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.

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

Wall shear stress topological skeleton independently predicts long-term restenosis after carotid bifurcation endarterectomy

Wall Shear Stress (WSS) topological skeleton, composed by fixed points and the manifolds linking them, reflects the presence of blood flow features associated to adverse vascular response. However, the influence of WSS topological skeleton on vascular pathophysiology is still underexplored. This study aimed to identify direct associations between the WSS topological skeleton and markers of vascular disease from real-world clinical longitudinal data of long-term restenosis after carotid endarterectomy (CEA). Personalized computational hemodynamic simulations were performed on a cohort of 13 carotid models pre-CEA and at 1 month after CEA. At 60 months after CEA, intima-media thickness (IMT) was measured to detect long-term restenosis. The analysis of the WSS topological skeleton was carried out by applying a Eulerian method based on the WSS vector field divergence. To provide objective thresholds for WSS topological skeleton quantitative analysis, a computational hemodynamic dataset of 46 ostensibly healthy carotid bifurcation models was considered. CEA interventions did not completely restore physiological WSS topological skeleton features. Significant associations emerged between IMT at 60 months follow-up and the exposure to (1) high temporal variation of WSS contraction/expansion (R2 = 0.51, p < 0.05), and (2) high fixed point residence times, weighted by WSS contraction/expansion strength (R2 = 0.53, p < 0.05). These WSS topological skeleton features were statistically independent from the exposure to low WSS, a previously reported predictor of long-term restenosis, therefore representing different hemodynamic stimuli and potentially impacting differently the vascular response. This study confirms the direct association between WSS topological skeleton and markers of vascular disease, contributing to elucidate the mechanistic link between flow disturbances and clinical observations of vascular lesions

Exploring wall shear stress spatiotemporal heterogeneity in coronary arteries combining correlation-based analysis and complex networks with computational hemodynamics

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress–based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries

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

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

Modeling methodology for defining a priori the hydrodynamics of a dynamic suspension bioreactor. Application to human induced pluripotent stem cell culture

Three-dimensional dynamic suspension is becoming an effective cell culture method for a wide range of bioprocesses, with an increasing number of bioreactors proposed for this purpose. The complex hydrodynamics establishing within these devices affects bioprocess outcomes and efficiency, and usually expensive in vitro trial-and-error experiments are needed to properly set the working parameters. Here we propose a methodology to define a priori the hydrodynamic working parameters of a dynamic suspension bioreactor, selected as a test case because of the complex hydrodynamics characterizing its operating condition. A combination of computational and analytical approaches was applied to generate operational guideline graphs for defining a priori specific working parameters. In detail, 43 simulations were performed under pulsed flow regime to characterize advective transport within the device depending on different operative conditions, i.e., culture medium flow rate and its duty cycle, cultured particle diameter, and initial particle suspension volume. The operational guideline graphs were then used to set specific hydrodynamic working parameters for an in vitro proof-of-principle test, where human induced pluripotent stem cell (hiPSC) aggregates were cultured for 24 h within the bioreactor. The in vitro findings showed that, under the selected pulsed flow regime, sedimentation was avoided, hiPSC aggregate circularity and viability were preserved, and culture heterogeneity was reduced, thus confirming the appropriateness of the a priori method. This methodology has the potential to be adaptable to other dynamic suspension devices to support experimental studies by providing in silico-based a priori knowledge, useful to limit costs and to optimize culture bioprocesses

Coronary Artery Stenting Affects Wall Shear Stress Topological Skeleton

Despite the important advancements in the stent technology for the treatment of diseased coronary arteries, major complications still affect the postoperative long-term outcome. The stent-induced flow disturbances, and especially the altered wall shear stress (WSS) profile at the strut level, play an important role in the pathophysiological mechanisms leading to stent thrombosis (ST) and in-stent restenosis (ISR). In this context, the analysis of the WSS topological skeleton is gaining more and more interest by extending the current understanding of the association between local hemodynamics and vascular diseases. This study aims to analyze the impact that a deployed coronary stent has on the WSS topological skeleton. Computational fluid dynamics (CFD) simulations were performed in three stented human coronary artery geometries reconstructed from clinical images. The selected cases presented stents with different designs (i.e., two contemporary drug-eluting stents and one bioresorbable scaffold) and included regions with stent malapposition or overlapping. A recently proposed Eulerian-based approach was applied to analyze the WSS topological skeleton features. The results highlighted that the presence of single or multiple stents within a coronary artery markedly impacts the WSS topological skeleton. In particular, repetitive patterns of WSS divergence were observed at the luminal surface, highlighting a WSS contraction action exerted proximal to the stent struts and a WSS expansion action distal to the stent struts. This WSS action pattern was independent from the stent design. In conclusion, these findings could contribute to a deeper understanding of the hemodynamics-driven processes underlying ST and ISR