Robert S

    2010-10-01

    Statins reduce cardiovascular events and cardiovascular and total mortality in persons at risk for and with coronary disease, but there remains a significant residual event rate, particularly in those with the atherogenic lipid phenotype that is characterized by a low high-density lipoprotein (HDL) cholesterol and increase in non-HDL cholesterol. Large outcome trials designed to assess the value of combining statins with other agents to target HDL cholesterol and non-HDL cholesterol will not be completed for a few years, but there is ample evidence for the clinician to consider combination therapy. The choices for therapies to supplement statins include niacin, fibrates, and omega-3 fatty acids. We present the argument that after therapeutic lifestyle changes, the first priority should be the maximally tolerated effective dose of a potent statin. Evidence supports the addition of niacin as the second agent. In some situations, high-dose omega-3 fatty acid therapy could be the first agent added to statins. Although fibrate monotherapy alone or in combination with non-statin low-density lipoprotein cholesterol-lowering agents can be effective in mixed hyperlipidemia when statins are not tolerated, the combination of statin+fibrate should be considered second-line therapy until the efficacy and safety are established. PMID:20920687

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

    PubMed

    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. Heliconia phenotypic diversity based on qualitative descriptors.

    PubMed

    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.

  9. SQL based cardiovascular ultrasound image classification.

    PubMed

    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.

  10. Cardiovascular

    NASA Video Gallery

    Overview of Cardiovascular research which addresses risks of space flight, including adaptive changes to the cephalad fluid shift (such as reduced circulating blood volume), potential for heart rhy...

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

    ClinicalTrials.gov

    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)

  12. Short-term mechanical stretch fails to differentiate human adipose-derived stem cells into cardiovascular cell phenotypes

    PubMed Central

    2014-01-01

    Background We and others have previously demonstrated that adipose-derived stem cells (ASCs) transplantation improve cardiac dysfunction post-myocardium infarction (MI) under hemodynamic stress in rats. The beneficial effects appear to be associated with pleiotropic factors due to a complex interplay between the transplanted ASCs and the microenvironment in the absence of cell transdifferentiation. In the present work, we tested the hypothesis that mechanical stretch per se could change human ASCs (hASCs) into cardiovascular cell phenotypes that might influence post-MI outcomes. Methods Human ASCs were obtained from patients undergoing liposuction procedures. These cells were stretched 12%, 1Hz up to 96 hours by using Flexercell 4000 system. Protein and gene expression were evaluated to identify cardiovascular cell markers. Culture medium was analyzed to determine cell releasing factors, and contraction potential was also evaluated. Results Mechanical stretch, which is associated with extracellular signal-regulated kinase (ERK) phosphorylation, failed to induce the expression of cardiovascular cell markers in human ASCs, and mesenchymal cell surface markers (CD29; CD90) remained unchanged. hASCs and smooth muscle cells (SMCs) displayed comparable contraction ability. In addition, these cells demonstrated a profound ability to secrete an array of cytokines. These two properties of human ASCs were not influenced by mechanical stretch. Conclusions Altogether, our findings demonstrate that hASCs secrete an array of cytokines and display contraction ability even in the absence of induction of cardiovascular cell markers or the loss of mesenchymal surface markers when exposed to mechanical stretch. These properties may contribute to beneficial post-MI cardiovascular outcomes and deserve to be further explored under the controlled influence of other microenvironment components associated with myocardial infarction, such as tissue hypoxia. PMID:24885410

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ED 06-3 BLOOD PRESSURE PHENOTYPE ASSOCIATED WITH CARDIOVASCULAR RISK IN YOUNG ADULTS.

    PubMed

    Yano, Yuichiro

    2016-09-01

    Younger adults (ages ≤50 years) are increasingly prone to stroke, chronic kidney disease (CKD), and worsening cardiovascular disease (CVD) mortality in the US. An alarming increase in prevalence of high blood pressure (BP) related to the obesity epidemic appears to underlie these adverse trends. However, what specific BP characteristics measured in young adulthood optimally predict incident CVD and CKD later in life remains to be determined. Therefore, an optimization of diagnostic and therapeutic strategies in BP management for young adults is challenging but essential. In my lecture, I will fill the gap, using results from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  16. 24-hour central blood pressure and intermediate cardiovascular phenotypes in untreated subjects

    PubMed Central

    Bednarek, Agnieszka; Jankowski, Piotr; Olszanecka, Agnieszka; Windak, Adam; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2014-01-01

    Background: Recently, 24-hour monitoring of central systolic blood pressure (SBP) has become available. However, the relation between end-organ damage and the 24-hour central SBP profile and variability has not so far been analyzed. Therefore, the aim of this cross-sectional study was to evaluate the relation between 24-hour central SBP, 24-hour central SBP profile as well as central SBP short-term variability and parameters of cardiac and vascular intermediate phenotypes. Methods: The study group consisted of 50 patients with newly diagnosed, untreated hypertension (age 40.4 ± 11.5 years, 35 men) and 50 normotensive subjects (age 38.3 ± 12.0 years, 35 men). Applanation tonometry of the radial artery and the “n-point forward moving average” method were used to determine 24-hour central SBP. Each study participant underwent echocardiography and carotid ultrasonography. Results: 24-hour, daytime, and nighttime central SBP was related to left ventricle end-diastole diameter (p < 0.05), left ventricular mass index (p < 0.001), relative wall thickness (p < 0.05), E/E’ ratio (p < 0.01), and left atrium volume (p < 0.01). The nocturnal central SBP fall was not related to any of the mentioned parameters, whereas parameters of short-term variability were related to IMT in hypertensives only (p < 0.05). Conclusions: The present study showed that 24-hour central SBP is related to intermediate cardiac phenotypes as assessed by echocardiography whereas short-term central SBP variability is mainly related to vascular phenotype as determined by IMT. PMID:25628959

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

    PubMed

    Breton, Carrie V; Mack, Wendy J; Yao, Jin; Berhane, Kiros; Amadeus, Milena; Lurmann, Fred; Gilliland, Frank; McConnell, Rob; Hodis, Howard N; Künzli, Nino; Avol, Ed

    2016-01-01

    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.

  18. Agreement in cardiovascular risk rating based on anthropometric parameters

    PubMed Central

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

    2015-01-01

    Objective To investigate the agreement in evaluation of risk of developing cardiovascular diseases based on anthropometric parameters in young adults. Methods 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 (χ2) test was used to assess associations between categorical variables (p<0.05). Results 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. Conclusion 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. PMID:26466060

  19. Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat

    PubMed Central

    Morrissey, Catherine; Grieve, Ian C.; Heinig, Matthias; Atanur, Santosh; Petretto, Enrico; Pravenec, Michal; Hubner, Norbert

    2011-01-01

    The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. Quantitative trait transcript (QTT) analysis in the RI strains showed highly significant correlation between cis-eQTL transcript abundance and clinically relevant traits such as systolic blood pressure and blood glucose, with the physical location of a subset of the cis-eQTLs colocalizing with “physiological” QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain. These findings provide a basis for the functional testing and ultimate elucidation of the molecular basis of these metabolic and cardiovascular phenotypes. PMID:21846806

  20. Concept Design of Cardiovascular Stents Based on Load Identification

    NASA Astrophysics Data System (ADS)

    Liu, Q.

    2015-04-01

    The concept design is an important design phase for the cardiovascular stents. The topology optimization methods can be applied to the concept design of the cardiovascular stents. However, the interaction analysis between the stent and artery involves material nonlinearity, geometrical nonlinearity and boundary nonlinearity. The interaction analysis is not easy to be successful if these three types of nonlinearities are considered simultaneously. Therefore, the topology optimization process may be suspended if the nonlinear interaction analysis fails. The aim of this paper is to develop a design method to obtain the concept design of cardiovascular stents based on the load identification and homogenization method. A displacement control method is proposed to identify the design load of the cardiovascular stents. The identified design load is then applied to the stent and the nonlinear interaction analysis is replaced by the linear analysis. Further, the nonlinear analysis is completely avoided in the topology optimization process. The numerical results show that the proposed design method can obtain the legible concept design of cardiovascular stents.

  1. Cardiovascular Disease Could be Contained based on Currently Available Data!

    PubMed Central

    Ofodile, Okom Nkili F.C.

    2006-01-01

    Largely due to better control of infectious diseases and significant advances in biomedical research, life expectancy worldwide has increased dramatically in the last three decades. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as arthritis, Alzheimer's, Parkinson's, cardiovascular disease, cancer, osteoporosis, benign prostatic hyperplasia, and late-onset diabetes have increased and have become serious public health problem, as well. The etiology of these disorders is still incompletely understood, therefore, neither preventive strategies nor long-term effective treatment modalities are available for these disorders. In keeping with the aforementioned, the ultimate goal in cardiovascular research is to prevent the onset of cardiovascular episodes and thereby allow successful ageing without morbidity and cognitive decline. Herein, I argue that cardiovascular episodes could be contained with relatively simple approaches. Cardiovascular disorder is characterized by cellular and molecular changes that are commonplace in age-related diseases in other organ system, such alterations include increased level of oxidative stress, perturbed energy metabolism, and “horror autotoxicus” largely brought about by the perturbation of ubiquitin -proteasome system, and excessive oxidative stress damage to the cardiac muscle cells and tissues, and cross-reactions of specific antibodies against human heat shock protein 60 with that of mycobacterial heat shock protein 65.” Horror autotoxicus”, a Latin expression, is a term coined by Paul Ehrlich at the turn of the last century to describe autoimmunity to self, or the attack of “self” by immune system, which ultimately results to autoimmune condition. Based on the currently available data, the risk of cardiovascular episodes and several other age-related disorders, including cancer, Alzheimer's disease and diabetes, is known to be influenced by the nature and

  2. Cardiovascular disease could be contained based on currently available data!

    PubMed

    Ofodile, Okom Nkili F C

    2006-01-01

    Largely due to better control of infectious diseases and significant advances in biomedical research, life expectancy worldwide has increased dramatically in the last three decades. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as arthritis, Alzheimer's, Parkinson's, cardiovascular disease, cancer, osteoporosis, benign prostatic hyperplasia, and late-onset diabetes have increased and have become serious public health problem, as well. The etiology of these disorders is still incompletely understood, therefore, neither preventive strategies nor long-term effective treatment modalities are available for these disorders. In keeping with the aforementioned, the ultimate goal in cardiovascular research is to prevent the onset of cardiovascular episodes and thereby allow successful ageing without morbidity and cognitive decline. Herein, I argue that cardiovascular episodes could be contained with relatively simple approaches. Cardiovascular disorder is characterized by cellular and molecular changes that are commonplace in age-related diseases in other organ system, such alterations include increased level of oxidative stress, perturbed energy metabolism, and "horror autotoxicus" largely brought about by the perturbation of ubiquitin -proteasome system, and excessive oxidative stress damage to the cardiac muscle cells and tissues, and cross-reactions of specific antibodies against human heat shock protein 60 with that of mycobacterial heat shock protein 65. "Horror autotoxicus", a Latin expression, is a term coined by Paul Ehrlich at the turn of the last century to describe autoimmunity to self, or the attack of "self" by immune system, which ultimately results to autoimmune condition. Based on the currently available data, the risk of cardiovascular episodes and several other age-related disorders, including cancer, Alzheimer's disease and diabetes, is known to be influenced by the nature and level of food

  3. Novel epigenetic-based therapies useful in cardiovascular medicine

    PubMed Central

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

    2016-01-01

    Epigenetic modifications include DNA methylation, histone modifications, and microRNA. 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 CpG 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 microRNA targets through pharmacological tools is still under development. Indeed, large controlled trials are required to establish whether current possible candidate antisense microRNAs could offer better therapeutic benefits in clinical practice. Here, we updated therapeutic properties, side effects, and feasibility of emerging epigenetic-based strategies in cardiovascular diseases by highlighting specific problematic issues that still affect the development of large scale novel therapeutic protocols. PMID:26981216

  4. Cardiovascular effects of weightlessness and ground-based simulation

    NASA Technical Reports Server (NTRS)

    Sandler, Harold

    1988-01-01

    A large number of animal and human flight and ground-based studies were conducted to uncover the cardiovascular effects of weightlessness. Findings indicate changes in cardiovascular function during simulations and with spaceflight that lead to compromised function on reambulation and/or return to earth. This altered state termed cardiovascular deconditioning is most clearly manifest when in an erect body state. Hemodynamic parameters inidicate the presence of excessive tachnycardia, hypotension (leading to presyncope in one-third of the subjects), decreased heart volume, decreased plasma and circulating blood volumes and loss of skeletal muscle mass, particularly in the lower limbs. No clinically harmful effects were observed to date, but in-depth follow-ups were limited, as was available physiologic information. Available data concerning the causes for the observed changes indicate significant roles for mechanisms involved with body fluid-volume regulation, altered cardiac function, and the neurohumoral control of the control of the peripheral circulation. Satisfactory measures are not found. Return to preflight state was variable and only slightly dependent on flight duration. Future progress awaits availability of flight durations longer than several weeks.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Cardiovascular Response Identification Based on Nonlinear Support Vector Regression

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Su, Steven W.; Chan, Gregory S. H.; Celler, Branko G.; Cheng, Teddy M.; Savkin, Andrey V.

    This study experimentally investigates the relationships between central cardiovascular variables and oxygen uptake based on nonlinear analysis and modeling. Ten healthy subjects were studied using cycle-ergometry exercise tests with constant workloads ranging from 25 Watt to 125 Watt. Breath by breath gas exchange, heart rate, cardiac output, stroke volume and blood pressure were measured at each stage. The modeling results proved that the nonlinear modeling method (Support Vector Regression) outperforms traditional regression method (reducing Estimation Error between 59% and 80%, reducing Testing Error between 53% and 72%) and is the ideal approach in the modeling of physiological data, especially with small training data set.

  7. Microcomputer-based monitoring of cardiovascular functions in simulated microgravity

    NASA Astrophysics Data System (ADS)

    Tahvanainen, K.; Länsimies, E.; Tikkanen, P.; Hartikainen, J.; Kärki, T.; Lyyra, T.; Mäntysaari, M.

    A microcomputer-based system for non-invasive monitoring of cardiovascular system in simulated microgravity is described. The system evaluates automatically, accurately and interactively heart beat intervals, beat-to-beat non-invasive finger arterial blood pressure (systolic, diastolic, mean and pulse pressure) using a Finapres device and beat-to-beat changes of thoracic blood volume using impedance changes. In addition, beat-to-beat evaluation of cardiac mechanical function including left ventricular ejection time, diastolic time, systolic time intervals, left ventricular ejection fraction estimate and several other contractility parameters, left ventricular volume, stroke volume and cardiac output estimates are performed with high degree of automaticity.

  8. Glycemia and cardiovascular risk: challenging evidence based medicine

    PubMed Central

    Kitsios, K; Tsapas, A; Karagianni, P

    2011-01-01

    Optimal glycemic control is well known to reduce effectively the risk of micro vascular complications both in type 1 and type 2 diabetes mellitus. However the role of glycemic control in decreasing the risk of myocardial infarction and ischemic stroke, the leading causes of death in patients with diabetes, has been so far controversial. In this review, based on data recently reported from large interventional studies, we discuss the possible causal relationship between glycemia and cardiovascular outcomes in type 1 and type 2 diabetes. Strict glycemic control right from the diagnosis of the disease may be effective in reducing long term incidence of cardiovascular (CV) disease in both T1 and T2 diabetics. Nevertheless such a strategy could be potentially harmful for T2 diabetics with long duration of sub optimal glycemic control and already established CV complications. Treatment targets in these patients should be individualized taking into account other aspects of glycemic control and diabetes complications such as hypoglycemia and autonomic neuropathy. PMID:22435015

  9. Image-based phenotyping of plant disease symptoms

    PubMed Central

    Mutka, Andrew M.; Bart, Rebecca S.

    2015-01-01

    Plant diseases cause significant reductions in agricultural productivity worldwide. Disease symptoms have deleterious effects on the growth and development of crop plants, limiting yields and making agricultural products unfit for consumption. For many plant–pathogen systems, we lack knowledge of the physiological mechanisms that link pathogen infection and the production of disease symptoms in the host. A variety of quantitative high-throughput image-based methods for phenotyping plant growth and development are currently being developed. These methods range from detailed analysis of a single plant over time to broad assessment of the crop canopy for thousands of plants in a field and employ a wide variety of imaging technologies. Application of these methods to the study of plant disease offers the ability to study quantitatively how host physiology is altered by pathogen infection. These approaches have the potential to provide insight into the physiological mechanisms underlying disease symptom development. Furthermore, imaging techniques that detect the electromagnetic spectrum outside of visible light allow us to quantify disease symptoms that are not visible by eye, increasing the range of symptoms we can observe and potentially allowing for earlier and more thorough symptom detection. In this review, we summarize current progress in plant disease phenotyping and suggest future directions that will accelerate the development of resistant crop varieties. PMID:25601871

  10. Antibody-Based Assays for Phenotyping of Extracellular Vesicles

    PubMed Central

    Pugholm, Lotte Hatting; Revenfeld, Anne Louise Schacht; Søndergaard, Evo Kristina Lindersson; Jørgensen, Malene Møller

    2015-01-01

    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. PMID:26770974

  11. Temporal abstraction-based clinical phenotyping with Eureka!

    PubMed

    Post, Andrew R; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW's web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  12. Temporal Abstraction-based Clinical Phenotyping with Eureka!

    PubMed Central

    Post, Andrew R.; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M.; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H.

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW’s web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  13. Temporal abstraction-based clinical phenotyping with Eureka!

    PubMed

    Post, Andrew R; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW's web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption.

  14. Iron and iron-based alloys for temporary cardiovascular applications.

    PubMed

    Francis, A; Yang, Y; Virtanen, S; Boccaccini, A R

    2015-03-01

    In the last decade, biodegradable metals have emerged as a topic of interest for particular biomedical applications which require high strength to bulk ratio, including for cardiovascular stents. The advantages of biodegradable materials are related to the reduction of long term risks associated with the presence of permanent metal implants, e.g. chronic inflammation and in-stent restenosis. From a structural point of view, the analysis of the literature reveals that iron-based alloys used as temporary biodegradable stents have several advantages over Mg-based alloys in terms of ductility and strength. Efforts on the modification and tunability of iron-based alloys design and compositions have been mainly focused on controlling the degradation rate while retaining the mechanical integrity within a reasonable period. The early pre-clinical results of many iron-based alloys seem promising for future implants developments. This review discusses the available literature focusing mainly on: (i) Fe and Fe-based alloys design and fabrication techniques; (ii) in vitro and in vivo performance; (iii) cytotoxicity and cell viability tests.

  15. On-time clinical phenotype prediction based on narrative reports

    PubMed Central

    Bejan, Cosmin A.; Vanderwende, Lucy; Evans, Heather L.; Wurfel, Mark M.; Yetisgen-Yildiz, Meliha

    2013-01-01

    In this paper we describe a natural language processing system which is able to predict whether or not a patient exhibits a specific phenotype using the information extracted from the narrative reports associated with the patient. Furthermore, the phenotypic annotations from our report dataset were performed at the report level which allows us to perform the prediction of the clinical phenotype at any point in time during the patient hospitalization period. Our experiments indicate that an important factor in achieving better results for this problem is to determine how much information to extract from the patient reports in the time interval between the patient admission time and the current prediction time. PMID:24551325

  16. A training program in cardiovascular cell-based therapy: from the NHLBI Cardiovascular Cell Therapy Research Network.

    PubMed

    Petersen, John W; Winchester, David E; Park, Ki; Szady, Anita D; Della Rocca, Domenico G; Ahmed, Mustafa; Tassin, Hillary; Qi, Yanfei; Pepine, Carl J

    2014-01-01

    Stem/progenitor cell-based therapies offer novel treatment for many prevalent diseases. However, most physicians are not trained or introduced to cell therapy. We describe a model of a training program aimed at empowering physician-scientists with the knowledge and skills necessary for advancing the field of cardiovascular cell therapy. To date, five full-time scholars have completed this training program, obtained a full-time academic appointment in Cardiovascular Disease, and continue to actively contribute to the advancement of cell therapy applications. Another has returned to his parent institution to complete his PhD and several part-time scholars have continued in scholarly activities in other academic programs.

  17. Large Scale Analysis of Phenotype-Pathway Relationships Based on GWAS Results

    PubMed Central

    Brodie, Aharon; Tovia-Brodie, Oholi; Ofran, Yanay

    2014-01-01

    The widely used pathway-based approach for interpreting Genome Wide Association Studies (GWAS), assumes that since function is executed through the interactions of multiple genes, different perturbations of the same pathway would result in a similar phenotype. This assumption, however, was not systemically assessed on a large scale. To determine whether SNPs associated with a given complex phenotype affect the same pathways more than expected by chance, we analyzed 368 phenotypes that were studied in >5000 GWAS. We found 216 significant phenotype-pathway associations between 70 of the phenotypes we analyzed and known pathways. We also report 391 strong phenotype-phenotype associations between phenotypes that are affected by the same pathways. While some of these associations confirm previously reported connections, others are new and could shed light on the molecular basis of these diseases. Our findings confirm that phenotype-associated SNPs cluster into pathways much more than expected by chance. However, this is true for <20% (70/368) of the phenotypes. Different types of phenotypes show markedly different tendencies: Virtually all autoimmune phenotypes show strong clustering of SNPs into pathways, while most cancers and metabolic conditions, and all electrophysiological phenotypes, could not be significantly associated with any pathway despite being significantly associated with a large number of SNPs. While this may be due to missing data, it may also suggest that these phenotypes could result only from perturbations of specific genes and not from other perturbations of the same pathway. Further analysis of pathway-associated versus gene-associated phenotypes is, therefore, needed in order to understand disease etiology and in order to promote better drug target selection. PMID:25007247

  18. Cardiovascular responses to weightlessness and ground-based simulations

    NASA Technical Reports Server (NTRS)

    Sandler, H.

    1982-01-01

    Mission experience, from NASA and Soviet programs, on human cardiovascular responses to weightlessness, and the ability of bed rest studies to simulate these are discussed. In-flight effects include fluid shift to the upper body, decreased heart size, bone demineralization, orthostatic intolerance, and loss of exercise tolerance. All the cardiovascular changes that occur with weightlessness also occur with prolonged bed rest. They are most manifest when subjects stand suddenly, or undergo tilting or lower body negative pressure. The mechanisms which control these responses, e.g., the role of the central nervous system, are unclear.

  19. Gender-based differences in the cardiovascular response to standing

    NASA Technical Reports Server (NTRS)

    Gotshall, Robert W.; Tsai, Pai-Feng; Frey, Mary A. B.

    1991-01-01

    The cardiovascular responses of men and women to the stand test were compared by measuring respective values for heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance during a 5-min supine and a 5-min standing test in ten subjects of each gender. It was found that, while the male and female subjects had similar heart rate values, all other responses exhibited greater changes in men than in women. While differences in the height of the subjects did not account for differences in cardiovascular responses, no mechanism responsible for these differences could be identified.

  20. [Civilization stress, cardiovascular risk, evidence-based medicine, guidelines].

    PubMed

    Simon, Kornél

    2009-05-10

    Cardiovascular diseases have the pole-position on the list of morbidity and mortality statistics. Despite the great advances have been made in management of cardiovascular diseases, prevalence of these disorders increases worldwide, and even younger and younger ages are threatened. This phenomenon is strongly related to obesity and type 2 diabetes pandemic, which shows an unequivocal association with expansion of modernized life-style. The pathomechanism proposed to have central role is the chronic stress induced by civilized life-conduct. The authors criticizes the everyday practice suggested for management of cardiovascular diseases, focusing on normalization of cardiovascular risk factors, instead of fighting against the primary cause ie. chronic stress. There is growing evidence, that achieving the target values defined in guide-lines will not necessarily result in improvement of patient related clinical outcomes. The statistical approach generally practiced in randomized clinical trials is primarily striving for the drug-sale, instead of discovering novel pathophysiological relations. Pharmaceutical industry having decisive role in research and patient-care is mainly interested in profit-sharing, therefore patients' interest can not be optimally realized, and costs are unnecessarily augmented. Separation of patient-, and business-oriented medical care is an ethical question of fundamental importance.

  1. Complementary and Alternative Medicine and Cardiovascular Disease: An Evidence-Based Review

    PubMed Central

    Rabito, Matthew J.; Kaye, Alan David

    2013-01-01

    Complementary and alternative medicine (CAM) plays a significant role in many aspects of healthcare worldwide, including cardiovascular disease (CVD). This review describes some of the challenges of CAM in terms of scientific research. Biologically-based therapies, mind-body therapies, manipulative and body-based therapies, whole medical systems, and energy medicine are reviewed in detail with regard to cardiovascular risk factors and mediation or modulation of cardiovascular disease pathogenesis. CAM use among patients with CVD is prevalent and in many instances provides positive and significant effects, with biologically-based and mind-body therapies being the most commonly used treatment modalities. More rigorous research to determine the precise physiologic effects and long-term benefits on cardiovascular morbidity and mortality with CAM usage, as well as more open lines of communication between patients and physicians regarding CAM use, is essential when determining optimal treatment plans. PMID:23710229

  2. Complementary and alternative medicine and cardiovascular disease: an evidence-based review.

    PubMed

    Rabito, Matthew J; Kaye, Alan David

    2013-01-01

    Complementary and alternative medicine (CAM) plays a significant role in many aspects of healthcare worldwide, including cardiovascular disease (CVD). This review describes some of the challenges of CAM in terms of scientific research. Biologically-based therapies, mind-body therapies, manipulative and body-based therapies, whole medical systems, and energy medicine are reviewed in detail with regard to cardiovascular risk factors and mediation or modulation of cardiovascular disease pathogenesis. CAM use among patients with CVD is prevalent and in many instances provides positive and significant effects, with biologically-based and mind-body therapies being the most commonly used treatment modalities. More rigorous research to determine the precise physiologic effects and long-term benefits on cardiovascular morbidity and mortality with CAM usage, as well as more open lines of communication between patients and physicians regarding CAM use, is essential when determining optimal treatment plans. PMID:23710229

  3. Ontology-based cross-species integration and analysis of Saccharomyces cerevisiae phenotypes

    PubMed Central

    2012-01-01

    Ontologies are widely used in the biomedical community for annotation and integration of databases. Formal definitions can relate classes from different ontologies and thereby integrate data across different levels of granularity, domains and species. We have applied this methodology to the Ascomycete Phenotype Ontology (APO), enabling the reuse of various orthogonal ontologies and we have converted the phenotype associated data found in the SGD following our proposed patterns. We have integrated the resulting data in the cross-species phenotype network PhenomeNET, and we make both the cross-species integration of yeast phenotypes and a similarity-based comparison of yeast phenotypes across species available in the PhenomeBrowser. Furthermore, we utilize our definitions and the yeast phenotype annotations to suggest novel functional annotations of gene products in yeast. PMID:23046642

  4. Ontology-based cross-species integration and analysis of Saccharomyces cerevisiae phenotypes.

    PubMed

    Gkoutos, Georgios V; Hoehndorf, Robert

    2012-09-21

    Ontologies are widely used in the biomedical community for annotation and integration of databases. Formal definitions can relate classes from different ontologies and thereby integrate data across different levels of granularity, domains and species. We have applied this methodology to the Ascomycete Phenotype Ontology (APO), enabling the reuse of various orthogonal ontologies and we have converted the phenotype associated data found in the SGD following our proposed patterns. We have integrated the resulting data in the cross-species phenotype network PhenomeNET, and we make both the cross-species integration of yeast phenotypes and a similarity-based comparison of yeast phenotypes across species available in the PhenomeBrowser. Furthermore, we utilize our definitions and the yeast phenotype annotations to suggest novel functional annotations of gene products in yeast.

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

    PubMed Central

    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

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

    NASA Technical Reports Server (NTRS)

    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.

  7. From phenotype to gene: detecting disease-specific gene functional modules via a text-based human disease phenotype network construction.

    PubMed

    Zhang, Shihua; Zhang, Shi-Hua; Wu, Chao; Li, Xia; Chen, Xi; Jiang, Wei; Gong, Bin-Sheng; Li, Jiang; Yan, Yu-Qing

    2010-08-20

    Currently, some efforts have been devoted to the text analysis of disease phenotype data, and their results indicated that similar disease phenotypes arise from functionally related genes. These related genes work together, as a functional module, to perform a desired cellular function. We constructed a text-based human disease phenotype network and detected 82 disease-specific gene functional modules, each corresponding to a different phenotype cluster, by means of graph-based clustering and mapping from disease phenotype to gene. Since genes in such gene functional modules are functionally related and cause clinically similar diseases, they may share common genetic origin of their associated disease phenotypes. We believe the investigation may facilitate the ultimate understanding of the common pathophysiologic basis of associated diseases.

  8. A Zebrafish In Vivo Phenotypic Assay to Identify 3-Aminothiophene-2-Carboxylic Acid-Based Angiogenesis Inhibitors

    PubMed Central

    Papakyriakou, Athanasios; Kefalos, Panagiotis; Sarantis, Panagiotis; Tsiamantas, Christos; Xanthopoulos, Kleanthis P.

    2014-01-01

    Abstract Small molecules that inhibit angiogenesis are attractive drug candidates for cancer, retinopathies, and age-related macular degeneration. In vivo, phenotypic screening in zebrafish (Danio rerio) emerges as a powerful methodology to identify and optimize novel compounds with pharmacological activity. Zebrafish provides several advantages for in vivo phenotypic screens especially for angiogenesis, since it develops rapidly, externally, and does not rely on a functional cardiovascular system to survive for several days during development. In this study, we utilize a transgenic line that allows the noninvasive monitoring of angiogenesis at a cellular level. The inhibition of angiogenesis can be observed under a fluorescent stereoscope and quantified. To exemplify the versatility and robustness of the zebrafish screen, we have employed a series of 60 novel compounds that were designed based on a potent VEGFR2 inhibitor. Herein, we report their structure-based design, synthesis, and in vivo zebrafish screening for optimal activity, toxicity, and off-target effects, which revealed six reversible inhibitors of angiogenesis. PMID:25506802

  9. Epigenetic regulation in chondrocyte phenotype maintenance for cell-based cartilage repair

    PubMed Central

    Duan, Li; Liang, Yujie; Ma, Bin; Zhu, Weimin; Wang, Daping

    2015-01-01

    Loss of hyaline chondrocyte phenotype during the monolayer culture in vitro is a major obstacle for cell-based articular cartilage repair. Increasing evidence implicates an important role of the epigenetic regulation in maintaining the chondrocyte phenotype. DNA methylation, histone modifications and microRNAs have all been shown to contribute to chondrocyte dedifferentiation and hypertrophy. Moreover, the interplay among epigenetic regulators forms a complicated epigenetic network in regulating chondrocyte dedifferentiation. This review provides a detailed overview of the epigenetic regulation in maintaining the chondrocyte phenotype for chondrocyte-based cartilage repair. PMID:26807163

  10. Cardiovascular Deconditioning

    NASA Technical Reports Server (NTRS)

    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.

  11. [Cardiovascular safety of incretin-based antidiabetic treatment - results of completed clinical trials].

    PubMed

    Jermendy, György

    2016-04-17

    Several randomized, controlled clinical trials were initiated some years ago in order to evaluate the cardiovascular safety of the new antidiabetic drugs in patients with type 2 diabetes due to requirements from regulatory bodies. Four trials with incretin-based drugs (saxagliptin, alogliptin, sitagliptin and lixisenatide) have been completed so far. Based on the primary outcome endpoints of these trials no cardiovascular risks were found with incretins in patients with type 2 diabetes. As for saxagliptin, the hospitalization for heart failure was investigated as a secondary endpoint, and an increased risk was observed in the respective trial; however, this observation was widely debated later in the literature. Together with ongoing trials of other novel antihyperglycemic agents, these data will provide more robust evidence about the cardiovascular safety of incretin-based antidiabetic treatment in patients with type 2 diabetes. PMID:27063427

  12. [Research on Prevention and Treatment of Cardiovascular Disease by Translational Medicine Based Chinese Medicine].

    PubMed

    Lu, Shi-chao; Zhang, Jun-ping

    2015-05-01

    Translational medicine is inevitable in the development of modern medicine, and the uprising concept of translational medicine provides an opportunity for the development of Chinese medicine (CM). Their ideas are well communicated. There are two patterns of researching on CM based on translational medicine: 'literature to bench to bedside' and 'bench to bedside to bench'. CM has her advantages in preventing and treating cardiovascular disease. Effective methods for preventing and treating cardiovascular disease by CM should be further studied based on translational medicine concepts.

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

    PubMed Central

    Martínez Larrad, María Teresa; Corbatón Anchuelo, Arturo; Fernández Pérez, Cristina; Pérez Barba, Milagros; Lazcano Redondo, Yera; Serrano Ríos, Manuel

    2016-01-01

    Objectives Our aim was to investigate if genetic variations in the visfatin gene (SNPs rs7789066/ rs11977021/rs4730153) could modify the cardiovascular-risk (CV-risk) despite the metabolic phenotype (obesity and glucose tolerance). In addition, we investigated the relationship between insulin sensitivity and variations in visfatin gene. Material and Methods A population-based study in rural and urban areas of the Province of Segovia, Spain, was carried out in the period of 2001–2003 years. A total of 587 individuals were included, 25.4% subjects were defined as obese (BMI ≥30 Kg/m2). Results Plasma visfatin levels were significantly higher in obese subjects with DM2 than in other categories of glucose tolerance. The genotype AA of the rs4730153 SNP was significantly associated with fasting glucose, fasting insulin and HOMA-IR (Homeostasis model assessment-insulin resistance) after adjustment for gender, age, BMI and waist circumference. The obese individuals carrying the CC genotype of the rs11977021 SNP showed higher circulating levels of fasting proinsulin after adjustment for the same variables. The genotype AA of the rs4730153 SNP seems to be protective from CV-risk either estimated by Framingham or SCORE charts in general population; and in obese and non-obese individuals. No associations with CV-risk were observed for other studied SNPs (rs11977021/rs7789066). Conclusions In summary, this is the first study which concludes that the genotype AA of the rs4730153 SNP appear to protect against CV-risk in obese and non–obese individuals, estimated by Framingham and SCORE charts. Our results confirm that the different polymorphisms in the visfatin gene might be influencing the glucose homeostasis in obese individuals. PMID:27166797

  14. Automated, Computerized, Feature-Based Phenotype Analysis of Slit Lamp Images of the Mouse Lens

    PubMed Central

    Yuen, Jenny; Li, Yi; Shapiro, Linda G.; Clark, John I.; Arnett, Ernest; Sage, E. Helene; Brinkley, James F.

    2008-01-01

    Longitudinal studies of a variety of transgenic mouse models for lens development can create substantial challenges in database management and analysis. We report a novel, automated, feature-based informatics approach to screening lens phenotypes in a large database of slit lamp images. Digital slit lamp images of normal and abnormal lenses in eyes of wild type (wt), SC1 null and SPARC null transgenic mice were recorded for quantitative evaluation of their structural phenotype. The images were processed to improve the contrast of structural features that corresponded to rings of opacity and fluctuations in scattering intensity in the lenses. Measurable attributes were assigned to the features in the lens images and given as an output vector of 46 dimensions. Characteristic patterns correlated with the structural phenotype of each mutant and wt lens and a statistical fit for each phenotype was defined. The genotype was identified correctly in nearly 85% of the slit lamp images on the basis of an automated computer analysis of the lens structural phenotype. The automated computer algorithm has the potential to evaluate a large database of slit lamp images and distinguish mouse genotypes on the basis of lens phenotypes objectively using a neural network analysis of the structural features observed in the slit lamp images. The neural network approach is a promising technology for objective evaluation of genotype/phenotype relationships based on structural features and light scattering in lenses. Further improvements in the automated method can be expected to simplify and increase the accuracy and efficiency of the feature based analysis of structural phenotypes linked to genetic variation. PMID:18304532

  15. Community Based Cardiovascular Health Interventions in Vulnerable Populations: A Systematic Review

    PubMed Central

    Walton-Moss, Benita; Samuel, Laura; Nguyen, Tam H; Commodore-Mensah, Yvonne; Hayat, Matthew J.; Szanton, Sarah L.

    2013-01-01

    Background Although cardiovascular health has been improving for many Americans, this is not true of those in “vulnerable populations.” To address this growing disparity communities and researchers have worked for decades, and as a result of their work a growing body of literature supports the use of community engagement as a component of successful interventions. However, little literature synthesizes community-based interventions that address this disparity among a wide range of vulnerable populations. Objective This paper provides a critical review of community-based cardiovascular disease (CVD) interventions to improve cardiovascular health behaviors and factors among vulnerable populations based on the American Heart Association’s 7 metrics of ideal cardiovascular health. Methods In February 2011, four databases (PubMed, PsychInfo, CINAHL, and Scopus) were searched using the following keywords: vulnerable populations OR healthcare disparities AND cardiovascular disease AND clinical trials OR public health practice AND English. Results This search strategy resulted in the retrieval of 7,120 abstracts. Each abstract was reviewed by at least two authors and eligibility for the systematic review was confirmed after reading the full article. Thirty two studies met eligibility criteria. Education was the most common intervention (41%), followed by counseling or support (38%), and exercise classes (28%). Half of the interventions were multi-component. Health care providers were the most frequent interventionists. Interventions aimed at decreasing blood pressure were the most promising while behavior change interventions were the most challenging. Almost all of the interventions were at the individual level, and were proof of concept or efficacy trials. Conclusions This analysis provides a step towards understanding the current literature on cardiovascular interventions for vulnerable population. The next step should be integrating the identified successful

  16. Epigenetics and cardiovascular disease.

    PubMed

    Webster, Andrew L H; Yan, Matthew Shu-Ching; Marsden, Philip A

    2013-01-01

    A commonly-assumed paradigm holds that the primary genetic determinant of cardiovascular disease resides within the DNA sequence of our genes. This paradigm can be challenged. For example, how do sequence changes in the non-coding region of the genome influence phenotype? Why are all diseases not shared between identical twins? Part of the answer lies in the fact that the environment or exogenous stimuli clearly influence disease susceptibility, but it was unclear in the past how these effects were signalled to the static DNA code. Epigenetics is providing a newer perspective on these issues. Epigenetics refers to chromatin-based mechanisms important in the regulation of gene expression that do not involve changes to the DNA sequence per se. The field can be broadly categorized into three areas: DNA base modifications (including cytosine methylation and cytosine hydroxymethylation), post-translational modifications of histone proteins, and RNA-based mechanisms that operate in the nucleus. Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health. This paper reviews the principles governing epigenetic regulation, discusses their presently-understood importance in cardiovascular disease, and considers the growing significance we are likely to attribute to epigenetic contributions in the future, as they provide new mechanistic insights and a host of novel clinical applications. PMID:23261320

  17. [Nuclear magnetic resonance based metabolic phenotyping for patient evaluations in operating rooms and intensive care units].

    PubMed

    Blaise, B J; Gouel-Chéron, A; Floccard, B; Monneret, G; Plaisant, F; Chassard, D; Javouhey, E; Claris, O; Allaouchiche, B

    2014-03-01

    Metabolic phenotyping consists in the identification of subtle and coordinated metabolic variations associated with various pathophysiological stimuli. Different analytical methods, such as nuclear magnetic resonance, allow the simultaneous quantification of a large number of metabolites. Statistical analyses of these spectra thus lead to the discrimination between samples and the identification of a metabolic phenotype corresponding to the effect under study. This approach allows the extraction of candidate biomarkers and the recovery of perturbed metabolic networks, driving to the generation of biochemical hypotheses (pathophysiological mechanisms, diagnostic tests, therapeutic targets…). Metabolic phenotyping could be useful in anaesthesiology and intensive care medicine for the evaluation, monitoring or diagnosis of life-threatening situations, to optimise patient managements. This review introduces the physical and statistical fundamentals of NMR-based metabolic phenotyping, describes the work already achieved by this approach in anaesthesiology and intensive care medicine. Finally, potential areas of interest are discussed for the perioperative and intensive management of patients, from newborns to adults.

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

    PubMed

    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.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed Central

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

    2014-01-01

    Molecular oxygen is indispensable for cellular viability and function. Hypoxia is a stress condition in which oxygen demand exceeds supply. Low cellular oxygen content induces a number of molecular changes to activate regulatory pathways responsible for increasing the oxygen supply and optimizing cellular metabolism under limited oxygen conditions. Hypoxia plays critical roles in the pathobiology of many diseases, such as cancer, heart failure, myocardial ischemia, stroke, and chronic lung diseases. Although the complicated associations between hypoxia and cardiovascular (and cerebrovascular) diseases (CVD) have been recognized for some time, there are few studies that investigate their biological link from a systems biology perspective. In this study, we integrate hypoxia genes, CVD genes, and the human protein interactome in order to explore the relationship between hypoxia and cardiovascular diseases at a systems level. We show that hypoxia genes are much closer to CVD genes in the human protein interactome than that expected by chance. We also find that hypoxia genes play significant bridging roles in connecting different cardiovascular diseases. We construct an hypoxia-CVD bipartite network and find several interesting hypoxia-CVD modules with significant Gene Ontology (GO) similarity. Finally, we show that hypoxia genes tend to have more CVD interactors in the human interactome than in random networks of matching topology. Based on these observations, we can predict novel genes that may be associated with CVD. This network-based association study gives us a broad view of the relationships between hypoxia and cardiovascular diseases and provides new insights into the role of hypoxia in cardiovascular biology. PMID:25530704

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

    ERIC Educational Resources Information Center

    Reinagel, Adam; Speth, Elena Bray

    2016-01-01

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

  3. Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene silencing.

    PubMed

    Yamamoto-Hino, Miki; Yoshida, Hideki; Ichimiya, Tomomi; Sakamura, Sho; Maeda, Megumi; Kimura, Yoshinobu; Sasaki, Norihiko; Aoki-Kinoshita, Kiyoko F; Kinoshita-Toyoda, Akiko; Toyoda, Hidenao; Ueda, Ryu; Nishihara, Shoko; Goto, Satoshi

    2015-06-01

    Glycan structures are synthesized by a series of reactions conducted by glycosylation-related (GR) proteins such as glycosyltransferases, glycan-modifying enzymes, and nucleotide-sugar transporters. For example, the common core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O-xylosyltransferase, β1,4-galactosyltransferase I, β1,3-galactosyltransferase II, and β1,3-glucuronyltransferase. This raises the possibility that functional impairment of GR proteins involved in synthesis of the same glycan might result in the same phenotypic abnormality. To examine this possibility, comprehensive silencing of genes encoding GR and proteoglycan core proteins was conducted in Drosophila. Drosophila GR candidate genes (125) were classified into five functional groups for synthesis of GAGs, N-linked, O-linked, Notch-related, and unknown glycans. Spatiotemporally regulated silencing caused a range of malformed phenotypes that fell into three types: extra veins, thick veins, and depigmentation. The clustered phenotypes reflected the biosynthetic pathways of GAGs, Fringe-dependent glycan on Notch, and glycans placed at or near nonreducing ends (herein termed terminal domains of glycans). Based on the phenotypic clustering, CG33145 was predicted to be involved in formation of terminal domains. Our further analysis showed that CG33145 exhibited galactosyltransferase activity in synthesis of terminal N-linked glycans. Phenotypic clustering, therefore, has potential for the functional prediction of novel GR genes. PMID:25940448

  4. Survival of patients with mixed phenotype acute leukemias: A large population-based study.

    PubMed

    Shi, Runhua; Munker, Reinhold

    2015-06-01

    Little is known about the incidence and treatment outcome of patients with acute biphenotypic leukemias. The World Health Organization (WHO) established the term of acute leukemia of ambiguous phenotype in 2001 (revised in 2008) introducing the term of mixed phenotype acute leukemias. Using the database of the Surveillance, Epidemiology, and End Results registry (SEER), we identified 313 patients with mixed phenotype acute leukemias and compared them with 14,739 patients with acute lymphoblastic leukemia and 34,326 patients with acute myelogenous leukemias diagnosed between 2001 and 2011. As a further control group, 1777 patients were included who were not classified as myeloid, lymphoid or biphenotypic (other acute leukemias). The incidence of mixed phenotype acute leukemias is 0.35 cases/1,000,000 person-years. In a multivariate analysis, the prognosis depends strongly on age (as with other leukemias) and it has the worst outcome of all four types of leukemia. However, the prognosis has improved, comparing 2001-2005 with 2006-2011. We present the first comprehensive, population-based study of acute biphenotypic or mixed phenotype acute leukemias according to the WHO classification. Especially in older patients, the prognosis is unfavorable and new treatments should be investigated.

