Lipids and Cardiovascular Organ Damage in Type 2 Diabetes Mellitus

One of the mechanisms underlying increased cardiovascular (CV) risk in patients with type 2 diabetes mellitus is atherogenic dyslipidemia, that is characterized by elevated triglycerides and free fatty acids (FFAs) levels, low levels of high-density lipoprotein cholesterol (HDL) and an excess of small dense low-density lipoprotein particles (sdLDLs). Each component of atherogenic dyslipidemia is associated with CV events and triggers alterations at different levels of CV system through different pathways. FFAs and sdLDLs induce endothelial dysfunction, intima-media thickening, plaque formation and arterial stiffening through increase in oxidative stress and inflammation and promoting lipid accumulation and smooth muscle cells (SMCs) proliferation in vascular wall. In contrast, HDL exerts protective effect on arterial wall by increasing nitric oxide availability, by reverse cholesterol transport and by suppression of SMCs proliferation and migration. FFAs overload results in a switch in myocardial substrate utilization, causing changes in myocardial energy metabolism and an increase in baseline oxygen consumption. Accumulation of toxic lipid intermediates in myocardium provokes damage of cellular membrane integrity, organelle dysfunction and apoptosis with consequent decrease in myocardial performance. The structural and functional changes in myocardium can be reversed by therapy with reconstructed HDL. Therefore, the impact of atherogenic dyslipidemia on CV system is not limited on accelerated atherosclerosis, but causes different organ damages that must be considered in their complexity

Therapeutic implications of immunogenic cell death in human cancer

Dendritic cells (DCs) are central to the adoptive immune response, and their function is regulated by diverse signals in a context-specific manner. Different DCs have been described in physiologic conditions, inflammation, and cancer, prompting a series of questions on how adoptive immune responses, or tolerance, develop against tumors. Increasing evidence suggests that tumor treatments induce a dramatic change on tumor-infiltrating lymphocytes and, in particular, on some DC subtypes. In this review, we summarize the latest evidence on the role of DCs in cancer and preliminary evidence on chemotherapy-associated antigens identified in human cancers

Carotid-femoral pulse wave velocity estimated by an ultrasound system

To date, regional aortic stiffness can be evaluated by the reference tonometric technique via the pulse wave velocity (PWV) measured in two points: the carotid and the femoral arteries. Based on a similar intersecting tangent algorithm, we have developed a new method for the determination of carotid-femoral PWV using a high-resolution echo tracking ultrasound system. Herein, PWV can be computed from the measurement of the transit time between the foot of the carotid diameter waveform and the foot of the femoral diameter waveform. The study was carried out on 50 consecutive patients at rest (29 men, mean age 30 ± 18 yrs) recruited on the occasion of a vascular screening for atherosclerosis. Carotid-femoral PWV was determined by a trained operator using a tonometric technique, (PWVpp, PulsePen, Italy), and an echotracking ultrasound system, (PWVus, e-tracking Alpha 10, Aloka, Japan). Relationship between PWVpp and PWVus was evaluated by linear regression. A Pearson’s correlation coefficient of r=0.95 was found between both variables (95% confidence interval 0.90-0.99; P<0.0001; PWVus= 0,91*PWVpp+0.44). The Bland–Altman plot comparing PWVpp and PWVus showed a systematic offset of -0.07 m.s-1 with a limit of agreement from -1,33 to 1,19 m.s-1. Our results show an excellent and significant correlation between both techniques which confirms that ultrasound system can provide a reliable estimate of the regional aortic stiffness like the tonometric technique does. Additional studies are now needed to show the simplicity of the measurement using ultrasound system while maintaining reliability even in overweight patients

Combined Diffusion-Relaxometry MRI to Identify Dysfunction in the Human Placenta

Purpose: A combined diffusion-relaxometry MR acquisition and analysis pipeline for in-vivo human placenta, which allows for exploration of coupling between T2* and apparent diffusion coefficient (ADC) measurements in a sub 10 minute scan time. Methods: We present a novel acquisition combining a diffusion prepared spin-echo with subsequent gradient echoes. The placentas of 17 pregnant women were scanned in-vivo, including both healthy controls and participants with various pregnancy complications. We estimate the joint T2*-ADC spectra using an inverse Laplace transform. Results: T2*-ADC spectra demonstrate clear quantitative separation between normal and dysfunctional placentas. Conclusions: Combined T2*-diffusivity MRI is promising for assessing fetal and maternal health during pregnancy. The T2*-ADC spectrum potentially provides additional information on tissue microstructure, compared to measuring these two contrasts separately. The presented method is immediately applicable to the study of other organs

Mapping complex cell morphology in the grey matter with double diffusion encoding MR: a simulation study

This paper investigates the impact of cell body (soma) size and branching of cellular projections on diffusion MR imaging (dMRI) and spectroscopy (dMRS) signals for both standard single diffusion encoding (SDE) and more advanced double diffusion encoding (DDE) measurements using numerical simulations. The aim is to study the ability of dMRI/dMRS to characterize the complex morphology of brain grey matter, focusing on these two distinctive features. To this end, we employ a recently developed framework to create realistic meshes for Monte Carlo simulations, covering a wide range of soma sizes and branching orders of cellular projections, for diffusivities reflecting both water and metabolites. For SDE sequences, we assess the impact of soma size and branching order on the signal b-value dependence as well as the time dependence of the apparent diffusion coefficient (ADC). For DDE sequences, we assess their impact on the mixing time dependence of the signal angular modulation and of the estimated microscopic anisotropy, a promising contrast derived from DDE measurements. The SDE results show that soma size has a measurable impact on both the b-value and diffusion time dependence, for both water and metabolites. On the other hand, branching order has little impact on either, especially for water. In contrast, the DDE results show that soma size has a measurable impact on the signal angular modulation at short mixing times and the branching order significantly impacts the mixing time dependence of the signal angular modulation as well as of the derived microscopic anisotropy, for both water and metabolites. Our results confirm that soma size can be estimated from SDE based techniques, and most importantly, show for the first time that DDE measurements show sensitivity to the branching of cellular projections, paving the way for non-invasive characterization of grey matter morphology

