Global and directional activation maps for cardiac mapping in electrophysiology

Abstract Cardiac mapping is a necessary step for accurate diagnostics in cardiology. I

Comparison of cardiovascular health profiles across population surveys from five high- to low-income countries

Aims With the greatest burden of cardiovascular disease morbidity and mortality increasingly observed in lower-income countries least prepared for this epidemic, focus is widening from risk factor management alone to primordial prevention to maintain high levels of cardiovascular health (CVH) across the life course. To facilitate this, the American Heart Association (AHA) developed CVH scoring guidelines to evaluate and track CVH. We aimed to compare the prevalence and trajectories of high CVH across the life course using nationally representative adult CVH data from five diverse high- to low-income countries. Methods Surveys with CVH variables (physical activity, cigarette smoking, body mass, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the United States (US). Participants were included if they were 18-69y, not pregnant, and had data for these CVH metrics. Comparable data were harmonized and each of the CVH metrics was scored using AHA guidelines as high (2), moderate (1), or low (0) to create total CVH scores with higher scores representing better CVH. High CVH prevalence by age was compared creating country CVH trajectories. Results The analysis included 28,092 adults (Ethiopia n=7686, 55.2% male; Bangladesh n=6731, 48.4% male; Brazil n=7241, 47.9 % male; England n=2691, 49.5% male, and the US n=3743, 50.3% male). As country income level increased, prevalence of high CVH decreased (>90% in Ethiopia, >68% in Bangladesh and under 65% in the remaining countries). This pattern remained using either five or all six CVH metrics and following exclusion of underweight participants. While a decline in CVH with age was observed for all countries, higher income countries showed lower prevalence of high CVH already by age 18y. Excess body weight appeared the main driver of poor CVH in higher income countries, while current smoking was highest in Bangladesh. Conclusion Harmonization of nationally representative survey data on CVH trajectories with age in 5 highly diverse countries supports our hypothesis that CVH decline with age may be universal. Interventions to promote and preserve high CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where CVH remains relatively high, protection of whole societies from risk factor epidemics may still be feasible.This study was funded with support from the Institute for Global Health, Northwestern University [Catalyzer Award No. 1005]; from the DSI-NRF Centre of Excellence in Human Development hosted at the University of the Witwatersrand in South Africa, and the support of the University of the Witwatersrand research office

Ocean acidification and temperature rise: effects on calcification during early development of the cuttlefish Sepia officinalis

This study investigated the effects of seawater pH (i.e., 8.10, 7.85 and 7.60) and temperature (16 and 19 °C) on (a) the abiotic conditions in the fluid surrounding the embryo (viz. the perivitelline fluid), (b) growth, development and (c) cuttlebone calcification of embryonic and juvenile stages of the cephalopod Sepia officinalis. Egg swelling increased in response to acidification or warming, leading to an increase in egg surface while the interactive effects suggested a limited plasticity of the swelling modulation. Embryos experienced elevated pCO2 conditions in the perivitelline fluid (>3-fold higher pCO2 than that of ambient seawater), rendering the medium under-saturated even under ambient conditions. The growth of both embryos and juveniles was unaffected by pH, whereas 45Ca incorporation in cuttlebone increased significantly with decreasing pH at both temperatures. This phenomenon of hypercalcification is limited to only a number of animals but does not guarantee functional performance and calls for better mechanistic understanding of calcification processes

Regulation of the stem cell marker CD133 is independent of promoter hypermethylation in human epithelial differentiation and cancer

BackgroundEpigenetic control is essential for maintenance of tissue hierarchy and correct differentiation. In cancer, this hierarchical structure is altered and epigenetic control deregulated, but the relationship between these two phenomena is still unclear. CD133 is a marker for adult stem cells in various tissues and tumour types. Stem cell specificity is maintained by tight regulation of CD133 expression at both transcriptional and post-translational levels. In this study we investigated the role of epigenetic regulation of CD133 in epithelial differentiation and cancer.MethodsDNA methylation analysis of the CD133 promoter was done by pyrosequencing and methylation specific PCR; qRT-PCR was used to measure CD133 expression and chromatin structure was determined by ChIP. Cells were treated with DNA demethylating agents and HDAC inhibitors. All the experiments were carried out in both cell lines and primary samples.ResultsWe found that CD133 expression is repressed by DNA methylation in the majority of prostate epithelial cell lines examined, where the promoter is heavily CpG hypermethylated, whereas in primary prostate cancer and benign prostatic hyperplasia, low levels of DNA methylation, accompanied by low levels of mRNA, were found. Moreover, differential methylation of CD133 was absent from both benign or malignant CD133+/α2β1integrinhi prostate (stem) cells, when compared to CD133-/α2β1integrinhi (transit amplifying) cells or CD133-/α2β1integrinlow (basal committed) cells, selected from primary epithelial cultures. Condensed chromatin was associated with CD133 downregulation in all of the cell lines, and treatment with HDAC inhibitors resulted in CD133 re-expression in both cell lines and primary samples.ConclusionsCD133 is tightly regulated by DNA methylation only in cell lines, where promoter methylation and gene expression inversely correlate. This highlights the crucial choice of cell model systems when studying epigenetic control in cancer biology and stem cell biology. Significantly, in both benign and malignant prostate primary tissues, regulation of CD133 is independent of DNA methylation, but is under the dynamic control of chromatin condensation. This indicates that CD133 expression is not altered in prostate cancer and it is consistent with an important role for CD133 in the maintenance of the hierarchical cell differentiation patterns in cancer