  5. Phenotype-based clustering of glycosylation-related genes by RNAi-mediated gene silencing

    PubMed Central

    Yamamoto-Hino, Miki; Yoshida, Hideki; Ichimiya, Tomomi; Sakamura, Sho; Maeda, Megumi; Kimura, Yoshinobu; Sasaki, Norihiko; Aoki-Kinoshita, Kiyoko F; Kinoshita-Toyoda, Akiko; Toyoda, Hidenao; Ueda, Ryu; Nishihara, Shoko; Goto, Satoshi

    2015-01-01

    Glycan structures are synthesized by a series of reactions conducted by glycosylation-related (GR) proteins such as glycosyltransferases, glycan-modifying enzymes, and nucleotide-sugar transporters. For example, the common core region of glycosaminoglycans (GAGs) is sequentially synthesized by peptide-O-xylosyltransferase, β1,4-galactosyltransferase I, β1,3-galactosyltransferase II, and β1,3-glucuronyltransferase. This raises the possibility that functional impairment of GR proteins involved in synthesis of the same glycan might result in the same phenotypic abnormality. To examine this possibility, comprehensive silencing of genes encoding GR and proteoglycan core proteins was conducted in Drosophila. Drosophila GR candidate genes (125) were classified into five functional groups for synthesis of GAGs, N-linked, O-linked, Notch-related, and unknown glycans. Spatiotemporally regulated silencing caused a range of malformed phenotypes that fell into three types: extra veins, thick veins, and depigmentation. The clustered phenotypes reflected the biosynthetic pathways of GAGs, Fringe-dependent glycan on Notch, and glycans placed at or near nonreducing ends (herein termed terminal domains of glycans). Based on the phenotypic clustering, CG33145 was predicted to be involved in formation of terminal domains. Our further analysis showed that CG33145 exhibited galactosyltransferase activity in synthesis of terminal N-linked glycans. Phenotypic clustering, therefore, has potential for the functional prediction of novel GR genes. PMID:25940448

  6. Preventing cardiovascular disease through community-based risk reduction: the Bootheel Heart Health Project.

    PubMed Central

    Brownson, R C; Smith, C A; Pratt, M; Mack, N E; Jackson-Thompson, J; Dean, C G; Dabney, S; Wilkerson, J C

    1996-01-01

    OBJECTIVES. The purpose of this study was to determine whether a community-based risk reduction project affected behavioral risk factors for cardiovascular disease. METHODS. Community-based activities (e.g., exercise groups, healthy cooking demonstrations, blood pressure and cholesterol screenings, and cardiovascular disease education) were conducted in six southeastern Missouri counties. Evaluation involved population-based, cross-sectional samples of adult residents of the state and the intervention region. Weighted prevalence estimates were calculated for self-reported physical inactivity, cigarette smoking, consumption of fruits and vegetables, overweight, and cholesterol screening. RESULTS. Physical inactivity decreased within the intervention region, that is, in communities where heart health coalitions were developed and among respondents who were aware of these coalitions. In addition, the prevalence rates for reports of cholesterol screening within the past 2 years were higher for respondents in areas with coalitions and among persons who were aware of the coalitions. CONCLUSIONS. Even with modest resources, community-based interventions show promise in reducing self-reported risk for cardiovascular disease within a relatively brief period. PMID:8633737

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

    PubMed Central

    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; 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; 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; Davey Smith, George; Mukamal, Kenneth; Psaty, Bruce M; Wilson, James G; Lange, Leslie A; Hamidovic, Ajna; Hingorani, Aroon D; Nordestgaard, Børge G; Bobak, Martin; Leon, David A; Langenberg, Claudia; Palmer, Tom M; Reiner, Alex P; Keating, Brendan J; Dudbridge, Frank

    2014-01-01

    Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for

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

    PubMed

    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.

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

    PubMed

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

    2015-01-01

    Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein target and disease modification, a phenotypic endpoint. Fragment-based drug discovery is a target-based approach that typically involves the screening of a relatively small number of fragment-like (molecular weight <300) molecules that efficiently cover chemical space. Here, we report a fragment screening on TbrPDEB1, an essential cyclic nucleotide phosphodiesterase (PDE) from Trypanosoma brucei, and human PDE4D, an off-target, in a workflow in which fragment hits and a series of close analogs are subsequently screened for antiparasitic activity in a phenotypic panel. The phenotypic panel contained T. brucei, Trypanosoma cruzi, Leishmania infantum, and Plasmodium falciparum, the causative agents of human African trypanosomiasis (sleeping sickness), Chagas disease, leishmaniasis, and malaria, respectively, as well as MRC-5 human lung cells. This hybrid screening workflow has resulted in the discovery of various benzhydryl ethers with antiprotozoal activity and low toxicity, representing interesting starting points for further antiparasitic optimization. PMID:25231971

  10. The cardiovascular safety of incretin-based therapies: a review of the evidence

    PubMed Central

    2013-01-01

    Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with diabetes and therefore managing cardiovascular (CV) risk is a critical component of diabetes care. As incretin-based therapies are effective recent additions to the glucose-lowering treatment armamentarium for type 2 diabetes mellitus (T2D), understanding their CV safety profiles is of great importance. Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with beneficial effects on CV risk factors, including weight, blood pressure and lipid profiles. Encouragingly, mechanistic studies in preclinical models and in patients with acute coronary syndrome suggest a potential cardioprotective effect of native GLP-1 or GLP-1 receptor agonists following ischaemia. Moreover, meta-analyses of phase 3 development programme data indicate no increased risk of major adverse cardiovascular events (MACE) with incretin-based therapies. Large randomized controlled trials designed to evaluate long-term CV outcomes with incretin-based therapies in individuals with T2D are now in progress, with the first two reporting as this article went to press. PMID:24011363

  11. Project Joy: faith based cardiovascular health promotion for African American women.

    PubMed Central

    Yanek, L. R.; Becker, D. M.; Moy, T. F.; Gittelsohn, J.; Koffman, D. M.

    2001-01-01

    OBJECTIVE: The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies: a standard behavioral group intervention, the standard intervention supplemented with spiritual strategies, or self-help strategies. METHODS: Women were screened at baseline and after one year of participation. The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering. Because spiritual strategies were added to the standard intervention by participants themselves, the results from both active groups were similar and, thus, combined for comparisons with the self-help group. RESULTS: A total of 529 women from 16 churches enrolled. Intervention participants exhibited significant improvements in body weight (-1.1 lbs), waist circumference (-0.66 inches), systolic blood pressure (-1.6 mmHg), dietary energy (-117 kcal), dietary total fat (-8 g), and sodium intake (-145 mg). The self-help group did not. In the active intervention group, women in the top decile for weight loss at one year had even larger, clinically meaningful changes in risk outcomes (-19.8 lbs). CONCLUSIONS: Intervention participants achieved clinically important improvements in cardiovascular disease risk profiles one year after program initiation, which did not occur in the self-help group. Church-based interventions can significantly benefit the cardiovascular health of African American women. PMID:11889276

  12. Integration of Team-Based Learning Strategies Into a Cardiovascular Module

    PubMed Central

    Johnson, Jeremy L.; Ripley, Toni L.

    2010-01-01

    Objectives To integrate components of team-based learning (TBL) into a cardiovascular module to increase students' responsibility for their own learning and actively engage students across 2 campuses in patient cases. Design An existing cardiovascular course module was modified by replacing 8 hours of lectures with self-directed learning (SDL) assignments and transforming case discussion sessions using TBL methodologies. Case discussions were delivered using TBL methods to increase engagement of all students across both campuses while maintaining a low faculty-to-student ratio in the classrooms. Readiness assurance quizzes were performed with each SDL assignment and TBL case session. Assessment Student and faculty satisfaction improved with the addition of SDL assignments and TBL cases without adverse effects on grades in the wake of the 14% decrease in lecture time. Total faculty time required increased primarily in the first year because of development of course materials. Conclusion A modified TBL format was successfully integrated into a lecture-based cardiovascular module, resulting in improved student and faculty satisfaction with the course and no adverse effect on student performance. PMID:20414450

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

    PubMed

    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.

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

    PubMed

    Reinagel, Adam; Bray Speth, Elena

    2016-01-01

    In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students' understanding of 1) the origin of variation in a population and 2) how genes/alleles determine phenotypes. Guided by theory on hierarchical development of systems-thinking skills, we scaffolded instruction and assessment so that students would first focus on articulating isolated relationships between pairs of molecular genetics structures and then integrate these relationships into an explanatory network. We analyzed models students generated on two exams to assess whether students' learning of molecular genetics progressed along the theoretical hierarchical sequence of systems-thinking skills acquisition. With repeated practice, peer discussion, and instructor feedback over the course of the semester, students' models became more accurate, better contextualized, and more meaningful. At the end of the semester, however, more than 25% of students still struggled to describe phenotype as an output of protein function. We therefore recommend that 1) practices like modeling, which require connecting genes to phenotypes; and 2) well-developed case studies highlighting proteins and their functions, take center stage in molecular genetics instruction. PMID:26903496

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

    PubMed Central

    Reinagel, Adam; Bray Speth, Elena

    2016-01-01

    In an introductory biology course, we implemented a learner-centered, model-based pedagogy that frequently engaged students in building conceptual models to explain how genes determine phenotypes. Model-building tasks were incorporated within case studies and aimed at eliciting students’ understanding of 1) the origin of variation in a population and 2) how genes/alleles determine phenotypes. Guided by theory on hierarchical development of systems-thinking skills, we scaffolded instruction and assessment so that students would first focus on articulating isolated relationships between pairs of molecular genetics structures and then integrate these relationships into an explanatory network. We analyzed models students generated on two exams to assess whether students’ learning of molecular genetics progressed along the theoretical hierarchical sequence of systems-thinking skills acquisition. With repeated practice, peer discussion, and instructor feedback over the course of the semester, students’ models became more accurate, better contextualized, and more meaningful. At the end of the semester, however, more than 25% of students still struggled to describe phenotype as an output of protein function. We therefore recommend that 1) practices like modeling, which require connecting genes to phenotypes; and 2) well-developed case studies highlighting proteins and their functions, take center stage in molecular genetics instruction. PMID:26903496

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

    PubMed

    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. PMID:26598329

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

    PubMed

    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.

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

    PubMed

    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.

  19. Novel imaging-based phenotyping strategies for dissecting crosstalk in plant development.

    PubMed

    Fraas, Simon; Lüthen, Hartwig

    2015-08-01

    In an era of genomics, proteomics, and metabolomics a large number of mutants are available. The discovery of their phenotypes is fast becoming the bottleneck of molecular plant physiology. This crisis can be overcome by imaging-based phenotyping, an emerging, rapidly developing and innovative approach integrating plant and computer science. A tremendous amount of digital image data are automatically analysed using techniques of 'machine vision'. This minireview will shed light on the available imaging strategies and discuss standard methods for the automated analysis of images to give the non-bioinformatic reader an idea how the new technology works. A number of successful platforms will be described and the prospects that image-based phenomics may offer for elucidating hormonal cross-talk and molecular growth physiology will be discussed.

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

    PubMed

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

    2015-05-19

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

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

    PubMed

    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. PMID:26214591

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

    PubMed

    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.

  3. Beyond volume: hospital-based healthcare technology as a predictor of mortality for cardiovascular patients in Korea

    PubMed Central

    Kim, Jae-Hyun; Lee, Yunhwan; Park, Eun-Cheol

    2016-01-01

    Abstract To examine whether hospital-based healthcare technology is related to 30-day postoperative mortality rates after adjusting for hospital volume of cardiovascular surgical procedures. This study used the National Health Insurance Service–Cohort Sample Database from 2002 to 2013, which was released by the Korean National Health Insurance Service. A total of 11,109 cardiovascular surgical procedure patients were analyzed. The primary analysis was based on logistic regression models to examine our hypothesis. After adjusting for hospital volume of cardiovascular surgical procedures as well as for all other confounders, the odds ratio (OR) of 30-day mortality in low healthcare technology hospitals was 1.567-times higher (95% confidence interval [CI] = 1.069–2.297) than in those with high healthcare technology. We also found that, overall, cardiovascular surgical patients treated in low healthcare technology hospitals, regardless of the extent of cardiovascular surgical procedures, had the highest 30-day mortality rate. Although the results of our study provide scientific evidence for a hospital volume–mortality relationship in cardiovascular surgical patients, the independent effect of hospital-based healthcare technology is strong, resulting in a lower mortality rate. As hospital characteristics such as clinical pathways and protocols are likely to also play an important role in mortality, further research is required to explore their respective contributions. PMID:27310998

  4. Early life factors in relation to cardiovascular risk and cardiovascular disease in old age in Bergen: a Norwegian retrospective cohort study based on the Hordaland Health Study (HUSK)

    PubMed Central

    Stewart, Robert; Knapstad, Marit; Øverland, Simon; Mykletun, Arnstein

    2014-01-01

    Summary Objectives The fetal origins of adult disease hypothesis describes associations found for fetal or early-life exposures with cardiovascular risk and disease in adulthood. The extension or not of these associations into old age has received less attention. We investigated if maternal health and family circumstances were associated with cardiovascular risk factors and cardiovascular disease (CVD) in late life and discuss results in light of possible selection effects and measurement error. Design A retrospective cohort study based on community survey. We examined 224 possible associations between anthropometric measures, maternal health information and family socioeconomic status at birth versus CVD and CVD-related risk factors 72–74 years later. Participants Of 3341 participants in a community survey of people aged 72–74 years, we were able to trace birth records from a historical archive in a broadly representative subsample of 480. Setting Bergen, Norway Main outcome measures Established cardiovascular risk factors and indicators of CVD. Results Only 11 (4.9%) of these associations were found to be statistically significant, and no strong or consistent patterns in the associations between exposures and outcomes were found. Conclusions There was little evidence in this relatively elderly sample for an association between early life factors and CVD outcomes of clinical or public health relevance. Further research is required to confirm the extent to which a diminution of early life influences into old age, if genuine, can be accounted for by selective mortality, systematic bias or by dilution of effects due to competing risk factors. PMID:25057406

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

    PubMed

    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.

  6. Cost effectiveness of cardiovascular disease prevention strategies: a perspective on EU food based dietary guidelines.

    PubMed

    Brunner, E; Cohen, D; Toon, L

    2001-04-01

    For policymakers considering strategy options for the prevention of cardiovascular disease (CVD) the distinction between effectiveness and cost effectiveness is critical. When cost limitations apply, an evaluation of cost effectiveness is essential if a rational decision is to be made. Policy changes and resource reallocation have opportunity costs, and therefore it is necessary to compare the cost of health gains achievable by means of different policies. Here the broad question is: How cost effective are diet change strategies compared to other measures aimed at reducing cardiovascular disease in EU member states? An overview of published studies of cost-effectiveness in the primary and secondary prevention of cardiovascular disease was conducted. Few comprehensive studies were available. Estimated costs per life year gained were as follows: population-based healthy eating Pound Sterling 14-560; smoking cessation Pound Sterling 300-790; nurse screening and life style advice Pound Sterling 900 (minimum); simvastatin (HMGCoA reductase inhibitor) Pound Sterling 6200-11,300. Cost effectiveness is dependent on the underlying level of CVD risk in the target population, and the duration of the achieved alterations in behaviours and risk factors. The limited evidence from these studies tends to support the view that health protection strategies which promote healthy eating are likely to be more cost-effective than strategies involving modern cholesterol-lowering drugs, screening and advice in primary care, and are comparable to or less expensive per year of life saved than anti-smoking strategies. Given the considerable diversity in food habits, health care and public health systems among current and prospective EU member states, careful appraisal of the policy options within each member state is desirable to ensure that health gain is maximised. EU wide food based dietary guidelines are potentially the basis of large health gains in Europe, and cost

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

    PubMed Central

    Günter, Julia; Wolint, Petra; Bopp, Annina; Steiger, Julia; Cambria, Elena; Hoerstrup, Simon P.; Emmert, Maximilian Y.

    2016-01-01

    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. PMID:27073399

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

    PubMed

    Cho, Samuel Sunghwan; Kim, Yongkang; Yoon, Joon; Seo, Minseok; Shin, Su-Kyung; Kwon, Eun-Young; Kim, Sung-Eun; Bae, Yun-Jung; Lee, Seungyeoun; Sung, Mi-Kyung; Choi, Myung-Sook; Park, Taesung

    2016-01-01

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

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

    PubMed Central

    Firmann, Mathieu; Mayor, Vladimir; Vidal, Pedro Marques; Bochud, Murielle; Pécoud, Alain; Hayoz, Daniel; Paccaud, Fred; Preisig, Martin; Song, Kijoung S; Yuan, Xin; Danoff, Theodore M; Stirnadel, Heide A; Waterworth, Dawn; Mooser, Vincent; Waeber, Gérard; Vollenweider, Peter

    2008-01-01

    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. PMID:18366642

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

    PubMed

    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. PMID:25570321

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

    PubMed

    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.

  12. A Community-Based Participatory Planning Process and Multilevel Intervention Design: Toward Eliminating Cardiovascular Health Inequities

    PubMed Central

    Schulz, Amy J.; Israel, Barbara A.; Coombe, Chris M.; Gaines, Causandra; Reyes, Angela G.; Rowe, Zachary; Sand, Sharon; Strong, Larkin L.; Weir, Sheryl

    2010-01-01

    The elimination of persistent health inequities requires the engagement of multiple perspectives, resources and skills. Community-based participatory research is one approach to developing action strategies that promote health equity by addressing contextual as well as individual level factors, and that can contribute to addressing more fundamental factors linked to health inequity. Yet many questions remain about how to implement participatory processes that engage local insights and expertise, are informed by the existing public health knowledge base, and build support across multiple sectors to implement solutions. We describe a CBPR approach used to conduct a community assessment and action planning process, culminating in development of a multilevel intervention to address inequalities in cardiovascular disease in Detroit, Michigan. We consider implications for future efforts to engage communities in developing strategies toward eliminating health inequities. PMID:21873580

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

    PubMed

    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.

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

    PubMed

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

    2015-03-01

    The mechanical properties of biological cells have long been considered as inherent markers of biological function and disease. However, the screening and active sorting of heterogeneous populations based on serial single-cell mechanical measurements has not been demonstrated. Here we present a novel monolithic glass chip for combined fluorescence detection and mechanical phenotyping using an optical stretcher. A new design and manufacturing process, involving the bonding of two asymmetrically etched glass plates, combines exact optical fiber alignment, low laser damage threshold and high imaging quality with the possibility of several microfluidic inlet and outlet channels. We show the utility of such a custom-built optical stretcher glass chip by measuring and sorting single cells in a heterogeneous population based on their different mechanical properties and verify sorting accuracy by simultaneous fluorescence detection. This offers new possibilities of exact characterization and sorting of small populations based on rheological properties for biological and biomedical applications. PMID:25537986

  15. Systematic analysis, comparison, and integration of disease based human genetic association data and mouse genetic phenotypic information

    PubMed Central

    2010-01-01

    Background The genetic contributions to human common disorders and mouse genetic models of disease are complex and often overlapping. In common human diseases, unlike classical Mendelian disorders, genetic factors generally have small effect sizes, are multifactorial, and are highly pleiotropic. Likewise, mouse genetic models of disease often have pleiotropic and overlapping phenotypes. Moreover, phenotypic descriptions in the literature in both human and mouse are often poorly characterized and difficult to compare directly. Methods In this report, human genetic association results from the literature are summarized with regard to replication, disease phenotype, and gene specific results; and organized in the context of a systematic disease ontology. Similarly summarized mouse genetic disease models are organized within the Mammalian Phenotype ontology. Human and mouse disease and phenotype based gene sets are identified. These disease gene sets are then compared individually and in large groups through dendrogram analysis and hierarchical clustering analysis. Results Human disease and mouse phenotype gene sets are shown to group into disease and phenotypically relevant groups at both a coarse and fine level based on gene sharing. Conclusion This analysis provides a systematic and global perspective on the genetics of common human disease as compared to itself and in the context of mouse genetic models of disease. PMID:20092628

  16. Dissecting the phenotypic components of crop plant growth and drought responses based on high-throughput image analysis.

    PubMed

    Chen, Dijun; Neumann, Kerstin; Friedel, Swetlana; Kilian, Benjamin; Chen, Ming; Altmann, Thomas; Klukas, Christian

    2014-12-01

    Significantly improved crop varieties are urgently needed to feed the rapidly growing human population under changing climates. While genome sequence information and excellent genomic tools are in place for major crop species, the systematic quantification of phenotypic traits or components thereof in a high-throughput fashion remains an enormous challenge. In order to help bridge the genotype to phenotype gap, we developed a comprehensive framework for high-throughput phenotype data analysis in plants, which enables the extraction of an extensive list of phenotypic traits from nondestructive plant imaging over time. As a proof of concept, we investigated the phenotypic components of the drought responses of 18 different barley (Hordeum vulgare) cultivars during vegetative growth. We analyzed dynamic properties of trait expression over growth time based on 54 representative phenotypic features. The data are highly valuable to understand plant development and to further quantify growth and crop performance features. We tested various growth models to predict plant biomass accumulation and identified several relevant parameters that support biological interpretation of plant growth and stress tolerance. These image-based traits and model-derived parameters are promising for subsequent genetic mapping to uncover the genetic basis of complex agronomic traits. Taken together, we anticipate that the analytical framework and analysis results presented here will be useful to advance our views of phenotypic trait components underlying plant development and their responses to environmental cues.

  17. Analysis of root growth from a phenotyping data set using a density-based model.

    PubMed

    Kalogiros, Dimitris I; Adu, Michael O; White, Philip J; Broadley, Martin R; Draye, Xavier; Ptashnyk, Mariya; Bengough, A Glyn; Dupuy, Lionel X

    2016-02-01

    Major research efforts are targeting the improved performance of root systems for more efficient use of water and nutrients by crops. However, characterizing root system architecture (RSA) is challenging, because roots are difficult objects to observe and analyse. A model-based analysis of RSA traits from phenotyping image data is presented. The model can successfully back-calculate growth parameters without the need to measure individual roots. The mathematical model uses partial differential equations to describe root system development. Methods based on kernel estimators were used to quantify root density distributions from experimental image data, and different optimization approaches to parameterize the model were tested. The model was tested on root images of a set of 89 Brassica rapa L. individuals of the same genotype grown for 14 d after sowing on blue filter paper. Optimized root growth parameters enabled the final (modelled) length of the main root axes to be matched within 1% of their mean values observed in experiments. Parameterized values for elongation rates were within ±4% of the values measured directly on images. Future work should investigate the time dependency of growth parameters using time-lapse image data. The approach is a potentially powerful quantitative technique for identifying crop genotypes with more efficient root systems, using (even incomplete) data from high-throughput phenotyping systems.

  18. Analysis of root growth from a phenotyping data set using a density-based model.

    PubMed

    Kalogiros, Dimitris I; Adu, Michael O; White, Philip J; Broadley, Martin R; Draye, Xavier; Ptashnyk, Mariya; Bengough, A Glyn; Dupuy, Lionel X

    2016-02-01

    Major research efforts are targeting the improved performance of root systems for more efficient use of water and nutrients by crops. However, characterizing root system architecture (RSA) is challenging, because roots are difficult objects to observe and analyse. A model-based analysis of RSA traits from phenotyping image data is presented. The model can successfully back-calculate growth parameters without the need to measure individual roots. The mathematical model uses partial differential equations to describe root system development. Methods based on kernel estimators were used to quantify root density distributions from experimental image data, and different optimization approaches to parameterize the model were tested. The model was tested on root images of a set of 89 Brassica rapa L. individuals of the same genotype grown for 14 d after sowing on blue filter paper. Optimized root growth parameters enabled the final (modelled) length of the main root axes to be matched within 1% of their mean values observed in experiments. Parameterized values for elongation rates were within ±4% of the values measured directly on images. Future work should investigate the time dependency of growth parameters using time-lapse image data. The approach is a potentially powerful quantitative technique for identifying crop genotypes with more efficient root systems, using (even incomplete) data from high-throughput phenotyping systems. PMID:26880747

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

    NASA Astrophysics Data System (ADS)

    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 (<10 kPa) of the tri-block copolymer PCL-PDMS-PCL affected cardiovascular differentiation of embryonic stem cells, the range of 60-100 MPa PCL-PDMS-PCL showed little influence on the differentiation. Then different size (30-140 mum) of microspheres were fabricated from PCL-PDMS-PCL copolymers and incorporated within embryoid bodies (EBs). Mesoderm differentiation was induced using bone morphogenetic protein (BMP)-4 for cardiovascular differentiation. Differential expressions of mesoderm progenitor marker KDR and vascular markers CD31 and VE-cadherin were observed for the cells differentiated from EBs incorporated with microspheres of different size, while little difference was observed for cardiac marker alpha-actinin expression. Small size of microspheres (30 mum) resulted in higher expression of KDR while medium size of microspheres (94 mum) resulted in higher CD31 and VE-cadherin expression. This study indicated that the biophysical properties of PCL-based copolymers impacted stem cell lineage commitment, which should be considered for drug delivery and tissue engineering applications.

  20. Solexa-Sequencing Based Transcriptome Study of Plaice Skin Phenotype in Rex Rabbits (Oryctolagus cuniculus)

    PubMed Central

    Pan, Lei; Liu, Yan; Wei, Qiang; Xiao, Chenwen; Ji, Quanan; Bao, Guolian; Wu, Xinsheng

    2015-01-01

    Background Fur is an important genetically-determined characteristic of domestic rabbits; rabbit furs are of great economic value. We used the Solexa sequencing technology to assess gene expression in skin tissues from full-sib Rex rabbits of different phenotypes in order to explore the molecular mechanisms associated with fur determination. Methodology/Principal Findings Transcriptome analysis included de novo assembly, gene function identification, and gene function classification and enrichment. We obtained 74,032,912 and 71,126,891 short reads of 100 nt, which were assembled into 377,618 unique sequences by Trinity strategy (N50=680 nt). Based on BLAST results with known proteins, 50,228 sequences were identified at a cut-off E-value ≥ 10-5. Using Blast to Gene Ontology (GO), Clusters of Orthologous Groups (KOG) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we obtained several genes with important protein functions. A total of 308 differentially expressed genes were obtained by transcriptome analysis of plaice and un-plaice phenotype animals; 209 additional differentially expressed genes were not found in any database. These genes included 49 that were only expressed in plaice skin rabbits. The novel genes may play important roles during skin growth and development. In addition, 99 known differentially expressed genes were assigned to PI3K-Akt signaling, focal adhesion, and ECM-receptor interactin, among others. Growth factors play a role in skin growth and development by regulating these signaling pathways. We confirmed the altered expression levels of seven target genes by qRT-PCR. And chosen a key gene for SNP to found the differentially between plaice and un-plaice phenotypes rabbit. Conclusions/Significance The rabbit transcriptome profiling data provide new insights in understanding the molecular mechanisms underlying rabbit skin growth and development. PMID:25955442

  1. Laser-based optoelectronic system for therapy by medical treatment of cardiovascular diseases

    NASA Astrophysics Data System (ADS)

    Chtchoupak, Oleg S.; Shpilevoj, Boris N.; Zapaeva, Natlia L.

    1996-01-01

    The method and design of a system for the laser treatment of ischemic heart disease is presented. Our conceptual approach to the development of the system is based on the theoretical and experimental works of the east and west scientists about positive influence of low intensity laser irradiation in the near infrared range by treatment of cardiovascular diseases. The method and system allow active influence on the subepicardial collateral blood circulation with near infrared (NIR) laser irradiation in wavelength ranges of 0.86-1.06 mkm. The presented technique makes it possible to achieve a higher effectiveness of treatment due to individual choice of radiation parameters on the basis of analysis of the patient conditions before and after laser therapy and due to simultaneous affection at several points of the human body. Finally, results of the tests are presented, which prove given methods.

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

    PubMed

    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.

  3. Novel stem cell-based drug discovery platforms for cardiovascular disease.

    PubMed

    Adams, William J; García-Cardeña, Guillermo

    2012-10-01

    The complexity and diversity of many human diseases pose significant hurdles to the development of novel therapeutics. New scientific and technological advances, such as pharmacogenetics, provide valuable frameworks for understanding genetic predisposition to disease and tools for diagnosis and drug development. However, another framework is emerging based on recent scientific advances, one we suggest to call pharmacoempirics. Pharmacoempirics takes advantage of merging two nascent fields: first, the generation of induced pluripotent stem cells, which are differentiated into mature cell types and represent patient-specific genetic backgrounds, and, second, bioengineering advances allowing sophisticated re-creation of human pathophysiology in laboratory settings. The combination of these two innovative technologies should allow new experimentation on disease biology and drug discovery, efficacy, and toxicology unencumbered by hypothesis generation and testing. In this review, we discuss the challenges and promises of this exciting new type of discovery platform and outline its implementation for cardiovascular drug discovery.

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

    PubMed Central

    Nunes, Allancer DC; Ramalho, Laylla S; Souza, Álvaro PS; Mendes, Elizabeth P; Colugnati, Diego B; Zufelato, Nícholas; Sousa, Marcelo H; Bakuzis, Andris F; Castro, Carlos H

    2014-01-01

    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 rate or arterial blood pressure in conscious rats. In summary, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications. PMID:25031535

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

    PubMed Central

    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

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

    PubMed

    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

  7. 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.

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    Background Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. Methods We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG). Results Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (< 0.40 g/L). Twelve (10.5%), 28 (24%) and 9 (7.7%) patients had a 10-year risk of coronary heart disease ≥ 10% according to the Framingham, D:A:D, and Rama-EGAT score, respectively. Fifty one (44.4%) and 36 (31.3%) patients had not reached their LDL target according to IDSA-AACTG and French recommendations, respectively. Conclusion Prevalence of dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention. PMID:27579612

  9. Shift-work and cardiovascular disease: a population-based 22-year follow-up study.

    PubMed

    Hublin, Christer; Partinen, Markku; Koskenvuo, Karoliina; Silventoinen, Karri; Koskenvuo, Markku; Kaprio, Jaakko

    2010-05-01

    Studies on the association between shift-work and cardiovascular disease (CVD), in particular coronary heart disease (CHD), have given conflicting results. In this prospective population-based study we assessed the association of shift-work with three endpoints: CHD mortality, disability retirement due to CVD, and incident hypertension. A cohort of 20,142 adults (the Finnish Twin Cohort) was followed from 1982 to 2003. Type of working time (daytime/nighttime/shift-work) was assessed by questionnaires in 1975 (response rate 89%) and in 1981 (84%). Causes of death, information on disability retirement and hypertension medication were obtained from nationwide official registers. Cox proportional hazard models were used to obtain hazard ratios (HR) for each endpoint by type of working time. Adjustments were made for 14 socio-demographic and lifestyle covariates. 76.9% were daytime workers and 9.5% shift-workers both in 1975 and in 1981. During the follow-up, 857 deaths due to CHD, 721 disability retirements due to CVD, and 2,642 new cases of medicated hypertension were observed. However, HRs for shift-work were not significant (mortality HR men 1.09 and women 1.22; retirement 1.15 and 0.96; hypertension 1.15 and 0.98, respectively). The results were essentially similar after full adjustments for all covariates. Within twin pairs, no association between shift work and outcome was observed. Our results do not support an association between shift-work and cardiovascular morbidity. PMID:20229313

  10. An Investigation of the Potential for a Computer-based Tutorial Program Covering the Cardiovascular System to Replace Traditional Lectures.

    ERIC Educational Resources Information Center

    Dewhurst, D. G.; Williams, A. D.

    1998-01-01

    Presents the results of a comparative study to evaluate the effectiveness of two interactive computer-based learning (CBL) programs, covering the cardiovascular system, as an alternative to lectures for first year undergraduate students at a United Kingdom University. Discusses results in relation to the design of evaluative studies and the future…

  11. A Systematic Review of Internet-Based Worksite Wellness Approaches for Cardiovascular Disease Risk Management: Outcomes, Challenges & Opportunities

    PubMed Central

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

    2014-01-01

    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. PMID:24421894

  12. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

    PubMed

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-Ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-Aki K; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-05-20

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID:26822934

  13. Taxonomy of breast cancer based on normal cell phenotype predicts outcome

    PubMed Central

    Santagata, Sandro; Thakkar, Ankita; Ergonul, Ayse; Wang, Bin; Woo, Terri; Hu, Rong; Harrell, J. Chuck; McNamara, George; Schwede, Matthew; Culhane, Aedin C.; Kindelberger, David; Rodig, Scott; Richardson, Andrea; Schnitt, Stuart J.; Tamimi, Rulla M.; Ince, Tan A.

    2014-01-01

    Accurate classification is essential for understanding the pathophysiology of a disease and can inform therapeutic choices. For hematopoietic malignancies, a classification scheme based on the phenotypic similarity between tumor cells and normal cells has been successfully used to define tumor subtypes; however, use of normal cell types as a reference by which to classify solid tumors has not been widely emulated, in part due to more limited understanding of epithelial cell differentiation compared with hematopoiesis. To provide a better definition of the subtypes of epithelial cells comprising the breast epithelium, we performed a systematic analysis of a large set of breast epithelial markers in more than 15,000 normal breast cells, which identified 11 differentiation states for normal luminal cells. We then applied information from this analysis to classify human breast tumors based on normal cell types into 4 major subtypes, HR0–HR3, which were differentiated by vitamin D, androgen, and estrogen hormone receptor (HR) expression. Examination of 3,157 human breast tumors revealed that these HR subtypes were distinct from the current classification scheme, which is based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Patient outcomes were best when tumors expressed all 3 hormone receptors (subtype HR3) and worst when they expressed none of the receptors (subtype HR0). Together, these data provide an ontological classification scheme associated with patient survival differences and provides actionable insights for treating breast tumors. PMID:24463450

  14. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies

    PubMed Central

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-aki K.; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-01-01

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module (“Kibo”) on the International Space Station. The CBEF provides “space-based controls” by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments. PMID:26822934

  15. Ground-based assessment of JAXA mouse habitat cage unit by mouse phenotypic studies.

    PubMed

    Shimbo, Miki; Kudo, Takashi; Hamada, Michito; Jeon, Hyojung; Imamura, Yuki; Asano, Keigo; Okada, Risa; Tsunakawa, Yuki; Mizuno, Seiya; Yagami, Ken-Ichi; Ishikawa, Chihiro; Li, Haiyan; Shiga, Takashi; Ishida, Junji; Hamada, Juri; Murata, Kazuya; Ishimaru, Tomohiro; Hashimoto, Misuzu; Fukamizu, Akiyoshi; Yamane, Mutsumi; Ikawa, Masahito; Morita, Hironobu; Shinohara, Masahiro; Asahara, Hiroshi; Akiyama, Taishin; Akiyama, Nobuko; Sasanuma, Hiroki; Yoshida, Nobuaki; Zhou, Rui; Wang, Ying-Ying; Ito, Taito; Kokubu, Yuko; Noguchi, Taka-Aki K; Ishimine, Hisako; Kurisaki, Akira; Shiba, Dai; Mizuno, Hiroyasu; Shirakawa, Masaki; Ito, Naoki; Takeda, Shin; Takahashi, Satoru

    2016-05-20

    The Japan Aerospace Exploration Agency developed the mouse Habitat Cage Unit (HCU) for installation in the Cell Biology Experiment Facility (CBEF) onboard the Japanese Experimental Module ("Kibo") on the International Space Station. The CBEF provides "space-based controls" by generating artificial gravity in the HCU through a centrifuge, enabling a comparison of the biological consequences of microgravity and artificial gravity of 1 g on mice housed in space. Therefore, prior to the space experiment, a ground-based study to validate the habitability of the HCU is necessary to conduct space experiments using the HCU in the CBEF. Here, we investigated the ground-based effect of a 32-day housing period in the HCU breadboard model on male mice in comparison with the control cage mice. Morphology of skeletal muscle, the thymus, heart, and kidney, and the sperm function showed no critical abnormalities between the control mice and HCU mice. Slight but significant changes caused by the HCU itself were observed, including decreased body weight, increased weights of the thymus and gastrocnemius, reduced thickness of cortical bone of the femur, and several gene expressions from 11 tissues. Results suggest that the HCU provides acceptable conditions for mouse phenotypic analysis using CBEF in space, as long as its characteristic features are considered. Thus, the HCU is a feasible device for future space experiments.

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

    PubMed

    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. PMID:25703386

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

    PubMed

    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.

  18. Development and evaluation of a field-based high-throughput phenotyping platform

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physiological and developmental traits that vary over time are difficult to phenotype under relevant growing conditions. In response to this challenge, we developed a novel system for phenotyping dynamic traits in the field. System performance was evaluated on a field experiment of 25 Pima cotton cu...

  19. "Heart Smart"--A Staff Development Model for a School-Based Cardiovascular Health Intervention.

    ERIC Educational Resources Information Center

    Downey, Ann M.; And Others

    1988-01-01

    Cardiovascular (CV) risk-related behavior patterns are acquired during childhood; therefore CV intervention programs must begin at an early age. A CV health promotion program developed for elementary students is described. (JD)

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

    EPA Science Inventory

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

  1. A simple regression-based method to map quantitative trait loci underlying function-valued phenotypes.

    PubMed

    Kwak, Il-Youp; Moore, Candace R; Spalding, Edgar P; Broman, Karl W

    2014-08-01

    Most statistical methods for quantitative trait loci (QTL) mapping focus on a single phenotype. However, multiple phenotypes are commonly measured, and recent technological advances have greatly simplified the automated acquisition of numerous phenotypes, including function-valued phenotypes, such as growth measured over time. While methods exist for QTL mapping with function-valued phenotypes, they are generally computationally intensive and focus on single-QTL models. We propose two simple, fast methods that maintain high power and precision and are amenable to extensions with multiple-QTL models using a penalized likelihood approach. After identifying multiple QTL by these approaches, we can view the function-valued QTL effects to provide a deeper understanding of the underlying processes. Our methods have been implemented as a package for R, funqtl. PMID:24931408

  2. A simple regression-based method to map quantitative trait loci underlying function-valued phenotypes.

    PubMed

    Kwak, Il-Youp; Moore, Candace R; Spalding, Edgar P; Broman, Karl W

    2014-08-01

    Most statistical methods for quantitative trait loci (QTL) mapping focus on a single phenotype. However, multiple phenotypes are commonly measured, and recent technological advances have greatly simplified the automated acquisition of numerous phenotypes, including function-valued phenotypes, such as growth measured over time. While methods exist for QTL mapping with function-valued phenotypes, they are generally computationally intensive and focus on single-QTL models. We propose two simple, fast methods that maintain high power and precision and are amenable to extensions with multiple-QTL models using a penalized likelihood approach. After identifying multiple QTL by these approaches, we can view the function-valued QTL effects to provide a deeper understanding of the underlying processes. Our methods have been implemented as a package for R, funqtl.

  3. Negative biomarker-based male fertility evaluation: sperm phenotypes associated with molecular-level anomalies

    PubMed Central

    Sutovsky, Peter; Aarabi, Mahmoud; Miranda-Vizuete, Antonio; Oko, Richard

    2015-01-01

    Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery. PMID:25999356

  4. Pulse blood pressure and cardiovascular mortality in a population-based cohort of elderly Costa Ricans

    PubMed Central

    Rosero-Bixby, L; Coto-Yglesias, F; Dow, W H

    2016-01-01

    We studied the relationships between blood pressure (BP), pulse pressure (PP) and cardiovascular (CV) death in older adults using data from 2346 participants enrolled in the Costa Rican CRELES study, mean age 76 years (s.d. 10.2), 31% qualified as wide PP. All covariates included and analyzed were collected prospectively as part of a 4-year home-based follow-up; mortality was tracked for an additional 3 years, identifying 266 CV deaths. Longitudinal data revealed little change over time in systolic BP (SBP), a decline in diastolic BP, and widening of PP. Wide PP was associated with higher risk of CV death but only among individuals receiving antihypertensive drug therapy. Individuals with both wide PP and receiving therapy had 2.6 hazard rate of CV death relative to people with normal-PP plus not taking treatment (TRT), even adjusting for SBP. Increasing PP between visits was significantly associated to higher CV death independently of TRT status. SBP and DBP were not significantly associated to CV death when the effect of PP was controlled for. Conclusion: elderly hypertensive patients with wide or increasing PP, especially if receiving TRT, are the highest CV risk group, thus must be carefully assessed, monitored and treated with caution. PMID:26674758

  5. tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs

    PubMed Central

    Xu, Rong; Wang, QuanQiu

    2015-01-01

    Targeted cancer drugs are often associated with unexpectedly high cardiovascular (CV) adverse events. Systematic approaches to studying CV events associated with targeted anticancer drugs have high potential for elucidating the complex pathways underlying targeted anti-cancer drugs. In this study, we built tcTKB, a comprehensive CV toxicity knowledge base for targeted cancer drugs, by extracting drug-CV pairs from five large-scale and complementary data sources. The data sources include FDA drug labels (44,979 labels), the FDA Adverse Event Reporting System (FAERS) (4,285,097 records), the Canada Vigilance Adverse Reaction Online Database (CVAROD) (1,107,752 records), published biomedical literature (21,354,075 records), and published full-text articles from the Journal of Oncology (JCO) (13,855 articles). tcTKB contains 14,351 drug-CV pairs for 45 targeted anticancer drugs and 1,842 CV events. We demonstrate that CV events positively correlate with drug target genes and drug metabolism genes, demonstrating that tcTKB in combination with other data resources, could facilitate our understanding of targeted anticancer drugs and their associated CV toxicities. PMID:26958275

  6. Glyphosate-based herbicides potently affect cardiovascular system in mammals: review of the literature.

    PubMed

    Gress, Steeve; Lemoine, Sandrine; Séralini, Gilles-Eric; Puddu, Paolo Emilio

    2015-04-01

    In glyphosate (G)-based herbicides (GBHs), the declared active principle G is mixed with several adjuvants that help it to penetrate the plants' cell membranes and its stabilization and liposolubility. Its utilization is growing with genetically modified organisms engineered to tolerate GBH. Millions of farmers suffer poisoning and death in developing countries, and occupational exposures and suicide make GBH toxicity a worldwide concern. As GBH is found in human plasma, widespread hospital facilities for measuring it should be encouraged. Plasma determination is an essential prerequisite for risk assessment in GBH intoxication. Only when standard ECGs were performed, at least one abnormal ECG was detected in the large majority of cases after intoxication. QTc prolongation and arrhythmias along with first-degree atrioventricular block were observed after GBH intoxication. Thus, life-threatening arrhythmias might be the cause of death in GBH intoxication. Cardiac cellular effects of GBH were reviewed along with few case reports in men and scanty larger studies. We observed in two mammalian species (rats and rabbits) direct cardiac electrophysiological changes, conduction blocks and arrhythmias among GBH-mediated effects. Plasmatic (and urine) level determinations of G and electrocardiographic Holter monitoring seem warranted to ascertain whether cardiovascular risk among agro-alimentary workers might be defined.

