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Sample records for cardiovascular phenotypes based

  1. Echocardiographic Speckle-Tracking Based Strain Imaging for Rapid Cardiovascular Phenotyping in Mice

    PubMed Central

    Bauer, Michael; Cheng, Susan; Jain, Mohit; Ngoy, Soeun; Theodoropoulos, Catherine; Trujillo, Anna; Lin, Fen-Chiung; Liao, Ronglih

    2012-01-01

    Rationale High-sensitivity in vivo phenotyping of cardiac function is essential for evaluating genes of interest and novel therapies in small animal models of cardiovascular disease. Transthoracic echocardiography is the principal method currently used for assessing cardiac structure and function; however, standard echocardiographic techniques are relatively insensitive to early or subtle changes in cardiac performance, particularly in mice. Objective To develop and validate an echocardiographic strain imaging methodology for sensitive and rapid cardiac phenotyping in small animal models. Methods and Results Herein, we describe a modified echocardiographic technique that utilizes speckle-tracking based strain analysis for the non-invasive evaluation of cardiac performance in adult mice. This method is found to be rapid, reproducible, and highly sensitive in assessing both regional and global left ventricular (LV) function. Compared to conventional echocardiographic measures of LV structure and function, peak longitudinal strain and strain rate were able to detect changes in adult mouse hearts at an earlier time point following myocardial infarction (post-MI) and predicted the later development of adverse LV remodeling. Moreover, speckle-tracking based strain analysis was able to clearly identify subtle improvement in LV function that occurred early in response to standard post-MI cardiac therapy. Conclusions Our results highlight the utility of speckle-tracking based strain imaging for detecting discrete functional alterations in mouse models of cardiovascular disease in an efficient and comprehensive manner. Echocardiography speckle-tracking based strain analysis represents a method for relatively high-throughput and sensitive cardiac phenotyping, particularly in evaluating emerging cardiac agents and therapies in mice. PMID:21372284

  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. The cardiovascular phenotype of a mouse model of acromegaly.

    PubMed

    Izzard, Ashley S; Emerson, Michael; Prehar, Sukhpal; Neyses, Ludwig; Trainer, Peter; List, Edward O; Kopchick, John J; Heagerty, Anthony M

    2009-10-01

    Although, it is accepted that there is an excess of cardiovascular mortality in acromegaly, it is uncertain whether this is due to the direct effects of growth hormone-induced-cardiomyopathy or is a consequence of atherosclerosis secondary to the metabolic syndrome often observed in this condition. Direct comparison of a mouse model of acromegaly to a mouse model of Laron's syndrome allowed us to carry out detailed phenotyping and better understand the role GH plays in the circulatory system. Transgenic mice that overexpress the growth hormone gene (GH) developed gigantism, including insulin resistance and higher blood pressures commensurate with increased body mass. In these giant mice, the hearts were hypertrophied but haemodynamic studies suggested contractile function was normal. Segments of small arteries mounted in a pressure myograph showed vascular wall hypertrophy but a preserved lumen diameter. Vascular contractile function was normal. Mice in which the GH receptor gene was disrupted or 'knocked out' were dwarf and had low blood pressure, small hearts and blood vessels but a normally functioning circulation. Correlations of body mass with cardiovascular parameters suggested that blood pressure and structural characteristics develop in line with body size. In this transgenic mouse model of acromegaly, there is cardiac and vascular hypertrophy commensurate with GH excess but normal function. Our findings support the contention that the excess mortality in this condition may be due to the development of hypertrophic cardiomyopathy rather than increased rates of atherosclerotic coronary artery disease.

  4. Age-dependent heterogeneity of familiar hypertrophic cardiomyopathy phenotype: a role of cardiovascular magnetic resonance.

    PubMed

    Glaveckaitė, Sigita; Rudys, Alfredas; Mikštienė, Violeta; Valevičienė, Nomeda; Palionis, Darius; Laucevičius, Aleksandras

    2013-01-01

    In this case report, we present familiar hypertrophic cardiomyopathy with age-dependent heterogeneity of the disease phenotype among the members of one family who carry the same mutation of the myosin-binding protein C gene. Phenotypic heterogeneity is common in patients with familial forms of hypertrophic cardiomyopathy, both in clinical expression and outcome. Compared with other noninvasive cardiac imaging modalities, cardiovascular magnetic resonance provides an opportunity to more accurately characterize the varying phenotypic presentations of hypertrophic cardiomyopathy.

  5. Association of central and peripheral blood pressures with intermediate cardiovascular phenotypes.

    PubMed

    Roman, Mary J; Devereux, Richard B

    2014-06-01

    In conclusion, numerous studies have documented a superior relation of central over brachial BP to intermediate cardiovascular phenotypes or cardiovascular target organ damage. In general, PP has been more strongly related to vascular disease, whereas systolic pressure seems to be a more important determinant of LVH. The similarity of findings in a wide variety of patient-based and population-based studies as well as a broad range of ethnicities supports the robust nature of this phenomenon. Although data regarding the superiority of central over brachial PP with regard to LV diastolic dysfunction are preliminary, the importance of LVH, female sex, and aging as underlying risk factors for HFPEF suggests that more extensive evaluation is likely to reveal a stronger relation of central than peripheral BP with this additional measure of target organ involvement. Finally, limited data suggesting a more important impact of reversing hypertensive cardiovascular hypertrophy by lowering central pressure for a given brachial pressure require confirmation in larger, longitudinal intervention studies.

  6. [Scientific evidence of the mediterranean diet effects in determining intermediate and final cardiovascular disease phenotypes].

    PubMed

    Sotos-Prieto, Mercedes; Zulet, Maria Angeles; Corella, Dolores

    2010-01-23

    The follow-up of the Mediterranean Diet (MD) has been associated with lower mortality and morbidity from cardiovascular diseases. However, it is important to evaluate the scientific evidence provided by published articles. Therefore, in order to analyze the literature on the overall effects of MD on intermediate and final disease phenotypes, we reviewed the findings from 30 selected experimental and observational studies. We analyzed the effect of MD on all-cause mortality, cardiovascular mortality, recurrence of cardiovascular events, lipid profile, inflammatory markers, blood pressure and fasting blood glucose levels. In general, MD was found to have beneficial effects on final and intermediate disease phenotypes. However, more randomized, controlled interventional studies on the overall effects of MD offering the highest level of scientific evidence are needed before adequate dietary recommendations concerning the primary prevention of cardiovascular disease can be given. Copyright 2008 Elsevier España, S.L. All rights reserved.

  7. Is there any relationship between different phenotypes of metabolic syndrome and cardiovascular mortality rate?

    PubMed Central

    Khosravi, Alireza; Ahmadzadeh, Sareh; Gharipour, Mojgan; Golshahi, Jafar; Sadeghi, Masoumeh; Jozan, Mahnaz; Sarrafzadegan, Nizal

    2016-01-01

    Background: This study aimed to focus on different phenotypes of metabolic syndrome (MetS) and their impact on the cardiovascular disease (CVD) events among a sample of the Iranian population. Materials and Methods: The Isfahan cohort study is a population-based, on-going longitudinal study of adults aged 35 years old or more, living in urban and rural areas of three counties in central Iran namely Isfahan, Najafabad and Arak. Participants were selected by multistage random sampling and were recruited to reflect the age, sex and urban/rural distribution of the community. The sample was restricted to subjects with MetS based on the National Cholesterol Education Program Adult Treatment Panel III criteria and no history of coronary heart disease, stroke, or cancer at the time of the baseline clinical examination. Results: Among different phenotypes of MetS components, clustering of high triglycerides (TGs), low high-density lipoprotein (HDL) and abdominal obesity (ABO) was the most related to the all-cause mortality among women and followed in order by high TGs, hypertension (HTN) and ABO. In men, the highest rate of all-cause mortality was related to high TGs, low HDL, and HTN. Clustering of four components (high TGs, low HDL and HTN and obesity) is the most related to all-cause mortality in the both sexes (12.1% in men, and 21.5% in women). Conclusion: This study showed different phenotypes of MetS related with all-cause mortality rate and existing HTN in the phenotype of MetS increased the incidence of CVD mortality. PMID:28028525

  8. Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

    PubMed Central

    Joseph, Jacob; Loscalzo, Joseph

    2013-01-01

    Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease. PMID:23434902

  9. Cardiovascular phenotype in Turner syndrome--integrating cardiology, genetics, and endocrinology.

    PubMed

    Mortensen, Kristian H; Andersen, Niels H; Gravholt, Claus H

    2012-10-01

    Cardiovascular disease is emerging as a cardinal trait of Turner syndrome, being responsible for half of the 3-fold excess mortality. Turner syndrome has been proposed as an independent risk marker for cardiovascular disease that manifests as congenital heart disease, aortic dilation and dissection, valvular heart disease, hypertension, thromboembolism, myocardial infarction, and stroke. Risk stratification is unfortunately not straightforward because risk markers derived from the general population inadequately identify the subset of females with Turner syndrome who will suffer events. A high prevalence of endocrine disorders adds to the complexity, exacerbating cardiovascular prognosis. Mounting knowledge about the prevalence and interplay of cardiovascular and endocrine disease in Turner syndrome is paralleled by improved understanding of the genetics of the X-chromosome in both normal health and disease. At present in Turner syndrome, this is most advanced for the SHOX gene, which partly explains the growth deficit. This review provides an up-to-date condensation of current state-of-the-art knowledge in Turner syndrome, the main focus being cardiovascular morbidity and mortality. The aim is to provide insight into pathogenesis of Turner syndrome with perspectives to advances in the understanding of genetics of the X-chromosome. The review also incorporates important endocrine features, in order to comprehensively explain the cardiovascular phenotype and to highlight how raised attention to endocrinology and genetics is important in the identification and modification of cardiovascular risk.

  10. Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports.

    PubMed

    Yasuda, Kazushi; Morihana, Eiji; Fusazaki, Naoki; Ishikawa, Shiro

    2016-01-01

    Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for.

  11. Cardiovascular Malformations in CHARGE Syndrome with DiGeorge Phenotype: Two Case Reports

    PubMed Central

    Morihana, Eiji; Fusazaki, Naoki; Ishikawa, Shiro

    2016-01-01

    Both CHARGE syndrome and DiGeorge anomaly are frequently accompanied by cardiovascular malformations. Some specific cardiovascular malformations such as interrupted aortic arch type B and truncus arteriosus are frequently associated with 22q11.2 deletion syndrome, while conotruncal defects and atrioventricular septal defects are overrepresented in patients with CHARGE syndrome. CHD7 gene mutation is identified in approximately two-thirds of patients with CHARGE syndrome, and chromosomal microdeletion at 22q11.2 is found in more than 95% of patients with 22q11.2 deletion syndrome. CHARGE syndrome is occasionally accompanied by DiGeorge phenotype. We report two patients with dysmorphic features of both CHARGE syndrome and 22q11.2 deletion syndrome. Although both of the two cases did not have 22q11.2 deletion, they had typical dysmorphic features of 22q11.2 deletion syndrome including cardiovascular malformations such as interrupted aortic arch type B. They also had characteristic features of CHARGE syndrome including ear malformation, genital hypoplasia, limb malformation, and endocrinological disorders. CHD7 gene mutation was confirmed in one of the two cases. When a patient with cardiovascular malformations frequently associated with 22q11.2 deletion syndrome does not have 22q11.2 deletion, we suggest that associated malformations characteristic of CHARGE syndrome should be searched for. PMID:27957375

  12. Cervical artery dissection expands the cardiovascular phenotype in FBN1-related Weill-Marchesani syndrome.

    PubMed

    Newell, Kelsey; Smith, Wendy; Ghoshhajra, Brian; Isselbacher, Eric; Lin, Angela; Lindsay, Mark E

    2017-09-01

    Weill-Marchesani syndrome (WMS) is a rare form of acromelic dysplasia that is characterized by distinctive skeletal, ocular, and cardiovascular abnormalities. Previously described cardiac manifestations of WMS include aortic and pulmonary valve stenosis, mitral valve prolapse, mitral stenosis, and QTc prolongation. Autosomal dominant forms of WMS result from heterozygous pathogenic variants in FBN1, a gene with a well characterized role in the pathogenesis of thoracic aortic aneurysm (TAA) in the context of Marfan syndrome. In contrast, only one patient has been reported with aortic disease in WMS. Although the risk of aortic dissection from preceding TAA remains the leading cause of morbidity for individuals with Marfan syndrome, rare reports of arterial dissection in the peripheral vasculature have been described. Peripheral artery dissection has not been previously reported in other FBN1-related diseases. We describe a three generation family with FBN1-related WMS whose cardiovascular manifestations include TAA and cervical artery dissection, thus expanding the cardiovascular phenotype of WMS. Further research is required to quantify these risks and establish appropriate recommendations for cardiovascular imaging, medical management, and prophylactic surgical intervention in individuals with FBN1--related acromelic dysplasia. © 2017 Wiley Periodicals, Inc.

  13. Effects of perinatal, late foetal, and early embryonic insults on the cardiovascular phenotype in experimental animal models and humans.

    PubMed

    Meister, Theo Arthur; Rexhaj, Emrush; Rimoldi, Stefano Flavio; Scherrer, Urs; Sartori, Claudio

    2016-11-01

    Cardiovascular diseases are the main cause of mortality and morbidity in Western countries, but the underlying mechanisms are still poorly understood. Genetic polymorphisms, once thought to represent a major determinant of cardiovascular risk, individually and collectively, only explain a tiny fraction of phenotypic variation and disease risk in humans. It is now clear that non-genetic factors, i.e., factors that modify gene activity without changing the DNA sequence and that are sensitive to the environment can cause important alterations of the cardiovascular phenotype in experimental animal models and humans. Here, we will review recent studies demonstrating that distinct pathological events during the perinatal (transient perinatal hypoxemia), late foetal (preeclampsia), and early embryonic (assisted reproductive technologies) periods induce profound alterations of the cardiovascular phenotype in humans and experimental animals. Moreover, we will provide evidence that epigenetic modifications are contributing importantly to this problem and are conferring the potential for its transmission to subsequent generations.

  14. 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

  15. Clinical phenotype clustering in cardiovascular risk patients for the identification of responsive metabotypes after red wine polyphenol intake.

    PubMed

    Vázquez-Fresno, Rosa; Llorach, Rafael; Perera, Alexandre; Mandal, Rupasri; Feliz, Miguel; Tinahones, Francisco J; Wishart, David S; Andres-Lacueva, Cristina

    2016-02-01

    This study aims to evaluate the robustness of clinical and metabolic phenotyping through, for the first time, the identification of differential responsiveness to dietary strategies in the improvement of cardiometabolic risk conditions. Clinical phenotyping of 57 volunteers with cardiovascular risk factors was achieved using k-means cluster analysis based on 69 biochemical and anthropometric parameters. Cluster validation based on Dunn and Figure of Merit analysis for internal coherence and external homogeneity were employed. k-Means produced four clusters with particular clinical profiles. Differences on urine metabolomic profiles among clinical phenotypes were explored and validated by multivariate orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) models. OSC-PLS-DA of (1)H-NMR data revealed that model comparing "obese and diabetic cluster" (OD-c) against "healthier cluster" (H-c) showed the best predictability and robustness in terms of explaining the pairwise differences between clusters. Considering these two clusters, distinct groups of metabolites were observed following an intervention with wine polyphenol intake (WPI; 733 equivalents of gallic acid/day) per 28days. Glucose was significantly linked to OD-c metabotype (P<.01), and lactate, betaine and dimethylamine showed a significant trend. Tartrate (P<.001) was associated with wine polyphenol intervention (OD-c_WPI and H-c_WPI), whereas mannitol, threonine methanol, fucose and 3-hydroxyphenylacetate showed a significant trend. Interestingly, 4-hydroxyphenylacetate significantly increased in H-c_WPI compared to OD-c_WPI and to basal groups (P<.05)-gut microbial-derived metabolite after polyphenol intake-, thereby exhibiting a clear metabotypic intervention effect. Results revealed gut microbiota responsive phenotypes to wine polyphenols intervention. Overall, this study illustrates a novel metabolomic strategy for characterizing interindividual responsiveness to dietary

  16. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. CD4(+)CD28(null) T lymphocyte frequency, a new marker of cardiovascular risk: relationship with polycystic ovary syndrome phenotypes.

    PubMed

    Moro, Francesca; Morciano, Andrea; Tropea, Anna; Sagnella, Francesca; Palla, Carola; Scarinci, Elisa; Cosentino, Nicola; Niccoli, Giampaolo; Liuzzo, Giovanna; Crea, Filippo; Lanzone, Antonio; Apa, Rosanna

    2012-12-01

    To study the frequency of CD4(+)CD28(null) T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index-matched healthy women. Retrospective cohort observational study. Unit of human reproductive pathophysiology, university hospital. A total of 167 PCOS patients and 102 control subjects. None. CD4(+)CD28(null) T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. CD4(+)CD28(null) frequency was significantly higher in all PCOS groups than in control subjects. CD4(+)CD28(null) frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2-7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1-5.8), H + O (3%, range 1.8-4.7), and H + PCO (2.63%, range 1.2-4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4(+)CD28(null) frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9-5.8). Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4(+)CD28(null) frequency. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

    Aslibekyan, S; Jensen, MK; Campos, H; Linkletter, CD; Loucks, EB; Ordovas, JM; Deka, R; Rimm, EB; Baylin, A

    2013-01-01

    BACKGROUND/OBJECTIVES 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 ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS MI cases (n = 1650) were matched to population-based controls (n = 1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses’ Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). RESULTS Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values = 0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value = 0.04). However, the observed associations were not replicated in independent populations. CONCLUSION Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI. PMID:22293571

  1. Cardiovascular Effects of Incretin-Based Therapies.

    PubMed

    White, William B; Baker, William L

    2016-01-01

    The incretin-based therapies, dipeptidyl peptidase-4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) analogs, are important new classes of therapy for type 2 diabetes mellitus (T2DM). These agents prolong the action of the incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), by inhibiting their breakdown. The incretin hormones improve glycemic control in T2DM by increasing insulin secretion and suppressing glucagon levels. The cardiovascular (CV) effects of the incretin-based therapies have been of substantial interest since 2008, when the US Food and Drug Administration began to require that all new therapies for diabetes undergo rigorous assessment of CV safety through large-scale CV outcome trials. This article reviews the most recent CV outcome trials of the DPP-4 inhibitors (SAVOR-TIMI 53, EXAMINE, and TECOS) as evidence that the incretin-based therapies have acceptable CV safety profiles for patients with T2DM. The studies differ with regard to patient population, trial duration, and heart failure outcomes but show similar findings for CV death, nonfatal myocardial infarction, and stroke, as well as hospitalization for unstable angina.

  2. A network-based phenotype mapping approach to identify genes that modulate drug response phenotypes

    PubMed Central

    Cairns, Junmei; Ung, Choong Yong; da Rocha, Edroaldo Lummertz; Zhang, Cheng; Correia, Cristina; Weinshilboum, Richard; Wang, Liewei; Li, Hu

    2016-01-01

    To better address the problem of drug resistance during cancer chemotherapy and explore the possibility of manipulating drug response phenotypes, we developed a network-based phenotype mapping approach (P-Map) to identify gene candidates that upon perturbed can alter sensitivity to drugs. We used basal transcriptomics data from a panel of human lymphoblastoid cell lines (LCL) to infer drug response networks (DRNs) that are responsible for conferring response phenotypes for anthracycline and taxane, two common anticancer agents use in clinics. We further tested selected gene candidates that interact with phenotypic differentially expressed genes (PDEGs), which are up-regulated genes in LCL for a given class of drug response phenotype in triple-negative breast cancer (TNBC) cells. Our results indicate that it is possible to manipulate a drug response phenotype, from resistant to sensitive or vice versa, by perturbing gene candidates in DRNs and suggest plausible mechanisms regulating directionality of drug response sensitivity. More important, the current work highlights a new way to formulate systems-based therapeutic design: supplementing therapeutics that aim to target disease culprits with phenotypic modulators capable of altering DRN properties with the goal to re-sensitize resistant phenotypes. PMID:27841317

  3. Cardiovascular

    NASA Image and Video Library

    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...

  4. 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)

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

    PubMed

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

    2015-01-01

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

  6. Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities.

    PubMed

    Tonni, Gabriele; Lituania, Mario; Chitayat, David; Bonasoni, Maria Paola; Keating, Sarah; Thompson, Megan; Shannon, Patrick

    2014-12-01

    Trisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. The first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. Complete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy. Copyright © 2014. Published by Elsevier B.V.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. [Programming of cardiovascular phenotype by pharmacological intervention in early developmental stages: prevention of hypertension].

    PubMed

    Zemancíková, A; Török, J

    2011-01-01

    Cardiovascular diseases, including hypertension, represent serious medical and social problem because they affect many people in industrialized countries in the world and, unfortunately, their incidence has not decreasing tendency. Human essential hypertension is a chronic, slowly developing disease, which is a consequence of abnormalities in the development of cardiovascular system and its regulation, which are subsequently reflected in pathological rise of blood pressure. In general, blood pressure increases slowly and gradually and this may last several years. Myocardial hypertrophy and structural alterations of the vessel system frequently occur. As hypertension is already established, then complete normalization of blood pressure is difficult to obtain. Therefore, it is necessary to focus on its prevention, this means, to intervene before blood pressure elevation in individuals with significant genetic predisposition to this disease. Moreover, it is well known that cardiovascular system of the young organism is very sensitive to various environmental influences, and one can expect that it may also be more susceptible to vasoactive substances in prevention and treatment of cardiovascular diseases. Hypertension and its pharmacological treatment should therefore be studied with regard to the maturity of an individual. In accordance with the hypothesis of developmental plasticity of organisms, it may be possible (by pharmacological intervention in early ontogenetic stages of predisposed individual) to achieve such a setting of structural and functional parameters which could reduce the subsequent clinical manifestation of genetically induced hypertensive state.

  9. Arterial hypertension in migraine: Role of familial history and cardiovascular phenotype.

    PubMed

    Babayan, Laura; Mamontov, Oleg V; Amelin, Alexander V; Bogachev, Mikhail; Kamshilin, Alexei A

    2017-03-01

    Recent studies indicate that migraine is associated with increased risk of cardiovascular diseases. However, links between autonomic cardiovascular regulation, arterial hypertension (AH) and migraine are still little explored. In this study, we evaluated autonomic regulation in migraine patients with and without hypertension. We studied 104 patients with migraine, aged 34±10 y, including 28 with and 76 without hypertension (M+AH and M-AH groups, respectively). The control group consisted of 88 healthy volunteers matched by age and sex. The autonomic regulation of circulation was examined with the tilt-table test, deep-breathing and Valsalva Maneuver, handgrip test, cold-stress induced vasoconstriction, arterial baroreflex, and blood pressure variability measurements. We found that migraine patients with concomitant hypertension demonstrated reduced arterial baroreflex, whereas other parameters of cardiac autonomic regulation were unchanged. In contrast, most indicators of vasomotor reactivity (blood pressure response to the hand-grip, Valsalva maneuver and cold vasoconstriction) were enhanced in migraine patients with no significant differences between migraine patients with and without hypertension. Patients from both M+AH and M-AH groups more commonly had a family history of cardiovascular disorders. Our data revealed increased vasomotor reactivity in migraine patients, with or without concomitant hypertension. This was associated with the family history of cardiovascular diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Molecular and Clinical Based Cardiovascular Care Program

    DTIC Science & Technology

    2007-01-01

    pathogenesis of coronary artery, peripheral vascular , and cerebrovascular disease . Impairment of endothelial function has been demonstrated after high...cardio’Va~ ct•b.r disease , Subsequently, ultrnlow-fat diets (:;;1.0% of totlll caloric intake as fat), emphasi?.in,g the amount ra.thcr th<•.o the...cardiovascular disease at the molecular disease stage and identify biomarkers predictive of sub- clinical CVD; and 3) Relate genomic/proteomic changes to the

  11. Kinect system in home-based cardiovascular rehabilitation.

    PubMed

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

    2017-01-01

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

  12. Cardiovascular manifestations in Marfan syndrome and related diseases; multiple genes causing similar phenotypes.

    PubMed

    Cook, J R; Carta, L; Galatioto, J; Ramirez, F

    2015-01-01

    Cardiovascular abnormalities are the major cause of morbidity and mortality in Marfan syndrome (MFS) and a few clinically related diseases that share, with MFS, the pathogenic contribution of dysregulated transforming growth factor β (TGFβ) signaling. They include Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome, aneurysm-osteoarthritis syndrome and syndromic thoracic aortic aneurysms. Unlike the causal association of MFS with mutations in an extracellular matrix protein (ECM), the aforementioned conditions are due to defects in components of the TGFβ pathway. While TGFβ antagonism is being considered as a potential new therapy for these heritable syndromes, several points still need to be clarified in relevant animal models before this strategy could be safely applied to patients. Among others, unresolved issues include whether elevated TGFβ signaling is responsible for all MFS manifestations and is the common trigger of disease in MFS and related conditions. The scope of our review is to highlight the clinical and experimental findings that have forged our understanding of the natural history and molecular pathogenesis of cardiovascular manifestations in this group of syndromic conditions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. 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.

  14. Development of a Claims-based Frailty Indicator Anchored to a Well-established Frailty Phenotype.

    PubMed

    Segal, Jodi B; Chang, Hsien-Yen; Du, Yu; Walston, Jeremy D; Carlson, Michelle C; Varadhan, Ravi

    2017-07-01

    Fried and colleagues described a frailty phenotype measured in the Cardiovascular Health Study (CHS). This phenotype is manifest when ≥3 of the following are present: low grip strength, low energy, slowed waking speed, low physical activity, or unintentional weight loss. We sought to approximate frailty phenotype using only administrative claims data to enable frailty to be assessed without physical performance measures. We used the CHS cohort data linked to participants Medicare claims. The reference standard was the frailty phenotype measured at visits 5 and 9. With penalized logistic regression, we developed a parsimonious index for predicting the frailty phenotype using a linear combination of diagnoses, operationalized with claims data. We assessed the predictive validity of frailty index by examining how well it predicted common aging-related outcomes including hospitalization, disability, and death. There were 4454 CHS participants from 4 clinical sites. In total, 84% were white, 58% were women and their mean age was 72 years at enrollment. Approximately 11% of the cohort was frail. The model had an area under the receiver operating curve of 0.75 to concurrently predict a frailty phenotype. This Claims-based Frailty Indicator significantly predicted death (odds ratio, 1.84), time to death (hazards ratio, 1.71), number of hospital admissions (incidence rate ratio, 1.74), and nursing home admission (odds ratio, 1.47) in models adjusted for age and sex. Claims data alone can be used to classify individuals as frail and nonfrail. The Claims-based Frailty Indicator might be used in research with large datasets for confounding adjustment or risk prediction. The indicator might also be used for emergency preparedness for identification of regions enriched with frail individuals.

  15. Carotid intima-media thickness, dietary intake, and cardiovascular phenotypes in adolescents: relation to metabolic syndrome.

    PubMed

    Croymans, Daniel M; Sanchez, Albert; Barth, Jacques D; Roberts, Christian K

    2010-04-01

    Little is known about the interrelationships between metabolic syndrome (MS), uric acid, and early carotid atherosclerosis with diet in adolescents. We investigated associations among diet, carotid intima-media thickness (cIMT), MS, uric acid, and other cardiovascular risk factors in adolescents. Two hundred forty-nine adolescents from 3 high schools in Central California-a predominately Hispanic (n = 119, 16.1 +/- 0.9 years old, 94% Hispanic), a mixed-ethnicity (n = 94, 15.7 +/- 1.2 years old), and a Seventh-day Adventist (SDA) (n = 33, 17.0 +/- 1.3 years old) high school-were assessed for cIMT, blood lipids, uric acid, blood glucose, systolic and diastolic blood pressure, body mass index (BMI), and dietary intake. Compared with SDA adolescents, the predominately Hispanic and mixed-ethnicity high school adolescents exhibited higher low-density lipoprotein and BMI percentile, whereas adolescents from the SDA and mixed-ethnicity high schools exhibited lower uric acid and fasting glucose levels than those from the Hispanic high school. After adjusting for age and sex, cIMT was only correlated with systolic blood pressure percentile (r = 0.16, P < .01). Controlling for age, levels of uric acid were correlated with BMI percentile (males: r = 0.59, P < .001; females: r = 0.24, P < .01), low-density lipoprotein (males: r = 0.40, P < .001; females: r = 0.20, P < .01), and total cholesterol in males (r = 0.38, P < .001). Despite no significant differences in the high school frequency of MS risk factors, 59% of adolescents had one or more MS risk factors. A relationship was noted between the number of MS risk factors and uric acid (P < .002). Most of the adolescents presented MS risk factors independent of ethnicity or a purportedly healthier lifestyle (SDA). Uric acid association with MS and its risk factors suggests its potentially heightened importance for the assessment of adolescent cardiovascular health. Published by Elsevier Inc.

  16. 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

  17. A cardiovascular phenotype in warfarin-resistant Vkorc1 mutant rats

    PubMed Central

    Kohn, Michael H.; Price, Roger E.; Pelz, Hans-Joachim

    2009-01-01

    Summary Background The inhibition of the vitamin K cycle by warfarin promotes arterial calcification in the rat. Conceivably, genetically determined vitamin K-deficiency owing to a mutant epoxide reductase subcomponent 1 (Vkorc1) gene, a key component of the vitamin K cycle, might also promote arterial calcification. In the absence of an available Vkorc1 gene knockout model we used a wild-derived Vkorc1 mutant rat strain (Rattus norvegicus) to explore the validity of this hypothesis. Methods We provide histopathological descriptions of a naturally occurring Vkorc1 gene knockdown: wild-derived lab-reared rats that are resistant to the anticoagulant warfarin owing to a non-synonymous mutation in the Vkorc1 gene (Vkorc1Y->C), which, in vitro, reduces the basal activity of the vitamin K epoxide reductase enzyme complex by ~52%. H&E stained sections of heart and kidney were compared between homozygous Vkorc1Y->C/ Y->C, heterozygous Vkorc1Y->C/+ and wildtype Vkorc1+/+ rats of both sexes. Results We observed that the aorta of the heart was mineralized in the Vkorc1Y->C/ Y->C male rats but lesions were virtually absent from Vkorc1Y->C/+ and Vkorc1+/+ male and all female rats. The renal arteries were mineralized in Vkorc1Y->C/ Y->C and Vkorc1Y->C/+ mutant rats, regardless of sex. Conclusions Results support a hypothesis that posits that Vkorc1 genetic polymorphisms reducing basal enzyme activity could affect cardiovascular health, with dependencies on genotype, sex, and tissue. The undercarboxylation of the vitamin K-dependent Matrix Gla protein may be the crucial component of the pathway promoting this mineralization. PMID:19884975

  18. PROC, PROCR, and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study

    PubMed Central

    Reiner, Alexander P.; Carty, Cara L.; Jenny, Nancy S.; Nievergelt, Caroline; Cushman, Mary; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Kuller, Lewis H.; Lange, Leslie A.

    2010-01-01

    Background & Objectives Genes encoding protein C anticoagulant pathways are candidates for athero-thrombotic and other aging-related disorders. Methods Using a tagSNP approach, and data from the Cardiovascular Health Study (CHS), we assessed associations of common polymorphisms of PROC, PROS1, and PROCR with (1) plasma protein C, soluble protein C receptor (sEPCR), and protein S levels measured in a sub-sample of 336 participants at study entry; (2) risk of incident clinical outcomes (coronary heart disease or CHD, stroke, and mortality) in 4,547 participants during follow-up. Secondarily, we explored associations between plasma protein C, S, and sEPCR levels and other candidate genes involved in thrombosis, inflammation, and aging. Results The PROCR Ser219Gly polymorphism (rs867186) was strongly associated with higher sEPCR levels, explaining 75% of the phenotypic variation. The Ser219Gly variant was also associated with higher levels of circulating protein C antigen. An IL10 polymorphism was associated with higher free protein S levels. The minor alleles of PROC rs2069901 and PROS1 rs4857343 were weakly associated with lower protein C and free protein S levels, respectively. There was no association between PROCR Ser219Gly and risk of CHD, stroke, or mortality. The minor allele of another common PROCR tagSNP, rs2069948, was associated with lymphoid PROCR mRNA expression and with increased risk of incident stroke and all-cause mortality, and decreased healthy survival during follow-up. Conclusions A common PROCR variant may be associated with decreased healthy survival in older adults. Additional studies are warranted to establish the role of PROCR variants in ischemic and aging-related disorders. PMID:18680534

  19. High density lipoproteins-based therapies for cardiovascular disease

    PubMed Central

    Gao, Xuan; Yuan, Shujun

    2010-01-01

    Atherosclerosis is the leading cause of death in developed countries. High density lipoproteins (HDL) cholesterol level correlates inversely with the risk of cardiovascular diseases. Thus, HDL has obtained lots of interest for drug development. In this review, we summarized the mechanisms for the antiatherogenic function of HDL, current HDL-based drugs in clinical use and the future direction for HDL-based therapy development. PMID:21187875

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

    PubMed

    Kawel-Boehm, Nadine; Bluemke, David A

    2017-07-01

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

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

    PubMed

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

    2017-02-15

    Polycystic ovary syndrome (PCOS) is a common condition in women of reproductive age. 2 PCOS phenotypes (classic and ovulatory) are currently recognized as the most prevalent, with important differences in terms of cardiometabolic features. We studied the performance of different adiposity indexes to predict preclinical metabolic alterations and cardiovascular risk in 234 women with PCOS (173 with classic and 61 with ovulatory PCOS) and 129 controls. Performance of waist circumference, waist-to-height ratio, conicity index, lipid accumulation product, and visceral adiposity index was assessed based on HOMA-IR ≥ 3.8 as reference standard for screening preclinical metabolic alterations and cardiovascular risk factors in each group. Lipid accumulation product had the best accuracy for classic PCOS, and visceral adiposity index had the best accuracy for ovulatory PCOS. By applying the cutoff point of lipid accumulation product<34, we identified a subgroup of patients without cardiometabolic alterations (P<0.05) in the group with classic PCOS, a population at higher risk for hypertension, dyslipidemia, and impaired glucose tolerance. In ovulatory PCOS, visceral adiposity index ≥ 1.32 was capable of detecting women with significantly higher blood pressure and less favorable glycemic and lipid variables as compared to ovulatory PCOS with lower visceral adiposity index (P<0.05). These results suggest LAP ≥ 34 as the best marker for classic PCOS, and VAI ≥ 1.32 for ovulatory PCOS women. Both indexes can be easily calculated with measures obtained in routine clinical practice and may be useful to detect cardiometabolic risk and secure early interventions.

  2. Evidence-based practice strategies for cardiovascular care.

    PubMed

    Hatfield, Linda; Mulvey, Suzanne; Marleau-Webb, Avis; Bower, Laura; Polomano, Rosemary C

    2004-01-01

    Evidence-based practice (EBP) is a problem-solving approach utilizing the best available information to support clinical decisions. The cardiovascular literature sufficiently supports the adoption of EBP to reduce practice variations and improve patient outcomes. However, the ability to appraise evidence and determine the best ways to implement evidence into practice remains a challenge for most clinicians and administrators. Our discussion assesses the quality of evidence and the benefits of evidence-based approaches to care, but also frames the distinctions among research-based, evidence-based, and best practice. Organizational infrastructure is key to developing EBP approaches and sustaining high quality of care.

  3. Association between KCNJ11 E23K genotype and cardiovascular and glucose metabolism phenotypes in older men and women.

    PubMed

    Yi, Yang; Dongmei, Liu; Phares, Dana A; Weiss, Edward P; Brandauer, Josef; Hagberg, James M

    2008-01-01

    Our objective was to investigate the relationship between the E23K genetic variant in the KCNJ11 gene, which encodes for the Kir6.2 subunit of the inward rectifier K+ channel family, and glucose and insulin metabolism and cardiovascular (CV) function in the sedentary state and their responses to exercise training. Two hundred and fourteen healthy sedentary men and women aged 50-75 years old and free of CV disease and type 2 diabetes underwent baseline testing (maximal oxygen consumption (Vo2max), body composition and glucose tolerance). One hundred and sixty-three of them repeated these tests after 24 weeks of exercise training while on a low-fat diet. At baseline, age, height, body fat, resting systolic blood pressure and all glucose and insulin metabolism markers did not differ among E23K genotype groups. In women at baseline, E23K genotype was associated with body weight, body mass index, Vo2max (ml kg(-1) min(-1), l min(-1)) and maximal minute ventilation. In men at baseline, E23K genotype was significantly associated with maximal heart rate, maximal respiratory exchange ratio and diastolic blood pressure at rest. Numerous glucose and insulin metabolism and CV function phenotypes changed significantly with exercise training in the total population. The E23K genotype did not significantly influence any of these training-induced changes. Thus, the common E23K genetic variant at the KCNJ11 gene locus was significantly associated with CV function in the untrained state, although the associations appear to differ between men and women. However, this variant has no significant effect on training-induced CV and glucose and insulin metabolism adaptations.

