Search

Lina Shibib,1 Mo Al-Qaisi,1 Nicola Guess,2 Alexander D Miras,3 Steve E Greenwald,4 Marc Pelling,1 Ahmed Ahmed1 1Department of Surgery and Cancer, Imperial College London, London, UK; 2Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, UK; 3School of Medicine, Ulster University, Coleraine, UK; 4Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UKCorrespondence: Mo Al-Qaisi, Email mrcgp74@yahoo.co.ukAbstract: This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose “excursions” being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins – prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.Keywords: glycemic response, post-prandial, hyperglycemia, diabetes, acarbose, GLP-1, metformin, plant fibre, whey protein, gastric emptying, intestinal absorption, glycemic index, glucose excursion

Lina Shibib,1 Mo Al-Qaisi,1 Ahmed Ahmed,1 Alexander D Miras,2 David Nott,1 Marc Pelling,1 Stephen E Greenwald,3 Nicola Guess4 1Department of Surgery and Cancer, Imperial College London, London, UK; 2Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; 3Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK; 4School of Life Sciences, Westminster University, London, UKCorrespondence: Mo Al-Qaisi, Imperial Weight Centre, Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY, UK, Tel +44 7968 016315, Email mrcgp74@yahoo.co.ukAbstract: Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.Keywords: weight loss, very low energy, very low calorie, bariatric surgery, orlistat, electrical muscle stimulation, low carbohydrate, behaviour change, diabetes reversal, diabetes remission

Falls among the elderly are a common and serious health risk that can lead to physical injuries and other complications. To promptly detect and respond to fall events, radar-based fall detection systems have gained widespread attention. In this paper, a deep learning model is proposed based on the frequency spectrum of radar signals, called the convolutional bidirectional long short-term memory (CB-LSTM) model. The introduction of the CB-LSTM model enables the fall detection system to capture both temporal sequential and spatial features simultaneously, thereby enhancing the accuracy and reliability of the detection. Extensive comparison experiments demonstrate that our model achieves an accuracy of 98.83% in detecting falls, surpassing other relevant methods currently available. In summary, this study provides effective technical support using the frequency spectrum and deep learning methods to monitor falls among the elderly through the design and experimental validation of a radar-based fall detection system, which has great potential for improving quality of life for the elderly and providing timely rescue measures.

Background: The curved planar reformation (CPR) technique is one of the most commonly used methods in clinical practice to locate coronary arteries in medical images., Purpose: The artery centerline is the cornerstone for the generation of the CPR image. Here, we describe the development of a new fully automatic artery centerline tracker with the aim of increasing the efficiency and accuracy of the process., Methods: We propose a COronary artery Centerline Tracker (COACT) framework which consists of an ostium point finder (OPFinder) model, an intersection point detector (IPDetector) model and a set of centerline tracking strategies. The output of OPFinder is the ostium points. The function of the IPDetector is to predict the intersections of a sample sphere and the centerlines. The centerline tracking process starts from two ostium points detected by the OPFinder, and combines the results of the IPDetector with a series of strategies to gradually reconstruct the coronary artery centerline tree., Results: Two coronary CT angiography (CCTA) datasets were used to validate the models. Dataset1 contains 160 cases (32 for test and 128 for training) and dataset2 contains 70 cases (20 for test and 50 for training). The results show that the average distance between the ostium points predicted by the OPFinder and the manually annotated ostium points was 0.88 mm, which is similar to the differences between the results obtained by two observers (0.85 mm). For the IPDetector, the average overlap of the predicted and ground truth intersection points was 97.82% and this is also close to the inter-observer agreement of 98.50%. For the entire coronary centerline tree, the overlap between the results obtained by COACT and the gold standard was 94.33%, which is slightly lower than the inter-observer agreement, 98.39%., Conclusions: We have developed a fully automatic centerline tracking method for CCTA scans and achieved a satisfactory result. The proposed algorithms are also incorporated in the medical image analysis platform TIMESlice (https://slice-doc.netlify.app) for further studies., (© 2023 American Association of Physicists in Medicine.)

Background and Objective: Aortic blood pressure (ABP) is a more effective prognostic indicator of cardiovascular disease than peripheral blood pressure. A highly accurate algorithm for non-invasively deriving the ABP wave, based on ultrasonic measurement of aortic flow combined with peripheral pulse wave measurements, has been proposed elsewhere. However, it has remained at the proof-of-concept stage because it requires a priori knowledge of the ABP waveform to calculate aortic pulse wave velocity (PWV). The objective of this study is to transform this proof-of-concept algorithm into a clinically feasible technique., Methods: We used the Bramwell-Hill equation to non-invasively calculate aortic PWV which was then used to reconstruct the ABP waveform from non-invasively determined aortic blood flow velocity, aortic diameter, and radial pressure. The two aortic variables were acquired by an ultrasound system from 90 subjects, followed by recordings of radial pressure using a SphygmoCor device. The ABPs estimated by the new algorithm were compared with reference values obtained by cardiac catheterization (invasive validation, 8 subjects aged 62.3 ± 12.7 years) and a SphygmoCor device (non-invasive validation, 82 subjects aged 45.0 ± 17.8 years)., Results: In the invasive comparison, there was good agreement between the estimated and directly measured pressures: the mean error in systolic blood pressure (SBP) was 1.4 ± 0.8 mmHg; diastolic blood pressure (DBP), 0.9 ± 0.8 mmHg; mean blood pressure (MBP), 1.8 ± 1.2 mmHg and pulse pressure (PP), 1.4 ± 1.1 mmHg. In the non-invasive comparison, the estimated and directly measured pressures also agreed well: the errors being: SBP, 2.0 ± 1.4 mmHg; DBP, 0.8 ± 0.1 mmHg; MBP, 0.1 ± 0.1 mmHg and PP, 2.3 ± 1.6 mmHg. The significance of the differences in mean errors between calculated and reference values for SBP, DBP, MBP and PP were assessed by paired t-tests. The agreement between the reference methods and those obtained by applying the new approach was also expressed by correlation and Bland-Altman plots., Conclusion: The new method proposed here can accurately estimate ABP, allowing this important variable to be obtained non-invasively, using standard, well validated measurement techniques. It thus has the potential to relocate ABP estimation from a research environment to more routine use in the cardiac clinic., Short Abstract: A highly accurate algorithm for non-invasively deriving the ABP wave has been proposed elsewhere. However, it has remained at the proof-of-concept stage because it requires a priori knowledge of the ABP waveform to calculate aortic pulse wave velocity (PWV). This study aims to transform this proof-of-concept algorithm into a clinically feasible technique. We used the Bramwell-Hill equation to non-invasively calculate aortic PWV which was then used to reconstruct the ABP waveform. The ABPs estimated by the new algorithm were compared with reference values obtained by cardiac catheterization or a SphygmoCor device. The results showed that there was good agreement between the estimated and directly measured pressures. The new method proposed can accurately estimate ABP, allowing this important variable to be obtained non-invasively, using standard, well validated measurement techniques. It thus has the potential to relocate ABP estimation from a research environment to more routine use in the cardiac clinic., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coronary artery segmentation is an essential procedure in the computer-aided diagnosis of coronary artery disease. It aims to identify and segment the regions of interest in the coronary circulation for further processing and diagnosis. Currently, automatic segmentation of coronary arteries is often unreliable because of their small size and poor distribution of contrast medium, as well as the problems that lead to over-segmentation or omission. To improve the performance of convolutional-neural-network (CNN) based coronary artery segmentation, we propose a novel automatic method, DR-LCT-UNet, with two innovative components: the Dense Residual (DR) module and the Local Contextual Transformer (LCT) module. The DR module aims to preserve unobtrusive features through dense residual connections, while the LCT module is an improved Transformer that focuses on local contextual information, so that coronary artery-related information can be better exploited. The LCT and DR modules are effectively integrated into the skip connections and encoder-decoder of the 3D segmentation network, respectively. Experiments on our CorArtTS2020 dataset show that the dice similarity coefficient (DSC), Recall, and Precision of the proposed method reached 85.8%, 86.3% and 85.8%, respectively, outperforming 3D-UNet (taken as the reference among the 6 other chosen comparison methods), by 2.1%, 1.9%, and 2.1%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Xu, Wang, Yang, Sun, Yang and Greenwald.)