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

    PubMed Central

    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

  8. Cell-based phenotypic screening of mast cell degranulation unveils kinetic perturbations of agents targeting phosphorylation

    PubMed Central

    Qin, Shenlu; Wang, Xumeng; Wu, Huanwen; Xiao, Peng; Cheng, Hongqiang; Zhang, Xue; Ke, Yuehai

    2016-01-01

    Mast cells play an essential role in initiating allergic diseases. The activation of mast cells are controlled by a complicated signal network of reversible phosphorylation, and finding the key regulators involved in this network has been the focus of the pharmaceutical industry. In this work, we used a method named Time-dependent cell responding profile (TCRP) to track the process of mast cell degranulation under various perturbations caused by agents targeting phosphorylation. To test the feasibility of this high-throughput cell-based phenotypic screening method, a variety of biological techniques were used. We further screened 145 inhibitors and clustered them based on the similarities of their TCRPs. Stat3 phosphorylation has been widely reported as a key step in mast cell degranulation. Interestingly, our TCRP results showed that a Stat3 inhibitor JSI124 did not inhibit degranulation like other Stat3 inhibitors, such as Stattic, clearly inhibited degranulation. Regular endpoint assays demonstrated that the distinctive TCRP of JSI124 potentially correlated with the ability to induce apoptosis. Consequently, different agents possibly have disparate functions, which can be conveniently detected by TCRP. From this perspective, our TCRP screening method is reliable and sensitive when it comes to discovering and selecting novel compounds for new drug developments. PMID:27502076

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Prevalence of the American Heart Association's “Ideal Cardiovascular Health” Metrics in a Rural, Cross‐sectional, Community‐Based Study: The Heart of New Ulm Project

    PubMed Central

    Kim, Jacqueline I.; Sillah, Arthur; Boucher, Jackie L.; Sidebottom, Abbey C.; Knickelbine, Thomas

    2013-01-01

    Background The American Heart Association (AHA) recently created the construct of “ideal cardiovascular health” based on 7 cardiovascular health metrics to measure progress toward their 2020 Impact Goal. The present study applied this construct to assess the baseline cardiovascular health of a rural population targeted with a community‐based cardiovascular disease prevention program. Methods and Results The sample consists of 4754 New Ulm, Minn, adult residents who participated in either the 2009 or 2011 community heart health screenings offered by the Hearts Beat Back: The Heart of New Ulm (HONU) Project (mean age 52.1 years, 58.3% women). Data collected at the screenings were analyzed to replicate the AHA's ideal cardiovascular health measure and the 7 metrics that comprise the construct. Screening participants met, on average (±SD), 3.4 (±1.4) ideal cardiovascular health metrics. Only 1.0% of participants met the AHA's definition of ideal health in all metrics and 7.1% met ≤1 ideal health metric. Higher proportions of women met the ideal category in all metrics except physical activity. Women over the age of 60 were less likely to meet the ideal category for cholesterol and hypertension than were men in the same age range. Conclusion Prevalence of ideal cardiovascular health is extremely low in this rural population. To make progress toward the 2020 Impact Goal, targeted community‐based interventions must be implemented based on the most prevalent cardiovascular risk factors. PMID:23619743

  11. Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy

    PubMed Central

    Giandhari, Jennifer; Basson, Adriaan E.; Sutherland, Katherine; Parry, Chris M.; Cane, Patricia A.; Coovadia, Ashraf; Kuhn, Louise; Hunt, Gillian

    2016-01-01

    Protease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV-1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicative in vitro assay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of the gag gene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of

  12. Mitochondria and Cardiovascular Aging

    PubMed Central

    Dai, Dao-Fu; Ungvari, Zoltan

    2013-01-01

    Old age is a major risk factor for cardiovascular diseases. Several lines of evidence in experimental animal models have indicated the central role of mitochondria both in lifespan determination and cardiovascular aging. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and biogenesis as well as the crosstalk between mitochondria and cellular signaling in cardiac and vascular aging. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans (left ventricular hypertrophy, fibrosis and diastolic dysfunction), while the phenotype of vascular aging include endothelial dysfunction, reduced vascular elasticity and chronic vascular inflammation. Both cardiac and vascular aging involve neurohormonal signaling (e.g. renin-angiotensin, adrenergic, insulin-IGF1 signaling) and cell-autonomous mechanisms. The potential therapeutic strategies to improve mitochondrial function in aging and cardiovascular diseases are also discussed, with a focus on mitochondrial-targeted antioxidants, calorie restriction, calorie restriction mimetics and exercise training. PMID:22499901

  13. Cardiovascular Risk Profile at the Onset of Psoriatic Arthritis: a Population-based, Cohort Study

    PubMed Central

    Ernste, F.C.; Sánchez-Menéndez, M.; Wilton, K. M.; Crowson, C.S.; Matteson, E.L.; Kremers, H. Maradit

    2015-01-01

    Objective The role of cardiovascular disease (CVD) risk factors in psoriatic arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk factors at initial onset of PsA and compared the observed incidence of CVD events with that predicted by the Framingham risk score (FRS) to determine its applicability in this patient population. Methods A population-based incidence cohort of 158 patients with PsA who fulfilled ClASsification of Psoriatic ARthritis (CASPAR) criteria for PsA in 1989–2008 was assembled. Medical records were reviewed to ascertain CVD risk factors and CVD events. Future risk of CVD disease was estimated using the FRS algorithm. Results Mean age was 43.4 years (range: 19–74 years), 61% were men and 44% were obese (body mass index ≥30kg/m2). Fifty-four (34%) patients presented with ≥2 CVD risk factors at PsA incidence. Among 126 patients aged ≥ 30 years at PsA incidence with no prior history of CVD, 33% had FRS ≥10% with 11% having FRS ≥ 20% and 18 experienced a CVD event in the first 10 years of disease duration. The 10 year cumulative incidence of CVD events was 17% (95% confidence interval [CI]: 10–24%), almost twice as high as the predicted incidence based on the FRS (Standardized incidence ratio: 1.80; 95% CI: 1.14–2.86; p=0.012). Conclusion The majority of newly diagnosed PsA patients have a >10% risk of CVD disease within 10 years of PsA incidence. The CVD risk in these patients is higher than expected and underestimated by the FRS. PMID:25581120

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

    PubMed

    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.

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

    PubMed

    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.

  16. Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study

    PubMed Central

    Fung, Chunkit; Fossa, Sophie D.; Milano, Michael T.; Sahasrabudhe, Deepak M.; Peterson, Derick R.; Travis, Lois B.

    2015-01-01

    Purpose Increased risks of incident cardiovascular disease (CVD) in patients with testicular cancer (TC) given chemotherapy in European studies were largely restricted to long-term survivors and included patients from the 1960s. Few population-based investigations have quantified CVD mortality during, shortly after, and for two decades after TC diagnosis in the era of cisplatin-based chemotherapy. Patients and Methods Standardized mortality ratios (SMRs) for CVD and absolute excess risks (AERs; number of excess deaths per 10,000 person-years) were calculated for 15,006 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2010) who initially received chemotherapy (n = 6,909) or surgery (n = 8,097) without radiotherapy and accrued 60,065 and 81,227 person-years of follow-up, respectively. Multivariable modeling evaluated effects of age, treatment, extent of disease, and other factors on CVD mortality. Results Significantly increased CVD mortality occurred after chemotherapy (SMR, 1.36; 95% CI, 1.03 to 1.78; n = 54) but not surgery (SMR, 0.81; 95% CI, 0.60 to 1.07; n = 50). Significant excess deaths after chemotherapy were restricted to the first year after TC diagnosis (SMR, 5.31; AER, 13.90; n = 11) and included cerebrovascular disease (SMR, 21.72; AER, 7.43; n = 5) and heart disease (SMR, 3.45; AER, 6.64; n = 6). In multivariable analyses, increased CVD mortality after chemotherapy was confined to the first year after TC diagnosis (hazard ratio, 4.86; 95% CI, 1.25 to 32.08); distant disease (P < .05) and older age at diagnosis (P < .01) were independent risk factors. Conclusion This is the first population-based study, to our knowledge, to quantify short- and long-term CVD mortality after TC diagnosis. The increased short-term risk of CVD deaths should be further explored in analytic studies that enumerate incident events and can serve to develop comprehensive evidence-based approaches

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

    PubMed

    Navarro, Julio C Acosta; Prado, Silvia M Cárdenas; Cárdenas, Pedro Acosta; Santos, Raul D; Caramelli, Bruno

    2010-01-01

    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.

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

    PubMed Central

    Acosta Navarro, Julio C; Cárdenas Prado, Silvia M; Cárdenas, Pedro Acosta; Santos, Raul D; Caramelli, Bruno

    2010-01-01

    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. PMID:21120310

  19. Cardiovascular Drug Discovery: A Perspective from a Research-Based Pharmaceutical Company

    PubMed Central

    Gromo, G.; Mann, J.; Fitzgerald, J.D.

    2014-01-01

    The theme of this review is to summarize the evolving processes in cardiovascular drug discovery and development within a large pharmaceutical company. Emphasis is placed on the contrast between the academic and industrial research operating environments, which can influence the effectiveness of research collaboration between the two constituencies, but which plays such an important role in drug innovation. The strategic challenges that research directors face are also emphasized. The need for improved therapy in many cardiovascular indications remains high, but the feasibility in making progress, despite the advances in molecular biology and genomics, is also assessed. PMID:24890831

  20. Cardiovascular drug discovery: a perspective from a research-based pharmaceutical company.

    PubMed

    Gromo, G; Mann, J; Fitzgerald, J D

    2014-06-02

    The theme of this review is to summarize the evolving processes in cardiovascular drug discovery and development within a large pharmaceutical company. Emphasis is placed on the contrast between the academic and industrial research operating environments, which can influence the effectiveness of research collaboration between the two constituencies, but which plays such an important role in drug innovation. The strategic challenges that research directors face are also emphasized. The need for improved therapy in many cardiovascular indications remains high, but the feasibility in making progress, despite the advances in molecular biology and genomics, is also assessed.

  1. Automatic machine learning based prediction of cardiovascular events in lung cancer screening data

    NASA Astrophysics Data System (ADS)

    de Vos, Bob D.; de Jong, Pim A.; Wolterink, Jelmer M.; Vliegenthart, Rozemarijn; Wielingen, Geoffrey V. F.; Viergever, Max A.; Išgum, Ivana

    2015-03-01

    Calcium burden determined in CT images acquired in lung cancer screening is a strong predictor of cardiovascular events (CVEs). This study investigated whether subjects undergoing such screening who are at risk of a CVE can be identified using automatic image analysis and subject characteristics. Moreover, the study examined whether these individuals can be identified using solely image information, or if a combination of image and subject data is needed. A set of 3559 male subjects undergoing Dutch-Belgian lung cancer screening trial was included. Low-dose non-ECG synchronized chest CT images acquired at baseline were analyzed (1834 scanned in the University Medical Center Groningen, 1725 in the University Medical Center Utrecht). Aortic and coronary calcifications were identified using previously developed automatic algorithms. A set of features describing number, volume and size distribution of the detected calcifications was computed. Age of the participants was extracted from image headers. Features describing participants' smoking status, smoking history and past CVEs were obtained. CVEs that occurred within three years after the imaging were used as outcome. Support vector machine classification was performed employing different feature sets using sets of only image features, or a combination of image and subject related characteristics. Classification based solely on the image features resulted in the area under the ROC curve (Az) of 0.69. A combination of image and subject features resulted in an Az of 0.71. The results demonstrate that subjects undergoing lung cancer screening who are at risk of CVE can be identified using automatic image analysis. Adding subject information slightly improved the performance.

  2. Socioeconomic inequities and cardiovascular disease-related disability in China: A population-based study.

    PubMed

    Wang, Zhenjie; Cao, Chengfu; Guo, Chao; Chen, Gong; Chen, Hong; Zheng, Xiaoying

    2016-08-01

    The prevalence of disability has changed along with aggressive economic development in China. However, socioeconomic inequalities associated with cardiovascular disease (CVD)-related disability have not been explored. This is the first study to explore CVD-related disability among persons aged 45 years and older in China.Data were taken from the 2006 Second China National Sample Survey on Disability, which was a nationally representative, population-based survey. To derive a nationally representative sample, the survey used multistage, stratified, and cluster random sampling with probability proportional to size. We used standard weighting procedures to construct sample weights that considered the multistage, stratified, and cluster sampling survey scheme. Associations between CVD-related disability risk and socioeconomic inequality were examined using logistic regression.In this study, the weighted prevalence of CVD-related disability was 1.84 per 100 persons (95% confidence interval [CI]: 1.80-1.89), and 73% of CVD-related disability consisted of a single disability, including speech, physical, and intellectual disabilities, whereas 23% of CVD-related disability consisted of multiple disabilities, that is, any combination of speech, physical, and intellectual disabilities. A higher risk of CVD-related disability was observed among rural residents than urban residents as well as among males than females. Age presented consistent increased associations with CVD-related disability. Education inequality was strongly associated with the risk of multiple disabilities.To address the challenge of CVD-related disability in China, the government should adjust its strategies for health care systems to prevent disability. The widening discrepancy between urban and rural areas indicates that the most important priorities for disability prevention in China are to reinforce health promotion in the working age population and to improve health services in rural communities. PMID

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

    PubMed Central

    Ricci, Natalia Aquaroni; Pessoa, Germane Silva; Ferriolli, Eduardo; Dias, Rosangela Correa; Perracini, Monica Rodrigues

    2014-01-01

    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 highly prevalent among the total sample. In addition, frail and pre-frail older people corresponded to a substantial proportion of those with more CVD risk factors, especially diabetes mellitus, highlighting the need for preventive strategies in order to avoid the co-occurrence of CVD and frailty. PMID:25336932

  4. Cardiovascular risk prediction: a comparative study of Framingham and quantum neural network based approach

    PubMed Central

    Narain, Renu; Saxena, Sanjai; Goyal, Achal Kumar

    2016-01-01

    Purpose Currently cardiovascular diseases (CVDs) are the main cause of death worldwide. Disease risk estimates can be used as prognostic information and support for treating CVDs. The commonly used Framingham risk score (FRS) for CVD prediction is outdated for the modern population, so FRS may not be accurate enough. In this paper, a novel CVD prediction system based on machine learning is proposed. Methods This study has been conducted with the data of 689 patients showing symptoms of CVD. Furthermore, the dataset of 5,209 CVD patients of the famous Framingham study has been used for validation purposes. Each patient’s parameters have been analyzed by physicians in order to make a diagnosis. The proposed system uses the quantum neural network for machine learning. This system learns and recognizes the pattern of CVD. The proposed system has been experimentally evaluated and compared with FRS. Results During testing, patients’ data in combination with the doctors’ diagnosis (predictions) are used for evaluation and validation. The proposed system achieved 98.57% accuracy in predicting the CVD risk. The CVD risk predictions by the proposed system, using the dataset of the Framingham study, confirmed the potential risk of death, deaths which actually occurred and had been recorded as due to myocardial infarction and coronary heart disease in the dataset of the Framingham study. The accuracy of the proposed system is significantly higher than FRS and other existing approaches. Conclusion The proposed system will serve as an excellent tool for a medical practitioner in predicting the risk of CVD. This system will be serving as an aid to medical practitioners for planning better medication and treatment strategies. An early diagnosis may be effectively made by using this system. An overall accuracy of 98.57% has been achieved in predicting the risk level. The accuracy is considerably higher compared to the other existing approaches. Thus, this system must be used

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

    PubMed Central

    Aljaafareh, Almotasembellah; Valle, Jose Ruben; Lin, Yu-Li; Kuo, Yong-Fang; Sharma, Gulshan

    2016-01-01

    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 prescription were

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

    PubMed

    Ehrenreich, Hannelore; Nave, Klaus-Armin

    2014-01-01

    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-called pro-autistic variants of

  7. Single base substitution in OsCDC48 is responsible for premature senescence and death phenotype in rice

    PubMed Central

    Huang, Qi‐Na; Shi, Yong‐Feng; Zhang, Xiao‐Bo; Song, Li‐Xin; Feng, Bao‐Hua; Wang, Hui‐Mei; Xu, Xia; Li, Xiao‐Hong; Guo, Dan

    2015-01-01

    Abstract A premature senescence and death 128 (psd128) mutant was isolated from an ethyl methane sulfonate‐induced rice IR64 mutant bank. The premature senescence phenotype appeared at the six‐leaf stage and the plant died at the early heading stage. psd128 exhibited impaired chloroplast development with significantly reduced photosynthetic ability, chlorophyll and carotenoid contents, root vigor, soluble protein content and increased malonaldehyde content. Furthermore, the expression of senescence‐related genes was significantly altered in psd128. The mutant trait was controlled by a single recessive nuclear gene. Using map‐based strategy, the mutation Oryza sativa cell division cycle 48 (OsCDC48) was isolated and predicted to encode a putative AAA‐type ATPase with 809 amino‐acid residuals. A single base substitution at position C2347T in psd128 resulted in a premature stop codon. Functional complementation could rescue the mutant phenotype. In addition, RNA interference resulted in the premature senescence and death phenotype. OsCDC48 was expressed constitutively in the root, stem, leaf and panicle. Subcellular analysis indicated that OsCDC48:YFP fusion proteins were located both in the cytoplasm and nucleus. OsCDC48 was highly conserved with more than 90% identity in the protein levels among plant species. Our results indicated that the impaired function of OsCDC48 was responsible for the premature senescence and death phenotype. PMID:26040493

  8. Diabetes and cardiovascular disease: focus on glucagon-like peptide-1 based therapies

    PubMed Central

    Stranges, Paul

    2012-01-01

    Type 2 diabetes is a well known risk factor for cardiovascular disease (CVD). While glycemic control has consistently been shown to prevent microvascular complications, large randomized trials have not demonstrated the same consistent beneficial effects of intensive glycemic control in improving cardiovascular (CV) outcomes. Thus, optimal glucose control alone is not sufficient to reduce CV risk. Aggressive management of CV risk factors such as blood pressure, lipids, and body weight is also necessary. A growing body of evidence suggests that the recently available glucagon-like peptide 1 receptor (GLP-1R) agonists have beneficial CV effects beyond glucose control. Studies have demonstrated beneficial effects in the myocardium, endothelium, vasculature and various markers of cardiovascular risk such as body weight, blood pressure and dyslipidemia. Despite the growing evidence, large, randomized, blinded clinical trials with hard CV endpoints have not been performed. Most human studies have been small, and have focused on surrogate endpoints. The findings need to be confirmed by prospective, randomized cardiovascular outcomes trials. In this review we examine the GLP-1R agonist data on weight reduction, blood pressure lowering, beneficial changes in dyslipidemia, and improvements in myocardial and endothelial function. The safety as well as potential role of these agents in treatment regimens for type 2 diabetes is also addressed. PMID:25083236

  9. Identification of Type 2 Diabetes Risk Factors Using Phenotypes Consisting of Anthropometry and Triglycerides based on Machine Learning.

    PubMed

    Lee, Bum Ju; Kim, Jong Yeol

    2016-01-01

    The hypertriglyceridemic waist (HW) phenotype is strongly associated with type 2 diabetes; however, to date, no study has assessed the predictive power of phenotypes based on individual anthropometric measurements and triglyceride (TG) levels. The aims of the present study were to assess the association between the HW phenotype and type 2 diabetes in Korean adults and to evaluate the predictive power of various phenotypes consisting of combinations of individual anthropometric measurements and TG levels. Between November 2006 and August 2013, 11,937 subjects participated in this retrospective cross-sectional study. We measured fasting plasma glucose and TG levels and performed anthropometric measurements. We employed binary logistic regression (LR) to examine statistically significant differences between normal subjects and those with type 2 diabetes using HW and individual anthropometric measurements. For more reliable prediction results, two machine learning algorithms, naive Bayes (NB) and LR, were used to evaluate the predictive power of various phenotypes. All prediction experiments were performed using a tenfold cross validation method. Among all of the variables, the presence of HW was most strongly associated with type 2 diabetes (p < 0.001, adjusted odds ratio (OR) = 2.07 [95% CI, 1.72-2.49] in men; p < 0.001, adjusted OR = 2.09 [1.79-2.45] in women). When comparing waist circumference (WC) and TG levels as components of the HW phenotype, the association between WC and type 2 diabetes was greater than the association between TG and type 2 diabetes. The phenotypes tended to have higher predictive power in women than in men. Among the phenotypes, the best predictors of type 2 diabetes were waist-to-hip ratio + TG in men (AUC by NB = 0.653, AUC by LR = 0.661) and rib-to-hip ratio + TG in women (AUC by NB = 0.73, AUC by LR = 0.735). Although the presence of HW demonstrated the strongest association with type 2 diabetes, the predictive power of the combined

  10. Identification of Type 2 Diabetes Risk Factors Using Phenotypes Consisting of Anthropometry and Triglycerides based on Machine Learning.

    PubMed

    Lee, Bum Ju; Kim, Jong Yeol

    2016-01-01

    The hypertriglyceridemic waist (HW) phenotype is strongly associated with type 2 diabetes; however, to date, no study has assessed the predictive power of phenotypes based on individual anthropometric measurements and triglyceride (TG) levels. The aims of the present study were to assess the association between the HW phenotype and type 2 diabetes in Korean adults and to evaluate the predictive power of various phenotypes consisting of combinations of individual anthropometric measurements and TG levels. Between November 2006 and August 2013, 11,937 subjects participated in this retrospective cross-sectional study. We measured fasting plasma glucose and TG levels and performed anthropometric measurements. We employed binary logistic regression (LR) to examine statistically significant differences between normal subjects and those with type 2 diabetes using HW and individual anthropometric measurements. For more reliable prediction results, two machine learning algorithms, naive Bayes (NB) and LR, were used to evaluate the predictive power of various phenotypes. All prediction experiments were performed using a tenfold cross validation method. Among all of the variables, the presence of HW was most strongly associated with type 2 diabetes (p < 0.001, adjusted odds ratio (OR) = 2.07 [95% CI, 1.72-2.49] in men; p < 0.001, adjusted OR = 2.09 [1.79-2.45] in women). When comparing waist circumference (WC) and TG levels as components of the HW phenotype, the association between WC and type 2 diabetes was greater than the association between TG and type 2 diabetes. The phenotypes tended to have higher predictive power in women than in men. Among the phenotypes, the best predictors of type 2 diabetes were waist-to-hip ratio + TG in men (AUC by NB = 0.653, AUC by LR = 0.661) and rib-to-hip ratio + TG in women (AUC by NB = 0.73, AUC by LR = 0.735). Although the presence of HW demonstrated the strongest association with type 2 diabetes, the predictive power of the combined

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

    PubMed Central

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

    2015-01-01

    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-term effect

  12. Proteomic-Based Detection of a Protein Cluster Dysregulated during Cardiovascular Development Identifies Biomarkers of Congenital Heart Defects

    PubMed Central

    Nath, Anjali K.; Krauthammer, Michael; Li, Puyao; Davidov, Eugene; Butler, Lucas C.; Copel, Joshua; Katajamaa, Mikko; Oresic, Matej; Buhimschi, Irina; Buhimschi, Catalin; Snyder, Michael; Madri, Joseph A.

    2009-01-01

    Background Cardiovascular development is vital for embryonic survival and growth. Early gestation embryo loss or malformation has been linked to yolk sac vasculopathy and congenital heart defects (CHDs). However, the molecular pathways that underlie these structural defects in humans remain largely unknown hindering the development of molecular-based diagnostic tools and novel therapies. Methodology/Principal Findings Murine embryos were exposed to high glucose, a condition known to induce cardiovascular defects in both animal models and humans. We further employed a mass spectrometry-based proteomics approach to identify proteins differentially expressed in embryos with defects from those with normal cardiovascular development. The proteins detected by mass spectrometry (WNT16, ST14, Pcsk1, Jumonji, Morca2a, TRPC5, and others) were validated by Western blotting and immunoflorescent staining of the yolk sac and heart. The proteins within the proteomic dataset clustered to adhesion/migration, differentiation, transport, and insulin signaling pathways. A functional role for several proteins (WNT16, ADAM15 and NOGO-A/B) was demonstrated in an ex vivo model of heart development. Additionally, a successful application of a cluster of protein biomarkers (WNT16, ST14 and Pcsk1) as a prenatal screen for CHDs was confirmed in a study of human amniotic fluid (AF) samples from women carrying normal fetuses and those with CHDs. Conclusions/Significance The novel finding that WNT16, ST14 and Pcsk1 protein levels increase in fetuses with CHDs suggests that these proteins may play a role in the etiology of human CHDs. The information gained through this bed-side to bench translational approach contributes to a more complete understanding of the protein pathways dysregulated during cardiovascular development and provides novel avenues for diagnostic and therapeutic interventions, beneficial to fetuses at risk for CHDs. PMID:19156209

  13. Community-based lifestyle modification of cardiovascular disease risks in middle-aged Japanese: a 27-month update.

    PubMed

    Fujii, Hiroko; Muto, Takashi; Haruyama, Yasuo; Nakade, Makiko; Kobayashi, Emiko; Ishisaki, Kaori; Yamasaki, Akiko

    2010-04-01

    Lifestyle modification is the cornerstone of preventive management for people with cardiovascular disease risks, such as obesity, hypertension, dyslipidemia and diabetes. This study investigated the effect of a 27-month community-based lifestyle intervention on the reduction of cardiovascular disease risks in middle-aged Japanese. Of 549 participants with cardiovascular disease risk factors of overweight, hypertension, dyslipidemia or diabetes enrolled in this non-randomized controlled study, 397 participants aged 39-71 years old completed all 3 serial surveys at baseline, 15 months and 27 months. For the intervention group (39 males and 174 females), 31 specific interventions including individual counselling and group sessions were conducted. The control group (64 males and 120 females) only received 7 newsletters providing health information and results of health checkups. Multiple logistic regression analysis adjusted for sex, each baseline risk category and age category showed that the proportion of those who were overweight or showed dyslipidemia risk were significantly lower in the intervention group only at 27 months [Odds ratio (OR): 0.43 (95% CI 0.20-0.94), OR: 0.43 (95% CI 0.21-0.87), respectively] and the proportion of those showing diabetes risk was significantly lower in the intervention group at both 15 months [OR: 0.42 (95% CI 0.18-0.97)] and 27 months [OR: 0.56 (95% CI 0.32-0.99)]. In conclusion, the 27-month community-based lifestyle modification of cardiovascular disease risks shows significant reductions in risks of diabetes, overweight and dyslipidemia in middle-aged Japanese.

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

    PubMed

    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 < 0.01). The coronary artery disease incidence in the 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 < 0.01). Over the stratified follow-up years, adjusted HRs were 1.22 (95% CI = 1.12-1.34) for arrhythmia and 1.14 (95% CI = 1.02-1.28) for coronary artery disease within 2 years after 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.

  15. Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study

    PubMed Central

    Gudbjörnsdottir, Soffia; Manhem, Karin; Rosengren, Annika; Svensson, Ann-Marie; Miftaraj, Mervete; Franzén, Stefan; Björck, Staffan

    2016-01-01

    Objectives To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Design Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. Setting 861 Swedish primary care units and hospital outpatient clinics. Participants 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Main outcome measures Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. Results The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Conclusions Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low

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

    PubMed

    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. PMID:27312886

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

    PubMed

    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.

  18. ZHENG May Contribute to Obesity Phenotypes Based on Body Composition: A Pilot Study on the Traditional Chinese Medicine Approach

    PubMed Central

    Tao, Feng; Lu, Hao; Oppert, Jean-Michel

    2014-01-01

    Objective. Obesity therapy needs new approaches to complement current phenotyping systems. This study aims to assess associations between the Traditional Chinese Medicine (TCM) ZHENG and obesity phenotypes. Methods. We assessed medical history and habitual physical activity and measured body composition, fasting plasma glucose and insulin, and lipids. We collected TCM data through face-to-face interview. ZHENG elements (essentials and locations) were identified by TCM practitioner. Primary ZHENG was assessed by cluster analysis. Results. In 140 consecutive subjects enrolled in a university clinic (body mass index (BMI): 39.9 ± 5.8 kg/m2), ZHENG essentials were identified as “QiXu,” “Re,” “YinXu,” and “TanShi” (totally 86.8%). Locations were “Shen,” “Wei,” “Pi,” and “Gan” (totally 91.8%). Four types of primary ZHENG were identified: A (37.1% of subjects), B (16.5%), C (35.7%), and D (10.7%). Subjects in type D showed elevated BMI, total fat mass (FM), FM index, trunk FM, and less physical activity, as compared with others. Subjects in type B changed regional body composition (reduced trunk FM% and elevated appendicular FM%). Biological parameters did not differ across primary ZHENG clusters. Conclusions. Obesity phenotypes based on body composition differ according to ZHENG in obese patients. This study is a first step toward understanding the contribution of TCM to obesity phenotyping. PMID:24711854

  19. Nanopatterned Human iPSC-based Model of a Dystrophin-Null Cardiomyopathic Phenotype

    PubMed Central

    Macadangdang, Jesse; Guan, Xuan; Smith, Alec S.T.; Lucero, Rachel; Czerniecki, Stefan; Childers, Martin K.; Mack, David L.; Kim, Deok-Ho

    2015-01-01

    Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro. PMID:26366230

  20. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma

    PubMed Central

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L.; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

  1. Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma.

    PubMed

    Zhu, Yitan; Li, Hui; Guo, Wentian; Drukker, Karen; Lan, Li; Giger, Maryellen L; Ji, Yuan

    2015-01-01

    Magnetic Resonance Imaging (MRI) has been routinely used for the diagnosis and treatment of breast cancer. However, the relationship between the MRI tumor phenotypes and the underlying genetic mechanisms remains under-explored. We integrated multi-omics molecular data from The Cancer Genome Atlas (TCGA) with MRI data from The Cancer Imaging Archive (TCIA) for 91 breast invasive carcinomas. Quantitative MRI phenotypes of tumors (such as tumor size, shape, margin, and blood flow kinetics) were associated with their corresponding molecular profiles (including DNA mutation, miRNA expression, protein expression, pathway gene expression and copy number variation). We found that transcriptional activities of various genetic pathways were positively associated with tumor size, blurred tumor margin, and irregular tumor shape and that miRNA expressions were associated with the tumor size and enhancement texture, but not with other types of radiomic phenotypes. We provide all the association findings as a resource for the research community (available at http://compgenome.org/Radiogenomics/). These findings pave potential paths for the discovery of genetic mechanisms regulating specific tumor phenotypes and for improving MRI techniques as potential non-invasive approaches to probe the cancer molecular status. PMID:26639025

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. Risk of Major Cardiovascular Events in Patients with Psoriatic Arthritis, Psoriasis and Rheumatoid Arthritis: A population-based cohort study

    PubMed Central

    Yu, YiDing; Haynes, Kevin; Love, Thorvardur Jon; Maliha, Samantha; Jiang, Yihui; Troxel, Andrea B.; Hennessy, Sean; Kimmel, Stephen E.; Margolis, David J.; Choi, Hyon; Mehta, Nehal N.; Gelfand, Joel M.

    2015-01-01

    Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and psoriasis without known PsA compared to the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994–2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the United Kingdom. Patients aged 18–89 with PsA, RA, or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents, and the composite outcome (MACE). Cox proportional hazards models were used to calculate the hazard ratios (HR) for each outcome adjusted for traditional risk factors. A priori we hypothesized an interaction between disease status and disease modifying anti-rheumatic drug (DMARD) use. Results Patients with PsA (N=8,706), RA (N=41,752), psoriasis (N=138,424) and unexposed controls (N=81,573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in PsA patients not prescribed a DMARD (HR 1.24, 95%CI: 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95%CI: 1.28 to 1.50, DMARD: HR 1.58, 95%CI: 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95%CI: 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95%CI: 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, psoriatic arthritis or rheumatoid arthritis. PMID:25351522

  4. Cardiovascular Comorbidities in Patients with Psoriasis: Risk Profile Including Carotide Ultrasonography Assessed in Hospital-based Case Control Study.

    PubMed

    Votrubova, Jana; Juzlova, Katerina; Dzambova, Martina; Hercogova, Jana; Gopfertova, Dana

    2016-08-01

    Psoriasis is a chronic inflammatory disease, and its comorbidities have attracted serious interest in recent years. The evidence that psoriasis is associated with systemic inflammation and significantly higher incidence of cardiovascular risk factors has already been described. The results of published studies are highly variable, the conclusions are ambiguous, and further epidemiological studies are needed for validation of published data. Therefore, we initiated a project aimed at identifying the association with cardiovascular risk factors, including early stages of atherosclerosis, that represent important comorbidities in patients with psoriasis. We carried out a hospital-based case-control study on 189 patients with chronic plaque psoriasis enrolled as cases. The control group consisted of 378 patients with other skin diseases complying with the same exclusion criteria who were recruited to the study as the controls. All participants underwent physical examination, blood tests, and measuring of blood pressure and waist circumference. Furthermore, we evaluated carotid intima-media thickness (CIMT) in a subset of 117 cases and controls (matched 1:2) with no history of cardiovascular disease. The results showed higher prevalence of hypertension, hyperlipidemia, waist circumference, weight, body-mass index (BMI), and C-reactive protein (CRP) level in patients with psoriasis than in controls. These parameters have been clearly demonstrated to be risk factors for the development of cardiovascular diseases. The associations between psoriasis and diastolic blood pressure, BMI value, and low-density lipoprotein (LDL) cholesterol were statistically significant in the binary data logistic model as well. CIMT was not significantly higher in patients compared with controls. PMID:27663919

  5. Visual Exploration of Genetic Association with Voxel-based Imaging Phenotypes in an MCI/AD Study

    PubMed Central

    Kim, Sungeun; Shen, Li; Saykin, Andrew J.; West, John D.

    2010-01-01

    Neuroimaging genomics is a new transdisciplinary research field, which aims to examine genetic effects on brain via integrated analyses of high throughput neuroimaging and genomic data. We report our recent work on (1) developing an imaging genomic browsing system that allows for whole genome and entire brain analyses based on visual exploration and (2) applying the system to the imaging genomic analysis of an existing MCI/AD cohort. Voxel-based morphometry is used to define imaging phenotypes. ANCOVA is employed to evaluate the effect of the interaction of genotypes and diagnosis in relation to imaging phenotypes while controlling for relevant covariates. Encouraging experimental results suggest that the proposed system has substantial potential for enabling discovery of imaging genomic associations through visual evaluation and for localizing candidate imaging regions and genomic regions for refined statistical modeling. PMID:19963597

  6. Cardiovascular Disease

    PubMed Central

    Grace, Sherry L; Fry, Rick; Cheung, Angela; Stewart, Donna E

    2004-01-01

    Health Issue Cardiovascular disease (CVD) is the leading cause of death in Canadian women and men. In general, women present with a wider range of symptoms, are more likely to delay seeking medial care and are less likely to be investigated and treated with evidence-based medications, angioplasty or coronary artery bypass graft than men. Key Findings In 1998, 78,964 Canadians died from CVD, almost half (39,197) were women. Acute myocardial infarction, which increases significantly after menopause, was the leading cause of death among women. Cardiovascular disease accounted for 21% of all hospital admissions for Canadian women over age 50 in 1999. Admissions to hospital for ischemic heart disease were more frequent for men, but the mean length of hospital stay was longer for women. Mean blood pressure increases with age in both men and women. After age 65, however, high blood pressure is more common among Canadian women. More than one-third of postmenopausal Canadian women have hypertension. Diabetes increases the mortality and morbidity associated with CVD in women more than it does in men. Depression also contributes to the incidence and recovery from CVD, particularly for women who experience twice the rate of depression as men. Data Gaps and Recommendations CVD needs to be recognized as a woman's health issue given Canadian mortality projections (particularly heart failure). Health professionals should be trained to screen, track, and address CVD risk factors among women, including hypertension, elevated lipid levels, smoking, physical inactivity, depression, diabetes and low socio-economic status. PMID:15345078

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

    PubMed Central

    Ashfaq, Tabinda

    2013-01-01

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

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

    PubMed

    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. A 'green' diet-based approach to cardiovascular health? Is inorganic nitrate the answer?

    PubMed

    Rathod, Krishnaraj Sinhji; Velmurugan, Shanti; Ahluwalia, Amrita

    2016-01-01

    Ingestion of fruit and vegetables rich in inorganic nitrate (NO(3)(-)) has emerged as an effective method for acutely elevating vascular nitric oxide (NO) levels through formation of an NO(2)(-) intermediate. As such a number of beneficial effects of NO(3)(-) and NO(2)(-) ingestion have been demonstrated including reductions in blood pressure, measures of arterial stiffness and platelet activity. The pathway for NO generation from such dietary interventions involves the activity of facultative oral microflora that facilitate the reduction of inorganic NO(3)(-), ingested in the diet, to inorganic NO(2)(-). This NO(2)(-) then eventually enters the circulation where, through the activity of one or more of a range of distinct NO(2)(-) reductases, it is chemically reduced to NO. This pathway provides an alternative route for in vivo NO generation that could be utilized for therapeutic benefit in those cardiovascular disease states where reduced bioavailable NO is thought to contribute to pathogenesis. Indeed, the cardiovascular benefits of NO(2)(-) and NO(3)(-) are now starting to be translated in patients in several clinical trials. In this review, we discuss recent evidence supporting the potential utility of delivery of NO(3)(-) or NO(2)(-) for the treatment of cardiovascular diseases.

  10. 5 Long-term acromegaly and associated cardiovascular complications: a case-based review.

    PubMed

    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.

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

    PubMed

    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. PMID:26630919

  12. Use of a Four-Tiered Graph to Parse the Factors Leading to Phenotypic Clustering in Bacteria: A Case Study Based on Samples from the Aletsch Glacier

    PubMed Central

    Rossetti, Valentina; Bagheri, Homayoun C.

    2013-01-01

    An understanding of bacterial diversity and evolution in any environment requires knowledge of phenotypic diversity. In this study, the underlying factors leading to phenotypic clustering were analyzed and interpreted using a novel approach based on a four-tiered graph. Bacterial isolates were organized into equivalence classes based on their phenotypic profile. Likewise, phenotypes were organized in equivalence classes based on the bacteria that manifest them. The linking of these equivalence classes in a four-tiered graph allowed for a quick visual identification of the phenotypic measurements leading to the clustering patterns deduced from principal component analyses. For evaluation of the method, we investigated phenotypic variation in enzyme production and carbon assimilation of members of the genera Pseudomonas and Serratia, isolated from the Aletsch Glacier in Switzerland. The analysis indicates that the genera isolated produce at least six common enzymes and can exploit a wide range of carbon resources, though some specialist species within the pseudomonads were also observed. We further found that pairwise distances between enzyme profiles strongly correlate with distances based on carbon profiles. However, phenotypic distances weakly correlate with phylogenetic distances. The method developed in this study facilitates a more comprehensive understanding of phenotypic clustering than what would be deduced from principal component analysis alone. PMID:23741454

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

    PubMed

    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. PMID:27321816

  14. Multi-parametric profiling network based on gene expression and phenotype data: a novel approach to developmental neurotoxicity testing.

    PubMed

    Nagano, Reiko; Akanuma, Hiromi; Qin, Xian-Yang; Imanishi, Satoshi; Toyoshiba, Hiroyoshi; Yoshinaga, Jun; Ohsako, Seiichiroh; Sone, Hideko

    2012-01-01

    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. PMID:22312247

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

    PubMed

    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.

  16. Introduction: Cardiovascular physics

    NASA Astrophysics Data System (ADS)

    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.

  17. Clinical Phenotype Classifications Based on Static Varus Alignment and Varus Thrust in Japanese Patients With Medial Knee Osteoarthritis

    PubMed Central

    Iijima, Hirotaka; Fukutani, Naoto; Fukumoto, Takahiko; Uritani, Daisuke; Kaneda, Eishi; Ota, Kazuo; Kuroki, Hiroshi; Matsuda, Shuichi

    2015-01-01

    Objective To investigate the association between knee pain during gait and 4 clinical phenotypes based on static varus alignment and varus thrust in patients with medial knee osteoarthritis (OA). Methods Patients in an orthopedic clinic (n = 266) diagnosed as having knee OA (Kellgren/Lawrence [K/L] grade ≥1) were divided into 4 phenotype groups according to the presence or absence of static varus alignment and varus thrust (dynamic varus): no varus (n = 173), dynamic varus (n = 17), static varus (n = 50), and static varus + dynamic varus (n = 26). The knee range of motion, spatiotemporal gait parameters, visual analog scale scores for knee pain, and scores on the Japanese Knee Osteoarthritis Measure were used to assess clinical outcomes. Multiple logistic regression analyses identified the relationship between knee pain during gait and the 4 phenotypes, adjusted for possible risk factors, including age, sex, body mass index, K/L grade, and gait velocity. Results Multiple logistic regression analysis showed that varus thrust without varus alignment was associated with knee pain during gait (odds ratio [OR] 3.30, 95% confidence interval [95% CI] 1.08–12.4), and that varus thrust combined with varus alignment was strongly associated with knee pain during gait (OR 17.1, 95% CI 3.19–320.0). Sensitivity analyses applying alternative cutoff values for defining static varus alignment showed comparable results. Conclusion Varus thrust with or without static varus alignment was associated with the occurrence of knee pain during gait. Tailored interventions based on individual malalignment phenotypes may improve clinical outcomes in patients with knee OA. PMID:26017348

  18. AIMAR survey on COPD phenotypes

    PubMed Central

    2014-01-01

    phenotype of emphysema. A medical history of exacerbations and the extent of deterioration of the spirometry parameters were considered to be the major indicators for COPD severity and clinical risk. In managing the frequent exacerbator phenotype, the therapeutic objectives – both for GPs and for specialists – included reducing airway inflammation, improving bronchial dilation, and reducing pulmonary hyperinflation. For this type of patients at high clinical risk, specialists selected a first-line therapeutic option based on a predetermined combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist bronchodilator (LABA) and a second-line three-drug therapy (combination of ICS and two long-acting bronchodilators), while GPs’ choices are more diversified, without a clear-cut prevalence of one type of treatment. In patients with COPD and concomitant cardiovascular diseases, frequently observed in clinical practice by all physicians, the combination of ICS and LABA was considered the first-choice option by the highest proportion of GPs (43%) and specialists (37%), while a smaller number of specialists (35%) opted for the long acting muscarinic antagonists (LAMA). Both GPs and specialists believe that therapeutic continuity is of primary importance for the achievement of clinical outcomes with all classes of drugs. Conclusions A good knowledge of COPD has been observed in a high percentage of GPs, indicating an increased awareness of this disease in Primary Health Care. The frequent exacerbator phenotype is viewed by all physicians as the most prevalent in clinical practice, bearing a high risk of hospitalization. For specialists, therapeutic measures aimed at reducing the number and severity of exacerbations are primarily based on the combination of inhaled corticosteroid and bronchodilator, presumably because of the complementary pharmacological action of its components, whereas while GPs’ choices tend to be more diversified. Adherence to medication

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

    PubMed

    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. Primary and Secondary Prevention of Cardiovascular Diseases: A Practical Evidence-Based Approach

    PubMed Central

    O'Keefe, James H.; Carter, Maia D.; Lavie, Carl J.

    2009-01-01

    Despite the fact that we possess highly effective tools for the primary and secondary prevention of myocardial infarction and other complications of atherosclerosis, coronary heart disease remains the most common cause of death in our society. Arterial inflammation and endothelial dysfunction play central roles in the pathogenesis of atherosclerosis and adverse cardiovascular (CV) events. Therapeutic lifestyle changes in conjunction with an aggressive multidrug regimen targeted toward the normalization of the major CV risk factors will neutralize the atherogenic milieu, reduce vascular inflammation, and markedly decrease the risk of adverse CV events and need for revascularization procedures. Specific CV risk factors and optimal therapies for primary and secondary prevention are discussed. PMID:19648392

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

    PubMed Central

    Hastie, David I.; Zeller, Tanja; Liquet, Benoit; Newcombe, Paul; Yengo, Loic; Wild, Philipp S.; Schillert, Arne; Ziegler, Andreas; Nielsen, Sune F.; Butterworth, Adam S.; Ho, Weang Kee; Castagné, Raphaële; Munzel, Thomas; Tregouet, David; Falchi, Mario; Cambien, François; Nordestgaard, Børge G.; Fumeron, Fredéric; Tybjærg-Hansen, Anne; Froguel, Philippe; Danesh, John; Petretto, Enrico; Blankenberg, Stefan; Tiret, Laurence; Richardson, Sylvia

    2013-01-01

    Genome-wide association studies (GWAS) yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-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 associated variants. This

  2. Genetic differences based on a beef terminal index are reflected in future phenotypic performance differences in commercial beef cattle.