  4. EHR-based phenotyping: Bulk learning and evaluation.

    PubMed

    Chiu, Po-Hsiang; Hripcsak, George

    2017-06-01

    In data-driven phenotyping, a core computational task is to identify medical concepts and their variations from sources of electronic health records (EHR) to stratify phenotypic cohorts. A conventional analytic framework for phenotyping largely uses a manual knowledge engineering approach or a supervised learning approach where clinical cases are represented by variables encompassing diagnoses, medicinal treatments and laboratory tests, among others. In such a framework, tasks associated with feature engineering and data annotation remain a tedious and expensive exercise, resulting in poor scalability. In addition, certain clinical conditions, such as those that are rare and acute in nature, may never accumulate sufficient data over time, which poses a challenge to establishing accurate and informative statistical models. In this paper, we use infectious diseases as the domain of study to demonstrate a hierarchical learning method based on ensemble learning that attempts to address these issues through feature abstraction. We use a sparse annotation set to train and evaluate many phenotypes at once, which we call bulk learning. In this batch-phenotyping framework, disease cohort definitions can be learned from within the abstract feature space established by using multiple diseases as a substrate and diagnostic codes as surrogates. In particular, using surrogate labels for model training renders possible its subsequent evaluation using only a sparse annotated sample. Moreover, statistical models can be trained and evaluated, using the same sparse annotation, from within the abstract feature space of low dimensionality that encapsulates the shared clinical traits of these target diseases, collectively referred to as the bulk learning set. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-01-01

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

  6. Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60-64 years in the 1946 British birth cohort study: an epidemiological study.

    PubMed

    Charakida, Marietta; Khan, Tauseef; Johnson, William; Finer, Nick; Woodside, John; Whincup, Peter H; Sattar, Naveed; Kuh, Diana; Hardy, Rebecca; Deanfield, John

    2014-08-01

    Excess body fat is associated with an increase in risk of type 2 diabetes and hypertension in adulthood and these risks can adversely affect progression of arterial disease. We aimed to assess the impact of lifelong patterns of adiposity on cardiovascular risk factors and carotid intima media thickness (cIMT) in later life in participants in the 1946 British birth cohort study. The National Survey of Health and Development Study was a nationally representative sample of 5362 singleton births to married parents in England, Scotland, and Wales, stratified by social class, during 1 week in March 1946. Our present study is based on the 60% of participants still alive and with a known present address in England, Scotland, or Wales who attended a clinic assessment after invitation aged 60-64 years. We included participants with lifetime adiposity measures, cardiovascular risk factors, and cIMT measured at 60-64 years. Participants were classified as normal weight or overweight or obese at each age (36, 43, 53, and 60-64 years) in adulthood, and childhood overweight was defined. Patterns of BMI change were identified and we used BMI to define adiposity status. We used multivariable linear regression to establish the cross-sectional association of BMI category at age 60-64 years with cIMT, adjusted for various confounders. We included 1273 (45%) of 2856 participants eligible in 2006-10 (at age 60-64 years) in this study. Compared with normal weight, overweight and obesity were associated with higher cIMT (0·029 mm, 95% CI 0·014-0·043) and systolic blood pressure (7·95 mm Hg, 5·86-10·0). Increased cIMT, systolic blood pressure, leptin, prevalence of diabetes, and reduced adiponectin were all associated with duration of exposure to adult adiposity (p<0·0001 for all). We noted little additional effect of childhood overweight. Individuals who dropped a BMI category in adulthood had lower cIMT (-0·034 mm, -0·056 to -0·013) and leptin concentrations (-0·4 ng/mL, -0

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. Enhanced lipid peroxidation and platelet activation as potential contributors to increased cardiovascular risk in the low-HDL phenotype.

    PubMed

    Vazzana, Natale; Ganci, Antonina; Cefalù, Angelo Baldassare; Lattanzio, Stefano; Noto, Davide; Santoro, Nicole; Saggini, Raoul; Puccetti, Luca; Averna, Maurizio; Davì, Giovanni

    2013-04-04

    Low high-density lipoprotein (HDL) levels are major predictors of cardiovascular (CV) events, even in patients on statin treatment with low-density lipoprotein (LDL) at target. In animal models HDLs protect LDL from oxidation and blunt platelet activation. Our study aimed to examine whether HDL levels are related to in vivo oxidative stress and platelet activation, as determinants of atherothrombosis. Urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, were measured in 65 coronary heart disease (CHD) normocholesterolemic patients with HDL ≤35 mg/dL, and in 47 CHD patients with HDL >35 mg/dL. The 2 eicosanoids were also measured before and after an intensive exercise program in sedentary people (n=18) and before and after fenofibrate treatment in otherwise healthy subjects with low HDL (n=10). Patients with HDL ≤35 mg/dL showed significantly higher urinary 8-iso-PGF2α (median [25th to 75th percentiles]: 289 [189 to 380] versus 216 [171 to 321] pg/mg creatinine, P=0.019) and 11-dehydro-TXB2 (563 [421 to 767] versus 372 [249 to 465] pg/mg creatinine, P=0.0001) than patients with higher HDL. A direct correlation was found between urinary 8-iso-PGF2α and 11-dehydro-TXB2 in the entire group of patients (ρ=0.77, P<0.0001). HDL levels were inversely related to both 8-iso-PGF2α (ρ=-0.32, P=0.001) and 11-dehydro-TXB2 (ρ=-0.52, P<0.0001). On multiple regression, only 8-iso-PGF2α (β=0.68, P<0.0001) and HDL level (β=-0.29, P<0.0001) were associated with urinary 11-dehydro-TXB2 excretion, independent of sex, age, smoking, hypertension, diabetes, previous myocardial infarction, total cholesterol, LDL, and triglycerides. Both intensive exercise and fenofibrate treatment significantly reduced the 2 eicosanoids in healthy subjects, in parallel with an HDL increase. A low HDL phenotype, both in CHD patients and in healthy subjects, is associated with increased lipid peroxidation and platelet activation

  12. Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.

    PubMed

    Guo, Tingwei; McDonald-McGinn, Donna; Blonska, Anna; Shanske, Alan; Bassett, Anne S; Chow, Eva; Bowser, Mark; Sheridan, Molly; Beemer, Frits; Devriendt, Koen; Swillen, Ann; Breckpot, Jeroen; Digilio, Maria C; Marino, Bruno; Dallapiccola, Bruno; Carpenter, Courtney; Zheng, Xin; Johnson, Jacob; Chung, Jonathan; Higgins, Anne Marie; Philip, Nicole; Simon, Tony J; Coleman, Karlene; Heine-Suner, Damian; Rosell, Jordi; Kates, Wendy; Devoto, Marcella; Goldmuntz, Elizabeth; Zackai, Elaine; Wang, Tao; Shprintzen, Robert; Emanuel, Beverly; Morrow, Bernice

    2011-11-01

    Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial /DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.2 could be responsible. To test this, a large sample size is needed. The TBX1 gene was sequenced in 360 consecutive 22q11DS patients. Rare and common variations were identified. We did not detect enrichment in rare SNP (single nucleotide polymorphism) number in those with or without a congenital heart defect. One exception was that there was increased number of very rare SNPs between those with normal heart anatomy compared to those with right-sided aortic arch or persistent truncus arteriosus, suggesting potentially protective roles in the SNPs for these phenotype-enrichment groups. Nine common SNPs (minor allele frequency, MAF > 0.05) were chosen and used to genotype the entire cohort of 1,022 22q11DS subjects. We did not find a correlation between common SNPs or haplotypes and cardiovascular phenotype. This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome. © 2011 Wiley Periodicals, Inc.

  13. 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.

  14. HPOSim: an R package for phenotypic similarity measure and enrichment analysis based on the human phenotype ontology.

    PubMed

    Deng, Yue; Gao, Lin; Wang, Bingbo; Guo, Xingli

    2015-01-01

    Phenotypic features associated with genes and diseases play an important role in disease-related studies and most of the available methods focus solely on the Online Mendelian Inheritance in Man (OMIM) database without considering the controlled vocabulary. The Human Phenotype Ontology (HPO) provides a standardized and controlled vocabulary covering phenotypic abnormalities in human diseases, and becomes a comprehensive resource for computational analysis of human disease phenotypes. Most of the existing HPO-based software tools cannot be used offline and provide only few similarity measures. Therefore, there is a critical need for developing a comprehensive and offline software for phenotypic features similarity based on HPO. HPOSim is an R package for analyzing phenotypic similarity for genes and diseases based on HPO data. Seven commonly used semantic similarity measures are implemented in HPOSim. Enrichment analysis of gene sets and disease sets are also implemented, including hypergeometric enrichment analysis and network ontology analysis (NOA). HPOSim can be used to predict disease genes and explore disease-related function of gene modules. HPOSim is open source and freely available at SourceForge (https://sourceforge.net/p/hposim/).

  15. HPOSim: An R Package for Phenotypic Similarity Measure and Enrichment Analysis Based on the Human Phenotype Ontology

    PubMed Central

    Deng, Yue; Gao, Lin; Wang, Bingbo; Guo, Xingli

    2015-01-01

    Background Phenotypic features associated with genes and diseases play an important role in disease-related studies and most of the available methods focus solely on the Online Mendelian Inheritance in Man (OMIM) database without considering the controlled vocabulary. The Human Phenotype Ontology (HPO) provides a standardized and controlled vocabulary covering phenotypic abnormalities in human diseases, and becomes a comprehensive resource for computational analysis of human disease phenotypes. Most of the existing HPO-based software tools cannot be used offline and provide only few similarity measures. Therefore, there is a critical need for developing a comprehensive and offline software for phenotypic features similarity based on HPO. Results HPOSim is an R package for analyzing phenotypic similarity for genes and diseases based on HPO data. Seven commonly used semantic similarity measures are implemented in HPOSim. Enrichment analysis of gene sets and disease sets are also implemented, including hypergeometric enrichment analysis and network ontology analysis (NOA). Conclusions HPOSim can be used to predict disease genes and explore disease-related function of gene modules. HPOSim is open source and freely available at SourceForge (https://sourceforge.net/p/hposim/). PMID:25664462

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

    PubMed Central

    2013-01-01

    Background Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. Methods We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. Results We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (p<0.0028, corrected for multiple testing for each trait). Peripheral white blood cell (PWBC) expression of FABP3 in a separate group of subjects (n=128) negatively

  17. Genetic Determinants of Osteoporosis: Common Bases to Cardiovascular Diseases?

    PubMed Central

    Marini, Francesca; Brandi, Maria Luisa

    2010-01-01

    Osteoporosis is the most common and serious age-related skeletal disorder, characterized by a low bone mass and bone microarchitectural deterioration, with a consequent increase in bone fragility and susceptibility to spontaneous fractures, and it represents a major worldwide health care problem with important implications for health care costs, morbidity and mortality. Today is well accepted that osteoporosis is a multifactorial disorder caused by the interaction between environment and genes that singularly exert modest effects on bone mass and other aspects of bone strength and fracture risk. The individuation of genetic factors responsible for osteoporosis predisposition and development is fundamental for the disease prevention and for the setting of novel therapies, before fracture occurrence. In the last decades the interest of the Scientific Community has been concentrated in the understanding the genetic bases of this disease but with controversial and/or inconclusive results. This review tries to summarize data on the most representative osteoporosis candidate genes. Moreover, since recently osteoporosis and cardiovascular diseases have shown to share common physiopathological mechanisms, this review also provides information on the current understanding of osteoporosis and cardiovascular diseases common genetic bases. PMID:20948561

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

    PubMed Central

    V, Alexandar; Nayar, Pradeep G.; Murugesan, R.; Mary, Beaulah; P, Darshana; Ahmed, Shiek S. S. J.

    2015-01-01

    Cardiovascular diseases (CVDs) account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD), hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies. PMID:26624015

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

    PubMed

    V, Alexandar; Nayar, Pradeep G; Murugesan, R; Mary, Beaulah; P, Darshana; Ahmed, Shiek S S J

    2015-01-01

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

  20. 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

  1. [Cardiovascular pharmacogenomics].

    PubMed

    Scibona, Paula; Angriman, Federico; Simonovich, Ventura; Heller, Martina M; Belloso, Waldo H

    2014-01-01

    Cardiovascular disease remains a major cause of morbidity and mortality worldwide. Current medical practice takes into account information based on population studies and benefits observed in large populations or cohorts. However, individual patients present great differences in both toxicity and clinical efficacy that can be explained by variations in adherence, unknown drug to drug interactions and genetic variability. The latter seems to explain from 20% up to 95% of patient to patient variability. Treating patients with cardiovascular disorders faces the clinician with the challenge to include genomic analysis into daily practice. There are several examples within cardiovascular disease of treatments that can vary in toxicity or clinical usefulness based on genetic changes. One of the main factors affecting the efficacy of Clopidogrel is the phenotype associated with polymorphisms in the gene CYP 2C9. Furthermore, regarding oral anticoagulants, changes in CYP2C9 and VKORC1 play an important role in changing the clinical response to anticoagulation. When analyzing statin treatment, one of their main toxicities (myopathy) can be predicted by the SLCO1B1 polymorphism. The potential for prediction of toxicity and clinical efficacy from the use of genetic analysis warrants further studies aiming towards its inclusion in daily clinical practice.

  2. Large-scale image-based screening and profiling of cellular phenotypes.

    PubMed

    Bougen-Zhukov, Nicola; Loh, Sheng Yang; Lee, Hwee Kuan; Loo, Lit-Hsin

    2017-02-01

    Cellular phenotypes are observable characteristics of cells resulting from the interactions of intrinsic and extrinsic chemical or biochemical factors. Image-based phenotypic screens under large numbers of basal or perturbed conditions can be used to study the influences of these factors on cellular phenotypes. Hundreds to thousands of phenotypic descriptors can also be quantified from the images of cells under each of these experimental conditions. Therefore, huge amounts of data can be generated, and the analysis of these data has become a major bottleneck in large-scale phenotypic screens. Here, we review current experimental and computational methods for large-scale image-based phenotypic screens. Our focus is on phenotypic profiling, a computational procedure for constructing quantitative and compact representations of cellular phenotypes based on the images collected in these screens. © 2016 International Society for Advancement of Cytometry.

  3. 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.

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

    PubMed

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

    2016-01-01

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

  5. Rapid Three-Dimensional Phenotyping of Cardiovascular Development in Mouse Embryos by Micro-CT with Iodine Staining

    PubMed Central

    Degenhardt, Karl; Wright, Alexander C.; Horng, Debra; Padmanabhan, Arun; Epstein, Jonathan A.

    2011-01-01

    Background Micro-computed tomography (micro-CT) has been used extensively in research to generate high-resolution three-dimensional images of calcified tissues in small animals nondestructively. It has been especially useful for the characterization of skeletal mutations, but limited in its utility for the analysis of soft tissue such as the cardiovascular system. Visualization of the cardiovascular system has been largely restricted to structures that can be filled with radiopaque intravascular contrast agents in adult animals. Recent ex vivo studies using osmium tetroxide, iodinated contrast agents, inorganic iodine and phosphotungstic acid have demonstrated the ability to stain soft tissues differentially, allowing for high inter-tissue contrast in micro-CT images. Here, we demonstrate the application of this technology for visualization of cardiovascular structures in developing mouse embryos using Lugol’s solution (aqueous potassium iodide plus iodine). Methods and Results We show the optimization of this method to obtain ex vivo micro-CT images of embryonic and neonatal mice with excellent soft-tissue contrast. We demonstrate the utility of this method to visualize key structures during cardiovascular development at various stages of embryogenesis. Our method benefits from the ease of sample preparation, low toxicity, and low cost. Furthermore, we show how multiple cardiac defects can be demonstrated by micro-CT in a single specimen with a known genetic lesion. Indeed, a previously undescribed cardiac venous abnormality is revealed in a PlexinD1 mutant mouse. Conclusions Micro-CT of iodine stained tissue is a valuable technique for the characterization of cardiovascular development and defects in mouse models of congenital heart disease. PMID:20190279

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

    PubMed

    Ehrenreich, H

    2013-05-01

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

  7. Automated image-based phenotypic analysis in zebrafish embryos

    PubMed Central

    Vogt, Andreas; Cholewinski, Andrzej; Shen, Xiaoqiang; Nelson, Scott; Lazo, John S.; Tsang, Michael; Hukriede, Neil A.

    2009-01-01

    Presently, the zebrafish is the only vertebrate model compatible with contemporary paradigms of drug discovery. Zebrafish embryos are amenable to automation necessary for high-throughput chemical screens, and optical transparency makes them potentially suited for image-based screening. However, the lack of tools for automated analysis of complex images presents an obstacle to utilizing the zebrafish as a high-throughput screening model. We have developed an automated system for imaging and analyzing zebrafish embryos in multi-well plates regardless of embryo orientation and without user intervention. Images of fluorescent embryos were acquired on a high-content reader and analyzed using an artificial intelligence-based image analysis method termed Cognition Network Technology (CNT). CNT reliably detected transgenic fluorescent embryos (Tg(fli1:EGFP)y1) arrayed in 96-well plates and quantified intersegmental blood vessel development in embryos treated with small molecule inhibitors of anigiogenesis. The results demonstrate it is feasible to adapt image-based high-content screening methodology to measure complex whole organism phenotypes. PMID:19235725

  8. Phenotype-Specific Association of Single-Nucleotide Polymorphisms with Heart Failure and Preserved Ejection Fraction: a Genome-Wide Association Analysis of the Cardiovascular Health Study.

    PubMed

    Kao, David P; Stevens, Laura M; Hinterberg, Michael A; Görg, Carsten

    2017-06-01

    Little is known about genetics of heart failure with preserved ejection fraction (HFpEF) in part because of the many comorbidities in this population. To identify single-nucleotide polymorphisms (SNPs) associated with HFpEF, we analyzed phenotypic and genotypic data from the Cardiovascular Health Study, which profiled patients using a 50,000 SNP array. Results were explored using novel SNP- and gene-centric tools. We performed analyses to determine whether some SNPs were relevant only in certain phenotypes. Among 3804 patients, 7 clinical factors and 9 SNPs were significantly associated with HFpEF; the most notable of which was rs6996224, a SNP associated with transforming growth factor-beta receptor 3. Most SNPs were associated with HFpEF only in the absence of a clinical predictor. Significant SNPs represented genes involved in myocyte proliferation, transforming growth factor-beta/erbB signaling, and extracellular matrix formation. These findings suggest that genetic factors may be more important in some phenotypes than others.

  9. Phenotype prediction based on genome-wide DNA methylation data

    PubMed Central

    2014-01-01

    Background DNA methylation (DNAm) has important regulatory roles in many biological processes and diseases. It is the only epigenetic mark with a clear mechanism of mitotic inheritance and the only one easily available on a genome scale. Aberrant cytosine-phosphate-guanine (CpG) methylation has been discussed in the context of disease aetiology, especially cancer. CpG hypermethylation of promoter regions is often associated with silencing of tumour suppressor genes and hypomethylation with activation of oncogenes. Supervised principal component analysis (SPCA) is a popular machine learning method. However, in a recent application to phenotype prediction from DNAm data SPCA was inferior to the specific method EVORA. Results We present Model-Selection-SPCA (MS-SPCA), an enhanced version of SPCA. MS-SPCA applies several models that perform well in the training data to the test data and selects the very best models for final prediction based on parameters of the test data. We have applied MS-SPCA for phenotype prediction from genome-wide DNAm data. CpGs used for prediction are selected based on the quantification of three features of their methylation (average methylation difference, methylation variation difference and methylation-age-correlation). We analysed four independent case–control datasets that correspond to different stages of cervical cancer: (i) cases currently cytologically normal, but will later develop neoplastic transformations, (ii, iii) cases showing neoplastic transformations and (iv) cases with confirmed cancer. The first dataset was split into several smaller case–control datasets (samples either Human Papilloma Virus (HPV) positive or negative). We demonstrate that cytology normal HPV+ and HPV- samples contain DNAm patterns which are associated with later neoplastic transformations. We present evidence that DNAm patterns exist in cytology normal HPV- samples that (i) predispose to neoplastic transformations after HPV infection and (ii

  10. Cranial base abnormalities in osteogenesis imperfecta: phenotypic and genotypic determinants.

    PubMed

    Cheung, Moira S; Arponen, Heidi; Roughley, Peter; Azouz, Michel E; Glorieux, Francis H; Waltimo-Sirén, Janna; Rauch, Frank

    2011-02-01

    Cranial base abnormalities are an important complication of osteogenesis imperfecta (OI), a hereditary bone fragility disorder that in most patients is caused by mutations affecting collagen type I. To elucidate which clinical characteristics are associated with the occurrence of cranial base abnormalities in OI, we compared cephalometric results of 187 OI patients (median age 12.0 years, range 3.4 to 47 years; 96 female) with those of 191 healthy subjects and related findings to clinical descriptors of the disease. Overall, 41 patients (22%) had at least one unambiguously abnormal skull base measure. Multivariate logistic regression analysis in patients with OI types I, III, and IV (n = 169) revealed that height Z-score [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.43-0.66, p < .001]--but not age, gender, scleral hue, lumbar spine areal bone mineral density, or a history of bisphosphonate treatment--was a significant independent determinant of skull base abnormalities. Among patients with a height Z-score below -3, 48% had a skull base abnormality regardless of whether they had received bisphosphonate treatment in the first year of life or not. Genotype-phenotype correlations were evaluated in patients with detectable mutations in COL1A1 or COL1A2, the genes coding for collagen type I (n = 140). Skull base abnormalities were present in 6% of patients with haploinsufficiency (frameshift or nonsense) mutations, in 43% of patients with helical glycine substitutions caused by COL1A1 mutations, in 32% of patients with helical glycine substitutions owing to COL1A2 mutations, and in 17% of patients with splice-site mutations affecting either COL1A1 or COL1A2. However, multivariate logistic regression analysis showed that height Z-score but not the type of collagen type I mutation was independently associated with the prevalence of skull base abnormalities. In conclusion, this study shows that clinical severity of OI, as expressed by the height Z-score, was

  11. 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

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

    PubMed Central

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

    2016-01-01

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

  13. Symptoms and esophageal motility based on phenotypic findings of scleroderma.

    PubMed

    Tang, D M; Pathikonda, M; Harrison, M; Fisher, R S; Friedenberg, F K; Parkman, H P

    2013-01-01

    Scleroderma esophagus is characterized by ineffective peristalsis and reduced esophageal sphincter pressure. Esophageal disease in scleroderma can precede cutaneous manifestations and has been associated with Raynaud's phenomenon (RP) and pulmonary fibrosis (PF). The objective of the study is to evaluate the impact of cutaneous findings, RP, and PF on demographics, symptoms, and esophageal motility in patients with scleroderma. Scleroderma patients with esophageal involvement were included after review of esophageal manometries and charts over a 6-year period. High-resolution esophageal manometry was performed. Patients completed a symptom questionnaire. The study enrolled 28 patients (22 females; mean age 50.3 ± 12.8 years) with scleroderma esophagus. Patients without skin involvement (n= 12) reported more severe heartburn (P= 0.02), while those with cutaneous findings (n= 16) had more frequent dysphagia with solids (P= 0.02). Patients with RP (n= 22) had lower amplitude of distal esophageal contractions (P= 0.01) than those without RP (n= 6). Patients with PF (n= 11) reported more severe coughing and wheezing (both P= 0.03) than those without lung disease (n= 17). This study highlights subgroups of patients with scleroderma esophagus according to phenotypic findings of dermatologic changes, RP, and PF. Heartburn and dysphagia are important symptoms that may be associated with different stages of disease progression based on skin changes in scleroderma. RP was associated with greater esophageal dysmotility. Coughing and wheezing were more severe in patients with PF.

  14. Next Generation Image-Based Phenotyping of Root System Architecture

    NASA Astrophysics Data System (ADS)

    Davis, T. W.; Shaw, N. M.; Cheng, H.; Larson, B. G.; Craft, E. J.; Shaff, J. E.; Schneider, D. J.; Piñeros, M. A.; Kochian, L. V.

    2016-12-01

    The development of the Plant Root Imaging and Data Acquisition (PRIDA) hardware/software system enables researchers to collect digital images, along with all the relevant experimental details, of a range of hydroponically grown agricultural crop roots for 2D and 3D trait analysis. Previous efforts of image-based root phenotyping focused on young cereals, such as rice; however, there is a growing need to measure both older and larger root systems, such as those of maize and sorghum, to improve our understanding of the underlying genetics that control favorable rooting traits for plant breeding programs to combat the agricultural risks presented by climate change. Therefore, a larger imaging apparatus has been prototyped for capturing 3D root architecture with an adaptive control system and innovative plant root growth media that retains three-dimensional root architectural features. New publicly available multi-platform software has been released with considerations for both high throughput (e.g., 3D imaging of a single root system in under ten minutes) and high portability (e.g., support for the Raspberry Pi computer). The software features unified data collection, management, exploration and preservation for continued trait and genetics analysis of root system architecture. The new system makes data acquisition efficient and includes features that address the needs of researchers and technicians, such as reduced imaging time, semi-automated camera calibration with uncertainty characterization, and safe storage of the critical experimental data.

  15. Cardiovascular and genitourinary anomalies in patients with duplications within the Williams syndrome critical region: phenotypic expansion and review of the literature.

    PubMed

    Zarate, Yuri A; Lepard, Tiffany; Sellars, Elizabeth; Kaylor, Julie A; Alfaro, Maria P; Sailey, Charles; Schaefer, G Bradley; Collins, R Thomas

    2014-08-01

    Williams syndrome results from a microdeletion of approximately 1.5 Mb of chromosome 7q11.23. Several patients have been reported with the reciprocal microduplication in association with a variety of phenotypic features including cognitive impairment and typical facial features, though only a few have had birth defects. We report on three probands with duplications within 7q11.23 of variable sizes; two with cardiovascular involvement including aortic dilation and the other with unilateral renal and gonadal agenesis. We offer a comparison with previously reported cases of duplications of 7q11.23. In light of the present cases, we recommend undertaking echocardiographic and renal ultrasound evaluation of patients with documented 7q11.23 duplications. Further, this cytogenetic abnormality should be part of the differential diagnosis for patients with aortic dilation, as well as those with unilateral renal and gonadal agenesis. © 2014 Wiley Periodicals, Inc.

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    2015-12-01

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

  18. 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.

  19. 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

  20. Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study.

    PubMed

    Leening, Maarten J G; Ferket, Bart S; Steyerberg, Ewout W; Kavousi, Maryam; Deckers, Jaap W; Nieboer, Daan; Heeringa, Jan; Portegies, Marileen L P; Hofman, Albert; Ikram, M Arfan; Hunink, M G Myriam; Franco, Oscar H; Stricker, Bruno H; Witteman, Jacqueline C M; Roos-Hesselink, Jolien W

    2014-11-17

    To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. Prospective population based cohort study. People living in the community in Rotterdam, the Netherlands. 8419 participants (60.9% women) aged ≥ 55 and free from cardiovascular disease at baseline. First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were -7 for any cardiovascular disease, -102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and -1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease

  1. Apolipoprotein E genotype and the cardiovascular disease risk phenotype: impact of sex and adiposity (the FINGEN study).

    PubMed

    Kofler, Bettina M; Miles, Elizabeth A; Curtis, Peter; Armah, Christopher K; Tricon, Sabine; Grew, Jilly; Napper, Frances L; Farrell, Leslie; Lietz, Georg; Packard, Christopher J; Caslake, Muriel J; Mathers, John C; Williams, Christine M; Calder, Philip C; Minihane, Anne Marie

    2012-04-01

    Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype. A greater impact of genotype on TC:HDL-C was observed in females, which explained 16% of the variability in this outcome versus 6% in males. APOE genotype was also associated with plasma C-reactive protein and adhesion molecule concentrations (P<0.05), with significant genotype × BMI interactions observed. Our observations indicate that the association between the APOE genotype and CHD risk is unlikely to be homogenous and highlights the risk of inaccurate estimations of genotype-phenotype associations in population subgroups without appropriate stratification for sex and adiposity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. 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

  3. 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.

  4. 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.

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

    PubMed

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

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

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

    PubMed Central

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI), chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs) equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping. PMID:28713402

  7. Molecular Bases and Phenotypic Determinants of Aromatase Excess Syndrome

    PubMed Central

    Fukami, Maki; Shozu, Makio; Ogata, Tsutomu

    2012-01-01

    Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens. PMID:22319526

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

    PubMed

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

    2013-11-01

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

  9. Standards-Based Procedural Phenotyping: The Arden Syntax on i2b2.

    PubMed

    Mate, Sebastian; Castellanos, Ixchel; Ganslandt, Thomas; Prokosch, Hans-Ulrich; Kraus, Stefan

    2017-01-01

    Phenotyping, or the identification of patient cohorts, is a recurring challenge in medical informatics. While there are open source tools such as i2b2 that address this problem by providing user-friendly querying interfaces, these platforms lack semantic expressiveness to model complex phenotyping algorithms. The Arden Syntax provides procedural programming language construct, designed specifically for medical decision support and knowledge transfer. In this work, we investigate how language constructs of the Arden Syntax can be used for generic phenotyping. We implemented a prototypical tool to integrate i2b2 with an open source Arden execution environment. To demonstrate the applicability of our approach, we used the tool together with an Arden-based phenotyping algorithm to derive statistics about ICU-acquired hypernatremia. Finally, we discuss how the combination of i2b2's user-friendly cohort pre-selection and Arden's procedural expressiveness could benefit phenotyping.

  10. Functional foods and cardiovascular disease risk: building the evidence base.

    PubMed

    Moore, Lynn L

    2011-10-01

    To review the concept of functional foods and to summarize recent evidence on functional foods and cardiovascular disease (CVD) risk. Recent studies have examined the use of antioxidant vitamins and found no support for a beneficial effect on CVD risk, lipid levels or blood pressure. The evolving data also provide little support for a cardioprotective effect of soy protein. The role of soluble fiber in cardiovascular health has been of interest for many years and new studies support important beneficial effects on lipids as well as total CVD risk. In addition, the benefits of fish intake and nut consumption have been recently affirmed. Two promising areas of investigation from a functional food perspective are studies of phytosterols and milk-derived tripeptides. Plant stanol esters have been shown to have strong lipid-lowering effects, whereas milk-derived tripeptides directly benefited blood pressure. The functional food market has grown exponentially in recent years. Our understanding of the health benefits of foods and nutrients is continually evolving. Careful attention to the strength of the scientific evidence will help to ensure that it is used appropriately to guide the development of the next generation of health-promoting functional foods.

  11. Perspectives on cardiovascular effects of incretin-based drugs: From bedside to bench, return trip.

    PubMed

    Luconi, Michaela; Cantini, Giulia; Ceriello, Antonio; Mannucci, Edoardo

    2017-08-15

    Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood. This review is aimed at collecting and summarizing available evidence from experimental and mechanistic studies on the action of GLP1-RA and DPP4i on the cardiovascular system, both deriving from clinical and pre-clinical sources. The results of cardiovascular outcome trials are interpreted on the basis of the experimental preclinical data available, paying particular attention to the heart failure results, and suggesting some novel intriguing hypotheses to explain some of the unexpected findings of cardioprotection of incretin-based drugs. In particular, we discuss the possible contribution to the incretin cardiovascular effects of a direct cardiac action of GLP-1 metabolites through GLP-1 receptor-independent pathways, and of DPP4 substrates other than GLP-1. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  12. Resilin-Based Hybrid Hydrogels for Cardiovascular Tissue Engineering

    PubMed Central

    McGann, Christopher L.; Levenson, Eric A.

    2013-01-01

    The outstanding elastomeric properties of natural resilin, an insect protein, have motivated the engineering of resilin-like polypeptides (RLPs) as a potential material for cardiovascular tissue engineering. The RLPs, which incorporate biofunctional domains for cell-matrix interactions, are cross-linked into RLP–PEG hybrid hydrogels via a Michael-type addition of cysteine residues on the RLP with vinyl sulfones of an end-functionalized multi-arm star PEG. Oscillatory rheology indicated the useful mechanical properties of these materials. Assessments of cell viability via con-focal microscopy clearly show the successful encapsulation of human aortic adventitial fibroblasts in the three-dimensional matrices and the adoption of a spread morphology following 7 days of culture. PMID:23956463

  13. Ten-year follow-up of cluster-based asthma phenotypes in adults. A pooled analysis of three cohorts.

    PubMed

    Boudier, Anne; Curjuric, Ivan; Basagaña, Xavier; Hazgui, Hana; Anto, Josep M; Bousquet, Jean; Bridevaux, Pierre O; Dupuis-Lozeron, Elise; Garcia-Aymerich, Judith; Heinrich, Joachim; Janson, Christer; Künzli, Nino; Leynaert, Bénédicte; de Marco, Roberto; Rochat, Thierry; Schindler, Christian; Varraso, Raphaëlle; Pin, Isabelle; Probst-Hensch, Nicole; Sunyer, Jordi; Kauffmann, Francine; Siroux, Valérie

    2013-09-01

    The temporal stability of adult asthma phenotypes identified using clustering methods has never been addressed. Longitudinal cluster-based methods may provide novel insights in the study of the natural history of asthma. To compare the stability of cluster-based asthma phenotype structures a decade apart in adults and to address the individuals' phenotypic transition across these asthma phenotypes. The latent transition analysis was applied on longitudinal data (twice, 10 yr apart) from 3,320 adults with asthma who took part in the European Community Respiratory Health Survey, the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, or the Epidemiological Study on Genetics and Environment of Asthma. Nine variables covering personal and phenotypic characteristics measured twice, 10 years apart, were simultaneously considered. Latent transition analysis identifies seven asthma phenotypes (prevalence range, 8.4-20.8%), mainly characterized by the level of asthma symptoms (low, moderate, high), the allergic status, and pulmonary function. Phenotypes observed 10 years apart showed strong similarities. The probability of membership in the same asthma phenotype at both times varied across phenotypes from 54 to 88%. Different transition patterns were observed across phenotypes. Transitions toward increased asthma symptoms were more frequently observed among nonallergic phenotypes as compared with allergic phenotypes. Results showed a strong stability of the allergic status over time. Adult asthma phenotypes identified by a clustering approach, 10 years apart, were highly consistent. This study is the first to model the probabilities of transitioning over time between comprehensive asthma phenotypes.

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

    PubMed Central

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

    2014-01-01

    Background Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO) phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1) whether community-based exercise training transitions MAO adults to metabolically healthy, and 2) whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness. Methods and results Metabolic syndrome components were measured in 332 adults (190 women, 142 men) before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index ≥30 kg · m2) adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO). After community exercise, 27/68 (40%) MAO individuals (P<0.05) transitioned to metabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64). Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1–65.4; P<0.05) and 7.5 (95% confidence interval: 1.5–37.5; P<0.05) times more likely to transition from MAO to MHO, respectively. Conclusion Community-based exercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the greatest increase in fitness were significantly more likely to become metabolically healthy. Community exercise may be an effective model for primary prevention of cardiovascular disease. PMID:25120373

  15. 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.

  16. 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

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

    PubMed

    Franchi, Daniele; Cini, Davide; Iervasi, Giorgio

    2011-01-01

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

  18. A knowledge-based, automated method for phenotyping in the EHR using only clinical pathology reports.

    PubMed

    Yahi, Alexandre; Tatonetti, Nicholas P

    2015-01-01

    The secondary use of electronic health records (EHR) represents unprecedented opportunities for biomedical discovery. Central to this goal is, EHR-phenotyping, also known as cohort identification, which remains a significant challenge. Complex phenotypes often require multivariate and multi-scale analyses, ultimately leading to manually created phenotype definitions. We present Ontology-driven Reports-based Phenotyping from Unique Signatures (ORPheUS), an automated approach to EHR-phenotyping. To do this we identify unique signatures of abnormal clinical pathology reports that correspond to pre-defined medical terms from biomedical ontologies. By using only the clinical pathology, or "lab", reports we are able to mitigate clinical biases enabling researchers to explore other dimensions of the EHR. We used ORPheUS to generate signatures for 858 diseases and validated against reference cohorts for Type 2 Diabetes Mellitus (T2DM) and Atrial Fibrillation (AF). Our results suggest that our approach, using solely clinical pathology reports, is an effective as a primary screening tool for automated clinical phenotyping.

  19. Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study.

    PubMed

    Atzler, Dorothee; Gore, M Odette; Ayers, Colby R; Choe, Chi-un; Böger, Rainer H; de Lemos, James A; McGuire, Darren K; Schwedhelm, Edzard

    2014-11-01

    The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) μmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (β-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease. © 2014 American Heart Association, Inc.

  20. 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.

  1. Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study.