Automatic coronary artery segmentation is of great value in diagnosing coronary disease. In this paper, we propose an automatic coronary artery segmentation method for coronary computerized tomography angiography (CCTA) images based on a deep convolutional neural network. The proposed method consists of three steps. First, to improve the efficiency and effectiveness of the segmentation, a 2D DenseNet classification network is utilized to screen out the non-coronary-artery slices. Second, we propose a coronary artery segmentation network based on the 3D-UNet, which is capable of extracting, fusing and rectifying features efficiently for accurate coronary artery segmentation. Specifically, in the encoding process of the 3D-UNet network, we adapt the dense block into the 3D-UNet so that it can extract rich and representative features for coronary artery segmentation; In the decoding process, 3D residual blocks with feature rectification capability are applied to improve the segmentation quality further. Third, we introduce a Gaussian weighting method to obtain the final segmentation results. This operation can highlight the more reliable segmentation results at the center of the 3D data blocks while weakening the less reliable segmentations at the block boundary when merging the segmentation results of spatially overlapping data blocks. Experiments demonstrate that our proposed method achieves a Dice Similarity Coefficient (DSC) value of 0.826 on a CCTA dataset constructed by us. The code of the proposed method is available at https://github.com/alongsong/3D_CAS.

Background and Objective: Aortic pressure (P a ) is important for the diagnosis of cardiovascular disease. However, its direct measurement is invasive, not risk-free, and relatively costly. In this paper, a new simplified Kalman filter (SKF) algorithm is employed for the reconstruction of the P a waveform using dual peripheral artery pressure waveforms., Methods: P a waveforms obtained in a previous study were collected from 25 patients. Simultaneously, radial and femoral pressure waveforms were generated from two simulation experiments, using transfer functions. In the first, the transfer function is a known finite impulse response; and in the second, it is derived from a tube-load model. To analyze the performance of the proposed SKF algorithm, variable amounts of noise were added to the observed output signal, to give a range of signal-to-noise ratios (SNRs). Additionally, central aortic, brachial and femoral pressure waveforms were simultaneously collected from 2 Sprague-Dawley rats and the measured and reconstructed P a waveforms were compared., Results: The proposed SKF algorithm outperforms canonical correlation analysis (CCA), which is the current state-of-the-art blind system identification method for the non-invasive estimation of central aortic blood pressure. It is also shown that the proposed SKF algorithm is more noise-tolerant than the CCA algorithm over a wide range of SNRs., Conclusion: The simulations and animal experiments illustrate that the proposed SKF algorithm is accurate and stable in the face of low SNRs. Improved methods for estimating central blood pressure as a measure of cardiac load adds to their value as a prognostic and diagnostic tool., (Copyright © 2022. Published by Elsevier B.V.)

Background and Objective: Arterial stiffness, commonly assessed by carotid-femoral pulse wave velocity (cfPWV), is an independent biomarker for cardiovascular disease. The measurement of cfPWV, however, has been considered impractical for routine clinical application. Pulse wave analysis using a single pulse wave measurement in the radial artery is a convenient alternative. This study aims to identify pulse wave features for a more accurate estimation of cfPWV from a single radial pulse wave measurement., Methods: From a dataset of 140 subjects, cfPWV was measured and the radial pulse waveform was recorded for 30 s twice in succession. Features were extracted from the waveforms in the time and frequency domains, as well as by wave separation analysis. All-possible regressions with bootstrapping, McHenry's select algorithm, and support vector regression were applied to compute models for cfPWV estimation., Results: The correlation coefficients between the measured and estimated cfPWV were r = 0.81, r = 0.81, and r = 0.8 for all-possible regressions, McHenry's select algorithm, and support vector regression, respectively. The features selected by all-possible regressions are physiologically interpretable. In particular, the amplitude ratio of the diastolic peak to the notch of the radial pulse waveform (R n,d r,P ) is shown to be correlated with cfPWV. This correlation was further evaluated and found to be independent of wave reflections using a dataset (n = 3,325) of simulated pulse waves., Conclusions: The proposed method may serve as a convenient surrogate for the measurement of cfPWV. R n,d r,P is associated with aortic pulse wave velocity and this association may not be dependent on wave reflection., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Arterial stiffness, as measured by pulse wave velocity, for the early non-invasive screening of cardiovascular disease is becoming ever more widely used and is an independent prognostic indicator for a variety of pathologies including arteriosclerosis. Carotid-femoral pulse wave velocity (cfPWV) is regarded as the gold standard for aortic stiffness. Existing algorithms for cfPWV estimation have been shown to have good repeatability and accuracy, however, further assessment is needed, especially when signal quality is compromised. We propose a method for calculating cfPWV based on a simplified tube-load model, which allows for the propagation and reflection of the pulse wave. In-vivo cfPWV measurements from 57 subjects and numerical cfPWV data based on a one-dimensional model were used to assess the method and its performance was compared to three other existing approaches (waveform matching, intersecting tangent, and cross-correlation). The cfPWV calculated using the simplified tube-load model had better repeatability than the other methods (Intra-group Correlation Coefficient, ICC = 0.985). The model was also more accurate than other methods (deviation, 0.13 ms -1 ) and was more robust when dealing with noisy signals. We conclude that the determination of cfPWV based on the proposed model can accurately and robustly evaluate arterial stiffness., (© 2022. The Author(s).)