    PubMed

    Connolly, S M; Cromie, A R; Berry, D P

    2016-05-01

    The increased demand for animal-derived protein and energy for human consumption will have to be achieved through a combination of improved animal genetic merit and better management strategies. The objective of the present study was to quantify whether differences in genetic merit among animals materialised into phenotypic differences in commercial herds. Carcass phenotypes on 156 864 animals from 7301 finishing herds were used, which included carcass weight (kg), carcass conformation score (scale 1 to 15), carcass fat score (scale 1 to 15) at slaughter as well as carcass price. The price per kilogram and the total carcass value that the producer received for the animal at slaughter was also used. A terminal index, calculated in the national genetic evaluations, was obtained for each animal. The index was based on pedigree index for calving performance, feed intake and carcass traits from the national genetic evaluations. Animals were categorised into four terminal index groups on the basis of genetic merit estimates that were derived before the expression of the phenotypic information by the validation animals. The association between terminal index and phenotypic performance at slaughter was undertaken using mixed models; whether the association differed by gender (i.e. young bulls, steers and heifers) or by early life experiences (animals born in a dairy herd or beef herd) was also investigated. The regression coefficient of phenotypic carcass weight, carcass conformation and carcass fat on their respective estimated breeding values (EBVs) was 0.92 kg, 1.08 units and 0.79 units, respectively, which is close to the expectation of one. Relative to animals in the lowest genetic merit group, animals in the highest genetic merit group had, on average, a 38.7 kg heavier carcass, with 2.21 units greater carcass conformation, and 0.82 units less fat. The superior genetic merit animals were, on average, slaughtered 6 days younger than their inferior genetic merit

  3. Genetic differences based on a beef terminal index are reflected in future phenotypic performance differences in commercial beef cattle.

    PubMed

    Connolly, S M; Cromie, A R; Berry, D P

    2016-05-01

    The increased demand for animal-derived protein and energy for human consumption will have to be achieved through a combination of improved animal genetic merit and better management strategies. The objective of the present study was to quantify whether differences in genetic merit among animals materialised into phenotypic differences in commercial herds. Carcass phenotypes on 156 864 animals from 7301 finishing herds were used, which included carcass weight (kg), carcass conformation score (scale 1 to 15), carcass fat score (scale 1 to 15) at slaughter as well as carcass price. The price per kilogram and the total carcass value that the producer received for the animal at slaughter was also used. A terminal index, calculated in the national genetic evaluations, was obtained for each animal. The index was based on pedigree index for calving performance, feed intake and carcass traits from the national genetic evaluations. Animals were categorised into four terminal index groups on the basis of genetic merit estimates that were derived before the expression of the phenotypic information by the validation animals. The association between terminal index and phenotypic performance at slaughter was undertaken using mixed models; whether the association differed by gender (i.e. young bulls, steers and heifers) or by early life experiences (animals born in a dairy herd or beef herd) was also investigated. The regression coefficient of phenotypic carcass weight, carcass conformation and carcass fat on their respective estimated breeding values (EBVs) was 0.92 kg, 1.08 units and 0.79 units, respectively, which is close to the expectation of one. Relative to animals in the lowest genetic merit group, animals in the highest genetic merit group had, on average, a 38.7 kg heavier carcass, with 2.21 units greater carcass conformation, and 0.82 units less fat. The superior genetic merit animals were, on average, slaughtered 6 days younger than their inferior genetic merit

  4. Hypertriglyceridemic waist phenotype and associated lifestyle factors in a national population of youths: CASPIAN Study.

    PubMed

    Alavian, Seyed-Moayed; Motlagh, Mohammad Esmaeil; Ardalan, Gelayol; Motaghian, Molouk; Davarpanah, Amir Hossein; Kelishadi, Roya

    2008-06-01

    The objectives of the current study, that is the first of its kind, were to determine the prevalence of the hypertriglyceridemic waist (HW) phenotype in a nationally representative sample of children, as well as the metabolic risk factors identified by HW, and to identify lifestyle habits related to this phenotype. This national survey was conducted on 4811 representative school-students. We assessed the sensitivity and specificity of the HW phenotype for abnormal anthropometric and biochemical factors by using receiver operator characteristic curves. We determined the association of dietary patterns (obtained by factor analysis), physical activity level and some environmental factors with the HW phenotype. Overall, 8.52% of participants had the HW phenotype. Those children with the HW phenotype were more likely to have cardiovascular risk factors, notably for overweight and hypercholesterolemia. The dietary pattern characterized by junk foods increased the odds of having the HW phenotype, OR = 1.426 (95%CI, 1.109, 1.892), whereas the other dietary pattern including healthy foods decreased this odds, OR = 0.874 (95%CI, 0.765, 0.998). The risk of the HW phenotype rose with the consumption of solid hydrogenated fat as well as white-flour bread. Low education of parents and a positive family history of diabetes mellitus, obesity and or premature cardiovascular disease were the other risk factors for the HW phenotype. Low levels of physical activity significantly increased the risk of having the HW phenotype. The HW phenotype can be used as an accurate and easy tool for screening children at metabolic risk in population-based studies.

  5. Target Identification of Compounds from a Cell Viability Phenotypic Screen Using a Bead/Lysate-Based Affinity Capture Platform.

    PubMed

    Tang, Hua; Duggan, Shannon; Richardson, Paul L; Marin, Violeta; Warder, Scott E; McLoughlin, Shaun M

    2016-02-01

    The pharmaceutical industry has been continually challenged by dwindling target diversity. To obviate this trend, phenotypic screens have been adopted, complementing target-centric screening approaches. Phenotypic screens identify drug leads using clinically relevant and translatable mechanisms, remaining agnostic to targets. While target anonymity is advantageous early in the drug discovery process, it poses challenges to hit progression, including the development of backup series, retaining desired pharmacology during optimization, discovery of markers, and understanding mechanism-driven toxicity. Consequently, significant effort has been expended to elaborate the targets and mechanisms at work for promising screening hits. Affinity capture is commonly leveraged, where the compounds are linked to beads and targets are abstracted from cell homogenates. This technique has proven effective for identifying targets of kinase, PARP, and HDAC inhibitors, and examples of new targets have been reported. Herein, a three-pronged approach to target deconvolution by affinity capture is described, including the implementation of a uniqueness index that helps discriminate between bona fide targets and background. The effectiveness of this approach is demonstrated using characterized compounds that act on known and noncanonical target classes. The platform is subsequently applied to phenotypic screening hits, identifying candidate targets. The success rate of bead-based affinity capture is discussed.

  6. Simulating Brain Tumor Heterogeneity with a Multiscale Agent-Based Model: Linking Molecular Signatures, Phenotypes and Expansion Rate

    PubMed Central

    Zhang, Le; Strouthos, Costas G.; Wang, Zhihui; Deisboeck, Thomas S.

    2008-01-01

    We have extended our previously developed 3D multi-scale agent-based brain tumor model to simulate cancer heterogeneity and to analyze its impact across the scales of interest. While our algorithm continues to employ an epidermal growth factor receptor (EGFR) gene-protein interaction network to determine the cells’ phenotype, it now adds an implicit treatment of tumor cell adhesion related to the model’s biochemical microenvironment. We simulate a simplified tumor progression pathway that leads to the emergence of five distinct glioma cell clones with different EGFR density and cell ‘search precisions’. The in silico results show that microscopic tumor heterogeneity can impact the tumor system’s multicellular growth patterns. Our findings further confirm that EGFR density results in the more aggressive clonal populations switching earlier from proliferation-dominated to a more migratory phenotype. Moreover, analyzing the dynamic molecular profile that triggers the phenotypic switch between proliferation and migration, our in silico oncogenomics data display spatial and temporal diversity in documenting the regional impact of tumorigenesis, and thus support the added value of multi-site and repeated assessments in vitro and in vivo. Potential implications from this in silico work for experimental and computational studies are discussed. PMID:20047002

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

    PubMed

    Ceriello, Antonio; Gallo, Marco; Candido, Riccardo; De Micheli, Alberto; Esposito, Katherine; Gentile, Sandro; Medea, Gerardo

    2014-01-01

    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/m(2) or ≥30 kg/m(2)), 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 treatment is related to the identified phenotype. With one exception, these algorithms contain a stepwise approach for patients with type 2 diabetes who are metformin-intolerant. The glycemic targets (HbA1c, fasting/preprandial and postprandial glycemia) are also personalized. This accessible and easy to use algorithm may help physicians to choose a personalized treatment plan for each patient and to optimize it in a timely manner, thereby lessening clinical inertia. PMID:24971031

  8. [Cardiovascular prevention - 2016].

    PubMed

    Vértes, András; Szabados, Eszter

    2016-09-01

    Cardiovascular diseases are the main causes of premature death worldwide despite the fact that cardiovascular mortality decreased significantly in the last few decades in financially developed countries. This reduction is partly due to the modern medical and revascularisation treatments, and partly because of the effectiveness of prevention strategies such as lowering blood pressure and cholesterol level, as well as successful strategies against smoking. However, this positive trend is undermined by the striking growth in obesity and in type 2 diabetes mellitus, which could also be successfully controlled by lifestyle changes. This summary is based on an overview of the recent (2016) European Guideline for the Prevention of Cardiovascular Diseases. Here the authors describe preventive strategies and goals to be achieved, the most important lifestyle suggestions, and the secondary prevention medical treatment for patients with already established cardiovascular disease. Orv. Hetil., 2016, 157(38), 1526-1531. PMID:27640620

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

    PubMed

    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.

  10. Web-Based Interventions Targeting Cardiovascular Risk Factors in Middle-Aged and Older People: A Systematic Review and Meta-Analysis

    PubMed Central

    Beishuizen, Cathrien RL; Stephan, Blossom CM; van Gool, Willem A; Brayne, Carol; Peters, Ron JG; Andrieu, Sandrine; Kivipelto, Miia; Soininen, Hilkka; Busschers, Wim B; Moll van Charante, Eric P

    2016-01-01

    Background Web-based interventions can improve single cardiovascular risk factors in adult populations. In view of global aging and the associated increasing burden of cardiovascular disease, older people form an important target population as well. Objective In this systematic review and meta-analysis, we evaluated whether Web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people. Methods Embase, Medline, Cochrane and CINAHL were systematically searched from January 1995 to November 2014. Search terms included cardiovascular risk factors and diseases (specified), Web-based interventions (and synonyms) and randomized controlled trial. Two authors independently performed study selection, data-extraction and risk of bias assessment. In a meta-analysis, outcomes regarding treatment effects on cardiovascular risk factors (blood pressure, glycated hemoglobin A1c (HbA1C), low-density lipoprotein (LDL) cholesterol, smoking status, weight and physical inactivity) and incident cardiovascular disease were pooled with random effects models. Results A total of 57 studies (N=19,862) fulfilled eligibility criteria and 47 studies contributed to the meta-analysis. A significant reduction in systolic blood pressure (mean difference –2.66 mmHg, 95% CI –3.81 to –1.52), diastolic blood pressure (mean difference –1.26 mmHg, 95% CI –1.92 to –0.60), HbA1c level (mean difference –0.13%, 95% CI –0.22 to –0.05), LDL cholesterol level (mean difference –2.18 mg/dL, 95% CI –3.96 to –0.41), weight (mean difference –1.34 kg, 95% CI –1.91 to –0.77), and an increase of physical activity (standardized mean difference 0.25, 95% CI 0.10-0.39) in the Web-based intervention group was found. The observed effects were more pronounced in studies with short (<12 months) follow-up and studies that combined the Internet application with human support (blended care). No difference in incident cardiovascular disease

  11. Patient reactions to a web-based cardiovascular risk calculator in type 2 diabetes: a qualitative study in primary care

    PubMed Central

    Nolan, Tom; Dack, Charlotte; Pal, Kingshuk; Ross, Jamie; Stevenson, Fiona A; Peacock, Richard; Pearson, Mike; Spiegelhalter, David; Sweeting, Michael; Murray, Elizabeth

    2015-01-01

    Background Use of risk calculators for specific diseases is increasing, with an underlying assumption that they promote risk reduction as users become better informed and motivated to take preventive action. Empirical data to support this are, however, sparse and contradictory. Aim To explore user reactions to a cardiovascular risk calculator for people with type 2 diabetes. Objectives were to identify cognitive and emotional reactions to the presentation of risk, with a view to understanding whether and how such a calculator could help motivate users to adopt healthier behaviours and/or improve adherence to medication. Design and setting Qualitative study combining data from focus groups and individual user experience. Adults with type 2 diabetes were recruited through website advertisements and posters displayed at local GP practices and diabetes groups. Method Participants used a risk calculator that provided individualised estimates of cardiovascular risk. Estimates were based on UK Prospective Diabetes Study (UKPDS) data, supplemented with data from trials and systematic reviews. Risk information was presented using natural frequencies, visual displays, and a range of formats. Data were recorded and transcribed, then analysed by a multidisciplinary group. Results Thirty-six participants contributed data. Users demonstrated a range of complex cognitive and emotional responses, which might explain the lack of change in health behaviours demonstrated in the literature. Conclusion Cardiovascular risk calculators for people with diabetes may best be used in conjunction with health professionals who can guide the user through the calculator and help them use the resulting risk information as a source of motivation and encouragement. PMID:25733436

  12. Preliminary phenotypic map of chromosome 4p16 based on 4p deletions

    SciTech Connect

    Estabrooks, L.L.; Rao, K.W.; Aylsworth, A.S.

    1995-07-17

    We have collected and analyzed clinical information from 11 patients with chromosome 4p deletions or rearrangements characterized by various molecular techniques. Comparing the extent of these patients` deletions with their respective clinical presentations led to the proposal of a preliminary phenotypic map of chromosome 4p. This map consists of regions which, when deleted, are associated with specific clinical manifestations. Nonspecific changes such as mental and growth retardation are not localized, and probably result from the deletion of more than one gene or region. The region associated with most of the facial traits considered typical in Wolf-Hirschhorn syndrome (WHS) patients coincides with the currently proposed WHS critical region (WHSCR), but some anomalies commonly seen in WHS appear to map outside of the WHSCR. The observation of clinodactyly in 2 patients with nonoverlapping deletions allows assignment of these defects to at least 2 separate regions in 4p16. These initial observations and attempts at genotype/phenotype correlation lay the groundwork for identifying the genetic basis of these malformations, a common objective of gene mapping efforts and chromosome deletion studies. 12 refs., 2 figs., 1 tab.

  13. Image-Based High-Throughput Field Phenotyping of Crop Roots1[W][OPEN

    PubMed Central

    Bucksch, Alexander; Burridge, James; York, Larry M.; Das, Abhiram; Nord, Eric; Weitz, Joshua S.; Lynch, Jonathan P.

    2014-01-01

    Current plant phenotyping technologies to characterize agriculturally relevant traits have been primarily developed for use in laboratory and/or greenhouse conditions. In the case of root architectural traits, this limits phenotyping efforts, largely, to young plants grown in specialized containers and growth media. Hence, novel approaches are required to characterize mature root systems of older plants grown under actual soil conditions in the field. Imaging methods able to address the challenges associated with characterizing mature root systems are rare due, in part, to the greater complexity of mature root systems, including the larger size, overlap, and diversity of root components. Our imaging solution combines a field-imaging protocol and algorithmic approach to analyze mature root systems grown in the field. Via two case studies, we demonstrate how image analysis can be utilized to estimate localized root traits that reliably capture heritable architectural diversity as well as environmentally induced architectural variation of both monocot and dicot plants. In the first study, we show that our algorithms and traits (including 13 novel traits inaccessible to manual estimation) can differentiate nine maize (Zea mays) genotypes 8 weeks after planting. The second study focuses on a diversity panel of 188 cowpea (Vigna unguiculata) genotypes to identify which traits are sufficient to differentiate genotypes even when comparing plants whose harvesting date differs up to 14 d. Overall, we find that automatically derived traits can increase both the speed and reproducibility of the trait estimation pipeline under field conditions. PMID:25187526

  14. Image-based high-throughput field phenotyping of crop roots.

    PubMed

    Bucksch, Alexander; Burridge, James; York, Larry M; Das, Abhiram; Nord, Eric; Weitz, Joshua S; Lynch, Jonathan P

    2014-10-01

    Current plant phenotyping technologies to characterize agriculturally relevant traits have been primarily developed for use in laboratory and/or greenhouse conditions. In the case of root architectural traits, this limits phenotyping efforts, largely, to young plants grown in specialized containers and growth media. Hence, novel approaches are required to characterize mature root systems of older plants grown under actual soil conditions in the field. Imaging methods able to address the challenges associated with characterizing mature root systems are rare due, in part, to the greater complexity of mature root systems, including the larger size, overlap, and diversity of root components. Our imaging solution combines a field-imaging protocol and algorithmic approach to analyze mature root systems grown in the field. Via two case studies, we demonstrate how image analysis can be utilized to estimate localized root traits that reliably capture heritable architectural diversity as well as environmentally induced architectural variation of both monocot and dicot plants. In the first study, we show that our algorithms and traits (including 13 novel traits inaccessible to manual estimation) can differentiate nine maize (Zea mays) genotypes 8 weeks after planting. The second study focuses on a diversity panel of 188 cowpea (Vigna unguiculata) genotypes to identify which traits are sufficient to differentiate genotypes even when comparing plants whose harvesting date differs up to 14 d. Overall, we find that automatically derived traits can increase both the speed and reproducibility of the trait estimation pipeline under field conditions. PMID:25187526

  15. Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe.

    PubMed

    Thom, Simon; Field, Jane; Poulter, Neil; Patel, Anushka; Prabhakaran, Dorairaj; Stanton, Alice; Grobbee, Diederick E; Bots, Michiel L; Reddy, K Srinath; Cidambi, Raghu; Rodgers, Anthony

    2014-02-01

    The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward, yet in practice the adoption of such measures is disappointingly low, plus there is wide international variation in preventive therapies. Several barriers might explain this shortfall and variation, but the simplicity and economy of a polypill-based strategy might overcome some barriers. The 'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial assesses whether a polypill strategy (by combining aspirin, a statin and two blood pressure lowering agents) would improve adherence to guideline-indicated therapies and would lower both blood pressure and cholesterol, in people with established cardiovascular disease. UMPIRE, running in India and three European countries (England, Ireland and the Netherlands), is an open, randomised, controlled trial designed to include 1000 participants in India and 1000 in Europe, with a followup of 12-24 months. Participants were randomised to one of two versions of the polypill or relegated to usual care. The primary study outcomes were the self-reported use of aspirin, a statin and at least two blood pressure lowering agents; as well as changes in blood pressure and cholesterol. Secondary outcomes included: any cardiovascular events, reasons for stopping medications, serious adverse events and perceived changes in quality of life. Interpretation of the study data will be enhanced by health, economic and process-related evaluations. UMPIRE is registered with the European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250. The trial was part of the 'Single Pill Against Cardiovascular Events (SPACE)' collaboration, which encompasses the 'IMProving Adherence using Combination Therapy (IMPACT)' and 'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)' trials.

  16. Target-based vs. phenotypic screenings in Leishmania drug discovery: A marriage of convenience or a dialogue of the deaf?

    PubMed Central

    Reguera, Rosa M.; Calvo-Álvarez, Estefanía; Álvarez-Velilla, Raquel; Balaña-Fouce, Rafael

    2014-01-01

    Drug discovery programs sponsored by public or private initiatives pursue the same ambitious goal: a crushing defeat of major Neglected Tropical Diseases (NTDs) during this decade. Both target-based and target-free screenings have pros and cons when it comes to finding potential small-molecule leads among chemical libraries consisting of myriads of compounds. Within the target-based strategy, crystals of pathogen recombinant-proteins are being used to obtain three-dimensional (3D) structures in silico for the discovery of structure-based inhibitors. On the other hand, genetically modified parasites expressing easily detectable reporters are in the pipeline of target-free (phenotypic) screenings. Furthermore, lead compounds can be scaled up to in vivo preclinical trials using rodent models of infection monitoring parasite loads by means of cutting-edge bioimaging devices. As such, those preferred are fluorescent and bioluminescent readouts due to their reproducibility and rapidity, which reduces the number of animals used in the trials and allows for an earlier stage detection of the infective process as compared with classical methods. In this review, we focus on the current differences between target-based and phenotypic screenings in Leishmania, as an approach that leads to the discovery of new potential drugs against leishmaniasis. PMID:25516847

  17. A network-based approach for predicting key enzymes explaining metabolite abundance alterations in a disease phenotype

    PubMed Central

    2013-01-01

    Background The study of metabolism has attracted much attention during the last years due to its relevance in various diseases. The advance in metabolomics platforms allows us to detect an increasing number of metabolites in abnormal high/low concentration in a disease phenotype. Finding a mechanistic interpretation for these alterations is important to understand pathophysiological processes, however it is not an easy task. The availability of genome scale metabolic networks and Systems Biology techniques open new avenues to address this question. Results In this article we present a novel mathematical framework to find enzymes whose malfunction explains the accumulation/depletion of a given metabolite in a disease phenotype. Our approach is based on a recently introduced pathway concept termed Carbon Flux Paths (CFPs), which extends classical topological definition by including network stoichiometry. Using CFPs, we determine the Connectivity Curve of an altered metabolite, which allows us to quantify changes in its pathway structure when a certain enzyme is removed. The influence of enzyme removal is then ranked and used to explain the accumulation/depletion of such metabolite. For illustration, we center our study in the accumulation of two metabolites (L-Cystine and Homocysteine) found in high concentration in the brain of patients with mental disorders. Our results were discussed based on literature and found a good agreement with previously reported mechanisms. In addition, we hypothesize a novel role of several enzymes for the accumulation of these metabolites, which opens new strategies to understand the metabolic processes underlying these diseases. Conclusions With personalized medicine on the horizon, metabolomic platforms are providing us with a vast amount of experimental data for a number of complex diseases. Our approach provides a novel apparatus to rationally investigate and understand metabolite alterations under disease phenotypes. This work

  18. Candidate-based proteomics in the search for biomarkers of cardiovascular disease

    PubMed Central

    Anderson, Leigh

    2005-01-01

    The key concept of proteomics (looking at many proteins at once) opens new avenues in the search for clinically useful biomarkers of disease, treatment response and ageing. As the number of proteins that can be detected in plasma or serum (the primary clinical diagnostic samples) increases towards 1000, a paradoxical decline has occurred in the number of new protein markers approved for diagnostic use in clinical laboratories. This review explores the limitations of current proteomics protein discovery platforms, and proposes an alternative approach, applicable to a range of biological/physiological problems, in which quantitative mass spectrometric methods developed for analytical chemistry are employed to measure limited sets of candidate markers in large sets of clinical samples. A set of 177 candidate biomarker proteins with reported associations to cardiovascular disease and stroke are presented as a starting point for such a ‘directed proteomics’ approach. PMID:15611012

  19. Classification of cardiovascular time series based on different coupling structures using recurrence networks analysis.

    PubMed

    Ramírez Ávila, Gonzalo Marcelo; Gapelyuk, Andrej; Marwan, Norbert; Walther, Thomas; Stepan, Holger; Kurths, Jürgen; Wessel, Niels

    2013-08-28

    We analyse cardiovascular time series with the aim of performing early prediction of preeclampsia (PE), a pregnancy-specific disorder causing maternal and foetal morbidity and mortality. The analysis is made using a novel approach, namely the ε-recurrence networks applied to a phase space constructed by means of the time series of the variabilities of the heart rate and the blood pressure (systolic and diastolic). All the possible coupling structures among these variables are considered for the analysis. Network measures such as average path length, mean coreness, global clustering coefficient and scale-local transitivity dimension are computed and constitute the parameters for the subsequent quadratic discriminant analysis. This allows us to predict PE with a sensitivity of 91.7 per cent and a specificity of 68.1 per cent, thus validating the use of this method for classifying healthy and preeclamptic patients. PMID:23858486

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

    PubMed

    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.

  1. [Predisposition - obesity phenotype].

    PubMed

    Blüher, M

    2014-05-01

    Obesity belongs to the five most important health burdens in modern societies and reaches with ~20 % prevalence in Germany epidemic proportions. Obesity significantly increases the risk of developing metabolic (e. g. type 2 diabetes), cardiovascular, orthopaedic, psychologic and other disorders. Despite the well established epidemiologic relationship between obesity and these co-morbidities, there is a subgroup of metabolically healthy obese patients, which seems to be protected against metabolic and cardiovascular obesity related disorders. Compared to metabolically unhealthy or high risk obese patients, metabolically healthy obese individuals are characterized by preserved insulin sensitivity, lower liver fat content, lower visceral fat mass, as well as normal adipose tissue function. Noteworthy, metabolically healthy obese individuals do not significantly improve their obesity-associated risk for the development of type 2 diabetes and vascular diseases. Therefore, distinction between metabolically healthy from high-risk obese phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, pharmacological or bariatric surgery interventions. A stratified treatment approach considering these different obesity phenotypes should be introduced into clinical management of obese patients.

  2. IMPACTING POPULATION CARDIOVASCULAR HEALTH THROUGH A COMMUNITY-BASED PRACTICE NETWORK: UPDATE ON AN ASH-SUPPORTED COLLABORATIVE

    PubMed Central

    Egan, Brent M.; Laken, Marilyn A.; Wagner, C. Shaun; Mack, Sheryl S.; Seymour-Edwards, Kim; Dodson, John; Zhao, Yumin; Lackland, Daniel T.

    2011-01-01

    The Hypertension Initiative began in 1999 to help transition South Carolina from a leader in cardiovascular disease (CVD) to a model of heart and vascular health. Goals were to reduce heart disease and stroke 50% by promoting healthy lifestyles and access to effective care and medications. Continuing medical education was used to train providers, encourage physicians to become American Society of Hypertension (ASH) certified Hypertension Specialists and recruit practices into the community-based practice network (CBPN). Practice data audit with provider specific feedback is a key quality improvement tool. With ASH support, the CBPN has grown to 197 practices with ~1.6 million patients (~700,000 hypertensives). Clinical data are obtained from electronic health records and quarterly provider feedback reports generated. Hypertension, hypercholesterolemia and diabetes control rose and South Carolina improved from 51st to 35th in CVD mortality from 1995 to 2006. The Hypertension Initiative expanded to the Outpatient Quality Improvement Network to encompass comparative effectiveness research and other chronic diseases. Lessons learned include: trust enables success, addressing practice priorities powers participation, infrastructure support must be multilateral, strategic planning identifies opportunities and pitfalls. A collaborative practice network is attainable that produces positive, sustainable, and growing impacts on cardiovascular and other chronic diseases. PMID:21806763

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

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

    2012-01-01

    Abstract 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. PMID:23166458

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

    PubMed Central

    Drapikowski, Paweł; Kazimierczak-Grygiel, Ewa; Korecki, Dominik; Wiland-Szymańska, Justyna

    2016-01-01

    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. PMID:27355949

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

    PubMed

    Drapikowski, Paweł; Kazimierczak-Grygiel, Ewa; Korecki, Dominik; Wiland-Szymańska, Justyna

    2016-06-27

    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. Developing a Predictive Gene Classifier for Autism Spectrum Disorders Based upon Differential Gene Expression Profiles of Phenotypic Subgroups

    PubMed Central

    Hu, Valerie W.; Lai, Yinglei

    2013-01-01

    Autism spectrum disorders (ASD) are neurodevelopmental disorders which are currently diagnosed solely on the basis of abnormal stereotyped behavior as well as observable deficits in communication and social functioning. Although a variety of candidate genes have been identified on the basis of genetic analyses and up to 20% of ASD cases can be collectively associated with a genetic abnormality, no single gene or genetic variant is applicable to more than 1–2 percent of the general ASD population. In this report, we apply class prediction algorithms to gene expression profiles of lymphoblastoid cell lines (LCL) from several phenotypic subgroups of idiopathic autism defined by cluster analyses of behavioral severity scores on the Autism Diagnostic Interview-Revised diagnostic instrument for ASD. We further demonstrate that individuals from these ASD subgroups can be distinguished from nonautistic controls on the basis of limited sets of differentially expressed genes with a predicted classification accuracy of up to 94% and sensitivities and specificities of ~90% or better, based on support vector machine analyses with leave-one-out validation. Validation of a subset of the “classifier” genes by high-throughput quantitative nuclease protection assays with a new set of LCL samples derived from individuals in one of the phenotypic subgroups and from a new set of controls resulted in an overall class prediction accuracy of ~82%, with ~90% sensitivity and 75% specificity. Although additional validation with a larger cohort is needed, and effective clinical translation must include confirmation of the differentially expressed genes in primary cells from cases earlier in development, we suggest that such panels of genes, based on expression analyses of phenotypically more homogeneous subgroups of individuals with ASD, may be useful biomarkers for diagnosis of subtypes of idiopathic autism. PMID:24363828

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

    PubMed Central

    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

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

    PubMed Central

    2014-01-01

    Introduction Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: <25%; 25 to 50%; 50 to 75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0

  11. Dissecting the Phenotypic Components of Crop Plant Growth and Drought Responses Based on High-Throughput Image Analysis[W][OPEN

    PubMed Central

    Chen, Dijun; Neumann, Kerstin; Friedel, Swetlana; Kilian, Benjamin; Chen, Ming; Altmann, Thomas; Klukas, Christian

    2014-01-01

    Significantly improved crop varieties are urgently needed to feed the rapidly growing human population under changing climates. While genome sequence information and excellent genomic tools are in place for major crop species, the systematic quantification of phenotypic traits or components thereof in a high-throughput fashion remains an enormous challenge. In order to help bridge the genotype to phenotype gap, we developed a comprehensive framework for high-throughput phenotype data analysis in plants, which enables the extraction of an extensive list of phenotypic traits from nondestructive plant imaging over time. As a proof of concept, we investigated the phenotypic components of the drought responses of 18 different barley (Hordeum vulgare) cultivars during vegetative growth. We analyzed dynamic properties of trait expression over growth time based on 54 representative phenotypic features. The data are highly valuable to understand plant development and to further quantify growth and crop performance features. We tested various growth models to predict plant biomass accumulation and identified several relevant parameters that support biological interpretation of plant growth and stress tolerance. These image-based traits and model-derived parameters are promising for subsequent genetic mapping to uncover the genetic basis of complex agronomic traits. Taken together, we anticipate that the analytical framework and analysis results presented here will be useful to advance our views of phenotypic trait components underlying plant development and their responses to environmental cues. PMID:25501589

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

    PubMed Central

    Pron, G; Ieraci, L; Kaulback, K

    2012-01-01

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

  13. Epidemiology of Cardiovascular Malformations among Newborns in Monchegorsk (North-West Russia): a Register-Based Study

    PubMed Central

    Postoev, Vitaly A.; Talykova, Ljudmila V.; Vaktskjold, Arild

    2014-01-01

    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 new-borns, 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. Significance for public health Cardiovascular malformation is one of the most common groups of birth defects. It is considered an important public health issue, as these malformations are the main cause of infant deaths in developed countries. Precise estimates about the prevalence and perinatal survival are needed to organise and plan health care for such newborns. Our study is the first report from the Russian Federation based on data from population-based birth registers. PMID:25343136

  14. Cost effectiveness and equity of a community based cardiovascular disease prevention programme in Norsjö, Sweden.

    PubMed Central

    Lindholm, L; Rosén, M; Weinehall, L; Asplund, K

    1996-01-01

    STUDY OBJECTIVE: To evaluate the cost effectiveness and equity of a community based cardiovascular disease prevention programme. DESIGN: A prospective cross sectional design. SETTING: A community based intervention to reduce cardiovascular disease in the district of Norsjö (n = 5500), Sweden. The intervention was aimed at both the general population and at individuals thought to be at special risk, the emphasis being on changing dietary habits and reducing cholesterol concentrations. PARTICIPANTS: The participants were men and women aged 30-60 years. MAIN RESULTS: The mean serum cholesterol concentration in the Norsjö population was reduced by nearly 20% during the first six years of intervention. It was estimated that the programme's overall total societal costs were 363,000 pounds and estimates of the cost per year of life saved ranged from 14,900 pounds to net savings, according to different assumptions. Taking only health care costs and savings into account, the cost per year of life saved ranged from 1100 pounds to 4050 pounds. The results varied between different sex and age groups, but not between social classes. Even if a causal relationship exists between low cholesterol concentrations and excess mortality, the estimated side effects of lowering cholesterol values in Norsjö were negligible in comparison with the expected benefits. CONCLUSIONS: The community based intervention in Norsjö seems to be cost effective even under conservative assumptions. The approach used seems to have benefited all social classes. Cost effectiveness analyses that take consequences for equity into account are valuable tools in decision making. PMID:8762387

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

    PubMed Central

    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

  16. Sensory Ciliogenesis in Caenorhabditis elegans: Assignment of IFT Components into Distinct Modules Based on Transport and Phenotypic Profiles

    PubMed Central

    Ou, Guangshuo; Koga, Makato; Blacque, Oliver E.; Murayama, Takashi; Ohshima, Yasumi; Schafer, Jenny C.; Li, Chunmei; Yoder, Bradley K.

    2007-01-01

    Sensory cilium biogenesis within Caenorhabditis elegans neurons depends on the kinesin-2–dependent intraflagellar transport (IFT) of ciliary precursors associated with IFT particles to the axoneme tip. Here we analyzed the molecular organization of the IFT machinery by comparing the in vivo transport and phenotypic profiles of multiple proteins involved in IFT and ciliogenesis. Based on their motility in wild-type and bbs (Bardet-Biedl syndrome) mutants, IFT proteins were classified into groups with similar transport profiles that we refer to as “modules.” We also analyzed the distribution and transport of fluorescent IFT particles in multiple known ciliary mutants and 49 new ciliary mutants. Most of the latter mutants were snip-SNP mapped and one, namely dyf-14(ks69), was cloned and found to encode a conserved protein essential for ciliogenesis. The products of these ciliogenesis genes could also be assigned to the aforementioned set of modules or to specific aspects of ciliogenesis, based on IFT particle dynamics and ciliary mutant phenotypes. Although binding assays would be required to confirm direct physical interactions, the results are consistent with the hypothesis that the C. elegans IFT machinery has a modular design, consisting of modules IFT-subcomplex A, IFT-subcomplex B, and a BBS protein complex, in addition to motor and cargo modules, with each module contributing to distinct functional aspects of IFT or ciliogenesis. PMID:17314406

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

    PubMed Central

    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

  18. Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications.

    PubMed

    Galvin, Paul; Thompson, Damien; Ryan, Katie B; McCarthy, Anna; Moore, Anne C; Burke, Conor S; Dyson, Maya; Maccraith, Brian D; Gun'ko, Yurii K; Byrne, Michelle T; Volkov, Yuri; Keely, Chris; Keehan, Enda; Howe, Michael; Duffy, Conor; MacLoughlin, Ronan

    2012-02-01

    Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.

  19. Machine learning-based prediction of drug–drug interactions by integrating drug phenotypic, therapeutic, chemical, and genomic properties

    PubMed Central

    Cheng, Feixiong; Zhao, Zhongming

    2014-01-01

    Objective Drug–drug interactions (DDIs) are an important consideration in both drug development and clinical application, especially for co-administered medications. While it is necessary to identify all possible DDIs during clinical trials, DDIs are frequently reported after the drugs are approved for clinical use, and they are a common cause of adverse drug reactions (ADR) and increasing healthcare costs. Computational prediction may assist in identifying potential DDIs during clinical trials. Methods Here we propose a heterogeneous network-assisted inference (HNAI) framework to assist with the prediction of DDIs. First, we constructed a comprehensive DDI network that contained 6946 unique DDI pairs connecting 721 approved drugs based on DrugBank data. Next, we calculated drug–drug pair similarities using four features: phenotypic similarity based on a comprehensive drug–ADR network, therapeutic similarity based on the drug Anatomical Therapeutic Chemical classification system, chemical structural similarity from SMILES data, and genomic similarity based on a large drug–target interaction network built using the DrugBank and Therapeutic Target Database. Finally, we applied five predictive models in the HNAI framework: naive Bayes, decision tree, k-nearest neighbor, logistic regression, and support vector machine, respectively. Results The area under the receiver operating characteristic curve of the HNAI models is 0.67 as evaluated using fivefold cross-validation. Using antipsychotic drugs as an example, several HNAI-predicted DDIs that involve weight gain and cytochrome P450 inhibition were supported by literature resources. Conclusions Through machine learning-based integration of drug phenotypic, therapeutic, structural, and genomic similarities, we demonstrated that HNAI is promising for uncovering DDIs in drug development and postmarketing surveillance. PMID:24644270

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. dbPEC: a comprehensive literature-based database for preeclampsia related genes and phenotypes

    PubMed Central

    Uzun, Alper; Triche, Elizabeth W.; Schuster, Jessica; Dewan, Andrew T.; Padbury, James F.

    2016-01-01

    Preeclampsia is one of the most common causes of fetal and maternal morbidity and mortality in the world. We built a Database for Preeclampsia (dbPEC) consisting of the clinical features, concurrent conditions, published literature and genes associated with Preeclampsia. We included gene sets associated with severity, concurrent conditions, tissue sources and networks. The published scientific literature is the primary repository for all information documenting human disease. We used semantic data mining to retrieve and extract the articles pertaining to preeclampsia-associated genes and performed manual curation. We deposited the articles, genes, preeclampsia phenotypes and other supporting information into the dbPEC. It is publicly available and freely accessible. Previously, we developed a database for preterm birth (dbPTB) using a similar approach. Using the gene sets in dbPTB, we were able to successfully analyze a genome-wide study of preterm birth including 4000 women and children. We identified important genes and pathways associated with preterm birth that were not otherwise demonstrable using genome-wide approaches. dbPEC serves not only as a resources for genes and articles associated with preeclampsia, it is a robust source of gene sets to analyze a wide range of high-throughput data for gene set enrichment analysis. Database URL: http://ptbdb.cs.brown.edu/dbpec/ PMID:26946289

  4. dbPEC: a comprehensive literature-based database for preeclampsia related genes and phenotypes.

    PubMed

    Uzun, Alper; Triche, Elizabeth W; Schuster, Jessica; Dewan, Andrew T; Padbury, James F

    2016-01-01

    Preeclampsia is one of the most common causes of fetal and maternal morbidity and mortality in the world. We built a Database for Preeclampsia (dbPEC) consisting of the clinical features, concurrent conditions, published literature and genes associated with Preeclampsia. We included gene sets associated with severity, concurrent conditions, tissue sources and networks. The published scientific literature is the primary repository for all information documenting human disease. We used semantic data mining to retrieve and extract the articles pertaining to preeclampsia-associated genes and performed manual curation. We deposited the articles, genes, preeclampsia phenotypes and other supporting information into the dbPEC. It is publicly available and freely accessible. Previously, we developed a database for preterm birth (dbPTB) using a similar approach. Using the gene sets in dbPTB, we were able to successfully analyze a genome-wide study of preterm birth including 4000 women and children. We identified important genes and pathways associated with preterm birth that were not otherwise demonstrable using genome-wide approaches. dbPEC serves not only as a resources for genes and articles associated with preeclampsia, it is a robust source of gene sets to analyze a wide range of high-throughput data for gene set enrichment analysis. Database URL: http://ptbdb.cs.brown.edu/dbpec/. PMID:26946289

  5. A 16-Month Community-Based Intervention to Increase Aspirin Use for Primary Prevention of Cardiovascular Disease

    PubMed Central

    Duval, Sue; Luepker, Russell V.; Finnegan, John R.; LaMarre, Heather; Peterson, Kevin A.; Zantek, Nicole D.; Jacobs, Ginny; Straka, Robert J.; Miller, Karen H.; Hirsch, Alan T.

    2014-01-01

    Introduction Cardiovascular diseases are the leading causes of disability and death in the United States. Primary prevention of these events may be achieved through aspirin use. The ability of a community-based intervention to increase aspirin use has not been evaluated. The objective of this study was to evaluate an educational intervention implemented to increase aspirin use for primary prevention of cardiovascular disease in a small city in Minnesota. Methods A community-based intervention was implemented during 16 months in a medium-sized community in Minnesota. Messages for aspirin use were disseminated to individuals, health care professionals, and the general population. Independent cross-sectional samples of residents (men aged 45–79, women aged 55–79) were surveyed by telephone to identify candidates for primary prevention aspirin use, examine their characteristics, and determine regular aspirin use at baseline and after the campaign at 4 months and 16 months. Results In primary prevention candidates, regular aspirin use rates increased from 36% at baseline to 54% at 4 months (odds ratio = 2.05; 95% confidence interval, 1.09–3.88); the increase was sustained at 52% at 16 months (odds ratio = 1.89; 95% confidence interval, 1.02–3.49). The difference in aspirin use rates at 4 months and 16 months was not significant (P = .77). Conclusion Aspirin use rates for primary prevention remain low. A combined public health and primary care approach can increase and sustain primary prevention aspirin use in a community setting. PMID:24831287

  6. Severity of Depression, Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort

    PubMed Central

    Almas, Aysha; Forsell, Yvonne; Iqbal, Romaina; Janszky, Imre; Moller, Jette

    2015-01-01

    Background Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association. Methods We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases. Findings Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD. Conclusion This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress. PMID:26469703

  7. Nutrition and cardiovascular health.

    PubMed

    Berciano, Silvia; Ordovás, José M

    2014-09-01

    A multitude of studies have been published on the relationship between cardiovascular disease risk and a variety of nutrients, foods, and dietary patterns. Despite the well-accepted notion that diet has a significant influence on the development and prevention of cardiovascular disease, the foods considered healthy and harmful have varied over the years. This review aims to summarize the current scientific evidence on the cardioprotective effect of those foods and nutrients that have been considered healthy as well as those that have been deemed unhealthy at any given time in history. For this purpose, we reviewed the most recent literature using as keywords foods and nutrients (ie, meat, omega-3) and cardiovascular disease-related terms (ie, cardiovascular diseases, stroke). Emphasis has been placed on meta-analyses and Cochrane reviews. In general, there is a paucity of intervention studies with a high level of evidence supporting the benefits of healthy foods (ie, fruits and vegetables), whereas the evidence supporting the case against those foods considered less healthy (ie, saturated fat) seems to be weakened by most recent evidence. In summary, most of the evidence supporting the benefits and harms of specific foods and nutrients is based on observational epidemiological studies. The outcome of randomized clinical trials reveals a more confusing picture with most studies providing very small effects in one direction or another; the strongest evidence comes from dietary patterns. The current status of the relationship between diet and cardiovascular disease risk calls for more tailored recommendations based on genomic technologies.

  8. Cardiovascular Effect of Incretin-Based Therapy in Patients with Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis

    PubMed Central

    Kim, Je-Yon; Yang, Seungwon; Lee, Jangik I.; Chang, Min Jung

    2016-01-01

    Background To assess the cardiovascular (CV) risk associated with the use of incretin-based therapy in adult patients with type 2 diabetes mellitus (T2DM) primary prevention group with low CV risks. Methods The clinical studies on incretin-based therapy published in medical journals until August 2014 were comprehensively searched using MEDLINE, EMBASE and CENTRAL with no language restriction. The studies were systemically reviewed and evaluated for CV risks using a meta-analysis approach and where they meet the following criteria: clinical trial, incidence of predefined CV disease, T2DM with no comorbidities, age > 18 years old, duration of at least 12 weeks, incretin-based therapy compared with other antihyperglycaemic agents or placebo. Statistical analyses were performed using a Mantel-Haenszel (M-H) test. The odds ratios (OR) and their 95% confidence interval (CI) were estimated and displayed for comparison. Results A total of 75 studies comprising 45,648 patients with T2DM were selected. The pooled estimate demonstrated no significance in decreased CV risk with incretin-based therapy versus control (M-H OR, 0.90; 95% CI, 0.81–1.00). Conclusions This meta-analysis suggests that incretin-based therapy show no significant protective effect on CV events in T2DM primary prevention group with low CV risks. Prospective randomized controlled trials are required to confirm the results of this analysis. PMID:27078018

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

    PubMed

    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. PMID:9603614

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

    PubMed

    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.

  11. Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome1,2,3

    PubMed Central

    Dinday, Matthew T.

