Cross-Sectional Relationships of Proximal Aortic Stiffness and Left Ventricular Diastolic Function in Adults in the Community.

Background Stiffness of the proximal aorta may play a critical role in adverse left ventricular (LV)-vascular interactions and associated LV diastolic dysfunction. In a community-based sample, we sought to determine the association between proximal aortic stiffness measured by cardiovascular magnetic resonance (CMR) and several clinical measures of LV diastolic mechanics. Methods and Results Framingham Heart Study Offspring adults (n=1502 participants, mean 67±9 years, 54% women) with available 1.

A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia.

Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function.

Association of Exhaled Carbon Monoxide With Ideal Cardiovascular Health, Circulating Biomarkers, and Incidence of Heart Failure in the Framingham Offspring Study.

Background Exhaled carbon monoxide (eCO) is directly associated with traditional cardiovascular disease risk factors and incident cardiovascular disease. However, its relation with the cardiovascular health score and incidence of heart failure (HF) has not been investigated. Methods and Results We measured eCO in 3521 Framingham Heart Study Offspring participants attending examination cycle 6 (mean age 59 years, 53% women).

Natural History of Obesity Subphenotypes: Dynamic Changes Over Two Decades and Prognosis in the Framingham Heart Study.

Context: The natural histories of obesity subphenotypes are incompletely delineated.

Objectives: To investigate dynamic changes in obesity subphenotypes and associations with outcomes.

Design, Setting, Participants, And Measurements: Framingham Offspring Cohort participants (n = 4291) who attended the examination cycles 2 (1979 to 1983) to 7 (1998 to 2001), which included 26,508 participant observations.

Metabolic Predictors of Change in Vascular Function: Prospective Associations From a Community-Based Cohort.

Vascular function varies with age because of physiological and pathological factors. We examined relations of longitudinal change in vascular function with change in metabolic traits. Longitudinal changes in vascular function and metabolic traits were examined in 5779 participants (mean age, 49.

Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

Importance: In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials.

Objective: To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT.

Robust fluorescent labelling of micropipettes for use in fluorescence microscopy: application to the observation of a mosquito borne parasite infection.

The ability to monitor micropipette injections with a high-resolution fluorescent microscope has utility for a variety of applications. Herein, different approaches were tested for creating broad-band fluorescently labelled glass micropipettes including: UV cured glass glues, baked glass enamel containing fluorescent dyes as well as nanodiamonds attached during pipette formation in the microforge. The most robust and simplest approach was to use labelled baked enamel on the exterior of the pipette.

Heritability and risks associated with early onset hypertension: multigenerational, prospective analysis in the Framingham Heart Study.

 To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death. Multigenerational, prospective cohort study. Framingham Heart Study.

Risk for hypertension crosses generations in the community: a multi-generational cohort study.

Aims: Parental hypertension is known to predict high blood pressure (BP) in children. However, the extent to which risk for hypertension is conferred across multiple generations, notwithstanding the impact of environmental factors, is unclear. Our objective was therefore to evaluate the degree to which risk for hypertension extends across multiple generations of individuals in the community.

Aortic-Brachial Arterial Stiffness Gradient and Cardiovascular Risk in the Community: The Framingham Heart Study.

A recent study reported that the aortic-brachial arterial stiffness gradient, defined as carotid-radial/carotid-femoral pulse wave velocity (PWV ratio), predicts all-cause mortality better than carotid-femoral pulse wave velocity (CFPWV) alone in dialysis patients. However, the prognostic significance of PWV ratio for cardiovascular disease (CVD) in the community remains unclear. Accordingly, we assessed the correlates and prognostic value of the PWV ratio in 2114 Framingham Heart Study participants (60±10 years; 56% women) free of overt CVD.

Relative Contributions of Arterial Stiffness and Hypertension to Cardiovascular Disease: The Framingham Heart Study.

Background: The presence and implications of abnormal arterial stiffness, a potential independent predictor of outcomes, in community-dwelling treated hypertensives is unknown. Furthermore, limited data exist regarding the risk of cardiovascular disease (CVD) associated with arterial stiffness across the entire range of blood pressure.

Methods And Results: We measured carotid-femoral pulse wave velocity (PWV) and classical CVD risk factors in 2127 community-dwelling participants (mean age 60 years, 57% women) of The Framingham Offspring Cohort.

Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways.

A subset of high-risk Human Papillomaviruses (HPVs) are the causative agents of a large number of human cancers, of which cervical is the most common. Two viral oncoproteins, E6 and E7, contribute directly towards the development and maintenance of malignancy. A characteristic feature of the E6 oncoproteins from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at its C-terminus, which confers interaction with cellular proteins harbouring PDZ domains.