    PubMed

    Stegemann, Christin; Pechlaner, Raimund; Willeit, Peter; Langley, Sarah R; Mangino, Massimo; Mayr, Ursula; Menni, Cristina; Moayyeri, Alireza; Santer, Peter; Rungger, Gregor; Spector, Tim D; Willeit, Johann; Kiechl, Stefan; Mayr, Manuel

    2014-05-06

    The bulk of cardiovascular disease risk is not explained by traditional risk factors. Recent advances in mass spectrometry allow the identification and quantification of hundreds of lipid species. Molecular lipid profiling by mass spectrometry may improve cardiovascular risk prediction. Lipids were extracted from 685 plasma samples of the prospective population-based Bruneck Study (baseline evaluation in 2000). One hundred thirty-five lipid species from 8 different lipid classes were profiled by shotgun lipidomics with the use of a triple-quadrupole mass spectrometer. Levels of individual species of cholesterol esters (CEs), lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines (PEs), sphingomyelins, and triacylglycerols (TAGs) were associated with cardiovascular disease over a 10-year observation period (2000-2010, 90 incident events). Among the lipid species with the strongest predictive value were TAGs and CEs with a low carbon number and double-bond content, including TAG(54:2) and CE(16:1), as well as PE(36:5) (P=5.1 × 10⁻⁷, 2.2 × 10⁻⁴, and 2.5 × 10⁻³, respectively). Consideration of these 3 lipid species on top of traditional risk factors resulted in improved risk discrimination and classification for cardiovascular disease (cross-validated ΔC index, 0.0210 [95% confidence interval, 0.0010-0.0422]; integrated discrimination improvement, 0.0212 [95% confidence interval, 0.0031-0.0406]; and continuous net reclassification index, 0.398 [95% confidence interval, 0.175-0.619]). A similar shift in the plasma fatty acid composition was associated with cardiovascular disease in the UK Twin Registry (n=1453, 45 cases). This study applied mass spectrometry-based lipidomics profiling to population-based cohorts and identified molecular lipid signatures for cardiovascular disease. Molecular lipid species constitute promising new biomarkers that outperform the conventional biochemical measurements of lipid classes currently used in

  2. A cell-based phenotypic assay to identify cardioprotective agents

    PubMed Central

    Guo, Stephanie; Olm-Shipman, Adam; Walters, Andrew; Urciuoli, William R.; Devito, Stefanie; Nadtochiy, Sergiy M.; Wojtovich, Andrew P.; Brookes, Paul S.

    2012-01-01

    Rationale Tissue ischemia/reperfusion (IR) injury underlies several leading causes of death such as heart-attack and stroke. The lack of clinical therapies for IR injury may be partly due to the difficulty of adapting IR injury models to high-throughput screening (HTS). Objective To develop a model of IR injury that is both physiologically relevant and amenable to HTS. Methods and Results A micro-plate based respirometry apparatus was used. Controlling gas flow in the plate head space, coupled with the instrument’s mechanical systems, yielded a 24 well model of IR injury in which H9c2 cardiomyocytes were transiently trapped in a small volume, rendering them ischemic. Following initial validation with known protective molecules, the model was used to screen a 2000 molecule library, with post IR cell death as an endpoint. pO2 and pH monitoring in each well also afforded metabolic data. Ten protective, detrimental and inert molecules from the screen were subsequently tested in a Langendorff perfused heart model of IR injury, revealing strong correlations between the screening endpoint and both recovery of cardiac function (negative r2=0.66), and infarct size (positive, r2=0.62). Relationships between the effects of added molecules on cellular bioenergetics, and protection against IR injury, were also studied. Conclusion This novel cell-based assay can predict either protective or detrimental effects on IR injury in the intact heart. Its application may help identify therapeutic or harmful molecules. PMID:22394516

  3. Effect of hydroxyapatite-based biomaterials on human osteoblast phenotype.

    PubMed

    Trombelli, L; Penolazzi, L; Torreggiani, E; Farina, R; Lambertini, E; Vecchiatini, R; Piva, R

    2010-03-01

    The present study evaluated human primary osteoblasts and two different osteoblast-like cell lines behaviour when cultured in presence of different hydroxyapatite-based (HA) biomaterials (SINTlife-FIN-CERAMICA S.p.a., Faenza, Italy; Bio-Oss, Geistlich Biomaterials, Woulhusen, Switzerland; Biostite-GABA Vebas, San Giuliano Milanese, MI, Italy), focusing attention on the effect of HA/Biostite in terms of modulation of osteoblastic differentiation. Analysis were about adhesion, proliferation and mineralization activity. Runt-related transcription factor 2 (Runx2), Estrogen Receptor alpha (ERalfa) expression and alkaline phosphatase activity (ALP) were measured as osteoblastic differentiation markers. Determination of viable cells was done with MTT colorimetric assay. Scanning electron microscopy (SEM) analysis was performed on biomaterial-treated cells. All hydroxyapatite-based biomaterials didn't affect cells morphology and viability, whereas only presence of HA/Biostite improved cells adhesion, growth and differentiation. Adhesion and spreading of the primary cells on HA/Biostite were the same showed by two different osteoblast-like cell lines. These results have important implications for both tissue-engineered bone grafts and enhancement of HA implants performance, to develop new teeth's supporting structure therapies and replacement.

  4. Cardiovascular modeling of congenital heart disease based on neonatal echocardiographic images.

    PubMed

    Nakao, Megumi; Maeda, Kazuma; Haraguchi, Ryo; Kurosaki, Ken-ichi; Kagisaki, Koji; Shiraishi, Isao; Nakazawa, Kazuo; Minato, Kotaro

    2012-01-01

    This paper proposes a 3-D cardiovascular modeling system based on neonatal echocardiographic images. With the system, medical doctors can interactively construct patient-specific cardiovascular models, and share the complex topology and the shape information. For the construction of cardiovascular models with a variety of congenital heart diseases, we propose a set of algorithms and interface that enable editing of the topology and shape of the 3-D models. In order to facilitate interactivity, the centerline and radius of the vessels are used to edit the surface of the heart vessels. This forms a skeleton where the centerlines of blood vessel serve as the nodes and edges, while the radius of the blood vessel is given as an attribute value to each node. Moreover, parent-child relationships are given to each skeleton. They are expressed as the directed acyclic graph, where the skeletons are viewed as graph nodes and the connecting points are graph edges. The cardiovascular models generated from some patient data confirmed that the developed technique is capable of constructing cardiovascular disease models in a tolerable timeframe. It is successful in representing the important structures of the patient-specific heart vessels for better understanding in preoperative planning and electric medical recording of the congenital heart disease.

  5. Prevention of cardiovascular events by treating hypertension in older adults: an evidence-based approach.

    PubMed

    Firdaus, Muhammad; Sivaram, Chittur A; Reynolds, Dwight W

    2008-03-01

    Hypertension in older adults is not well controlled in clinical practice. Isolated systolic hypertension is often more difficult to manage. A systematic PubMed search was conducted to look for evidence showing benefits of lowering blood pressure (BP) in older hypertensive adults. Lowering BP in these individuals significantly reduces the risk of coronary artery disease, stroke, and cardiovascular and all-cause mortality. Based on trial evidence, a low-dose diuretic should be considered the most appropriate first-step treatment for preventing cardiovascular morbidity and mortality. Therapy with >1 medication is often necessary to reduce BP in these patients. There is unequivocal evidence that cardiovascular events can be prevented in older adults, even those older than 80 years, by treating hypertension.

  6. Worksite-based cardiovascular risk screening and management: a feasibility study.

    PubMed

    Padwal, Raj; Rashead, Mohammad; Snider, Jonathan; Morrin, Louise; Lehman, Agnes; Campbell, Norm Rc

    2017-01-01

    Established cardiovascular risk factors are highly prevalent and contribute substantially to cardiovascular morbidity and mortality because they remain uncontrolled in many Canadians. Worksite-based cardiovascular risk factor screening and management represent a largely untapped strategy for optimizing risk factor control. In a 2-phase collaborative demonstration project between Alberta Health Services (AHS) and the Alberta Newsprint Company (ANC), ANC employees were offered cardiovascular risk factor screening and management. Screening was performed at the worksite by AHS nurses, who collected baseline history, performed automated blood pressure measurement and point-of-care testing for lipids and A1c, and calculated 10-year Framingham risk. Employees with a Framingham risk score of ≥10% and uncontrolled blood pressure, dyslipidemia, or smoking were offered 6 months of pharmacist case management to optimize their risk factor control. In total, 87 of 190 (46%) employees volunteered to undergo cardiovascular risk factor screening. Mean age was 44.5±11.9 years, 73 (83.9%) were male, 14 (16.1%) had hypertension, 4 (4.6%) had diabetes, 12 (13.8%) were current smokers, and 9 (10%) had dyslipidemia. Of 36 employees with an estimated Framingham risk score of ≥10%, 21 (58%) agreed to receive case management and 15 (42%) attended baseline and 6-month follow-up case management visits. Statistically significant reductions in left arm systolic blood pressure (-8.0±12.4 mmHg; p=0.03) and triglyceride levels (-0.8±1.4 mmol/L; p=0.04) occurred following case management. These findings demonstrate the feasibility and usefulness of collaborative, worksite-based cardiovascular risk factor screening and management. Expansion of this type of partnership in a cost-effective manner is warranted.

  7. Towards building a disease-phenotype knowledge base: extracting disease-manifestation relationship from literature

    PubMed Central

    Xu, Rong; Li, Li; Wang, QuanQiu

    2013-01-01

    Motivation: Systems approaches to studying phenotypic relationships among diseases are emerging as an active area of research for both novel disease gene discovery and drug repurposing. Currently, systematic study of disease phenotypic relationships on a phenome-wide scale is limited because large-scale machine-understandable disease–phenotype relationship knowledge bases are often unavailable. Here, we present an automatic approach to extract disease–manifestation (D-M) pairs (one specific type of disease–phenotype relationship) from the wide body of published biomedical literature. Data and Methods: Our method leverages external knowledge and limits the amount of human effort required. For the text corpus, we used 119 085 682 MEDLINE sentences (21 354 075 citations). First, we used D-M pairs from existing biomedical ontologies as prior knowledge to automatically discover D-M–specific syntactic patterns. We then extracted additional pairs from MEDLINE using the learned patterns. Finally, we analysed correlations between disease manifestations and disease-associated genes and drugs to demonstrate the potential of this newly created knowledge base in disease gene discovery and drug repurposing. Results: In total, we extracted 121 359 unique D-M pairs with a high precision of 0.924. Among the extracted pairs, 120 419 (99.2%) have not been captured in existing structured knowledge sources. We have shown that disease manifestations correlate positively with both disease-associated genes and drug treatments. Conclusions: The main contribution of our study is the creation of a large-scale and accurate D-M phenotype relationship knowledge base. This unique knowledge base, when combined with existing phenotypic, genetic and proteomic datasets, can have profound implications in our deeper understanding of disease etiology and in rapid drug repurposing. Availability: http://nlp.case.edu/public/data/DMPatternUMLS/ Contact: rxx@case.edu PMID:23828786

  8. 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…

  9. 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…

  10. A community pharmacy-based cardiovascular risk screening service implemented in Iran

    PubMed Central

    Hakimzadeh, Negar; Najafi, Sheyda; Javadi, Mohammad R.; Hadjibabaie, Molouk

    2017-01-01

    Background: Cardiovascular disease is a major health concern around the world. Objective: To assess the outcomes and feasibility of a pharmacy-based cardiovascular screening in an urban referral community pharmacy in Iran. Methods: A cross sectional study was conducted in a referral community pharmacy. Subjects aged between 30-75 years without previous diagnose of cardiovascular disease or diabetes were screened. Measurement of all major cardiovascular risk factors, exercise habits, medical conditions, medications, and family history were investigated. Framingham risk score was calculated and high risk individuals were given a clinical summary sheet signed by a clinical pharmacist and were encouraged to follow up with their physician. Subjects were contacted one month after the recruitment period and their adherence to the follow up recommendation was recorded. Results: Data from 287 participants were analyzed and 146 were referred due to at least one abnormal laboratory test. The results showed 26 patients with cardiovascular disease risk greater than 20%, 32 high systolic blood pressure, 22 high diastolic blood pressures, 50 high total cholesterol levels, 108 low HDL-C levels, and 22 abnormal blood glucose levels. Approximately half of the individuals who received a follow up recommendation had made an appointment with their physician. Overall, 15.9% of the individuals received medications and 15.9% received appropriate advice for risk factor modification. Moreover, 7.5% were under evaluation by a physician. Conclusion: A screening program in a community pharmacy has the potential to identify patients with elevated cardiovascular risk factor. A plan for increased patient adherence to follow up recommendations is required. PMID:28690693

  11. Community-based incidence rate of cardiovascular disease and mortality in 50-75 year old adults.

    PubMed

    López-Suárez, A; Bascuñana-Quirell, A; Elvira-González, J; Beltrán-Robles, M; Aboza-Lobatón, A; Solís-Díaz, R

    2013-01-01

    Updated information on the incidence of the principal cardiovascular diseases (CVD) and cardiovascular mortality is not available in Spain. We have studied the incidence rate of new cases of myocardial infarction, heart failure, stroke and cardiovascular mortality in the adult population in Sanlúcar de Barrameda (Spain). A community-based prospective follow-up study was conducted. The study enrolled 858 participants aged 50-75 years who were randomly selected from the population and followed-up for 5 years. Age and gender-adjusted incidence rates of cardiovascular disease and cardiovascular mortality were calculated, obtaining complete information for 855 participants. Prognostic risk factors of new cases of cardiovascular disease were obtained using Cox proportional hazard modeling. The community-based incidence rate of heart failure was 455/100.000 persons-year. The incidence of myocardial infarction, stroke and cardiovascular mortality (506, 216 and 225/100.000 persons-year, respectively) was also very elevated. Male gender, family history of early cardiovascular disease, diabetes, hypertension and sedentary life style were independent risk factors of cardiovascular disease. The community-based incidence rate of heart failure in Sanlúcar de Barrameda (Spain) is very high, and it is the first to be reported in Spain. The incidence of myocardial infarction is among the highest in Spain. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  12. 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. Published by Elsevier Ltd.

  13. 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. © 2015 The Authors. Genes to Cells published by Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

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

    PubMed

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

    2016-08-22

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed

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

    2005-11-02

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

  17. Genotype-based clinical trials in cardiovascular disease

    PubMed Central

    Pereira, Naveen L.; Sargent, Daniel J.; Farkouh, Michael E.; Rihal, Charanjit S.

    2015-01-01

    Consensus practice guidelines and the implementation of clinical therapeutic advances are usually based on the results of large, randomized clinical trials (RCTs). However, RCTs generally inform us on an average treatment effect for a presumably homogeneous population, but therapeutic interventions rarely benefit the entire population targeted. Indeed, multiple RCTs have demonstrated that interindividual variability exists both in drug response and in the development of adverse effects. The field of pharmacogenomics promises to deliver the right drug to the right patient. Substantial progress has been made in this field, with advances in technology, statistical and computational methods, and the use of cell and animal model systems. However, clinical implementation of pharmacogenetic principles has been difficult because RCTs demonstrating benefit are lacking. For patients, the potential benefits of performing such trials include the individualization of therapy to maximize efficacy and minimize adverse effects. These trials would also enable investigators to reduce sample size and hence contain costs for trial sponsors. Multiple ethical, legal, and practical issues need to be considered for the conduct of genotype-based RCTs. Whether pre-emptive genotyping embedded in electronic health records will preclude the need for performing genotype-based RCTs remains to be seen. PMID:25940926

  18. A sequence-based map of Arabidopsis genes with mutant phenotypes.

    PubMed

    Meinke, David W; Meinke, Laura K; Showalter, Thomas C; Schissel, Anna M; Mueller, Lukas A; Tzafrir, Iris

    2003-02-01

    The classical genetic map of Arabidopsis contains 462 genes with mutant phenotypes. Chromosomal locations of these genes have been determined over the past 25 years based on recombination frequencies with visible and molecular markers. The most recent update of the classical map was published in a special genome issue of Science that dealt with Arabidopsis (D.W. Meinke, J.M. Cherry, C. Dean, S.D. Rounsley, M. Koornneef [1998] Science 282: 662-682). We present here a comprehensive list and sequence-based map of 620 cloned genes with mutant phenotypes. This map documents for the first time the exact locations of large numbers of Arabidopsis genes that give a phenotype when disrupted by mutation. Such a community-based physical map should have broad applications in Arabidopsis research and should serve as a replacement for the classical genetic map in the future. Assembling a comprehensive list of genes with a loss-of-function phenotype will also focus attention on essential genes that are not functionally redundant and ultimately contribute to the identification of the minimal gene set required to make a flowering plant.

  19. Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of Neuroinflammation Effective in Alzheimer's Disease Models.

    PubMed

    Zhou, Wei; Zhong, Guifa; Fu, Sihai; Xie, Hui; Chi, Tianyan; Li, Luyi; Rao, Xiurong; Zeng, Shaogao; Xu, Dengfeng; Wang, Hao; Sheng, Guoqing; Ji, Xing; Liu, Xiaorong; Ji, Xuefei; Wu, Donghai; Zou, Libo; Tortorella, Micky; Zhang, Kejian; Hu, Wenhui

    2016-11-16

    Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic screening is making a resurgence in drug discovery process as an alternative to target-focused approaches. Herein, we employed microglia-based phenotypic screenings to search for small molecules that modulate the release of detrimental proinflammatory cytokines. The identified novel pharmacological inhibitor of neuroinflammation (named GIBH-130) was validated to alter phenotypes of neuroinflammation in AD brains. Notably, this molecule exhibited comparable in vivo efficacy of cognitive impairment relief to donepezil and memantine respectively in both β amyloid-induced and APP/PS1 double transgenic Alzheimer's murine models at a substantially lower dose (0.25 mg/kg). Therefore, GIBH-130 constitutes a unique chemical probe for pathogenesis research and drug development of AD, and it also suggests microglia-based phenotypic screenings that target neuroinflammation as an effective and feasible strategy to identify novel anti-AD agents.

  20. [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.

  1. The multiscale backbone of the human phenotype network based on biological pathways

    PubMed Central

    2014-01-01

    Background Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. Results The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. Conclusions We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases’ common biology, and in the elaboration of diagnosis and treatments. PMID:24460644

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

    PubMed

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

    2017-10-01

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

  3. 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.

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

    PubMed

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

    2013-01-01

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

  5. Two distinct symptom-based phenotypes of depression in epilepsy yield specific clinical and etiological insights.

    PubMed

    Rayner, Genevieve; Jackson, Graeme D; Wilson, Sarah J

    2016-11-01

    Depression is common but underdiagnosed in epilepsy. A quarter of patients meet criteria for a depressive disorder, yet few receive active treatment. We hypothesize that the presentation of depression is less recognizable in epilepsy because the symptoms are heterogeneous and often incorrectly attributed to the secondary effects of seizures or medication. Extending the ILAE's new phenomenological approach to classification of the epilepsies to include psychiatric comorbidity, we use data-driven profiling of the symptoms of depression to perform a preliminary investigation of whether there is a distinctive symptom-based phenotype of depression in epilepsy that could facilitate its recognition in the neurology clinic. The psychiatric and neuropsychological functioning of 91 patients with focal epilepsy was compared with that of 77 healthy controls (N=168). Cluster analysis of current depressive symptoms identified three clusters: one comprising nondepressed patients and two symptom-based phenotypes of depression. The 'Cognitive' phenotype (base rate=17%) was characterized by symptoms taking the form of self-critical cognitions and dysphoria and was accompanied by pervasive memory deficits. The 'Somatic' phenotype (7%) was characterized by vegetative depressive symptoms and anhedonia and was accompanied by greater anxiety. It is hoped that identification of the features of these two phenotypes will ultimately facilitate improved detection and diagnosis of depression in patients with epilepsy and thereby lead to appropriate and timely treatment, to the benefit of patient wellbeing and the potential efficacy of treatment of the seizure disorder. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed Central

    2013-01-01

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

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

    PubMed

    Kariuki, Jacob K; Stuart-Shor, Eileen M; Leveille, Suzanne G; Hayman, Laura L

    2013-12-28

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

  8. 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

  9. 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

  10. 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

  11. [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. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

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

    PubMed Central

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

    2015-01-01

    Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants’ diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods. PMID:26054936

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

    PubMed

    Ispolatov, Iaroslav; Madhok, Vaibhav; Doebeli, Michael

    2016-02-07

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

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

    PubMed

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

    2015-08-30

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

  15. Upright water-based exercise to improve cardiovascular and metabolic health: a qualitative review.

    PubMed

    Meredith-Jones, Kim; Waters, Debra; Legge, Michael; Jones, Lynnette

    2011-04-01

    Research regarding the benefits of exercise for cardiovascular and metabolic health is extensive and well-documented. However, weight-bearing exercise may not be suitable for individuals with orthopaedic or musculoskeletal limitations, excess adiposity or other medical conditions. Water-based exercise may provide an attractive alternative to land-based exercise for achieving improved health and fitness in these populations. Although swimming is a popular form of water-based exercise it requires specific skills and is often undertaken at intensities that may not be safely prescribed in patient populations. Therefore upright, water-based exercise has been suggested as a viable water-based alternative. However, surprisingly little is known about the effects of upright water-based exercise on improvements in cardiovascular and metabolic health. Limited evidence from water-based studies indicate that regular deep or shallow water exercise can exert beneficial effects on cardiorespiratory fitness, strength, and body fat distribution. However, the impacts of water-based exercise on lipid profile, bodyweight, and carbohydrate metabolism are still unclear. Further studies are warranted to establish the effects of non-swimming, water-based exercise on cardiometabolic risks in humans.

  16. USAT: A Unified Score-based Association Test for Multiple Phenotype-Genotype Analysis

    PubMed Central

    Ray, Debashree; Pankow, James S.; Basu, Saonli

    2016-01-01

    Genome-wide Association Studies (GWASs) for complex diseases often collect data on multiple correlated endo-phenotypes. Multivariate analysis of these correlated phenotypes can improve the power to detect genetic variants. Multivariate analysis of variance (MANOVA) can perform such association analysis at a GWAS level, but the behavior of MANOVA under different trait models has not been carefully investigated. In this paper, we show that MANOVA is generally very powerful for detecting association but there are situations, such as when a genetic variant is associated with all the traits, where MANOVA may not have any detection power. In these situations, marginal model based methods, however, perform much better than multivariate methods. We investigate the behavior of MANOVA, both theoretically and using simulations, and derive the conditions where MANOVA loses power. Based on our findings, we propose a unified score-based test statistic USAT that can perform better than MANOVA in such situations and nearly as well as MANOVA elsewhere. Our proposed test reports an approximate asymptotic p-value for association and is computationally very efficient to implement at a GWAS level. We have studied through extensive simulations the performance of USAT, MANOVA and other existing approaches and demonstrated the advantage of using the USAT approach to detect association between a genetic variant and multivariate phenotypes. We applied USAT to data from three correlated traits collected on 5, 816 Caucasian individuals from the Atherosclerosis Risk in Communities (ARIC, The ARIC Investigators [1989]) Study and detected some interesting associations. PMID:26638693

  17. 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

  18. Potential applications of RNA interference-based therapeutics in the treatment of cardiovascular disease.

    PubMed

    Hassan, Ali

    2006-06-01

    RNA interference (RNAi) in eukaryotes is a recently identified phenomenon in which small double stranded RNA molecules called short interfering RNA (siRNA) interact with messenger RNA (mRNA) containing homologous sequences in a sequence-specific manner. Ultimately, this interaction results in degradation of the target mRNA. Because of the high sequence specificity of the RNAi process, and the apparently ubiquitous expression of the endogenous protein components necessary for RNAi, there appears to be little limitation to the genes that can be targeted for silencing by RNAi. Thus, RNAi has enormous potential, both as a research tool and as a mode of therapy. Several recent patents have described advances in RNAi technology that are likely to lead to new treatments for cardiovascular disease. These patents have described methods for increased delivery of siRNA to cardiovascular target tissues, chemical modifications of siRNA that improve their pharmacokinetic characteristics, and expression vectors capable of expressing RNAi effectors in situ. Though RNAi has only recently been demonstrated to occur in mammalian tissues, work has advanced rapidly in the development of RNAi-based therapeutics. Recently, therapeutic silencing of apoliporotein B, the ligand for the low density lipoprotein receptor, has been demonstrated in adult mice by systemic administration of chemically modified siRNA. This demonstrates the potential for RNAi-based therapeutics, and suggests that the future for RNAi in the treatment of cardiovascular disease is bright.

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

    PubMed

    Schulte, Christian; Zeller, Tanja

    2015-02-01

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

  20. A decline in earning losses associated with a community-based cardiovascular disease prevention project.

    PubMed

    Kottke, T E; Puska, P; Feldman, R; Salonen, J T; Tuomilehto, J

    1982-07-01

    Permanent and temporary disability pension award data and survey data were used to estimate the lower bound of earning losses related to cardiovascular disease during a community-based cardiovascular disease prevention program in Eastern Finland. Earning losses due to death totaled $39.94 million but were not affected by the project. Earning losses due to permanent disability totalled +29.01 million and were $4.25 million less than expected (p less than 0.025). Earning losses due to temporary disability were $10.91 million and were not affected by the project. Total earning losses attributable to cardiovascular disease during the project period were $79.86 million, and total decline in earning losses was +4.25 million. Project implementation costs were less than one per cent of total earning losses and were equal to approximately 17 per cent of the decline in these losses attributable to the project. The findings suggest that community-based heart disease prevention programs have the potential of more than paying for themselves through an associated decline in lost earnings.

  1. Integration of team-based learning strategies into a cardiovascular module.

    PubMed

    Conway, Susan E; Johnson, Jeremy L; Ripley, Toni L

    2010-03-10

    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. 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. 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. 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.

  2. 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

  3. Hemodynamic instability in the critically ill neonate: An approach to cardiovascular support based on disease pathophysiology.

    PubMed

    Giesinger, Regan E; McNamara, Patrick J

    2016-04-01

    Hemodynamic disturbance in the sick neonate is common, highly diverse in underlying pathophysiology and dynamic. Dysregulated systemic and cerebral blood flow is hypothesized to have a negative impact on neurodevelopmental outcome and survival. An understanding of the physiology of the normal neonate, disease pathophysiology, and the properties of vasoactive medications may improve the quality of care and lead to an improvement in survival free from disability. In this review we present a modern approach to cardiovascular therapy in the sick neonate based on a more thoughtful approach to clinical assessment and actual pathophysiology. Targeted neonatal echocardiography offers a more detailed insight into disease processes and offers longitudinal assessment, particularly response to therapeutic intervention. The pathophysiology of common neonatal conditions and the properties of cardiovascular agents are described. In addition, we outline separate treatment algorithms for various hemodynamic disturbances that are tailored to clinical features, disease characteristics and echocardiographic findings. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  4. Targeting Proteases in Cardiovascular Diseases by Mass Spectrometry-Based Proteomics

    PubMed Central

    Klingler, Diana; Hardt, Markus

    2012-01-01

    Proteases hydrolyze peptide bonds, thereby controlling the function of proteins and peptides on the posttranslational level. In the cardiovascular system, proteases play pivotal roles in the regulation of blood pressure, coagulation and other essential physiological processes. Accordingly, proteases are prime targets for therapeutic interventions and diagnostics. Proteases are part of complex proteolytic networks comprised of enzymes, inhibitors, activators, substrates and cleavage products. Analyzing these networks on a system-wide level is essential to understanding cardiovascular function and how dysregulation can lead to pathological conditions. Mass spectrometry-based quantitative and dynamic proteomics approaches are leading the way to enhance our knowledge of proteolytic networks such as the renin-angiotensin-system. Here, we critically review proteomics tools utilized in protease biology and provide an overview on how these methods can be used to characterize and validate protease function. PMID:22511707

  5. 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.

  6. 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. Copyright © 2016 The American Physiological Society.

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

    PubMed

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

    2017-02-28

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

  8. Phenotyping: Using Machine Learning for Improved Pairwise Genotype Classification Based on Root Traits

    PubMed Central

    Zhao, Jiangsan; Bodner, Gernot; Rewald, Boris

    2016-01-01

    Phenotyping local crop cultivars is becoming more and more important, as they are an important genetic source for breeding – especially in regard to inherent root system architectures. Machine learning algorithms are promising tools to assist in the analysis of complex data sets; novel approaches are need to apply them on root phenotyping data of mature plants. A greenhouse experiment was conducted in large, sand-filled columns to differentiate 16 European Pisum sativum cultivars based on 36 manually derived root traits. Through combining random forest and support vector machine models, machine learning algorithms were successfully used for unbiased identification of most distinguishing root traits and subsequent pairwise cultivar differentiation. Up to 86% of pea cultivar pairs could be distinguished based on top five important root traits (Timp5) – Timp5 differed widely between cultivar pairs. Selecting top important root traits (Timp) provided a significant improved classification compared to using all available traits or randomly selected trait sets. The most frequent Timp of mature pea cultivars was total surface area of lateral roots originating from tap root segments at 0–5 cm depth. The high classification rate implies that culturing did not lead to a major loss of variability in root system architecture in the studied pea cultivars. Our results illustrate the potential of machine learning approaches for unbiased (root) trait selection and cultivar classification based on rather small, complex phenotypic data sets derived from pot experiments. Powerful statistical approaches are essential to make use of the increasing amount of (root) phenotyping information, integrating the complex trait sets describing crop cultivars. PMID:27999587

  9. Phenotyping: Using Machine Learning for Improved Pairwise Genotype Classification Based on Root Traits.

    PubMed

    Zhao, Jiangsan; Bodner, Gernot; Rewald, Boris

    2016-01-01

    Phenotyping local crop cultivars is becoming more and more important, as they are an important genetic source for breeding - especially in regard to inherent root system architectures. Machine learning algorithms are promising tools to assist in the analysis of complex data sets; novel approaches are need to apply them on root phenotyping data of mature plants. A greenhouse experiment was conducted in large, sand-filled columns to differentiate 16 European Pisum sativum cultivars based on 36 manually derived root traits. Through combining random forest and support vector machine models, machine learning algorithms were successfully used for unbiased identification of most distinguishing root traits and subsequent pairwise cultivar differentiation. Up to 86% of pea cultivar pairs could be distinguished based on top five important root traits (Timp5) - Timp5 differed widely between cultivar pairs. Selecting top important root traits (Timp) provided a significant improved classification compared to using all available traits or randomly selected trait sets. The most frequent Timp of mature pea cultivars was total surface area of lateral roots originating from tap root segments at 0-5 cm depth. The high classification rate implies that culturing did not lead to a major loss of variability in root system architecture in the studied pea cultivars. Our results illustrate the potential of machine learning approaches for unbiased (root) trait selection and cultivar classification based on rather small, complex phenotypic data sets derived from pot experiments. Powerful statistical approaches are essential to make use of the increasing amount of (root) phenotyping information, integrating the complex trait sets describing crop cultivars.

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

    PubMed Central

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

    2012-01-01

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

  11. Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues.

    PubMed

    Chen, Desu; Sarkar, Sumona; Candia, Julián; Florczyk, Stephen J; Bodhak, Subhadip; Driscoll, Meghan K; Simon, Carl G; Dunkers, Joy P; Losert, Wolfgang

    2016-10-01

    Cell morphology has been identified as a potential indicator of stem cell response to biomaterials. However, determination of cell shape phenotype in biomaterials is complicated by heterogeneous cell populations, microenvironment heterogeneity, and multi-parametric definitions of cell morphology. To associate cell morphology with cell-material interactions, we developed a shape phenotyping framework based on support vector machines. A feature selection procedure was implemented to select the most significant combination of cell shape metrics to build classifiers with both accuracy and stability to identify and predict microenvironment-driven morphological differences in heterogeneous cell populations. The analysis was conducted at a multi-cell level, where a "supercell" method used average shape measurements of small groups of single cells to account for heterogeneous populations and microenvironment. A subsampling validation algorithm revealed the range of supercell sizes and sample sizes needed for classifier stability and generalization capability. As an example, the responses of human bone marrow stromal cells (hBMSCs) to fibrous vs flat microenvironments were compared on day 1. Our analysis showed that 57 cells (grouped into supercells of size 4) are the minimum needed for phenotyping. The analysis identified that a combination of minor axis length, solidity, and mean negative curvature were the strongest early shape-based indicator of hBMSCs response to fibrous microenvironment.

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

    PubMed

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

    2017-02-21

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

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

    PubMed Central

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

    2017-01-01

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

  14. Grape colour phenotyping: development of a method based on the reflectance spectrum.

    PubMed

    Rustioni, Laura; Basilico, Roberto; Fiori, Simone; Leoni, Alessandra; Maghradze, David; Failla, Osvaldo

    2013-01-01

    The colour of fruit is an important quality factor for cultivar classification and phenotyping techniques. Besides the subjective visual evaluation, new instruments and techniques can be used. This work aims at developping an objective, fast, easy and non-destructive method as a useful support for evaluating grapes' colour under different cultural and environmental conditions, as well as for breeding process and germplasm evaluation, supporting the plant characterization and the biodiversity preservation. Colours of 120 grape varieties were studied using reflectance spectra. The classification was realized using cluster and discriminant analysis. Reflectance of the whole berries surface was also compared with absorption properties of single skin extracts. A phenotyping method based on the reflectance spectra was developed, producing reliable colour classifications. A cultivar-independent index for pigment content evaluation has also been obtained. This work allowed the classification of the berry colour using an objective method. Copyright © 2013 John Wiley & Sons, Ltd.

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

    DOE PAGES

    Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; ...

    2017-02-21

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

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

    PubMed

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

    2017-10-01

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

  17. MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis.

    PubMed

    Tauhid, Shahamat; Neema, Mohit; Healy, Brian C; Weiner, Howard L; Bakshi, Rohit

    2014-11-15

    While disease categories (i.e. clinical phenotypes) of multiple sclerosis (MS) are established, there remains MRI heterogeneity among patients within those definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that they represent partly different processes in MS. We assessed the ability of MRI-based categorization of cerebral lesions and atrophy in individual patients to identify distinct phenotypes. We studied 175 patients with MS [age (mean ± SD) 42.7 ± 9.1 years, 124 (71%) women, Expanded Disability Status (EDSS) score 2.5 ± 2.3, n = 18 (10%) clinically isolated demyelinating syndrome (CIS), n=115 (66%) relapsing-remitting (RR), and n = 42 (24%) secondary progressive (SP)]. Brain MRI measures included T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (to assess whole brain atrophy). Medians were used to create bins for each parameter, with patients assigned a low or high severity score. Four MRI phenotype categories emerged: Type I = low T2LV/mild atrophy [n = 67 (38%); CIS = 14, RR = 47, SP = 6]; Type II = high T2LV/mild atrophy [n = 21 (12%); RR = 19, SP = 2]; Type III = low T2LV/high atrophy [n = 21 (12%); CIS = 4, RR = 16, SP = 1]; and Type IV = high T2LV/high atrophy [n = 66 (38%); RR = 33, S P = 33]. Type IV was the most disabled and was the only group showing a correlation between T2LV vs. BPF and MRI vs. EDSS score (all p < 0.05). We described MRI-categorization based on the relationship between lesions and atrophy in individual patients to identify four phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many have a dissociation. Longitudinal studies will help define the stability of these patterns and their role in risk stratification. Copyright © 2014. Published by Elsevier B.V.

  18. Variations on cardiovascular risk factors in metabolic syndrome after consume of a citrus-based juice.

    PubMed

    Mulero, Juana; Bernabé, Juana; Cerdá, Begoña; García-Viguera, Cristina; Moreno, Diego A; Albaladejo, Maria Dolores; Avilés, Francisco; Parra, Soledad; Abellán, José; Zafrilla, Pilar

    2012-06-01

    Inflammation and oxidative stress plays a critical role in cardiovascular disease and metabolic syndrome often occurs with these two variables. The aim of the study is to estimate variations on cardiovascular risk factors in Metabolic Syndrome patients after consume of a citrus-based juice compared with control groups. The study comprised 20 healthy subjects and 33 patients with Metabolic Syndrome. 18 patients consume daily 300 mL of a citrus-based juice during 6 month and 15 patients consume 300 mL of a placebo beverage. The control group consumes a citrus-based juice. Before, at fourth month and at sixth month after treatment the following parameters were determined: lipid profile, oxidized LDL, C-Reactive Protein and Homocysteine. The study was carried out in accordance with the Helsinki Declaration, and the Ethical Committee of the San Antonio Catholic University and approved the protocol (6 November 2006, register number: 1424). After six months of citrus-based juice consuming, there is significant differences at 95% confidence in oxidized LDL, C-Reactive Protein, and Homocysteine in Metabolic Syndrome patients who consume citrus-based juice. We have not found significant differences in other groups. Consume of citrus-based juice improve lipid profile and inflammation markers in Metabolic Syndrome patients. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma.

