Finite Element Modeling Application in Forensic Practice: A Periprosthetic Femoral Fracture Case Study

The incidence of periprosthetic fractures has rapidly increased in the last two decades and has been the cause of a large number of revision surgeries and permanent physical disability for many patients, as well as a significant socioeconomic burden for many nations. This research deals with a periprosthetic femur fracture real event, occurred following a total hip arthroplasty and treated with one of the most widespread internal fixation methods: the implant of a periprosthetic femur plate system. A Finite Element analysis was performed to investigate the implanted femur plate break after a short follow-up and to understand the plate break causes. Such events are currently object of forensic debate as more and more often hospitals, surgeons, and medical device manufacturers are denounced by patients to whom similar events occur. In this work, different load situations acting on the femur during daily and incidental activities were simulated, in order to validate the correct behavior of the plate, according to the intended use recommended by the manufacturer. The analysis demonstrates that the plate failure can occur in situations of unconventional loading such as that caused by stumbling and in presence of incomplete bone healing

Different water and light regimes affect ionome composition in grapevine (Vitis vinifera L.)

Many inorganic cations play a major role in winemaking processes and wine quality. For this reason, chemistry at the elemental level ("ionomic") of the grape berry is of concern not only to the viticulturist, but also to the oenologist due to their direct impact on juice and must composition, which in turn affect wine quality. The aim of this research was to evaluate the effect of reduced irrigation and incident light (by means of micronized calcite) on the berry skin ionome of the Italian red grape 'Aglianico'. The study was carried out in a five-years-old vineyard (Vitis vinifera L. 'Aglianico') located in Southern Italy. Half of the plants (IRR) were drip irrigated, whereas the other half were not irrigated (NIR). Half of IRR and NIR plants were treated with Megagreen® micronized calcite. In all the treatments, plant water status and gas exchange were determined. The mean values of stem water potential (ψw) during the experiment were –1.02 and –1.10 MPa in IRR and NIR, respectively. The calcite treatments did not show changes in ψw values if compared to the untreated ones. The values of gas exchange were not statistically different among the four treatments. Grape berries were separated into three groups of mass, and the levels of macroelements, microelements and lanthanides were measured. Irrigation and calcite significantly affected macroelements distribution in all the three groups of mass, with Fe, Cu and Zn being significantly higher in the IRR and calcite-treated treatments. The effect of irrigation on the changes in microelement levels was significant for some elements. Calcite-treated vines showed higher mean values of Co, Cd, Hg and Pb. Regarding lanthanides, in calcite-untreated vines, irrigation determined significant decreases in average La, Ce, Nd, whereas in calcite-treated vines, increases in the mean concentrations of Ce, Nd, Sm, Gd, Dy, Er and Yb were found. Generally, lanthanide levels did not change between calcite-treated and untreated vines, and in all the treatments Lu resulted to be the most abundant one. Macroelements, microelements and lanthanide levels generally decreased with decreasing berry weight. The dynamics of the extractability of metals from grape berries to must during fermentation could be used to predict wine quality during the following processes and for wine traceability purposes.

A Eulerian method to analyze wall shear stress fixed points and manifolds in cardiovascular flows

Based upon dynamical systems theory, a fixed point of a vector field such as the wall shear stress (WSS) at the luminal surface of a vessel is a point where the vector field vanishes. Unstable/stable manifolds identify contraction/expansion regions linking fixed points. The significance of such WSS topological features lies in their strong link with “disturbed” flow features like flow stagnation, separation and reversal, deemed responsible for vascular dysfunction initiation and progression. Here, we present a Eulerian method to analyze WSS topological skeleton through the identification and classification of WSS fixed points and manifolds in complex vascular geometries. The method rests on the volume contraction theory and analyzes the WSS topological skeleton through the WSS vector field divergence and Poincare´ index. The method is here applied to computational hemodynamics models of carotid bifurcation and intracranial aneurysm. An in-depth analysis of the time dependence of the WSS topological skeleton along the cardiac cycle is provided, enriching the information obtained from cycle-average WSS. Among the main findings, it emerges that on the carotid bifurcation, instantaneous WSS fixed points co-localize with cycle-average WSS fixed points for a fraction of the cardiac cycle ranging from 0 to 14.5 % ; a persistent instantaneous WSS fixed point confined on the aneurysm dome does not co-localize with the cycle-average low-WSS region. In conclusion, the here presented approach shows the potential to speed up studies on the physiological significance of WSS topological skeleton in cardiovascular flows, ultimately increasing the chance of finding mechanistic explanations to clinical observations

On the association between helical flow and plaque progression in coronary arteries

Arterial hemodynamics is markedly characterized by the presence of helical flow (HF) patterns, whose physiological significance has been investigated in recent years, in particular with respect to the atheroprotective role played by specific HF structures. However, a gap in knowledge still exist on the significance of HF in coronary arteries, a prominent site of atherosclerotic plaque formation. The aim of this study is to carry out, in a representative sample of 15 swine coronary arteries, a systematic analysis of HF and wall thickness using computational fluid dynamics and intravascular ultrasound imaging. In detail, here we investigate possible associations of HF with (1) atherogenic wall shear stress (WSS) phenotypes, and (2) atherosclerotic plaque progression (in a follow up study). Our findings demonstrate for the first time that: (1) HF naturally characterizes coronary hemodynamics; (2) unfavourable conditions of WSS are strongly inversely associated with helicity intensity; (3) HF intensity protects against atherosclerotic plaque growth

Does the inflow velocity profile influence physiologically relevant flow patterns in computational hemodynamic models of left anterior descending coronary artery?

