Computer simulation of three-dimensional plaque formation and progression in the carotid artery

Atherosclerosis is becoming the number one cause of death worldwide. In this study, three-dimensional computer model of plaque formation and development for human carotid artery is developed. The three-dimensional blood flow is described by the Navier-Stokes equation, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modeled by a convection-diffusion equation. The low-density lipoproteins transports in lumen of the vessel and through the vessel tissue are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. Fluid-structure interaction is used to estimate effective wall stress analysis. Plaque growth functions for volume progression are correlated with shear stress and effective wall stress distribution. We choose two specific patients from MRI study with significant plaque progression

Myocardial blood flow regulation in infarcted patients with stress-induced normalization of negative T waves

The correlation of stress-induced normalization of negative T waves (NTW) with regional myocardial blood flow (MBF) regulation and tissue viability remains still dented

Effects of Sapropterin on Endothelium-Dependent Vasodilation in Patients With CADASIL: A Randomized Controlled Trial

Background and Purpose-Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients

Womersley Number-Based Estimates of Blood Flow Rate in Doppler Analysis: In Vivo Validation by Means of Phase-Contrast MRI

The aim of this paper, was to present an in vivo validation of the Womersley number-based formula, by means of 2-D cine phase-contrast MRI (PCMRI)

Relationship between Pre-Implant Interleukin-6 Levels, Inflammatory Response, and Early Outcome in Patients Supported by Left Ventricular Assist Device: A Prospective Study

Purpose: The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among preimplant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients. Methods: In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA $11 was considered as main adverse outcome. Length of ICU-stay, 1 weektSOFA score, hospitalisation and 3-month survival were considered additional end-points. Results: During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score$11. Pre-implant level of IL-6 $ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group. Conclusions: LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome

Time-course of plasma NT-proc-type natriuretic peptide in end-stage heart failure patients supported by left ventricular assist device implant

Purpose: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) as well as the respective amino-terminal NT-proANP and NT-proBNP have now been well established as predictors of outcome in patients with heart failure (HF). C-type natriuretic peptide (CNP) and NT-proCNP are increased in HF patients as a function of disease severity, supporting a role for these peptides in the pathophysiology of HF, but their modifications during left ventricular assist device (LVAD) implant are lacking. Aim of this study was to evaluate the time-course of natriuretic peptides in end-stage HF patients undergoing LVAD implant in order to recognize new reliable predictive biomakers of cardiac recovery during LVAD. Methods: Five end-stage HF patients (NYHA class III and IV; age: 57?11 yrs; LVEF%<20) undergoing LVAD implantation were studied. Clinical hemodynamic evaluation and blood samples were obtained at admission (T1) and at 4, 24, 72 hrs and 1, 2, 4 weeks (T2-T7) after LVAD implant. NT-proANP and NT-proCNP were measured in plasma EDTA and aprotinin samples by a direct ELISA () while NT-proBNP by the Elecsys? 2010 analyzer. Results: The NT-proCNP time-course during LVAD was the following: T1=88.8?12.8 pg/ml; T2=144?29.8; T3=241.6?86.8 (p<0.05 vs T1); T4=229.7?66.4; T5=162.3?66.5; T6=175.3?47.7; T7=76.9?8 (p=ns vs T1). NT-proANP showed a similar pathway while NT-proBNP is reduced after LVAD implant (T1=4.1?2.2 ng/ml; T3=3.0?0.4), remaining lower than at baseline until 4 weeks (T7=3.1?0.9 ng/ml). NT-proCNP positively correlated with NT-proANP (p=0.03) while no correlation was found with NT-proBNP. Conclusions: This study reports for the first time original data on NT-proCNP levels after LVAD as a function of the time. The natriuretic peptides are differently modulated by LVAD, although all peptides resulted reduced after 4 weeks from implantation. The parallel determination of these effectors could allow us to obtain an integrated description of pathophysiological changes occurring during mechanical support

Paraoxonase 1 L55M, Q192R and paraoxonase 2 S311C alleles in atherothrombosis

Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation

Is the Oxidant/Antioxidant Status Altered in CADASIL Patients?

The altered aggregation of proteins in non-native conformation is associated with endoplasmic reticulum derangements, mitochondrial dysfunction and excessive production of reactive oxygen species. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary systemic vasculopathy, caused by NOTCH3 mutations within the receptor extracellular domain, that lead to abnormal accumulation of the mutated protein in the vascular wall. NOTCH3 misfolding could cause free radicals increase also in CADASIL. Aim of the study was to verify whether CADASIL patients have increased oxidative stress compared to unrelated healthy controls. We enrolled 15 CADASIL patients and 16 gender- and age-matched healthy controls with comparable cardiovascular risk factor. Blood and plasma reduced and total aminothiols (homocysteine, cysteine, glutathione, cysteinylglycine) were measured by HPLC and plasma 3- nitrotyrosine by ELISA. Only plasma reduced cysteine (Pr-Cys) and blood reduced glutathione (Br-GSH) concentrations differed between groups: in CADASIL patients Br-GSH levels were higher (p = 0.019) and Pr-Cys lower (p = 0.010) than in controls. No correlation was found between Br-GSH and Pr-Cys either in CADASIL patients (rho 0.25, P=0.36) or in controls (rho -0.15, P=0.44). Conversely, 3- nitrotyrosine values were similar in CADASIL and healthy subjects (p = 0.82). The high levels of antioxidant molecules and low levels of oxidant mediators found in our CADASIL population might either be expression of an effective protective action against free radical formation at an early stage of clinical symptoms or they could suggest that oxidative stress is not directly involved in the pathogenesis of CADASIL

Neopterin levels are independently associated with cardiac remodeling in patients with chronic heart failure

Neopterin, a marker of inflammation and monocyte activation, is found increased in patients with heart failure (HF). This study investigates whether neopterin levels correlate with left ventricular (LV) remodeling and brain natriuretic peptide (BNP), a marker of cardiac stress, in chronic HF (CHF) patients with different severity of disease. The relationship between elevated neopterin levels and LV enlargement in CHF patients suggests a crucial role of monocyte activation in the development of cardiac dysfunction in CHF patients. Assessment of neopterin levels is a potential biomarker to evaluate the progression of LV remodeling in CHF patients

Preliminary experimental analysis of Reservoir Computing approach for balance assessment

Evaluation of balance stability in elderly people is of prominent relevance in the field of health monitoring. Recently, the use of Wii Balance Board has been proposed as valid alternative to clinical balance tests, such as the widely used Berg Balance Scale (BBS) test, allowing to measure and analyze static features such as the duration or the speed of assessment of patients' center of pressure. In an innovative way, in this paper we propose to take into consideration the whole temporal information generated by the balance board, analyzing it by means of dynamical neural networks. In particular, using Recurrent Neural Networks implemented according to the Reservoir Computing paradigm, we propose to estimate the BBS score from the temporal data generated by the execution of one simple exercise on the balance board. Preliminary experimental assessments of the proposed approach on a real-world dataset show promising results