Generating Functions for Coherent Intertwiners

We study generating functions for the scalar products of SU(2) coherent intertwiners, which can be interpreted as coherent spin network evaluations on a 2-vertex graph. We show that these generating functions are exactly summable for different choices of combinatorial weights. Moreover, we identify one choice of weight distinguished thanks to its geometric interpretation. As an example of dynamics, we consider the simple case of SU(2) flatness and describe the corresponding Hamiltonian constraint whose quantization on coherent intertwiners leads to partial differential equations that we solve. Furthermore, we generalize explicitly these Wheeler-DeWitt equations for SU(2) flatness on coherent spin networks for arbitrary graphs.Comment: 31 page

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Recommendations for cardiovascular health and disease surveillance for 2030 and beyond: A policy statement from the american heart association

The release of the American Heart Association's 2030 Impact Goal and associated metrics for success underscores the importance of cardiovascular health and cardiovascular disease surveillance systems for the acquisition of information sufficient to support implementation and evaluation. The aim of this policy statement is to review and comment on existing recommendations for and current approaches to cardiovascular surveillance, identify gaps, and formulate policy implications and pragmatic recommendations for transforming surveillance of cardiovascular disease and cardiovascular health in the United States. The development of community platforms coupled with widespread use of digital technologies, electronic health records, and mobile health has created new opportunities that could greatly modernize surveillance if coordinated in a pragmatic matter. However, technology and public health and scientific mandates must be merged into action. We describe the action and components necessary to create the cardiovascular health and cardiovascular disease surveillance system of the future, steps in development, and challenges that federal, state, and local governments will need to address. Development of robust policies and commitment to collaboration among professional organizations, community partners, and policy makers are critical to ultimately reduce the burden of cardiovascular disease and improve cardiovascular health and to evaluate whether national health goals are achieved

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

INTRODUCTION: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). METHODS: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. RESULTS: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. CONCLUSION: This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

Factors Associated With the Use of a Salt Substitute in Rural China.

Importance: Lowering sodium intake reduces blood pressure and may reduce the risk of cardiovascular diseases. The use of reduced-sodium salt (a salt substitute) may achieve sodium reduction, but its effectiveness may be associated with the context of its use. Objective: To identify factors associated with the use of salt substitutes in rural populations in China within the Salt Substitute and Stroke Study, a large-scale cluster randomized trial. Design, Setting, and Participants: This sequential mixed-methods qualitative evaluation, conducted from July 2 to August 28, 2018, in rural communities across 3 provinces in China, included a quantitative survey, collection of 24-hour urine samples, and face-to-face interviews. A random subsample of trial participants, selected from the 3 provinces, completed the quantitative survey (n = 1170) and provided urine samples (n = 1025). Interview respondents were purposively selected from the intervention group based on their different ranges of urinary sodium excretion levels. Statistical analysis was performed from September 18, 2018, to February 22, 2019. Exposures: The intervention group of the Salt Substitute and Stroke Study was provided with the free salt substitute while the control group continued to use regular salt. Main Outcomes and Measures: Knowledge, attitudes, and behaviors regarding the use of the salt substitute were measured using quantitative surveys, and urinary sodium levels were measured using 24-hour urine samples. Contextual factors were explored through semistructured interviews and integrated findings from surveys and interviews. Results: A total of 1170 individuals participated in the quantitative survey. Among the 1025 participants with successful urine samples, the mean (SD) age was 67.4 (7.5) years, and 502 (49.0%) were female. The estimated salt intake of participants who believed that high salt intake was good for health was higher; however, it was not significantly different (0.84 g/d [95% CI, -0.04 to 1.72 g/d]) from those who believed that high salt intake was bad for health. Thirty individuals participated in the qualitative interviews (18 women [60.0%]; mean [SD] age, 70.3 [6.0] years). Quantitative and qualitative data indicated high acceptability of and adherence to the salt substitute. Contextual factors negatively associated with the use of the salt substitute included a lack of knowledge about the benefits associated with salt reduction and consumption of high-sodium pickled foods. In addition, reduced antihypertensive medication was reported by a few participants using the salt substitute. Conclusions and Relevance: This study suggests that lack of comprehensive understanding of sodium reduction and salt substitutes and habitual consumption of high-sodium foods (such as pickled foods) were the main barriers to the use of salt substitutes to reduce sodium intake. These factors should be considered in future population-based, sodium-reduction interventions