Ballistocardiography (BCG) is considered a good alternative to HRV analysis with its non-contact and unobtrusive acquisition characteristics. However, consensus about its validity has not yet been established. In this study, 50 healthy subjects (26.2 ± 5.5 years old, 22 females, 28 males) were invited. Comprehensive statistical analysis, including Coefficients of Variation (CV), Lin’s Concordance Correlation Coefficient (LCCC), and Bland-Altman analysis (BA ratio), were utilized to analyze the consistency of BCG and ECG signals in HRV analysis. If the methods gave different answers, the worst case was taken as the result. Measures of consistency such as Mean, SDNN, LF gave good agreement (the absolute value of CV difference < 2%, LCCC > 0.99, BA ratio < 0.1) between J-J (BCG) and R-R intervals (ECG). pNN50 showed moderate agreement (the absolute value of CV difference < 5%, LCCC > 0.95, BA ratio < 0.2), while RMSSD, HF, LF/HF indicated poor agreement (the absolute value of CV difference ≥ 5% or LCCC ≤ 0.95 or BA ratio ≥ 0.2). Additionally, the R-R intervals were compared with P-P intervals extracted from the pulse wave (PW). Except for pNN50, which exhibited poor agreement in this comparison, the performances of the HRV indices estimated from the PW and the BCG signals were similar.

Background: The ideal treatment strategy for stable three-vessel coronary artery disease (CAD) patients are difficult to determine and for patients undergoing conservative treatment, imaging evidence of coronary atherosclerotic severity progression remains limited. Epicardial fat volume (EFV) on coronary CT angiography (CCTA) has been considered to be associated with coronary atherosclerosis. Therefore, this study aims to evaluate the relationship between EFV level and coronary atherosclerosis severity in three-vessel CAD., Methods: This retrospective study enrolled 252 consecutive patients with three-vessel CAD and 252 normal control group participants who underwent CCTA between January 2018 and December 2019. A semi-automatic method was developed for EFV quantification on CCTA images, standardized by body surface area. Coronary atherosclerosis severity was evaluated and scored by the number of coronary arteries with ≥ 50% stenosis on coronary angiography. Patients were subdivided into groups on the basis of lesion severity: mild (score = 3 vessels, n = 85), moderate (3.5 vessels ≤ score < 4 vessels, n = 82), and severe (4 vessels ≤ score ≤ 7 vessels, n = 85). The independent sample t-test, analysis of variance, and logistic regression analysis were used to evaluate the associations between EFV level and severity of coronary atherosclerosis., Results: Compared with normal controls, three-vessel CAD patients had significantly higher EFV level (65 ± 22 mL/m 2 vs. 48 ± 19 mL/m 2 ; P < 0.001). In patients with three-vessel CAD, there was a progressive decline in EFV level as the score of coronary atherosclerosis severity increased, especially in those patients with a body mass index (BMI) ≥ 25 kg/m 2 (75 ± 21 mL/m 2 vs. 72 ± 22 mL/m 2 vs. 62 ± 17 mL/m 2 ; P < 0.05). Multivariable regression analysis showed that both BMI (OR 3.40, 95% CI 2.00-5.78, P < 0.001) and the score of coronary atherosclerosis severity (OR 0.49, 95% CI 0.26-0.93, P < 0.05) were independently related to the change of EFV level., Conclusion: Three-vessel CAD patients do have higher EFV level than the normal controls. While, there may be an inverse relationship between EFV level and the severity of coronary atherosclerosis in patients with three-vessel CAD., (© 2022. The Author(s).)

Background: At present, coronary artery disease (CAD) is the leading cause of death worldwide. Many studies have shown that CAD is strongly associated with the motion characteristics of the coronary arteries. Although cardiovascular imaging technology has been widely used for the diagnosis of CAD, the motion parameters of the heart and coronary arteries cannot be directly calculated from the images. In this paper, we propose a point set registration method with global and local topology constraints to quantify coronary artery movement., Methods: The global constraint is the motion coherence of the point set which enforces the smoothness of the displacement field. The local linear embedding based topological structure and the local feature descriptor i.e., the 3D shape context, are designed to retain the local structure of the point set. We incorporate these constraints into a maximum likelihood framework and derive an expectation-maximization algorithm to obtain the transformation function between the two point sets. The proposed method was compared with four existing algorithms using simulated data and applied to the real data obtained from 4D CT angiograms., Results: For the simulation data, the proposed method achieves a lower registration error than the comparison algorithms. For the real data, the proposed method shows that, in most cases, the right coronary artery achieves a larger velocity than the left anterior descending and left circumflex branches, and there are three well-defined velocity peaks, during the cardiac cycle for these branches., Conclusion: The proposed approach is feasible and effective in quantifying coronary artery movement and thus adds to the diagnostic power of coronary imaging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Myocardial infarction (MI) is one of the most common cardiovascular diseases, frequently resulting in death. Early and accurate diagnosis is therefore important, and the electrocardiogram (ECG) is a simple and effective method for achieving this. However, it requires assessment by a specialist; so many recent works have focused on the automatic assessment of ECG signals., Methods: For the detection and localization of MI, deep learning models have been proposed, but the diagnostic accuracy of this approaches still need to be improved. Moreover, with deep learning methods the way in which a given result was achieved lacks interpretability. In this study, ECG data was obtained from the PhysioBank open access database, and was analyzed as follows. Firstly, the 12-lead ECG signal was preprocessed to identify each beat and obtain each heart interval. Secondly, a multi-scale deep learning model combined with a residual network and attention mechanism was proposed, where the input was the 12-lead ECG recording. Through the SENet model and the Grad-CAM algorithm, the weighting of each lead was calculated and visualized. Using existing knowledge of the way in which different types of MI gave characteristic patterns in specific ECG leads, the model was used to provisionally diagnose the type of MI according to the characteristics of each of the 12 ECG leads., Results: Ten types of MI anterior, anterior lateral, anterior septal, inferior, inferior lateral, inferior posterior, inferior posterior lateral, lateral, posterior, and posterior lateral were diagnosed. The average accuracy, sensitivity, and specificity for MI detection of all lesion types was 99.98, 99.94, and 99.98%, respectively; and the average accuracy, sensitivity, and specificity for MI localization was 99.79, 99.88, and 99.98%, respectively., Conclusion: When compared to existing models based on traditional machine learning methods, convolutional neural networks and recurrent neural networks, the results showed that the proposed model had better diagnostic performance, being superior in accuracy, sensitivity, and specificity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Liu, Zhang, Xu, Zhu, Cui, Geng, Han and Greenwald.)