    PubMed

    Machens, Andreas; Dralle, Henning

    2007-05-01

    Since DNA tests have enabled reliable identification of asymptomatic RET (rearranged during transfection) gene carriers, myriads of publications have appeared on genotype-phenotype relationships. A comprehensive appraisal of this body of evidence using evidence-based methodology is pending. This study was based on systematic evaluation of the literature using evidence-based criteria. (1) There is a distinct age-related progression of hereditary medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2) Among the high-risk RET mutations, those in codon 634 cause higher penetrance rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma, and parathyroid hyperplasia/adenoma) than mutations in codons 609, 611, 618, and 620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA-based screening is superior to calcitonin-based screening in asymptomatic RET carriers (grade C). (4) Using a worst-case scenario, i.e., considering the earliest finding of MTC in asymptomatic RET carriers, pre-emptive thyroidectomy should be performed before that time (grade C) to be truly prophylactic. Specifically, for carriers of highest-risk mutations (codon 918): within the first year of life; for carriers of high-risk mutations (codon 609, 611, 618, 620, 630, and 634): before the age of 5 years; and for carriers of least-high risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5-10 years. Strict adherence to these grade C recommendations can result in undertreatment of the former (codon 634) and overtreatment of the latter. These genotype-phenotype correlations provide a solid foundation on which to base surgical concepts, leaving little room for randomized controlled clinical trials.

  20. A High-Throughput, Field-Based Phenotyping Technology for Tall Biomass Crops.

    PubMed

    Salas Fernandez, Maria G; Bao, Yin; Tang, Lie; Schnable, Patrick S

    2017-08-01

    Recent advances in omics technologies have not been accompanied by equally efficient, cost-effective, and accurate phenotyping methods required to dissect the genetic architecture of complex traits. Even though high-throughput phenotyping platforms have been developed for controlled environments, field-based aerial and ground technologies have only been designed and deployed for short-stature crops. Therefore, we developed and tested Phenobot 1.0, an auto-steered and self-propelled field-based high-throughput phenotyping platform for tall dense canopy crops, such as sorghum (Sorghum bicolor). Phenobot 1.0 was equipped with laterally positioned and vertically stacked stereo RGB cameras. Images collected from 307 diverse sorghum lines were reconstructed in 3D for feature extraction. User interfaces were developed, and multiple algorithms were evaluated for their accuracy in estimating plant height and stem diameter. Tested feature extraction methods included the following: (1) User-interactive Individual Plant Height Extraction (UsIn-PHe) based on dense stereo three-dimensional reconstruction; (2) Automatic Hedge-based Plant Height Extraction (Auto-PHe) based on dense stereo 3D reconstruction; (3) User-interactive Dense Stereo Matching Stem Diameter Extraction; and (4) User-interactive Image Patch Stereo Matching Stem Diameter Extraction (IPaS-Di). Comparative genome-wide association analysis and ground-truth validation demonstrated that both UsIn-PHe and Auto-PHe were accurate methods to estimate plant height, while Auto-PHe had the additional advantage of being a completely automated process. For stem diameter, IPaS-Di generated the most accurate estimates of this biomass-related architectural trait. In summary, our technology was proven robust to obtain ground-based high-throughput plant architecture parameters of sorghum, a tall and densely planted crop species. © 2017 American Society of Plant Biologists. All Rights Reserved.

  1. A High-Throughput, Field-Based Phenotyping Technology for Tall Biomass Crops1[OPEN

    PubMed Central

    2017-01-01

    Recent advances in omics technologies have not been accompanied by equally efficient, cost-effective, and accurate phenotyping methods required to dissect the genetic architecture of complex traits. Even though high-throughput phenotyping platforms have been developed for controlled environments, field-based aerial and ground technologies have only been designed and deployed for short-stature crops. Therefore, we developed and tested Phenobot 1.0, an auto-steered and self-propelled field-based high-throughput phenotyping platform for tall dense canopy crops, such as sorghum (Sorghum bicolor). Phenobot 1.0 was equipped with laterally positioned and vertically stacked stereo RGB cameras. Images collected from 307 diverse sorghum lines were reconstructed in 3D for feature extraction. User interfaces were developed, and multiple algorithms were evaluated for their accuracy in estimating plant height and stem diameter. Tested feature extraction methods included the following: (1) User-interactive Individual Plant Height Extraction (UsIn-PHe) based on dense stereo three-dimensional reconstruction; (2) Automatic Hedge-based Plant Height Extraction (Auto-PHe) based on dense stereo 3D reconstruction; (3) User-interactive Dense Stereo Matching Stem Diameter Extraction; and (4) User-interactive Image Patch Stereo Matching Stem Diameter Extraction (IPaS-Di). Comparative genome-wide association analysis and ground-truth validation demonstrated that both UsIn-PHe and Auto-PHe were accurate methods to estimate plant height, while Auto-PHe had the additional advantage of being a completely automated process. For stem diameter, IPaS-Di generated the most accurate estimates of this biomass-related architectural trait. In summary, our technology was proven robust to obtain ground-based high-throughput plant architecture parameters of sorghum, a tall and densely planted crop species. PMID:28620124

  2. 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. © 2015 American Heart Association, Inc.

  3. 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

  4. Unmanned aerial platform-based multi-spectral imaging for field phenotyping of maize.

    PubMed

    Zaman-Allah, M; Vergara, O; Araus, J L; Tarekegne, A; Magorokosho, C; Zarco-Tejada, P J; Hornero, A; Albà, A Hernández; Das, B; Craufurd, P; Olsen, M; Prasanna, B M; Cairns, J

    2015-01-01

    Recent developments in unmanned aerial platforms (UAP) have provided research opportunities in assessing land allocation and crop physiological traits, including response to abiotic and biotic stresses. UAP-based remote sensing can be used to rapidly and cost-effectively phenotype large numbers of plots and field trials in a dynamic way using time series. This is anticipated to have tremendous implications for progress in crop genetic improvement. We present the use of a UAP equipped with sensors for multispectral imaging in spatial field variability assessment and phenotyping for low-nitrogen (low-N) stress tolerance in maize. Multispectral aerial images were used to (1) characterize experimental fields for spatial soil-nitrogen variability and (2) derive indices for crop performance under low-N stress. Overall, results showed that the aerial platform enables to effectively characterize spatial field variation and assess crop performance under low-N stress. The Normalized Difference Vegetation Index (NDVI) data derived from spectral imaging presented a strong correlation with ground-measured NDVI, crop senescence index and grain yield. This work suggests that the aerial sensing platform designed for phenotyping studies has the potential to effectively assist in crop genetic improvement against abiotic stresses like low-N provided that sensors have enough resolution for plot level data collection. Limitations and future potential uses are also discussed.

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

    PubMed

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

    2017-06-01

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

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

    PubMed Central

    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

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

    PubMed Central

    Nolte, Arne W; Sheets, H David

    2005-01-01

    Background Hybridization receives attention because of the potential role that it may play in generating evolutionary novelty. An explanation for the emergence of novel phenotypes is given by transgressive segregation, which, if frequent, would imply an important evolutionary role for hybridization. This process is still rarely studied in natural populations as samples of recent hybrids and their parental populations are needed. Further, the detection of transgressive segregation requires phenotypes that can be easily quantified and analysed. We analyse variability in body shape of divergent populations of European sculpins (Cottus gobio complex) as well as natural hybrids among them. Results A distance-based method is developed to assign unknown specimens to known groups based on morphometric data. Apparently, body shape represents a highly informative set of characters that parallels the discriminatory power of microsatellite markers in our study system. Populations of sculpins are distinct and "unknown" specimens can be correctly assigned to their source population based on body shape. Recent hybrids are intermediate along the axes separating their parental groups but display additional differentiation that is unique and coupled with the hybrid genetic background. Conclusion There is a specific hybrid shape component in natural sculpin hybrids that can be best explained by transgressive segregation. This inference of how hybrids differ from their ancestors provides basic information for future evolutionary studies. Furthermore, our approach may serve to assign candidate specimens to their source populations based on morphometric data and help in the interpretation of population differentiation. PMID:15987531

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

    PubMed

    Nolte, Arne W; Sheets, H David

    2005-06-29

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

  9. A novel transmission-based test of association for multivariate phenotypes: an application to systolic and diastolic blood pressure levels

    PubMed Central

    2014-01-01

    Unlike case-control studies, family-based tests for association are protected against population stratification. Complex genetic traits are often governed by quantitative precursors and it has been argued that it may be a more powerful strategy to analyze these quantitative precursors instead of the clinical end point trait. Although methods have been developed for family-based association tests for single quantitative traits, it is of interest to develop such methods for multivariate phenotypes. We propose a novel transmission-based approach based on a trio design using a simple logistic regression to test for association with a multivariate phenotype. We use our proposed method to analyze data on systolic and diastolic blood pressure levels provided in Genetic Analysis Workshop 18. However, we find that the bivariate analysis of the two phenotypes did not provide more promising results compared to univariate analyses, suggesting a possibility of a different set of major genetic variants modulating the two phenotypes. PMID:25519341

  10. Ultrasound assessment of subclinical cardiovascular disease in a community-based multiethnic population and comparison to the Framingham score.

    PubMed

    Abe, Yukio; Rundek, Tanja; Sciacca, Robert R; Jin, Zhezhen; Sacco, Ralph L; Homma, Shunichi; Di Tullio, Marco R

    2006-11-15

    The presence of subclinical cardiovascular disease has been documented to indicate high coronary risk. This study investigated the impact of subclinical cardiovascular disease derived from echocardiography and carotid ultrasonography on traditional coronary risk stratification using the Framingham risk score (FRS) in a community-based, multiethnic population. Echocardiography and carotid ultrasonography were performed in 1,445 subjects (aged >39 years; 40% men; 53% Hispanic, 20% white, 24% black) from the Northern Manhattan Study. Subclinical cardiovascular disease was defined as the presence of left ventricular hypertrophy and/or carotid plaque greater than the gender-specific 75th percentile of the left ventricular mass index and maximal carotid plaque thickness distribution. The prevalence of subclinical cardiovascular disease was examined in each FRS category (low, intermediate, and high risk). In subjects with low or intermediate FRSs, 35% had subclinical cardiovascular disease (low FRS 29%, intermediate FRS 42%). In the intermediate FRS category, subclinical cardiovascular disease was significantly more prevalent in women than in men (53% vs 32%, p <0.0001) and in black and white subjects than in Hispanics (59% and 46% vs 33%, p <0.0001 and p = 0.040, respectively). In conclusion, the ultrasound assessment of subclinical cardiovascular disease may help reclassify 1/3 of subjects with low or intermediate FRSs into higher risk groups. In the intermediate FRS category, FRS appears to underestimate the coronary risk more in women than in men and more in whites and especially in blacks than in Hispanics.

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

    PubMed Central

    2013-01-01

    Endothelial dysfunction or loss is the early event that leads to a host of severe cardiovascular diseases, such as atherosclerosis, hypertension, brain stroke, myocardial infarction, and peripheral artery disease. Ageing is regarded among the most detrimental risk factor for vascular endothelium and predisposes the subject to atheroscleorosis and inflammatory states even in absence of traditional comorbid conditions. Standard treatment to restore blood perfusion through stenotic arteries are surgical or endovascular revascularization. Unfortunately, ageing patients are not the most amenable candidates for such interventions, due to high operative risk or unfavourable vascular involvement. It has recently been suggested that the transplantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) might constitute an alternative and viable therapeutic option for these individuals. Albeit pre-clinical studies demonstrated the feasibility of EPC-based therapy to recapitulate the diseased vasculature of young and healthy animals, clinical studies provided less impressive results in old ischemic human patients. One hurdle associated to this kind of approach is the senescence of autologous EPCs, which are less abundant in peripheral blood and display a reduced pro-angiogenic activity. Conversely, umbilical cord blood (UCB)-derived EPCs are more suitable for cellular therapeutics due to their higher frequency and sensitivity to growth factors, such as vascular endothelial growth factor (VEGF). An increase in intracellular Ca2+ concentration is central to EPC activation by VEGF. We have recently demonstrated that the Ca2+ signalling machinery driving the oscillatory Ca2+ response to this important growth factor is different in UCB-derived EPCs as compared to their peripheral counterparts. In particular, we focussed on the so-called endothelial colony forming cells (ECFCs), which are the only EPC population belonging to the endothelial lineage and able to

  12. TIPS: a system for automated image-based phenotyping of maize tassels.

    PubMed

    Gage, Joseph L; Miller, Nathan D; Spalding, Edgar P; Kaeppler, Shawn M; de Leon, Natalia

    2017-01-01

    The maize male inflorescence (tassel) produces pollen necessary for reproduction and commercial grain production of maize. The size of the tassel has been linked to factors affecting grain yield, so understanding the genetic control of tassel architecture is an important goal. Tassels are fragile and deform easily after removal from the plant, necessitating rapid measurement of any shape characteristics that cannot be retained during storage. Some morphological characteristics of tassels such as curvature and compactness are difficult to quantify using traditional methods, but can be quantified by image-based phenotyping tools. These constraints necessitate the development of an efficient method for capturing natural-state tassel morphology and complementary automated analytical methods that can quickly and reproducibly quantify traits of interest such as height, spread, and branch number. This paper presents the Tassel Image-based Phenotyping System (TIPS), which provides a platform for imaging tassels in the field immediately following removal from the plant. TIPS consists of custom methods that can quantify morphological traits from profile images of freshly harvested tassels acquired with a standard digital camera in a field-deployable light shelter. Correlations between manually measured traits (tassel weight, tassel length, spike length, and branch number) and image-based measurements ranged from 0.66 to 0.89. Additional tassel characteristics quantified by image analysis included some that cannot be quantified manually, such as curvature, compactness, fractal dimension, skeleton length, and perimeter. TIPS was used to measure tassel phenotypes of 3530 individual tassels from 749 diverse inbred lines that represent the diversity of tassel morphology found in modern breeding and academic research programs. Repeatability ranged from 0.85 to 0.92 for manually measured phenotypes, from 0.77 to 0.83 for the same traits measured by image-based methods, and from 0

  13. A case-control observational study of insulin resistance and metabolic syndrome among the four phenotypes of polycystic ovary syndrome based on Rotterdam criteria.

    PubMed

    Jamil, Avin S; Alalaf, Shahla K; Al-Tawil, Namir G; Al-Shawaf, Talha

    2015-01-16

    Polycystic ovary syndrome (PCOS) is associated with an increased risk of insulin resistance (IR), metabolic syndrome (MetS), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Metabolic aspects of the four PCOS phenotypes remain to be fully defined. The aim of this study was to compare metabolic parameters and insulin resistance among the four PCOS phenotypes defined according to the Rotterdam criteria and to determine predictors of these complications. A total of 526 reproductive-aged women were included in this observational case-control study. Of these, 263 were diagnosed as a PCOS based on Rotterdam criteria and 263 infertile women with no evidence of PCOS were recruited as controls. Biochemical, metabolic and insulin resistance parameters were compared in the two groups and the frequency of MetS and IR were compared among the four phenotypes. Data were analyzed for statistical significance using Student's t-test and one way analysis of variance followed by a post-hoc test (least significant difference). Chi-square tests were used to compare proportions. Univariate and multivariate logistic regression analyses were also applied. IR was identified in 112 (42.6%) of the PCOS women and 45 (17.1%) of the control (P <0.001). There were no significant differences in the frequency of IR and MetS between the four PCOS phenotypes. Homeostatic model assessment for IR (HOMA-IR) ≥3.8 was the most common IR parameter in PCOS and control groups. Women with oligo-anovulation (O) and PCO morphology (P) had a significantly lower level of 2-h postprandial insulin compared to women with O, P and hyperandrogenism (H) phenotypes. Logistic regression analysis showed that body mass index, waist circumference, triglyceride/high-density lipoprotein ratio (cardiovascular risk), HOMA-IR and glucose abnormalities (T2DM) were associated with increased risk of having MetS (P < 0.05). PCOS women with (O + P) show milder endocrine and metabolic abnormalities

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

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-12-1-0535 TITLE: A Multiplex Cancer /Testis Antigen-Based Biomarker Panel to Predict the Aggressive Phenotype of Prostate... Cancer PRINCIPAL INVESTIGATOR: Dr. Robert W. Veltri CONTRACTING ORGANIZATION: Johns Hopkins University Baltimore, MD 21218-2680 REPORT DATE...COVERED 30Sep2012 - 29Jun2016 4. TITLE AND SUBTITLE: A Multiplex Cancer /Testis Antigen-Based Biomarker Panel to Predict the Aggressive Phenotype of

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

    PubMed

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

    2016-06-01

    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.

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

    PubMed

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

    2017-12-06

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

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

    PubMed

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

    2017-02-01

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

  18. Cardiovascular consequences of high-performance aircraft maneuvers: implications for effective countermeasures and laboratory-based simulations.

    PubMed

    Scott, Jessica M; Esch, Ben T A; Goodman, Len S; Bredin, Shannon S D; Haykowsky, Mark J; Warburton, Darren E R

    2007-04-01

    The gravitational stress encountered by pilots of high-performance aircraft can cause dramatic shifts in blood volume and circulatory pressure, thus placing the cardiovascular system under significant stress, sometimes resulting in loss of consciousness due to cerebral under-perfusion. Since pilots experience both increased and decreased gravitational stress in high-risk environments, it is important not only to examine the cardiovascular effects of altered gravitational exposure, but also to create effective countermeasures that will increase pilot safety. In this review, we discuss the cardiovascular consequences of rapid changes in gravitational forces. We also examine the effectiveness of the countermeasures that have been developed to combat gravity-induced loss of consciousness. Finally, we examine those current laboratory-based techniques that simulate hyper-gravity and the "push-pull effect"; making it possible to investigate the cardiovascular mechanisms responsible for maintaining cerebral perfusion and consciousness.

  19. 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

  20. Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

    PubMed Central

    Chatziioannou, Aristotelis; Georgiadis, Panagiotis; Hebels, Dennie G.; Liampa, Irene; Valavanis, Ioannis; Bergdahl, Ingvar A.; Johansson, Anders; Palli, Domenico; Chadeau-Hyam, Marc; Siskos, Alexandros P.; Keun, Hector; Botsivali, Maria; de Kok, Theo M. C. M.; Pérez, Almudena Espín; Kleinjans, Jos C. S.; Vineis, Paolo; Kyrtopoulos, Soterios A.; Gottschalk, Ralph; van Leeuwen, Danitsja; Timmermans, Leen; Bendinelli, Benedetta; Kelly, Rachel; Vermeulen, Roel; Portengen, Lutzen; Saberi-Hosnijeh, Fatemeh; Melin, Beatrice; Hallmans, Göran; Lenner, Per; Athersuch, Toby J.; Kogevinas, Manolis; Stephanou, Euripides G.; Myridakis, Antonis; Fazzo, Lucia; De Santis, Marco; Comba, Pietro; Kiviranta, Hannu; Rantakokko, Panu; Airaksinen, Riikka; Ruokojärvi, Päivi; Gilthorpe, Mark; Fleming, Sarah; Fleming, Thomas; Tu, Yu-Kang; Jonsson, Bo; Lundh, Thomas; Chen, Wei J.; Lee, Wen-Chung; Hsiao, Chuhsing Kate; Chien, Kuo-Liong; Kuo, Po-Hsiu; Hung, Hung; Liao, Shu-Fen

    2017-01-01

    We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment. PMID:28225026

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

    PubMed Central

    Ji, Seung Taek; Yun, Jisoo

    2017-01-01

    The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs) are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration. PMID:28303152

  2. Model-Based Assessment of Cardiovascular Autonomic Control in Children with Obstructive Sleep Apnea

    PubMed Central

    Chaicharn, Jarree; Lin, Zheng; Chen, Maida L.; Ward, Sally L.D.; Keens, Thomas; Khoo, Michael C. K.

    2009-01-01

    Study Objectives: To quantitatively assess daytime autonomic cardiovascular control in pediatric subjects with and without obstructive sleep apnea syndrome (OSAS). Design: Respiration, R-R intervals, and noninvasive continuous blood pressure were monitored in awake subjects in the supine and standing postures, as well as during cold face stimulation. Setting: Sleep disorders laboratory in a hospital setting. Participants: Ten pediatric patients (age 11.4 ± 3.6 years) with moderate to severe OSAS (obstructive apnea-hypopnea index = 21.0 ± 6.6/ h) before treatment and 10 age-matched normal control subjects (age 11.5 ± 3.7 years). Measurements and Results: Spectral analysis of heart rate variability revealed that high-frequency power was similar and the ratio of low- to high-frequency power was lower in subjects with OSAS vs control subjects. The closed-loop minimal model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and a baroreflex component, whereas blood pressure variability was assumed to result from the direct effects of respiration and fluctuations in cardiac output. Baroreflex gain was lower in subjects with OSAS vs control subjects. Under orthostatic stress, respiratory-cardiac coupling gain decreased in both subject groups, but baroreflex gain decreased only in controls. The model was extended to incorporate time-varying parameter changes for analysis of the data collected during cold face stimulation: cardiac output gain increased in controls but remained unchanged in OSAS. Conclusions: Our findings suggest that vagal modulation of the heart remains relatively normal in pediatric subjects with OSAS. However, baseline cardiovascular sympathetic activity is elevated, and reactivity to autonomic challenges is impaired. Citation: Chaicharn J; Lin Z; Chen ML; Ward SLD; Keens T; Khoo MCK. Model-based assessment of cardiovascular autonomic control in children with obstructive sleep apnea. SLEEP 2009

  3. Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort

    PubMed Central

    Stürmer, Til; Hasselbach, Petra; Amelang, Manfred

    2006-01-01

    Objective To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. Design Follow-up of population based cohort. Setting Heidelberg, Germany. Participants 5114 women and men aged 40-65 in 1992-5. Main outcome measures Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. Results During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits—anger control, psychoticism, and symptoms of depression—were not consistently associated with myocardial infarction, stroke, or cancer. Conclusion Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer. PMID:16687457

  4. Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort.

    PubMed

    Stürmer, Til; Hasselbach, Petra; Amelang, Manfred

    2006-06-10

    To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. Follow-up of population based cohort. Heidelberg, Germany. 5114 women and men aged 40-65 in 1992-5. Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits--anger control, psychoticism, and symptoms of depression--were not consistently associated with myocardial infarction, stroke, or cancer. Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer.

  5. Model-based cardiovascular disease diagnosis: a preliminary in-silico study.

    PubMed

    Ebrahimi Nejad, Shiva; Carey, Jason P; McMurtry, M Sean; Hahn, Jin-Oh

    2017-04-01

    In this study, we developed and examined the feasibility of a model-based system identification approach to cardiovascular disease diagnosis. The basic premise of the approach is that it may be possible to diagnose cardiovascular disease from disease-induced alterations in the arterial mechanical properties manifested in the proximal and distal arterial blood pressure waveforms. It first individualizes the lumped-parameter model of wave propagation and reflection in the artery using the measurement of proximal and distal arterial blood pressure waveforms. Then, it employs a diagnosis logic, in the form of disease-specific patterns in model parameters, referred as [Formula: see text] and pulse transit time. The longitudinal change in these parameters is used to diagnose the presence of peripheral artery disease and arterial stiffening. We illustrated the feasibility of the proposed approach by testing it in a full-scale in-silico arterial tree simulation. The results showed that the approach exhibited superior sensitivity to ankle-brachial index and convenience to carotid-femoral pulse wave velocity: The model parameters [Formula: see text] and [Formula: see text] responded with up to 100 and 40 % changes to peripheral artery disease with up to 50 % arterial blockage whereas the change in ankle-brachial index was [Formula: see text]; the same parameters responded with up to 300 and 40 % changes to up to 100 % arterial stiffening while pulse transit time changed by up to 24 %. Together with the development of more convenient techniques for the measurement of arterial blood pressure waveforms, the proposed approach may evolve into a viable alternative to the state-of-the-art techniques for cardiovascular disease diagnosis.

  6. 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

  7. 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. © 2014 American Society of Plant Biologists. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    Inhibitory control is subserved in part by discrete regions of the prefrontal cortex whose functionality may be altered according to specific trait-based phenotypes. Using a unified model of normal range personality traits, we examined activation within lateral and medial aspects of the prefrontal cortex during a manual go/no-go task. Evoked hemodynamic oxygenation within the prefrontal cortex was measured in 106 adults using a 16-channel continuous-wave functional near-infrared spectroscopy system. Within lateral regions of the prefrontal cortex, greater activation was associated with higher trait levels of extraversion, agreeableness and conscientiousness, and lower neuroticism. Higher agreeableness was also related to more activation in the medial prefrontal cortex during inhibitory control. These results suggest that personality traits reflecting greater emotional stability, extraversion, agreeableness and conscientiousness may be associated with more efficient recruitment of control processes subserved by lateral regions of the prefrontal cortex. These findings highlight key links between trait-based phenotypes and neural activation patterns in the prefrontal cortex underlying inhibitory control. PMID:26163672

  9. Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer

    PubMed Central

    Le Dévédec, Sylvia; Waldman, Yedael Y; Stein, Gideon Y; van de Water, Bob

    2014-01-01

    Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. We build >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. We utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, is experimentally validated and the metabolic effects of MLYCD depletion investigated. Furthermore, we tested cell-specific predicted responses to the inhibition of metabolic enzymes, and successfully inferred the prognosis of cancer patients based on their PRIME-derived individual GSMMs. These results lay a computational basis and a counterpart experimental proof of concept for future personalized metabolic modeling applications, enhancing the search for novel selective anticancer therapies. DOI: http://dx.doi.org/10.7554/eLife.03641.001 PMID:25415239

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

    PubMed

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

    2016-01-01

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

  11. Allopurinol Therapy in Gout Patients Does Not Associate with Beneficial Cardiovascular Outcomes: A Population-Based Matched-Cohort Study

    PubMed Central

    Kok, Victor C.; Horng, Jorng-Tzong; Chang, Wan-Shan; Hong, Ya-Fang; Chang, Tzu-Hao

    2014-01-01

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

  12. 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

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

    PubMed

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

    2015-01-01

    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. 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. The rabbit transcriptome profiling data provide new insights in understanding the molecular mechanisms underlying rabbit skin growth and development.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2016-04-01

    To conduct a large, population-based study on cardiovascular disease (CVD) in breast cancer (BC) survivors treated in 1989 or later. A large, population-based cohort comprising 70,230 surgically treated stage I to III BC patients diagnosed before age 75 years between 1989 and 2005 was linked with population-based registries for CVD. Cardiovascular disease risks were compared with the general population, and within the cohort using competing risk analyses. Compared with the general Dutch population, BC patients had a slightly lower CVD mortality risk (standardized mortality ratio 0.92, 95% confidence interval [CI] 0.88-0.97). Only death due to valvular heart disease was more frequent (standardized mortality ratio 1.28, 95% CI 1.08-1.52). Left-sided radiation therapy after mastectomy increased the risk of any cardiovascular event compared with both surgery alone (subdistribution hazard ratio (sHR) 1.23, 95% CI 1.11-1.36) and right-sided radiation therapy (sHR 1.19, 95% CI 1.04-1.36). Radiation-associated risks were found for not only ischemic heart disease, but also for valvular heart disease and congestive heart failure (CHF). Risks were more pronounced in patients aged <50 years at BC diagnosis (sHR 1.48, 95% CI 1.07-2.04 for left- vs right-sided radiation therapy after mastectomy). Left- versus right-sided radiation therapy after wide local excision did not increase the risk of all CVD combined, yet an increased ischemic heart disease risk was found (sHR 1.14, 95% CI 1.01-1.28). Analyses including detailed radiation therapy information showed an increased CVD risk for left-sided chest wall irradiation alone, left-sided breast irradiation alone, and internal mammary chain field irradiation, all compared with right-sided breast irradiation alone. Compared with patients not treated with chemotherapy, chemotherapy used ≥1997 (ie, anthracyline-based chemotherapy) increased the risk of CHF (sHR 1.35, 95% CI 1.00-1.83). Radiation therapy regimens used in BC treatment

  16. [A data base of a thoracic and cardiovascular department: information on 1001 patients].

    PubMed

    Tonella, Tatiana; Massari, Ferdinando Maria; Khirani, Sonia; Blasi, Francesco; Magrini, Fabio

    2012-01-01

    The Authors illustrate the results derived from a data base of a thoracic and cardiovascular Department, comprehensive of 1001 patients (464 M and 537 F, average age 71, minimum age 18 and maximum age 101). The conducted analysis results in several considerations: the cause of patient's hospitalization was not relevant to the direct expertise of the Department in the 27,5% of the cases and the profile of the typical-patient is of an elderly person (73% of the cases over 65 years old), basically overweight or obese (35% of the cases with BMI > 25) and with medium-low cultural level (70% of the cases not over middle school); moreover our patients, although under poly-therapy before hospitalization, were discharged with a number of prescribed medicines even more plentiful. The data base of the Department proved to be a useful tool both to instantaneously monitor the departmental activity and also to rationalize the pharmacological therapies.

  17. 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

  18. A community-based participatory planning process and multilevel intervention design: toward eliminating cardiovascular health inequities.

    PubMed

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

    2011-11-01

    The elimination of persistent health inequities requires the engagement of multiple perspectives, resources, and skills. Community-based participatory research (CBPR) 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. This article describes 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. The authors consider implications for future efforts to engage communities in developing strategies toward eliminating health inequities.

  19. A Web-Based Approach to Address Cardiovascular Risks in Managers: Results of a Randomized Trial

    PubMed Central

    Bennett, Joel B.; Broome, Kirk M.; Pilley, Ashleigh; Gilmore, Phillip

    2011-01-01

    Objectives To examine whether a web-based health and leadership development program—designed specifically for managers—was associated with changes in self-reported and biometric indicators of cardiovascular risk (CVD) within the context of a randomized control trial. Methods 145 managers from eight organizations participated in a 6-month Internet-based program or a control condition. They completed pre- and posttest assessments that included both self-reported attitudes (on diet, exercise, and mental health) and biometric measures (e.g., body weight, waist circumference). Results The intervention was associated with improvements in dietary attitudes, dietary self-efficacy, and exercise, and reductions in distress symptoms. Women in the program reduced their waist circumference significantly more than controls. Conclusions The program showed promise for reducing CVD risk factors. Similar results across diverse organizations suggest the program may be useful across industry types. PMID:21785368

  20. 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.

  1. Pivotal Cytoprotective Mediators and Promising Therapeutic Strategies for Endothelial Progenitor Cell-Based Cardiovascular Regeneration

    PubMed Central

    Kim, Sujin

    2016-01-01

    Cardiovascular diseases (CVDs), including atherosclerosis, stroke, and myocardial infarction, is a major cause of death worldwide. In aspects of cell therapy against CVD, it is generally accepted that endothelial progenitor cells (EPCs) are potent neovascular modulators in ischemic tissues. In response to ischemic injury signals, EPCs located in a bone marrow niche migrate to injury sites and form new vessels by secreting various vasculogenic factors including VEGF, SDF-1, and FGF, as well as by directly differentiating into endothelial cells. Nonetheless, in ischemic tissues, most of engrafted EPCs do not survive under harsh ischemic conditions and nutrient depletion. Therefore, an understanding of diverse EPC-related cytoprotective mediators underlying EPC homeostasis in ischemic tissues may help to overcome current obstacles for EPC-mediated cell therapy for CVDs. Additionally, to enhance EPC's functional capacity at ischemic sites, multiple strategies for cell survival should be considered, that is, preconditioning of EPCs with function-targeting drugs including natural compounds and hormones, virus mediated genetic modification, combined therapy with other stem/progenitor cells, and conglomeration with biomaterials. In this review, we discuss multiple cytoprotective mediators of EPC-based cardiovascular repair and propose promising therapeutic strategies for the treatment of CVDs. PMID:28090210

  2. A new classification system for primary lymphatic dysplasias based on phenotype.

    PubMed

    Connell, F; Brice, G; Jeffery, S; Keeley, V; Mortimer, P; Mansour, S

    2010-05-01

    Traditional classification systems for lymphoedema are of limited use for the diagnosis of specific forms of primary lymphoedema. The understanding of primary lymphoedema has been impeded by confusing terminology and a tendency to simply divide patients into three categories based on the age of onset: lymphoedema congenita manifests at or shortly after birth, lymphoedema praecox is apparent before the age of 35 years and lymphoedema tarda manifests thereafter. The clinical presentation in the spectrum of primary lymphoedema disorders is very variable; the phenotypes of primary lymphoedema conditions vary in the age of onset, site of the oedema, inheritance patterns, associated features and genetic causes. Different inheritance patterns are recognised and there are numerous associated anomalies. Some subgroups, such as Milroy disease and Lymphoedema distichiasis, are well characterised, but others are not. A new clinical classification for primary lymphoedema has been developed as a diagnostic algorithm. Its use is demonstrated on 333 probands referred to our lymphoedema clinic. Grouping patients by accurate phenotyping facilitates molecular investigations, understanding of inheritance patterns, and the natural history of different types of primary lymphoedema. Descriptions of the diagnostic categories, some of which have not been previously clearly defined as distinct clinical entities, are illustrated by clinical cases.

  3. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes.

    PubMed

    Dominguez, Eduardo; Galmozzi, Andrea; Chang, Jae Won; Hsu, Ku-Lung; Pawlak, Joanna; Li, Weiwei; Godio, Cristina; Thomas, Jason; Partida, David; Niessen, Sherry; O'Brien, Paul E; Russell, Aaron P; Watt, Matthew J; Nomura, Daniel K; Cravatt, Benjamin F; Saez, Enrique

    2014-02-01

    Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3, also known as Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We further show that Ces3 activity is markedly elevated during adipocyte differentiation. Treatment of two mouse models of obesity-diabetes with a Ces3 inhibitor ameliorates multiple features of metabolic syndrome, illustrating the power of the described strategy to accelerate the identification and pharmacologic validation of new therapeutic targets.

  4. Genetic algorithm based approach to optimize phenotypical traits of virtual rice.

    PubMed

    Ding, Weilong; Xu, Lifeng; Wei, Yang; Wu, Fuli; Zhu, Defeng; Zhang, Yuping; Max, Nelson

    2016-08-21

    How to select and combine good traits of rice to get high-production individuals is one of the key points in developing crop ideotype cultivation technologies. Existing cultivation methods for producing ideal plants, such as field trials and crop modeling, have some limits. In this paper, we propose a method based on a genetic algorithm (GA) and a functional-structural plant model (FSPM) to optimize plant types of virtual rice by dynamically adjusting phenotypical traits. In this algorithm, phenotypical traits such as leaf angles, plant heights, the maximum number of tiller, and the angle of tiller are considered as input parameters of our virtual rice model. We evaluate the photosynthetic output as a function of these parameters, and optimized them using a GA. This method has been implemented on GroIMP using the modeling language XL (eXtended L-System) and RGG (Relational Growth Grammar). A double haploid population of rice is adopted as test material in a case study. Our experimental results show that our method can not only optimize the parameters of rice plant type and increase the amount of light absorption, but can also significantly increase crop yield. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Modularity-based credible prediction of disease genes and detection of disease subtypes on the phenotype-gene heterogeneous network.

    PubMed

    Yao, Xin; Hao, Han; Li, Yanda; Li, Shao

    2011-05-20

    Protein-protein interaction networks and phenotype similarity information have been synthesized together to discover novel disease-causing genes. Genetic or phenotypic similarities are manifested as certain modularity properties in a phenotype-gene heterogeneous network consisting of the phenotype-phenotype similarity network, protein-protein interaction network and gene-disease association network. However, the quantitative analysis of modularity in the heterogeneous network and its influence on disease-gene discovery are still unaddressed. Furthermore, the genetic correspondence of the disease subtypes can be identified by marking the genes and phenotypes in the phenotype-gene network. We present a novel network inference method to measure the network modularity, and in particular to suggest the subtypes of diseases based on the heterogeneous network. Based on a measure which is introduced to evaluate the closeness between two nodes in the phenotype-gene heterogeneous network, we developed a Hitting-Time-based method, CIPHER-HIT, for assessing the modularity of disease gene predictions and credibly prioritizing disease-causing genes, and then identifying the genetic modules corresponding to potential subtypes of the queried phenotype. The CIPHER-HIT is free to rely on any preset parameters. We found that when taking into account the modularity levels, the CIPHER-HIT method can significantly improve the performance of disease gene predictions, which demonstrates modularity is one of the key features for credible inference of disease genes on the phenotype-gene heterogeneous network. By applying the CIPHER-HIT to the subtype analysis of Breast cancer, we found that the prioritized genes can be divided into two sub-modules, one contains the members of the Fanconi anemia gene family, and the other contains a reported protein complex MRE11/RAD50/NBN. The phenotype-gene heterogeneous network contains abundant information for not only disease genes discovery but also

  7. Emerging Affinity-Based Proteomic Technologies for Large-Scale Plasma Profiling in Cardiovascular Disease.

    PubMed

    Smith, J Gustav; Gerszten, Robert E

    2017-04-25

    Plasma biomarkers that reflect molecular states of the cardiovascular system are central for clinical decision making. Routinely used plasma biomarkers include troponins, natriuretic peptides, and lipoprotein particles, yet interrogate only a modest subset of pathways relevant to cardiovascular disease. Systematic profiling of a larger portion of circulating plasma proteins (the plasma proteome) will provide opportunities for unbiased discovery of novel markers to improve diagnostic or predictive accuracy. In addition, proteomic profiling may inform pathophysiological understanding and point to novel therapeutic targets. Obstacles for comprehensive proteomic profiling include the immense size and structural heterogeneity of the proteome, and the broad range of abundance levels, as well. Proteome-wide, untargeted profiling can be performed in tissues and cells with tandem mass spectrometry. However, applications to plasma are limited by the need for complex preanalytical sample preparation stages limiting sample throughput. Multiplexing of targeted methods based on capture and detection of specific proteins are therefore receiving increasing attention in plasma proteomics. Immunoaffinity assays are the workhorse for measuring individual proteins but have been limited for proteomic applications by long development times, cross-reactivity preventing multiplexing, specificity issues, and incomplete sensitivity to detect proteins in the lower range of the abundance spectrum (below picograms per milliliter). Emerging technologies to address these issues include nucleotide-labeled immunoassays and aptamer reagents that can be automated for efficient multiplexing of thousands of proteins at high sample throughput, coupling of affinity capture methods to mass spectrometry for improved specificity, and ultrasensitive detection systems to measure low-abundance proteins. In addition, proteomics can now be integrated with modern genomics tools to comprehensively relate

  8. TIPS: A system for automated image-based phenotyping of maize tassels

    DOE PAGES

    Gage, Joseph L.; Miller, Nathan D.; Spalding, Edgar P.; ...

