1,213 research outputs found

    Placental origins of health & disease:Therapeutic opportunities

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    Placental origins of health & disease:Therapeutic opportunities

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    Effects of municipal smoke-free ordinances on secondhand smoke exposure in the Republic of Korea

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    ObjectiveTo reduce premature deaths due to secondhand smoke (SHS) exposure among non-smokers, the Republic of Korea (ROK) adopted changes to the National Health Promotion Act, which allowed local governments to enact municipal ordinances to strengthen their authority to designate smoke-free areas and levy penalty fines. In this study, we examined national trends in SHS exposure after the introduction of these municipal ordinances at the city level in 2010.MethodsWe used interrupted time series analysis to assess whether the trends of SHS exposure in the workplace and at home, and the primary cigarette smoking rate changed following the policy adjustment in the national legislation in ROK. Population-standardized data for selected variables were retrieved from a nationally representative survey dataset and used to study the policy action’s effectiveness.ResultsFollowing the change in the legislation, SHS exposure in the workplace reversed course from an increasing (18% per year) trend prior to the introduction of these smoke-free ordinances to a decreasing (−10% per year) trend after adoption and enforcement of these laws (β2 = 0.18, p-value = 0.07; β3 = −0.10, p-value = 0.02). SHS exposure at home (β2 = 0.10, p-value = 0.09; β3 = −0.03, p-value = 0.14) and the primary cigarette smoking rate (β2 = 0.03, p-value = 0.10; β3 = 0.008, p-value = 0.15) showed no significant changes in the sampled period. Although analyses stratified by sex showed that the allowance of municipal ordinances resulted in reduced SHS exposure in the workplace for both males and females, they did not affect the primary cigarette smoking rate as much, especially among females.ConclusionStrengthening the role of local governments by giving them the authority to enact and enforce penalties on SHS exposure violation helped ROK to reduce SHS exposure in the workplace. However, smoking behaviors and related activities seemed to shift to less restrictive areas such as on the streets and in apartment hallways, negating some of the effects due to these ordinances. Future studies should investigate how smoke-free policies beyond public places can further reduce the SHS exposure in ROK

    Echo Particle Image/Tracking Velocimetry: Technical Development and In Vivo Applications in Cardiovascular and Cerebrovascular Flows

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    Contrast-enhanced ultrasound (CEUS) imaging utilizes intravascular echogenic microbubbles (1-5μm in diameter) to visualize the blood flow in various organs. In this dissertation, we develop and implement techniques for analyzing the motions of microbubbles to quantify cardiovascular and cerebrovascular flows. Obtaining accurate bubble center locations from noisy CEUS images is a primary challenge. Since the bubble trace is typically modeled as a point scatter convolved with a point spread function (PSF), techniques including blind deconvolution, supervised, and self-supervised learning are introduced and calibrated for identifying the PSF and locating the bubble center. The enhanced CEUS images enable echo particle image velocimetry (echo-PIV) for characterizing 2D cardiovascular flows, and the global-optimized Kalman filter-based echo particle tracking velocimetry (echo-PTV) for determining bubble trajectories which are subsequently used for mapping the cerebral and ocular microcirculation at a spatial resolution of 20μm. These techniques are applied to two applications. First, echo-PIV is used for monitoring the aortic root flow in an adult pig undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO), a life support technology whose parameters can be optimized based on the aortic root hemodynamics. Phase-averaged and instantaneous flow fields show that, for the pig with severe myocardial ischemia, the cardiac ejection velocity, velocity-time integral, and mean arterial pressure (MAP) reach their peak at an ECMO flow rate of 3.0L/min, indicating an optimal flow rate that provides adequate support. Second, we investigate non-invasive methods for estimating intracranial pressure (ICP), a critical parameter for hydrocephalus patients that cannot be invasively measured safely. Echo-PTV is used to map cerebral and ocular microcirculation of pediatric hydrocephalus porcine models for inferring ICP. Results show that accounting for pulse pressure, highly correlated relationships between ICP and cortical microcirculation density are obtained with correlation coefficients beyond 0.85. For cerebral ischemia, nondimensionalized cortical micro-perfusion decreases by an order of magnitude when the ICP exceeds 50% of MAP. Moreover, retinal microcirculation also shows a highly correlated relationship with ICP when accounting for pulse pressure. These findings suggest that CEUS-based microcirculation measurement is a plausible noninvasive method for evaluating the ICP and detecting brain ischemia

    Identifying matrix metalloproteinases as a therapeutic target to protect the coronary microvascular endothelial glycocalyx in diabetic cardiomyopathy