Purpose: Epicardial fat is the adipose tissue between the serosal pericardial wall layer and the visceral layer. It is distributed mainly around the atrioventricular groove, atrial septum, ventricular septum and coronary arteries. Studies have shown that the density, thickness, volume and other characteristics of epicardial adipose tissue (EAT) are independently correlated with a variety of cardiovascular diseases. Given this association, the accurate determination of EAT volume is an essential aim of future research. Therefore, the purpose of this study was to establish a framework for fully automatic EAT segmentation and quantification in coronary computed tomography angiography (CCTA) scans., Methods: A set of 103 scans are randomly selected from our medical center. An automatic pipeline has been developed to segment and quantify the volume of EAT. First, a multi-slice deep neural network is used to simultaneously segment the pericardium in multiple adjacent slices. Then a deformable model is employed to reduce false positive and negative regions in the segmented binary pericardial images. Finally, the pericardium mask is used to define the region of interest (ROI) and the threshold method is utilized to extract the pixels ranging from -175 Hounsfield units (HU) to -15 HU for the segmentation of EAT., Results: The Dice indices of the pericardial segmentation using the proposed method with respect to the manual delineation results of two radiology experts were 97.1%  ±  0.7% and 96.9%  ±  0.6%, respectively. The inter-observer variability was also assessed, resulting in a Dice index of 97.0%  ±  0.7%. For the EAT segmentation results, the Dice indices between the proposed method and the two radiology experts were 93.4%  ±  1.5% and 93.3%  ±  1.3%, respectively, and the same measurement between the experts themselves was 93.6%  ±  1.9%. The Pearson's correlation coefficients between the EAT volumes computed from the results of the proposed method and the manual delineation by the two experts were 1.00 and 0.99 and the same coefficients between the experts was 0.99., Conclusions: This work describes the development of a fully automatic EAT segmentation and quantification method from CCTA scans and the results compare favorably with the assessments of two independent experts. The proposed method is also packaged with a graphical user interface which can be found at https://github.com/MountainAndMorning/EATSeg., (© 2021 American Association of Physicists in Medicine.)

Background: Central aortic pressure (CAP) as the major load on the left heart is of great importance in the diagnosis of cardiovascular disease. Studies have pointed out that CAP has a higher predictive value for cardiovascular disease than peripheral artery pressure (PAP) measured by means of traditional sphygmomanometry. However, direct measurement of the CAP waveform is invasive and expensive, so there remains a need for a reliable and well validated non-invasive approach., Methods: In this study, a multi-channel Newton (MCN) blind system identification algorithm was employed to noninvasively reconstruct the CAP waveform from two PAP waveforms. In simulation experiments, CAP waveforms were recorded in a previous study, on 25 patients and the PAP waveforms (radial and femoral artery pressure) were generated by FIR models. To analyse the noise-tolerance of the MCN method, variable amounts of noise were added to the peripheral signals, to give a range of signal-to-noise ratios. In animal experiments, central aortic, brachial and femoral pressure waveforms were simultaneously recorded from 2 Sprague-Dawley rats. The performance of the proposed MCN algorithm was compared with the previously reported cross-relation and canonical correlation analysis methods., Results: The results showed that the root mean square error of the measured and reconstructed CAP waveforms and less noise-sensitive using the MCN algorithm was smaller than those of the cross-relation and canonical correlation analysis approaches., Conclusion: The MCN method can be exploited to reconstruct the CAP waveform. Reliable estimation of the CAP waveform from non-invasive measurements may aid in early diagnosis of cardiovascular disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The tendon interfascicular matrix (IFM) binds tendon fascicles together. As a result of its low stiffness behaviour under small loads, it enables non-uniform loading and increased overall extensibility of tendon by facilitating fascicle sliding. This function is particularly important in energy storing tendons, with previous studies demonstrating enhanced extensibility, recovery and fatigue resistance in the IFM of energy storing compared to positional tendons. However, the compositional specialisations within the IFM that confer this behaviour remain to be elucidated. It is well established that the IFM is rich in elastin, therefore we sought to test the hypothesis that elastin depletion (following elastase treatment) will significantly impact IFM, but not fascicle, mechanical properties, reducing IFM resilience in all samples, but to a greater extent in younger tendons, which have a higher elastin content. Using a combination of quasi-static and fatigue testing, and optical imaging, we confirmed our hypothesis, demonstrating that elastin depletion resulted in significant decreases in IFM viscoelasticity, fatigue resistance and recoverability compared to untreated samples, with no significant changes to fascicle mechanics. Ageing had little effect on fascicle or IFM response to elastase treatment. This study offers a first insight into the functional importance of elastin in regional specific tendon mechanics. It highlights the important contribution of elastin to IFM mechanical properties, demonstrating that maintenance of a functional elastin network within the IFM is essential to maintain IFM and thus tendon integrity. STATEMENT OF SIGNIFICANCE: Developing effective treatments or preventative measures for musculoskeletal tissue injuries necessitates the understanding of healthy tissue function and mechanics. By establishing the contribution of specific proteins to tissue mechanical behaviour, key targets for therapeutics can be identified. Tendon injury is increasingly prevalent and chronically debilitating, with no effective treatments available. Here, we investigate how elastin modulates tendon mechanical behaviour, using enzymatic digestion combined with local mechanical characterisation, and demonstrate for the first time that removing elastin from tendon affects the mechanical properties of the interfascicular matrix specifically, resulting in decreased recoverability and fatigue resistance. These findings provide a new level of insight into tendon hierarchical mechanics, important for directing development of novel therapeutics for tendon injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Portable devices for collecting electrocardiograms (ECGs) and telemedicine systems for diagnosis are available to residents in deprived areas, but ECGs collected by non-professionals are not necessarily reliable and may impair the accuracy of diagnosis. We propose an algorithm for accurate ECG quality assessment, which can help improve the reliability of ECGs collected by portable devices., Approach: Using challenge data from CinC (2019), signals were classified as 'acceptable' and 'unacceptable' by annotators. The training set contained 998 12-lead ECGs and the test set contained 500. A 998 × 84 feature matrix, S, was formed by feature extraction and three basic models were obtained through training SVM, DT and NBC on S. The feature subsets S1, S2 and S3 were obtained by dimensionality reduction on S using SVM, DT and NBC, respectively. Three other basic models were obtained through training SVM on S1, DT on S2 and NBC on S3. By combining these six basic models, several integrated models were formed. An iterative method was proposed to select the integrated model with the highest accuracy on the training set. Having compared differences between the output labels and the original data labels, evaluation criteria were calculated., Main Results: An accuracy of 98.70% and 98.60% was achieved on the training and test datasets, respectively. High F1 score and Kappa values were also obtained., Significance: The proposed algorithm has advantages over previously reported approaches during automatic assessment of ECG quality and can thus help to reduce reliance on highly trained professionals when assessing the quality of ECGs.

