Evaluation of effect of highly standardized aqueous extract of roots and leaves of Withania somnifera on cold pressor test induced cardiovascular changes in healthy human subjects

Background: Stress is an important cardiovascular risk factor. Cold pressor test (CPT) is a simple, validated, non-invasive test used to measure stress induced changes in cardiovascular parameters. The objective of this study was to evaluate effect of Withania somnifera extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects.Methods: This was a double-blind, placebo controlled, crossover study. Participants were randomized to receive either two capsules of Withania somnifera extract 250 mg or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters heart rate, aortic pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and at end of treatment. After washout period of 10 days, subjects crossed over to other treatment group and same procedure was repeated. Safety assessments were done at baseline and at end of treatment.Results: A total of 20 volunteers completed the study. Compared with baseline and placebo, Withania somnifera extract produced a significant decrease in mean percent change of arterial stiffness indices (AIx, radial and aortic BP). SEVR with CPT increased, however it was non-significant compared to baseline and placebo. Both treatments were well-tolerated and no serious adverse events were reported.Conclusions: Withania somnifera extract showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections, suggesting its beneficial effects in reducing stress induced cardiovascular changes. However, further clinical studies are warranted to evaluate these effects in patients with cardiovascular and other associated diseases

A Combined Linkage and Exome Sequencing Analysis for Electrocardiogram Parameters in the Erasmus Rucphen Family Study

Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 x 10(-4), minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 x 10(-3)) and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 x 10(-3)). Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval

National instruments labVIEW and video imaging technique for health status monitoring

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A combined linkage and exome sequencing analysis for electrocardiogram parameters in the Erasmus Rucphen family study

Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidat

CORRELAÇÃO ENTRE OBSTRUÇÃO ARTERIAL PERIFÉRICA E OBSTRUÇÃO DE VIAS AÉREAS EM PORTADORES DE DPOC NÃO REABILITADOS

A Doença Pulmonar Obstrutiva Crônica (DPOC) produz desordens fisiopatológicas respiratórias com severo comprometimento dos volumes pulmonares, podendo também ocasionar alterações extrapulmonares como as doenças arteriais periféricas (DAP). O estudo objetivou correlacionar o Índice Tornozelo-Braquial (ITB) com o Volume Expiratório Forçado no Primeiro Segundo (VEF1) e Fluxo Expiratório Forçado entre 25% e 75% da Capacidade Vital Forçada (FEF25-75%) em portadores de DPOC. Trata-se de um estudo correlacional com amostra selecionada por conveniência. Foram avaliados portadores de DPOC com estadiamentos Global Initiative for Chronic Obstructive Lung Disease (GOLD) entre II e IV. O ITB foi avaliado em membros superiores e membros inferiores através de esfigmomanômetro e doppler vascular portátil. A função pulmonar foi avaliada por espirometria digital, obtendo-se as variáveis capacidade vital forçada (CVF), VEF1 e FEF25-75%. Foram avaliados 12 indivíduos com média de idade de 66,58±6,1 anos e com Índice de Massa Corpórea de 29,21±6,7 Kg/m2. Houve predominância do sexo masculino (n=8, 66,7%). A média da CVF obtida foi de 2,44±0,78 L (0,9±18,1%pred); VEF1 de 1,33±0,45 L (50,4±15,5%pred), VEF25-75% de 0,65±0,32 L (26,9±16,6%pred) e do ITB de 0,88±0,12. Foi evidenciada correlação positiva moderada entre ITB e VEF1 (r= 0,684; p= 0,014). Nos portadores de DPOC avaliados, a presença de obstrução de via aérea alta apresentou-se relacionada à presença de doença arterial periférica

Blood pressure waveform contour analysis for assessing peripheral resistance changes in sepsis.

peer reviewedBACKGROUND: This paper proposes a methodology for helping bridge the gap between the complex waveform information frequently available in an intensive care unit and the simple, lumped values favoured for rapid clinical diagnosis and management. This methodology employs a simple waveform contour analysis approach to compare aortic, femoral and central venous pressure waveforms on a beat-by-beat basis and extract lumped metrics pertaining to the pressure drop and pressure-pulse amplitude attenuation as blood passes through the various sections of systemic circulation. RESULTS: Validation encompasses a comparison between novel metrics and well-known, analogous clinical metrics such as mean arterial and venous pressures, across an animal model of induced sepsis. The novel metric Ofe --> vc, the direct pressure offset between the femoral artery and vena cava, and the clinical metric, DeltaMP, the difference between mean arterial and venous pressure, performed well. However, Ofe --> vc reduced the optimal average time to sepsis detection after endotoxin infusion from 46.2 min for DeltaMP to 11.6 min, for a slight increase in false positive rate from 1.8 to 6.2%. Thus, the novel Ofe --> vc provided the best combination of specificity and sensitivity, assuming an equal weighting to both, of the metrics assessed. CONCLUSIONS: Overall, the potential of these novel metrics in the detection of diagnostic shifts in physiological behaviour, here driven by sepsis, is demonstrated