    2015-01-01

    Abstract Mutations in a voltage-gated sodium channel (SCN1A) result in Dravet Syndrome (DS), a catastrophic childhood epilepsy. Zebrafish with a mutation in scn1Lab recapitulate salient phenotypes associated with DS, including seizures, early fatality, and resistance to antiepileptic drugs. To discover new drug candidates for the treatment of DS, we screened a chemical library of ∼1000 compounds and identified 4 compounds that rescued the behavioral seizure component, including 1 compound (dimethadione) that suppressed associated electrographic seizure activity. Fenfluramine, but not huperzine A, also showed antiepileptic activity in our zebrafish assays. The effectiveness of compounds that block neuronal calcium current (dimethadione) or enhance serotonin signaling (fenfluramine) in our zebrafish model suggests that these may be important therapeutic targets in patients with DS. Over 150 compounds resulting in fatality were also identified. We conclude that the combination of behavioral and electrophysiological assays provide a convenient, sensitive, and rapid basis for phenotype-based drug screening in zebrafish mimicking a genetic form of epilepsy. PMID:26465006

  12. A systematic phenotypic screen of F-box genes through a tissue-specific RNAi-based approach in Drosophila.

    PubMed

    Dui, Wen; Lu, Wei; Ma, Jun; Jiao, Renjie

    2012-08-20

    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.

  13. Hereditary haemorrhagic telangiectasia: a questionnaire based study to delineate the different phenotypes caused by endoglin and ALK1 mutations

    PubMed Central

    Berg, J; Porteous, M; Reinhardt, D; Gallione, C; Holloway, S; Umasunthar, T; Lux, A; McKinnon, W; Marchuk, D; Guttmacher, A

    2003-01-01

    Background: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterised by mucocutaneous telangiectasis, epistaxis, gastrointestinal haemorrhage, and arteriovenous malformations in the lung and brain. Causative mutations for HHT have been identified in two genes, endoglin and ALK1, which encode proteins involved in serine-threonine kinase signalling in the endothelial cell. Methods: A number of people affected with HHT had completed a postal questionnaire as part of an international study to delineate the HHT phenotype. We identified questionnaires completed by subjects in whom we had identified a mutation in endoglin or ALK1. Further questionnaires were sent to families with known mutations. Data were only included from questionnaires returned by people known to carry disease causing mutations. Results: Questionnaires were completed by 83 subjects with known mutations. Of these, 49 had endoglin mutations (HHT1) and 34 had ALK1 mutations (HHT2). Subjects with HHT1 reported an earlier onset of epistaxis (p=0.01) and telangiectasis (p=0.0001) than those with HHT2. Pulmonary arteriovenous malformations were only reported in the endoglin mutation group in our study (p<0.001). Conclusions: Our questionnaire based study provides evidence that the HHT phenotype caused by mutations in endoglin (HHT1) is distinct from, and more severe than, HHT caused by mutations in ALK1 (HHT2). This has significant implications for diagnosis, screening, and treatment in the two different forms of HHT, as well as for understanding the pathogenesis of the disease. PMID:12920067

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

    PubMed Central

    Torstensson, Maia; Hansen, Annette Højmann; Leth-Møller, Katja; Jørgensen, Terese Sara Høj; Sahlberg, Marie; Andersson, Charlotte; Kristensen, Karl Emil; Ryg, Jesper; Weeke, Peter; Torp-Pedersen, Christian; Gislason, Gunnar; Holm, Ellen

    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, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides IRR 1.41 (1.28 to 1.55); IRR during the first 30 days of treatment with digoxin was 1.18 (1.02 to 1.37). Conclusions Use of furosemide, thiazides and digoxin was associated with elevated rates of fragility fractures among elderly individuals. This may warrant consideration when considering diuretic treatment of hypertension in elderly individuals. PMID:26715481

  15. Drug repositioning by kernel-based integration of molecular structure, molecular activity, and phenotype data.

    PubMed

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

    2013-01-01

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

  16. DNA Metabolism in Balance: Rapid Loss of a RecA-Based Hyperrec Phenotype.

    PubMed

    Bakhlanova, Irina V; Dudkina, Alexandra V; Wood, Elizabeth A; Lanzov, Vladislav A; Cox, Michael M; Baitin, Dmitry M

    2016-01-01

    The RecA recombinase of Escherichia coli has not evolved to optimally promote DNA pairing and strand exchange, the key processes of recombinational DNA repair. Instead, the recombinase function of RecA protein represents an evolutionary compromise between necessary levels of recombinational DNA repair and the potentially deleterious consequences of RecA functionality. A RecA variant, RecA D112R, promotes conjugational recombination at substantially enhanced levels. However, expression of the D112R RecA protein in E. coli results in a reduction in cell growth rates. This report documents the consequences of the substantial selective pressure associated with the RecA-mediated hyperrec phenotype. With continuous growth, the deleterious effects of RecA D112R, along with the observed enhancements in conjugational recombination, are lost over the course of 70 cell generations. The suppression reflects a decline in RecA D112R expression, associated primarily with a deletion in the gene promoter or chromosomal mutations that decrease plasmid copy number. The deleterious effects of RecA D112R on cell growth can also be negated by over-expression of the RecX protein from Neisseria gonorrhoeae. The effects of the RecX proteins in vivo parallel the effects of the same proteins on RecA D112R filaments in vitro. The results indicate that the toxicity of RecA D112R is due to its persistent binding to duplex genomic DNA, creating barriers for other processes in DNA metabolism. A substantial selective pressure is generated to suppress the resulting barrier to growth. PMID:27124470

  17. DNA Metabolism in Balance: Rapid Loss of a RecA-Based Hyperrec Phenotype

    PubMed Central

    Bakhlanova, Irina V.; Dudkina, Alexandra V.; Wood, Elizabeth A.; Lanzov, Vladislav A.; Cox, Michael M.; Baitin, Dmitry M.

    2016-01-01

    The RecA recombinase of Escherichia coli has not evolved to optimally promote DNA pairing and strand exchange, the key processes of recombinational DNA repair. Instead, the recombinase function of RecA protein represents an evolutionary compromise between necessary levels of recombinational DNA repair and the potentially deleterious consequences of RecA functionality. A RecA variant, RecA D112R, promotes conjugational recombination at substantially enhanced levels. However, expression of the D112R RecA protein in E. coli results in a reduction in cell growth rates. This report documents the consequences of the substantial selective pressure associated with the RecA-mediated hyperrec phenotype. With continuous growth, the deleterious effects of RecA D112R, along with the observed enhancements in conjugational recombination, are lost over the course of 70 cell generations. The suppression reflects a decline in RecA D112R expression, associated primarily with a deletion in the gene promoter or chromosomal mutations that decrease plasmid copy number. The deleterious effects of RecA D112R on cell growth can also be negated by over-expression of the RecX protein from Neisseria gonorrhoeae. The effects of the RecX proteins in vivo parallel the effects of the same proteins on RecA D112R filaments in vitro. The results indicate that the toxicity of RecA D112R is due to its persistent binding to duplex genomic DNA, creating barriers for other processes in DNA metabolism. A substantial selective pressure is generated to suppress the resulting barrier to growth. PMID:27124470

  18. Cross-sectional study of diet, physical activity, television viewing and sleep duration in 233 110 adults from the UK Biobank; the behavioural phenotype of cardiovascular disease and type 2 diabetes

    PubMed Central

    Cassidy, Sophie; Chau, Josephine Y; Catt, Michael; Bauman, Adrian; Trenell, Michael I

    2016-01-01

    Objectives Simultaneously define diet, physical activity, television (TV) viewing, and sleep duration across cardiometabolic disease groups, and investigate clustering of non-diet lifestyle behaviours. Design Cross-sectional observational study. Setting 22 UK Biobank assessment centres across the UK. Participants 502 664 adults aged 37–63 years old, 54% women. 4 groups were defined based on disease status; ‘No disease’ (n=103 993), ‘cardiovascular disease’ (CVD n=113 469), ‘Type 2 diabetes without CVD’ (n=4074) and ‘Type 2 diabetes + CVD’ (n=11 574). Main outcomes Diet, physical activity, TV viewing and sleep duration. Results People with ‘CVD’ report low levels of physical activity (<918 MET min/week, OR (95% CI) 1.23 (1.20 to 1.25)), high levels of TV viewing (>3 h/day; 1.42 (1.39 to 1.45)), and poor sleep duration (<7, >8 h/night; 1.37 (1.34 to 1.39)) relative to people without disease. People with ‘Type 2 diabetes + CVD’ were more likely to report low physical activity (1.71 (1.64 to 1.78)), high levels of TV viewing (1.92 (1.85 to 1.99)) and poor sleep duration (1.52 (1.46 to1.58)) relative to people without disease. Non-diet behaviours were clustered, with people with ‘CVD’ or ‘Type 2 diabetes + CVD’ more likely to report simultaneous low physical activity, high TV viewing and poor sleep duration than those without disease (2.15 (2.03 to 2.28) and 3.29 (3.02 to 3.58), respectively). By contrast, 3 in 4 adults with ‘Type 2 diabetes’, and 2 in 4 adults with ‘CVD’ have changed their diet in the past 5 years, compared with only 1 in 4 in the ‘No disease’ group. Models were adjusted for gender, age, body mass index, Townsend Deprivation Index, ethnicity, alcohol intake, smoking and meeting fruit/vegetable guidelines. Conclusions Low physical activity, high TV and poor sleep duration are prominent unaddressed high-risk characteristics of both CVD and type 2 diabetes, and are likely to be clustered

  19. The Drosophila phenotype ontology

    PubMed Central

    2013-01-01

    Background Phenotype ontologies are queryable classifications of phenotypes. They provide a widely-used means for annotating phenotypes in a form that is human-readable, programatically accessible and that can be used to group annotations in biologically meaningful ways. Accurate manual annotation requires clear textual definitions for terms. Accurate grouping and fruitful programatic usage require high-quality formal definitions that can be used to automate classification. The Drosophila phenotype ontology (DPO) has been used to annotate over 159,000 phenotypes in FlyBase to date, but until recently lacked textual or formal definitions. Results We have composed textual definitions for all DPO terms and formal definitions for 77% of them. Formal definitions reference terms from a range of widely-used ontologies including the Phenotype and Trait Ontology (PATO), the Gene Ontology (GO) and the Cell Ontology (CL). We also describe a generally applicable system, devised for the DPO, for recording and reasoning about the timing of death in populations. As a result of the new formalisations, 85% of classifications in the DPO are now inferred rather than asserted, with much of this classification leveraging the structure of the GO. This work has significantly improved the accuracy and completeness of classification and made further development of the DPO more sustainable. Conclusions The DPO provides a set of well-defined terms for annotating Drosophila phenotypes and for grouping and querying the resulting annotation sets in biologically meaningful ways. Such queries have already resulted in successful function predictions from phenotype annotation. Moreover, such formalisations make extended queries possible, including cross-species queries via the external ontologies used in formal definitions. The DPO is openly available under an open source license in both OBO and OWL formats. There is good potential for it to be used more broadly by the Drosophila

  20. A Multifaceted Nurse- and Web-Based Intervention for Improving Adherence to Treatment in Patients With Cardiovascular Disease: Rationale and Design of the MIRROR Trial

    PubMed Central

    2016-01-01

    Background Poor adherence to medication is one of the limitations in the treatment of cardiovascular diseases, thereby increasing the risk of premature death, hospital admissions, and related costs. There is a need for simple and easy-to-implement interventions that are based on patients’ perspectives, beliefs, and perceptions of their illness and medication. Objective The objective is to test the effectivity of this intervention to improve medication adherence in patients with established cardiovascular disease, that is, in secondary prevention. Methods In this study the effect of a personalized visualization of cardiovascular risk levels through a website aiming at supporting self management in combination with a group consultation and communication intervention by a nurse on adherence to treatment in 600 patients with manifest cardiovascular diseases will be assessed. The health belief model was chosen as main theoretical model for the intervention. Results Primary outcome is adherence to treatment calculated by refill data. Secondary outcomes include the Beliefs about Medication Questionnaire and the Modified Morisky Scale. Patients are followed for one year. Results are expected by 2015. Conclusions This study assesses adherence to treatment in a high-risk cardiovascular population by applying an intervention that addresses patients’ capacity and practical barriers as well as patients’ beliefs and perceptions of their illness and medication. ClinicalTrial ClinicalTrials.gov NCT01449695; https://clinicaltrials.gov/ct2/show/NCT01449695 (Archived by WebCite at http://www.webcitation.org/6kCzkIKH3) PMID:27624877

  1. Advancing cardiovascular tissue engineering

    PubMed Central

    Truskey, George A.

    2016-01-01

    Cardiovascular tissue engineering offers the promise of biologically based repair of injured and damaged blood vessels, valves, and cardiac tissue. Major advances in cardiovascular tissue engineering over the past few years involve improved methods to promote the establishment and differentiation of induced pluripotent stem cells (iPSCs), scaffolds from decellularized tissue that may produce more highly differentiated tissues and advance clinical translation, improved methods to promote vascularization, and novel in vitro microphysiological systems to model normal and diseased tissue function. iPSC technology holds great promise, but robust methods are needed to further promote differentiation. Differentiation can be further enhanced with chemical, electrical, or mechanical stimuli. PMID:27303643

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  3. Transgenerational epigenetics: the role of maternal effects in cardiovascular development.

    PubMed

    Ho, Dao H

    2014-07-01

    Transgenerational epigenetics, the study of non-genetic transfer of information from one generation to the next, has gained much attention in the past few decades due to the fact that, in many instances, epigenetic processes outweigh direct genetic processes in the manifestation of aberrant phenotypes across several generations. Maternal effects, or the influences of maternal environment, phenotype, and/or genotype on offsprings' phenotypes, independently of the offsprings' genotypes, are a subcategory of transgenerational epigenetics. Due to the intimate role of the mother during early development in animals, there is much interest in investigating the means by which maternal effects can shape the individual. Maternal effects are responsible for cellular organization, determination of the body axis, initiation and maturation of organ systems, and physiological performance of a wide variety of species and biological systems. The cardiovascular system is the first to become functional and can significantly influence the development of other organ systems. Thus, it is important to elucidate the role of maternal effects in cardiovascular development, and to understand its impact on adult cardiovascular health. Topics to be addressed include: (1) how and when do maternal effects change the developmental trajectory of the cardiovascular system to permanently alter the adult's cardiovascular phenotype, (2) what molecular mechanisms have been associated with maternally induced cardiovascular phenotypes, and (3) what are the evolutionary implications of maternally mediated changes in cardiovascular phenotype?

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

    NASA Astrophysics Data System (ADS)

    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

  5. A novel synthesized sulfonamido-based gallic acid--LDQN-C: effects on chondrocytes growth and phenotype maintenance.

    PubMed

    Lu, Zhenhui; Wei, Shixiu; Wu, Huayu; Lin, Xiao; Lin, Cuiwu; Liu, Buming; Zheng, Li; Zhao, Jinmin

    2014-12-01

    Chondrocyte based therapy is promising to treat symptomatic chondral and osteochondral lesions. Growth factors to accelerate the proliferation and retain the phenotype of chondrocytes in vitro are imperative. However, the high cost and rapid degradation of growth factors limited their further application. Therefore, it is significant to find substitutes that can preserve chondrocytes phenotype and ensure sufficient cells for cytotherapy. Antioxidant and anti-inflammatory agents or their derivatives that have effect on arthritis may be an alternative. In this study, we synthesized sulfonamido-based gallate - LDQN-C and investigated its effect on rat articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycans (GAGs) synthesis and cartilage specific gene expression. Results showed that LDQN-C could enhance secretion and synthesis of cartilage extracellular matrix (ECM) by up-regulating expression levels of aggrecan, collagen II and Sox9 genes compared to the GA treated group and control group. Expression of collagen type II was effectively up-regulated while collagen I was down-regulated, which demonstrated that the inhibition of chondrocytes dedifferentiation by LDQN-C. Range of 1.36×10(-9)M to 1.36×10(-7)M is recommended dose of LDQN-C, among which the most profound response was observed with 1.36×10(-8)M. GA at concentration of 0.125μg/mL was compared. This study might provide a basis for the development of a novel agent for the treatment of articular cartilage defect.

  6. Phenotype Standardization for Statin-Induced Myotoxicity

    PubMed Central

    Alfirevic, A; Neely, D; Armitage, J; Chinoy, H; Cooper, R G; Laaksonen, R; Carr, D F; Bloch, K M; Fahy, J; Hanson, A; Yue, Q-Y; Wadelius, M; Maitland-van Der Zee, A H; Voora, D; Psaty, B M; Palmer, C N A; Pirmohamed, M

    2014-01-01

    Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy. PMID:24897241

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

    PubMed Central

    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 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 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, transcriptomics data integration, and rational strain design. In each case we demonstrate how this approach can lead to improved phenotype predictions and a deeper understanding of the genotype-to-phenotype link. In particular, we show that a large fraction of reaction-based designs obtained by current strain design methods are not actually feasible, and show how our approach allows using the same methods to obtain feasible gene-based designs. We also show, by extensive comparison with experimental 13C-flux data, how simple reformulations of different simulation methods with gene-wise objective functions result in improved prediction accuracy. The model transformation proposed in this work enables existing constraint-based methods to be used at the gene level without modification. This automatically leverages phenotype analysis from reaction to gene level, improving the biological insight that can be obtained from genome-scale models. PMID:27711110

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

    PubMed

    Levert, Maxime; Zamfir, Oana; Clermont, Olivier; Bouvet, Odile; Lespinats, Sylvain; Hipeaux, Marie Claire; Branger, Catherine; Picard, Bertrand; Saint-Ruf, Claude; Norel, Françoise; Balliau, Thierry; Zivy, Michel; Le Nagard, Hervé; Cruveiller, Stéphane; Cruvellier, Stéphane; Chane-Woon-Ming, Béatrice; Nilsson, Susanna; Gudelj, Ivana; Phan, Katherine; Ferenci, Thomas; Tenaillon, Olivier; Denamur, Erick

    2010-09-30

    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 process and that

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

    PubMed Central

    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.

    2016-01-01

    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 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. PMID:27412535

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

    PubMed

    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.

  11. Deconstructing Oppositional Defiant Disorder: Clinic-Based Evidence for an Anger/Irritability Phenotype

    ERIC Educational Resources Information Center

    Drabick, Deborah A. G.; Gadow, Kenneth D.

    2012-01-01

    Objective: To examine risk factors and co-occurring symptoms associated with mother-reported versus teacher-reported anger/irritability symptoms (AIS) of oppositional defiant disorder (ODD) in a clinic-based sample of 1,160 youth aged 6 through 18 years. Method: Participants completed a background history questionnaire (mothers), school…

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

    PubMed Central

    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

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

    PubMed

    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

  14. Adherence to a home-based exercise program and incidence of cardiovascular disease in type 2 diabetes patients.

    PubMed

    Shinji, S; Shigeru, M; Ryusei, U; Mitsuru, M; Shigehiro, K

    2007-10-01

    The aim of this study was to examine the association between adherence to a home-based exercise program and the incidence of cardiovascular disease (CVD) in patients with type 2 diabetes. We investigated 102 patients with type 2 diabetes aged 35 to 75 years, and followed them prospectively for 17.2 months. Before enrollment, all patients received a traditional exercise prescription. The exercise program consisted of a daily walking exercise at home for 20 - 30 minutes. Self-reported adherence to the exercise program and the incidence of CVD were confirmed by information obtained from telephone interviews. There were 38 dropouts among the patients in the exercise program. Dropouts were significantly younger than completers. The rate of obesity was significantly higher among the dropouts than among the completers. No differences were observed between the two groups for gender, history of CVD and other clinical characteristics. During the follow-up, we documented 8 new cases of CVD. The incidence of CVD during the follow-up was 1.56 percent among the program completers and 18.4 percent among the dropouts. Adherence to the home-based exercise was inversely related to the incidence of CVD (p < 0.01). These associations persisted after adjustment for age and other covariates. In conclusion, adherence to an exercise program is associated with a reduced incidence of CVD among patients with type 2 diabetes. PMID:17436204

  15. Stress indicators based on airborne thermal imagery for field phenotyping a heterogeneous tree population for response to water constraints.

    PubMed

    Virlet, Nicolas; Lebourgeois, Valentine; Martinez, Sébastien; Costes, Evelyne; Labbé, Sylvain; Regnard, Jean-Luc

    2014-10-01

    As field phenotyping of plant response to water constraints constitutes a bottleneck for breeding programmes, airborne thermal imagery can contribute to assessing the water status of a wide range of individuals simultaneously. However, the presence of mixed soil-plant pixels in heterogeneous plant cover complicates the interpretation of canopy temperature. Moran's Water Deficit Index (WDI = 1-ETact/ETmax), which was designed to overcome this difficulty, was compared with surface minus air temperature (T s-T a) as a water stress indicator. As parameterization of the theoretical equations for WDI computation is difficult, particularly when applied to genotypes with large architectural variability, a simplified procedure based on quantile regression was proposed to delineate the Vegetation Index-Temperature (VIT) scatterplot. The sensitivity of WDI to variations in wet and dry references was assessed by applying more or less stringent quantile levels. The different stress indicators tested on a series of airborne multispectral images (RGB, near-infrared, and thermal infrared) of a population of 122 apple hybrids, under two irrigation regimes, significantly discriminated the tree water statuses. For each acquisition date, the statistical method efficiently delineated the VIT scatterplot, while the limits obtained using the theoretical approach overlapped it, leading to inconsistent WDI values. Once water constraint was established, the different stress indicators were linearly correlated to the stem water potential among a tree subset. T s-T a showed a strong sensitivity to evaporative demand, which limited its relevancy for temporal comparisons. Finally, the statistical approach of WDI appeared the most suitable for high-throughput phenotyping.

  16. Stress indicators based on airborne thermal imagery for field phenotyping a heterogeneous tree population for response to water constraints

    PubMed Central

    Virlet, Nicolas; Lebourgeois, Valentine; Martinez, Sébastien; Costes, Evelyne; Labbé, Sylvain; Regnard, Jean-Luc

    2014-01-01

    As field phenotyping of plant response to water constraints constitutes a bottleneck for breeding programmes, airborne thermal imagery can contribute to assessing the water status of a wide range of individuals simultaneously. However, the presence of mixed soil–plant pixels in heterogeneous plant cover complicates the interpretation of canopy temperature. Moran’s Water Deficit Index (WDI = 1–ETact/ETmax), which was designed to overcome this difficulty, was compared with surface minus air temperature (T s–T a) as a water stress indicator. As parameterization of the theoretical equations for WDI computation is difficult, particularly when applied to genotypes with large architectural variability, a simplified procedure based on quantile regression was proposed to delineate the Vegetation Index–Temperature (VIT) scatterplot. The sensitivity of WDI to variations in wet and dry references was assessed by applying more or less stringent quantile levels. The different stress indicators tested on a series of airborne multispectral images (RGB, near-infrared, and thermal infrared) of a population of 122 apple hybrids, under two irrigation regimes, significantly discriminated the tree water statuses. For each acquisition date, the statistical method efficiently delineated the VIT scatterplot, while the limits obtained using the theoretical approach overlapped it, leading to inconsistent WDI values. Once water constraint was established, the different stress indicators were linearly correlated to the stem water potential among a tree subset. T s–T a showed a strong sensitivity to evaporative demand, which limited its relevancy for temporal comparisons. Finally, the statistical approach of WDI appeared the most suitable for high-throughput phenotyping. PMID:25080086

  17. Stress indicators based on airborne thermal imagery for field phenotyping a heterogeneous tree population for response to water constraints.

    PubMed

    Virlet, Nicolas; Lebourgeois, Valentine; Martinez, Sébastien; Costes, Evelyne; Labbé, Sylvain; Regnard, Jean-Luc

    2014-10-01

    As field phenotyping of plant response to water constraints constitutes a bottleneck for breeding programmes, airborne thermal imagery can contribute to assessing the water status of a wide range of individuals simultaneously. However, the presence of mixed soil-plant pixels in heterogeneous plant cover complicates the interpretation of canopy temperature. Moran's Water Deficit Index (WDI = 1-ETact/ETmax), which was designed to overcome this difficulty, was compared with surface minus air temperature (T s-T a) as a water stress indicator. As parameterization of the theoretical equations for WDI computation is difficult, particularly when applied to genotypes with large architectural variability, a simplified procedure based on quantile regression was proposed to delineate the Vegetation Index-Temperature (VIT) scatterplot. The sensitivity of WDI to variations in wet and dry references was assessed by applying more or less stringent quantile levels. The different stress indicators tested on a series of airborne multispectral images (RGB, near-infrared, and thermal infrared) of a population of 122 apple hybrids, under two irrigation regimes, significantly discriminated the tree water statuses. For each acquisition date, the statistical method efficiently delineated the VIT scatterplot, while the limits obtained using the theoretical approach overlapped it, leading to inconsistent WDI values. Once water constraint was established, the different stress indicators were linearly correlated to the stem water potential among a tree subset. T s-T a showed a strong sensitivity to evaporative demand, which limited its relevancy for temporal comparisons. Finally, the statistical approach of WDI appeared the most suitable for high-throughput phenotyping. PMID:25080086

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

    PubMed Central

    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 which disturb the ECG signal. Image synchronization is thus less reliable and yields artefacts in CMR images. Methods A strategy based on Independent Component Analysis (ICA) was pursued in this work to enhance the ECG contribution and attenuate the MHD effect. ICA was applied to 12-lead ECG signals recorded inside a 7 T MR scanner. An automatic source identification procedure was proposed to identify an independent component (IC) dominated by the ECG signal. The identified IC was then used for detecting the R-peaks. The presented ICA-based method was compared to other R-peak detection methods using 1) the raw ECG signal, 2) the raw vectorcardiogram (VCG), 3) the state-of-the-art gating technique based on the VCG, 4) an updated version of the VCG-based approach and 5) the ICA of the VCG. Results ECG signals from eight volunteers were recorded inside the MR scanner. Recordings with an overall length of 87 min accounting for 5457 QRS complexes were available for the analysis. The records were divided into a training and a test dataset. In terms of R-peak detection within the test dataset, the proposed ICA-based algorithm achieved a detection performance with an average sensitivity (Se) of 99.2%, a positive predictive value (+P) of 99.1%, with an average trigger delay and jitter of 5.8 ms and 5.0 ms, respectively. Long term stability of the demixing matrix was shown based on two measurements of the same subject, each being separated by one year, whereas an averaged detection

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

    PubMed Central

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

    2014-01-01

    We report on a female fetus noted to have severe malformative type of skeletal dysplasia on ultrasonography done at 35 weeks gestation. The girl died shortly after birth. Clinical examination showed a fetus with severe dwarfism, extensive long and short bones, and bone deficiencies associated with multiple dislocations. Computed tomography (CT) scan-based phenotype showed a complex constellation of malformations consistent with the diagnosis of Grebe syndrome. Parents being first cousins (consanguineous marriage) strongly suggests autosomal recessive pattern of inheritance. To our knowledge, this is the first report of neonatal death dwarfism of Grebe syndrome analyzed by CT scan-based phenotype. PMID:25337439

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

    ERIC Educational Resources Information Center

    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…

  1. Cardiovascular Disease Consequences of CKD.

    PubMed

    Go, Alan S

    2016-07-01

    Chronic kidney disease, defined as reduced glomerular filtration rate (estimated using serum creatinine- and/or serum cystatin C-based equations) or excess urinary protein excretion, affects approximately 13% of adult Americans and is linked to a variety of clinical complications. Although persons with end-stage renal disease requiring chronic dialysis therapy experience a substantially high cardiovascular burden, whether mild-to-moderate chronic kidney disease is an independent risk factor for fatal and nonfatal cardiovascular events has been more controversial. This review evaluates the current evidence about the clinical and subclinical cardiovascular consequences associated with chronic kidney disease of varying levels of severity. In addition, it discusses the predictors of adverse cardiovascular outcomes while also focusing on recent insights into the relationships between chronic kidney disease and cardiovascular disease from the Chronic Renal Insufficiency Cohort study, a large current prospective cohort study of adults from across the spectrum of chronic kidney disease. PMID:27475660

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

    PubMed Central

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

    2015-01-01

    With the rapid and widespread adoption of mobile devices, mobile phones offer an opportunity to deliver cardiovascular disease (CVD) interventions. This study evaluated the efficacy of a mobile phone-based lifestyle intervention aimed at reducing the overall CVD risk at a health management center in Guangzhou, China. We recruited 589 workers from eight work units. Based on a group-randomized design, work units were randomly assigned either to receive the mobile phone-based lifestyle interventions or usual care. The reduction in 10-year CVD risk at 1-year follow-up for the intervention group was not statistically significant (–1.05%, p = 0.096). However, the mean risk increased significantly by 1.77% (p = 0.047) for the control group. The difference of the changes between treatment arms in CVD risk was –2.83% (p = 0.001). In addition, there were statistically significant changes for the intervention group relative to the controls, from baseline to year 1, in systolic blood pressure (–5.55 vs. 6.89 mmHg; p < 0.001), diastolic blood pressure (–6.61 vs. 5.62 mmHg; p < 0.001), total cholesterol (–0.36 vs. –0.10 mmol/L; p = 0.005), fasting plasma glucose (–0.31 vs. 0.02 mmol/L; p < 0.001), BMI (–0.57 vs. 0.29 kg/m2; p < 0.001), and waist hip ratio (–0.02 vs. 0.01; p < 0.001). Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China. PMID:26694436

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

    PubMed

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

    2015-12-01

    With the rapid and widespread adoption of mobile devices, mobile phones offer an opportunity to deliver cardiovascular disease (CVD) interventions. This study evaluated the efficacy of a mobile phone-based lifestyle intervention aimed at reducing the overall CVD risk at a health management center in Guangzhou, China. We recruited 589 workers from eight work units. Based on a group-randomized design, work units were randomly assigned either to receive the mobile phone-based lifestyle interventions or usual care. The reduction in 10-year CVD risk at 1-year follow-up for the intervention group was not statistically significant (-1.05%, p = 0.096). However, the mean risk increased significantly by 1.77% (p = 0.047) for the control group. The difference of the changes between treatment arms in CVD risk was -2.83% (p = 0.001). In addition, there were statistically significant changes for the intervention group relative to the controls, from baseline to year 1, in systolic blood pressure (-5.55 vs. 6.89 mmHg; p < 0.001), diastolic blood pressure (-6.61 vs. 5.62 mmHg; p < 0.001), total cholesterol (-0.36 vs. -0.10 mmol/L; p = 0.005), fasting plasma glucose (-0.31 vs. 0.02 mmol/L; p < 0.001), BMI (-0.57 vs. 0.29 kg/m²; p < 0.001), and waist hip ratio (-0.02 vs. 0.01; p < 0.001). Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China. PMID:26694436

  4. Thirty-year risk of cardiovascular disease in senior medical students – based on the StudHeart study

    PubMed Central

    Morawiec, Robert; Janikowski, Kamil

    2016-01-01

    Introduction Long-term risk functions highlight the need of prophylaxis in youth before the first symptoms of cardiovascular disease (CVD) occur. Aim On the basis of data obtained in the StudHeart study, the aim of this report was to evaluate the 30-year risk of CVD based on the risk scale developed by the Framingham Heart Study (FHS). Material and methods Seven hundred and one students aged 22–27 (mean age: 24 ±1.42) from the 5th and 6th year of the medical faculties of the Medical University of Lodz were included in the study. The StudHeart study was based on an anonymous survey comprising 12 questions. Based on the answers the authors evaluated the 30-year risk of CVD in each respondent using an on-line calculator that allows one to evaluate: general CVD risk including coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, heart failure and hard CVD risk including coronary death, myocardial infarction and stroke. Results Elevated general 30-year CVD risk occurred in 23.18% of students, while hard CVD risk was elevated in 16.91% of respondents. In both cases elevated risk occurred more often in men (general CVD risk: 43.46% male vs. 8.93% female, p < 0.001 and hard CVD risk: 29.33% male vs. 8.19% female, p < 0.001). Elevation of the risk was mainly caused by overweight, obesity and smoking cigarettes. Conclusions Based on FHS 30-Year CVD risk, elevated risk occurred in almost one-fourth of students. Prophylactic actions should be performed, especially in men. PMID:27516798

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

    PubMed

    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 < 0.001), diastolic blood pressure (-6.61 vs. 5.62 mmHg; p < 0.001), total cholesterol (-0.36 vs. -0.10 mmol/L; p = 0.005), fasting plasma glucose (-0.31 vs. 0.02 mmol/L; p < 0.001), BMI (-0.57 vs. 0.29 kg/m²; p < 0.001), and waist hip ratio (-0.02 vs. 0.01; p < 0.001). Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China.

  6. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity.

    PubMed

    Keogh, M J; Aribisala, B S; He, J; Tulip, E; Butteriss, D; Morris, C; Gorman, G; Horvath, R; Chinnery, P F; Blamire, Andrew M

    2015-10-01

    Neuroferritinopathy is an autosomal dominant adult-onset movement disorder which occurs due to mutations in the ferritin light chain gene (FTL). Extensive iron deposition and cavitation are observed post-mortem in the basal ganglia, but whether more widespread pathological changes occur, and whether they correlate with disease severity is unknown. 3D-T1w and quantitative T2 whole brain MRI scans were performed in 10 clinically symptomatic patients with the 460InsA FTL mutation and 10 age-matched controls. Voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) were subsequently performed. Clinical assessment using the Unified Dystonia Rating Scale (UDRS) and Unified Huntington's Disease Rating Scale (UHDRS) was undertaken in all patients. VBM detected significant tissue changes within the substantia nigra, midbrain and dentate together with significant cerebellar atrophy in patients (FWE, p < 0.05). Iron deposition in the caudate head and cavitation in the lateral globus pallidus correlated with UDRS score (p < 0.001). There were no differences between groups with VBR. Our data show that progressive iron accumulation in the caudate nucleus, and cavitation of the globus pallidus correlate with disease severity in neuroferritinopathy. We also confirm sub-clinical cerebellar atrophy as a feature of the disease. We suggest that VBM is an effective technique to detect regions of iron deposition and cavitation, with potential wider utility to determine radiological markers of disease severity for all NBIA disorders. PMID:26142024

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

    PubMed Central

    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

  8. Nanotechnology in cardiovascular medicine.

    PubMed

    Patel, Devang N; Bailey, Steven R

    2007-04-01

    Nanotechnology is a new field of science and technology that has already had significant impact in the development of novel products in industry. In medicine, application of nanotechnology has the potential to develop new imaging agents, pharmaceutical drugs and medical devices with unique physical and chemical properties. This article reviews the potential for various nanoparticles in cardiovascular imaging and therapeutics, nanoporous structures for sensing and implant based drug delivery, and self-assembled monolayers for surface modification and implant based drug delivery.

  9. Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients

    PubMed Central

    Saaresranta, Tarja; Hedner, Jan; Bonsignore, Maria R.; Riha, Renata L.; McNicholas, Walter T.; Penzel, Thomas; Anttalainen, Ulla; Kvamme, John Arthur; Pretl, Martin; Sliwinski, Pawel; Verbraecken, Johan; Grote, Ludger

    2016-01-01

    Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ≥5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness (“EDS”) and nocturnal sleep problems other than OSA (labelled as “insomnia”): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/non-insomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0±25.5/h vs. 27.9±22.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188–1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. Conclusions Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS. PMID:27701416

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    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. PMID:27752263

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

    PubMed

    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.

  13. Results of a five-year community-based programme for cardiovascular disease prevention: the ATS-Sardegna Campaign.

    PubMed

    Muntoni, S; Stabilini, L; Stabilini, M; Muntoni, S

    1999-01-01

    The objective of this study was to evaluate the effects of the ATS-Sardegna Campaign on lifestyle and cardiovascular disease (CVD) risk factors in the Sardinian population. The Campaign was a community-based public health action programme funded by the Sardinian Government with a view to prevent CVD and promote healthy behaviour. It was also part of the Targeted Project FAT.MA. of the Italian National Research Council (CNR), with the main purpose of evaluating the effects of this public health initiative after a five-year intervention. The evaluation was effected with three parallel procedures: individual interviews with 1486 randomly chosen people; assessment of eating patterns through a food-frequency questionnaire; measurement of the mean levels of the major CVD risk factors in 1729 randomly chosen subjects (1044 in the calendar year 1992, and 685 in 1995, two and five years, respectively, after the beginning of the Campaign). Overall, we recorded a favourable trend in eating habits in both sexes; a significant decrease in LDL-cholesterol in males, and in systolic and diastolic blood pressure in both sexes; a non-significant decrease in prevalence of smokers among males and increase among females. The ATS-Sardegna Campaign was the first CVD prevention programme in Italy to have attained reduction in the risk profile of an entire region at the lowest ever borne cost.

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

    PubMed

    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.

  15. Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy.

    PubMed

    Murphy, Sinead L; Anderson, Jason H; Kapplinger, Jamie D; Kruisselbrink, Teresa M; Gersh, Bernard J; Ommen, Steve R; Ackerman, Michael J; Bos, J Martijn

    2016-04-01

    Genetic testing for hypertrophic cardiomyopathy (HCM) can provide an important clinical marker for disease outcome and family screening. This study set out to validate our recently developed phenotype-based HCM genotype predictor score. Patients clinically diagnosed with HCM and evaluated by genetic counselors comprised the study cohort. Genotype score was derived based on clinical and echocardiographic variables. Total score was correlated with the yield of genetic testing. Of 564 HCM patients, 198 sought genetic testing (35 %; 55 % male; mean age at diagnosis, 50 ± 20 years). Of these, 101 patients (51 %) were genotype positive for a HCM-associated genetic mutation (55 % male; mean age at diagnosis, 42 ± 18 years). Cochran-Armitage analysis showed similar, statistically significant trends of increased yields for higher genotype scores for both the original and study cohort. Validated by the current study, this scoring system provides an easy-to-use, clinical tool to aid in determining the likelihood of a positive HCM genetic test. PMID:26914223

  16. Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy

    PubMed Central

    Murphy, Sinead L.; Anderson, Jason H.; Kapplinger, Jamie D.; Kruisselbrink, Teresa M.; Gersh, Bernard J.; Ommen, Steve R.; Ackerman, Michael J.; Bos, J. Martijn

    2016-01-01

    Genetic testing for hypertrophic cardiomyopathy (HCM) can provide an important clinical marker for disease outcome and family screening. This study set out to validate our recently developed phenotype-based HCM genotype predictor score. Patients clinically diagnosed with HCM and evaluated by genetic counselors comprised the study cohort. Genotype score was derived based on clinical and echocardio-graphic variables. Total score was correlated with the yield of genetic testing. Of 564 HCM patients, 198 sought genetic testing (35 %; 55 % male; mean age at diagnosis, 50 ±20 years). Of these, 101 patients (51 %) were genotype positive for a HCM-associated genetic mutation (55 % male; mean age at diagnosis, 42 ± 18 years). Cochran-Armitage analysis showed similar, statistically significant trends of increased yields for higher genotype scores for both the original and study cohort. Validated by the current study, this scoring system provides an easy-to-use, clinical tool to aid in determining the likelihood of a positive HCM genetic test. PMID:26914223

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

    PubMed Central

    Altadill, Tatiana; Campoy, Irene; Lanau, Lucia; Gill, Kirandeep; Rigau, Marina; Gil-Moreno, Antonio; Reventos, Jaume; Byers, Stephen; Colas, Eva; Cheema, Amrita K.

    2016-01-01

    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. PMID:26974972

  18. Simultaneous MEMS-based electro-mechanical phenotyping of breast cancer

    PubMed Central

    Pandya, Hardik J.; Park, Kihan; Chen, Wenjin; Chekmareva, Marina A.; Foran, David J.; Desai, Jaydev P.

    2015-01-01

    Carcinomas are the most commonly diagnosed cancers originating in the skin, lungs, breasts, pancreas, and other organs and glands. In most of the cases, the microenvironment within the tissue changes with the progression of disease. A key challenge is to develop a device capable of providing quantitative indicators in diagnosing cancer by measuring alteration in electrical and mechanical property of the tissues from the onset of malignancy. We demonstrate micro-electro-mechanical-systems (MEMS) based flexible polymer microsensor array capable of simultaneously measuring electro-mechanical properties of the breast tissues cores (1mm in diameter and 10μm in thickness) from onset through progression of the cancer. The electrical and mechanical signatures obtained from the tissue cores shows the capability of the device to clearly demarcate the specific stages of cancer in epithelial and stromal regions providing quantitative indicators facilitating the diagnosis of breast cancer. The present study shows that electro-mechanical properties of the breast tissue core at the micro-level are different than those at the macro-level. PMID:26224116

  19. Conceptual Models of Frailty: The Sarcopenia Phenotype.

    PubMed

    Afilalo, Jonathan

    2016-09-01

    Population aging has redefined cardiovascular medicine toward multifaceted patient-oriented care, with frailty emerging as a fundamental concept. The definition of frailty is ardently debated between opposing constructs: phenotypic criteria and accumulated deficits. Phenotypic criteria revolve around age-related loss of muscle mass and strength, known as sarcopenia. Skeletal muscle is crucial for functioning, mobility, energetics, and is the body's primary reservoir for amino acids. Sarcopenia can be assessed objectively, serving as an incremental predictor of adverse health outcomes and a therapeutic target for muscle-building interventions. Thus, the sarcopenia phenotype should be the central focus of frailty assessment and intervention. PMID:27568870

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

    PubMed

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

    2015-03-09

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

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

    NASA Astrophysics Data System (ADS)

    Aragón, A. M.; Hernando-Rydings, M.; Hernando, A.; Marín, P.

    2015-08-01

    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.

  2. Framingham Ten-Year General Cardiovascular Disease Risk: Agreement between BMI-Based and Cholesterol-Based Estimates in a South Asian Convenience Sample

    PubMed Central

    Jones, Charlotte A.; Ross, Leanne; Surani, Nadia; Dharamshi, Narissa; Karmali, Karima

    2015-01-01

    The goal of this analysis was to determine the agreement between body mass index-based and cholesterol-based ten-year Framingham general cardiovascular disease risk scores among a convenience sample of 773 South Asian Canadian adults attending community-based screening clinics. Scores were calculated using age, systolic blood pressure, antihypertensive use, current smoking, diabetes, and total cholesterol and high density lipoprotein (for cholesterol-based risk) or height and weight (for body mass index-based risk). Mean risk score differences (body mass index-based risk minus cholesterol-based risk) were estimated using paired t-tests. Bland-Altman plots were used to assess agreement between scores. Finally, agreement across risk categories (low [<10%], moderate [10% to <20%], high [> = 20%]) was examined using the kappa statistic. Average agreement between the two risk scores was quite good overall (mean differences of 0.6% for men and 0.5% for women), but increased to about 3% among participants 60–74 years of age. However, Bland-Altman plots revealed that the differences between the two scores and the variability of the differences increased with increasing average 10-year risk. In terms of clinical importance, the limits of agreement were reasonable for women < 60 years (95% confidence interval: -3.2% to 3.1%), but of concern for women 60-74 years (95% confidence interval: -6.0% to 12.3%), men < 60 years (95% confidence interval: -7.1% to 7.3%) and men 6-074 years (95% confidence interval: -13.8% to 18.8%). Agreement across categories was moderate for most sex and age groups examined (kappa values: 0.51 for women < 60 years, 0.50 for women 60-74 years, 0.65 for men < 60 years), except for men 60-74 years, where agreement was only fair (kappa = 0.26). In light of these disagreements, evaluation of a participant’s change in cardiovascular disease risk over time will necessitate use of the same risk score (i.e., either body mass index-based or cholesterol-based

  3. Bi-content micro-collagen chip provides contractility-based biomechanical readout for phenotypic drug screening with expanded and profiled targets.