The accurate measurement of the arterial pulse wave is beneficial to clinical health assessment and is important for the effective diagnosis of many types of cardiovascular disease. A variety of sensors have been developed for the non-invasive detection of these waves, but the type of sensor has an impact on the measurement results. Therefore, it is necessary to compare and analyze the signals obtained under a range of conditions using various pulse sensors to aid in making an informed choice of the appropriate type. From the available types we have selected four: a piezoresistive strain gauge sensor (PESG) and a piezoelectric Millar tonometer (the former with the ability to measure contact force), a circular film acceleration sensor, and an optical reflection sensor. Pulse wave signals were recorded from the left radial, carotid, femoral, and digital arteries of 60 subjects using these four sensors. Their performance was evaluated by analyzing their susceptibilities to external factors (contact force, measuring site, and ambient light intensity) and by comparing their stability and reproducibility. Under medium contact force, the peak-to-peak amplitude of the signals was higher than that at high and low force levels and the variability of signal waveform was small. The optical sensor was susceptible to ambient light. Analysis of the intra-class correlation coefficients (ICCs) of the pulse wave parameters showed that the tonometer and accelerometer had good stability (ICC > 0.80), and the PESG and optical sensor had moderate stability (0.46 < ICC < 0.86). Intra-observer analysis showed that the tonometer and accelerometer had good reproducibility (ICC > 0.75) and the PESG and optical sensor had moderate reproducibility (0.42 < ICC < 0.91). Inter-observer analysis demonstrated that the accelerometer had good reproducibility (ICC > 0.85) and the three other sensors had moderate reproducibility (0.52 < ICC < 0.96). We conclude that the type of sensor and measurement site affect pulse wave characteristics and the careful selection of appropriate sensor and measurement site are required according to the research and clinical need. Moreover, the influence of external factors such as contact pressure and ambient light should be fully taken into account., (Copyright © 2020 Wang, Wang, Sun, Yao, Hao, Xu and Greenwald.)

Background: It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals., Methods: To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm 2 ). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments., Results: To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented., Conclusions: The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5-500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments.

Objective: Remote photoplethysmography (rPPG) can achieve non-contact measurement of heart rate (HR) from a continuous video sequence by scanning the skin surface. However, practical applications are still limited by factors such as non-rigid facial motion and head movement. In this work, a detailed system framework for remotely estimating heart rate from facial videos under various movement conditions is described., Approach: After the rPPG signal has been obtained from a defined region of the facial skin, a method, termed 'Project&#95;ICA', based on a skin reflection model, is employed to extract the pulse signal from the original signal., Main Results: To evaluate the performance of the proposed algorithm, a dataset containing 112 videos including the challenges of various skin tones, body motion and HR recovery after exercise was created from 28 participants., Significance: The results show that Project&#95;ICA, when evaluated by several criteria, provides a more accurate and robust estimate of HR than most existing methods, although problems remain in obtaining reliable measurements from dark-skinned subjects.

Key Points: Intrauterine growth restriction (IUGR), induced by maternal undernutrition, leads to impaired aortic development. This is followed by hypertrophic remodelling associated with accelerated growth during lactation. Fetal nutrient restriction is associated with increased aortic compliance at birth and at weaning, but not in adult animals. This mechanical alteration may be related to a decreased perinatal collagen deposition. Aortic elastin scaffolds purified from young male and female IUGR animals also exhibit increased compliance, only maintained in adult IUGR females. These mechanical alterations may be related to differences in elastin deposition and remodelling. Fetal undernutrition induces similar aortic structural and mechanical alterations in young male and female rats. Our data argue against an early mechanical cause for the sex differences in hypertension development induced by maternal undernutrition. However, the larger compliance of elastin in adult IUGR females may contribute to the maintenance of a normal blood pressure level., Abstract: Fetal undernutrition programmes hypertension development, males being more susceptible. Deficient fetal elastogenesis and vascular growth is a possible mechanism. We investigated the role of aortic mechanical alterations in a rat model of hypertension programming, evaluating changes at birth, weaning and adulthood. Dams were fed ad libitum (Control) or 50% of control intake during the second half of gestation (maternal undernutrition, MUN). Offspring aged 3 days, 21 days and 6 months were studied. Blood pressure was evaluated in vivo. In the thoracic aorta we assessed gross structure, mechanical properties (intact and purified elastin), collagen and elastin content and internal elastic lamina (IEL) organization. Only adult MUN males developed hypertension (systolic blood pressure: MUN males  = 176.6 ± 5.6 mmHg; Control males  = 136.1 ± 4.9 mmHg). At birth MUN rats were lighter, with smaller aortic cross-sectional area (MUN males  = (1.51 ± 0.08) × 10 5  μm 2 , Control males  = (2.8 ± 0.04) × 10 5  μm 2 ); during lactation MUN males and females exhibited catch-up growth and aortic hypertrophy (MUN males  = (14.5 ± 0.5) × 10 5  μm 2 , Control males  = (10.4 ± 0.9) × 10 5  μm 2 ), maintained until adulthood. MUN aortas were more compliant until weaning (functional stiffness: MUN males  = 1.0 ± 0.04; Control males  = 1.3 ± 0.03), containing less collagen with larger IEL fenestrae, returning to normal in adulthood. Purified elastin from young MUN offspring was more compliant in both sexes; only MUN adult females maintained larger elastin compliance (slope: MUN females  = 24.1 ± 1.9; Control females  = 33.3 ± 2.8). Fetal undernutrition induces deficient aortic development followed by hypertrophic remodelling and larger aortic compliance in the perinatal period, with similar alterations in collagen and elastin in both sexes. The observed alterations argue against an initial mechanical cause for sex differences in hypertension development. However, the maintenance of high elastin compliance in adult females might protect them against blood pressure rise., (© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.)

Objective: This study aimed to compare differences in cardiorespiratory function between untreated hypertensive subjects (UHS) and healthy subjects (HS) during cardiopulmonary exercise testing (CPET). Additionally, it also aimed to explore the potential mechanisms of different exercise responses in cardiorespiratory function before, during and after CPET. Methods: Thirty subjects (15 UHS and 15 HS) were enrolled. Photoplethysmography (PPG), respiratory signal, and ECG were simultaneously collected while subjects were performing CPET. Fiducial points (a, b, c, d, e) were extracted from the second derivative of the PPG (SDPPG), and the ratios b/a, c/a, d/a, e/a, and (b-c-d-e)/a (named Aging Index, AGI) were calculated as markers of systolic and diastolic function. Additionally, respiratory rate was calculated and analyzed. Results: Before CPET, there were no significant differences in b/a, d/a, and AGI between two groups. However, after CPET, b/a (-0.9 ± 0.19 vs. -1.06 ± 0.19, p -value = 0.03) and AGI (-0.49 ± 0.75 vs. -1.15 ± 0.59, p -value = 0.011) of the UHS group were significantly higher than those of the HS. The d/a (-0.32 ± 0.24 vs. -0.14 ± 0.17, p -value = 0.024), and c/a (-0.33 ± 0.26 vs. -0.07 ± 0.19, p -value = 0.004) were significantly lower in UHS than those in HS. In contrast, before CPET, e/a (0.22 ± 0.11 vs. 0.32 ± 0.09, p -value = 0.007) in UHS was significantly lower than that in HS, while after CPET there was no significant difference between the two groups in this variable. In addition, during CPET, AGI ( p -value = 0.003), and respiratory rate ( p -value = 0.000) in UHS were significantly higher in comparison with before CPET. Conclusions: Different exercise responses showed the differences of cardiorespiratory function between UHS and HS. These differences not only can highlight the CV risk of UHS, but also can predict the appearance of arterial stiffness in UHS. Additionally, during CPET, significant differences in AGI, autonomic nervous function and respiratory activity assessed by respiratory rate were found between the two groups in comparison with before CPET.