    2017-03-31

    Here, the maize male inflorescence (tassel) produces pollen necessary for reproduction and commercial grain production of maize. The size of the tassel has been linked to factors affecting grain yield, so understanding the genetic control of tassel architecture is an important goal. Tassels are fragile and deform easily after removal from the plant, necessitating rapid measurement of any shape characteristics that cannot be retained during storage. Some morphological characteristics of tassels such as curvature and compactness are difficult to quantify using traditional methods, but can be quantified by image-based phenotyping tools. Lastly, these constraints necessitate the development of an efficientmore » method for capturing natural-state tassel morphology and complementary automated analytical methods that can quickly and reproducibly quantify traits of interest such as height, spread, and branch number.« less

  9. System response time and method of pay: cardiovascular stress effects in computer-based tasks.

    PubMed

    Schleifer, L M; Okogbaa, O G

    1990-12-01

    Psychophysiological effects of computer system response time (slow vs. rapid) and method of pay (incentive vs. nonincentive) were assessed in a computer-based data entry task among forty-five professional typists. Cardiovascular responses (i.e., heart rate and blood pressure) were monitored on a regular basis over four consecutive workdays. Heart rate and blood pressure did not vary significantly with slow or rapid response times. Incentive pay, however, significantly increased blood pressure and decreased heart rate variability across the workdays compared to nonincentive pay. Irrespective of response time or method of pay, performance of the data entry task for sustained periods of time was associated with reduced heart rate and increased heart rate variability. This temporal effect was indicative of reduced effort or increased mental fatigue. The results of this study suggest that incentive pay programmes in data entry work may produce stress-related physiological reactivity among healthy workers.

  10. 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.

  11. Model-based parameter estimation using cardiovascular response to orthostatic stress

    NASA Technical Reports Server (NTRS)

    Heldt, T.; Shim, E. B.; Kamm, R. D.; Mark, R. G.

    2001-01-01

    This paper presents a cardiovascular model that is capable of simulating the short-term (< or approximately equal to 3 min) transient hemodynamic response to gravitational stress and a gradient-based optimization method that allows for the automated estimation of model parameters from simulated or experimental data. We perform a sensitivity analysis of the transient heart rate response to determine which parameters of the model impact the heart rate dynamics significantly. We subsequently include only those parameters in the estimation routine that impact the transient heart rate dynamics substantially. We apply the estimation algorithm to both simulated and real data and showed that restriction to the 20 most important parameters does not impair our ability to match the data.

  12. Brooding Rumination and Cardiovascular Reactivity to a Laboratory-based Interpersonal Stressor

    PubMed Central

    Woody, Mary L.; Burkhouse, Katie L.; Birk, Samantha L.; Gibb, Brandon E.

    2015-01-01

    There is a well-known link between stress and depression, but diathesis-stress models suggest that not all individuals are equally susceptible to stress. The current study examined if brooding rumination, a known risk factor for depression, influences cardiovascular reactivity to a laboratory-based interpersonal stressor. Sixty-five women watched a baseline video and were exposed to an interpersonal stressor while high frequency heart rate variability (HRV) was collected. We found that women who endorsed higher levels of brooding rumination exhibited greater HRV withdrawal from baseline to stressor, an effect that was maintained when we controlled for levels of depression. This physiological vulnerability, when combined with high levels of stress, may be one mechanism underlying how brooding rumination increases depression risk. PMID:25512247

  13. 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.

  14. Model-based parameter estimation using cardiovascular response to orthostatic stress

    NASA Technical Reports Server (NTRS)

    Heldt, T.; Shim, E. B.; Kamm, R. D.; Mark, R. G.

    2001-01-01

    This paper presents a cardiovascular model that is capable of simulating the short-term (< or approximately equal to 3 min) transient hemodynamic response to gravitational stress and a gradient-based optimization method that allows for the automated estimation of model parameters from simulated or experimental data. We perform a sensitivity analysis of the transient heart rate response to determine which parameters of the model impact the heart rate dynamics significantly. We subsequently include only those parameters in the estimation routine that impact the transient heart rate dynamics substantially. We apply the estimation algorithm to both simulated and real data and showed that restriction to the 20 most important parameters does not impair our ability to match the data.

  15. Accuracy of Phenotyping of Autistic Children Based on Internet Implemented Parent Report

    PubMed Central

    Lee, Hane; Marvin, Alison R.; Watson, Tamara; Piggot, Judith; Law, J. Kiely; Law, Paul A.; Constantino, John N.; Nelson, Stanley F.

    2013-01-01

    While strong familial evidence supports a substantial genetic contribution to the etiology of autism spectrum disorders (ASD), specific genetic abnormalities have been identified in only a small minority of all cases. In order to comprehensively delineate the genetic components of autism including the identification of rare and common variants, overall sample sizes an order of magnitude larger than those currently under study are critically needed. This will require rapid and scalable subject assessment paradigms that obviate clinic-based time-intensive behavioral phenotyping, which is a rate-limiting step. Here, we test the accuracy of a web-based approach to autism phenotyping implemented within the Interactive Autism Network (IAN). Families who were registered with the IAN and resided near one of the three study sites were eligible for the study. One hundred seven children ascertained from this pool who were verbal, age 4–17 years, and had Social Communication Questionnaire (SCQ) scores ≥12 (a profile that characterizes a majority of ASD -affected children in IAN) underwent a clinical confirmation battery. One hundred five of the 107 children were ASD positive (98%) by clinician’s best estimate. One hundred four of these individuals (99%) were ASD positive by developmental history using the Autism Diagnostic Interview-Revised (ADI-R) and 97 (93%) were positive for ASD by developmental history and direct observational assessment (Autism Diagnostic Observational Schedule or expert clinician observation). These data support the reliability and feasibility of the IAN-implemented parent-report paradigms for the ascertainment of clinical ASD for large-scale genetic research. PMID:20552678

  16. 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

  17. Entropy-based complexity of the cardiovascular control in Parkinson disease: comparison between binning and k-nearest-neighbor approaches.

    PubMed

    Porta, Alberto; Bari, Vlasta; Bassani, Tito; Marchi, Andrea; Tassin, Stefano; Canesi, Margherita; Barbic, Franca; Furlan, Raffaello

    2013-01-01

    Entropy-based approaches are frequently used to quantify complexity of short-term cardiovascular control from spontaneous beat-to-beat variability of heart period (HP) and systolic arterial pressure (SAP). Among these tools the ones optimizing a critical parameter such as the pattern length are receiving more and more attention. This study compares two entropy-based techniques for the quantification of complexity making use of completely different strategies to optimize the pattern length. Comparison was carried out over HP and SAP variability series recorded from 12 Parkinson's disease (PD) patients without orthostatic hypotension or symptoms of orthostatic intolerance and 12 age-matched healthy control (HC) subjects. Regardless of the method, complexity of cardiovascular control increased in PD group, thus suggesting the early impairment of cardiovascular function.

  18. Cardiovascular disease prevention in Ghana: feasibility of a faith-based organizational approach

    PubMed Central

    Huang, Keng-Yen; Shinners, Daniel; Levy, Andrea; Ayernor, Kojo; de-Graft Aikins, Ama; Ogedegbe, Olugbenga

    2011-01-01

    Abstract Objective To examine the feasibility of using community health workers (CHWs) to implement cardiovascular disease (CVD) prevention programmes within faith-based organizations in Accra, Ghana. Methods Faith-based organization capacity, human resources, health programme sustainability/barriers and community members’ knowledge were evaluated. Data on these aspects were gathered through a mixed method design consisting of in-depth interviews and focus groups with 25 church leaders and health committee members from five churches, and of a survey of 167 adult congregants from two churches. Findings The delivery of a CVD prevention programme in faith-based organizations by CHWs is feasible. Many faith-based organizations already provide health programmes for congregants and involve non-health professionals in their health-care activities, and most congregants have a basic knowledge of CVD. Yet despite the feasibility of the proposed approach to CVD prevention through faith-based organizations, sociocultural and health-care barriers such as poverty, limited human and economic resources and limited access to health care could hinder programme implementation. Conclusion The barriers to implementation identified in this study need to be considered when defining CVD prevention programme policy and planning. PMID:21897485

  19. 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

  20. Plant-Based Nutrition: An Essential Component of Cardiovascular Disease Prevention and Management.

    PubMed

    Patel, Hena; Chandra, Sonal; Alexander, Sarah; Soble, Jeffrey; Williams, Kim Allan

    2017-09-08

    This review aims to summarize and discuss the role of plant-based nutrition as an adjunct to the management of cardiovascular disease (CVD). Discussion of nutrition and the benefits of a plant-based diet should be highlighted during healthcare provider visits as an essential part of the overall CVD prevention and management care plan. Evidence from prospective cohort studies indicates that a high consumption of predominantly plant-based foods, such as fruit and vegetables, nuts, and whole grains, is associated with a significantly lower risk of CVD. The protective effects of these foods are likely mediated through their multiple beneficial nutrients, including mono- and polyunsaturated fatty acids, omega-3 fatty acids, antioxidant vitamins, minerals, phytochemicals, fiber, and plant protein. In addition, minimizing intake of animal proteins has been shown to decrease the prevalence of CVD risk factors. Substantial evidence indicates that plant-based diets can play an important role in preventing and treating CVD and its risk factors. Such diets deserve more emphasis in dietary recommendations.

  1. Community-based cardiovascular health promotion in Argentina. A systematic review.

    PubMed

    Bardach, Ariel Esteban; Elorriaga, Natalia; Alcaraz, Andrea Olga; Rubinstein, Adolfo Luis; Tavella, Julio Marcelo

    2017-01-30

    In Argentina, cardiovascular disease (CVD) accounts for 30% of deaths and more than 600 000 disability-adjusted life years. However, no reviews describing local studies on interventions to address CVD risk factors have been identified. The purpose of this study is to characterize those population-based interventions and public policies implemented in Argentina to reduce the burden of cardiovascular disease with an adequate evaluation of their impact on population health. We conducted a systematic review of studies that assessed interventions in health promotion and/or primary prevention conducted in adult populations of Argentina, addressing specific CVD factors, from 1999 to 2016. We searched major bibliographic databases, grey literature, ministries and secretariats of health, and academic national libraries. Key informants, non-governmental organizations, universities, hospitals and experts were also contacted. We applied specific inclusion criteria. We assessed the methodological quality of the studies and reported the effectiveness and impact of population interventions and policies, as well as process evaluations' characteristics. After removing duplicates we identified 1686 references from databases. After reviewing title and abstracts 18 studies were selected, five of them corresponded to evaluations of public policies-all addressing tobacco smoking. We presented a structured review of each experience. Most of the studies were deemed to entail moderate or high risk of bias. We summarized the findings and characteristics of these studies, including implementation strategies, process and impact evaluation. This is the first systematic review of interventions focused on primary prevention and health promotion to counter CVD and diabetes in Argentina. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Outcomes of an integrated community-based nurse-led cardiovascular disease prevention programme

    PubMed Central

    Connolly, S B; Kotseva, K; Jennings, C; Atrey, A; Jones, J; Brown, A; Bassett, P; Wood, D A

    2017-01-01

    Background National guidance for England recommends that cardiovascular disease (CVD) should be managed as a family of diseases in the community. Here, we describe the results of such an approach. Methods Patients with established CVD or who were at high multifactorial risk (HRI) underwent a 12-week community-based nurse-led prevention programme (MyAction) that included lifestyle and risk factor management, prescription of medication and weekly exercise and education sessions. Results Over a 6-year period, 3232 patients attended an initial assessment; 63% were male, and 48% belonged to black and minority ethnic groups. 56% attended an end-of-programme assessment, and 33% attended a one year assessment. By the end of the programme, there was a significant reduction in smoking prevalence but only in HRI (−3.7%, p<0.001). Mediterranean diet score increased in both CVD (+1.2, p<0.001) and HRI (+1.5; p<0.001), as did fitness levels (CVD +0.8 estimated Mets maximum, p<0.001, HRI +0.9 estimated Mets maximum, p<0.001) and the proportions achieving their physical activity targets (CVD +40%, p<0.001, HRI +37%, p<0.001). There were significant increases in proportions achieving their blood pressure (CVD +15.4%, p<0.001, HRI +25%, p<0.001 and low-density lipoprotein cholesterol targets (CVD +6%, p=0.004, HRI +23%, p<0.001). Statins and antihypertensive medications significantly increased in HRI. Significant improvements in depression scores and quality-of-life measures were also seen. The majority of improvements were maintained at 1 year. Conclusion These results demonstrate that an integrated vascular prevention programme is feasible in practice and reduces cardiovascular risk in patients with established CVD and in those at high multifactorial risk. PMID:28255098

  3. Assessment of the relationship between periodontal disease and cardiovascular disorders: a questionnaire-based study

    PubMed Central

    IONEL, ANCA; LUCACIU, ONDINE; BONDOR, COSMINA; MOGA, MINODORA; ILEA, ARANKA; FEURDEAN, CLAUDIA; BUHĂŢEL, DAN; HURUBEANU, LUCIA; CÂMPIAN, RADU SEPTIMIU

    2016-01-01

    Background and aims Periodontitis is an inflammatory disease, characterized by the loss of connective tissue and alveolar bone. There is an increasing evidence that periodontitis is associated with a number of chronic diseases. The aim of this study was to analyze the correlation between periodontitis and certain systemic diseases by identifying their risk factors in a population from North-West Romania. Methods A questionnaire-based study was conducted on participants ≥45 years of age in 4 dentistry or family medicine practices from the Cluj and Bihor counties, Romania, over a time frame spanning two months. The interviewer-administered questionnaire included 42 items assessing risk factors for periodontal and cardiovascular disease, current diagnostic and medical treatment of the participants, their diet and oral hygiene habits. Results Of 108 participants included in the study, 63 (58.3%) declared a previous diagnosis of periodontitis. A significant difference was observed between the participants with declared diagnosis of periodontitis (PD+) and participants without declared diagnosis of periodontitis (PD−) for fresh fruit consumption (p=0.01) and increased sport activity (p=0.009). A significant difference between groups was observed in the case of smoking duration (p=0.047), participants with >10 years of smoking were more likely to declare a diagnosis of periodontitis. Also, PD+ participants were more likely to have a family history of periodontal disease (p<0.001). Multivariate analyses suggested periodontitis as a predictive variable for atherosclerotic coronary artery disease with an OR of 4.85 (95% confidence interval 1.01–23.29, p=0.049). Conclusion Our study found a statistically significant association between periodontal disease and a known family history of periodontal disorders and smoking duration. Daily intake of fresh fruit and increased sport activities were found to be protective factors against periodontal disease, while periodontitis

  4. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study.

    PubMed

    Loza, Matthew J; Djukanovic, Ratko; Chung, Kian Fan; Horowitz, Daniel; Ma, Keying; Branigan, Patrick; Barnathan, Elliot S; Susulic, Vedrana S; Silkoff, Philip E; Sterk, Peter J; Baribaud, Frédéric

    2016-12-15

    Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was "mild, good lung function, early onset", with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a "moderate, hyper-responsive, eosinophilic" phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a "mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic" phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a "severe uncontrolled, severe reversible obstruction, mixed granulocytic" phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Focusing on the biology of the four clinical

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

    PubMed

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

    2013-10-01

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

  6. 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

  7. 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.

  8. 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

  9. 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.

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

    PubMed

    Hendriks, Marleen; Brewster, Lizzy; Wit, Ferdinand; Bolarinwa, Oladimeji Akeem; Odusola, Aina Olufemi; Redekop, William; Bindraban, Navin; Vollaard, Albert; Alli, Shade; Adenusi, Peju; Agbede, Kayode; Akande, Tanimola; Lange, Joep; Schultsz, Constance

    2011-03-25

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

  11. 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.

  12. 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…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  14. 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. Copyright © 2014 by the Genetics Society of America.

  15. Assessment of the Cardiovascular Risk of Olmesartan Medoxomil-Based Treatment: Meta-Analysis of Individual Patient Data.

    PubMed

    Wang, Antonia C; Stellmacher, Ulf; Schumi, Jennifer; Tu, Nora; Reimitz, Paul-Egbert

    2016-12-01

    Results from two long-term studies (ROADMAP and ORIENT) indicated a numerical imbalance in the number of cardiovascular deaths between the olmesartan medoxomil (OM) and placebo groups. Our objective was to conduct an individual patient data meta-analysis to provide more complete information regarding OM-associated cardiovascular risks and/or benefits. We created an integrated database based on 191 clinical trials from the OM development program. Events were identified and adjudicated by an independent, blinded clinical events committee. The incidence of major cardiovascular events and total mortality for OM versus placebo/active control were evaluated, and the effect of OM on cardiovascular mortality (main endpoint of interest) and morbidity was calculated using a two-stage approach (Tian method). A total of 46 studies (~27,000 patients) met the US FDA-specified inclusion criteria (phase II-IV randomized, double-blind, placebo- or active-controlled studies [OM-based monotherapy or combination, double-blind period ≥28 days] and adult patients). The incidence of known adjudicated endpoints in the analysis of all studies combined was low among OM (0.11-0.53 %) and placebo/active control (0.08-0.76 %) groups. For cardiovascular mortality, the estimated risk difference (OM vs. control) was 0.00070 (95 % confidence interval [CI] -0.0011 to 0.0024; p = 0.60); the risk difference for each endpoint was <1/1000, with no statistically significant difference between groups. Results were similar with and without ROADMAP and ORIENT. The results from this meta-analysis did not show a clinically meaningful or statistically significant difference in cardiovascular risk between OM and the placebo/active control groups, and thus did not corroborate the numerical imbalance observed in ROADMAP and ORIENT.

  16. Use of biological based therapy in patients with cardiovascular diseases in a university-hospital in New York City

    PubMed Central

    Chagan, Larisa; Bernstein, Diane; Cheng, Judy WM; Kirschenbaum, Harold L; Rozenfeld, Vitalina; Caliendo, Gina C; Meyer, Joanne; Mehl, Bernard

    2005-01-01

    Background The use of complementary and alternative products including Biological Based Therapy (BBT) has increased among patients with various medical illnesses and conditions. The studies assessing the prevalence of BBT use among patients with cardiovascular diseases are limited. Therefore, an evaluation of BBT in this patient population would be beneficial. This was a survey designed to determine the effects of demographics on the use of Biological Based Therapy (BBT) in patients with cardiovascular diseases. The objective of this study was to determine the effect of the education level on the use of BBT in cardiovascular patients. This survey also assessed the perceptions of users regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug interactions. Method The survey instrument was designed to assess the findings. Patients were interviewed from February 2001 to December 2002. 198 inpatients with cardiovascular diseases (94 BBT users and 104 non-users) in a university hospital were included in the study. Results Users had a significantly higher level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p = 0.003). Top 10 BBT products used were vitamin E [41(43.6%)], vitamin C [30(31.9%)], multivitamins [24(25.5%)], calcium [19(20.2%)], vitamin B complex [17(18.1%)], fish oil [12(12.8%)], coenzyme Q10 [11(11.7%)], glucosamine [10(10.6%)], magnesium [8(8.5%)] and vitamin D [6(6.4%)]. Sixty percent of users' physicians knew of the BBT use. Compared to non-users, users believed BBT to be safer (p < 0.001) and more effective (p < 0.001) than prescription drugs. Forty-two potential drug-BBT interactions were identified. Conclusion Incidence of use of BBT in cardiovascular patients is high (47.5%), as is the risk of potential drug interaction. Health care providers need to monitor BBT use in patients with cardiovascular diseases. PMID:15745441

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

    PubMed

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

    2017-10-01

    Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

  18. Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood.

    PubMed

    Guo, Quan; Duffy, Simon P; Matthews, Kerryn; Islamzada, Emel; Ma, Hongshen

    2017-07-26

    The separation of leukocytes from whole blood is a prerequisite for many biological assays. Traditional methods require significant sample volumes and are often undesirable because they expose leukocytes to harsh physical or chemical treatment. Existing microfluidic approaches can work with smaller volumes, but lack selectivity. In particular, the selectivity of microfluidic systems based on microfiltration is limited by fouling due to clogging. Here, we developed a method to separate leukocytes from whole blood using the microfluidic ratchet mechanism, which filters the blood sample using a matrix of micrometer-scale tapered constrictions. Deforming single cells through such constrictions requires directionally asymmetrical forces, which enables oscillatory flow to create a ratcheting transport that depends on cell size and deformability. Simultaneously, oscillatory flow continuously agitates the cells to limit the contact time with the filter microstructure to prevent adsorption and clogging. We show this device is capable of isolating leukocytes from whole blood with 100% purity (i.e. no contaminant erythrocytes) and <2% leukocytes loss. We further demonstrate the potential to phenotypically sort leukocytes to enrich for granulocytes and lymphocytes subpopulations. Together, this process provides a sensitive method to isolate and sort leukocytes directly from whole blood based on their biophysical properties.

  19. Plant Chemical Genetics: From Phenotype-Based Screens to Synthetic Biology[OPEN

    PubMed Central

    2017-01-01

    The treatment of a biological system with small molecules to specifically perturb cellular functions is commonly referred to as chemical biology. Small molecules are used commercially as drugs, herbicides, and fungicides in different systems, but in recent years they are increasingly exploited as tools for basic research. For instance, chemical genetics involves the discovery of small-molecule effectors of various cellular functions through screens of compound libraries. Whereas the drug discovery field has largely been driven by target-based screening approaches followed by drug optimization, chemical genetics in plant systems tends to be fueled by more general phenotype-based screens, opening the possibility to identify a wide range of small molecules that are not necessarily directly linked to the process of interest. Here, we provide an overview of the current progress in chemical genetics in plants, with a focus on the discoveries regarding small molecules identified in screens designed with a basic biology perspective. We reflect on the possibilities that lie ahead and discuss some of the potential pitfalls that might be encountered upon adopting a given chemical genetics approach. PMID:28275150

  20. 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.

  1. A model-based framework for the phenotypic characterization of the flowering of Medicago truncatula.

    PubMed

    Moreau, Delphine; Salon, Christophe; Munier-Jolain, Nathalie

    2007-02-01

    To facilitate the phenotypic characterization of Medicago truncatula, our aim was to provide a framework of analysis of flowering in response to environmental factors. The flowering of the line A17 was analysed in different conditions of temperature, duration of vernalization and photoperiod. Flowering was characterized using three descriptors at the axis level: the position of the first reproductive node (1RN), the date of beginning of flowering (DBF) and the florochron (RFa-1) corresponding to the reciprocal of the rate of progression of flowering along each axis. As for vegetative development, it was found that flowering could be analysed as a function of thermal time using a base temperature (Tb) of 5 degrees C. Vernalization displayed a sound impact on the flowering. For all the studied axes, increasing the duration of vernalization lowered the 1RN and hastened the DBF. By contrast, for most of the studied axes, RFa-1 was only slightly affected by vernalization. For the branch B0, RFa-1 was a genotypic constant when thermal time was used. Considering B0 as a reference axis, an ecophysiological model was developed to simulate the impact of environmental factors on the three components of flowering. Concrete practical applications of the model-based framework presented herein are proposed for helping the genetic and genomic studies of M. truncatula.

  2. 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

  3. A randomized controlled trial of water-based exercise for cardiovascular fitness in individuals with chronic stroke

    PubMed Central

    Chu, Kelly S; Eng, Janice J; Dawson, Andrew S; Harris, Jocelyn E.; Ozkaplan, Atila; Gylfadóttir, Sif

    2011-01-01

    Objective To evaluate the effect of an 8-week water-based exercise program (experimental group) over an upper extremity function program (control group) to increase cardiovascular fitness within a community setting for individuals with stroke. Design Single-blind randomized controlled trial Setting Public community centre Participants 12 community-dwelling individuals who have had a stroke with mild to moderate motor deficits; volunteer sample Intervention Experimental and control groups participated in group exercise programs undertaken in one hour sessions, three times per week for 8 weeks. The experimental group undertook chest deep water exercises at targeted heart rates. The control group performed arm and hand exercises while sitting. Main Outcome Measures The primary outcome measure was cardiovascular fitness (VO2max). Secondary measures were maximal workload, muscle strength, gait speed, and the Berg Balance Score. Results The experimental group attained significant improvements over the control group in cardiovascular fitness, maximal workload, gait speed, and paretic lower extremity muscle strength. The relatively short program (8 weeks) of water-based exercise resulted in a large improvement (22%) in cardiovascular fitness in a small group of individuals with stroke with relatively high function. Conclusions A water-based exercise program can be undertaken in the community as a group program and may be an effective means to promote fitness in individuals with stroke. PMID:15179638

  4. Comparison of competing risks models based on cumulative incidence function in analyzing time to cardiovascular diseases.

    PubMed

    Dianatkhah, Minoo; Rahgozar, Mehdi; Talaei, Mohammad; Karimloua, Masoud; Sadeghi, Masoumeh; Oveisgharan, Shahram; Sarrafzadegan, Nizal

    2014-01-01

    Competing risks arise when the subject is exposed to more than one cause of failure. Data consists of the time that the subject failed and an indicator of which risk caused the subject to fail. With three approaches consisting of Fine and Gray, binomial, and pseudo-value, all of which are directly based on cumulative incidence function, cardiovascular disease data of the Isfahan Cohort Study were analyzed. Validity of proportionality assumption for these approaches is the basis for selecting appropriate models. Such as for the Fine and Gray model, establishing proportionality assumption is necessary. In the binomial approach, a parametric, non-parametric, or semi-parametric model was offered according to validity of assumption. However, pseudo-value approaches do not need to establish proportionality. Following fitting the models to data, slight differences in parameters and variances estimates were seen among models. This showed that semi-parametric multiplicative model and the two models based on pseudo-value approach could be used for fitting this kind of data. We would recommend considering the use of competing risk models instead of normal survival methods when subjects are exposed to more than one cause of failure.

  5. Obesity-related inflammation & cardiovascular disease: efficacy of a yoga-based lifestyle intervention.

    PubMed

    Sarvottam, Kumar; Yadav, Raj Kumar

    2014-06-01

    Obesity is a global health burden and its prevalence is increasing substantially due to changing lifestyle. Chronic adiposity is associated with metabolic imbalance leading to dyslipidaemia, diabetes, hypertension and cardiovascular diseases (CVD). Adipose tissue acts as an endocrine organ releasing several adipocytokines, and is associated with increased levels of tissue and circulating inflammatory biomolecules causing vascular inflammation and atherogenesis. Further, inflammation is also associated independently with obesity as well as CVD. Keeping this in view, it is possible that a reduction in weight may lead to a decrease in inflammation, resulting in CVD risk reduction, and better management of patients with CVD. Lifestyle intervention has been endorsed by several health authorities in prevention and management of chronic diseases. A yoga-based lifestyle intervention appears to be a promising option in reducing the risk for CVD as well as management of patients with CVD as it is simple to follow and cost-effective with high compliance. The efficacy of such lifestyle intervention programmes is multifaceted, and is achieved via reduction in weight, obesity-related inflammation and stress, thereby culminating into risk reduction towards several chronic diseases including CVD. In this review, the association between obesity-related inflammation and CVD, and the role of yoga-based lifestyle intervention in prevention and management of CVD are discussed.

  6. Cardiovascular disease and diagnosis of amyotrophic lateral sclerosis: A population based study.

    PubMed

    Kioumourtzoglou, Marianthi-Anna; Seals, Ryan M; Gredal, Ole; Mittleman, Murray A; Hansen, Johnni; Weisskopf, Marc G

    Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disease of unknown etiology. We investigated the association between ALS diagnosis and prior cardiovascular disease (CVD), and CVD-specific, hospital admissions in the Danish population. We conducted a population based nested case-control study, including 3182 Danish residents diagnosed with ALS at age ≥20 years (1982-2009) and 100 randomly selected controls for each case, matched on age, gender and vital status. We estimated odds ratios (OR) associated with CVD, and CVD-specific hospital admissions, adjusting for socioeconomic and marital status, region of residence and past diabetes and obesity diagnoses. The estimated adjusted OR for any CVD admission at least three years prior to the date of ALS diagnosis was 1.15 (95% CI 1.04-1.27). Our results varied across cause-specific admissions; for atherosclerosis the OR was 1.36 (95% CI 1.02-1.80) and for ischemic heart disease 1.14 (95% CI 0.99-1.31), while we observed no association with hypertensive and cerebrovascular diseases. Adjusting for or stratifying by COPD status, a cigarette-smoking correlate, did not change our results. In conclusion, in our population based study we found evidence for a moderately elevated association with CVD that was stronger for specific conditions, such as atherosclerosis. Our findings may have important implications for ALS pathogenesis.

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

    PubMed

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

    2010-05-01

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

  8. Comparative analysis of a novel disease phenotype network based on clinical manifestations

    PubMed Central

    Chen, Yang; Zhang, Xiang; Zhang, Guo-qiang; Xu, Rong

    2015-01-01

    Systems approaches to analyzing disease phenotype networks in combination with protein functional interaction networks have great potential in illuminating disease pathophysiological mechanisms. While many genetic networks are readily available, disease phenotype networks remain largely incomplete. In this study, we built a large-scale Disease Manifestation Network (DMN) from 50,543 highly accurate disease-manifestation semantic relationships in the United Medical Language System (UMLS). Our new phenotype network contains 2305 nodes and 373,527 weighted edges to represent the disease phenotypic similarities. We first compared DMN with the networks representing genetic relationships among diseases, and demonstrated that the phenotype clustering in DMN reflects common disease genetics. Then we compared DMN with a widely-used disease phenotype network in previous gene discovery studies, called mimMiner, which was extracted from the textual descriptions in Online Mendelian Inheritance in Man (OMIM). We demonstrated that DMN contains different knowledge from the existing phenotype data source. Finally, a case study on Marfan syndrome further proved that DMN contains useful information and can provide leads to discover unknown disease causes. Integrating DMN in systems approaches with mimMiner and other data offers the opportunities to predict novel disease genetics. We made DMN publicly available at nlp/case.edu/public/data/DMN. PMID:25277758

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  11. A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.

    PubMed

    Esposito, Marta; Szadocka, Sára; Degiacomi, Giulia; Orena, Beatrice S; Mori, Giorgia; Piano, Valentina; Boldrin, Francesca; Zemanová, Júlia; Huszár, Stanislav; Barros, David; Ekins, Sean; Lelièvre, Joel; Manganelli, Riccardo; Mattevi, Andrea; Pasca, Maria Rosalia; Riccardi, Giovanna; Ballell, Lluis; Mikušová, Katarína; Chiarelli, Laurent R

    2017-06-09

    Despite its great potential, the target-based approach has been mostly unsuccessful in tuberculosis drug discovery, while whole cell phenotypic screening has delivered several active compounds. However, for many of these hits, the cellular target has not yet been identified, thus preventing further target-based optimization of the compounds. In this context, the newly validated drug target CTP synthetase PyrG was exploited to assess a target-based approach of already known, but untargeted, antimycobacterial compounds. To this purpose the publically available GlaxoSmithKline antimycobacterial compound set was assayed, uncovering a series of 4-(pyridin-2-yl)thiazole derivatives which efficiently inhibit the Mycobacterium tuberculosis PyrG enzyme activity, one of them showing low activity against the human CTP synthetase. The three best compounds were ATP binding site competitive inhibitors, with Ki values ranging from 3 to 20 μM, but did not show any activity against a small panel of different prokaryotic and eukaryotic kinases, thus demonstrating specificity for the CTP synthetases. Metabolic labeling experiments demonstrated that the compounds directly interfere not only with CTP biosynthesis, but also with other CTP dependent biochemical pathways, such as lipid biosynthesis. Moreover, using a M. tuberculosis pyrG conditional knock-down strain, it was shown that the activity of two compounds is dependent on the intracellular concentration of the CTP synthetase. All these results strongly suggest a role of PyrG as a target of these compounds, thus strengthening the value of this kind of approach for the identification of new scaffolds for drug development.

  12. Clarification of pathway-specific inhibition by Fourier transform ion cyclotron resonance/mass spectrometry-based metabolic phenotyping studies.

    PubMed

    Oikawa, Akira; Nakamura, Yukiko; Ogura, Tomonori; Kimura, Atsuko; Suzuki, Hideyuki; Sakurai, Nozomu; Shinbo, Yoko; Shibata, Daisuke; Kanaya, Shigehiko; Ohta, Daisaku

    2006-10-01

    We have developed a metabolic profiling scheme based on direct-infusion Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). The scheme consists of: (1) reproducible data collection under optimized FT-ICR/MS analytical conditions; (2) automatic mass-error correction and multivariate analyses for metabolome characterization using a newly developed metabolomics tool (DMASS software); (3) identification of marker metabolite candidates by searching a species-metabolite relationship database, KNApSAcK; and (4) structural analyses by an MS/MS method. The scheme was applied to metabolic phenotyping of Arabidopsis (Arabidopsis thaliana) seedlings treated with different herbicidal chemical classes for pathway-specific inhibitions. Arabidopsis extracts were directly infused into an electrospray ionization source on an FT-ICR/MS system. Acquired metabolomics data were comprised of mass-to-charge ratio values with ion intensity information subjected to principal component analysis, and metabolic phenotypes from the herbicide treatments were clearly differentiated from those of the herbicide-free treatment. From each herbicide treatment, candidate metabolites representing such metabolic phenotypes were found through the KNApSAcK database search. The database search and MS/MS analyses suggested dose-dependent accumulation patterns of specific metabolites including several flavonoid glycosides. The metabolic phenotyping scheme on the basis of FT-ICR/MS coupled with the DMASS program is discussed as a general tool for high throughput metabolic phenotyping studies.

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

    PubMed Central

    Fernandez-Mendoza, Julio; Calhoun, Susan L.; Vgontzas, Alexandros N.; Li, Yun; Gaines, Jordan; Liao, Duanping; Bixler, Edward O.

    2016-01-01

    Based on previous studies on the role of objective sleep duration in predicting morbidity in individuals with insomnia, we examined the role of objective sleep duration in differentiating behavioral profiles in adolescents with insomnia symptoms. Adolescents from the Penn State Child Cohort (n = 397, ages 12–23, 54.7% male) underwent a nine-hour polysomnography (PSG), clinical history, physical examination and psychometric testing, including the Child or Adult Behavior Checklist and Pediatric Behavior Scale. Insomnia symptoms were defined as a self-report of difficulty falling and/or staying asleep and objective “short” sleep duration as a PSG total sleep time ≤7 h. A significant interaction showed that objective short sleep duration modified the association of insomnia symptoms with internalizing problems. Consistently, adolescents with insomnia symptoms and short sleep duration were characterized by depression, rumination, mood dysregulation and social isolation, while adolescents with insomnia symptoms and normal sleep duration were characterized by rule-breaking and aggressive behaviors and, to a lesser extent, rumination. These findings indicate that objective sleep duration is useful in differentiating behavioral profiles among adolescents with insomnia symptoms. The insomnia with objective short sleep duration phenotype is associated with an increased risk of depression earlier in the lifespan than previously believed. PMID:27983580

  14. Next-Generation Mapping of Complex Traits with Phenotype-Based Selection and Introgression

    PubMed Central

    Earley, Eric J.; Jones, Corbin D.