    PubMed

    Zhao, Hui; Zhou, Lyu; Zhang, Qiang; Zhou, Xiaoying; Zhang, Yonghui; Chen, Huijun; Du, Yanan

    2015-09-01

    Phenotypic screening has regained momentum in the pharmaceutical industry owing to its success over target-based screening. Most phenotypic screening relies on nonspecific biochemical readouts regarding cellular viability, which hampers the discovery of novel drug mechanisms of action (MOAs). Here we present a Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes cellular contractility as a biomechanics-related phenotype for drug screening. Bi-content analysis of cell contractility (imaged by iPhone) and viability suggests that the label-free contractility-based analysis exhibits superior sensitivity to compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton), resulting in a enlarged target pool for drug assessment. Six typical readout patterns of drug response are summarized according to the relative positions of the contraction/viability curves, and drug targets are profiled into three categories (biomechanical, biochemical and housekeeping) by 3CChip, which will benefit subsequent target identification. The simple-to-use and effective 3CChip offers a robust platform for micro-tissue-based functional screening and may lead to a new era of mechanism-informed phenotypic drug discovery. PMID:26219255

  4. Field-based high-throughput plant phenotyping reveals the temporal patterns of quantitative trait loci associated with stress-responsive traits in cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To dissect the genetic basis of dynamic adaptive traits under relevant growing conditions, we employed a field-based, high-throughput plant phenotyping (HTPP) system that deployed four sets of sensors to simultaneously measure canopy temperature, reflectance, and height on a cotton (Gossypium hirsut...

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

    PubMed Central

    Namdar, Hossein; Taban Sadeghi, Mohammadreza; Sabourimoghaddam, Hassan; Sadeghi, Babak; Ezzati, Davoud

    2014-01-01

    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. PMID:25320667

  6. Cardiovascular disease risk factors in relation to smoking behaviour and history: a population-based cohort study

    PubMed Central

    Keto, Jaana; Ventola, Hanna; Jokelainen, Jari; Linden, Kari; Keinänen-Kiukaanniemi, Sirkka; Timonen, Markku; Ylisaukko-oja, Tero; Auvinen, Juha

    2016-01-01

    Objective To investigate how individual risk factors for cardiovascular disease (CVD) (blood pressure, lipid levels, body mass index, waist and hip circumference, use of antihypertensive or hypolipidemic medication, and diagnosed diabetes) differ in people aged 46 years with different smoking behaviour and history. Methods This population-based cohort study is based on longitudinal data from the Northern Finland Birth Cohort 1966 project. Data were collected at the 31-year and 46-year follow-ups, when a total of 5038 and 5974 individuals participated in clinical examinations and questionnaires. Data from both follow-ups were available for 3548 participants. In addition to individual CVD risk factors, Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms were used to assess the absolute risk of a CVD event within the next decade. Results The differences in individual risk factors for CVD reached statistical significance for some groups, but the differences were not consistent or clinically significant. There were no clinically significant differences in CVD risk as measured by Framingham or SCORE algorithms between never smokers, recent quitters and former smokers (7.5%, 7.4%, 8.1% for men; 3.3%, 3.0%, 3.2% for women; p<0.001). Conclusions The effect of past or present smoking on individual CVD risk parameters such as blood pressure and cholesterol seems to be of clinically minor significance in people aged 46 years. In other words, smoking seems to be above all an independent risk factor for CVD in the working-age population. Quitting smoking in working age may thus reduce calculated CVD risk nearly to the same level with people who have never smoked. PMID:27493759

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Evidence to support church-based health promotion programmes for African Canadians at risk for cardiovascular disease.

    PubMed

    Tomlinson, Sherldine

    2011-12-01

    High quality management of cardiovascular disease is a critical health issue for people of African descent as this group is more likely than the general population to have greater coexisting cardiovascular comorbidities. The higher than average rates of cardiovascular conditions among Black populations are a cause for concern. In an effort to combat the disproportionate number of African Americans experiencing cardiovascular conditions a significant number of churches within the African American community have initiated health promotion programmes and/or services. Health organisations and agencies in the United States are keen to support and encourage these programmes for cardiovascular disease risk populations (i.e. African Americans and other minority groups, such as the Hispanic community). Indeed these health organisations and agencies recognise the need to promote healthier habits among African Americans and other minority groups as statistics continue to show health disparities among these populations within the US health care system. This paper attempts to encourage Canadian health agencies, organizations and practitioners to support similar CBHPPs initiatives for the African Canadian population. The historical significance of the church in Black Canadian communities is also examined.

  9. Temporal trends in cardiovascular disease risk factors among white, South Asian, Chinese and black groups in Ontario, Canada, 2001 to 2012: a population-based study

    PubMed Central

    Chiu, Maria; Maclagan, Laura C; Tu, Jack V; Shah, Baiju R

    2015-01-01

    Objectives To determine ethnic-specific temporal trends in cardiovascular risk factors in Ontario between 2001 and 2012. Design A population-based repeated cross-sectional study. Setting Ontario, Canada. Participants 219 276 participants of the Canadian Community Health Survey (205 326 white, 5620 South Asian, 4368 Chinese and 3962 black) during the period 2001 to 2012. Main outcome measures Age-standardised ethnic-sex-specific prevalence of cardiovascular risk factors for three time periods: 2001–2004, 2005–2008 and 2009–2012 among Canada's four major ethnic groups: white, South Asian, Chinese and black. Results During the study period, the prevalence of diabetes increased 2.3-fold (p=0.0001) among South Asian males and 1.9-fold (p=0.02) among black females. The prevalence of obesity (body mass index ≥30 kg/m2) increased over time across all ethnic groups, with the largest relative increases observed among males of Chinese (2.1-fold increase, p=0.04) and black (1.7-fold increase, p=0.06) descent. The prevalence of hypertension increased the most among black females. Smoking prevalence decreased by more than 20% among South Asian, Chinese and white females. Overall, South Asian males and black males and females showed the greatest declines in cardiovascular health over the study period. Conclusions We observed important ethnic differences in the temporal trends in cardiovascular risk factor profiles in Ontario. Awareness of the direction and magnitude of these risk factor trends may be useful in informing targeted strategies for preventing cardiovascular diseases in multiethnic populations. PMID:26260346

  10. 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

    PubMed Central

    Roussel, Ronan; Chaignot, Christophe; Weill, Alain; Travert, Florence; Hansel, Boris; Marre, Michel; Ricordeau, Philippe; Alla, François; Allemand, Hubert

    2015-01-01

    Background and Aim 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. Design 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. Methods 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. Results 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) and after 540 days (HR>540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR<540 = 0.95 (95% CI: 0.78–1.16) and HR>540 = 1.73 (1.28–2.32). Conclusion Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy. PMID:26398765

  11. Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population-based cohort study of 32,308 one-year survivors.

    PubMed

    Gudmundsdottir, Thorgerdur; Winther, Jeanette F; de Fine Licht, Sofie; Bonnesen, Trine G; Asdahl, Peter H; Tryggvadottir, Laufey; Anderson, Harald; Wesenberg, Finn; Malila, Nea; Hasle, Henrik; Olsen, Jørgen H

    2015-09-01

    The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population-based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one-year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0-2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person-years. At the end of follow-up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ∼500-600 per 100,000 person-years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5-5.9), valvular dysfunction (4.6; 3.8-5.5) and cerebrovascular diseases (3.7; 3.4-4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow-up for this rapidly growing population.

  12. Candidate foods in the Asia-Pacific region for cardiovascular protection: relevance of grains and grain-based foods to coronary heart disease.

    PubMed

    McBurney, M I

    2001-01-01

    This review elucidates the importance of healthy dietary and lifestyle habits to reduce morbidity and mortality associated with coronary heart disease (CHD), stroke and cardiovascular diseases. Given published evidence of the poor compliance, increased cost, and decreased benefit/risk ratios of medical therapies, individuals (and populations) are encouraged to adopt healthy life habits. The three most atherogenic dietary risk factors are saturated fat, cholesterol and obesity. Dietary patterns associated with the consumption of grains and grain-based foods predict risk of CHD independently of other life habits. Epidemiological and intervention studies elucidating the strong protective associations of grains, cereal fibers and anti-oxidant vitamins on CHD are reviewed. In summary, the consumption of grains and grain-based cereals is repeatedly associated with the ingestion of many nutrients, e.g., dietary fiber and anti-oxidants, that alter energy balance and nutrient intakes to positively affect cardiovascular health, especially when combined with healthy life habits,

  13. Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

    PubMed

    Sadaie, Mahito; Dillon, Christian; Narita, Masako; Narita, Masashi; Young, Andrew R J; Cairney, Claire J; Godwin, Lauren S; Torrance, Christopher J; Bennett, Dorothy C; Keith, W Nicol; Narita, Masashi

    2015-09-01

    Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.

  14. Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition

    PubMed Central

    Sadaie, Mahito; Dillon, Christian; Narita, Masashi; Young, Andrew R. J.; Cairney, Claire J.; Godwin, Lauren S.; Torrance, Christopher J.; Bennett, Dorothy C.; Keith, W. Nicol; Narita, Masashi

    2015-01-01

    Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target. PMID:26133385

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

    PubMed

    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. PMID:26809099

  16. CRISPR-Cas9D10A nickase-based genotypic and phenotypic screening to enhance genome editing

    PubMed Central

    Chiang, Ting-Wei Will; le Sage, Carlos; Larrieu, Delphine; Demir, Mukerrem; Jackson, Stephen P.

    2016-01-01

    The RNA-guided Cas9 nuclease is being widely employed to engineer the genomes of various cells and organisms. Despite the efficient mutagenesis induced by Cas9, off-target effects have raised concerns over the system’s specificity. Recently a “double-nicking” strategy using catalytic mutant Cas9D10A nickase has been developed to minimise off-target effects. Here, we describe a Cas9D10A-based screening approach that combines an All-in-One Cas9D10A nickase vector with fluorescence-activated cell sorting enrichment followed by high-throughput genotypic and phenotypic clonal screening strategies to generate isogenic knockouts and knock-ins highly efficiently, with minimal off-target effects. We validated this approach by targeting genes for the DNA-damage response (DDR) proteins MDC1, 53BP1, RIF1 and P53, plus the nuclear architecture proteins Lamin A/C, in three different human cell lines. We also efficiently obtained biallelic knock-in clones, using single-stranded oligodeoxynucleotides as homologous templates, for insertion of an EcoRI recognition site at the RIF1 locus and introduction of a point mutation at the histone H2AFX locus to abolish assembly of DDR factors at sites of DNA double-strand breaks. This versatile screening approach should facilitate research aimed at defining gene functions, modelling of cancers and other diseases underpinned by genetic factors, and exploring new therapeutic opportunities. PMID:27079678

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

    PubMed

    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.

  18. Phenotypic characterization of Vibrio vulnificus biotype 2, a lipopolysaccharide-based homogeneous O serogroup within Vibrio vulnificus.

    PubMed Central

    Biosca, E G; Oliver, J D; Amaro, C

    1996-01-01

    In this study, we have reevaluated the taxonomic position of biotype 2 of Vibrio vulnificus. For this purpose, we have biochemically and serologically characterized 83 biotype 2 strains from diseased eels, comparing them with 17 biotype 1 strains from different sources. Selected strains were also molecularly analyzed and tested for eel and mouse pathogenicity. Results have shown that biotype 2 (i) is biochemically homogeneous, indole production being the main trait that distinguishes it from biotype 1, (ii) presents small variations in DNA restriction profiles and outer membrane protein patterns, some proteins being immunologically related to outer membrane proteins from biotype 1, (iii) expresses a common lipopolysaccharide (LPS) profile, which is immunologically identical among strains and distinct from that of LPS of tested biotype 1 strains, and (iv) contains at least two high-Mr plasmids. Regarding host range, we have confirmed that both biotypes are pathogenic for mice but only biotype 2 is pathogenic for eels. On the basis of these data, we propose that biotype 2 of V. vulnificus constitutes an LPS-based O serogroup which is phenotypically homogeneous and pathogenic for eels. In this article, the serogroup is designated serogroup E (for eels). PMID:8975619

  19. Quantification of oxidative stress phenotypes based on high-throughput growth profiling of protein kinase and phosphatase knockouts.

    PubMed

    Altıntaş, Ali; Martini, Jacopo; Mortensen, Uffe H; Workman, Christopher T

    2016-02-01

    Cellular responses to oxidative stress are important for restoring redox balance and ensuring cell survival. Genetic defects in response factors can lead to impaired response to oxidative damage and contribute to disease and aging. In single cell organisms, such as yeasts, the integrity of the oxidative stress response can be observed through its influences on growth characteristics. In this study, we investigated the time-dependent batch growth effects as a function of oxidative stress levels in protein kinase and phosphatase deletion backgrounds of Saccharomyces cerevisiae. In total, 41 different protein kinases and phosphatase mutants were selected for their known activities in oxidative stress or other stress response pathways and were investigated for their dosage-dependent response to hydrogen peroxide. Detailed growth profiles were analyzed after the induction of stress for growth rate, lag time duration and growth efficiency, and by a novel method to identify stress-induced diauxic shift delay. This approach extracts more phenotypic information than traditional plate-based methods due to the assessment of time dynamics in the time scale of minutes. With this approach, we were able to identify surprisingly diverse sensitivity and resistance patterns as a function of gene knockout.

  20. CRISPR-Cas9(D10A) nickase-based genotypic and phenotypic screening to enhance genome editing.

    PubMed

    Chiang, Ting-Wei Will; le Sage, Carlos; Larrieu, Delphine; Demir, Mukerrem; Jackson, Stephen P

    2016-01-01

    The RNA-guided Cas9 nuclease is being widely employed to engineer the genomes of various cells and organisms. Despite the efficient mutagenesis induced by Cas9, off-target effects have raised concerns over the system's specificity. Recently a "double-nicking" strategy using catalytic mutant Cas9(D10A) nickase has been developed to minimise off-target effects. Here, we describe a Cas9(D10A)-based screening approach that combines an All-in-One Cas9(D10A) nickase vector with fluorescence-activated cell sorting enrichment followed by high-throughput genotypic and phenotypic clonal screening strategies to generate isogenic knockouts and knock-ins highly efficiently, with minimal off-target effects. We validated this approach by targeting genes for the DNA-damage response (DDR) proteins MDC1, 53BP1, RIF1 and P53, plus the nuclear architecture proteins Lamin A/C, in three different human cell lines. We also efficiently obtained biallelic knock-in clones, using single-stranded oligodeoxynucleotides as homologous templates, for insertion of an EcoRI recognition site at the RIF1 locus and introduction of a point mutation at the histone H2AFX locus to abolish assembly of DDR factors at sites of DNA double-strand breaks. This versatile screening approach should facilitate research aimed at defining gene functions, modelling of cancers and other diseases underpinned by genetic factors, and exploring new therapeutic opportunities. PMID:27079678

  1. High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling

    PubMed Central

    Larrouy-Maumus, Gerald; Gilleron, Martine; Ewann, Fanny; Christophe, Thierry; Fenistein, Denis; Jang, Jichan; Jang, Mi-Seon; Park, Sei-Jin; Rauzier, Jean; Carralot, Jean-Philippe; Shrimpton, Rachel; Genovesio, Auguste; Gonzalo-Asensio, Jesus A.; Puzo, Germain; Martin, Carlos; Brosch, Roland; Stewart, Graham R.; Gicquel, Brigitte; Neyrolles, Olivier

    2010-01-01

    The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis of over 11,000 Mycobacterium tuberculosis mutants. This very stringent assay makes use of fluorescent staining for intracellular acidic compartments, and automated confocal microscopy to quantitatively determine the intracellular localization of M. tuberculosis. We characterised the ten mutants that traffic most frequently into acidified compartments early after phagocytosis, suggesting that they had lost their ability to arrest phagosomal maturation. Molecular analysis of these mutants revealed mainly disruptions in genes involved in cell envelope biogenesis (fadD28), the ESX-1 secretion system (espL/Rv3880), molybdopterin biosynthesis (moaC1 and moaD1), as well as in genes from a novel locus, Rv1503c-Rv1506c. Most interestingly, the mutants in Rv1503c and Rv1506c were perturbed in the biosynthesis of acyltrehalose-containing glycolipids. Our results suggest that such glycolipids indeed play a critical role in the early intracellular fate of the tubercle bacillus. The unbiased approach developed here can be easily adapted for functional genomics study of intracellular pathogens, together with focused discovery of new anti-microbials. PMID:20844580

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    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

  5. Hyperuricemia, Cardiovascular Disease, and Hypertension

    PubMed Central

    Kuwabara, Masanari

    2016-01-01

    In recent years, there has been an increase in the prevalence of hyperuricemia, and the latter has attracted attention as an adult lifestyle-associated disease, together with hypertension, diabetes, and dyslipidemia. Although hyperuricemia is known to be an independent risk factor for hypertension, whether it is an independent risk factor for cardiovascular disease remains controversial. Recently, some small-scale interventional studies on antihyperuricemic medications showed that the latter improved angina symptoms and prevented cardiovascular disease. Here, we will mainly explain the cause of hyperuricemia and the associations between hyperuricemia, hypertension, and cardiovascular disease based on the latest published evidence. PMID:27195245

  6. Cardiovascular group

    NASA Technical Reports Server (NTRS)

    Blomqvist, Gunnar

    1989-01-01

    As a starting point, the group defined a primary goal of maintaining in flight a level of systemic oxygen transport capacity comparable to each individual's preflight upright baseline. The goal of maintaining capacity at preflight levels would seem to be a reasonable objective for several different reasons, including the maintenance of good health in general and the preservation of sufficient cardiovascular reserve capacity to meet operational demands. It is also important not to introduce confounding variables in whatever other physiological studies are being performed. A change in the level of fitness is likely to be a significant confounding variable in the study of many organ systems. The principal component of the in-flight cardiovascular exercise program should be large-muscle activity such as treadmill exercise. It is desirable that at least one session per week be monitored to assure maintenance of proper functional levels and to provide guidance for any adjustments of the exercise prescription. Appropriate measurements include evaluation of the heart-rate/workload or the heart-rate/oxygen-uptake relationship. Respiratory gas analysis is helpful by providing better opportunities to document relative workload levels from analysis of the interrelationships among VO2, VCO2, and ventilation. The committee felt that there is no clear evidence that any particular in-flight exercise regimen is protective against orthostatic hypotension during the early readaptation phase. Some group members suggested that maintenance of the lower body muscle mass and muscle tone may be helpful. There is also evidence that late in-flight interventions to reexpand blood volume to preflight levels are helpful in preventing or minimizing postflight orthostatic hypotension.

  7. Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

    PubMed Central

    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

  8. Integrating binary traits with quantitative phenotypes for association mapping of multivariate phenotypes.

    PubMed

    Mukhopadhyay, Indranil; Saha, Sujayam; Ghosh, Saurabh

    2011-01-01

    Clinical binary end-point traits are often governed by quantitative precursors. Hence it may be a prudent strategy to analyze a clinical end-point trait by considering a multivariate phenotype vector, possibly including both quantitative and qualitative phenotypes. A major statistical challenge lies in integrating the constituent phenotypes into a reduced univariate phenotype for association analyses. We assess the performances of certain reduced phenotypes using analysis of variance and a model-free quantile-based approach. We find that analysis of variance is more powerful than the quantile-based approach in detecting association, particularly for rare variants. We also find that using a principal component of the quantitative phenotypes and the residual of a logistic regression of the binary phenotype on the quantitative phenotypes may be an optimal method for integrating a binary phenotype with quantitative phenotypes to define a reduced univariate phenotype. PMID:22373144

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

    PubMed

    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.

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

    PubMed

    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

  11. A Community-based Cross-sectional Study of Cardiovascular Risk in a Rural Community of Puducherry

    PubMed Central

    Shrivastava, Saurabh R.; Ghorpade, Arun G.; Shrivastava, Prateek S.

    2015-01-01

    Background: The World Health Organization (WHO) / International Society of Hypertension (ISH) risk prediction chart can predict the risk of cardiovascular events in any population. Aim: To assess the prevalence of cardiovascular risk factors and to estimate the cardiovascular risk using the WHO/ISH risk charts. Materials and Methods: A cross-sectional study was done from November 2011 to January 2012 in a rural area of Puducherry. Method of sampling was a single stage cluster random sampling, and subjects were enrolled depending on their suitability with the inclusion and exclusion criteria. The data collection tool was a piloted and semi-structured questionnaire, while WHO/ISH cardiovascular risk prediction charts for the South-East Asian region was used to predict the cardiovascular risk. Institutional Ethics committee permission was obtained before the start of the study. Statistical analysis was done using SPSS version 16 and appropriate statistical tests were applied. Results: The mean age in years was 54.2 (±11.1) years with 46.7% of the participants being male. On application of the WHO/ISH risk prediction charts, almost 17% of the study subjects had moderate or high risk for a cardiovascular event. Additionally, high salt diet, alcohol use and low HDL levels, were identified as the major CVD risk factors. Conclusion: To conclude, stratification of people on the basis of risk prediction chart is a major step to have a clear idea about the magnitude of the problem. The findings of the current study revealed that there is a high burden of CVD risk in the rural Puducherry. PMID:26900417

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

    PubMed

    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

  13. Community Engagement to Optimize the Use of Web-Based and Wearable Technology in a Cardiovascular Health and Needs Assessment Study: A Mixed Methods Approach

    PubMed Central

    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

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

    PubMed

    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.

  15. Salud para su Corazón: a community-based Latino cardiovascular disease prevention and outreach model.

    PubMed

    Alcalay, R; Alvarado, M; Balcazar, H; Newman, E; Huerta, E

    1999-10-01

    Cardiovascular disease (CVD) is the leading cause of death for Latinos living in the United States. This population is generally unaware of important lifestyle or behavioral changes that can prevent CVD. The National Heart, Lung, and Blood Institute (NHLBI) designed and implemented Salud para su Corazón (Health for Your Heart), a culturally appropriate, community-based, theory-driven intervention model. NHLBI's goals were: (1) to design an intervention model appropriate to Latino populations; (2) to pilot test the model in a specific community with the objectives of increasing awareness about heart disease, raising knowledge about CVD prevention, and promoting heart-healthy lifestyles; and (3) to disseminate the model and the materials developed to other communities with similar needs. An agency-community partnership, under the leadership of the Community Alliance for Heart Health, guided all stages of the community intervention project. The multimedia bilingual community intervention included television telenovela format public service announcements (PSAs), radio programs, brochures, recipe booklets, charlas, a promotores training manual, and motivational videos. An evaluation survey assessed the impact of the intervention. A pre-post intervention survey was conducted with more than 300 participants, and results showed that the respondents were substantially more aware of risk factors for CVD, and had greatly increased their knowledge of ways to prevent heart disease. Dissemination efforts have resulted in numerous requests by health organizations, universities, and health maintenance organizations (HMOs) for educational materials and communication strategies produced by Salud para su Corazón. In addition, Univision, the largest Spanish-language broadcast television network, is airing the initiative's PSAs. Also, training seminars for promotores are being conducted in different regions of the United States, and several locations are planning to replicate this

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

    SciTech Connect

    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.

  17. Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen

    PubMed Central

    2013-01-01

    Background HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. Results Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. Conclusions Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I. PMID:24229420

  18. From volume to value? Can a value-based approach help deliver the ambitious aims of the NHS cardiovascular disease outcomes strategy?

    PubMed

    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. PMID:24619245

  19. Cardiovascular physiology in space flight

    NASA Technical Reports Server (NTRS)

    Charles, John B.; Bungo, Michael W.

    1991-01-01

    The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.

  20. Marathon run: cardiovascular adaptation and cardiovascular risk.

    PubMed

    Predel, Hans-Georg

    2014-11-21

    The first marathon run as an athletic event took place in the context of the Olympic Games in 1896 in Athens, Greece. Today, participation in a 'marathon run' has become a global phenomenon attracting young professional athletes as well as millions of mainly middle-aged amateur athletes worldwide each year. One of the main motives for these amateur marathon runners is the expectation that endurance exercise (EE) delivers profound beneficial health effects. However, with respect to the cardiovascular system, a controversial debate has emerged whether the marathon run itself is healthy or potentially harmful to the cardiovascular system, especially in middle-aged non-elite male amateur runners. In this cohort, exercise-induced increases in cardiac biomarkers-troponin and brain natriuretic peptide-and acute functional cardiac alterations have been observed and interpreted as potential cardiac damage. Furthermore, in the cohort of 40- to 65-year-old males engaged in intensive EE, a significant risk for the development of atrial fibrillation has been identified. Fortunately, recent studies demonstrated a normalization of the cardiac biomarkers and the functional alterations within a short time frame. Therefore, these alterations may be perceived as physiological myocardial reactions to the strenuous exercise and the term 'cardiac fatigue' has been coined. This interpretation is supported by a recent analysis of 10.9 million marathon runners demonstrating that there was no significantly increased overall risk of cardiac arrest during long-distance running races. In conclusion, intensive and long-lasting EE, e.g. running a full-distance Marathon, results in high cardiovascular strain whose clinical relevance especially for middle-aged and older athletes is unclear and remains a matter of controversy. Furthermore, there is a need for evidence-based recommendations with respect to medical screening and training strategies especially in male amateur runners over the age of

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

    EPA Science Inventory

    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. Cardiovascular instrumentation for spaceflight

    NASA Technical Reports Server (NTRS)

    Schappell, R. T.; Polhemus, J. T.; Ganiaris, N. J.

    1976-01-01

    The observation mechanisms dealing with pressure, flow, morphology, temperature, etc. are discussed. The approach taken in the performance of this study was to (1) review ground and space-flight data on cardiovascular function, including earlier related ground-based and space-flight animal studies, Mercury, Gemini, Apollo, Skylab, and recent bed-rest studies, (2) review cardiovascular measurement parameters required to assess individual performance and physiological alternations during space flight, (3) perform an instrumentation survey including a literature search as well as personal contact with the applicable investigators, (4) assess instrumentation applicability with respect to the established criteria, and (5) recommend future research and development activity. It is concluded that, for the most part, the required instrumentation technology is available but that mission-peculiar criteria will require modifications to adapt the applicable instrumentation to a space-flight configuration.

  3. Cardiovascular adaptation to spaceflight

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Watenpaugh, D. E.

    1996-01-01

    This article reviews recent flight and ground-based studies of cardiovascular adaptation to spaceflight. Prominent features of microgravity exposure include loss of gravitational pressures, relatively low venous pressures, headward fluid shifts, plasma volume loss, and postflight orthostatic intolerance and reduced exercise capacity. Many of these short-term responses to microgravity extend themselves during long-duration microgravity exposure and may be explained by altered pressures (blood and tissue) and fluid balance in local tissues nourished by the cardiovascular system. In this regard, it is particularly noteworthy that tissues of the lower body (e.g., foot) are well adapted to local hypertension on Earth, whereas tissues of the upper body (e.g., head) are not as well adapted to increase in local blood pressure. For these and other reasons, countermeasures for long-duration flight should include reestablishment of higher, Earth-like blood pressures in the lower body.

  4. Stress and atherosclerotic cardiovascular disease.

    PubMed

    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.

  5. Hypothetical Exposure Limits for Oil-Based Metalworking Fluids and Cardiovascular Mortality in a Cohort of Autoworkers: Structural Accelerated Failure Time Models in a Public Health Framework

    PubMed Central

    Picciotto, Sally; Peters, Annette; Eisen, Ellen A.

    2015-01-01

    Occupational exposure to aerosolized particles of oil-based metalworking fluid was recently linked to deaths from ischemic heart disease. The current recommended exposure limits might be insufficient. Studying cardiovascular mortality is challenging because symptoms can induce sicker workers to reduce their exposure, causing healthy-worker survivor bias. G-estimation of accelerated failure time models reduces this bias and permits comparison of multiple exposure interventions. Michigan autoworkers from the United AutoWorkers–General Motors cohort (n = 38,666) were followed from 1941 through 1994. Separate binary variables indicated whether annual exposure exceeded a series of potential limits. Separate g-estimation analyses for each limit yielded the total number of life-years that could have been saved among persons who died from specific cardiovascular causes by enforcing that exposure limit. Banning oil-based fluids would have saved an estimated 4,003 (95% confidence interval: 2,200, 5,807) life-years among those who died of ischemic heart disease. Estimates for cardiovascular disease overall, acute myocardial infarction, and cerebrovascular disease were 3,500 (95% confidence interval: 1,350, 5,651), 2,932 (95% confidence interval: 1,587, 4,277), and 917 (95% confidence interval: −80, 1,913) life-years, respectively. A limit of 0.01 mg/m3 would have had a similar impact on cerebrovascular disease but one only half as great on ischemic heart disease. Analyses suggest that limiting exposure to metalworking fluids could have saved many life-years lost to cardiovascular diseases in this cohort. PMID:25816818

  6. Hypothetical exposure limits for oil-based metalworking fluids and cardiovascular mortality in a cohort of autoworkers: structural accelerated failure time models in a public health framework.

    PubMed

    Picciotto, Sally; Peters, Annette; Eisen, Ellen A

    2015-04-15

    Occupational exposure to aerosolized particles of oil-based metalworking fluid was recently linked to deaths from ischemic heart disease. The current recommended exposure limits might be insufficient. Studying cardiovascular mortality is challenging because symptoms can induce sicker workers to reduce their exposure, causing healthy-worker survivor bias. G-estimation of accelerated failure time models reduces this bias and permits comparison of multiple exposure interventions. Michigan autoworkers from the United AutoWorkers-General Motors cohort (n = 38,666) were followed from 1941 through 1994. Separate binary variables indicated whether annual exposure exceeded a series of potential limits. Separate g-estimation analyses for each limit yielded the total number of life-years that could have been saved among persons who died from specific cardiovascular causes by enforcing that exposure limit. Banning oil-based fluids would have saved an estimated 4,003 (95% confidence interval: 2,200, 5,807) life-years among those who died of ischemic heart disease. Estimates for cardiovascular disease overall, acute myocardial infarction, and cerebrovascular disease were 3,500 (95% confidence interval: 1,350, 5,651), 2,932 (95% confidence interval: 1,587, 4,277), and 917 (95% confidence interval: -80, 1,913) life-years, respectively. A limit of 0.01 mg/m(3) would have had a similar impact on cerebrovascular disease but one only half as great on ischemic heart disease. Analyses suggest that limiting exposure to metalworking fluids could have saved many life-years lost to cardiovascular diseases in this cohort. PMID:25816818

  7. A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer

    PubMed Central

    Eiró, Noemí; Fernandez-Garcia, Belen; Vázquez, Julio; del Casar, José M; González, Luis O; Vizoso, Francisco J

    2015-01-01

    The objective of the present work was to evaluate the impact of the phenotype of both mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs) in early breast cancer patients, specifically assessed as to their expression of MMP/TIMP relative to their position within the tumor (i.e., localization at the tumor center or invasive front) and the occurrence of distant metastases.. An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)−1, −2, −7, −9, −11, −13 and −14, tissue inhibitors of metalloproteinase (TIMP)−1, −2 and −3, both at tumor center and at invasive front, in 107 patients with primary ductal invasive breast tumors. Data were analyzed by unsupervised hierarchical clustering analysis. Our results indicated that MMP-11 expression by MICs, and TIMP-2 expression by CAFs at either the tumor center or the invasive front, were the most potent independent prognostic factors for predicting the clinical outcome of patients. Using the unsupervised hierarchical clustering analysis, we found well-defined clusters of cases identifying subgroups of tumors showing a high molecular profile of MMPs/TIMPs expression by stromal cells (CAFs and MICs), both at the tumor center and at the invasive front, which were strongly associated with a higher prevalence of distant metastasis. In addition, we found combinations of these clusters defining subpopulations of breast carcinomas differing widely in their clinical outcome. The results presented here identify biologic markers useful to categorize patients into different subgroups based on their tumor stroma, which may contribute to improved understanding of the prognosis of breast cancer patients. PMID:26140253

  8. Epigenetic programming and risk: the birthplace of cardiovascular disease?

    PubMed

    Vinci, Maria Cristina; Polvani, Gianluca; Pesce, Maurizio

    2013-06-01

    Epigenetics, through control of gene expression circuitries, plays important roles in various physiological processes such as stem cell differentiation and self renewal. This occurs during embryonic development, in different tissues, and in response to environmental stimuli. The language of epigenetic program is based on specific covalent modifications of DNA and chromatin. Thus, in addition to the individual identity, encoded by sequence of the four bases of the DNA, there is a cell type identity characterized by its positioning in the epigenetic "landscape". Aberrant changes in epigenetic marks induced by environmental cues may contribute to the development of abnormal phenotypes associated with different human diseases such as cancer, neurological disorders and inflammation. Most of the epigenetic studies have focused on embryonic development and cancer biology, while little has been done to explore the role of epigenetic mechanisms in the pathogenesis of cardiovascular disease. This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function. PMID:22773406

  9. Proceedings of a conference on Cardiovascular Bioinstrumentation

    NASA Technical Reports Server (NTRS)

    Ballard, Rodney W.; Fuller, Charles A.; Mains, Richard; Finger, Herbert J.

    1988-01-01

    The Ames Research Center (ARC) has a long history in the development of cardiovascular (CV) instrumentation for human and animal research. The ARC Cardiovascular Research Lab under the Space Physiology Branch, Space Research Directorate, supports both ground-based and space-based animal and human research goals. The Cardiovascular Research Laboratory was established at ARC in the mid 1960's to conduct ground-based animal research and support development of advanced cardiovascular instrumentation applicable to spaceflight. The ARC Biomedical Research Program also conducts human studies with a CV instrumentation focus.

  10. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events.

    PubMed

    Kario, Kazuomi

    2016-07-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events. PMID:27482253

  11. Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events

    PubMed Central

    2016-01-01

    Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based 'anticipation medicine' predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events. PMID:27482253

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

    PubMed Central

    Li, Chien-Hsun; Chen, Hung-An; Yeh, Chia-Lun; Chiu, Shih-Hsiang; Lin, Wei-Chun; Cheng, Yu-Pin; Tsai, Tsen-Fang; Ho, Shinn-Ying

    2015-01-01

    Background and Objectives 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. Methods 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. Results 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. Conclusions 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. PMID:26406879

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

    ERIC Educational Resources Information Center

    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…

  14. A base substitution in the promoter associated with the human haptoglobin 2-1 modified phenotype decreases transcriptional activity and responsiveness to interleukin-6 in human hepatoma cells

    SciTech Connect

    Grant, D.J.; Maeda, N. )

    1993-05-01

    An A-to-C base substitution at nucleotide position -61 in the promoter region of the human haptoglobin gene (Hp) has been shown to be strongly associated with the haptoglobin 2-1 modified (Hp2-1mod) phenotype. In order to investigate whether this base substitution is the cause of reduced expression of the Hp[sup 2] allele relative to the Hp[sup 1] allele in individuals with the Hp2-1mod phenotype, the authors used the chloramphenicol acetyl transferase (CAT) expression system to evaluate promoter function. In HepG2 cells, which normally express their endogenous haptoglobin genes, CAT plasmid constructs with the -61C base change in the promoter had about 10-fold-lower transcriptional activity after transfection than did the Hp control construct. The -61C substitution also rendered the construct unresponsive to treatment by interleukin-6 after transfection into Hep3B2 cells, which normally do not express haptoglobin but do so in response to stimulation by acute-phase reactants. In addition, two base substitutions, T to A and A to G, at positions -104 and -55G, respectively, in the promoter region of the Hp[sup 1] allele, are also associated with the Hp2-1mod phenotype. CAT constructs with both substitutions (-104A-55G) and with one substitution (-55G) showed activity similar to that in the Hp control when transfected into both HepG2 and Hep3B2 cells, although interleukin-6 induction was less than with the Hp control construct. These results further support the hypothesis that the Hp2-1mod phenotype results, in part, from the -61C mutation in the promoter region of the Hp[sup 2] gene.

  15. Cardiovascular physiology and diseases of the rabbit.

    PubMed

    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.

  16. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

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

    2014-09-01

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

  17. Three Measures of Forest Fire Smoke Exposure and Their Associations with Respiratory and Cardiovascular Health Outcomes in a Population-Based Cohort

    PubMed Central

    Brauer, Michael; MacNab, Ying C.; Kennedy, Susan M.

    2011-01-01

    Background: During the summer of 2003 numerous fires burned in British Columbia, Canada. Objectives: We examined the associations between respiratory and cardiovascular physician visits and hospital admissions, and three measures of smoke exposure over a 92-day study period (1 July to 30 September 2003). Methods: A population-based cohort of 281,711 residents was identified from administrative data. Spatially specific daily exposure estimates were assigned to each subject based on total measurements of particulate matter (PM) ≤ 10 μm in aerodynamic diameter (PM10) from six regulatory tapered element oscillating microbalance (TEOM) air quality monitors, smoke-related PM10 from a CALPUFF dispersion model run for the study, and a SMOKE exposure metric for plumes visible in satellite images. Logistic regression with repeated measures was used to estimate associations with each outcome. Results: The mean (± SD) exposure based on TEOM-measured PM10 was 29 ± 31 μg/m3, with an interquartile range of 14–31 μg/m3. Correlations between the TEOM, smoke, and CALPUFF metrics were moderate (0.37–0.76). Odds ratios (ORs) for a 30-μg/m3 increase in TEOM-based PM10 were 1.05 [95% confidence interval (CI), 1.03–1.06] for all respiratory physician visits, 1.16 (95% CI, 1.09–1.23) for asthma-specific visits, and 1.15 (95% CI, 1.00–1.29) for respiratory hospital admissions. Associations with cardiovascular outcomes were largely null. Conclusions: Overall we found that increases in TEOM-measured PM10 were associated with increased odds of respiratory physician visits and hospital admissions, but not with cardiovascular health outcomes. Results indicating effects of fire smoke on respiratory outcomes are consistent with previous studies, as are the null results for cardiovascular outcomes. Some agreement between TEOM and the other metrics suggests that exposure assessment tools that are independent of air quality monitoring may be useful with further refinement. PMID

  18. An automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans.

    PubMed

    Maglioni, Silvia; Arsalan, Nayna; Franchi, Luigi; Hurd, Alexander; Opipari, Anthony W; Glick, Gary D; Ventura, Natascia

    2015-11-01

    Mitochondria are multifunctional organelles that play a central role in cellular homeostasis. Severe mitochondrial dysfunction leads to life-threatening diseases in humans and accelerates the aging process. Surprisingly, moderate reduction of mitochondrial function in different species has anti-aging effects. High-throughput screenings in the nematode Caenorhabditis elegans lead to the identification of several pro-longevity genetic and pharmacological interventions. Large-scale screens, however, are manual, subjective, time consuming and costly. These limitations could be reduced by the identification of automatically quantifiable biomarkers of healthy aging. In this study we exploit the distinct and reproducible phenotypes described in C. elegans upon different levels of mitochondrial alteration to develop an automated high-content strategy to identify new potential pro-longevity interventions. Utilizing the microscopy platform Cellomics ArrayScan Reader, we optimize a workflow to automatically and reliably quantify the discrete phenotypic readouts associated with different degrees of silencing of mitochondrial respiratory chain regulatory proteins, and validate the approach with mitochondrial-targeting drugs known to extend lifespan in C. elegans. Finally, we report that a new mitochondrial ATPase modulator matches our screening phenotypic criteria and extends nematode's lifespan thus providing the proof of principle that our strategy could be exploited to identify novel mitochondrial-targeted drugs with pro-longevity activity. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

  19. Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

    PubMed

    Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

    2015-09-18

    Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

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

    PubMed Central

    Camiciottoli, Gianna; Bigazzi, Francesca; Magni, Chiara; Bonti, Viola; Diciotti, Stefano; Bartolucci, Maurizio; Mascalchi, Mario; Pistolesi, Massimo

    2016-01-01

    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 significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and

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

    PubMed Central

    Camiciottoli, Gianna; Bigazzi, Francesca; Magni, Chiara; Bonti, Viola; Diciotti, Stefano; Bartolucci, Maurizio; Mascalchi, Mario; Pistolesi, Massimo

    2016-01-01

    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 significantly in predominant emphysema, and ischemic heart disease and PVD prevailed in mild COPD. All cardiovascular comorbidities prevailed significantly in predominant airway phenotype of COPD and mild COPD severity. Conclusion Specific comorbidities prevail in different phenotypes of COPD; this fact may be relevant to identify patients at risk for specific, phenotype-related comorbidities. The highest prevalence of comorbidities in patients with mild disease indicates that these patients should be investigated for coexisting diseases or syndromes even in the less severe, pauci-symptomatic stages of COPD. The simple method employed to phenotype and

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

    PubMed Central

    Cecchini, Diego; Ines Mattioli, Maria; Cassetti, Julia; Chan, Debora; Cassetti, Isabel

    2014-01-01

    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

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

    PubMed Central

    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

  4. The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.

    PubMed

    Singleton, B K; Green, C A; Avent, N D; Martin, P G; Smart, E; Daka, A; Narter-Olaga, E G; Hawthorne, L M; Daniels, G

    2000-01-01

    Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)

  5. Reactive Oxygen Species in Cardiovascular Disease

    PubMed Central

    Sugamura, Koichi; Keaney, John F.

    2011-01-01

    Based on the ‘free-radical theory’ of disease, researchers have been trying to elucidate the role of oxidative stress from free radicals in cardiovascular disease. Considerable data indicate that ROS and oxidative stress are important features of cardiovascular diseases including atherosclerosis, hypertension, and congestive heart failure. However, blanket strategies with antioxidants to ameliorate cardiovascular disease have not generally yielded favorable results. However, our understanding or reactive oxygen species has evolved to the point that we now realize these species have important roles in physiology as well as pathophysiology. Thus, it is overly simplistic to assume a general antioxidant strategy will yield specific effects on cardiovascular disease. Indeed, there are several sources of reactive oxygen species that are known to be active in the cardiovascular system. This review will address our understanding of reactive oxygen species sources in cardiovascular disease and both animal and human data defining how reactive oxygen species contribute to physiology and pathology. PMID:21627987

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

    NASA Technical Reports Server (NTRS)

    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.

  7. Determination of Cutoff Values for DEXA-Based Body Composition Measurements for Determining Metabolic and Cardiovascular Health

    PubMed Central

    Lang, Pierre-Olivier; Trivalle, Christophe; Vogel, Thomas; Proust, Jacques; Papazyan, Jean-Pierre; Dramé, Moustapha

    2015-01-01

    Abstract The two components of the body weight (i.e., fat mass and muscle mass) appeared to be of high interest to consider in predicting metabolic health related risks. We aimed to determine cutoff values for fat mass index (FMI) and muscle mass index (MMI), FM/MM, and BMI for metabolic and cardiovascular health. This study was a cross-sectional analysis study conducted in a center of preventive medicine. It included 616 consecutive outpatients: mean age was 56.0±10.0 years (74.6% aged ≥50), and 61.4% were female. Fat and muscle mass were obtained with dual energy X-ray absorptiometry scan analyses. Metabolically unhealthy individuals were defined as people with biological features of dyslipidemia, hyperuricemia, diabetes, and/or hepatitis steatosis. Documented hypertension and/or atherosclerosis of at least one major artery defined individuals with cardiovascular complications. Receiver-operating characteristic curve analysis revealed that the cutoff values for MMI, FMI, and FM/MM were respectively 18.8kg/m2 (sensitivity [Se]=58%; specificity [Sp]=59%), 5.5kg/m2 (Se=61%; Sp=62%), and 0.31 (Se=62%; Sp=62%) in men; and 14.1kg/m2 (Se=52%; Sp=54%), 5.5kg/m2 (Se=65%; Sp=67%), 0.39 (Se=73%; Sp=73%) in women for predicting metabolic health. Values were 19.3kg/m2 (Se=58%; Sp=59%), 7.0kg/m2 (Se=61%; Sp=62%) and 0.49 (Se=62%; Sp=62%) in men; and 15.7kg/m2 (Se=58%; Sp=59%), 6.4kg/m2 (Se=61%; Sp=62%) and 0.35 (Se=62%; Sp=62%) in women for cardiovascular complications. Whatever the outcomes considered, the Youden indexes for BMI values were systematically below 25 kg/m2, except for cardiovascular complications in men, where the threshold for the best Se/Sp was 25.7 kg/m2. These cutoff values for FMI, MMI, and FM/MM could be of practical value for the clinical evaluation of a deficit in MM with or without excess of FM. They complement the classical concept of BMI in a more qualitative manner and extend the analysis of its impact on health outcomes to all BMI categories

  8. Cardiovascular Disease and Diabetes

    MedlinePlus

    ... Blood Pressure Tools & Resources Stroke More Cardiovascular Disease & Diabetes Updated:Mar 23,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  9. The neuronal noradrenaline transporter, anxiety and cardiovascular disease.