Background: Exercise is accepted as an important contribution to the rehabilitation of patients with cardiovascular disease (CVD). This study aims to better understand the possible causes for lack of consensus and reviews the effects of three exercise modalities (aerobic, resistance and combined exercise) on central hemodynamics, arterial stiffness and cardiac function for better rehabilitation strategies in CVD., Methods: The electronic data sources, Cochrane Library, MEDLINE, Web of Science, EBSCO (CINAHL), and ScienceDirect from inception to July 2017 were searched for randomized controlled trials (RCTs) investigating the effect of exercise modalities in adult patients with CVD. The effect size was estimated as mean differences (MD) with 95% confidence intervals (CI). Subgroup analysis and meta-regression were used to study potential moderating factors., Results: Thirty-eight articles describing RCTs with a total of 2089 patients with CVD were included. The pooling revealed that aerobic exercise [MD(95%CI) = -5.87 (-8.85, -2.88), P = 0.0001] and resistance exercise [MD(95%CI) = -7.62 (-10.69, -4.54), P<0.00001] significantly decreased aortic systolic pressure (ASP). Resistance exercise significantly decreased aortic diastolic pressure [MD(95%CI) = -4(-5.63, -2.37), P<0.00001]. Aerobic exercise significantly decreased augmentation index (AIx) based on 24-week exercise duration and patients aged 50-60 years. Meanwhile, aerobic exercise significantly improved carotid-femoral pulse wave velocity (cf-PWV) [MD(95%CI) = -0.42 (-0.83, -0.01), P = 0.04], cardiac output (CO) [MD(95% CI) = 0.36(0.08, 0.64), P = 0.01] and left ventricular ejection fraction (LVEF) [MD(95%CI) = 3.02 (2.11, 3.93), P<0.00001]. Combined exercise significantly improved cf-PWV [MD(95%CI) = -1.15 (-1.95, -0.36), P = 0.004] and CO [MD(95% CI) = 0.9 (0.39, 1.41), P = 0.0006]., Conclusions: Aerobic and resistance exercise significantly decreased ASP, and long-term aerobic exercise reduced AIx. Meanwhile, aerobic and combined exercise significantly improved central arterial stiffness and cardiac function in patients with CVD. These findings suggest that a well-planned regime could optimize the beneficial effects of exercise and can provide some evidence-based guidance for those involved in cardiovascular rehabilitation of patients with CVD., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Rice bran protein hydrolysates (RBPH) contain highly nutritional proteins and antioxidant compounds which show benefits against metabolic syndrome (MetS). Increased arterial stiffness and the components of MetS have been shown to be associated with an increased risk of cardiovascular disease. This study aimed to investigate whether RBPH could alleviate the metabolic disorders, arterial stiffening, vascular remodeling, and oxidative stress in rats fed a high-carbohydrate and high-fat (HCHF) diet., Methods: Male Sprague-Dawley rats were fed either a standard chow and tap water or a HCHF diet and 15 % fructose solution for 16 weeks. HCHF rats were treated orally with RBPH (250 or 500 mg/kg/day) for the final 6 weeks of the experimental period., Results: Rats fed with HCHF diet had hyperglycemia, insulin resistance, dyslipidemia, hypertension, increased aortic pulse wave velocity, aortic wall hypertrophy and vascular remodeling with increased MMP-2 and MMP-9 expression. RBPH supplementation significantly alleviated these alterations (P < 0.05). Moreover, RBPH reduced the levels of angiotensin-converting enzyme (ACE) and tumor necrosis factor-alpha in plasma. Oxidative stress was also alleviated after RBPH treatment by decreasing plasma malondialdehyde, reducing superoxide production and suppressing p47 phox NADPH oxidase expression in the vascular tissues of HCHF rats. RBPH increased plasma nitrate/nitrite level and up-regulated eNOS expression in the aortas of HCHF-diet-fed rats, indicating that RBPH increased NO production., Conclusion: RBPH mitigate the deleterious effects of HCHF through potential mechanisms involving enhanced NO bioavailability, anti-ACE, anti-inflammatory and antioxidant properties. RBPH could be used as dietary supplements to minimize oxidative stress and vascular alterations triggered by MetS.

Tendon is composed of fascicles bound together by the interfascicular matrix (IFM). Energy storing tendons are more elastic and extensible than positional tendons; behaviour provided by specialisation of the IFM to enable repeated interfascicular sliding and recoil. With ageing, the IFM becomes stiffer and less fatigue resistant, potentially explaining why older tendons become more injury-prone. Recent data indicates enrichment of elastin within the IFM, but this has yet to be quantified. We hypothesised that elastin is more prevalent in energy storing than positional tendons, and is mainly localised to the IFM. Further, we hypothesised that elastin becomes disorganised and fragmented, and decreases in amount with ageing, especially in energy storing tendons. Biochemical analyses and immunohistochemical techniques were used to determine elastin content and organisation, in young and old equine energy storing and positional tendons. Supporting the hypothesis, elastin localises to the IFM of energy storing tendons, reducing in quantity and becoming more disorganised with ageing. These changes may contribute to the increased injury risk in aged energy storing tendons. Full understanding of the processes leading to loss of elastin and its disorganisation with ageing may aid in the development of treatments to prevent age related tendinopathy.

Aims: To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes., Methods: In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100,000 IU vitamin D2 (ergocalciferol) or 100,000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation., Results: The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: -0.05% [95% confidence interval (CI) -0.11, 0.02] or -0.51 mmol/mol (95% CI -1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI -0.04, 0.08) or 0.19 mmol/mol (95% CI -0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: -0.68 m/s (95% CI -1.31, -0.05); D3 versus placebo -0.73 m/s (95% CI -1.42, -0.03)]. No important safety issues were identified., Conclusions: Short-term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness., (© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

As a first step towards an acoustic localisation device for coronary stenosis to provide a non-invasive means of diagnosing arterial disease, measurements are reported for an agar-based tissue mimicking material (TMM) of the shear wave propagation velocity, attenuation and viscoelastic constants, together with one dimensional quasi-static elastic moduli and Poisson's ratio. Phase velocity and attenuation coefficients, determined by generating and detecting shear waves piezo-electrically in the range 300 Hz-2 kHz, were 3.2-7.5 ms(-1) and 320 dBm(-1). Quasi-static Young's modulus, shear modulus and Poisson's ratio, obtained by compressive or shear loading of cylindrical specimens were 150-160 kPa; 54-56 kPa and 0.37-0.44. The dynamic Young's and shear moduli, derived from fitting viscoelastic internal variables by an iterative statistical inverse solver to freely oscillating specimens were 230 and 33 kPa and the corresponding relaxation times, 0.046 and 0.036 s. The results were self-consistent, repeatable and provide baseline data required for the computational modelling of wave propagation in a phantom.

Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance, hypertension and dyslipidemia. Ferulic acid (FA) is the major phenolic compound found in rice oil and various fruits and vegetables. In this study, we examined the beneficial effects of FA in minimizing insulin resistance, vascular dysfunction and remodeling in a rat model of high-carbohydrate, high-fat diet-induced metabolic changes, which is regarded as an analogue of metabolic syndrome (MS) in man. Male Sprague-Dawley rats were fed a high carbohydrate, high fat (HCHF) diet and 15% fructose in drinking water for 16 weeks, where control rats were fed with standard chow diet and tap water. FA (30 or 60 mg/kg) was orally administered to the HCHF and control rats during the last six weeks of the study. We observed that FA significantly improved insulin sensitivity and lipid profiles, and reduced elevated blood pressure, compared to untreated controls (p < 0.05). Moreover, FA also improved vascular function and prevented vascular remodeling of mesenteric arteries. The effects of FA in HCHF-induced MS may be realized through suppression of oxidative stress by down-regulation of p47phox, increased nitric oxide (NO) bioavailability with up-regulation of endothelial nitric oxide synthase (eNOS) and suppression of tumor necrosis factor-α (TNF-α). Our results suggest that supplementation of FA may have health benefits by minimizing the cardiovascular complications of MS and alleviating its symptoms.

Background: Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice., Methods: Male ICR mice received CdCl2 (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment., Results: Administration of CdCl2 significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues., Conclusions: Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure.

Oxidative stress plays a role in maintaining high arterial blood pressure and contributes to the vascular changes that lead to hypertension. Consumption of polyphenol-rich foods has demonstrated their beneficial role in the prevention and treatment of hypertension. Curcumin (CUR), a phenolic compound present in the rhizomes of turmeric, possesses cardiovascular protective, anti-inflammatory and antioxidant properties. The present study was designed to investigate the protective effect of CUR on 2kidney-1clip (2K-1C)-induced hypertension, endothelial dysfunction, vascular remodeling and oxidative stress in male Sprague-Dawley rats. Sham operated or 2K-1C rats were treated with CUR at a dose of 50 or 100 mg/kg/day (or vehicle). After 6 weeks of treatment, CUR ameliorated hemodynamic performance in 2K-1C hypertensive rats (P< 0.05), by reducing blood pressure, increasing hindlimb blood flow and decreasing hindlimb vascular resistance. Hemodynamic restoration was associated with a reduction in plasma angiotensin converting enzyme level. Endothelium-dependent vasorelaxation, in response to acetylcholine, of aortic rings isolated from 2K-1C hypertensive rats-treated with CUR was significantly increased (P< 0.05). CUR also attenuated hypertension-induced oxidative stress and vascular structural modifications. These effects were associated with elevated plasma nitrate/nitrite, upregulated eNOS expression, downregulated p47phox NADPH oxidase and decreased superoxide production in the vascular tissues. The overall findings of this study suggest the mechanisms responsible for the antihypertensive action of CUR in 2K-1C hypertension-induced endothelial dysfunction and vascular remodeling involve the improvement NO bioavailability and a reduction in oxidative stress., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To compare cardiac function at 10 years of age in four groups of monochorionic diamniotic (MCDA) twin pairs: uncomplicated MCDA twins (n = 6) (Group 1); twins that had had twin-twin transfusion syndrome (TTTS) managed by amnioreduction (TTTS-amnio, n = 9) (Group 2) or laser photocoagulation (TTTS-laser, n = 10) (Group 3); and dichorionic diamniotic controls (DCDA, n = 6) (Group 4)., Methods: Echocardiograms optimizing apical four-chamber and short-axis left ventricular views were stored for offline speckle-tracking analysis, blinded to twin type. Myocardial long-axis shortening and lengthening velocities were measured using pulsed Doppler ultrasound at the cardiac base. M-mode measurements of fractional shortening (short axis) and maximal excursion of the atrioventricular annulus (four-chamber) were recorded. Syngo Vector Velocity Imaging software tracked left ventricular myocardial motion offline to produce free wall strain, strain rate and rotation. Intertwin pair and group differences were investigated using ANOVA., Results: Cardiac measurements were within the normal ranges for 10-year-olds. No significant within-twin-pair and intergroup differences were found in current size, heart rates, strain or strain rate. Compared to DCDA controls, TTTS twins showed less cardiac rotation (TTTS-laser, P < 0.001 and TTTS-amnio, P = 0.054) with significant intertwin reduction in the ex-recipient (TTTS-amnio, P = 0.006) and larger MCDA twins (P = 0.027) compared with their cotwins. A similar pattern was seen in left ventricular early diastolic mitral valve tissue velocity (MVE') in all monochorionic groups, but only achieving significance in TTTS-amnio twins (P = 0.037). Intrapair differences in rotation and MVE' were significantly different following treatment at Quintero stages III or IV., Conclusions: Within-twin-pair patterns of left ventricular rotation and diastolic function differ at 10 years of age in ex-recipients of TTTS twins treated with amnioreduction compared with those treated by laser photocoagulation and controls. ., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

A current thrust in medical research is the development of a non-invasive method for detection, localization, and characterization of an arterial stenosis (a blockage or partial blockage in an artery). A method has been proposed to detect shear waves in the chest cavity which have been generated by disturbances in the blood flow resulting from a stenosis. In order to develop this methodology further, we use one-dimensional shear wave experimental data from novel acoustic phantoms to validate a corresponding viscoelastic mathematical model. We estimate model parameters which give a good fit (in a sense to be precisely defined) to the experimental data, and use asymptotic error theory to provide confidence intervals for parameter estimates. Finally, since a robust error model is necessary for accurate parameter estimates and confidence analysis, we include a comparison of absolute and relative models for measurement error.

We revisit a method originally introduced by Werder et al. (in Comput. Methods Appl. Mech. Engrg., 190:6685-6708, 2001) for temporally discontinuous Galerkin FEMs applied to a parabolic partial differential equation. In that approach, block systems arise because of the coupling of the spatial systems through inner products of the temporal basis functions. If the spatial finite element space is of dimension D and polynomials of degree r are used in time, the block system has dimension ( r + 1) D and is usually regarded as being too large when r > 1. Werder et al. found that the space-time coupling matrices are diagonalizable over [Formula: see text] for r ⩽ 100, and this means that the time-coupled computations within a time step can actually be decoupled. By using either continuous Galerkin or spectral element methods in space, we apply this DG-in-time methodology, for the first time, to second-order wave equations including elastodynamics with and without Kelvin-Voigt and Maxwell-Zener viscoelasticity. An example set of numerical results is given to demonstrate the favourable effect on error and computational work of the moderately high-order (up to degree 7) temporal and spatio-temporal approximations, and we also touch on an application of this method to an ambitious problem related to the diagnosis of coronary artery disease. Copyright © 2014 The Authors. International Journal for Numerical Methods in Engineering published by John Wiley & Sons Ltd.