    2011-01-01

    Finding the genes underlying complex traits is difficult. We show that new sequencing technology combined with traditional genetic techniques can efficiently identify genetic regions underlying a complex and quantitative behavioral trait. As a proof of concept we used phenotype-based introgression to backcross loci that control innate food preference in Drosophila simulans into the genomic background of D. sechellia, which expresses the opposite preference. We successfully mapped D. simulans introgression regions in a small mapping population (30 flies) with whole-genome resequencing using light coverage (∼1×). We found six loci contributing to D. simulans food preference, one of which overlaps a previously discovered allele. This approach is applicable to many systems, does not rely on laborious marker development or genotyping, does not require existing high quality reference genomes, and needs only small mapping populations. Because introgression is used, researchers can scale mapping population size, replication, and number of backcross generations to their needs. Finally, in contrast to more widely used mapping techniques like F2 bulk-segregant analysis, our method produces near-isogenic lines that can be kept and reused indefinitely. PMID:21940681

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

    PubMed Central

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

    2016-01-01

    Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors. PMID:27791177

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

    PubMed

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

    2016-10-24

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

  18. [Two base deletion of the alpha (1,2) fucosyltransferase gene responsible for para-Bombay phenotype].

    PubMed

    Zhu, Fa-ming; Xu, Xian-guo; Hong, Xiao-zhen; Yan, Li-xing

    2004-06-01

    To probe into the molecular genetics basis for para-Bombay phenotype. Red blood cell phenotype of the proband was characterized by serological techniques. Exons 6 and 7 of ABO gene, the entire coding region of alpha(1,2) fucosyltransferase (FUT1) gene and FUT2 gene were amplified by polymerase chain reaction (PCR) from genomic DNA of the proband respectively. The PCR products were excised and purified from agarose gels and were directly sequenced. AG at 547-552 deletion homozygous allele was found in the proband, which caused a reading frame shift and a premature stop codon. Parents of proband were heterozygous carriers. Two base deletion at position 547-552 of alpha (1,2) fucosyltransferase gene may cause para-Bombay phenotype.

  19. Surface feature based classification of plant organs from 3D laserscanned point clouds for plant phenotyping

    PubMed Central

    2013-01-01

    Background Laserscanning recently has become a powerful and common method for plant parameterization and plant growth observation on nearly every scale range. However, 3D measurements with high accuracy, spatial resolution and speed result in a multitude of points that require processing and analysis. The primary objective of this research has been to establish a reliable and fast technique for high throughput phenotyping using differentiation, segmentation and classification of single plants by a fully automated system. In this report, we introduce a technique for automated classification of point clouds of plants and present the applicability for plant parameterization. Results A surface feature histogram based approach from the field of robotics was adapted to close-up laserscans of plants. Local geometric point features describe class characteristics, which were used to distinguish among different plant organs. This approach has been proven and tested on several plant species. Grapevine stems and leaves were classified with an accuracy of up to 98%. The proposed method was successfully transferred to 3D-laserscans of wheat plants for yield estimation. Wheat ears were separated with an accuracy of 96% from other plant organs. Subsequently, the ear volume was calculated and correlated to the ear weight, the kernel weights and the number of kernels. Furthermore the impact of the data resolution was evaluated considering point to point distances between 0.3 and 4.0 mm with respect to the classification accuracy. Conclusion We introduced an approach using surface feature histograms for automated plant organ parameterization. Highly reliable classification results of about 96% for the separation of grapevine and wheat organs have been obtained. This approach was found to be independent of the point to point distance and applicable to multiple plant species. Its reliability, flexibility and its high order of automation make this method well suited for the demands of

  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. [Possible ways of managing cardiovascular prevention: polypharmacy, additional payment or application of evidence based medicine?].

    PubMed

    Gohlke, H

    2005-06-01

    The financial balance of the health care system has changed dramatically due to a longer life expectancy and improved treatment options in elderly patients. More than 80% of cardiovascular events are lifestyle related and potentially preventable. Lifestyle modification is therefore the causal approach to decrease cardiovascular events. Improvement of nutrition and activity habits and prevention of cigarette smoking should start in the kindergarten, school and later at the workplace. A co-operation between medical societies and government institutions is necessary to achieve a population wide modification of lifestyle habits to lower the incidence of cardiovascular events in the population. Individual risk stratification is the basis for pharmacological prevention of cardiovascular events. The concept of the polypill has to be tested in controlled randomised studies.

  2. 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...

  3. 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

  4. Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective.

    PubMed

    Psaltis, Peter J; Simari, Robert D; Rodriguez-Porcel, Martin

    2012-01-01

    Despite preclinical promise, the progress of cell-based therapy to clinical cardiovascular practice has been slowed by several challenges and uncertainties that have been highlighted by the conflicting results of human trials. Most telling has been the revelation that current strategies fall short of achieving sufficient retention and engraftment of cells to meet the ambitious objective of myocardial regeneration. This has sparked novel research into the refinement of cell biology and delivery to overcome these shortcomings. Within this context, molecular imaging has emerged as a valuable tool for providing noninvasive surveillance of cell fate in vivo. Direct and indirect labelling of cells can be coupled with clinically relevant imaging modalities, such as radionuclide single photon emission computed tomography and positron emission tomography, and magnetic resonance imaging, to assess their short- and long-term distributions, along with their viability, proliferation and functional interaction with the host myocardium. This review details the strengths and limitations of the different cell labelling and imaging techniques and their potential application to the clinical realm. We also consider the broader, multifaceted utility of imaging throughout the cell therapy process, providing a discussion of its considerable value during cell delivery and its importance during the evaluation of cardiac outcomes in clinical studies.

  5. 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.

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

    PubMed

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

    2016-08-01

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

  7. Evidence-based cardiovascular care. Family physicians' views of obstacles and opportunities.

    PubMed Central

    Putnam, Wayne; Twohig, Peter L.; Burge, Frederick I.; Jackson, Lois A.; Cox, Jafna L.

    2004-01-01

    OBJECTIVE: To explore obstacles to and opportunities for applying specific lifestyle and pharmacologic recommendations on chronic ischemic heart disease. DESIGN: Qualitative study. SETTING: Rural, town, and city settings in Nova Scotia. PARTICIPANTS: Fifty family physicians caring for patients with cardiovascular (CV) disease. METHOD: Nine focus groups were conducted, audiotaped, and transcribed. Seven recommendations had been selected for discussion based on their relevance to primary care, strength, and class of supporting evidence. Analysis was guided by grounded-theory methodology. MAIN FINDINGS: "Ischemic events" can be powerful motivators for change, whereas the asymptomatic nature of CV risks and distant outcomes can form obstacles. Trust built through previous experiences and the opportunity to repeat important messages can facilitate application of evidence, but patient-physician relationships can also pose obstacles. CONCLUSION: Physicians can take steps to improve care, but success at reducing CV risks depends upon active involvement of many health professionals and community resources. Future guideline implementation should focus on patient-oriented issues, such as comorbidity and treatment preferences. PMID:15526877

  8. Emerging roles for integrated imaging modalities in cardiovascular cell-based therapeutics: a clinical perspective

    PubMed Central

    Psaltis, Peter J.; Simari, Robert D.

    2012-01-01

    Despite preclinical promise, the progress of cell-based therapy to clinical cardiovascular practice has been slowed by several challenges and uncertainties that have been highlighted by the conflicting results of human trials. Most telling has been the revelation that current strategies fall short of achieving sufficient retention and engraftment of cells to meet the ambitious objective of myocardial regeneration. This has sparked novel research into the refinement of cell biology and delivery to overcome these shortcomings. Within this context, molecular imaging has emerged as a valuable tool for providing noninvasive surveillance of cell fate in vivo. Direct and indirect labelling of cells can be coupled with clinically relevant imaging modalities, such as radionuclide single photon emission computed tomography and positron emission tomography, and magnetic resonance imaging, to assess their short- and long-term distributions, along with their viability, proliferation and functional interaction with the host myocardium. This review details the strengths and limitations of the different cell labelling and imaging techniques and their potential application to the clinical realm. We also consider the broader, multifaceted utility of imaging throughout the cell therapy process, providing a discussion of its considerable value during cell delivery and its importance during the evaluation of cardiac outcomes in clinical studies. PMID:21901381

  9. 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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

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

    2017-02-24

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

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

    PubMed Central

    2013-01-01

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

  13. Changes in cardiovascular function based on adrenalin and norepinephrine metabolism in ovariectomized rats.

    PubMed

    Jiang, Hai; Bai, Wenpei; Wang, Wenjuan; Zhang, Jing; Wang, Ke; Liu, Yao; Liu, Shuya; Jia, Jing; Qin, Lihua

    2017-05-01

    Menopause is a cardiovascular risk factor in women, and cardiovascular changes during perimenopause can increase the risk. We observed the influence of plasma adrenalin and norepinephrine and their metabolites on the cardiovascular system and the rectification effect of estrogen in ovariectomized rats. Fifty-four adult female Sprague-Dawley rats were randomly divided into sham (Sham), ovariectomized (OVX), or ovariectomized+estrogen treatment groups (OVX+E), with 18 rats in each. The Sham and OVX groups were given normal saline and the OVX+E group was given estradiol valerate beginning 2weeks after ovariectomy and continuing for 4weeks. Radioimmunoassay, high-performance liquid chromatography, high-performance liquid chromatography-tandem mass spectrometry, and chromatography-spectrophotometry were used to detect estradiol, adrenalin, norepinephrine, metanephrine, and normetanephrine in plasma and vanillylmandelic acid in urine. Echocardiography, Doppler blood flow detection technologyand hamnatodynamometer were applied to assess cardiovascular function. After ovariectomy, levels of estrogen reduced, adrenalin and metanephrine increased, and norepinephrine and normetanephrine in the plasma and vanillylmandelic acid in urine decreased. Symptoms indicative of cardiac diastolic dysfunction, including decreased diastolic left ventricular cavity capacity, increased wall thickness and decreased cardiac rate were observed. Different degrees of vasomotor dysfunction appeared in different peripheral positions, and the tail vessels were in relatively systolic conditions. However, the claw pad vessels were diastolic. Besides, blood pressure also increased. After ovariectomy, estrogen levels reduced and the metabolic processes of adrenalin and norepinephrine changed, which impacted cardiovascular functions. Changes of adrenalin and norepinephrine and its metabolites were correlated with the cardiovascular function. Cardiovascular disease occurred during the perimenopausal

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

    PubMed

    Zankari, Ea; Hasman, Henrik; Kaas, Rolf Sommer; Seyfarth, Anne Mette; Agersø, Yvonne; Lund, Ole; Larsen, Mette Voldby; Aarestrup, Frank M

    2013-04-01

    Antimicrobial susceptibility testing of bacterial isolates is essential for clinical diagnosis, to detect emerging problems and to guide empirical treatment. Current phenotypic procedures are sometimes associated with mistakes and may require further genetic testing. Whole-genome sequencing (WGS) may soon be within reach even for routine surveillance and clinical diagnostics. The aim of this study was to evaluate WGS as a routine tool for surveillance of antimicrobial resistance compared with current phenotypic procedures. Antimicrobial susceptibility tests were performed on 200 isolates originating from Danish pigs, covering four bacterial species. Genomic DNA was purified from all isolates and sequenced as paired-end reads on the Illumina platform. The web servers ResFinder and MLST (www.genomicepidemiology.org) were used to identify acquired antimicrobial resistance genes and MLST types (where MLST stands for multilocus sequence typing). ResFinder results were compared with phenotypic antimicrobial susceptibility testing results using EUCAST epidemiological cut-off values and MLST types. A total of 3051 different phenotypic tests were performed; 482 led to the categorizing of isolates as resistant and 2569 as susceptible. Seven cases of disagreement between tested and predicted susceptibility were observed, six of which were related to spectinomycin resistance in Escherichia coli. Correlation between MLST type and resistance profiles was only observed in Salmonella Typhimurium, where isolates belonging to sequence type (ST) 34 were more resistant than ST19 isolates. High concordance (99.74%) between phenotypic and predicted antimicrobial susceptibility was observed. Thus, antimicrobial resistance testing based on WGS is an alternative to conventional phenotypic methods.

  15. Diagnosis of cardiovascular abnormalities from compressed ECG: a data mining-based approach.

    PubMed

    Sufi, Fahim; Khalil, Ibrahim

    2011-01-01

    Usage of compressed ECG for fast and efficient telecardiology application is crucial, as ECG signals are enormously large in size. However, conventional ECG diagnosis algorithms require the compressed ECG packets to be decompressed before diagnosis can be performed. This added step of decompression before performing diagnosis for every ECG packet introduces unnecessary delay, which is undesirable for cardiovascular diseased (CVD) patients. In this paper, we are demonstrating an innovative technique that performs real-time classification of CVD. With the help of this real-time classification of CVD, the emergency personnel or the hospital can automatically be notified via SMS/MMS/e-mail when a life-threatening cardiac abnormality of the CVD affected patient is detected. Our proposed system initially uses data mining techniques, such as attribute selection (i.e., selects only a few features from the compressed ECG) and expectation maximization (EM)-based clustering. These data mining techniques running on a hospital server generate a set of constraints for representing each of the abnormalities. Then, the patient's mobile phone receives these set of constraints and employs a rule-based system that can identify each of abnormal beats in real time. Our experimentation results on 50 MIT-BIH ECG entries reveal that the proposed approach can successfully detect cardiac abnormalities (e.g., ventricular flutter/fibrillation, premature ventricular contraction, atrial fibrillation, etc.) with 97% accuracy on average. This innovative data mining technique on compressed ECG packets enables faster identification of cardiac abnormality directly from the compressed ECG, helping to build an efficient telecardiology diagnosis system.

  16. Comparison of a modified longitudinal simulation-based advanced cardiovascular life support to a traditional advanced cardiovascular life support curriculum in third-year medical students.

    PubMed

    Ko, Paul Y; Scott, Jay M; Mihai, Aurel; Grant, William D

    2011-10-01

    Simulation is an effective tool for teaching medical students in cardiac arrest management. The purpose of this article is to compare the efficacy of a traditional Advanced Cardiovascular Life Support (ACLS) course versus a modified longitudinal ACLS course using high-fidelity simulation in medical students. One group enrolled in a 2-day traditional ACLS course while another group participated in independent learning over 2 weeks and 2 simulation sessions using Laerdal Sim-Man. The modified curriculum also included environmental fidelity with simulation, access to materials electronically, smaller class sizes, and integration of real experiences in the Emergency Department into their learning. Student performance was measured with a scripted, videotaped mega code, followed by a survey. We enrolled 21 students in a traditional ACLS program and 29 students in the simulation-based program (15 and 26 videos available for analysis). There was no difference in Time to Initiate CPR or Time to Shock between the groups, but the modified curriculum group demonstrated higher performance scores. They also felt better prepared to run the code during a simulation and in a hospital setting compared to students in the traditional ACLS curriculum. Students in a modified longitudinal simulation-based ACLS curriculum demonstrated better proficiency in learning ACLS compared to a traditional curriculum.

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

    PubMed Central

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

    2011-01-01

    Model Organism Databases, including the various plant genome databases, collect and enable access to massive amounts of heterogeneous information, including sequence data, gene product information, images of mutant phenotypes, etc, as well as textual descriptions of many of these entities. While a variety of basic browsing and search capabilities are available to allow researchers to query and peruse the names and attributes of phenotypic data, next-generation search mechanisms that allow querying and ranking of text descriptions are much less common. In addition, the plant community needs an innovative way to leverage the existing links in these databases to search groups of text descriptions simultaneously. Furthermore, though much time and effort have been afforded to the development of plant-related ontologies, the knowledge embedded in these ontologies remains largely unused in available plant search mechanisms. Addressing these issues, we have developed a unique search engine for mutant phenotypes from MaizeGDB. This advanced search mechanism integrates various text description sources in MaizeGDB to aid a user in retrieving desired mutant phenotype information. Currently, descriptions of mutant phenotypes, loci and gene products are utilized collectively for each search, though expansion of the search mechanism to include other sources is straightforward. The retrieval engine, to our knowledge, is the first engine to exploit the content and structure of available domain ontologies, currently the Plant and Gene Ontologies, to expand and enrich retrieval results in major plant genomic databases. Database URL: http:www.PhenomicsWorld.org/QBTA.php PMID:21558151

  18. 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

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

    PubMed

    Hanrieder, Jörg; Wicher, Grzegorz; Bergquist, Jonas; Andersson, Malin; Fex-Svenningsen, Asa

    2011-07-01

    The development of powerful analytical techniques for specific molecular characterization of neural cell types is of central relevance in neuroscience research for elucidating cellular functions in the central nervous system (CNS). This study examines the use of differential protein expression profiling of mammalian neural cells using direct analysis by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). MALDI-MS analysis is rapid, sensitive, robust, and specific for large biomolecules in complex matrices. Here, we describe a newly developed and straightforward methodology for direct characterization of rodent CNS glial cells using MALDI-MS-based intact cell mass spectrometry (ICMS). This molecular phenotyping approach enables monitoring of cell growth stages, (stem) cell differentiation, as well as probing cellular responses towards different stimulations. Glial cells were separated into pure astroglial, microglial, and oligodendroglial cell cultures. The intact cell suspensions were then analyzed directly by MALDI-TOF-MS, resulting in characteristic mass spectra profiles that discriminated glial cell types using principal component analysis. Complementary proteomic experiments revealed the identity of these signature proteins that were predominantly expressed in the different glial cell types, including histone H4 for oligodendrocytes and S100-A10 for astrocytes. MALDI imaging MS was performed, and signature masses were employed as molecular tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination of different cell types with molecular specificity.

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

    PubMed Central

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

    2010-01-01

    Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility. PMID:20368443

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

    PubMed

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

    2011-05-04

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

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

    PubMed

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

    2016-10-07

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

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

    PubMed

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

    2015-07-01

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

  4. 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

  5. Emergence of a dynamic resource partitioning based on the coevolution of phenotypic plasticity in sympatric species.

    PubMed

    Suzuki, Reiji; Arita, Takaya

    2014-07-07

    This paper investigates the coevolutionary dynamics of the phenotypic plasticity in the context of overlap avoidance behaviors of shared niches in sympatric species. Especially, we consider whether and how a differentiation of phenotypic plasticity can emerge under the assumption that there are no initial asymmetric relationships among coevolving species. We construct a minimal model where several different species participate in a partitioning of their shared niches, and evolve their behavioral plasticity to avoid an overlap of their niche use. By conducting evolutionary experiments with various conditions of the number of species and niches, we show that the two different types of asymmetric distributions of phenotypic plasticity emerge depending on the settings of the degree of congestion of the shared niches. In both cases, all species tended to obtain the similar amount of fitness regardless of such differences in their plasticity. We also show that the emerged distributions are coevolutionarily stable in general. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2013-05-29

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

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

    PubMed Central

    2013-01-01

    Background Like other indigenous peoples, the Sami have been exposed to the huge pressures of colonisation, rapid modernisation and subsequent marginalisation. Previous studies among indigenous peoples show that colonialism, rapid modernisation and marginalisation is accompanied by increased stress, an unhealthy cardiovascular risk factor profile and disease burden. Updated data on the general burden of cardiovascular disease among the Sami is lacking. The primary objective of this study was to assess the relationship between marginalisation and self-reported lifetime cardiovascular disease (CVD) by minority/majority status in the rural Sami population of Norway. Methods A cross-sectional population-based study (the SAMINOR study) was carried out in 2003-2004. The overall participation rate was 60.9% and a total of 4027 Sami individuals aged 36-79 years were included in the analyses. Data was collected by self-administrated questionnaires and a clinical examination. Results The logistic regression showed that marginalised Sami living in Norwegian dominated areas were more than twice as likely to report CVD as non-marginalised Sami living in Sami majority areas (OR 2.10, 95% CI: 1.40-3.14). No sex difference was found in the effects of marginalisation on self-reported life-time cardiovascular disease. Moderate to no intermediate effects were seen after including established CVD risk factors. Conclusions This study showed that marginalised Sami living in Norwegian dominated areas were more than twice as likely as non-marginalised Sami from Sami majority areas to report lifetime cardiovascular disease (CVD). Moderate to no intermediate effects were seen after including established CVD risk factors, which suggest little difference in lifestyle related factors. Chronic stress exposure following marginalisation may however be a plausible explanation for some of the observed excess of CVD. PMID:23718264

  8. Cardiovascular complications and mortality after diabetes diagnosis for South Asian and Chinese patients: a population-based cohort study.

    PubMed

    Shah, Baiju R; Victor, J Charles; Chiu, Maria; Tu, Jack V; Anand, Sonia S; Austin, Peter C; Manuel, Douglas G; Hux, Janet E

    2013-09-01

    Many non-European ethnic groups have an increased risk for diabetes; however, the published literature demonstrates considerable uncertainty about the rates of diabetes complications among minority populations. The objective of this study was to determine the risks of cardiovascular complications and of mortality after diabetes diagnosis for South Asian and Chinese patients, compared with European patients. A population-based cohort study identified all 491,243 adults with newly diagnosed diabetes in Ontario, Canada, between April 2002 and March 2009. Subjects were followed until March 2011 for the first occurrence of any cardiovascular complication of diabetes (coronary artery disease, stroke, or lower-extremity amputation) and for all-cause mortality. Median follow-up was 4.7 years. The crude incidence of cardiovascular complications after diabetes diagnosis was 17.9 per 1,000 patient-years among European patients, 12.0 among South Asian patients, and 7.7 among Chinese patients. After adjusting for baseline characteristics, the cause-specific hazard ratios (HRs) for cardiovascular complications relative to European patients were 0.95 (95% CI 0.90-1.00; P = 0.056) and 0.50 (0.46-0.53; P < 0.001) for South Asian and Chinese patients, respectively. Mortality was lower for both minority groups (adjusted HR for South Asian patients 0.56 [95% CI 0.52-0.60]; P < 0.001; for Chinese patients 0.58 [0.55-0.62]; P < 0.001). Chinese patients were at substantially lower risk than European patients for cardiovascular complications after diabetes diagnosis, whereas South Asian patients were at comparable risk. Mortality after diabetes diagnosis was markedly lower for both minority populations.

  9. Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort

    PubMed Central

    Gaziano, Thomas A; Young, Cynthia R; Fitzmaurice, Garrett; Atwood, Sidney; Gaziano, J Michael

    2008-01-01

    Summary Background Around 80% of all cardiovascular deaths occur in developing countries. Assessment of those patients at high risk is an important strategy for prevention. Since developing countries have limited resources for prevention strategies that require laboratory testing, we assessed if a risk prediction method that did not require any laboratory tests could be as accurate as one requiring laboratory information. Methods The National Health and Nutrition Examination Survey (NHANES) was a prospective cohort study of 14 407 US participants aged between 25–74 years at the time they were first examined (between 1971 and 1975). Our follow-up study population included participants with complete information on these surveys who did not report a history of cardiovascular disease (myocardial infarction, heart failure, stroke, angina) or cancer, yielding an analysis dataset N=6186. We compared how well either method could predict first-time fatal and non-fatal cardiovascular disease events in this cohort. For the laboratory-based model, which required blood testing, we used standard risk factors to assess risk of cardiovascular disease: age, systolic blood pressure, smoking status, total cholesterol, reported diabetes status, and current treatment for hypertension. For the non-laboratory-based model, we substituted body-mass index for cholesterol. Findings In the cohort of 6186, there were 1529 first-time cardiovascular events and 578 (38%) deaths due to cardiovascular disease over 21 years. In women, the laboratory-based model was useful for predicting events, with a c statistic of 0·829. The c statistic of the non-laboratory-based model was 0·831. In men, the results were similar (0·784 for the laboratory-based model and 0·783 for the non-laboratory-based model). Results were similar between the laboratory-based and non-laboratory-based models in both men and women when restricted to fatal events only. Interpretation A method that uses non-laboratory-based

  10. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype.

  11. 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

  12. A population-based approach to define body-composition phenotypes.

    PubMed

    Prado, Carla M M; Siervo, Mario; Mire, Emily; Heymsfield, Steven B; Stephan, Blossom C M; Broyles, Stephanie; Smith, Steven R; Wells, Jonathan C K; Katzmarzyk, Peter T

    2014-06-01

    Abnormal body compositions such as high adiposity (HA), low muscle mass (LM), or a combination of the 2 [high adiposity with low muscle mass (HA-LM)] are relevant phenotypes, but data on their prevalence and impact on health are still limited. This is largely because of a lack of a consensus definition for these conditions. Of particular interest is the HA-LM phenotype, also termed "sarcopenic obesity," which may confer greater health risk. We propose a new approach for operationalizing abnormal body-composition phenotypes in a representative adult population. Whole-body dual-energy X-ray absorptiometry data obtained from the 1999-2004 NHANES were analyzed for 13,236 subjects aged ≥18 y (maximum weight and height of 136 kg and 1.96 m, respectively). Sex- and body mass index (BMI)-specific decile groups of appendicular skeletal muscle index (ASMI; kg/m²) and fat mass index (FMI; kg/m²) were developed. Cutoffs for HA and LM were incorporated into a diagnostic framework to characterize 4 specific body-composition phenotypes-low adiposity with high muscle mass, high adiposity with high muscle mass, low adiposity with low muscle mass, and HA-LM-and a subclassification of the phenotypes into classes I, II, and III. Abnormal phenotypes were prevalent across the age spectrum and BMI categories. The association between ASMI or FMI and age was modified by sex and BMI. The prevalence of HA-LM in the whole sample was 10.3% in women and 15.2% in men. The prevalence of all subclasses of HA-LM in obese women and men was 14.7% and 22.9%, respectively. HA-LM class III was more prevalent in obese men (2.3%) than in obese women (0.3%). We developed sex- and BMI-specific reference curves to harmonize the classification of body-composition phenotypes. The application of this classification will be particularly useful in the identification of cases of sarcopenic obesity. The association of these phenotypes with metabolic deregulation and increased disease risk awaits verification.

  13. Automated Discovery and Quantification of Image-Based Complex Phenotypes: A Twin Study of Drusen Phenotypes in Age-Related Macular Degeneration

    PubMed Central

    Quellec, Gwenole; Russell, Stephen R.; Seddon, Johanna M.; Reynolds, Robyn; Scheetz, Todd; Mahajan, Vinit B.; Stone, Edwin M.

    2011-01-01

    Purpose. Determining the relationships between phenotype and genotype of many disorders can improve clinical diagnoses, identify disease mechanisms, and enhance therapy. Most genetic disorders result from interaction of many genes that obscure the discovery of such relationships. The hypothesis for this study was that image analysis has the potential to enable formalized discovery of new visible phenotypes. It was tested in twins affected with age-related macular degeneration (AMD). Methods. Fundus images from 43 monozygotic (MZ) and 32 dizygotic (DZ) twin pairs with AMD were examined. First, soft and hard drusen were segmented. Then newly defined phenotypes were identified by using drusen distribution statistics that significantly separate MZ from DZ twins. The ACE model was used to identify the contributions of additive genetic (A), common environmental (C), and nonshared environmental (E) effects on drusen distribution phenotypes. Results. Four drusen distribution characteristics significantly separated MZ from DZ twin pairs. One encoded the quantity, and the remaining three encoded the spatial distribution of drusen, achieving a zygosity prediction accuracy of 76%, 74%, 68%, and 68%. Three of the four phenotypes had a 55% to 77% genetic effect in an AE model, and the fourth phenotype showed a nonshared environmental effect (E model). Conclusions. Computational discovery of genetically determined features can reveal quantifiable AMD phenotypes that are genetically determined without explicitly linking them to specific genes. In addition, it can identify phenotypes that appear to result predominantly from environmental exposure. The approach is rapid and unbiased, suitable for large datasets, and can be used to reveal unknown phenotype–genotype relationships. PMID:22039249

  14. Cardiovascular Imaging in Mice

    PubMed Central

    Phoon, Colin K.L.; Turnbull, Daniel H.

    2016-01-01

    The mouse is the mammalian model of choice for investigating cardiovascular biology, given our ability to manipulate it by genetic, pharmacologic, mechanical, and environmental means. Imaging is an important approach to phenotyping both function and structure of cardiac and vascular components. This review details commonly used imaging approaches, with a focus on echocardiography and magnetic resonance imaging and brief overviews of other imaging modalities. We also briefly outline emerging imaging approaches but caution that reliability and validity data may be lacking. PMID:26928662

  15. 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

  16. Defining Optimal Health Range for Thyroid Function Based on the Risk of Cardiovascular Disease.

    PubMed

    Chaker, Layal; Korevaar, Tim I M; Rizopoulos, Dimitris; Collet, Tinh-Hai; Völzke, Henry; Hofman, Albert; Rodondi, Nicolas; Cappola, Anne R; Peeters, Robin P; Franco, Oscar H

    2017-08-01

    Reference ranges of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are defined by their distribution in apparently healthy populations (2.5th and 97.5th percentiles), irrespective of disease risk, and are used as cutoffs for defining and clinically managing thyroid dysfunction. To provide proof of concept in defining optimal health ranges of thyroid function based on cardiovascular disease (CVD) mortality risk. In all, 9233 participants from the Rotterdam Study (mean age, 65.0 years) were followed up (median, 8.8 years) from baseline to date of death or end of follow-up period (2012), whichever came first (689 cases of CVD mortality). We calculated 10-year absolute risks of CVD mortality (defined according to the SCORE project) using a Fine and Gray competing risk model per percentiles of TSH and FT4, modeled nonlinearly and with sex and age adjustments. Overall, FT4 level >90th percentile was associated with a predicted 10-year CVD mortality risk >7.5% (P = 0.005). In men, FT4 level >97th percentile was associated with a risk of 10.8% (P < 0.001). In participants aged ≥65 years, absolute risk estimates were <10.0% below the 30th percentile (∼14.5 pmol/L or 1.10 ng/dL) and ≥15.0% above the 97th percentile of FT4 (∼22 pmol/L or 1.70 ng/dL). We describe absolute 10-year CVD mortality risks according to thyroid function (TSH and FT4) and suggest that optimal health ranges for thyroid function can be defined according to disease risk and are possibly sex and age dependent. These results need to be replicated with sufficient samples and representative populations.

  17. 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.

  18. Cardiovascular Events in Patients with Atherothrombotic Disease: A Population-Based Longitudinal Study in Taiwan

    PubMed Central

    Lee, Wen-Hsien; Hsu, Po-Chao; Chu, Chun-Yuan; Su, Ho-Ming; Lee, Chee-Siong; Yen, Hsueh-Wei; Lin, Tsung-Hsien; Voon, Wen-Chol; Lai, Wen-Ter; Sheu, Sheng-Hsiung

    2014-01-01

    Background Atherothrombotic diseases including cerebrovascular disease (CVD), coronary artery disease (CAD), and peripheral arterial disease (PAD), contribute to the major causes of death in the world. Although several studies showed the association between polyvascular disease and poor cardiovascular (CV) outcomes in Asian population, there was no large-scale study to validate this relationship in this population. Methods and Results This retrospective cohort study included patients with a diagnosis of CVD, CAD, or PAD from the database contained in the Taiwan National Health Insurance Bureau during 2001–2004. A total of 19954 patients were enrolled in this study. The atherothrombotic disease score was defined according to the number of atherothrombotic disease. The study endpoints included acute coronary syndrome (ACS), all strokes, vascular procedures, in hospital mortality, and so on. The event rate of ischemic stroke (18.2%) was higher than that of acute myocardial infarction (5.7%) in our patients (P = 0.0006). In the multivariate Cox regression analyses, the adjusted hazard ratios (HRs) of each increment of atherothrombotic disease score in predicting ACS, all strokes, vascular procedures, and in hospital mortality were 1.41, 1.66, 1.30, and 1.14, respectively (P≦0.0169). Conclusions This large population-based longitudinal study in patients with atherothrombotic disease demonstrated the risk of subsequent ischemic stroke was higher than that of subsequent AMI. In addition, the subsequent adverse CV events including ACS, all stroke, vascular procedures, and in hospital mortality were progressively increased as the increase of atherothrombotic disease score. PMID:24647769

  19. 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

  20. Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: population based study.

    PubMed Central

    Everson, S. A.; Lynch, J. W.; Chesney, M. A.; Kaplan, G. A.; Goldberg, D. E.; Shade, S. B.; Cohen, R. D.; Salonen, R.; Salonen, J. T.

    1997-01-01

    OBJECTIVE: To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. DESIGN: Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. SETTING: Eastern Finland. SUBJECTS: 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. MAIN OUTCOME MEASURES: Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. RESULTS: Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P < 0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. CONCLUSIONS: Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis. PMID:9055713

  1. 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

  2. [Cardiovascular screening].

    PubMed

    Pellizzari, Barbara; Siddu, Andrea; Ferro, Antonio; Colonna, Manuela; Mantovani, William; Valsecchi, Massimo; Marensi, Lorenzo; Moro, Alessandro; Brusaferro, Silvio; Cinquetti, Sandro

    2014-01-01

    To evaluate, through active call, lifestyles of an asymptomatic population in order to identify hyperglycaemic subjects and/or high-blood pressure sufferers to dispatch to their GP to perform suitable checking, and subjects to invite to a cardiovascular disease prevention programme because of their lifestyles. Between April 2011 and March 2013, all healthy residents in 6 Local Health Authorities of Regione Veneto aged 45-59 years were invited to join a cardiovascular disease prevention programme. All participants were evaluated through an administered lifestyle questionnaire. Parameters such as blood pressure (BP), glycemia, waist circumference and body mass index were collected and recorded. Participants also received counseling, informational materials on lifestyle and were invited to individual or group health promotion initiatives in relation to personal risk factors. Among the invited, 60.84%(10,346/17,004) adhered. Subjects without risks factors were 23.95%. Subjects with lifestyle risk factors but normal BP and glycemia were 56.59%, while those with altered values for BP and glycemia were 13.9%. The 5.55% of the respondents was not eligible for the study. The results confirmthat a preventive programme based on the citizens active call by the Department of prevention could be an effective tool to identify asymptomatic individuals with unknown hypertension and/or hyperglycaemia and to offer lifestyle interventions to lower the risk of cardiovascular diseases. Since the results were positive, the the Regional Veneto Centre for Disease Prevention and Control (CCMR - Veneto) presented a similar project to the Ministry of Health, involving 12 Italian Regions.

  3. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  5. 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

  6. Glucocorticoids and the Cardiovascular System.

    PubMed

    Goodwin, Julie E

    2015-01-01

    Glucocorticoids affect the developing and mature cardiovascular system in profound and, at times, contradictory ways. The glucocorticoid receptor is ubiquitous in most cell types and conserved across species, highlighting its importance in development and homeostasis. Despite the fact that the glucocorticoid receptor is widely expressed, tissue-specific effects of glucocorticoids may have pronounced effects on whole organism phenotypes. Here we will review the interactions between glucocorticoids and the cardiovascular system.

  7. Obesity and Cardiovascular Disease.

    PubMed

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

    2016-05-27

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

  8. 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

  9. Fixed-dose isosorbide dinitrate-hydralazine: race-based cardiovascular medicine benefit or mirage?

    PubMed

    Ferdinand, Keith C

    2008-01-01

    Race is not a scientific category, but African Americans have increased prevalence and severity of heart failure. The African American Heart Failure trial showed the benefit of a combination of isosorbide dinitrate (a nitric oxide donor) and hydralazine (an antioxidant). Future research may unmask the reason for cardiovascular differences in therapy.

  10. Risk of cardiovascular disease among patients with sarcoidosis: a population-based retrospective cohort study, 1976-2013.

    PubMed

    Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L

    2017-02-01

    A higher incidence of cardiovascular disease (CVD) has been observed in several chronic inflammatory diseases. However, data on sarcoidosis are limited.In this study, 345 patients with incident sarcoidosis in Olmsted County (Minnesota, USA) during 1976-2013 were identified based on comprehensive medical record review. 345 sex- and age-matched comparators were also identified from the same underlying population. Medical records were individually reviewed for CVD, including coronary artery disease, congestive heart failure, atrial fibrillation, cerebrovascular accident, transient ischaemic attack, peripheral arterial disease and abdominal aortic aneurysm. Cox proportional hazards models with adjustment for age, sex, calendar year and cardiovascular risk factors were used to compare the rate of development of CVD between cases and comparators.The prevalence of CVD before the index date was not significantly different between the two groups. Adjusting for age, sex and calendar year, the risk of incident CVD after the index date was significantly elevated among patients with sarcoidosis with an adjusted hazard ratio of 1.57 (95% CI 1.15-2.16). Adjustment for cardiovascular risk factors yielded an adjusted hazard ratio of 1.65 (95% CI 1.08-2.53). Significantly increased risk was also observed for several types of CVD, including coronary artery disease, congestive heart failure, atrial fibrillation and cerebrovascular accident.Increased incidence of CVD among patients with sarcoidosis was demonstrated in this population-based cohort, even after controlling for baseline traditional atherosclerotic risk factors.

  11. Phenotiki: an open software and hardware platform for affordable and easy image-based phenotyping of rosette-shaped plants.