    PubMed

    Esler, Murray; Alvarenga, Marlies; Pier, Ciaran; Richards, Jeff; El-Osta, Assam; Barton, David; Haikerwal, Deepak; Kaye, David; Schlaich, Markus; Guo, Ling; Jennings, Garry; Socratous, Flora; Lambert, Gavin

    2006-07-01

    Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients. Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic 'co-morbidity' perhaps underlies the clinical concordance. Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac

  10. Infection and Cardiovascular Disease

    ClinicalTrials.gov

    2016-02-17

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Myocardial Infarction; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Atherosclerosis

  11. Association between Floods and Acute Cardiovascular Diseases: A Population-Based Cohort Study Using a Geographic Information System Approach

    PubMed Central

    Vanasse, Alain; Cohen, Alan; Courteau, Josiane; Bergeron, Patrick; Dault, Roxanne; Gosselin, Pierre; Blais, Claudia; Bélanger, Diane; Rochette, Louis; Chebana, Fateh

    2016-01-01

    Background: Floods represent a serious threat to human health beyond the immediate risk of drowning. There is few data on the potential link between floods and direct consequences on health such as on cardiovascular health. This study aimed to explore the impact of one of the worst floods in the history of Quebec, Canada on acute cardiovascular diseases (CVD). Methods: A cohort study with a time series design with multiple control groups was built with the adult population identified in the Quebec Integrated Chronic Disease Surveillance System. A geographic information system approach was used to define the study areas. Logistic regressions were performed to compare the occurrence of CVD between groups. Results: The results showed a 25%–27% increase in the odds in the flooded population in spring 2011 when compared with the population in the same area in springs 2010 and 2012. Besides, an increase up to 69% was observed in individuals with a medical history of CVD. Conclusion: Despite interesting results, the association was not statistically significant. A possible explanation to this result can be that the population affected by the flood was probably too small to provide the statistical power to answer the question, and leaves open a substantial possibility for a real and large effect. PMID:26828511

  12. Identification of the Single Base Change Causing the Callipyge Muscle Hypertrophy Phenotype, the Only Known Example of Polar Overdominance in Mammals

    PubMed Central

    Freking, Brad A.; Murphy, Susan K.; Wylie, Andrew A.; Rhodes, Simon J.; Keele, John W.; Leymaster, Kreg A.; Jirtle, Randy L.; Smith, Timothy P.L.

    2002-01-01

    A small genetic region near the telomere of ovine chromosome 18 was previously shown to carry the mutation causing the callipyge muscle hypertrophy phenotype in sheep. Expression of this phenotype is the only known case in mammals of paternal polar overdominance gene action. A region surrounding two positional candidate genes was sequenced in animals of known genotype. Mutation detection focused on an inbred ram of callipyge phenotype postulated to have inherited chromosome segments identical-by-descent with exception of the mutated position. In support of this hypothesis, this inbred ram was homozygous over 210 Kb of sequence, except for a single heterozygous base position. This single polymorphism was genotyped in multiple families segregating the callipyge locus (CLPG), providing 100% concordance with animals of known CLPG genotype, and was unique to descendants of the founder animal. The mutation lies in a region of high homology among mouse, sheep, cattle, and humans, but not in any previously identified expressed transcript. A substantial open reading frame exists in the sheep sequence surrounding the mutation, although this frame is not conserved among species. Initial functional analysis indicates sequence encompassing the mutation is part of a novel transcript expressed in sheep fetal muscle we have named CLPG1. [The sequence data described in this paper have been submitted to GenBank under the following accession numbers: G74891-G75331 for all STS generated; AF401294 for the amplicon identifying the specific callipyge mutation; AF533009 for the partial expressed transcript.] PMID:12368241

  13. BreedVision--a multi-sensor platform for non-destructive field-based phenotyping in plant breeding.

    PubMed

    Busemeyer, Lucas; Mentrup, Daniel; Möller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans Peter; Reif, Jochen C; Würschum, Tobias; Müller, Joachim; Rahe, Florian; Ruckelshausen, Arno

    2013-02-27

    To achieve the food and energy security of an increasing World population likely to exceed nine billion by 2050 represents a major challenge for plant breeding. Our ability to measure traits under field conditions has improved little over the last decades and currently constitutes a major bottleneck in crop improvement. This work describes the development of a tractor-pulled multi-sensor phenotyping platform for small grain cereals with a focus on the technological development of the system. Various optical sensors like light curtain imaging, 3D Time-of-Flight cameras, laser distance sensors, hyperspectral imaging as well as color imaging are integrated into the system to collect spectral and morphological information of the plants. The study specifies: the mechanical design, the system architecture for data collection and data processing, the phenotyping procedure of the integrated system, results from field trials for data quality evaluation, as well as calibration results for plant height determination as a quantified example for a platform application. Repeated measurements were taken at three developmental stages of the plants in the years 2011 and 2012 employing triticale (×Triticosecale Wittmack L.) as a model species. The technical repeatability of measurement results was high for nearly all different types of sensors which confirmed the high suitability of the platform under field conditions. The developed platform constitutes a robust basis for the development and calibration of further sensor and multi-sensor fusion models to measure various agronomic traits like plant moisture content, lodging, tiller density or biomass yield, and thus, represents a major step towards widening the bottleneck of non-destructive phenotyping for crop improvement and plant genetic studies.

  14. BreedVision--a multi-sensor platform for non-destructive field-based phenotyping in plant breeding.

    PubMed

    Busemeyer, Lucas; Mentrup, Daniel; Möller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans Peter; Reif, Jochen C; Würschum, Tobias; Müller, Joachim; Rahe, Florian; Ruckelshausen, Arno

    2013-01-01

    To achieve the food and energy security of an increasing World population likely to exceed nine billion by 2050 represents a major challenge for plant breeding. Our ability to measure traits under field conditions has improved little over the last decades and currently constitutes a major bottleneck in crop improvement. This work describes the development of a tractor-pulled multi-sensor phenotyping platform for small grain cereals with a focus on the technological development of the system. Various optical sensors like light curtain imaging, 3D Time-of-Flight cameras, laser distance sensors, hyperspectral imaging as well as color imaging are integrated into the system to collect spectral and morphological information of the plants. The study specifies: the mechanical design, the system architecture for data collection and data processing, the phenotyping procedure of the integrated system, results from field trials for data quality evaluation, as well as calibration results for plant height determination as a quantified example for a platform application. Repeated measurements were taken at three developmental stages of the plants in the years 2011 and 2012 employing triticale (×Triticosecale Wittmack L.) as a model species. The technical repeatability of measurement results was high for nearly all different types of sensors which confirmed the high suitability of the platform under field conditions. The developed platform constitutes a robust basis for the development and calibration of further sensor and multi-sensor fusion models to measure various agronomic traits like plant moisture content, lodging, tiller density or biomass yield, and thus, represents a major step towards widening the bottleneck of non-destructive phenotyping for crop improvement and plant genetic studies. PMID:23447014

  15. Selection of parents for crossing based on genotyping and phenotyping for stripe rust (Puccinia striiformis) resistance and agronomic traits in bread wheat breeding.

    PubMed

    Khan, Muhammad Irfaq; Khan, Mir Ajab; Khan, Abdul Jabbar; Khattak, Gul Sanat Shah; Mohammad, Tila; Ahmad, Mushtaq

    2011-01-01

    Bread wheat (Triticum aestivum L.) germplasm consisting of 45 genotypes were clustered phenotypically using ten morphological traits and Area Under Disease Progress Curve (AUDPC) as measure of stripe rust resistance. The clustering was ratified by using twenty three molecular markers (SSR, EST and STS) linked to stripe rust (Puccinia striiformis f. sp. tritici) resistant QTLs. The aim was to asses the extent of genetic variability among the genotypes in order to select the parents for crossing between the resistant and susceptible genotypes with respect to stripe rust. The Euclidian dissimilarity values resulted from phenotypic data regarding morphological traits and AUDPC were used to construct a dendrogram for clustering the accessions. Using un-weighted pair group method with arithmetic means, another dendrogram resulted from the similarity coefficient values was used to distinguish the genotypes with respect to stripe rust. Clustering based on phenotypic data produced two major groups and five clusters (with Euclidian dissimilarity ranging from 244 to 16.16) whereas genotypic data yielded two major groups and four clusters (with percent similarity coefficient values ranging from 0.1 to 46.0) to separate the gene pool into highly resistant, resistant, moderately resistant, moderately susceptible and susceptible genotypes. With few exceptions, the outcome of both type of clustering was almost similar and resistant as well as susceptible genotypes came in the same clusters of molecular genotyping as yielded by phenotypic clustering. As a result seven genotypes (Bakhtawar-92, Frontana, Saleem 2000, Tatara, Inqilab-91, Fakhre Sarhad and Karwan) of diverse genetic background were selected for pyramiding stripe rust resistant genes as well as some other agronomic traits after hybridization.

  16. Cardiovascular effects of microgravity: evolution of understanding

    NASA Technical Reports Server (NTRS)

    Short, H. D.

    1998-01-01

    The understanding of cardiovascular effects of spaceflight has evolved throughout the course of the American manned spaceflight program. Originally descriptive in nature, the present understanding is based on empiric measurements of vascular volume, cardiac output, vascular reflexes, and peripheral and central autonomic control. More detailed understanding of cardiovascular effects has allowed us to separate those symptoms from symptoms caused by musculoskeletal or neurovestibular abnormalities.

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

    PubMed Central

    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

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

    PubMed Central

    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

  19. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

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

    2014-09-01

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

  20. Model-based genotype-phenotype mapping used to investigate gene signatures of immune sensitivity and resistance in melanoma micrometastasis

    PubMed Central

    Santos, Guido; Nikolov, Svetoslav; Lai, Xin; Eberhardt, Martin; Dreyer, Florian S.; Paul, Sushmita; Schuler, Gerold; Vera, Julio

    2016-01-01

    In this paper, we combine kinetic modelling and patient gene expression data analysis to elucidate biological mechanisms by which melanoma becomes resistant to the immune system and to immunotherapy. To this end, we systematically perturbed the parameters in a kinetic model and performed a mathematical analysis of their impact, thereby obtaining signatures associated with the emergence of phenotypes of melanoma immune sensitivity and resistance. Our phenotypic signatures were compared with published clinical data on pretreatment tumor gene expression in patients subjected to immunotherapy against metastatic melanoma. To this end, the differentially expressed genes were annotated with standard gene ontology terms and aggregated into metagenes. Our method sheds light on putative mechanisms by which melanoma may develop immunoresistance. Precisely, our results and the clinical data point to the existence of a signature of intermediate expression levels for genes related to antigen presentation that constitutes an intriguing resistance mechanism, whereby micrometastases are able to minimize the combined anti-tumor activity of complementary responses mediated by cytotoxic T cells and natural killer cells, respectively. Finally, we computationally explored the efficacy of cytokines used as low-dose co-adjuvants for the therapeutic anticancer vaccine to overcome tumor immunoresistance. PMID:27113331

  1. [Animal models of cardiovascular disease].

    PubMed

    Chorro, Francisco J; Such-Belenguer, Luis; López-Merino, Vicente

    2009-01-01

    The use of animal models to study cardiovascular disease has made a substantial contribution to increasing our understanding of disease pathogenesis, has led to the development of diagnostic techniques, and has made it possible to verify the effectiveness of different preventative and therapeutic approaches, whether pharmacological or interventional. The main limitations stem from differences between human and experimentally induced pathology, in terms of both genetic regulatory mechanisms and factors that influence cardiovascular function. The experimental models and preparations used in cardiovascular research include those based on isolated cells or tissues or structures immersed in organ baths. The Langendorff system enables isolated perfused hearts to be studied directly under conditions of either no load or controlled loading. In small mammals, a number of models have been developed of cardiovascular conditions that result from spontaneous genetic mutations or, alternatively, that may be induced by specific genomic modification. One of the techniques employed is gene transfer, which can involve the controlled induction of mutations that result in the expression of abnormalities associated with the development of a broad range of different types of cardiovascular disease. Larger animals are used in experimental models in which it is important that physiological regulatory and homeostatic mechanisms are present.

  2. Finding our way through phenotypes.

    PubMed

    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. PMID:25562316

  3. Finding Our Way through Phenotypes

    PubMed Central

    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. PMID:25562316

  4. Finding our way through phenotypes.

    PubMed

    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.

  5. Multivariate Analysis of Genotype-Phenotype Association.

    PubMed

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  6. Cardiovascular disease prevention and health promotion with the transcendental meditation program and Maharishi consciousness-based health care.

    PubMed

    Schneider, Robert H; Walton, Kenneth G; Salerno, John W; Nidich, Sanford I

    2006-01-01

    This article summarizes the background, rationale, and clinical research on a traditional system of natural health care that may be useful in the prevention of cardiovascular disease (CVD) and promotion of health. Results recently reported include reductions in blood pressure, psychosocial stress, surrogate markers for atherosclerotic CVD, and mortality. The randomized clinical trials conducted so far have involved applications to both primary and secondary prevention as well as to health promotion more generally. The results support the applicability of this approach for reducing ethnic health disparities associated with environmental and psychosocial stress. Proposed mechanisms for the effects of this traditional system include enhanced resistance to physiological and psychological stress and improvements in homeostatic and self-repair processes. This system may offer clinical and cost effectiveness advantages for health care, particularly in preventive cardiology.

  7. Cardiovascular Disease Prevention and Health Promotion with the Transcendental Meditation Program and Maharishi Consciousness-Based Health Care

    PubMed Central

    Schneider, Robert H.; Walton, Kenneth G.; Salerno, John W.; Nidich, Sanford I.

    2008-01-01

    This article summarizes the background, rationale, and clinical research on a traditional system of natural health care that may be useful in the prevention of cardiovascular disease (CVD) and promotion of health. Results recently reported indude reductions in blood pressure, psychosocial stress, surrogate markers for atherosclerotic CVD, and mortality. The randomized clinical trials conducted so far have involved applications to both primary and secondary prevention as well as to health promotion more generally. The results support the applicability of this approach for reducing ethnic health disparities associated with environmental and psychosocial stress. Proposed mechanisms for the effects of this traditional system include enhanced resistance to physiological and psychological stress and improvements in homeostatic and self-repair processes. This system may offer clinical and cost effectiveness advantages for health care, particularly in preventive cardiology. PMID:16938913

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

    SciTech Connect

    Nanda, Akash; Chen, Ming-Hui; Moran, Brian J.; Braccioforte, Michelle H.; D'Amico, Anthony V.

    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.

  9. Search of phenotype related candidate genes using gene ontology-based semantic similarity and protein interaction information: application to Brugada syndrome.

    PubMed

    Massanet, Raimon; Gallardo-Chacon, Joan-Josep; Caminal, Pere; Perera, Alexandre

    2009-01-01

    This work presents a methodology for finding phenotype candidate genes starting from a set of known related genes. This is accomplished by automatically mining and organizing the available scientific literature using Gene Ontology-based semantic similarity. As a case study, Brugada syndrome related genes have been used as input in order to obtain a list of other possible candidate genes related with this disease. Brugada anomaly produces a typical alteration in the Electrocardiogram and carriers of the disease show an increased probability of sudden death. Results show a set of semantically coherent proteins that are shown to be related with synaptic transmission and muscle contraction physiological processes.

  10. [Changes in the prescription of cardiovascular prevention drugs in France between 1995 and 2003: factors influencing the gap between evidence base medicine and clinical practice].

    PubMed

    Philippe, François; Cambou, Jean-Pierre; Danchin, Nicolas; Thomas, Daniel

    2005-12-01

    Dramatic progresses have occurred during the past 10 years in the field of cardiovascular secondary prevention. Many randomized trials have established the efficacy of statins, antiplatelet agents, beta-blockers and ACE inhibitors for reducing cardiovascular mortality, myocardial infarction and stroke in patients with coronary heart disease. Since 2002, American and European guidelines have emphasized the importance of optimal utilization of those four main therapeutic classes. Nevertheless, drugs prescription registries conducted in France since 1995 revealed a persistent gap between evidence based medicine and clinical practice, only a minority of patient received an optimal treatment. Some factors associated with lower rate prescription have been identified: elderly patients, female gender, missing of LDL-cholesterol measurement, history of peripheral artery disease or stroke, and finally the difficulty of observance. At this time, optimization of management of these patients require a systematic measurement of LDL-cholestererol level for all patients with CAD, PAD or history of stroke, a larger prescription of statins in female patients and in elderly particularly for secondary prevention. Increasing observance which is the main challenge could involved the utilization of fixed drugs associations.

  11. MRI-Based Computational Fluid Dynamics in Experimental Vascular Models: Toward the Development of an Approach for Prediction of Cardiovascular Changes During Prolonged Space Missions

    NASA Technical Reports Server (NTRS)

    Spirka, T. A.; Myers, J. G.; Setser, R. M.; Halliburton, S. S.; White, R. D.; Chatzimavroudis, G. P.

    2005-01-01

    A priority of NASA is to identify and study possible risks to astronauts health during prolonged space missions [l]. The goal is to develop a procedure for a preflight evaluation of the cardiovascular system of an astronaut and to forecast how it will be affected during the mission. To predict these changes, a computational cardiovascular model must be constructed. Although physiology data can be used to make a general model, a more desirable subject-specific model requires anatomical, functional, and flow data from the specific astronaut. MRI has the unique advantage of providing images with all of the above information, including three-directional velocity data which can be used as boundary conditions in a computational fluid dynamics (CFD) program [2,3]. MRI-based CFD is very promising for reproduction of the flow patterns of a specific subject and prediction of changes in the absence of gravity. The aim of this study was to test the feasibility of this approach by reconstructing the geometry of MRI-scanned arterial models and reproducing the MRI-measured velocities using CFD simulations on these geometries.

  12. 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.

    PubMed

    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.

  13. PHYSIOLAB: A cardiovascular laboratory

    NASA Astrophysics Data System (ADS)

    Cauquil, D.; Laffaye, C.; Camus, A. L.; Weerts, G.; Gratchev, V.; Alferova, I.; Kotovskaya, A.

    PHYSIOLAB is a cardio-vascular laboratory designed by CNES in cooperation with IMBP, with double scientific and medical goals: • a better understanding of the basic mechanisms involved in blood pressure and heart rate regulation, in order to predict and control the phenomenon of cardio-vascular deconditionning. • a real-time monitoring of cosmonauts during functionnal tests. Launched to the MIR station in 1996, this laboratory was set up and used for the first time by Claudie André-Deshays during the French mission ≪ Cassiopeia ≫. The scientific program is performed pre, post and in-flight to study phenomena related to the transition to microgravity as well as the return to the earth conditions. Particular emphasis was placed on the development of the real-time telemetry to monitor LBNP test. This function was successfull during the Cassiopeia mission, providing the medical team at TSOUP (MIR Control Center in Moscow) with efficient means to control the physiological state of the cosmonaut. Based on the results of this first mission, IMBP and CNES will go on using Physiolab with Russian crews. CNES will take advantage of the upcoming French missions on MIR to improve the system, and intends to develop a new laboratory for the International Space Station.

  14. Optimization in Cardiovascular Modeling

    NASA Astrophysics Data System (ADS)

    Marsden, Alison L.

    2014-01-01

    Fluid mechanics plays a key role in the development, progression, and treatment of cardiovascular disease. Advances in imaging methods and patient-specific modeling now reveal increasingly detailed information about blood flow patterns in health and disease. Building on these tools, there is now an opportunity to couple blood flow simulation with optimization algorithms to improve the design of surgeries and devices, incorporating more information about the flow physics in the design process to augment current medical knowledge. In doing so, a major challenge is the need for efficient optimization tools that are appropriate for unsteady fluid mechanics problems, particularly for the optimization of complex patient-specific models in the presence of uncertainty. This article reviews the state of the art in optimization tools for virtual surgery, device design, and model parameter identification in cardiovascular flow and mechanobiology applications. In particular, it reviews trade-offs between traditional gradient-based methods and derivative-free approaches, as well as the need to incorporate uncertainties. Key future challenges are outlined, which extend to the incorporation of biological response and the customization of surgeries and devices for individual patients.

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

    PubMed

    Oliveira, Gustavo B F; Avezum, Alvaro; Roever, Leonardo

    2015-01-01

    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, the evidence describing the incidence of acute myocardial infarction, the underlying risk factors, and the clinical outcomes of those who have this acute ischemic coronary event has largely been based on studies conducted in developed countries, with limited data for women and usually of 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, multiethnic 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 non-communicable 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 study, which is the largest global initiative of nearly 200,000 adults aged 35-70 years, 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 and mortality. PMID:26664903

  16. Misfolded N-CoR is Linked to the Ectopic Reactivation of CD34/Flt3-Based Stem-Cell Phenotype in Promyelocytic and Monocytic Acute Myeloid Leukemia

    PubMed Central

    Nin, Dawn Sijin; Li, Feng; Visvanathan, Sridevi; Khan, Matiullah

    2015-01-01

    Nuclear receptor co-repressor (N-CoR) is the key component of generic co-repressor complex essential for the transcriptional control of genes involved in cellular hemostasis. We have recently reported that N-CoR actively represses Flt3, a key factor of hematopoietic stem cells (HSC) self-renewal and growth, and that de-repression of Flt3 by the misfolded N-CoR plays an important role in the pathogenesis of promyelocytic and monocytic acute myeloid leukemia (AML). The leukemic cells derived from the promyelocytic and monocytic AML are distinctly characterized by the ectopic reactivation of stem cell phenotypes in relatively committed myeloid compartment. However, the molecular mechanism underlying this phenomenon is not known. Here, we report that N-CoR function is essential for the commitment of primitive hematopoietic cells to the cells of myeloid lineage and that loss of N-CoR function due to misfolding is linked to the ectopic reactivation of generic stem cell phenotypes in promyelocytic and monocytic AML. Analysis of N-CoR and Flt3 transcripts in mouse hematopoietic cells revealed a positive correlation between N-CoR level and the commitment of myeloid cells and an inverse correlation between N-CoR and Flt3 levels in primitive as well as committed myeloid cells. Enforced N-CoR expression in mouse HSCs inhibited their growth and self-renewal potentials and promoted maturation toward cells of myeloid lineage, suggesting a role of N-CoR in the commitment of cells of myeloid lineage. In contrast to AML cells with natively folded N-CoR, primary and secondary promyelocytic and monocytic AML cells harboring the misfolded N-CoR were highly positive for Flt3 and myeloid antigen-based HSC marker CD34. Genetic and therapeutic restoration of N-CoR conformation significantly down-regulated the CD34 levels in monocytic AML cells, suggesting an important role of N-CoR in the suppression of CD34-based HSC phenotypes. These findings collectively suggest that N-CoR is crucial

  17. Endothelial retention and phenotype on carbonized cardiovascular implant surfaces

    PubMed Central

    Frendl, Chris; Tucker, Scott; Khan, Nadeem; Esch, Mandy; Kanduru, Shrinidhi; Cao, Thong M.; García, Andrés J.; King, Michael R.; Butcher, Jonathan T.

    2014-01-01

    Heart valve disease is an increasing clinical burden for which there is no effective treatment outside of prosthetic replacement. Over the last 20 years, clinicians have increasingly preferred the use of biological prosthetics to mechanical valves despite their superior durability because of the lifelong anticoagulation therapy that is required. Mechanical valve surface engineering has largely focused on being as non-thrombogenic as possible, but despite decades of iteration has had insufficient impact on the anticoagulation burden. In this study, we systematically evaluate the potential for endothelialization of the pyrolytic carbon surface used in mechanical valves. We compared adsorbed adhesion ligand type (collagen I, fibronectin, laminin, and purified adhesion domain fragments GFOGER and FN7-10) and concentration on endothelial adhesion rates and adhesion strength on Medtronic-Hall prosthetic valve surfaces. Regardless of ligand type or concentration, endothelial adhesion strengthening was insufficient for their intended ultra-high shear stress environment. We then hypothesized that microfabricated trenches would reduce shear stress to tolerable levels while maintaining endothelial access to the flow stream, thereby promoting a confluent and anticoagulant endothelial monolayer. Computational fluid dynamics simulations predicted an empirical relationship of channel width, depth, and spacing that would maintain interior surface shear stress within tolerable levels. Endothelial cells seeded to confluence in these channels retained a confluent monolayer when exposed to 600 dynes/cm2 shear stress for 48 hours regardless of applied adhesive ligand. Furthermore, sheared EC expressed a mature anti-coagulant profile, including endothelial nitric oxide synthase (eNOS), VE-cadherin, and significantly downregulated plasminogen activator inhibitor-1 (PAI-1). As a final test, channeled pyrolytic carbon surfaces with confluent EC reduced human platelet adhesion 1000-fold over pyrolytic carbon alone. These results advance a promising biohybrid approach to enable active moderation of local coagulative response in mechanical heart valves, which could significantly extend the utility of this important treatment for heart valve disease. PMID:24952977

  18. Changes of individual perception in psychosocial stressors related to German reunification in 1989/1990 and cardiovascular risk factors and cardiovascular diseases in a population-based study in East Germany

    PubMed Central

    Kluttig, Alexander; Werdan, Karl; Nuding, Sebastian; Greiser, Karin Halina; Kuss, Oliver; Markus, Marcello Ricardo Paulista; Schmidt, Carsten Oliver; Völzke, Henry; Krabbe, Christine; Haerting, Johannes

    2016-01-01

    Objectives Aim was to examine the relationship between individually perceived changes in psychosocial stressors associated with German reunification and cardiovascular effects. We hypothesised that higher levels of psychosocial stress related to German reunification were associated with an increase in cardiovascular risk factors and cardiovascular diseases (CVDs). Design Cross-sectional data from 2 cohort studies in East Germany were used: Cardiovascular Disease, Living and Ageing in Halle Study (CARLA), and Study of Health in Pomerania (SHIP). Setting 2 populations in East Germany. Participants CARLA study: 1779 participants, aged 45–83 years at baseline (812 women), SHIP study: 4308 participants, aged 20–79 years at baseline (2193 women). Primary and secondary outcome measures Psychosocial stressors related to reunification were operationalised by the Reunification Stress Index (RSI; scale from 0 to 10). This index was composed of questions that were related to individually perceived changes in psychosocial stressors (occupational, financial and personal) after reunification. To examine the associations between the RSI and each stressor separately with cardiovascular risk factors and CVD, regression models were used. Results RSI was associated with CVD in women (RR=1.15, 95% CI 1.00 to 1.33). Cardiovascular risk factors were associated with RSI for both men and women, with strongest associations between RSI and diabetes in women (RR=1.10, 95% CI 1.01 to 1.20) and depressive disorders in men (RR=1.15, 95% CI 1.07 to 2.77). The change in occupational situation related to reunification was the major contributing psychosocial stressor. We observed a strong association with CVD in women who experienced occupational deterioration after reunification (RR=4.04, 95% CI 1.21 to 13.43). Conclusions Individually perceived deterioration of psychosocial stressors (occupational, financial and personal) related to German reunification was associated with cardiovascular

  19. Phenotypic and functional characterization of earthworm coelomocyte subsets: Linking light scatter-based cell typing and imaging of the sorted populations.

    PubMed

    Engelmann, Péter; Hayashi, Yuya; Bodó, Kornélia; Ernszt, Dávid; Somogyi, Ildikó; Steib, Anita; Orbán, József; Pollák, Edit; Nyitrai, Miklós; Németh, Péter; Molnár, László

    2016-12-01

    Flow cytometry is a common approach to study invertebrate immune cells including earthworm coelomocytes. However, the link between light-scatter- and microscopy-based phenotyping remains obscured. Here we show, by means of light scatter-based cell sorting, both subpopulations (amoebocytes and eleocytes) can be physically isolated with good sort efficiency and purity confirmed by downstream morphological and cytochemical applications. Immunocytochemical analysis using anti-EFCC monoclonal antibodies combined with phalloidin staining has revealed antigenically distinct, sorted subsets. Screening of lectin binding capacity indicated wheat germ agglutinin (WGA) as the strongest reactor to amoebocytes. This is further evidenced by WGA inhibition assays that suggest high abundance of N-acetyl-d-glucosamine in amoebocytes. Post-sort phagocytosis assays confirmed the functional differences between amoebocytes and eleocytes, with the former being in favor of bacterial engulfment. This study has proved successful in linking flow cytometry and microscopy analysis and provides further experimental evidence of phenotypic and functional heterogeneity in earthworm coelomocyte subsets. PMID:27349970

  20. [Treatment of patients with type 2 diabetes mellitus: cardiovascular safety of incretin-based therapy supported by the ELIXA and TECOS trials].

    PubMed

    Avogaro, Angelo

    2016-04-01

    The risk of morbidity and mortality from cardiovascular disease in patients with type 2 diabetes is about 2-fold higher compared to their non-diabetic counterparts. In December 2008, the Food and Drug Administration published guidelines for the evaluation of cardiovascular risk in new antidiabetic therapies. A shift of emphasis occurred from short-term glycated hemoglobin-centered trials to trials testing cardiovascular safety. The SAVOR-TIMI 53 and the EXAMINE trials with the dipeptidyl peptidase 4 (DPP-4) inhibitors saxagliptin and alogliptin were cardiovascular neutral. The publication of the results of the TECOS trial with sitagliptin, another DPP-4 inhibitor, the American Diabetes Association 2015 presentation of the ELIXA trial with lixisenatide, the first cardiovascular safety trial with glucagon-like peptide 1 receptor agonists, have also been completed. They both show cardiovascular neutrality in very high-risk diabetic patients. The results of these trials are interpreted in the context of diabetic treatment. PMID:27093207

  1. Effect of a Web-Based Behavior Change Program on Weight Loss and Cardiovascular Risk Factors in Overweight and Obese Adults at High Risk of Developing Cardiovascular Disease: Randomized Controlled Trial

    PubMed Central

    Watson, Sinead; Woodside, Jayne V; Ware, Lisa J; Hunter, Steven J; McGrath, Alanna; Cardwell, Christopher R; Appleton, Katherine M; Young, Ian S

    2015-01-01

    Background Web-based programs are a potential medium for supporting weight loss because of their accessibility and wide reach. Research is warranted to determine the shorter- and longer-term effects of these programs in relation to weight loss and other health outcomes. Objective The aim was to evaluate the effects of a Web-based component of a weight loss service (Imperative Health) in an overweight/obese population at risk of cardiovascular disease (CVD) using a randomized controlled design and a true control group. Methods A total of 65 overweight/obese adults at high risk of CVD were randomly allocated to 1 of 2 groups. Group 1 (n=32) was provided with the Web-based program, which supported positive dietary and physical activity changes and assisted in managing weight. Group 2 continued with their usual self-care (n=33). Assessments were conducted face-to-face. The primary outcome was between-group change in weight at 3 months. Secondary outcomes included between-group change in anthropometric measurements, blood pressure, lipid measurements, physical activity, and energy intake at 3, 6, and 12 months. Interviews were conducted to explore participants’ views of the Web-based program. Results Retention rates for the intervention and control groups at 3 months were 78% (25/32) vs 97% (32/33), at 6 months were 66% (21/32) vs 94% (31/33), and at 12 months were 53% (17/32) vs 88% (29/33). Intention-to-treat analysis, using baseline observation carried forward imputation method, revealed that the intervention group lost more weight relative to the control group at 3 months (mean –3.41, 95% CI –4.70 to –2.13 kg vs mean –0.52, 95% CI –1.55 to 0.52 kg, P<.001), at 6 months (mean –3.47, 95% CI –4.95 to –1.98 kg vs mean –0.81, 95% CI –2.23 to 0.61 kg, P=.02), but not at 12 months (mean –2.38, 95% CI –3.48 to –0.97 kg vs mean –1.80, 95% CI –3.15 to –0.44 kg, P=.77). More intervention group participants lost ≥5% of their baseline body

  2. NIH Mouse Metabolic Phenotyping Centers: the power of centralized phenotyping

    PubMed Central

    Kent Lloyd, K. C.; Cline, Gary W.; Wasserman, David H.

    2013-01-01

    The Mouse Metabolic Phenotyping Centers (MMPCs) were founded in 2001 by the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high-quality phenotyping services for mouse models of diabetes, obesity, and their complications. The intent is to allow researchers to take optimum advantage of the many new mouse models produced in labs and in high-throughput public efforts. The six MMPCs are located at universities around the country and perform complex metabolic tests in intact mice and hormone and analyte assays in tissues on a fee-for-service basis. Testing is subsidized by the NIH in order to reduce the barriers for mouse researchers. Although data derived from these tests belong to the researcher submitting mice or tissues, these data are archived after publication in a public database run by the MMPC Coordinating and Bioinformatics Unit. It is hoped that data from experiments performed in many mouse models of metabolic diseases, using standard protocols, will be useful in understanding the nature of these complex disorders. The current areas of expertise include energy balance and body composition, insulin action and secretion, whole-body and tissue carbohydrate and lipid metabolism, cardiovascular and renal function, and metabolic pathway kinetics. In addition to providing services, the MMPC staff provides expertise and advice to researchers, and works to develop and refine test protocols to best meet the community’s needs in light of current scientific developments. Test technology is disseminated by publications and through annual courses. PMID:22940748

  3. A metabolic phenotype based on mitochondrial ribosomal protein expression as a predictor of lymph node metastasis in papillary thyroid carcinoma.

    PubMed

    Lee, Jandee; Seol, Mi-Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee-Hyun; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-01-01

    Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized. The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features. GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P < 0

  4. A Metabolic Phenotype Based on Mitochondrial Ribosomal Protein Expression as a Predictor of Lymph Node Metastasis in Papillary Thyroid Carcinoma

    PubMed Central

    Lee, Jandee; Seol, Mi-Youn; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Shin, Dong Yeob; Nam, Kee-Hyun; Lee, Eun Jig; Chung, Woong Youn; Jo, Young Suk

    2015-01-01

    Abstract Metabolic reprogramming has been regarded as an essential component of malignant transformation. However, the clinical significance of metabolic heterogeneity remains poorly characterized. The aim of this study was to characterize metabolic heterogeneity in thyroid cancers via the analysis of the expression of mitochondrial ribosomal proteins (MRPs) and genes involved in oxidative phosphorylation (OxPhos), and investigate potential prognostic correlations. Gene set enrichment analysis (GSEA) verified by reverse transcription polymerase chain reaction and gene network analysis was performed using public repository data. Cross-sectional observational study was conducted to classify papillary thyroid cancer (PTC) by the expression of MRP L44 (MRPL44) messenger RNA (mRNA), and to investigate the clinicopathological features. GSEA clearly showed that the expression of OxPhos and MRP gene sets was significantly lower in primary thyroid cancer than in matched normal thyroid tissue. However, 8 of 49 primary thyroid tumors (16.3%) in the public repository did not show a reduction in OxPhos mRNA expression. Remarkably, strong positive correlations between MRPL44 expression and those of OxPhos and MRPs such as reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 α subcomplex, 5; succinate dehydrogenase complex, subunit D; cytochrome c, somatic; adenosine triphosphate synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9); and MRP S5 (MRPS5) (P < 0.0001) were clearly denoted, suggesting that MRPL44 is a representative marker of OxPhos and MRP expressions. In laboratory experiments, metabolic heterogeneity in oxygen consumption, extracellular acidification rates (ECARs), and amounts of OxPhos complexes were consistently observed in BCPAP, TPC1, HTH-7, and XTC.UC1 cell lines. In PTCs, metabolic phenotype according to OxPhos amount defined by expression of MRPL44 mRNA was significantly related to lymph node metastasis (LNM) (P

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

    PubMed

    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.

  6. Gender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: results from the DIAD study.

    PubMed

    Tandon, Suman; Wackers, Frans J T; Inzucchi, Silvio E; Bansal, Shanti; Staib, Lawrence H; Chyun, Deborah A; Davey, Janice A; Young, Lawrence H

    2012-04-01

    Gender differences in cardiovascular outcomes were compared in asymptomatic men and women with type 2 diabetes (T2DM) in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Of 1123 participants, 290 men and 271 women were randomised to screening with stress myocardial perfusion imaging (MPI); 311 men and 251 women were randomised to no screening. Follow-up was 4.8±0.9 years for the occurrence of cardiac events (CE; cardiac death or non-fatal myocardial infarction). The frequency of abnormal screening was similar in men (24%) and women (19%), (p=0.2), although women trended to have smaller MPI abnormalities. CE rates were lower in women than men (1.7% vs. 3.8%, p=0.04). No CEs occurred in 17 high-risk (UKPDS risk engine) women, whereas 14 (11.2%) occurred in 125 high-risk men. Asymptomatic women with T2DM have significantly better cardiac outcomes than their male counterparts and represent a subgroup for which screening for coronary artery disease does not appear warranted.

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

    PubMed

    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.

  8. Habitual Sleep Duration and Insomnia and the Risk of Cardiovascular Events and All-cause Death: Report from a Community-Based Cohort

    PubMed Central

    Chien, Kuo-Liong; Chen, Pei-Chung; Hsu, Hsiu-Ching; Su, Ta-Chen; Sung, Fung-Chang; Chen, Ming-Fong; Lee, Yuan-Teh

    2010-01-01

    Study Objectives: To investigate the relationship between sleep duration and insomnia severity and the risk of all-cause death and cardiovascular disease (CVD) events Design: Prospective cohort study Setting: Community-based Participants: A total of 3,430 adults aged 35 years or older Intervention: None Measurements and Results: During a median 15.9 year (interquartile range, 13.1 to 16.9) follow-up period, 420 cases developed cardiovascular disease and 901 cases died. A U-shape association between sleep duration and all-cause death was found: the age and gender-adjusted relative risks (95% confidence interval [CI]) of all-cause death (with 7 h of daily sleep being considered for the reference group) for individuals reporting ≤ 5 h, 6 h, 8 h, and ≥ 9 h were 1.15 (0.91–1.45), 1.02 (0.85–1.25), 1.05 (0.88–1.27), and 1.43 (1.16–1.75); P for trend, 0.019. However, the relationship between sleep duration and risk of CVD were linear. The multivariate-adjusted relative risk (95% CI) for all-cause death (using individuals without insomnia) were 1.02 (0.86–1.20) for occasional insomnia, 1.15 (0.92–1.42) for frequent insomnia, and 1.70 (1.16–2.49) for nearly everyday insomnia (P for trend, 0.028). The multivariate adjusted relative risk (95% CI) was 2.53 (1.71–3.76) for all-cause death and 2.07 (1.11–3.85) for CVD rate in participants sleeping ≥9 h and for those with frequent insomnia. Conclusions: Sleep duration and insomnia severity were associated with all-cause death and CVD events among ethnic Chinese in Taiwan. Our data indicate that an optimal sleep duration (7–8 h) predicted fewer deaths. Citation: Chien K; Chen P; Hsu H; Su T; Sung F; Chen M; Lee Y. Habitual sleep duration and insomnia and the risk of cardiovascular events and all-cause death: report from a community-based cohort. SLEEP 2010;33(2):177–184. PMID:20175401

  9. Obesity and cardiovascular disease.

    PubMed

    Jokinen, E

    2015-02-01

    Cardiovascular disease is the most common cause of mortality in rich countries and today it has the same meaning for health care as the epidemics of past centuries had for medicine in earlier times: 50% of the population in these countries die of cardiovascular disease. The amount of cardiovascular disease is also increasing in the developing countries together with economic growth. By 2015 one in three deaths will globally be due to cardiovascular diseases. Coronary heart disease is a chronic disease that starts in childhood, even if the symptoms first occur in the middle age. The risks for coronary heart disease are well-known: lipid disorders, especially high serum LDL-cholesterol concentration, high blood pressure, tobacco smoking, obesity, diabetes, male gender and physical inactivity. Obesity is both an independent risk factor for cardiovascular disease but is also closely connected with several other risk factors. This review focuses on the connection between overweight or obesity and cardiovascular disease. PMID:25387321

  10. Racism and cardiovascular disease: implications for nursing.

    PubMed

    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.

  11. Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2014-01-01

    Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.

  12. Population-based versus high-risk strategies for the prevention of cardiovascular diseases in low- and middle-income countries.

    PubMed

    Babu, Ramesh B; Alam, Mohammed; Helis, Eftyhia; Fodor, J George

    2012-01-01

    Cardiovascular diseases (CVD) are now the number one cause of death in low- and middle-income countries (LMIC), such as those in South East Asia (SEA). It is projected that SEA countries will have the greatest total number of deaths due to non-communicable diseases (NCDs) by 2020. In low resource countries, the rising burden of CVDs imposes severe economic consequences that range from impoverishment of families to high health system costs and the weakening of country economies. There are two possible options to be considered for addressing this issue: a "population-based strategy" and/or a "high risk" strategy. The question is, what is the optimal way to reduce the excessive burden of these diseases in the LMICs. We believe that by applying systematic policy and smoking cessation programs with proven effectiveness, there is a chance that the high smoking prevalence, particularly among SEA. PMID:23102379

  13. Project həli?dx(w)/Healthy Hearts Across Generations: development and evaluation design of a tribally based cardiovascular disease prevention intervention for American Indian families.

    PubMed

    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

    2012-08-01

    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 həli?dx(w)/Healthy Hearts Across Generations project, an AIAN-run, tribally based randomized controlled trial (January 2010-June 2012) designed to evaluate a culturally appropriate CVD risk prevention program for AI parents residing in the Pacific Northwest of the United States. At-risk AIAN adults (n = 135) were randomly assigned to either a CVD prevention intervention arm or a comparison arm focusing on increasing family cohesiveness, communication, and connectedness. Both year-long conditions included 1 month of motivational interviewing counseling followed by personal coach contacts and family life-skills classes. Blood chemistry, blood pressure, body mass index, food intake, and physical activity were measured at baseline and at 4- and 12-month follow-up times.

  14. Pathological phenotypes and in vivo DNA cleavage by unrestrained activity of a phosphorothioate-based restriction system in Salmonella.

    PubMed

    Cao, Bo; Cheng, Qiuxiang; Gu, Chen; Yao, Fen; DeMott, Michael S; Zheng, Xiaoqing; Deng, Zixin; Dedon, Peter C; You, Delin

    2014-08-01

    Prokaryotes protect their genomes from foreign DNA with a diversity of defence mechanisms, including a widespread restriction-modification (R-M) system involving phosphorothioate (PT) modification of the DNA backbone. Unlike classical R-M systems, highly partial PT modification of consensus motifs in bacterial genomes suggests an unusual mechanism of PT-dependent restriction. In Salmonella enterica, PT modification is mediated by four genes dptB-E, while restriction involves additional three genes dptF-H. Here, we performed a series of studies to characterize the PT-dependent restriction, and found that it presented several features distinct with traditional R-M systems. The presence of restriction genes in a PT-deficient mutant was not lethal, but instead resulted in several pathological phenotypes. Subsequent transcriptional profiling revealed the expression of > 600 genes was affected by restriction enzymes in cells lacking PT, including induction of bacteriophage, SOS response and DNA repair-related genes. These transcriptional responses are consistent with the observation that restriction enzymes caused extensive DNA cleavage in the absence of PT modifications in vivo. However, overexpression of restriction genes was lethal to the host in spite of the presence PT modifications. These results point to an unusual mechanism of PT-dependent DNA cleavage by restriction enzymes in the face of partial PT modification.

  15. RNA interference-based gene silencing of phytoene synthase impairs growth, carotenoids, and plastid phenotype in Oncidium hybrid orchid.