Epidemiology of cardiovascular disease: recent novel outlooks on risk factors and clinical approaches.

Introduction: Cardiovascular (CVD) risk assessment with traditional risk factors (age, sex, blood pressure, lipids, smoking and diabetes) has remained relatively invariant over the past decades despite some inaccuracies associated with this approach. However, the search for novel, robust and cost-effective risk markers of CVD risk is ongoing.

Areas Covered: A large share of the major developments in CVD risk prediction during the past five years has been made in large-scale biomarker discovery and the so called 'omics' - the rapidly growing fields of genomics, transcriptomics, epigenetics and metabolomics.

Relations of Central Hemodynamics and Aortic Stiffness with Left Ventricular Structure and Function: The Framingham Heart Study.

Background: The differing relations of steady and pulsatile components of central hemodynamics and aortic stiffness with cardiac dimensions and function have not been fully elucidated.

Methods And Results: Central hemodynamics and carotid-femoral pulse wave velocity (CFPWV, a measure of aortic stiffness) were measured by arterial tonometry in 5799 participants of the Framingham Heart Study (mean age 51 years, 54% women) and related to echocardiographic left ventricular (LV) dimensions and systolic and diastolic function using multivariable-adjusted partial Pearson correlations. Mean arterial pressure (MAP, steady component of central blood pressure) was associated positively with LV wall thickness (r=0.

Circulating Adipokines and Vascular Function: Cross-Sectional Associations in a Community-Based Cohort.

Adipokines may be potential mediators of the association between excess adiposity and vascular dysfunction. We assessed the cross-sectional associations of circulating adipokines with vascular stiffness in a community-based cohort of younger adults. We related circulating concentrations of leptin and leptin receptor, adiponectin, retinol-binding protein 4, and fatty acid-binding protein 4 to vascular stiffness measured by arterial tonometry in 3505 Framingham Third Generation cohort participants free of cardiovascular disease (mean age 40 years, 53% women).

The association between reduction in inflammation and changes in lipoprotein levels and HDL cholesterol efflux capacity in rheumatoid arthritis.

Background: Potent anti-inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low-density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high-density lipoprotein (HDL) cholesterol efflux capacity.

Secular trends in echocardiographic left ventricular mass in the community: the Framingham Heart Study.

Objective: To investigate secular trends in echocardiographically determined left ventricular mass (LVM).

Design, Setting And Participants: Longitudinal community-based cohort study in Framingham, Massachussetts. LVM was calculated from routine echocardiography in 4320 participants (52% women) of the Framingham offspring cohort at examination cycles 4 (1987-1991), 5 (1991-1995), 6 (1995-1998) and 8 (2005-2008), totalling 13 971 person-observations.

Influence of residual stress/strain on the biomechanical stability of vulnerable coronary plaques: potential impact for evaluating the risk of plaque rupture.

In a vulnerable plaque (VP), rupture often occurs at a site of high stress within the cap. It is also known that vessels do not become free of stress when all external loads are removed. Previous studies have shown that such residual stress/strain (RS/S) tends to make the stress distribution more uniform throughout the media of a normal artery.

Enzyme I: the gateway to the bacterial phosphoenolpyruvate:sugar phosphotransferase system.

Regulatory aspects of the bacterial phosphoenolpyruvate (PEP):sugar phosphotransferase system (PTS) are reviewed. The structure and conformational stability of the first protein (enzyme I) of the PTS, as well as the requirement for enzyme I to dimerize for autophosphorylation by PEP in the presence of MgCl2 are discussed.

NMR spectral analysis of kinetic data using natural lineshapes.

An automated rapid data analysis scheme for NMR spectroscopy time course studies is presented. This method uses a high signal-to-noise reference spectrum collected at the beginning of a time course as a lineshape model to analyze subsequent low signal-to-noise data collected with higher time resolution. The method is fast (approximately 1 s to evaluate two peaks in a 2K spectrum) and easily implemented on NMR spectrometer computers.

Experimental preparations and models for MRS.

Magnetic resonance spectroscopy (MRS) has been most extensively applied to the study of animal models and not humans. The major reason for this extensive animal research is due to the nature of the early magnetic resonance high-field magnets, which only permitted the study of isolated cells, tissues, or small animals. However, equally important was the necessity of using animal models in the investigation of both the MRS technique itself and the actual biochemistry and physiology it interrogates.

Saturation and inversion transfer studies of creatine kinase kinetics in rabbit skeletal muscle in vivo.

The steady-state kinetics of the creatine kinase reaction in rabbit skeletal muscle in vivo was investigated using inversion and saturation magnetization transfer techniques. Both techniques determined the forward rate of this reaction (creatine phosphate ATP) as approximately 0.3 s-1.