    PubMed

    Minervini, Massimo; Giuffrida, Mario V; Perata, Pierdomenico; Tsaftaris, Sotirios A

    2017-04-01

    Phenotyping is important to understand plant biology, but current solutions are costly, not versatile or are difficult to deploy. To solve this problem, we present Phenotiki, an affordable system for plant phenotyping that, relying on off-the-shelf parts, provides an easy to install and maintain platform, offering an out-of-box experience for a well-established phenotyping need: imaging rosette-shaped plants. The accompanying software (with available source code) processes data originating from our device seamlessly and automatically. Our software relies on machine learning to devise robust algorithms, and includes an automated leaf count obtained from 2D images without the need of depth (3D). Our affordable device (~€200) can be deployed in growth chambers or greenhouse to acquire optical 2D images of approximately up to 60 adult Arabidopsis rosettes concurrently. Data from the device are processed remotely on a workstation or via a cloud application (based on CyVerse). In this paper, we present a proof-of-concept validation experiment on top-view images of 24 Arabidopsis plants in a combination of genotypes that has not been compared previously. Phenotypic analysis with respect to morphology, growth, color and leaf count has not been performed comprehensively before now. We confirm the findings of others on some of the extracted traits, showing that we can phenotype at reduced cost. We also perform extensive validations with external measurements and with higher fidelity equipment, and find no loss in statistical accuracy when we use the affordable setting that we propose. Device set-up instructions and analysis software are publicly available ( http://phenotiki.com).

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

    PubMed Central

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

    2017-01-01

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

  13. Early physiological markers of cardiovascular risk in community based adolescents with a depressive disorder.

    PubMed

    Waloszek, Joanna M; Byrne, Michelle L; Woods, Michael J; Nicholas, Christian L; Bei, Bei; Murray, Greg; Raniti, Monika; Allen, Nicholas B; Trinder, John

    2015-04-01

    Depression is recognised as an independent cardiovascular risk factor in adults. Identifying this relationship early on in life is potentially important for the prevention of cardiovascular disease (CVD). This study investigated whether clinical depression is associated with multiple physiological markers of CVD risk in adolescents from the general community. Participants aged 12-18 years were recruited from the general community and screened for depressive symptoms. Individuals with high and low depressive symptoms were administered a diagnostic interview. Fifty participants, 25 with a current depressive episode and 25 matched healthy controls, subsequently completed cardiovascular assessments. Variables assessed were automatic brachial and continuous beat-to-beat finger arterial blood pressure, heart rate, vascular functioning by pulse amplitude tonometry following reactive hyperaemia and pulse transit time (PTT) at rest. Blood samples were collected to measure cholesterol, glucose and glycohaemoglobin levels and an index of cumulative risk of traditional cardiovascular risk factors was calculated. Depressed adolescents had a significantly lower reactive hyperaemia index and shorter PTT, suggesting deterioration in vascular integrity and structure. Higher fasting glucose and triglyceride levels were also observed in the depressed group, who also had higher cumulative risk scores indicative of increased engagement in unhealthy behaviours and higher probability of advanced atherosclerotic lesions. The sample size and number of males who completed all cardiovascular measures was small. Clinically depressed adolescents had poorer vascular functioning and increased CVD risk compared to controls, highlighting the need for early identification and intervention for the prevention of CVD in depressed youth. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-03-14

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

  15. 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.

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

    PubMed

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

    2015-12-22

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

  17. 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

  18. 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

  19. Guilt by Association: A Phenotype-Based View of the Plant Phosphoinositide Network.

    PubMed

    Gerth, Katharina; Lin, Feng; Menzel, Wilhelm; Krishnamoorthy, Praveen; Stenzel, Irene; Heilmann, Mareike; Heilmann, Ingo

    2017-04-28

    Eukaryotic membranes contain small amounts of phospholipids that have regulatory effects on the physiological functions of cells, tissues, and organs. Phosphoinositides (PIs)-the phosphorylated derivatives of phosphatidylinositol-are one example of such regulatory lipids. Although PIs were described in plants decades ago, their contribution to the regulation of physiological processes in plants is not well understood. In the past few years, evidence has emerged that PIs are essential for plant function and development. Recently reported phenotypes associated with the perturbation of different PIs suggest that some subgroups of PIs influence specific processes. Although the molecular targets of PI-dependent regulation in plants are largely unknown, the effects of perturbed PI metabolism can be used to propose regulatory modules that involve particular downstream targets of PI regulation. This review summarizes phenotypes associated with the perturbation of the plant PI network to categorize functions and suggest possible downstream targets of plant PI regulation.

  20. 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

  1. Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles.

    PubMed Central

    Arredondo-Vega, F X; Santisteban, I; Daniels, S; Toutain, S; Hershfield, M S

    1998-01-01

    Adenosine deaminase (ADA) deficiency causes lymphopenia and immunodeficiency due to toxic effects of its substrates. Most patients are infants with severe combined immunodeficiency disease (SCID), but others are diagnosed later in childhood (delayed onset) or as adults (late onset); healthy individuals with "partial" ADA deficiency have been identified. More than 50 ADA mutations are known; most patients are heteroallelic, and most alleles are rare. To analyze the relationship of genotype to phenotype, we quantitated the expression of 29 amino acid sequence-altering alleles in the ADA-deleted Escherichia coli strain SO3834. Expressed ADA activity of wild-type and mutant alleles ranged over five orders of magnitude. The 26 disease-associated alleles expressed 0.001%-0.6% of wild-type activity, versus 5%-28% for 3 alleles from "partials." We related these data to the clinical phenotypes and erythrocyte deoxyadenosine nucleotide (dAXP) levels of 52 patients (49 immunodeficient and 3 with partial deficiency) who had 43 genotypes derived from 42 different mutations, including 28 of the expressed alleles. We reduced this complexity to 13 "genotype categories," ranked according to the potential of their constituent alleles to provide ADA activity. Of 31 SCID patients, 28 fell into 3 genotype categories that could express <=0.05% of wild-type ADA activity. Only 2 of 21 patients with delayed, late-onset, or partial phenotypes had one of these "severe" genotypes. Among 37 patients for whom pretreatment metabolic data were available, we found a strong inverse correlation between red-cell dAXP level and total ADA activity expressed by each patient's alleles in SO3834. Our system provides a quantitative framework and ranking system for relating genotype to phenotype. PMID:9758612

  2. Metabolite Profiling and Cardiovascular Event Risk: A Prospective Study of Three Population-Based Cohorts

    PubMed Central

    Würtz, Peter; Havulinna, Aki S; Soininen, Pasi; Tynkkynen, Tuulia; Prieto-Merino, David; Tillin, Therese; Ghorbani, Anahita; Artati, Anna; Wang, Qin; Tiainen, Mika; Kangas, Antti J; Kettunen, Johannes; Kaikkonen, Jari; Mikkilä, Vera; Jula, Antti; Kähönen, Mika; Lehtimäki, Terho; Lawlor, Debbie A; Gaunt, Tom R; Hughes, Alun D; Sattar, Naveed; Illig, Thomas; Adamski, Jerzy; Wang, Thomas J; Perola, Markus; Ripatti, Samuli; Vasan, Ramachandran S; Raitakari, Olli T; Gerszten, Robert E; Casas, Juan-Pablo; Chaturvedi, Nish; Ala-Korpela, Mika; Salomaa, Veikko

    2015-01-01

    Background High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. Methods and Results We applied quantitative NMR metabolomics to identify biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the SABRE study (n=2622; 573 events) and British Women’s Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes and medication. When further adjusting for routine lipids, four metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation: 1.18 [95%CI 1.12–1.24]; P=4×10−10) and monounsaturated fatty acid levels (1.17 [1.11–1.24]; P=1×10−8) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89 [0.84–0.94]; P=6×10−5) and docosahexaenoic acid levels (0.90 [0.86–0.95]; P=5×10−5) were associated with lower risk. A risk score incorporating these four biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the two validation cohorts (relative integrated discrimination improvement 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5–10% risk range (net reclassification 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). Conclusions Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high

  3. Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

    PubMed

    Würtz, Peter; Havulinna, Aki S; Soininen, Pasi; Tynkkynen, Tuulia; Prieto-Merino, David; Tillin, Therese; Ghorbani, Anahita; Artati, Anna; Wang, Qin; Tiainen, Mika; Kangas, Antti J; Kettunen, Johannes; Kaikkonen, Jari; Mikkilä, Vera; Jula, Antti; Kähönen, Mika; Lehtimäki, Terho; Lawlor, Debbie A; Gaunt, Tom R; Hughes, Alun D; Sattar, Naveed; Illig, Thomas; Adamski, Jerzy; Wang, Thomas J; Perola, Markus; Ripatti, Samuli; Vasan, Ramachandran S; Raitakari, Olli T; Gerszten, Robert E; Casas, Juan-Pablo; Chaturvedi, Nish; Ala-Korpela, Mika; Salomaa, Veikko

    2015-03-03

    High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P=4×10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6×10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5×10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk

  4. Coreferentiality: A New Method for the Hypothesis-Based Analysis of Phenotypes Characterized by Multivariate Data

    PubMed Central

    Fesel, Constantin

    2012-01-01

    Many multifactorial biologic effects, particularly in the context of complex human diseases, are still poorly understood. At the same time, the systematic acquisition of multivariate data has become increasingly easy. The use of such data to analyze and model complex phenotypes, however, remains a challenge. Here, a new analytic approach is described, termed coreferentiality, together with an appropriate statistical test. Coreferentiality is the indirect relation of two variables of functional interest in respect to whether they parallel each other in their respective relatedness to multivariate reference data, which can be informative for a complex effect or phenotype. It is shown that the power of coreferentiality testing is comparable to multiple regression analysis, sufficient even when reference data are informative only to a relatively small extent of 2.5%, and clearly exceeding the power of simple bivariate correlation testing. Thus, coreferentiality testing uses the increased power of multivariate analysis, however, in order to address a more straightforward interpretable bivariate relatedness. Systematic application of this approach could substantially improve the analysis and modeling of complex phenotypes, particularly in the context of human study where addressing functional hypotheses by direct experimentation is often difficult. PMID:22479494

  5. Pharmacy-based interventions to reduce primary medication nonadherence to cardiovascular medications.

    PubMed

    Fischer, Michael A; Choudhry, Niteesh K; Bykov, Katsiaryna; Brill, Gregory; Bopp, Gregory; Wurst, Aaron M; Shrank, William H

    2014-12-01

    Primary medication nonadherence (PMN) occurs when patients do not fill new prescriptions. Interventions to reduce PMN have not been well described. To determine whether 2 pharmacy-based interventions could decrease PMN. Two sequential interventions with a control group were evaluated after completion. The automated intervention began in 2007 and consisted of phone calls to patients on the third and seventh days after a prescription was processed but remained unpurchased. The live intervention began in 2009 and used calls from a pharmacist or technician to patients who still had not picked up their prescriptions after 8 days. Patients with newly prescribed cardiovascular medications received at CVS community pharmacies. Patients with randomly selected birthdays served as the control population. Patient abandonment of new prescription, defined as not picking up medications within 30 days of initial processing at the pharmacy. The automated intervention included 852,612 patients and 1.2 million prescriptions, with a control group of 9282 patients and 13,178 prescriptions. The live intervention included 121,155 patients and 139,502 prescriptions with a control group of 2976 patients and 3407 prescriptions. The groups were balanced by age, sex, and patterns of prior prescription use. For the automated intervention, 4.2% of prescriptions were abandoned in the intervention group and 4.5% in the control group (P>0.1), with no significant differences for any individual classes of medications. The live intervention was used in a group that had not purchased prescriptions after 8 days and thus had much higher PMN. In this setting 36.9% of prescriptions were abandoned in the intervention group and 41.7% in the control group, a difference of 4.8% (P<0.0001). The difference in abandoned prescriptions for antihypertensives was 6.9% (P<0.0001) but for antihyperlipidemics was only 1.4% (P>0.1). Automated reminder calls had no effect on PMN. Live calls from pharmacists decreased

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

    PubMed

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

    2017-06-28

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

  7. FRET-based calcium imaging: a tool for high-throughput/content phenotypic drug screening in Alzheimer disease.

    PubMed

    Honarnejad, Kamran; Kirsch, Achim K; Daschner, Alexander; Szybinska, Aleksandra; Kuznicki, Jacek; Herms, Jochen

    2013-12-01

    Perturbed intracellular store calcium homeostasis is suggested to play a major role in the pathophysiology of Alzheimer disease (AD). A number of mechanisms have been suggested to underlie the impairment of endoplasmic reticulum calcium homeostasis associated with familial AD-linked presenilin 1 mutations (FAD-PS1). Without aiming at specifically targeting any of those pathophysiological mechanisms in particular, we rather performed a high-throughput phenotypic screen to identify compounds that can reverse the exaggerated agonist-evoked endoplasmic reticulum calcium release phenotype in HEK293 cells expressing FAD-PS1. For that purpose, we developed a fully automated high-throughput calcium imaging assay using a fluorescence resonance energy transfer-based calcium indicator at single-cell resolution. This novel robust assay offers a number of advantages compared with the conventional calcium measurement screening technologies. The assay was employed in a large-scale screen with a library of diverse compounds comprising 20,000 low-molecular-weight molecules, which resulted in the identification of 52 primary hits and 4 lead structures. In a secondary assay, several hits were found to alter the amyloid β (Aβ) production. In view of the recent failure of AD drug candidates identified by target-based approaches, such a phenotypic drug discovery paradigm may present an attractive alternative for the identification of novel AD therapeutics.

  8. 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.

  9. [Results of treatment of patients with prostatic adenoma using silodosin based on an assessment of the phenotype of male sexuality].

    PubMed

    Kogan, M I; Kireev, A Iu

    2013-01-01

    The article presents the results of treatment of 40 patients with prostatic adenoma using silodosin (urorec) at a dose of 8 mg per day. Patients were divided into three groups according to the phenotype of male sexuality based on author's questionnaire. Evaluation of treatment results was performed after 24-week follow-up period. There was a high therapeutic effect of silodosin in all groups of patients with prostatic adenoma, but the greatest effect in terms of reduction of urination disorders and increases of maximum urinary flow rate was achieved in men with normo- and hyposexuality compared with hypersexual men. The development of ejaculation disorders during treatment with silodosin in patients with prostatic adenoma is less typical for the patients with hypersexual phenotype.

  10. [Knowledge of modifiable risk factors for cardiovascular disease among women and the associated factors: a population-based study].

    PubMed

    Bonotto, Gabriel Missaggia; Mendoza-Sassi, Raul Andres; Susin, Lulie Rosane Odeh

    2016-01-01

    The scope of this study was to evaluate the knowledge of modifiable risk factors for cardiovascular disease and its distribution in terms of demographic, socioeconomic, behavioral and biological factors among women living in the State of Rio Grande. It was a cross-sectional population-based study, with the inclusion of women aged 18 years and over. Descriptive, bivariate and multivariable Poisson Regression analysis were performed. The outcome was defined as knowing three or more of the seven risk factors studied (75th percentile). Of the 1,593 respondents, 33% knew three or more factors. The outcome was independently associated with increased likelihood of knowledge among subjects in the 25-44 years old age group, non-white skin color, complete secondary education, higher income and having cardiovascular disease. On the other hand, sedentary women were less likely to have such knowledge. These findings indicate the need for educational activities for enhancing comprehension and knowledge of the factors associated with cardiovascular disease among women, particularly among the poorest and less educated.

  11. 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

  12. Cardiovascular Toxicity of Multi-Tyrosine Kinase Inhibitors in Advanced Solid Tumors: A Population-Based Observational Study

    PubMed Central

    Srikanthan, Amirrtha; Ethier, Josee-Lyne; Ocana, Alberto; Seruga, Bostjan; Krzyzanowska, Monika K.; Amir, Eitan

    2015-01-01

    Background Treatment with small molecule tyrosine kinase inhibitors (TKIs) has improved survival in many cancers, yet has been associated with an increased risk of adverse events. Warnings of cardiovascular events are common in drug labels of many TKIs. Despite these warnings, cardiovascular toxicity of patients treated with TKIs remains unclear. Here, we evaluate the cardiovascular outcomes of advanced cancer patients treated with small molecule tyrosine kinase inhibitors. Methods A population based cohort study was undertaken involving adults aged >18 years in Ontario, Canada, diagnosed with any advanced malignancy between 2006 and 2012. Data were extracted from linked administrative governmental databases. Adults with advanced cancer receiving TKIs were identified and followed throughout the time period. The main outcomes of interest were rates of hospitalization for ischemic heart disease (acute myocardial infarction and angina) or cerebrovascular accidents and death. Results 1642 patients with a mean age of 62.5 years were studied; 1046 were treated with erlotinib, 166 with sorafenib and 430 with sunitinib. Over the 380 day median follow-up period (range 6-1970 days), 1.1% of all patients had ischemic heart events, 0.7% had cerebrovascular accidents and 72.1% died. Rates of cardiovascular events were similar to age and gender-matched individuals without cancer. In a subgroup analysis of treatment patients with a prior history of ischemic heart disease, 3.3% had ischemic heart events while 1.2% had cerebrovascular accidents. Conclusions TKIs do not appear to increase the cause-specific hazard of ischemic heart disease and cerebrovascular accidents compared to age and gender-matched individuals without advanced cancer. PMID:25815472

  13. Predicting dementia in primary care patients with a cardiovascular health metric: a prospective population-based study.

    PubMed

    Hessler, Johannes Baltasar; Ander, Karl-Heinz; Brönner, Monika; Etgen, Thorleif; Förstl, Hans; Poppert, Holger; Sander, Dirk; Bickel, Horst

    2016-07-26

    Improving cardiovascular health possibly decreases the risk of dementia. Primary care practices offer a suitable setting for monitoring and controlling cardiovascular risk factors in the older population. The purpose of the study is to examine the association of a cardiovascular health metric including six behaviors and blood parameters with the risk of dementia in primary care patients. Participants (N = 3547) were insurants aged ≥55 of the largest German statutory health insurance company, who were enrolled in a six-year prospective population-based study. Smoking, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose were assessed by general practitioners at routine examinations. Using recommended cut-offs for each factor, the patients' cardiovascular health was classified as ideal, moderate, or poor. Behaviors and blood parameters sub-scores, as well as a total score, were calculated. Dementia diagnoses were retrieved from health insurance claims data. Results are presented as hazard ratios (HRs) and 95% confidence intervals (95% CIs). Over the course of the study 296 new cases of dementia occurred. Adjusted for age, sex, and education, current smoking (HR = 1.77, 95% CI 1.09-2.85), moderate (1.38, 1.05-1.81) or poor (1.81, 1.32-2.47) levels of physical activity, and poor fasting glucose levels (1.43, 1.02-2.02) were associated with an increased risk of dementia. Body mass index, blood pressure, and cholesterol were not associated with dementia. Separate summary scores for behaviors and blood values, as well as a total score showed no association with dementia. Sensitivity analyses with differently defined endpoints led to similar results. Due to complex relationships of body-mass index and blood pressure with dementia individual components cancelled each other out and rendered the sum-scores meaningless for the prediction of dementia.

  14. Clinical utility of creatinine- and cystatin C-based definition of renal function for risk prediction of primary cardiovascular events in patients with diabetes.

    PubMed

    Schöttker, Ben; Herder, Christian; Müller, Heiko; Brenner, Hermann; Rothenbacher, Dietrich

    2012-04-01

    To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS). CKD was defined as eGFR <60 mL/min/1.73 m(2), estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C-based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50-74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA(1c), and measures of model discrimination and reclassification were assessed. During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C-based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07-2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%. Only the cystatin C-based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.

  15. 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

  16. An automated, cost-effective and scalable, flood-and-drain based root phenotyping system for cereals.

    PubMed

    Slota, Michal; Maluszynski, Miroslaw; Szarejko, Iwona

    2016-01-01

    Genetic studies on the molecular mechanisms of the regulation of root growth require the characterisation of a specific root phenotype to be linked with a certain genotype. Such studies using classical labour-intensive methods are severely hindered due to the technical limitations that are associated with the impeded observation of the root system of a plant during its growth. The aim of the research presented here was to develop a reliable, cost-effective method for the analysis of a plant root phenotype that would enable the precise characterisation of the root system architecture of cereals. The presented method describes a complete system for automatic supplementation and continuous sensing of culture solution supplied to plants that are grown in transparent tubes containing a solid substrate. The presented system comprises the comprehensive pipeline consisting of a modular-based and remotely-controlled plant growth system and customized imaging setup for root and shoot phenotyping. The system enables an easy extension of the experimental capacity in order to form a combined platform that is comprised of parallel modules, each holding up to 48 plants. The conducted experiments focused on the selection of the most suitable conditions for phenotyping studies in barley: an optimal size of the glass beads, diameters of the acrylic tubes, composition of a medium, and a rate of the medium flow. The developed system enables an efficient, accurate and highly repeatable analysis of the morphological features of the root system of cereals. Because a simple and fully-automated control system is used, the experimental conditions can easily be normalised for different species of cereals. The scalability of the module-based system allows its capacity to be adjusted in order to meet the requirements of a particular experiment.

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

    PubMed

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

    2010-01-01

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

  18. Bronchiectasis and the risk of cardiovascular disease: a population-based study

    PubMed Central

    Navaratnam, Vidya; Millett, Elizabeth R C; Hurst, John R; Thomas, Sara L; Smeeth, Liam; Hubbard, Richard B; Brown, Jeremy

    2017-01-01

    Background There are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events. Methods We used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease. Results Pre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)). Conclusion The risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients. PMID:27573451

  19. 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

  20. 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.

  1. MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics.

    PubMed

    Tilstam, Pathricia V; Qi, Dake; Leng, Lin; Young, Lawrence; Bucala, Richard

    2017-07-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions that increasingly is being studied in different aspects of cardiovascular disease. MIF was first identified as a proinflammatory and pro-survival mediator within the immune system, and a second structurally related MIF family member, D-dopachrome tautomerase (a.k.a. MIF-2), was reported recently. Both MIF family members are released by myocardium and modulate the manifestations of cardiovascular disease, specifically in myocardial ischemia. Areas covered: A scientific overview is provided for the involvement of MIF family cytokines in the inflammatory pathogenesis of atherosclerosis, myocardial infarction, and ischemia-reperfusion injury. We summarize findings of experimental, human genetic and clinical studies, and suggest therapeutic opportunities for modulating the activity of MIF family proteins that potentially may be applied in a MIF allele specific manner. Expert opinion: Knowledge of MIF, MIF-2 and their receptor pathways are under active investigation in different types of cardiovascular diseases, and novel therapeutic opportunities are being identified. Clinical translation may be accelerated by accruing experience with MIF-directed therapies currently in human testing in cancer and autoimmunity.

  2. 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.

  3. Changes in cardiovascular risk factors after 5 years of implementation of a population-based program to reduce cardiovascular disease: The Heart of New Ulm Project.

    PubMed

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

    2016-05-01

    Population-based interventions aimed at reducing cardiovascular disease (CVD) hold significant potential and will be increasingly relied upon as the model for health care changes in the United States. The Heart of New Ulm Project is a population-based project with health care, community, and workplace interventions addressing multiple levels of the social-ecological model designed to reduce modifiable CVD risk factors in rural New Ulm, MN. The community is served by one health system, enabling the use of electronic health record data for surveillance. Electronic health record data were extracted at baseline (2008-2009) and 2 follow-up periods (2010-2011, 2012-2013) for residents aged 40 to 79 years. Generalized estimating equations were used to fit longitudinal models of the risk factors. Of 7,855 residents in the target population, 80% had electronic health record data for each period. The prevalence of at goal (blood pressure [BP] <140/90 mm Hg) and (low-density lipoprotein cholesterol [LDL-C] <130 mg/dL) increased from 79.3% to 86.4% and 68.9% to 71.1%, respectively, from baseline to 5 years, with the largest reductions in BP and LDL-C seen in individuals not at goal at baseline. Blood pressure and lipid-lowering medication use increased from 41.8% to 44.0% and 25.3% to 29.1%, respectively. The proportion at goal for glucose increased from 46.9% to 48.2%. The prevalence body mass index <30 kg/m(2) (55%) did not change, whereas the proportion at-goal for high-density lipoprotein decreased from 63.8% to 58%, and smoking showed an increase from 11.3% to 13.6%. In a community participating in a multifaceted, population-based project aimed at reducing modifiable CVD risk factors, significant improvements in BP, LDL-C, and glucose were observed for 5 years, and body mass index remained stable in a state where obesity was increasing. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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

  5. Older Adults, "Malignant" Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study).

    PubMed

    Seliger, Stephen L; de Lemos, James; Neeland, Ian J; Christenson, Robert; Gottdiener, John; Drazner, Mark H; Berry, Jarett; Sorkin, John; deFilippi, Christopher

    2015-06-01

    This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH). The natural history of LVH, an important risk factor for HF, is heterogeneous. NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression. Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers. The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH

  6. 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.

  7. Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen

    PubMed Central

    Cox, Jonathan A. G.; Mugumbate, Grace; Del Peral, Laura Vela-Glez; Jankute, Monika; Abrahams, Katherine A.; Jervis, Peter; Jackenkroll, Stefan; Perez, Arancha; Alemparte, Carlos; Esquivias, Jorge; Lelièvre, Joël; Ramon, Fernando; Barros, David; Ballell, Lluis; Besra, Gurdyal S.

    2016-01-01

    High-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of ‘hit’ compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a ‘hit’ molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target. PMID:27982051

  8. Electronic health records based phenotyping in next-generation clinical trials: a perspective from the NIH Health Care Systems Collaboratory.

    PubMed

    Richesson, Rachel L; Hammond, W Ed; Nahm, Meredith; Wixted, Douglas; Simon, Gregory E; Robinson, Jennifer G; Bauck, Alan E; Cifelli, Denise; Smerek, Michelle M; Dickerson, John; Laws, Reesa L; Madigan, Rosemary A; Rusincovitch, Shelley A; Kluchar, Cynthia; Califf, Robert M

    2013-12-01

    Widespread sharing of data from electronic health records and patient-reported outcomes can strengthen the national capacity for conducting cost-effective clinical trials and allow research to be embedded within routine care delivery. While pragmatic clinical trials (PCTs) have been performed for decades, they now can draw on rich sources of clinical and operational data that are continuously fed back to inform research and practice. The Health Care Systems Collaboratory program, initiated by the NIH Common Fund in 2012, engages healthcare systems as partners in discussing and promoting activities, tools, and strategies for supporting active participation in PCTs. The NIH Collaboratory consists of seven demonstration projects, and seven problem-specific working group 'Cores', aimed at leveraging the data captured in heterogeneous 'real-world' environments for research, thereby improving the efficiency, relevance, and generalizability of trials. Here, we introduce the Collaboratory, focusing on its Phenotype, Data Standards, and Data Quality Core, and present early observations from researchers implementing PCTs within large healthcare systems. We also identify gaps in knowledge and present an informatics research agenda that includes identifying methods for the definition and appropriate application of phenotypes in diverse healthcare settings, and methods for validating both the definition and execution of electronic health records based phenotypes.

  9. Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen.

    PubMed

    Cox, Jonathan A G; Mugumbate, Grace; Del Peral, Laura Vela-Glez; Jankute, Monika; Abrahams, Katherine A; Jervis, Peter; Jackenkroll, Stefan; Perez, Arancha; Alemparte, Carlos; Esquivias, Jorge; Lelièvre, Joël; Ramon, Fernando; Barros, David; Ballell, Lluis; Besra, Gurdyal S

    2016-12-16

    High-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of 'hit' compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a 'hit' molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target.

  10. 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

  11. GMP-based CD133+ cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy

    PubMed Central

    Gaipa, Giuseppe; Tilenni, Manuela; Straino, Stefania; Burba, Ilaria; Zaccagnini, Germana; Belotti, Daniela; Biagi, Ettore; Valentini, Marco; Perseghin, Paolo; Parma, Matteo; Campli, Cristiana Di; Biondi, Andrea; Capogrossi, Maurizio C; Pompilio, Giulio; Pesce, Maurizio

    2010-01-01

    Abstract The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133+ cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133+ cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133+ cells. Validation of CD133+ cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as ‘proofs of principle’ of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133+ cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133+ cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies. PMID:19627397

  12. Multicolor flow cytometry-based cellular phenotyping identifies osteoprogenitors and inflammatory cells in the osteoarthritic subchondral bone marrow compartment.

    PubMed

    Pippenger, B E; Duhr, R; Muraro, M G; Pagenstert, G I; Hügle, T; Geurts, J

    2015-11-01

    The cellular component of subchondral bone is thought to be responsible for aberrant bone remodeling in osteoarthritis (OA). Direct phenotypical analysis of the cellular compartment is critical to better understand the OA disease process. This study provides proof-of-principle for flow cytometry-based phenotyping of isolated subchondral trabecular bone (STB) marrow cells without prior use of cell culture techniques. Tibial plateaus were obtained from OA patients undergoing total knee arthroplasty. Subchondral bone chips were digested with collagenase IA and single cell suspensions were directly phenotyped using flow cytometry. Cells were analyzed for the expression of alkaline phosphatase (ALP) as osteoblast/osteoprogenitor marker and monocyte/macrophage markers (CD14, CD68, HLA-DR, CD115). MTT staining revealed abundant viable cells in the bone marrow compartment of STB prior to digestion, which were efficiently released by collagenase. Within the CD45-negative cell fraction, approximately 20% of the cells were positive for the early osteoblast/osteoprogenitor marker ALP. Within the CD45+ hematopoietic cell fraction, the majority of cells were of monocytic origin (>80%) displaying strong surface expression of CD14. Discreet macrophage populations (CD14+/HLA-DR+/CD68+) and putative osteoclast progenitors (CD45+/HLA-DR-/CD115+) were unequivocally identified. Osteoblast, macrophage and osteoclast progenitor presence in the subchondral bone unit (SBU) was confirmed by (immuno)histochemical staining for osteocalcin, CD68 and tartrate-resistant acid phosphatase, respectively. Flow cytometric analysis is a valuable methodology to study the cellular compartment of STB marrow. This method provides a proof of principle that the whole resident cell population can be directly phenotypically characterized without the prior use of cell culture techniques. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. Review of community-based interventions for prevention of cardiovascular diseases in low- and middle-income countries.

    PubMed

    van de Vijver, Steven; Oti, Samuel; Addo, Juliet; de Graft-Aikins, Ama; Agyemang, Charles

    2012-01-01

    An increasing burden of cardiovascular disease (CVD) is occurring in low- and middle-income countries (LMICs) as a result of urbanisation and globalisation. Low rates of awareness and treatment of risk factors worsen the prognosis in these settings. Prevention of CVD is proven to be cost effective and should be the main intervention. Insight into prevention programmes in LMIC is important in addressing the rising levels of these diseases. To evaluate the effectiveness of the community-based interventions for CVD prevention programmes in LMIC. A literature review with searches in the databases of PubMed, EMBASE, CINAHL, LILACS, African Index Medicus and Google Scholar between 1990 and May 2012. Twenty-six studies involving population-based and high-risk interventions have been included in this review. The content of the population intervention was mainly health promotion through media and health education, and the high-risk approach focused often on education of patients, training of health care providers and implementing treatment guidelines. A few studies had a single intervention on exercising or salt reduction. Most studies showed a significant reduction of cardiovascular risk ranging from lifestyle changes on diet, smoking and alcohol to biomedical outcomes like blood pressure, glucose levels or weight. Some studies showed improved management of risk factors like increased control of hypertension or adherence to medication. There have been effective community-based programmes aimed at reducing cardiovascular risk factors in LMIC but these have generally been limited to the urban poor. Health education with a focus on diet and salt, training of health care providers and implementing treatment guidelines form key elements in successful programmes.

  14. Effects of calcium channel blocker benidipine-based combination therapy on target blood pressure control and cardiovascular outcome: a sub-analysis of the COPE trial.

    PubMed

    Umemoto, Seiji; Ogihara, Toshio; Matsuzaki, Masunori; Rakugi, Hiromi; Ohashi, Yasuo; Saruta, Takao

    2017-04-01

    We compared three benidipine-based regimens-that is, benidipine plus angiotensin receptor blocker (ARB), β-blocker (BB) or thiazide-and found that the benidipine-BB combination was less beneficial in reducing the risk of stroke than the benidipine-thiazide combination. This sub-analysis sought to compare the effects of reaching a target blood pressure (BP) (<140/90 mm Hg) on the cardiovascular outcomes among the three benidipine-based treatment groups in the Combination Therapy of Hypertension to Prevent Cardiovascular Events trial. This sub-analysis included 3001 subjects to evaluate the achievement of target BP at a minimum of three points at 6-month intervals of clinical BP measurements during the study period. After randomization, the patients were categorized into two groups on the basis of achieved on-treatment target BP: a good control (GC) group achieving a BP⩾66.7% of the target and a poor control (PC) group with a BP <66.6% of the target. For each of the two control groups, outcomes were compared among the three treatment groups. The event rates for cardiovascular composite endpoints, stroke and hard cardiovascular events were higher in the PC group than the GC group (P=0.041, P=0.042 and P=0.038, respectively). Within the PC group, hazard ratios for the incidence of cardiovascular events were lower in the benidipine-thiazide group than in the benidipine-BB group (composite cardiovascular events: 2.04, P=0.033; stroke: 4.14, P=0.005; and hard cardiovascular events: 3.52, P=0.009). Within the GC group, the incidence of cardiovascular events was not different among the three treatment regimens. The benidipine-thiazide combination may provide better cardiovascular outcomes than the benidipine-BB combination even in patients with poor BP control.

  15. Effect of age on the relationship of occupational social class with prevalence of modifiable cardiovascular risk factors and cardiovascular diseases. A population-based cross-sectional study from European Prospective Investigation into Cancer - Norfolk (EPIC-Norfolk).

    PubMed

    Myint, Phyo K; Luben, Robert N; Welch, Ailsa A; Bingham, Sheila A; Wareham, Nicholas J; Khaw, Kay-Tee

    2006-01-01

    Previous studies on cardiovascular risk profile in different socioeconomic status were focused on younger populations and many of them have not been able to take into account age and sex differences. To investigate the relationship of occupational social class with the prevalence of cardiovascular disease risk factors and cardiovascular diseases in younger (<65 years) and older (>or=65 years) men and women. A population-based-cross sectional study was conducted in a general community in Norfolk, United Kingdom. Participants were 23,085 men and women aged 40-79 years, recruited from general practice age-sex registers as part of European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk). The prevalence of cardiovascular risk factors and cardiovascular diseases were examined. The prevalence of smoking was significantly higher in those in manual social classes particularly in the younger (<65) age group. Younger women in manual social classes were more likely to be smokers compared to older women in the same social class. Being in manual social classes was associated with higher cholesterol levels in women but lower cholesterol levels in men. Manual social class was associated with higher physical activity in those younger than 65 years but this association was reversed in those 65 years or older. Occupational social class is differently related to cardiovascular risk factors in individuals depending on their age and sex. This may reflect differences in behavior at work and leisure, which vary by sex and pre- and postretirement. Interventions to promote health and reduce social inequalities need to take age and gender into account. Copyright 2006 S. Karger AG, Basel.

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

    PubMed Central

    2013-01-01

    Background A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based text-mining approach that can automatically identify such definitions within text. Results Using an existing knowledge base of 156 autism phenotype definitions and an annotated corpus of 26 source articles containing such definitions, we evaluated and compared the average rank of correctly identified rule definition or corresponding rule template using both our semantic-based approach and a standard term-based approach. We examined three separate scenarios: (1) the snippet of text contained a definition already in the knowledge base; (2) the snippet contained an alternative definition for a concept in the knowledge base; and (3) the snippet contained a definition not in the knowledge base. Our semantic-based approach had a higher average rank than the term-based approach for each of the three scenarios (scenario 1: 3.8 vs. 5.0; scenario 2: 2.8 vs. 4.9; and scenario 3: 4.5 vs. 6.2), with each comparison significant at the p-value of 0.05 using the Wilcoxon signed-rank test. Conclusions Our work shows that leveraging existing domain knowledge in the information extraction of biomedical definitions significantly improves the correct identification of such knowledge within sentences. Our method can thus help researchers rapidly acquire knowledge about biomedical definitions that are specified and evolving within an ever-growing corpus of scientific publications. PMID:23937724

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

    PubMed

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

    2013-08-12

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

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

    PubMed

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

    2016-01-01

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

  19. Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor.

    PubMed

    Moore, Jeffrey R; Leinwand, Leslie; Warshaw, David M

    2012-07-20

    Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electric abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focus on mutations in the cardiac muscle molecular motor, myosin, and its associated light chains. Despite the >300 identified mutations, there is still no clear understanding of how these mutations within the same myosin molecule can lead to the dramatically different clinical phenotypes associated with HCM and DCM. Localizing mutations within myosin's molecular structure provides insight into the potential consequence of these perturbations to key functional domains of the motor. Review of biochemical and biophysical data that characterize the functional capacities of these mutant myosins suggests that mutant myosins with enhanced contractility lead to HCM, whereas those displaying reduced contractility lead to DCM. With gain and loss of function potentially being the primary consequence of a specific mutation, how these functional changes trigger the hypertrophic response and lead to the distinct HCM and DCM phenotypes will be the future investigative challenge.

  20. 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

  1. 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.

  2. 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

  3. Predicting neurological Adverse Drug Reactions based on biological, chemical and phenotypic properties of drugs using machine learning models.