This study aimed to utilise a tissue mimicking material (TMM) in order to embed in vitro carotid plaque tissue so that its acoustic properties could be assessed. Here, an International Electrotechnical Commission (IEC) agar-based TMM was adapted to a clear gel by removal of the particulates. This clear TMM was measured with sound speed at 1540 ms(-1) and an attenuation coefficient of 0.15 dB cm(-1)MHz(-1). Composite sound speed was then measured through the embedded material using a scanning acoustic microscope (SAM). Both broadband reflection and transmission techniques were performed on each plaque specimen in order to ensure the consistency of the measurement of sound speed, both at 21 °C and 37 °C. The plaque was measured at two temperatures to investigate any effect on the lipid content of the plaque. The contour maps from its associated attenuation plots were used to match the speed data to the photographic mask of the plaque outline. This physical matching was then used to derive the sound speed from the percentage composition seen in the histological data by solution of simultaneous equations. Individual speed values for five plaque components were derived; TMM, elastin, fibrous/collagen, calcification and lipid. The results for derived sound speed in the TMM were consistently close to the expected value of soft tissue, 1540 ms(-1). The fibrous tissue showed a mean value of 1584 ms(-1) at 37 °C. The derived sound speeds for elastic and lipid exhibited large inter-quartile ranges. The calcification had higher sound speed than the other plaque components at 1760-2000 ms(-1). The limitations here lay in the difficulties in the matching process caused by the inhomogeneity of the plaque material and shrinkage during the histological process. Future work may concentrate on more homogeneous material in order to derive sound speed data for separate components. Nevertheless, this study increases the known data ranges of the individual components within a plaque. This information may be used help to assess the mechanical properties and structural integrity and its associated vulnerability or risk of embolization in future diagnostic ultrasound techniques., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Increased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors., Methods: A total of 208 Thai subjects, aged 35-75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated., Results: Arterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype., Conclusions: Our findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.

Patients with thalassemia major are susceptible to cardiovascular complications by mechanisms not fully understood. Although overt cardiovascular complications usually occur after puberty, their underlying pathogenesis may begin much earlier. This study investigated whether there were early changes in vascular endothelial function and arterial stiffness in young patients with beta-thalassemia and hemoglobin E, and whether these changes were associated with oxidative stress and expression of antioxidant genes. The study recruited 30 pediatric patients and 30 age-matched control subjects. Compared with the control subjects, the patients had increased levels of oxidant biomarkers including malondialdehyde, protein carbonyl, and non-transferrin-bound iron and a decreased glutathione redox ratio. There were clear signs of vascular endothelial dysfunction and increased arterial stiffness, as shown by marked suppression of forearm blood flow after reactive hyperemia and increased pulse-wave velocity in the trunk and legs. The changes in FBF were associated with oxidative stress markers and free iron. An adaptive antioxidant gene response was activated in blood mononuclear cells, as shown by upregulation of GCLC and Bach-1 mRNA but downregulation of heme oxygenase-1 and thioredoxin mRNA. The results highlight the vascular changes seen even in young patients during treatment. These changes were associated with oxidative stress and suggest an adaptive response that serves to protect host cells from further oxidative damage.

We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case-control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.

The spherical anatomy of human and rat liver lobules implies that more central cells have less time to carry out their function than more peripherally located cells because blood flows past them more rapidly. This problem could be overcome if more centrilobular cells could operate at higher temperatures than periportal cells. This study presents evidence for such a temperature gradient. Firstly, we use mathematical modelling to demonstrate that temperature increases towards the centre of the lobule. Secondly, we examine the distribution of a heat-generating protein and of a heat-sensitive protein across the rat and human liver lobules. Double-antibody staining of healthy liver from rat and human was used for visual scoring and for automated histomorphometric quantitation of the localisation of uncoupling protein-2 (known to generate heat) and of the transient receptor potential-v4 protein (known as a highly temperature-sensitive membrane protein). Both these proteins were found to be located predominantly in the centrilobular region of liver lobules. These findings support the suggestion that temperature gradients across the liver lobule may have evolved as a solution to the problem of reduced contact time between blood and cells at the centre as compared to the periphery of mammalian liver lobules.

The microstructural orientation of vascular wall constituents is of interest to scientists and clinicians because alterations in their native states are associated with various cardiovascular diseases. In the arterial media, the orientation of these constituents is often described as circumferential. However, it has been noted that, just below the endothelial surface, the vascular wall constituents are oriented axially. To further study this reported change in orientation, and to resolve previous observations (which were made under conditions of no load), we used nonlinear optical microscopy to examine the orientation of collagen and elastin fibers in the inner medial region of bovine common carotid arteries. Images were obtained from this part of the arterial wall under varying degrees of mechanical strain: 0%, 10% axial, 10% circumferential, and 10% biaxial. We observed that close to the endothelium these components are aligned in the axial direction but abruptly change to a circumferential alignment at a depth of approximately 20 mum from the endothelial surface. The application of mechanical strain resulted in a significantly greater degree of fiber alignment, both collagen and elastin, in the strain direction, regardless of their initial unloaded orientation. Furthermore, variations in strain conditions resulted in an increase or a decrease in the overall degree of fiber alignment in the subendothelial layer depending on the direction of the applied strain. This high-resolution investigation adds more detail to existing descriptions of complex structure-function relationships in vascular tissue, which is essential for a better understanding of the pathophysiological processes resulting from injury, disease progression, and interventional therapies.

Tendon is multi-level fibre composite material, responsible for the transmission of forces from muscles to the skeleton. It is composed of a hierarchical arrangement of collagenous units surrounded by a proteoglycan-rich matrix, arranged to support strain transfer, and thus contribute to the mechanical behaviour of tendon. This study examines the effect of swelling and enzymatic degradation on structural integrity at different levels of the tendon hierarchy. Biochemical and microstructural analysis are used to examine the effects of incubation on the composition and swelling of the matrix, prior to a mechanical characterisation of sample integrity. Results indicated significant swelling of tendon fibrils and interfibrillar matrix after incubation in phosphate buffered saline, leading to a reduction in ultimate tensile load, with failure initiated between fibrils and sub-fibrils. In contrast, incubation with the enzyme chondroitinase ABC resulted in a total removal of glycosaminoglycan from the samples, and a subsequent reduction in the extent of swelling. These fascicles also demonstrated an increase in failure loads, with failure predominating between fibres. The findings from this work confirm the importance of the non-collagenous matrix components in controlling strain transfer within tendon structures. It also highlights the necessity to maintain samples within a suitable and controlled environment prior to testing.