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    Introduction:The coronary microvascular endothelial glycocalyx (EGlx) is a vital regulator of vascular permeability and EGlx damage contributes to the development of diabetic cardiomyopathy. Matrix metalloproteinases 2 and 9 (MMP2/9) have been identified as key enzymes in the degradation of EGlx components, notably syndecan 4, and are upregulated in diabetes. This thesis aimed to investigate if inhibition of MMP2/9 can protect the coronary microvascular EGlx, and improve diastolic function in diabetic cardiomyopathy.Methods:Type 1 diabetes was induced in FVB mice by streptozotocin (STZ) injections. Mice were treated with daily injections of the MMP2/9 inhibitor, SB-3CT, for 2 weeks from 7 weeks post STZ. Echocardiography was utilised to assess heart function and lectin staining for the measurement of EGlx depth. Immunolabelling of heart sections for albumin provided an indication of albumin extravasation. A mechanism of EGlx shedding was investigated in vitro in human coronary microvascular endothelial cells treated with tumour necrosis factor α and SB-3CT.Results:Diabetic mice developed diastolic dysfunction from 6 weeks post STZ. MMP2/9 inhibition reversed diastolic dysfunction, EGlx thinning and albumin extravasation in diabetic animals. In vitro, TNF-α caused an increase in MMP9 activity and syndecan 4 shedding from human coronary microvascular endothelial cells. Treatment with SB-3CT reduced syndecan 4 shedding.Conclusion:This thesis has identified MMPs as a therapeutic target to protect the coronary microvascular EGlx and improve diastolic function in diabetic cardiomyopathy

    Laser Micromachining: An Enabling Technology for Functional Surfaces and Materials

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    L'abstract è presente nell'allegato / the abstract is in the attachmen

    Hemodynamic Quantifications By Contrast-Enhanced Ultrasound:From In-Vitro Modelling To Clinical Validation

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    Photodynamic Therapy

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    This book is dedicated to a topic related to the effects of photodynamic therapy organized by Biomedicines in 2022 (https://www.mdpi.com/topics/photodynamic_therapy). In medicine, the use of photodynamic therapy for the treatment of oncological and non-oncological diseases has been widely documented and well codified. In dermatology, the use varies from oncological to the treatment of chronic wounds, as well as in cosmetology for photo-rejuvenation. The 19 manuscripts published in this book cover all aspects of this therapy, including the discovery of new natural and synthetic photosensitizers, biomaterials and nanotechnology, in vitro and in vivo studies, and clinical trials

    Quantitative Cardiac Magnetic Resonance Imaging Biomarkers for the Characterisation of Ischaemic Cardiomyopathy

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    Our understanding of the processes that determine outcomes in patients with ischaemic cardiomyopathy is based on conventional physiological concepts such as ischaemia and viability. Qualitative methods for characterising these processes tend to be binary and often fail to capture the complexity of the underlying biology. Importantly, these are perhaps inadequate to evaluate treatment effects, including the impact of coronary revascularisation. The aim of this thesis was to deploy novel quantitative cardiac magnetic resonance (CMR) techniques to evaluate and distinguish between the pathophysiological processes that determine outcomes in patients with ischaemic cardiomyopathy, through integration of anatomical, functional, perfusion and tissue characterisation information. The work is centred around the use of coronary artery bypass graft (CABG) surgery as the method for revascularisation, and focuses on the impact of myocardial blood flow alterations on cardiac physiology and clinical outcomes. In this work, I first evaluate the impact of surgical revascularisation on myocardial structure and function in patients with impaired left ventricular (LV) systolic function, using paired assessments before and after CABG. I found that at 6 months following revascularisation, despite improvement in functional capacity, more than a third of total myocardial segments examined are no longer considered revascularised. As a result, the overall augmentation in global myocardial blood flow (MBF) following CABG surgery is significantly blunted. There are however technical concerns regarding the quantitative estimation of myocardial blood flow in patients with coronary artery grafts, particularly in relation to the impact of long coronary grafts on contrast kinetics. I therefore evaluated the impact of arterial contrast delay on myocardial blood flow estimation in patients with left internal mammary artery (LIMA) grafts. I showed that absolute MBF estimation is minimally affected by delayed contrast arrival in patients with LIMA grafts, and that irrespective of graft patency, residual native disease severity is a key determinant of myocardial blood flow. Following these findings, I then assessed the prognostic impact of myocardial blood flow in a large cohort of patients with prior CABG. The only imaging study to date examining the prognostic role of quantitative perfusion indices in this population, it demonstrated that both stress MBF and myocardial perfusion reserve (MPR) independently predict adverse cardiovascular outcomes and all cause-mortality. Finally, using the existing quantitative perfusion technique and its associated framework, I co-developed and implemented a non-invasive, in-line method of measuring pulmonary transit time (PTT) and pulmonary blood volume (PBV) during routine CMR scanning. I then found that both imaging parameters can be used as independent quantitative prognostic biomarkers in patients with known or suspected coronary artery disease
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