    PubMed

    Jamal, Salma; Goyal, Sukriti; Shanker, Asheesh; Grover, Abhinav

    2017-04-13

    Adverse drug reactions (ADRs) have become one of the primary reasons for the failure of drugs and a leading cause of deaths. Owing to the severe effects of ADRs, there is an urgent need for the generation of effective models which can accurately predict ADRs during early stages of drug development based on integration of various features of drugs. In the current study, we have focused on neurological ADRs and have used various properties of drugs that include biological properties (targets, transporters and enzymes), chemical properties (substructure fingerprints), phenotypic properties (side effects (SE) and therapeutic indications) and a combinations of the two and three levels of features. We employed relief-based feature selection technique to identify relevant properties and used machine learning approach to generated learned model systems which would predict neurological ADRs prior to preclinical testing. Additionally, in order to explain the efficiency and applicability of the models, we tested them to predict the ADRs for already existing anti-Alzheimer drugs and uncharacterized drugs, respectively in side effect resource (SIDER) database. The generated models were highly accurate and our results showed that the models based on chemical (accuracy 93.20%), phenotypic (accuracy 92.41%) and combination of three properties (accuracy 94.18%) were highly accurate while the models based on biological properties (accuracy 82.11%) were highly informative.

  4. Effectiveness of a web-based protocol for the screening and phenotyping of individuals with Tourette syndrome for genetic studies.

    PubMed

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

    2012-12-01

    Genome-wide association studies (GWAS) and other emerging technologies offer great promise for the identification of genetic risk factors for complex psychiatric disorders, yet such studies are constrained by the need for large sample sizes. Web-based collection offers a relatively untapped resource for increasing participant recruitment. Therefore, we developed and implemented a novel web-based screening and phenotyping protocol for genetic studies of Tourette syndrome (TS), a childhood-onset neuropsychiatric disorder characterized by motor and vocal tics. Participants were recruited over a 13-month period through the membership of the Tourette Syndrome Association (TSA; n = 28,878). Of the TSA members contacted, 4.3% (1,242) initiated the questionnaire, and 79.5% (987) of these were enrollment eligible. 63.9% (631) of enrolled participants completed the study by submitting phenotypic data and blood specimens. Age was the only variable that predicted study completion; children and young adults were significantly less likely to be study completers than adults 26 and older. Compared to a clinic-based study conducted over the same time period, the web-based method yielded a 60% larger sample. Web-based participants were older and more often female; otherwise, the sample characteristics did not differ significantly. TS diagnoses based on the web-screen demonstrated 100% accuracy compared to those derived from in-depth clinical interviews. Our results suggest that a web-based approach is effective for increasing the sample size for genetic studies of a relatively rare disorder and that our web-based screen is valid for diagnosing TS. Findings from this study should aid in the development of web-based protocols for other disorders. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2014-01-01

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

  6. Isolation of an ES-Derived Cardiovascular Multipotent Cell Population Based on VE-Cadherin Promoter Activity

    PubMed Central

    Maltabe, Violetta A.; Barka, Eleonora; Kontonika, Marianthi; Florou, Dimitra; Kouvara-Pritsouli, Maria; Roumpi, Maria; Agathopoulos, Simeon; Kolettis, Theofilos M.

    2016-01-01

    Embryonic Stem (ES) or induced Pluripotent Stem (iPS) cells are important sources for cardiomyocyte generation, targeted for regenerative therapies. Several in vitro protocols are currently utilized for their differentiation, but the value of cell-based approaches remains unclear. Here, we characterized a cardiovascular progenitor population derived during ES differentiation, after selection based on VE-cadherin promoter (Pvec) activity. ESCs were genetically modified with an episomal vector, allowing the expression of puromycin resistance gene, under Pvec activity. Puromycin-surviving cells displayed cardiac and endothelial progenitor cells characteristics. Expansion and self-renewal of this cardiac and endothelial dual-progenitor population (CEDP) were achieved by Wnt/β-catenin pathway activation. CEDPs express early cardiac developmental stage-specific markers but not markers of differentiated cardiomyocytes. Similarly, CEDPs express endothelial markers. However, CEDPs can undergo differentiation predominantly to cTnT+ (~47%) and VE-cadherin+ (~28%) cells. Transplantation of CEDPs in the left heart ventricle of adult rats showed that CEDPs-derived cells survive and differentiate in vivo for at least 14 days after transplantation. A novel, dual-progenitor population was isolated during ESCs differentiation, based on Pvec activity. This lineage can self-renew, permitting its maintenance as a source of cardiovascular progenitor cells and constitutes a useful source for regenerative approaches. PMID:28101109

  7. 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

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

    PubMed

    Pey, Jon; Tobalina, Luis; de Cisneros, Joaquín Prada J; Planes, Francisco J

    2013-07-19

    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. 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. 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 contributes to the development of

  9. 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

  10. Renal function and attributable risk of death and cardiovascular hospitalization in patients with cardiovascular risk factors from a registry-based cohort: the Estudio Cardiovascular Valencia-risk study.

    PubMed

    Tellez-Plaza, Maria; Orozco-Beltran, Domingo; Gil-Guillen, Vicente; Pita-Fernandez, Salvador; Navarro-Pérez, Jorge; Pallares, Vicente; Valls, Francisco; Fernandez, Antonio; Perez-Navarro, Ana María; Sanchis, Carlos; Dominguez-Lucas, Alejandro; Martin-Moreno, Jose M; Redon, Josep

    2016-11-01

    Information about the attributable risk associated with renal dysfunction in patients with cardiovascular risk factors is lacking. We aimed to estimate the attributable risk associated with chronic kidney disease Epidemiology Collaboration-estimated glomerular filtration rate (eGFR), for all-cause mortality, and cardiovascular hospitalization. Prospective study of study participants with cardiovascular risk factors in 2008-2012. We included 52 007 cardiovascular disease-free men and women aged 30 years or older with hypertension, diabetes, or dyslipidemia, who underwent routine health examinations in primary care. A total of 6639 (12.8%) patients had eGFR below 60 ml/min per 1.73 m and among them 1782 (3.4%) had 45 ml/min per 1.73 m or lower. During an average follow-up time of 3.2 years, 54.12 deaths, 99.98 coronary heart disease (CHD) hospitalizations, and 90.64 stroke hospitalizations/10 000 person-years were recorded. The population attributable risks associated with having a GFR lower than 60 ml/min per 1.73 m were 6.9% (95% confidence interval = 2.07, 10.65) for all-cause mortality, 6.8% (4.3, 9.4) for CHD hospitalization, and 4.1% (1.02, 7.00) for stroke hospitalization. Participants with increasing number of cardiovascular risk factors displayed increasing population attributable risks associated to a GFR less than 60 ml/min per 1.73 m for all-cause mortality and CHD (P heterogeneity 0.002 and 0.05, respectively). In a large general practice cohort of patients with cardiovascular disease risk factors, decreasing eGFR levels were associated with additional attributed risk of mortality and cardiovascular disease. Our findings underscore that intensified efforts are needed to reduce the cardiovascular disease burden associated to chronic kidney disease.

  11. Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies

    PubMed Central

    McGettigan, Patricia; Henry, David

    2011-01-01

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

  12. 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.

  13. Does Simulation-Based Training Increase Athletic Training Students' Clinical Confidence and Competence in Performing a Cardiovascular Screening?

    PubMed

    Doherty-Restrepo, Jennifer L; Harrelson, K Erin; Swinnie, Tazjanne; Montalvo, Alicia M

    2017-01-01

    The incidence of sudden cardiac death (SCD) in athletes is higher than previously estimated. The need for increased screening to detect cardiac diseases in preparticipation physical examinations (PPE) has become a focus in athletic training. The use of simulation-based training in healthcare professionals' education has increased clinical confidence and competence, but research is limited. To examine if a simulation-based educational intervention can increase athletic training students' self-reported confidence and clinical competence in conducting a cardiovascular screening. Pretest-posttest design. 25 first-year athletic training students in a professional master's program participated. The intervention consisted of a standardized cardiovascular curriculum consisting of a 45-minute, interactive instructor-led session and a 45-minute audio session which included repetitions of heart murmurs. Learner self-reported confidence scale, multiple-choice knowledge exam, and objective structured clinical examination (OSCE) of cardiovascular assessment skills and auditory recognition of heart murmurs were recorded. Self-reported confidence increased significantly from 4.4±2.1 to 9.2±3.0 post-intervention (F=78.7, p<0.001) with a moderately high effect size (n2=0.789). Knowledge exam scores increased significantly from 11.0±2.5 to 13.6±4.0 post-intervention (F=5.3, p=0.031) with a low effect size (n2=0.191). The history-taking assessment of the OSCE increased significantly from 2.6±1.6 to 5.7±1.7 post-intervention (F=70.1, p<0.001) with a moderately high effect size (n2=0.751). The clinical skills assessment of the OSCE increased significantly from 4.1±2.8 to 15.6±1.6 post-intervention (F=415.4, p<0.001) with a high effect size (n2=0.952). Simulation-based training is an effective tool for increasing athletic training students' self-reported confidence and competence in conducting a cardiovascular screening.

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

    NASA Technical Reports Server (NTRS)

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

    2017-01-01

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

  15. 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.

  16. 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

  17. 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.

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

    PubMed

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

    2012-01-01

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

  19. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    PubMed

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-07

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.

  20. 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

  1. Successes and future outlook for microfluidics-based cardiovascular drug discovery.

    PubMed

    Skommer, Joanna; Wlodkowic, Donald

    2015-03-01

    The greatest advantage of using microfluidics as a platform for the assessment of cardiovascular drug action is its ability to finely regulate fluid flow conditions, including flow rate, shear stress and pulsatile flow. At the same time, microfluidics provide means for modifying the vessel geometry (bifurcations, stenoses, complex networks), the type of surface of the vessel walls, and for patterning cells in 3D tissue-like architecture, including generation of lumen walls lined with cells and heart-on-a-chip structures for mimicking ventricular cardiomyocyte physiology. In addition, owing to the small volume of required specimens, microfluidics is ideally suited to clinical situations whereby monitoring of drug dosing or efficacy needs to be coupled with minimal phlebotomy-related drug loss. In this review, the authors highlight potential applications for the currently existing and emerging technologies and offer several suggestions on how to close the development cycle of microfluidic devices for cardiovascular drug discovery. The ultimate goal in microfluidics research for drug discovery is to develop 'human-on-a-chip' systems, whereby several organ cultures, including the vasculature and the heart, can mimic complex interactions between the organs and body systems. This would provide in vivo-like pharmacokinetics and pharmacodynamics for drug ADMET assessment. At present, however, the great variety of available designs does not go hand in hand with their use by the pharmaceutical community.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Conrotto, Davide; Barattero, Roberta; Carbone, Mario; Gambino, Alessio; Sciannameo, Veronica; Ricceri, Fulvio; Conrotto, Federico; Broccoletti, Roberto; Arduino, Paolo G

    2017-06-19

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

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

    PubMed Central

    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/m2 or ≥30 kg/m2), occupational risk potentially related to hypoglycemia, chronic renal failure, and frail elderly status. Through self-monitoring of blood glucose, patients are phenotyped according to the occurrence of fasting/preprandial or postprandial hyperglycemia. In each of these six algorithms, the gradual choice of 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

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

    PubMed

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

    2015-04-15

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

  6. A Comprehensive Lifestyle Peer Group-Based Intervention on Cardiovascular Risk Factors: The Randomized Controlled Fifty-Fifty Program.

    PubMed

    Gómez-Pardo, Emilia; Fernández-Alvira, Juan Miguel; Vilanova, Marta; Haro, Domingo; Martínez, Ramona; Carvajal, Isabel; Carral, Vanesa; Rodríguez, Carla; de Miguel, Mercedes; Bodega, Patricia; Santos-Beneit, Gloria; Peñalvo, Jose Luis; Marina, Iñaki; Pérez-Farinós, Napoleón; Dal Re, Marian; Villar, Carmen; Robledo, Teresa; Vedanthan, Rajesh; Bansilal, Sameer; Fuster, Valentin

    2016-02-09

    Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global cardiovascular risk factor modification are lacking. This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors. A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group-based intervention group (IG) or a self-management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups. Participants' mean age was 42 ± 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 ± 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component. The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment

  7. 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

  8. Heparin-based self-assembling peptide scaffold reestablish chondrogenic phenotype of expanded de-differentiated human chondrocytes.

    PubMed

    Recha-Sancho, Lourdes; Semino, Carlos E

    2016-07-01

    The use of chondrocytes in cell-based therapies for cartilage lesions are limited by quantity and, therefore, require an in vitro expansion. As monolayer culture leads to de-differentiation, different culture techniques are currently under development to recover chondrocyte phenotype after cell expansion. In the present work, we studied the capacity of the bimolecular heparin-based self-assembling peptide scaffold (RAD16-I) as a three-dimensional (3D) culture system to foster reestablishment of chondrogenic phenotype of de-differentiated human Articular Chondrocytes (AC). The culture was performed in a serum-free medium under control and chondrogenic induction and good viability results were observed after 4 weeks of culture in both conditions. Cells changed their morphology to a more elongated shape and established a cellular network that induced the condensation of the constructs in the case of chondrogenic medium, leading to a compacted structure with improved mechanical properties. Specific extracellular matrix (ECM) proteins of mature cartilage, such as collagen type II and aggrecan were up-regulated under chondrogenic medium and significantly enhanced with the presence of heparin in the scaffold. 3D constructs became highly stained with toluidine blue dye after 4 weeks of culture, indicating the presence of synthetized proteoglycans (PGs) by the cells. Interestingly, the full viscoelastic behavior was closely related to that found in chicken native cartilage. Altogether, the results suggest that the 3D culture model described can help de-differentiated human chondrocytes to recover its cartilage phenotype. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1694-1706, 2016.

  9. HIV-1 Viral Load and Phenotypic Antiretroviral Drug Resistance Assays Based on Reverse Transcriptase Activity in Comparison to Amplification Based HIV-1 RNA and Genotypic Assays

    PubMed Central

    Napravnik, Sonia; Cachafeiro, Ada; Stewart, Paul; Eron, Joseph J.; Fiscus, Susan A.

    2009-01-01

    Background Amplification based HIV-1 viral load and genotypic resistance assays are expensive, technologically complex and may be difficult to implement in resource limited settings. Inexpensive, simpler assays are urgently needed. Objectives To determine the suitability of the ExaVir™ Load and ExaVir™ Drug assays for use in patient monitoring. Study Design Specimens from 108 adults were used to compare ExaVir™ Load HIV-1 RT to Amplicor HIV-1 Monitor® HIV-1 RNA, and ExaVir™ Drug phenotype to HIV GenoSure™ genotype. Results HIV-1 RT and HIV-1 RNA levels were comparable (Pearson correlation coefficient 0.83). Most (94%) had detectable results in both assays. The mean difference (HIV-1 RT minus HIV-1 RNA) was -0.21 log10 cps/mL equivalents. Relationship between HIV-1 RT and HIV-1 RNA was not affected by RT mutations, CD4 cell count, or efavirenz (EFV) or nevirapine (NVP) use. Phenotypes were generally consistent with genotype findings for EFV, but not for NVP. Most patients (93.9%) with phenotypic EFV resistance had at least one EFV mutation, while 78.0% of patients with phenotypic NVP resistance had at least one NVP mutation. Eleven of 49 samples tested for EFV susceptibility were found resistant (n=2) or with reduced susceptibility (n=9) despite the absence of genotypic resistance. Eleven of 45 samples tested for NVP susceptibility were found resistant (n=9) or with reduced susceptibility (n=2) with no evidence of genotypic mutations. Conclusions The ExaVir™ Load assay performed well and may be an alternative to amplification based techniques for HIV-1 RNA quantification. The ExaVir™ Drug assay for phenotypic resistance testing requires further evaluation, especially for NVP. PMID:19896416

  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. 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.

  12. 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

  13. Lactation and cardiovascular risk factors in mothers in a population-based study: the HUNT-study

    PubMed Central

    2012-01-01

    Background Lactation has beneficial short term effects on maternal metabolic health, but the long term effects are less well known. Methods We studied the association between lifetime duration of lactation and cardiovascular risk factors in mothers later in life among 21,368 parous women aged 20 to 85 years attending the second Nord-Trøndelag Health Study (HUNT2) in 1995–1997, Norway, a cross-sectional population-based study. General linear modelling was used to calculate mean values of known cardiovascular risk factor levels in five categories of lifetime duration of lactation. Logistic regression was conducted to estimate odds ratios of hypertension, obesity and diabetes. Results Among women aged 50 years or younger, lifetime duration of lactation was significantly and inversely associated with body mass index (P-trend, < 0.001), waist circumference (P-trend, < 0.001), systolic and diastolic blood pressure (both P-trends, < 0.001), and serum levels of triglycerides, total cholesterol and low density lipoprotein cholesterol (all P-trends, < 0.001) after adjustment for covariates. Parous women aged 50 years or younger who had never lactated had higher prevalence of hypertension, obesity and diabetes. In this age group, compared to women who had lactated for 24 months or more, parous women who had never lactated had an OR for hypertension of 1.88 (95% CI 1.41, 2.51), an OR for obesity of 3.37 (95% CI 2.51, 4.51) and an OR for diabetes of 5.87 (95% CI 2.25, 15.3). Among women older than 50 years there were no clear associations. Conclusion Lifetime duration of lactation was associated with long term reduced cardiovascular risk levels in mothers aged 50 years or younger. PMID:22713515

  14. Comparison of Heritability of Cystatin C‐ and Creatinine‐Based Estimates of Kidney Function and Their Relation to Heritability of Cardiovascular Disease

    PubMed Central

    Arpegård, Johannes; Viktorin, Alexander; Chang, Zheng; de Faire, Ulf; Magnusson, Patrik K. E.; Svensson, Per

    2015-01-01

    Background Decreased renal function is an established risk factor for cardiovascular disease (CVD). Causal mechanisms between estimates of renal function and CVD are intricate and investigation of the relative importance of genetic and environmental factors for the variability of these phenotypes could provide new knowledge. Methods and Results Cystatin C and creatinine levels in 12 313 twins were analyzed. Uni‐ and bivariate heritability for these traits and CVD was estimated through structured equation modelling and genome‐wide complex trait analysis (GCTA) in order to independently confirm additive genetic effects. Twin model‐estimated heritability of Cystatin C was 0.55 (95% confidence interval [CI], 0.49 to 0.60) in men, 0.63 (0.59 to 0.66) in women, and 0.60 (0.56 to 0.63) in both sexes combined. For creatinine, heritability estimates were in the same range. Heritability of CVD was 0.39 (0.02 to 0.67) in men and 0.20 (0.00 to 0.61) in women. The phenotypic correlation between Cystatin C and CVD correlation was 0.16 (0.12 to 0.20) in men and 0.17 (0.13 to 0.21) in women, whereas the genetic correlation in males was 0.41 (0.21 to 0.62) while it was non‐significant in females. Trough GCTA, the heritability of Cystatin C and creatinine in both sexes combined was estimated to 0.40 (SE 0.07, P=8E−9) and 0.19 (SE 0.07, P=0.003), respectively. Conclusions Twin model‐based heritability of Cystatin C was higher compared to previous studies. Co‐variation between Cystatin C and CVD in males was partly explained by additive genetic components, indicating that Cystatin C and CVD share genetic influences. The GCTA provided independent evidence for significant contribution of additive genetics to trait variance of Cystatin C. PMID:25589536

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

    PubMed

    Beishuizen, Cathrien R L; Stephan, Blossom C M; van Gool, Willem A; Brayne, Carol; Peters, Ron J G; Andrieu, Sandrine; Kivipelto, Miia; Soininen, Hilkka; Busschers, Wim B; Moll van Charante, Eric P; Richard, Edo

    2016-03-11

    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. 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. 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. 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 was found between groups (6 studies). Web-based interventions have

  16. 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

  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. Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles.

    PubMed

    Ou, Guangshuo; Koga, Makato; Blacque, Oliver E; Murayama, Takashi; Ohshima, Yasumi; Schafer, Jenny C; Li, Chunmei; Yoder, Bradley K; Leroux, Michel R; Scholey, Jonathan M

    2007-05-01

    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.

  19. 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

  20. Effect of crataegus usage in cardiovascular disease prevention: an evidence-based approach.

    PubMed

    Wang, Jie; Xiong, Xingjiang; Feng, Bo

    2013-01-01

    Hawthorn (Crataegus oxyacantha) is a widely used Chinese herb for treatment of gastrointestinal ailments and heart problems and consumed as food. In North America, the role of treatment for heart problems dates back to 1800. Currently, evidence is accumulating from various in vivo and in vitro studies that hawthorn extracts exert a wide range of cardiovascular pharmacological properties, including antioxidant activity, positive inotropic effect, anti-inflammatory effect, anticardiac remodeling effect, antiplatelet aggregation effect, vasodilating effect, endothelial protective effect, reduction of smooth muscle cell migration and proliferation, protective effect against ischemia/reperfusion injury, antiarrhythmic effect, lipid-lowering effect and decrease of arterial blood pressure effect. On the other hand, reviews of placebo-controlled trials have reported both subjective and objective improvement in patients with mild forms of heart failure (NYHA I-III), hypertension, and hyperlipidemia. This paper discussed the underlying pharmacology mechanisms in potential cardioprotective effects and elucidated the clinical applications of Crataegus and its various extracts.

  1. Effect of Crataegus Usage in Cardiovascular Disease Prevention: An Evidence-Based Approach

    PubMed Central

    Wang, Jie; Xiong, Xingjiang; Feng, Bo

    2013-01-01

    Hawthorn (Crataegus oxyacantha) is a widely used Chinese herb for treatment of gastrointestinal ailments and heart problems and consumed as food. In North America, the role of treatment for heart problems dates back to 1800. Currently, evidence is accumulating from various in vivo and in vitro studies that hawthorn extracts exert a wide range of cardiovascular pharmacological properties, including antioxidant activity, positive inotropic effect, anti-inflammatory effect, anticardiac remodeling effect, antiplatelet aggregation effect, vasodilating effect, endothelial protective effect, reduction of smooth muscle cell migration and proliferation, protective effect against ischemia/reperfusion injury, antiarrhythmic effect, lipid-lowering effect and decrease of arterial blood pressure effect. On the other hand, reviews of placebo-controlled trials have reported both subjective and objective improvement in patients with mild forms of heart failure (NYHA I–III), hypertension, and hyperlipidemia. This paper discussed the underlying pharmacology mechanisms in potential cardioprotective effects and elucidated the clinical applications of Crataegus and its various extracts. PMID:24459528

  2. Cardiovascular Disease Among Survivors of Adult-Onset Cancer: A Community-Based Retrospective Cohort Study.

    PubMed

    Armenian, Saro H; Xu, Lanfang; Ky, Bonnie; Sun, Canlan; Farol, Leonardo T; Pal, Sumanta Kumar; Douglas, Pamela S; Bhatia, Smita; Chao, Chun

    2016-04-01

    Cardiovascular diseases (CVDs), including ischemic heart disease, stroke, and heart failure, are well-established late effects of therapy in survivors of childhood and young adult (< 40 years at diagnosis) cancers; less is known regarding CVD in long-term survivors of adult-onset (≥ 40 years) cancer. A retrospective cohort study design was used to describe the magnitude of CVD risk in 36,232 ≥ 2-year survivors of adult-onset cancer compared with matched (age, sex, and residential ZIP code) noncancer controls (n = 73,545) within a large integrated managed care organization. Multivariable regression was used to examine the impact of cardiovascular risk factors (CVRFs; hypertension, diabetes, dyslipidemia) on long-term CVD risk in cancer survivors. Survivors of multiple myeloma (incidence rate ratio [IRR], 1.70; P < .01), carcinoma of the lung/bronchus (IRR, 1.58; P < .01), non-Hodgkin lymphoma (IRR, 1.41; P < .01), and breast cancer (IRR, 1.13; P < .01) had significantly higher CVD risk when compared with noncancer controls. Conversely, prostate cancer survivors had a lower CVD risk (IRR, 0.89; P < .01) compared with controls. Cancer survivors with two or more CVRFs had the highest risk of CVD when compared with noncancer controls with less than two CVRFs (IRR, 1.83 to 2.59; P < .01). Eight-year overall survival was significantly worse among cancer survivors who developed CVD (60%) when compared with cancer survivors without CVD (81%; P < .01). The magnitude of subsequent CVD risk varies according to cancer subtype and by the presence of CVRFs. Overall survival in survivors who develop CVD is poor, emphasizing the need for targeted prevention strategies for individuals at highest risk of developing CVD. © 2016 by American Society of Clinical Oncology.

  3. 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.

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

    PubMed

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

    2016-01-01

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

  5. 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.

  6. Nicotine dependence, depression, and gender: characterizing phenotypes based on withdrawal discomfort, response to smoking, and ability to abstain.

    PubMed

    Pomerleau, Ovide F; Pomerleau, Cynthia S; Mehringer, Ann M; Snedecor, Sandy M; Ninowski, Raphaela; Sen, Ananda

    2005-02-01

    Smoking is often viewed as a comprehensive phenotype rather than a complex set of traits involving intermediate phenotypes. To explore this issue in a laboratory setting, we tested 69 smokers stratified on depression, nicotine dependence, and gender. On the third day of an initial withdrawal period, we tested for differences among participants in uncued and cued craving and withdrawal; on the fourth day, we exposed them to a controlled dose of smoke and assessed them for physiological and hedonic effects and reduction of craving and withdrawal. Following resumption of smoking for at least a week, we then tested participants on their ability to abstain for an 11-day interval. During the withdrawal test, high-depressed smokers and men exhibited elevated craving and withdrawal scores overall, whereas no differences emerged for dependence. Cue exposure produced significant increases in craving but not withdrawal. During the smoke-exposure test, men were significantly more likely than women, and high-depressed smokers more likely than low-depressed smokers, to show evidence of experiencing pleasurable "buzzes." High-dependent smokers showed significant increases in diastolic blood pressure, possibly suggestive of greater sensitivity to nicotine. During the quit test, high-dependent smokers had more difficulty abstaining than low-dependent smokers, and women more than men; no differences emerged based on depression. Independently of group membership, inability to abstain was predicted by increased anxiety, depression, and difficulty concentrating in response to cue exposure. These findings provide support for the existence of phenotypes that can be distinguished by withdrawal symptomatology (primarily driven by depression) and ability to remain abstinent (primarily driven by dependence).

  7. 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

  8. Advantage of MALDI-TOF-MS over biochemical-based phenotyping for microbial identification illustrated on industrial applications.

    PubMed

    Urwyler, S K; Glaubitz, J

    2016-02-01

    Fast microbial identification is becoming increasingly necessary in industry to improve microbial control and reduce biocide consumption. We compared the performances of two systems based on MALDI-TOF MS (VITEK MS and BIOTYPER) and two based on biochemical testing (BIOLOG, VITEK 2 Compact) with genetic methods for the identification of environmental bacteria. At genus level both MALDI-TOF MS-based systems showed the lowest number of false (4%) and approx. 60% correct identifications. In contrast, the biochemical-based systems assigned 25% of the genera incorrectly. The differences were even more apparent at the species level. The BIOTYPER was most conservative, where assigning a species led to the lowest percentage of species identifications (54%) but also to the least wrong assignments (4%). The other three systems showed higher levels of false assignments: 8·7, 40 and 46% respectively. The genus identification performance on four industrial products of the BIOTYPER could be increased up to 94·3% (average 88% of 167 isolates) by evolving the database in a product specific manner. Comparison of the bacterial population in the example of paints, and raw materials used therein, at different production steps demonstrated unequivocally that the contamination of the final paint product originated not from the main raw material. MALDI-TOF-MS has revolutionized speed and precision of microbial identification for clinical isolates outperforming conventional methods. In contrast, few performance studies have been published so far focusing on suitability for particularly industrial applications, geomicrobiology and environmental analytics. This study evaluates the performance of this proteomic phenotyping on such industrial isolates in comparison with biochemical-based phenotyping and genotyping. Further the study exemplifies the power of MALDI-TOF-MS to trace cost-efficiently the dominating cultivable bacterial species throughout an industrial paint production process

  9. Dissecting Gene Expression Changes Accompanying a Ploidy-Based Phenotypic Switch

    PubMed Central

    Cromie, Gareth A.; Tan, Zhihao; Hays, Michelle; Jeffery, Eric W.; Dudley, Aimée M.

    2016-01-01

    Aneuploidy, a state in which the chromosome number deviates from a multiple of the haploid count, significantly impacts human health. The phenotypic consequences of aneuploidy are believed to arise from gene expression changes associated with the altered copy number of genes on the aneuploid chromosomes. To dissect the mechanisms underlying altered gene expression in aneuploids, we used RNA-seq to measure transcript abundance in colonies of the haploid Saccharomyces cerevisiae strain F45 and two aneuploid derivatives harboring disomies of chromosomes XV and XVI. F45 colonies display complex “fluffy” morphologies, while the disomic colonies are smooth, resembling laboratory strains. Our two disomes displayed similar transcriptional profiles, a phenomenon not driven by their shared smooth colony morphology nor simply by their karyotype. Surprisingly, the environmental stress response (ESR) was induced in F45, relative to the two disomes. We also identified genes whose expression reflected a nonlinear interaction between the copy number of a transcriptional regulatory gene on chromosome XVI, DIG1, and the copy number of other chromosome XVI genes. DIG1 and the remaining chromosome XVI genes also demonstrated distinct contributions to the effect of the chromosome XVI disome on ESR gene expression. Expression changes in aneuploids appear to reflect a mixture of effects shared between different aneuploidies and effects unique to perturbing the copy number of particular chromosomes, including nonlinear copy number interactions between genes. The balance between these two phenomena is likely to be genotype- and environment-specific. PMID:27836908

  10. 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

  11. A network-based method for mechanistic investigation of Shexiang Baoxin Pill’s treatment of cardiovascular diseases

    PubMed Central

    Fang, Hai-Yang; Zeng, Hua-Wu; Lin, Li-Mei; Chen, Xing; Shen, Xiao-Na; Fu, Peng; Lv, Chao; Liu, Qun; Liu, Run-Hui; Zhang, Wei-Dong; Zhao, Jing

    2017-01-01

    Shexiang Baoxin Pill (SBP), a traditional Chinese medicine formula, is commonly used to treat cardiovascular disease (CVD) in China. However, the complexity of composition and targets has deterred our understanding of its mechanism of action. Using network pharmacology-based approaches, we established the mechanism of action for SBP to treat CVD by analyzing protein-protein interactions and pathways. The computational results were confirmed at the gene expression level in microarray-based studies. Two of the SBP’s targets were further confirmed at the protein level by Western blot. In addition, we validated the theory that SBP’s plasma absorbed compounds play major therapeutic role in treating CVD. PMID:28272527

  12. Statin-based treatment for cardiovascular risk and non-alcoholic fatty liver disease. Killing two birds with one stone?

    PubMed

    Athyros, Vasilios G; Tziomalos, Konstantinos; Daskalopoulos, Georgios N; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2011-05-01

    Cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and may have a parallel course. Statin treatment alone or in combination with other drugs has a substantially beneficial effect on CVD morbidity and mortality. The question was if these regimens were harmful for the liver. Mounting data suggest that statin monotherapy or statin-based treatments are safe in patients with NAFLD and can improve liver tests and liver ultrasonographic evidence of NAFLD. Recent data suggest that statin-based therapies are beneficial to the liver and at the same time reduce CVD morbidity and mortality in patients with NAFLD more than in subjects without it. These findings suggest that with statins we are able to get two birds with one stone.

  13. Educational inequalities and cardiovascular risk factors. A cross-sectional population-based study in southern Spain.

    PubMed

    Morales-Asencio, José Miguel; Mancera-Romero, José; Bernal-Lopez, Rosa; Martos-Cerezuela, Ildefonso; Baca-Osorio, Antonio J; Moyano-Paris, Maria Teresa; Montiel-Murillo, Juana; Juncosa, Flores Perez; Perez, Rosa Sanchez; Tinahones, Francisco J; Gomez-Huelgas, Ricardo

    2013-05-01

    To determine the prevalence and distribution of modifiable cardiovascular risk factors focused on educational level differences, in an adult population in Southern Spain. Cross-sectional population-based study. Random sample from the adult population assigned to a Primary Health Care Centre in Málaga (Southern Spain), which attends 38,625 inhabitants. Level of education, physical activity, blood pressure, waist perimeter, body mass index, lipid profile, fasting plasma glucose, among others, were assessed. Final sample included 2,270 subjects with a mean age of 43.65 (SD: 16.65), 49.74% male and 50.26% female. 57.6% had none or only primary studies. Overweight was present in 55.8%, smokers were 27.6% and sedentary people 51.9%. Once adjusted by sex and age, all modifiable factors were lower in people with higher education. The highest risks were sedentarism (OR 1.95; 95% CI: 1.16-3.29) and hypertension (OR: 2.07 95% CI: 1.49-2.80) for those with lower education. There is a clear inverse gradient of cardiovascular risk factors and educational level in the study population. Public health and community nurses should develop strong interventions for this challenge and extend their influence to public policies focused on educational inequalities and health. © 2012 Wiley Periodicals, Inc.

  14. 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

  15. Impacting population cardiovascular health through a community-based practice network: update on an ASH-supported collaborative.

    PubMed

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

    2011-08-01

    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 by 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 approximately 1.6 million patients (approximately 700,000 hypertensives). Clinical data are obtained from electronic health records and quarterly provider feedback reports are generated. Hypertension, hypercholesterolemia, and diabetes control rose and South Carolina's ranking improved from 51st to 35th in CVD mortality from 1995 to 2006. The Hypertension Initiative expanded to the Outpatient Quality Improvement Network (O'QUIN) 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, and 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.

  16. 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.

  17. 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

  18. Post-myocardial infarction anxiety or depressive symptoms and risk of new cardiovascular events or death: a population-based longitudinal study.

    PubMed

    Larsen, Karen Kjær; Christensen, Bo; Nielsen, Tine Jepsen; Vestergaard, Mogens

    2014-01-01

    To examine the association between anxiety symptoms 3 months after myocardial infarction (MI) and/or new cardiovascular events and death, taking into account established risk factors, and to compare the results with those of the impact of depressive symptoms. Post-MI anxiety symptoms have been associated with a composite outcome of new cardiovascular events or death, but previous studies have not fully adjusted for potential confounders. It remains unclear whether anxiety symptoms are independently associated with both new cardiovascular events and death. A population-based cohort study of 896 persons (70% of eligible) with first-time MI between 1 January 2009 and 31 December 2009, completing the Hospital Anxiety and Depression Scale, were followed up until 31 July 2012. A total of 239 new cardiovascular events and 94 deaths occurred during 1975 person-years of follow-up. Cox proportional hazards models showed that anxiety symptoms were associated with both new cardiovascular events and death in analysis adjusted for age only. The estimates decreased when adjusted for dyspnea score, physical activity, and depressive symptoms, and anxiety symptoms were no longer associated with new cardiovascular events (hazard ratio [HR] = 1.02, 95% confidence interval [CI] = 0.98-1.07) or with death (HR = 0.94, 95% CI = 0.88-1.01). In fully adjusted models, depressive symptoms remained associated with death (HR = 1.13, 95% CI = 1.05-1.21), but not with new cardiovascular events (HR = 1.02, 95% CI = 0.99-1.06). Post-MI anxiety symptoms were not an independent prognostic risk factor for new cardiovascular events or for death, whereas depressive symptoms were associated with an increased risk of mortality.

  19. Population-based study of out-of-hospital sudden cardiovascular death: incidence and causes of death in middle-aged adults.

    PubMed

    Morentin, Benito; Audicana, Covadonga

    2011-01-01

    The data of mortality of out-of-hospital sudden cardiovascular death in middle-aged adults have been poorly characterized. The aim of this study is to analyze their epidemiological, clinical and pathological characteristics. Population observational study of all cardiovascular deaths in people 35-49 years old in Vizcaya between 2003 and 2008. The data of Mortality Register and Forensic Pathology Service were analyzed. The out-of-hospital sudden deaths subjected to forensic autopsy were identified. 216 of the 465 cardiovascular deaths were sudden deaths. The main cause was ischemic heart disease (N=140/216). Other conditions were: cardiomyopathies (N=32), cerebrovascular diseases (N=19) and sudden arrhythmic death in structurally normal hearts (N=10). The causes varied significantly in relation to gender and age. Ten percent had been diagnosed in life of a cardiovascular disease; 66% had cardiovascular risk factors and 27% had recently consumed ethanol and/or abuse drugs. The incidence of sudden death was 13.2/100,000 inhabitants/year, representing 46% of cardiovascular deaths. The incidence was 3.77 times higher in males than in females and increased with the age. The incidence of sudden death in Vizcaya was lower than in other industrialized countries. In middle-aged adults out-of-hospital sudden cardiac death is the first manifestation of disease in half of all cardiovascular deaths. One challenge in prevention is the development of strategies to identify the highest risk people within the general population at low risk. Studies based on forensic autopsies improve our understanding of cardiovascular mortality. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.