Patient-specific computational fluid dynamics is a powerful tool for investigating the hemodynamic risk in coronary arteries. Proper setting of flow boundary conditions in computational hemodynamic models of coronary arteries is one of the sources of uncertainty weakening the findings of in silico experiments, in consequence of the challenging task of obtaining in vivo 3D flow measurements within the clinical framework. Accordingly, in this study we evaluated the influence of assumptions on inflow velocity profile shape on coronary artery hemodynamics. To do that, (1) ten left anterior descending coronary artery (LAD) geometries were reconstructed from clinical angiography, and (2) eleven velocity profiles with realistic 3D features such as eccentricity and differently shaped (single- and double-vortex) secondary flows were generated analytically and imposed as inflow boundary conditions. Wall shear stress and helicity-based descriptors obtained prescribing the commonly used parabolic velocity profile were compared with those obtained with the other velocity profiles. Our findings indicated that the imposition of idealized velocity profiles as inflow boundary condition is acceptable as long the results of the proximal vessel segment are not considered, in LAD coronary arteries. As a pragmatic rule of thumb, a conservative estimation of the length of influence of the shape of the inflow velocity profile on LAD local hemodynamics can be given by the theoretical entrance length for cylindrical conduits in laminar flow conditions

N-4 Alkyl Cytosine Derivatives Synthesis: A New Approach

The selective N-4 alkylation of cytosine plays a critical role in the synthesis of biologically active molecules. This work focuses on the development of practical reaction conditions toward a regioselective synthesis of N-4-alkyl cytosine derivatives. The sequence includes a direct and selective sulfonylation at the N-1 site of the cytosine, followed by the alkylation of the amino siteusing KHMDS in CH2Cl2/THF mixture, providing a fast and efficient approach consistent withpyrimidine-based drug design

The Atheroprotective Nature of Helical Flow in Coronary Arteries

Arterial hemodynamics is markedly characterized by the presence of helical flow patterns. Previous observations suggest that arterial helical blood flow is of physiological significance, and that its quantitative analysis holds promise for clinical applications. In particular, it has been reported that distinguishable helical flow patterns are potentially atheroprotective in the carotid bifurcation as they suppress flow disturbances. In this context, there is a knowledge gap about the physiological significance of helical flow in coronary arteries, a prominent site of atherosclerotic plaque formation. This study aimed at the quantitative assessment of helical blood flow in coronary arteries, and to investigate its possible associations with vascular geometry and with atherogenic wall shear stress (WSS) phenotypes in a representative sample of 30 swine coronary arteries. This study demonstrates that in coronary arteries: (1) the hemodynamics is characterized by counter-rotating bi-helical flow structures; (2) unfavorable conditions of WSS are strongly and inversely associated with helicity intensity (r=-0.91; p<0.001), suggesting an atheroprotective role for helical flow in the coronary tree; (3) vascular torsion dictates helical flow features (r=0.64; p<0.001). The findings of this work support future studies on the role of helical flow in atherogenesis in coronary arteries

3D GRID-based pharmacophore and Metadynamics approaches for the rational design of N-Methyl β-sheet breaker peptides as inhibitors of the Alzheimer's Aβ-amyloid fibrillogenesis

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the loss of the cognitive functions and dementia. Several scientific evidences report that a central role in the pathogenesis of AD is played by the brain deposition of insoluble aggregates of β-amyloid protein (Aβ) proteins, thus causing neuronal cell death [1]. For this reason, one of the promising approach is to inhibit the aggregation of Aβ peptides. Because Aβ is self-assembling, one possible strategy to prevent this process is to use short peptide fragments homologous to the full-length wild-type Aβ protein. From this consideration, several short synthetic peptides were designed as beta-sheet breakers (BSB) [2]. In particular, the pentapetide Ac-LPFFD-NH2 (iAβ5p) exhibited a certain capability to inhibit Aβ fibrillogenesis [3]. iAβ5p analogs [4] were, then, designed by introducing N-Methylation at the amide bond nitrogen were also promising BSB. Here, we describe the methodological approach, which combines 3D GRID-based pharmacophore peptide screening with Well-Tempered Metadynamics simulations aimed to the discovery of novel N-Methylated BSB. This approach led us to identify two promising, cell permeable, N-Methylated peptides that were further evaluated for their BSB properties showing a significant improvement of the fibrillogenesis inhibition with respect to the lead iAβ5p

Exploring novel arterio-venous graft designs to reduce vascular access failure risk

Although arterio-venous grafts (AVGs) are the second best option as permanent vascular access for hemodialysis, this solution is still affected by a relevant failure rate associated with neointimal hyperplasia (IH), mainly located at the venous anastomosis, where abnormal hemodynamics occurs. In this study we use computational fluid dynamics (CFD) to investigate the impact of six innovative AVG designs on reducing the IH risk at the distal anastomosis in AVGs. Findings from simulations clearly show that using a helical shaped flow divider located in the venous side of the graft could assure a reduced hemodynamic risk of failure at the distal anastomosis, with a clinically irrelevant increase in pressure drop over the graft