    PubMed

    Liu, Jian-Xin; Chiou, Chung-Yi; Shen, Chin-Hui; Chen, Peng-Jen; Liu, Yao-Chung; Jian, Chin-Der; Shen, Xiao-Lan; Shen, Fu-Quan; Yeh, Kai-Wun

    2014-01-01

    Phytoene synthase (PSY) is the first rate-limiting regulatory enzyme in the carotenoid biosynthesis pathway. In order to modify the floral color pattern by reducing carotenoid contents, a phytoene synthase-RNAi construct was delivered into protocorm-like body (PLB) of Oncidium hybrid orchid. The transgenic orchids show down-regulated level of PSY and geranyl synthase gene. They displayed semi-dwarf phenotype and brilliant green leaves. The microscopic anatomy revealed development-arrested plastids with rare grana. The total carotenoid content was decreased and the efficiency of the photosynthetic electron transport was declined. The chlorophyll level and the expression of chlorophyll biosynthetic genes, such as OgGLUTR and OgCS were dramatically reduced. HPLC analysis showed that the endogenous level of gibberellic acid and abscisic acid in the dwarf transformants are 4-fold lower than in wild type plants. In addition, chilling tolerance of the transgenic Oncidium plants was reduced. The data showed that down-regulation of PSY resulted in alterations of gene expression in enzymes involved in many metabolic pathways, such as carotenoid, gibberellic acid, abscisic acid and chlorophyll biosynthetic pathway as well as causes predominant defects in plant growth and development. PMID:25221736

  16. A KNIME-Based Analysis of the Zebrafish Photomotor Response Clusters the Phenotypes of 14 Classes of Neuroactive Molecules.

    PubMed

    Copmans, Daniëlle; Meinl, Thorsten; Dietz, Christian; van Leeuwen, Matthijs; Ortmann, Julia; Berthold, Michael R; de Witte, Peter A M

    2016-06-01

    Recently, the photomotor response (PMR) of zebrafish embryos was reported as a robust behavior that is useful for high-throughput neuroactive drug discovery and mechanism prediction. Given the complexity of the PMR, there is a need for rapid and easy analysis of the behavioral data. In this study, we developed an automated analysis workflow using the KNIME Analytics Platform and made it freely accessible. This workflow allows us to simultaneously calculate a behavioral fingerprint for all analyzed compounds and to further process the data. Furthermore, to further characterize the potential of PMR for mechanism prediction, we performed PMR analysis of 767 neuroactive compounds covering 14 different receptor classes using the KNIME workflow. We observed a true positive rate of 25% and a false negative rate of 75% in our screening conditions. Among the true positives, all receptor classes were represented, thereby confirming the utility of the PMR assay to identify a broad range of neuroactive molecules. By hierarchical clustering of the behavioral fingerprints, different phenotypical clusters were observed that suggest the utility of PMR for mechanism prediction for adrenergics, dopaminergics, serotonergics, metabotropic glutamatergics, opioids, and ion channel ligands.

  17. Association of Holter-Based Measures Including T-wave Alternans with Risk of Sudden Cardiac Death in the Community-Dwelling Elderly: The Cardiovascular Health Study

    PubMed Central

    Stein, Phyllis K.; Sanghavi, Devang; Sotoodehnia, Nona; Siscovick, David S; Gottdiener, John

    2010-01-01

    Background Sudden cardiac death (SCD) can be the first manifestation of cardiovascular disease. Development of screening methods for higher / lower risk is critical. Methods The Cardiovascular Healthy Study (CHS) is a population-based study of risk factors for coronary heart disease and stroke those ≥65 years. N=49 (of 1649) with usable Holters and in normal sinus rhythm, suffered SCD during follow up and were matched with 2 controls, alive at the time of death of the case and not suffering SCD on follow up. Univariate and multivariate conditional logistic regression determined the association of Holter-based information and SCD. Results In univariate models, the upper half of VPC counts, abnormal heart rate turbulence, decreased normalized low frequency power, increased T-wave alternans (TWA) and decreased DFA1 (short-term fractal scaling exponent) were associated with SCD, but time domain HRV was not. In multivariate models, the upper half of VPC counts (OR=6.6) and having TWA ≥37µV on Ch2 (OR=4.8) were independently associated with SCD. Also, the upper half of VPC counts (OR=6.9) and having DFA1 <1.05 (OR=5.0) were independently associated with SCD. When additive effects were explored: having both higher VPCs and higher TWA was associated with an OR of 8.2 for SCD compared to 2.6 for having either. Also, having both higher VPCs and lower DFA1 was associated with an OR of 9.6 for SCD compared to 3.1 for having either. Conclusions Results support a potential role for 24-hour Holter recordings to identify older adults at increased or lower risk of SCD. PMID:20096853

  18. 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

    PubMed Central

    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. PMID:25993632

  19. 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.

    PubMed

    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.

  20. [Psoriasis and cardiovascular disease].

    PubMed

    Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela

    2013-01-01

    Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.

  1. Body Composition Indices and Single and Clustered Cardiovascular Disease Risk Factors in Adolescents: Providing Clinical-Based Cut-Points.

    PubMed

    Gracia-Marco, Luis; Moreno, Luis A; Ruiz, Jonatan R; Ortega, Francisco B; de Moraes, Augusto César Ferreira; Gottrand, Frederic; Roccaldo, Romana; Marcos, Ascensión; Gómez-Martínez, Sonia; Dallongeville, Jean; Kafatos, Anthony; Molnar, Denes; Bueno, Gloria; de Henauw, Stefaan; Widhalm, Kurt; Wells, Jonathan C

    2016-01-01

    The aims of the present study in adolescents were 1) to examine how various body composition-screening tests relate to single and clustered cardiovascular disease (CVD) risk factors, 2) to examine how lean mass and body fatness (independently of each other) relate to clustered CVD risk factors, and 3) to calculate specific thresholds for body composition indices associated with an unhealthier clustered CVD risk. We measured 1089 European adolescents (46.7% boys, 12.5-17.49years) in 2006-2007. CVD risk factors included: systolic blood pressure, maximum oxygen uptake, homeostasis model assessment, C-reactive protein (n=748), total cholesterol/high density lipoprotein cholesterol and triglycerides. Body composition indices included: height, body mass index (BMI), lean mass, the sum of four skinfolds, central/peripheral skinfolds, waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). Most body composition indices are associated with single CVD risk factors. The sum of four skinfolds, WHtR, BMI, WC and lean mass are strong and positively associated with clustered CVD risk. Interestingly, lean mass is positively associated with clustered CVD risk independently of body fatness in girls. Moderate and highly accurate thresholds for the sum of four skinfolds, WHtR, BMI, WC and lean mass are associated with an unhealthier clustered CVD risk (all AUC>0.773). In conclusion, our results support an association between most of the assessed body composition indices and single and clustered CVD risk factors. In addition, lean mass (independent of body fatness) is positively associated with clustered CVD risk in girls, which is a novel finding that helps to understand why an index such as BMI is a good index of CVD risk but a bad index of adiposity. Moderate to highly accurate thresholds for body composition indices associated with a healthier clustered CVD risk were found. Further studies with a longitudinal design are needed to confirm these findings

  2. Electronic health record-based assessment of cardiovascular health: The stroke prevention in healthcare delivery environments (SPHERE) study.

    PubMed

    Foraker, Randi E; Shoben, Abigail B; Kelley, Marjorie M; Lai, Albert M; Lopetegui, Marcelo A; Jackson, Rebecca D; Langan, Michael A; Payne, Philip R O

    2016-12-01

    < 3% of Americans have ideal cardiovascular health (CVH). The primary care encounter provides a setting in which to conduct patient-provider discussions of CVH. We implemented a CVH risk assessment, visualization, and decision-making tool that automatically populates with electronic health record (EHR) data during the encounter in order to encourage patient-centered CVH discussions among at-risk, yet under-treated, populations. We quantified five of the seven CVH behaviors and factors that were available in The Ohio State University Wexner Medical Center's EHR at baseline (May-July 2013) and compared values to those ascertained at one-year (May-July 2014) among intervention (n = 109) and control (n = 42) patients. The CVH of women in the intervention clinic improved relative to the metrics of body mass index (16% to 21% ideal) and diabetes (62% to 68% ideal), but not for smoking, total cholesterol, or blood pressure. Meanwhile, the CVH of women in the control clinic either held constant or worsened slightly as measured using those same metrics. Providers need easy-to-use tools at the point-of-care to help patients improve CVH. We demonstrated that the EHR could deliver such a tool using an existing American Heart Association framework, and we noted small improvements in CVH in our patient population. Future work is needed to assess how to best harness the potential of such tools in order to have the greatest impact on the CVH of a larger patient population. PMID:27486559

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

    PubMed

    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. PMID:21567248

  4. Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype

    PubMed Central

    Angell, H K; Gray, N; Womack, C; Pritchard, D I; Wilkinson, R W; Cumberbatch, M

    2013-01-01

    Background: Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC. Methods: Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells. Results: Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET−) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET− samples. Conclusion: By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques. PMID:23963148

  5. Ethnic disparities in cardiovascular health.

    PubMed

    Ofili, E

    2001-01-01

    Disparities in the cardiovascular outcomes of African-American patients is evident from national, regional, and local statistical data, as well as from the daily practice of medicine. This discussion highlights the complexity of ethnic disparities using a case-based approach with two typical cases from a cardiology practice. These cases underscore the complex interplay of the following factors in ethnic disparities. 1. Excess burden of cardiovascular risk factors in African Americans, with particular emphasis on high blood pressure, diabetes, obesity, physical inactivity, and psychosocial stress. 2. Inadequate knowledge of how personal risk factors are directly linked to atherosclerosis and heart disease. 3. Cultural factors in symptom recognition and health-care seeking behavior. 4. Economic factors influencing access to health care including prevention, diagnosis, and treatment. 5. A combination of psychosocial stress, racism, and frustration leading to sub-optimal interactions with the health care system. 6. Genetics of disease and predisposition to vascular disease and atherosclerosis. We must come to terms with these fundamental factors in the causation and, therefore, the resolution of ethnic disparities in cardiovascular health. Successful strategies must include: 1) partnerships for long-term, sustainable, population-wide strategies on risk factor modification; 2) models of culturally competent health care delivery; and 3) research on the gene-environment interactions, which cause the susceptibility of ethnic minorities to cardiovascular disease.

  6. Cell Therapy for Cardiovascular Regeneration

    PubMed Central

    2013-01-01

    A great numbers of cardiovascular disease patients all over the world are suffering in the poor outcomes. Under this situation, cardiac regeneration therapy to reorganize the postnatal heart that is defined as a terminal differentiated-organ is a very important theme and mission for human beings. However, the temporary success of several clinical trials using usual cell types with uncertain cell numbers has provided the transient effect of cell therapy to these patients. We therefore should redevelop the evidence of cell-based cardiovascular regeneration therapy, focusing on targets (disease, patient’s status, cardiac function), materials (cells, cytokines, genes), and methodology (transplantation route, implantation technology, tissue engineering). Meanwhile, establishment of the induced pluripotent stem (iPS) cells is an extremely innovative technology which should be proposed as embryonic stem (ES) cellularization of post natal somatic cells, and this application have also showed the milestones of the direct conversion to reconstruct cardiomyocyte from the various somatic cells, which does not need the acquisition of the re-pluripotency. This review discusses the new advance in cardiovascular regeneration therapy from cardiac regeneration to cardiac re-organization, which is involved in recent progress of on-going clinical trials, basic research in cardiovascular regeneration, and the possibility of tissue engineering technology. PMID:23825492

  7. A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

    PubMed

    Quek, Ruben G W; Fox, Kathleen M; Wang, Li; Li, Lu; Gandra, Shravanthi R; Wong, Nathan D

    2016-02-15

    The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk. PMID:26742468

  8. Association between hyperglycaemic crisis and long-term major adverse cardiovascular events: a nationwide population-based, propensity score-matched, cohort study

    PubMed Central

    Chang, Li-Hsin; Lin, Liang-Yu; Tsai, Ming-Tsun; How, Chorng-Kuang; Chiang, Jen-Huai; Hsieh, Vivian Chia-Rong; Hu, Sung-Yuan; Hsieh, Ming-Shun

    2016-01-01

    Objective Hyperglycaemic crisis was associated with significant intrahospital morbidity and mortality. However, the association between hyperglycaemic crisis and long-term cardiovascular outcomes remained unknown. This study aimed to investigate the association between hyperglycaemic crisis and subsequent long-term major adverse cardiovascular events (MACEs). Participants and methods This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database for the period of 1996–2012. A total of 2171 diabetic patients with hyperglycaemic crisis fit the inclusion criteria. Propensity score matching was used to match the baseline characteristics of the study cohort to construct a comparison cohort which comprised 8684 diabetic patients without hyperglycaemic crisis. The risk of long-term MACEs was compared between the two cohorts. Results Six hundred and seventy-six MACEs occurred in the study cohort and the event rate was higher than that in the comparison cohort (31.1% vs 24.1%, p<0.001). Patients with hyperglycaemic crisis were associated with a higher risk of long-term MACEs even after adjusting for all baseline characteristics and medications (adjusted HR=1.76, 95% CI 1.62 to 1.92, p<0.001). Acute myocardial infarction had the highest adjusted HR (adjusted HR=2.19, 95% CI 1.75 to 2.75, p<0.001) in the four types of MACEs, followed by congestive heart failure (adjusted HR=1.97, 95% CI 1.70 to 2.28, p<0.001). Younger patients with hyperglycaemic crisis had a higher risk of MACEs than older patients (adjusted HR=2.69 for patients aged 20–39 years vs adjusted HR=1.58 for patients aged >65 years). Conclusions Hyperglycaemic crisis was significantly associated with long-term MACEs, especially in the young population. Further prospective longitudinal study should be conducted for validation. PMID:27554106

  9. Effect of comprehensive cardiovascular disease risk management on longitudinal changes in carotid artery intima-media thickness in a community-based prevention clinic

    PubMed Central

    Cheng, Henry G.; Patel, Birju S.; Martin, Seth S.; Blaha, Michael; Doneen, Amy; Bale, Brad

    2016-01-01

    Introduction The aim of the study was to examine changes in carotid intima-media thickness (CIMT) and carotid plaque morphology in patients receiving multifactorial cardiovascular disease (CVD) risk factor management in a community-based prevention clinic. Quantitative changes in CIMT and qualitative changes in carotid plaque morphology may be measured non-invasively by ultrasound. Material and methods This is a retrospective study on a cohort of 324 patients who received multifactorial cardiovascular risk reduction treatment at a community prevention clinic. All patients received lipid-lowering medications (statin, niacin, and/or ezetimibe) and lifestyle modification. All patients underwent at least one follow-up CIMT measurement after starting their regimen. Annual biomarker, CIMT, and plaque measurements were analyzed for associations with CVD risk reduction treatment. Results Median time to last CIMT was 3.0 years. Compared to baseline, follow-up analysis of all treatment groups at 2 years showed a 52.7% decrease in max CIMT, a 3.0% decrease in mean CIMT, and an 87.0% decrease in the difference between max and mean CIMT (p < 0.001). Plaque composition changes occurred, including a decrease in lipid-rich plaques of 78.4% within the first 2 years (p < 0.001). After the first 2 years, CIMT and lipid-rich plaques continued to decline at reduced rates. Conclusion In a cohort of patients receiving comprehensive CVD risk reduction therapy, delipidation of subclinical carotid plaque and reductions in CIMT predominantly occurred within 2 years, and correlated with changes in traditional biomarkers. These observations, generated from existing clinical data, provide unique insight into the longitudinal on-treatment changes in carotid plaque. PMID:27478452

  10. Cadmium Exposure and Incident Cardiovascular Disease

    PubMed Central

    Tellez-Plaza, Maria; Guallar, Eliseo; Howard, Barbara V.; Umans, Jason G.; Francesconi, Kevin A.; Goessler, Walter; Silbergeld, Ellen K.; Devereux, Richard B.; Navas-Acien, Ana

    2014-01-01

    Background Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort. Methods We conducted a prospective cohort study of 3,348 American Indian adults aged 45–74 years from Arizona, Oklahoma and North and South Dakota who participated in the Strong Heart Study in 1989–1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008. Results The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval= 0.92 – 0.93). We identified 1,084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% confidence interval=1.21 – 1.70), and 1.34 for coronary heart disease mortality (1.10 – 1.63). The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11 – 1.38), 1.22 (1.08 – 1.38), 1.75 (1.17 – 2.59) and 1.39 (1.01 – 1.94), respectively. The associations were similar in most study subgroups including never-smokers. Conclusions Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and with increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor. PMID:23514838

  11. Cardiovascular disease among firefighters.

    PubMed

    Melius, J M

    1995-01-01

    The author reviews the literature of the past 20 years on heart disease among firefighters, covering the specific aspects of firefighting that may be related to potential cardiovascular disease. The author then outlines steps that can be taken to reduce the risks of developing cardiovascular disease.

  12. [Impact of anti-diabetic therapy based on glucagon-like peptide-1 receptor agonists on the cardiovascular risk of patients with type 2 diabetes mellitus].

    PubMed

    Camafort-Babkowski, Miguel

    2013-08-17

    Anti-diabetic drugs have, in addition to their well-known glucose lowering-effect, different effects in the rest of cardiovascular factors that are associated with diabetes mellitus. Glucagon-like peptide-1 (GLP-1) receptor agonists have recently been incorporated to the therapeutic arsenal of type 2 diabetes mellitus. The objective of this review is to summarize the available evidence on the effect of the GLP-1 receptor agonists on different cardiovascular risk factors, mediated by the effect of GLP-1 receptor agonists on the control of hyperglycaemia and the GLP-1 receptor agonists effect on other cardiovascular risk factors (weight control, blood pressure control, lipid profile and all other cardiovascular risk biomarkers). In addition, we present the emerging evidence with regards to the impact that GLP-1 receptor agonists therapy could have in the reduction of cardiovascular events and the currently ongoing studies addressing this issue.

  13. [Impact of anti-diabetic therapy based on glucagon-like peptide-1 receptor agonists on the cardiovascular risk of patients with type 2 diabetes mellitus].

    PubMed

    Camafort-Babkowski, Miguel

    2013-08-17

    Anti-diabetic drugs have, in addition to their well-known glucose lowering-effect, different effects in the rest of cardiovascular factors that are associated with diabetes mellitus. Glucagon-like peptide-1 (GLP-1) receptor agonists have recently been incorporated to the therapeutic arsenal of type 2 diabetes mellitus. The objective of this review is to summarize the available evidence on the effect of the GLP-1 receptor agonists on different cardiovascular risk factors, mediated by the effect of GLP-1 receptor agonists on the control of hyperglycaemia and the GLP-1 receptor agonists effect on other cardiovascular risk factors (weight control, blood pressure control, lipid profile and all other cardiovascular risk biomarkers). In addition, we present the emerging evidence with regards to the impact that GLP-1 receptor agonists therapy could have in the reduction of cardiovascular events and the currently ongoing studies addressing this issue. PMID:23332622

  14. A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype

    PubMed Central

    Hass, Johanna; Walton, Esther; Kirsten, Holger; Liu, Jingyu; Priebe, Lutz; Wolf, Christiane; Karbalai, Nazanin; Gollub, Randy; White, Tonya; Roessner, Veit; Müller, Kathrin U.; Paus, Tomas; Smolka, Michael N.; Schumann, Gunter; Scholz, Markus; Cichon, Sven; Calhoun, Vince; Ehrlich, Stefan

    2013-01-01

    Patients with schizophrenia and their siblings typically show subtle changes of brain structures, such as a reduction of hippocampal volume. Hippocampal volume is heritable, may explain a variety of cognitive symptoms of schizophrenia and is thus considered an intermediate phenotype for this mental illness. The aim of our analyses was to identify single-nucleotide polymorphisms (SNP) related to hippocampal volume without making prior assumptions about possible candidate genes. In this study, we combined genetics, imaging and neuropsychological data obtained from the Mind Clinical Imaging Consortium study of schizophrenia (n = 328). A total of 743,591 SNPs were tested for association with hippocampal volume in a genome-wide association study. Gene expression profiles of human hippocampal tissue were investigated for gene regions of significantly associated SNPs. None of the genetic markers reached genome-wide significance. However, six highly correlated SNPs (rs4808611, rs35686037, rs12982178, rs1042178, rs10406920, rs8170) on chromosome 19p13.11, located within or in close proximity to the genes NR2F6, USHBP1, and BABAM1, as well as four SNPs in three other genomic regions (chromosome 1, 2 and 10) had p-values between 6.75×10−6 and 8.3×10−7. Using existing data of a very recently published GWAS of hippocampal volume and additional data of a multicentre study in a large cohort of adolescents of European ancestry, we found supporting evidence for our results. Furthermore, allelic differences in rs4808611 and rs8170 were highly associated with differential mRNA expression in the cis-acting region. Associations with memory functioning indicate a possible functional importance of the identified risk variants. Our findings provide new insights into the genetic architecture of a brain structure closely linked to schizophrenia. In silico replication, mRNA expression and cognitive data provide additional support for the relevance of our findings. Identification of

  15. Thalassemia Phenotypes and Genotypes in Taiwan: A Retrospective Study Based on Thalassemia Screening of Young Men for Military Conscription.

    PubMed

    Lee, Hsiao-Wei; Han, Shao-Min; Yang, Youngsen; Lin, Tseng-Hsi; Tzeng, Huey-En; Chang, Kuang-Hsi; Hwang, Wen-Li; Teng, Chieh-Lin J

    2015-01-01

    Prenatal thalassemia studies from Taiwan show that one-third of fetuses with genetic abnormalities have β-thalassemia major (β-TM). However, the phenotypes and genotypes of adult thalassemia warrant further investigation. From September 2006 to April 2014, 741 male candidates drafted for military service with mean corpuscular volume (MCV) <80 fL and serum ferritin >20 µg/L were analyzed. The results showed that the detection rates of α- and β-thalassemia (α- an β-thal) were 50.20% (372/741) and 49.12% (364/741), respectively. Only five patients (0.67%) were diagnosed with both α- and β-thal. The - -(SEA)/αα mutation was found in 76.88% (286/372) of α-thal patients. Heterozygous mutations in IVS-II-654 (C > T) and codons 41/42 (-TCTT) accounted for 55.77% (203/364) of β-thal cases. The leukocyte counts for α- and β-thal were 6241.74 ± 1552.99 and 6622.87 ± 1814.41 × 10(9)/L, respectively (p = 0.007). The α-thal patients had lower red blood cell (RBC) mass (5.85 ± 0.44 × 10(12)/L vs. 6.09 ± 0.45 × 10(12)/L; p < 0.001) and higher hemoglobin (Hb) (12.82 ± 0.72 vs. 12.35 ± 0.71 g/dL; p < 0.001) than β-thal patients. Mean serum ferritin values were 169.67 and 241.36 µg/L, respectively, in α- and β-thal patients (p < 0.001), indicating more profound ineffective erythropoiesis in β-thal. Only four of the 741 patients underwent further hematological follow-up. Our study suggests that iron overload might be a potential problem in β-thal patients; therefore, regular follow-up is highly recommended.

  16. Cardiovascular Biology of the Incretin System

    PubMed Central

    Ussher, John R.; Drucker, Daniel J.

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1R agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus (T2DM). We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk:benefit ratio of incretin-based therapies will require completion of long term cardiovascular outcome studies currently underway in patients with T2DM. PMID:22323472

  17. 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

    ERIC Educational Resources Information Center

    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…

  18. Design of a Randomized Controlled Trial of a Web-Based Intervention to Reduce Cardiovascular Disease Risk Factors among Remote Reservation-Dwelling American Indian Adults with Type 2 Diabetes

    ERIC Educational Resources Information Center

    Henderson, Jeffrey A.; Chubak, Jessica; O'Connell, Joan; Ramos, Maria C.; Jensen, Julie; Jobe, Jared B.

    2012-01-01

    We describe a randomized controlled trial, the Lakota Oyate Wicozani Pi Kte (LOWPK) trial, which was designed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease (CVD) among a group of remote reservation-dwelling adult American Indian men and women with type 2 diabetes…

  19. Cardiovascular proteomics: tools to develop novel biomarkers and potential applications.

    PubMed

    Arab, Sara; Gramolini, Anthony O; Ping, Peipei; Kislinger, Thomas; Stanley, Brian; van Eyk, Jennifer; Ouzounian, Maral; MacLennan, David H; Emili, Andrew; Liu, Peter P

    2006-11-01

    Proteomics is the new systems biological approach to the study of proteins and protein variation on a large scale as a result of biological processes and perturbations. The field is undergoing a dramatic transformation, owing to the completion and annotation of the human genome as well as technological advances to study proteins on a large scale. The new science of proteomics can potentially yield novel biomarkers reflecting cardiovascular disease, establish earlier detection strategies, and monitor responses to therapy. Technological advances permit the unprecedented large-scale identification of peptide sequences in a biological sample with mass spectrometry, whereas gel-based techniques provide further refinement on the status of post-translational modification. The application of high throughput protein evaluation with a subset of predefined targets, identified through proteomics, microarray profiling, and pathway analysis in animal models and human tissues, is gaining momentum in research and clinical applications. Proteomic analysis has provided important insights into ischemic heart disease, heart failure, and cardiovascular pathophysiology. The combination of proteomic biomarkers with clinical phenotypes and genetic haplotype information can lead to a more precise diagnosis and therapy on an individual basis--the fundamental premise of "personalized medicine."

  20. Characterization of systemic metabolic phenotypes associated with subclinical atherosclerosis.

    PubMed

    Würtz, Peter; Soininen, Pasi; Kangas, Antti J; Mäkinen, Ville-Petteri; Groop, Per-Henrik; Savolainen, Markku J; Juonala, Markus; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Ala-Korpela, Mika

    2011-02-01

    Detailed molecular phenotyping gives insight into disease mechanisms and can individualize medical practice for improved risk assessment and treatment. We show in an epidemiological study (n = 4309) that the multi-metabolic profiles obtained by serum NMR metabonomics inherently associate with the extent of atherosclerosis already in preclinical stages. Data-driven analysis of the spectral profiles of healthy, young adults revealed three distinct metabolic phenotypes associated with high carotid intima-media thickness (IMT), a surrogate marker of cardiovascular disease. The phenotypes were characterized by varying combinations of well-known metabolic disturbances like elevated VLDL and LDL and low HDL levels. Low IMT was also associated with distinct metabolic phenotypes with lipoprotein as well as other biochemical characteristics partly opposing those found for the high IMT phenotypes. Profiles of low-molecular-weight metabolites quantified from the experimentation were also characteristic for the metabolic phenotypes and substantiate developments toward the use of multi-metabolic risk phenotypes. The methodology can be taken as a direct extension for the routine analytics used for the risk assessment of atherosclerosis; quantification of metabolites will complement and might even replace conventional lipid measurements. Serum NMR metabonomics is therefore anticipated as a rational option for comprehensive cardiovascular risk assessment.

  1. Sodium intake and cardiovascular health.

    PubMed

    O'Donnell, Martin; Mente, Andrew; Yusuf, Salim

    2015-03-13

    Sodium is an essential nutrient. Increasing sodium intake is associated with increasing blood pressure, whereas low sodium intake results in increased renin and aldosterone levels. Randomized controlled trials have reported reductions in blood pressure with reductions in sodium intake, to levels of sodium intake <1.5 g/d, and form the evidentiary basis for current population-wide guidelines recommending low sodium intake. Although low sodium intake (<2.0 g/d) has been achieved in short-term feeding clinical trials, sustained low sodium intake has not been achieved by any of the longer term clinical trials (>6-month duration). It is assumed that the blood pressure-lowering effects of reducing sodium intake to low levels will result in large reductions in cardiovascular disease globally. However, current evidence from prospective cohort studies suggests a J-shaped association between sodium intake and cardiovascular events, based on studies from >300 000 people, and suggests that the lowest risk of cardiovascular events and death occurs in populations consuming an average sodium intake range (3-5 g/d). The increased risk of cardiovascular events associated with higher sodium intake (>5 g/d) is most prominent in those with hypertension. A major deficit in the field is the absence of large randomized controlled trials to provide definitive evidence on optimal sodium intake for preventing cardiovascular events. Pending such trials, current evidence would suggest a recommendation for moderate sodium intake in the general population (3-5 g/d), with targeting the lower end of the moderate range among those with hypertension.

  2. [Intermediate phenotype of schizophrenia].

    PubMed

    Hashimoto, Ryota

    2013-04-01

    Genes are major contributors to schizophrenia. The intermediate phenotype concept represents a strategy for identifying risk genes for schizophrenia and for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in schizophrenia. Intermediate phenotypes are defined by being heritable, being able to measure quantitatively; being related to the disorder and its symptoms in the general population; being stable over time; showing increased expression in unaffected relatives of probands; and cosegregation with the disorder in families. Intermediate phenotypes in schizophrenia are neurocognition, neuroimaging, neurophysiology, etc. In this review, we present concept, recent work, and future perspective of intermediate phenotype.

  3. Toward performance-diverse small-molecule libraries for cell-based phenotypic screening using multiplexed high-dimensional profiling.

    PubMed

    Wawer, Mathias J; Li, Kejie; Gustafsdottir, Sigrun M; Ljosa, Vebjorn; Bodycombe, Nicole E; Marton, Melissa A; Sokolnicki, Katherine L; Bray, Mark-Anthony; Kemp, Melissa M; Winchester, Ellen; Taylor, Bradley; Grant, George B; Hon, C Suk-Yee; Duvall, Jeremy R; Wilson, J Anthony; Bittker, Joshua A; Dančík, Vlado; Narayan, Rajiv; Subramanian, Aravind; Winckler, Wendy; Golub, Todd R; Carpenter, Anne E; Shamji, Alykhan F; Schreiber, Stuart L; Clemons, Paul A

    2014-07-29

    High-throughput screening has become a mainstay of small-molecule probe and early drug discovery. The question of how to build and evolve efficient screening collections systematically for cell-based and biochemical screening is still unresolved. It is often assumed that chemical structure diversity leads to diverse biological performance of a library. Here, we confirm earlier results showing that this inference is not always valid and suggest instead using biological measurement diversity derived from multiplexed profiling in the construction of libraries with diverse assay performance patterns for cell-based screens. Rather than using results from tens or hundreds of completed assays, which is resource intensive and not easily extensible, we use high-dimensional image-based cell morphology and gene expression profiles. We piloted this approach using over 30,000 compounds. We show that small-molecule profiling can be used to select compound sets with high rates of activity and diverse biological performance.

  4. Long noncoding RNAs in cardiovascular diseases.

    PubMed

    Uchida, Shizuka; Dimmeler, Stefanie

    2015-02-13

    In recent year, increasing evidence suggests that noncoding RNAs play important roles in the regulation of tissue homeostasis and pathophysiological conditions. Besides small noncoding RNAs (eg, microRNAs), >200-nucleotide long transcripts, namely long noncoding RNAs (lncRNAs), can interfere with gene expressions and signaling pathways at various stages. In the cardiovascular system, studies have detected and characterized the expression of lncRNAs under normal physiological condition and in disease states. Several lncRNAs are regulated during acute myocardial infarction (eg, Novlnc6) and heart failure (eg, Mhrt), whereas others control hypertrophy, mitochondrial function and apoptosis of cardiomyocytes. In the vascular system, the endothelial-expressed lncRNAs (eg, MALAT1 and Tie-1-AS) can regulate vessel growth and function, whereas the smooth-muscle-expressed lncRNA smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA was recently shown to control the contractile phenotype of smooth muscle cells. This review article summarizes the data on lncRNA expressions in mouse and human and highlights identified cardiovascular lncRNAs that might play a role in cardiovascular diseases. Although our understanding of lncRNAs is still in its infancy, these examples may provide helpful insights how lncRNAs interfere with cardiovascular diseases.

  5. Lessons from operational cardiovascular studies in space

    NASA Technical Reports Server (NTRS)

    Charles, J. B.; Yelle, J.; Sawin, C. F.

    1996-01-01

    The Space Shuttle program has produced a database of information on the cardiovascular responses to spaceflight, based on in-flight as well as pre- and post-flight assessments undertaken as part of the assessment of the health, safety, and efficiency of Shuttle crews. The methods used in routine cardiovascular assessments of Space Shuttle astronauts are reviewed, and the major findings of these investigations are presented.

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

    PubMed

    Resaland, G K; Anderssen, S A; Holme, I M; Mamen, A; Andersen, L B

    2011-12-01

    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 at the I-school carried out 60 min of PA daily. The PA lessons were planned, organized and led by expert physical education (PE) teachers. In the C-school, children were offered the normal 45 min of PE twice weekly. The intervention resulted in a greater beneficial development in systolic (P=0.003) and diastolic (P=0.002) blood pressure, total cholesterol-to-high-density lipoprotein cholesterol ratio (P=0.011), triglyceride (P=0.030) and peak oxygen uptake (P<0.001) in I-school children than in C-school children. No significant differences were observed in waist circumference, body mass index and the homeostasis model assessment for insulin resistance between the two groups. Furthermore, the intervention, primarily carried out at moderate intensity, had the strongest impact in children with the least favorable starting point. In conclusion, a daily school-based PA intervention can beneficially modify children's CVD risk profile if the intervention has sufficient duration and includes a substantial amount of daily PA, and if the PA is implemented by expert PE teachers.

  7. Individual-, Family-, Community-, and Policy-Level Impact of a School-Based Cardiovascular Risk Detection Screening Program for Children in Underserved, Rural Areas: The CARDIAC Project

    PubMed Central

    Cottrell, Lesley; Murphy, Emily; Lilly, Christa L.; Ritchie, Susan K.; Minor, Valerie; Neal, William A.

    2013-01-01

    The Coronary Artery Risk Detection In Appalachian Communities (CARDIAC) Project has screened more than 80,000 children (10–12 years) for cardiovascular and diabetes risk factors over the past 15 years. Simultaneous referral and intervention efforts have also contributed to the overall program impact. In this study, we examined evidence of programmatic impact in the past decade at the individual, family, community, and policy levels from child screening outcomes, referral rates, participation in subsequent services, and policies that embed the activities of the project as a significant element. Within this period of time, fifth-grade overweight and obesity rates were maintained at a time when rates elsewhere increased. 107 children were referred for additional screening and treatment for probable familial hypercholesterolemia (FH); 82 family members were subsequently screened in family-based screening efforts. 58 grants were distributed throughout the state for community-appropriate obesity intervention. A state wellness policy embedded CARDIAC as the method of assessment and national child cholesterol screening guidelines were impacted by CARDIAC findings. The sustainability and successful impact of this school-based program within a largely underserved, rural Appalachian state are also discussed. PMID:23840946

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

    PubMed

    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.

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

    PubMed

    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. PMID:22271835

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

    ERIC Educational Resources Information Center

    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. Testosterone and Cardiovascular Disease

    PubMed Central

    Tambo, Amos; Roshan, Mohsin H.K.; Pace, Nikolai P.

    2016-01-01

    Cardiovascular disease [CVD] is a leading cause of mortality accounting for a global incidence of over 31%. Atherosclerosis is the primary pathophysiology underpinning most types of CVD. Historically, modifiable and non-modifiable risk factors were suggested to precipitate CVD. Recently, epidemiological studies have identified emerging risk factors including hypotestosteronaemia, which have been associated with CVD. Previously considered in the realms of reproductive biology, testosterone is now believed to play a critical role in the cardiovascular system in health and disease. The actions of testosterone as they relate to the cardiac vasculature and its implication in cardiovascular pathology is reviewed. PMID:27014372

  12. Cardiovascular disease screening.

    PubMed

    Duffy, Jennifer Y; Hameed, Afshan B

    2015-06-01

    Cardiovascular disease is the leading cause of death amongst women worldwide. Cardiovascular risk assessment and primary prevention are important strategies to improve morbidity and mortality. In additional to the traditional risk factors, pregnancy complications such as pre-eclampsia and gestational diabetes increment future risk of developing cardiovascular complications. Additionally, several serum biomarkers are valuable measures for both risk assessment and predictors of clinical outcomes in women. The purpose of this review is to describe current risk stratification schemes as well as outline the role of obstetric history and serum biomarkers in adjusting risk stratification in women. PMID:26143091

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

    PubMed Central

    Bovet, Pascal; Hirsiger, Philippe; Emery, Frédéric; De Bernardini, Jessica; Rossier, Christophe; Trebeljahr, Josefine; Hagon-Traub, Isabelle

    2011-01-01

    Background: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place. Intervention and methods: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was ≥7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program. Results: A total of 4222 participants (0.76% of all persons aged ≥18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG ≥ 7.8 mmol/L and 1.8% had both RBG ≥ 7.0 mmol/L and A1c ≥ 6.5. Untreated blood pressure ≥140/90 mmHg and/or untreated cholesterol ≥5.2 mmol/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

  14. Liposomes for cardiovascular targeting.

    PubMed

    Levchenko, Tatyana S; Hartner, William C; Torchilin, Vladimir P

    2012-04-01

    Liposome-based pharmaceuticals used within the cardiovascular system are reviewed in this article. The delivery of diagnostic and therapeutic agents by plain liposomes and liposomes with surface-attached targeting antibodies or polyethylene glycol to prolong their circulation time and accumulation at vascular injuries, ischemic zones or sites of thrombi are also discussed. An overview of the advantages and disadvantages of liposome-mediated in vitro, ex vivo and in vivo targeting is presented, including discussion of the targeting of liposomes to pathological sites on the blood vessel wall and a description of liposomes that can be internalized by endothelial cells. Diagnostic liposomes used to target myocardial infarction and the relative importance of liposome size, targetability of immunoliposomes and prolonged circulation time on the efficiency of sealing hypoxia-induced plasma membrane damage to cardiocytes are discussed as a promising approach for therapy. The progress in the use of targeted liposomal plasmids for the transfection of hypoxic cardiomyocytes and myocardium is presented. Stent-mediated liposomal-based drug delivery is also reviewed briefly. PMID:22834079

  15. Chemokines and cardiovascular risk.

    PubMed

    Aukrust, Pål; Halvorsen, Bente; Yndestad, Arne; Ueland, Thor; Øie, Erik; Otterdal, Kari; Gullestad, Lars; Damås, Jan K

    2008-11-01

    Based on the importance of inflammation in atherogenesis, recent work has focused on whether plasma markers of inflammation can noninvasively diagnose and prognosticate atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherosclerosis, potentially representing attractive therapeutic targets in atherosclerotic disorders, this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect upstream inflammatory activity, stable levels in individuals, and high stability of the actual protein (eg, long half-life and negligible circadian variation) are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (eg, interleukin- 8/CXCL8 and monocyte chemoattractant protein-1/CCL2) have shown to be predictive for future cardiac events in some studies, their role as clinical biomarkers is unclear, and their ability to predict subclinical atherosclerosis has been disappointing. Further prospective studies, including a larger number of patients, are needed to make any firm conclusion. Based on the participation of several chemokines in atherogenesis, it is possible that in the future, combined measurements of multiple chemokines could reveal as a "signature of disease" that can serve as a highly accurate method to assess for the presence of atherosclerotic disease. PMID:18669888

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

    PubMed

    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

  17. A systematic search for SNPs/haplotypes associated with disease phenotypes using a haplotype-based stepwise procedure

    PubMed Central

    Yang, Yin; Li, Shuying Sue; Chien, Jason W; Andriesen, Jessica; Zhao, Lue Ping

    2008-01-01

    Background Genotyping technologies enable us to genotype multiple Single Nucleotide Polymorphisms (SNPs) within selected genes/regions, providing data for haplotype association analysis. While haplotype-based association analysis is powerful for detecting untyped causal alleles in linkage-disequilibrium (LD) with neighboring SNPs/haplotypes, the inclusion of extraneous SNPs could reduce its power by increasing the number of haplotypes with each additional SNP. Methods Here, we propose a haplotype-based stepwise procedure (HBSP) to eliminate extraneous SNPs. To evaluate its properties, we applied HBSP to both simulated and real data, generated from a study of genetic associations of the bactericidal/permeability-increasing (BPI) gene with pulmonary function in a cohort of patients following bone marrow transplantation. Results Under the null hypothesis, use of the HBSP gave results that retained the desired false positive error rates when multiple comparisons were considered. Under various alternative hypotheses, HBSP had adequate power to detect modest genetic associations in case-control studies with 500, 1,000 or 2,000 subjects. In the current application, HBSP led to the identification of two specific SNPs with a positive validation. Conclusion These results demonstrate that HBSP retains the essence of haplotype-based association analysis while improving analytic power by excluding extraneous SNPs. Minimizing the number of SNPs also enables simpler interpretation and more cost-effective applications. PMID:19102730

  18. Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention

    PubMed Central

    Paulsen, Keith D.; Samkoe, Kimberley S.; Elliott, Jonathan T.; Hasan, Tayyaba; Strong, Theresa V.; Draney, Daniel R.; Feldwisch, Joachim

    2016-01-01

    Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective

  19. Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention.

    PubMed

    Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S; Elliott, Jonathan T; Hasan, Tayyaba; Strong, Theresa V; Draney, Daniel R; Feldwisch, Joachim

    2016-06-01

    Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective

  20. Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention.

    PubMed

    Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S; Elliott, Jonathan T; Hasan, Tayyaba; Strong, Theresa V; Draney, Daniel R; Feldwisch, Joachim

    2016-06-01

    Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near-infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective

  1. Phenotype definition in epilepsy.

    PubMed

    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. NT-proBNP Predicts Cardiovascular Death in the General Population Independent of Left Ventricular Mass and Function: Insights from a Large Population-Based Study with Long-Term Follow-Up

    PubMed Central

    Dietl, Alexander; Stark, Klaus; Zimmermann, Martina E.; Meisinger, Christa; Schunkert, Heribert; Birner, Christoph; Maier, Lars S.; Peters, Annette

    2016-01-01

    Aims B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) predict cardiovascular endpoints in patients and all-cause death in the general population. This was assigned to their association with clinical cardiac remodelling defined as changes in size, shape and function of the heart. The aim of this study was to evaluate whether NT-proBNP and BNP were associated with cardiovascular and overall death independent of clinical cardiac remodelling measured by echocardiography as left ventricular hypertrophy (LVH), diastolic dysfunction and left ventricular ejection fraction (EF). Methods and Results In a general population-based cohort study from Germany (KORA-S3) with subjects’ baseline age ranging from 25 to 74 years, cardiac morphology and function were assessed as left ventricular mass (LVM), diastolic dysfunction and EF by echocardiography and circulating NT-proBNP and BNP were measured at baseline. In 1,223 subjects with mortality follow-up information, we examined the association of baseline NT-proBNP and BNP with cardiovascular mortality (number of deaths = 52, median follow-up time = 12.9years) using Cox regression without and with adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF. The risk of cardiovascular mortality increased with higher NT-proBNP levels measured at baseline (hazard ratio HR = 1.67 per unit increment in logNT-proBNP, p = 2.78*10−4, adjusted for age and sex). This increased risk persisted after adjustment for cardiovascular risk factors, LVM, diastolic dysfunction and EF (HR = 1.73; p = 0.047). When excluding subjects with relevant LVH (LVM to body surface area > 149g/m2 in men / 122g/m2 in women), the NT-proBNP association with mortality was still significant (n = 1,138; number of deaths = 35; HR = 1.48; p = 0.04). We found similar results for BNP. Conclusion Our data confirms NT-proBNP and BNP as predictor of cardiovascular mortality in a large general population-based study with long-term follow

  3. Testosterone and Cardiovascular Disease.

    PubMed

    Kloner, Robert A; Carson, Culley; Dobs, Adrian; Kopecky, Stephen; Mohler, Emile R

    2016-02-01

    Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety. PMID:26846952

  4. Autophagy in cardiovascular biology

    PubMed Central

    Lavandero, Sergio; Chiong, Mario; Rothermel, Beverly A.; Hill, Joseph A.

    2015-01-01

    Cardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future. PMID:25654551

  5. Autophagy in cardiovascular biology.

    PubMed

    Lavandero, Sergio; Chiong, Mario; Rothermel, Beverly A; Hill, Joseph A

    2015-01-01

    Cardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

  6. Cardiovascular modeling and diagnostics

    SciTech Connect

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T.

    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.

  7. [Cardiovascular risk among firefighters].

    PubMed

    Serra, A

    2012-01-01

    Firefighting is a high-hazard job for hearth disease, smoke exposure, physical exertion, psychological stressors and noise increase cardiovascular risk among fire fighters. In U.S.A. during the period 1984-2011 45% of on-duty fire fighter fatalities were due to sudden cardiac death. Ho