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The Entrance, Australia

Skilton M.R.,University of Sydney | Sullivan T.R.,Royal Prince Alfred Hospital | Ayer J.G.,The Heart Center for Children | Ayer J.G.,University of Sydney | And 9 more authors.
Atherosclerosis | Year: 2014

Objective: Early life is an important period for determining future risk of cardiovascular disease. Carotid extra-medial thickness is a novel noninvasive measure that estimates arterial adventitial thickness, information concerning vascular health not captured by assessment of arterial intima-media thickness alone. We sought to determine whether fetal growth and early postnatal growth are associated with carotid extra-medial thickness in 8 year old children. Methods: Carotid extra-medial thickness was assessed by high-resolution ultrasound in 379 non-diabetic children aged 8-years, with complete data for birth weight, gestational age, early postnatal weight gain and carotid extra-medial thickness. Results: Weight gain during infancy, from birth to 18 months of age, was significantly and positively associated with carotid EMT (11μm per kg length-adjusted weight gain [95% CI 3, 18], P=0.007). This association was significantly stronger in boys than girls (Pheterogeneity=0.005). By contrast, there was no significant association between birth weight and carotid EMT (6μm/kg birth weight [95% CI-12, 24], P=0.51). Conclusion: Excessive weight gain during infancy is associated with increased carotid extra-medial thickness, indicating that the alterations to the vasculature associated with excessive early postnatal growth likely include arterial adventitial thickening. © 2014 Elsevier Ireland Ltd. Source

Ayer J.G.,Royal Prince Alfred Hospital | Ayer J.G.,Heart Research Institute | Ayer J.G.,The Heart Center for Children | Belousova E.G.,Woolcock Institute of Medical Research | And 6 more authors.
PLoS ONE | Year: 2011

Background: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. Objective: To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children. Methods: Data on brachial blood pressure, lung function (FEV 1, FVC, FEV 1/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates. Results: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R 2 =. 02, p = 0.03), FVC (standardised β = -0.29, b = -9.31, partial R 2 = 0.04, p<0.001) and FEV1/FVC (standardised β =. 13, b = 18.4, partial R 2 = 0.02, p = 0.04). Conclusion: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems. © 2011 Ayer et al. Source

Skilton M.R.,University of Sydney | Sullivan T.R.,Royal Prince Alfred Hospital | Ayer J.G.,The Heart Center for Children | Ayer J.G.,University of Sydney | And 6 more authors.
Atherosclerosis | Year: 2012

Objective: Structural modification of the arterial adventitia may be an early event in atherosclerosis. Carotid extra-medial thickness is a new measure of arterial adventitial thickness. We examined the association of cardiovascular risk factors with extra-medial thickness, in childhood. Methods: Carotid extra-medial thickness was assessed by high-resolution ultrasound in 389 non-diabetic children aged 8-years. A non-fasting blood sample was collected from 314 participants. Associations of gender, age, lipoproteins, blood pressure, BMI z-score, waist:height ratio and parental history of early vascular disease, with extra-medial thickness were examined. Results: Carotid extra-medial thickness was lower in girls (r= -163, P= .001) and directly associated with systolic (r= .128, P= .009), diastolic blood pressure (r= .130, P= .009), and height (r= .170, P= .0006). These associations remained after adjustment for carotid intima-media thickness. In multivariable analysis including carotid intima-media thickness, only gender and height were significantly associated with carotid extra-medial thickness. In gender-stratified analysis, the strongest associations with extra-medial thickness were BMI z-score (r= .181, P= .01), height (r= .210, P= .003) and diastolic blood pressure (r= .167, P= .02) for boys; and systolic blood pressure (r= .153, P= .03) and parental history of premature cardiovascular disease (r= .139, P= .05) for girls. The association of BMI z-score with extra-medial thickness differed by gender (P-interaction = .04). Conclusions: Carotid extra-medial thickness is independently associated with gender and height in childhood. Extra-medial thickness may provide important information concerning early arterial health, particularly related to the arterial adventitia. © 2012 Elsevier Ireland Ltd. Source

Fonoudi H.,Royan Institute for Stem Cell Biology and Technology | Ansari H.,Royan Institute for Stem Cell Biology and Technology | Abbasalizadeh S.,Royan Institute for Stem Cell Biology and Technology | Larijani M.R.,Royan Institute for Stem Cell Biology and Technology | And 19 more authors.
Stem Cells Translational Medicine | Year: 2015

Recent advances in the generation of cardiomyocytes (CMs) fromhumanpluripotent stemcells (hPSCs), in conjunctionwith the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy.We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precisemodulation of the differentiation process by smallmolecule activation ofWNT signaling, followed by inactivation of transforming growth factor-b andWNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CMspheroids containing virtually pure (∼90%) CMs in 10 days.Moreover, the developed differentiation strategywas universal,asdemonstratedbytestingmultiplehPSClines (5humanembryonic stem celland4humaninduciblePSClines)without cell sortingor selection.Theproducedh PSC-CMssuccessfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. © AlphaMed Press 2015. Source

Padley J.R.,The Heart Center for Children | Padley J.R.,University of Sydney | Cole A.D.,The Heart Center for Children | Pye V.E.,The Heart Center for Children | And 18 more authors.
Heart Lung and Circulation | Year: 2011

Background: We sought to compare overall mortality with neonatal outcomes over a five year period to define risk factors for mortality and service development priorities. Methods: A retrospective cohort study of surgical outcomes following repair or palliation of structural congenital heart defects January 2005-2010. We defined mortality according to contemporary international guidelines and classified surgical procedures using the Risk Adjustment in Congenital Heart Surgery (RACHS-1) score. The effect of age and weight at operation on mortality and annual variation in case-complexity and surgeon case-mix were assessed. Subgroup analysis was performed in patients who were ≤30 days at operation (neonates). Results: Overall mortality within 30 days of operation or prior to hospital discharge was 1.3 and 1.9%, respectively. Mortality was higher in neonates (6.8%) and low birth weight infants (≤2.5. kg) (12.1%). Mortality was similar in bypass versus non-bypass procedures (odds ratio 0.74, p=0.425). Annual mortality rates were consistent despite a marked increase in case-complexity. Neonates overall required longer periods of intensive care support and were more likely to suffer serious complications compared to older children. Age, weight and RACHS-1 score were independent risk factors for mortality on multivariate analysis. In neonates undergoing bypass procedures, only RACHS-1 score was a significant risk factor. Conclusions: This study provides an accurate and contemporary audit of mortality risk associated with congenital heart surgery. Outcomes compare favourably to international benchmarks but highlight the risks of morbidity and mortality associated with neonatal cardiac surgery. © 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Source

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