ConFiG: Contextual Fibre Growth to generate realistic axonal packing for diffusion MRI simulation

This paper presents Contextual Fibre Growth (ConFiG), an approach to generate white matter numerical phantoms by mimicking natural fibre genesis. ConFiG grows fibres one-by-one, following simple rules motivated by real axonal guidance mechanisms. These simple rules enable ConFiG to generate phantoms with tuneable microstructural features by growing fibres while attempting to meet morphological targets such as user-specified density and orientation distribution. We compare ConFiG to the state-of-the-art approach based on packing fibres together by generating phantoms in a range of fibre configurations including crossing fibre bundles and orientation dispersion. Results demonstrate that ConFiG produces phantoms with up to 20% higher densities than the state-of-the-art, particularly in complex configurations with crossing fibres. We additionally show that the microstructural morphology of ConFiG phantoms is comparable to real tissue, producing diameter and orientation distributions close to electron microscopy estimates from real tissue as well as capturing complex fibre cross sections. Signals simulated from ConFiG phantoms match real diffusion MRI data well, showing that ConFiG phantoms can be used to generate realistic diffusion MRI data. This demonstrates the feasibility of ConFiG to generate realistic synthetic diffusion MRI data for developing and validating microstructure modelling approaches

Impact of within-voxel heterogeneity in fibre geometry on spherical deconvolution

Axons in white matter have been shown to have varying geometries within a bundle using ex vivo imaging techniques, but what does this mean for diffusion MRI (dMRI) based spherical deconvolution (SD)? SD attempts to estimate the fibre orientation distribution function (fODF) by assuming a single dMRI fibre response function (FRF) for all white matter populations and deconvolving this FRF from the dMRI signal at each voxel to estimate the fODF. Variable fibre geometry within a bundle however suggests the FRF might not be constant even within a single voxel. We test what impact realistic fibre geometry has on SD by simulating the dMRI signal in a range of realistic white matter numerical phantoms, including synthetic phantoms and real axons segmented from electron microscopy. We demonstrate that variable fibre geometry leads to a variable FRF across axons and that in general no single FRF is effective to recover the underlying fibre orientation distribution function (fODF). This finding suggests that assuming a single FRF can lead to misestimation of the fODF, causing further downstream errors in techniques such as tractography

Sorgo para pastejo/corte e cobertura do solo no período de outono/inverno (safrinha) em Mato Grosso do Sul.

Em Mato Grosso do Sul, as principais culturas utilizadas para cobertura de solo na safrinha são o milheto, a aveia e o nabo (Hernani et al., 1995; Machado, 2003). Para pastejo, também são utilizadas essas espécies, com exceção do nabo. Devido ao risco de geadas, as espécies adaptadas ao clima frio, como a aveia e o nabo, são mais utilizadas na região sul do Estado. Na região norte, o milheto e o sorgo são mais produtivos no período de outono, porque o clima, apesar de seco, é quente, favorecendo as espécies tropicais. Em regiões com esta condição, o sorgo é muito utilizado para a produção de grãos, sendo recente sua utilização para a produção de palha e forragem. Pela sua tolerância a déficit hídrico e a baixas temperaturas, a cultura vem ganhando importância econômica no Estado. Este estudo teve como objetivo selecionar genótipos de sorgo para pastejo na safra de outono/inverno, em sucessão a soja.bitstream/item/38771/1/BP-200416.pd

Left ventricular ejection time, not heart rate, is an independent correlate of aortic pulse wave velocity.

Salvi P, Palombo C, Salvi GM, Labat C, Parati G, Benetos A. Left ventricular ejection time, not heart rate, is an independent correlate of aortic pulse wave velocity. J Appl Physiol 115: 1610–1617, 2013. First published September 19, 2013; doi:10.1152/japplphysiol.00475.2013.— Several studies showed a positive association between heart rate and pulse wave velocity, a sensitive marker of arterial stiffness. However, no study involving a large population has specifically addressed the dependence of pulse wave velocity on different components of the cardiac cycle. The aim of this study was to explore in subjects of different age the link between pulse wave velocity with heart period (the reciprocal of heart rate) and the temporal components of the cardiac cycle such as left ventricular ejection time and diastolic time. Carotid-femoral pulse wave velocity was assessed in 3,020 untreated subjects (1,107 men). Heart period, left ventricular ejection time, diastolic time, and early-systolic dP/dt were determined by carotid pulse wave analysis with high-fidelity applanation tonometry. An inverse association was found between pulse wave velocity and left ventricular ejection time at all ages (25 years, r2 0.043; 25–44 years, r2 0.103; 45–64 years, r2 0.079; 65–84 years, r2 0.044; 85 years, r2 0.022; P 0.0001 for all). A significant (P 0.0001) negative but always weaker correlation between pulse wave velocity and heart period was also found, with the exception of the youngest subjects (P0.20). A significant positive correlation was also found between pulse wave velocity and dP/dt (P 0.0001). With multiple stepwise regression analysis, left ventricular ejection time and dP/dt remained the only determinant of pulse wave velocity at all ages, whereas the contribution of heart period no longer became significant. Our data demonstrate that pulse wave velocity is more closely related to left ventricular systolic function than to heart period. This may have methodological and pathophysiological implications