Hemodynamic monitor for rapid, cost-effective assessment of peripheral vascular function

Worldwide, at least 200 million people are affected by peripheral vascular diseases (PVDs), including peripheral arterial disease (PAD), chronic venous insufficiency (CVI) and deep vein thrombosis (DVT). These diseases have considerable socioeconomic impacts due to their high prevalence, cost of investigation, treatment and their effects on quality of life. PVDs are often undiagnosed with up to 60% of patients with PVD remaining asymptomatic. Early diagnosis is essential for effective treatment and reducing socioeconomic costs, particularly in patients with diabetes where early endovascular treatment can prevent lower extremity amputation. However, available diagnostic methods simply do not meet the needs of clinicians. For example, duplex ultrasound or plethysmography are time-consuming methods, costly and require access to highly trained clinicians. Due to the cost and time requirements of such methods, they are often reserved for symptomatic patients. On the other hand, the Ankle Brachial Index (ABI) test is cheap but has poor sensitivity for those patients with diabetes and the elderly, both growing high-risk populations. There is an urgent need for new diagnostic tools to enable earlier intervention. Researchers at the MARCS Institute have developed a novel hemodynamic monitor platform named HeMo, specifically for the assessment of peripheral blood flow in the leg. This development aimed to provide a fast and low-cost diagnosis of both peripheral arterial disease and chronic venous insufficiency. This work first provides a comprehensive literature review of the existing non-invasive diagnostic devices developed since 1677 to highlight the need of development of a new blood monitoring tool. Second, it presents the simplified circuit of the HeMo device and provides series of pilot experiments with HeMo demonstrating its potential for diagnosis of both peripheral arterial disease and chronic venous insufficiency. Third, it presents a quantitative characterisation of the electrical behaviour of the electro-resistive band sensors with the development of an expansion/contraction simulator rig and using spectral analysis. The characterisation of the electro-resistive band was essential to understand the nonlinear electrical behaviour of such sensors and would be of interest for other users and uses of the electro-resistive band sensors. However, in another perspective this sinusoidal linear stretching movement and the presented method shows an example for the application of the presented rig, highlighting that the same technique could be used for characterisation of similar stretchable sensors. Fourth, it shows data from a healthy population, assessing the performance of HeMo compared to light reflection rheography (LRR sensor-VasoScreen 5000) for the assessment of venous function. Fifth, it presents human study data where the performance of HeMo is compared to photoplethysmography (PPG sensor-VasoScreen 5000) for the evaluation of the arterial function. Overall, the presented work here, steps toward development of the final version of a novel hemodynamic monitoring device, and its validation

An intelligent mHealth-based adjunct to improve the management of patients with cardiovascular disease

Regular recording of vital signs, modification of lifestyle behaviour and monitoring of health progress has been shown to be effective to better manage patients with cardiovascular disease (CVD). Despite this, there remain significant hospital readmissions due to CVD exacerbations. This thesis investigated if the readmission rate of CVD patients could be reduced through remote longitudinal monitoring of physiological measurements and by offering a mobile health (mHealth)-based adjunct to assist in lifestyle modification. The thesis also investigated if there was a relationship between patient engagement and their clinical outcomes. To improve the remote management of CVD patients, the architecture of an intelligent mHealth adjunct called Total Cardiac Care (TCC) was developed based around a smartphone app and wireless peripherals to record physiological data and patient activity. The system also enabled the clinician to regularly monitor the patients’ condition using a web portal, facilitating the timely interventions when deemed necessary. The proposed system feasibility was investigated in a pilot trial, where it was widely accepted by both younger and older CVD patients with a high satisfaction rate (89.5%). The participants also had a high engagement rate with the different monitoring features (BP 77.2%, weight 74.3% and activity 84.8%). The results of a randomised controlled trial in which CVD patients (n = 164) were randomly assigned to either the mHealth intervention group or a traditional care control group identified a significant reduction in the 6-month all-cause (21 vs 41, risk reduction 49%, p = 0.015) and cardiac readmission (11 vs 25, risk reduction 56%, p = 0.025) risk when comparing the intervention cohort against the control cohort. These results suggest that the mHealth adjunct could increase the CVD patient’s engagement and the monitoring of physiological measurements and activity along with modified lifestyle behaviour over the long term could improve their cardiac health and decrease adverse events. To predict the CVD patient’s exacerbation, a model capable of detecting worsening events based on the critical change in the longitudinal physiological trends was developed using telemonitoring data collected from the intervention cohort. The model correctly predicted the CVD exacerbation events with 86.4% sensitivity, 58.4% specificity and 59.7% accuracy. This highlights that the integration of an exacerbation prediction model with the mHealth adjunct could enhance the quality of remote monitoring care provided to CVD patients