Simplified mitral valve modeling for prospective clinical application of left ventricular fluid dynamics

The fluid dynamics inside the left ventricle of the human heart is considered a potential indicator of long term cardiovascular outcome. In this respect, numerical simulations can play an important role for integrating existing technology to reproduce flow details and even conditions associated to virtual therapeutic solutions. Nevertheless, numerical models encounter serious practical difficulties in describing the interaction between flow and surrounding tissues due to the limited information inherently available in real clinical applications. This study presents a computational method for the fluid dynamics inside the left ventricle designed to be efficiently integrated in clinical scenarios. It includes an original model of the mitral valve dynamics, which describes an asymptotic behavior for tissues with no elastic stiffness other than the constrain of the geometry obtained from medical imaging; in particular, the model provides an asymptotic description without requiring details of tissue properties that may not be measurable in vivo. The advantages of this model with respect to a valveless orifice and its limitations with respect to a complete tissue modeling are verified. Its performances are then analyzed in details to ensure a correct interpretation of results. It represents a potential option when information about tissue mechanical properties is insufficient for the implementations of a full fluid-structure interaction approach

Trauma of the frontal region is influenced by the volume of frontal sinuses. A finite element study

Anatomy of frontal sinuses varies individually, from differences in volume and shape to a rare case when the sinuses are absent. However, there are scarce data related to influence of these variations on impact generated fracture pattern. Therefore, the aim of this study was to analyse the influence of frontal sinus volume on the stress distribution and fracture pattern in the frontal region. The study included four representative Finite Element models of the skull. Reference model was built on the basis of computed tomography scans of a human head with normally developed frontal sinuses. By modifying the reference model, three additional models were generated: a model without sinuses, with hypoplasic, and with hyperplasic sinuses. A 7.7 kN force was applied perpendicularly to the forehead of each model, in order to simulate a frontal impact. The results demonstrated that the distribution of impact stress in frontal region depends on the frontal sinus volume. The anterior sinus wall showed the highest fragility in case with hyperplasic sinuses, whereas posterior wall/inner plate showed more fragility in cases with hypoplasic and undeveloped sinuses. Well-developed frontal sinuses might, through absorption of the impact energy by anterior wall, protect the posterior wall and intracranial contents.This work was supported in part by grants from the Serbian Ministry of Education, Science and Technological Development III45005, III41007, ON174028 and EU project FP7 ICT SIFEM 600933

Modeling Alzheimer’s disease related phenotypes in the Ts65Dn mouse: impact of age on Aβ, Tau, pTau, NfL, and behavior

IntroductionPeople with DS are highly predisposed to Alzheimer’s disease (AD) and demonstrate very similar clinical and pathological features. Ts65Dn mice are widely used and serve as the best-characterized animal model of DS.MethodsWe undertook studies to characterize age-related changes for AD-relevant markers linked to Aβ, Tau, and phospho-Tau, axonal structure, inflammation, and behavior.ResultsWe found age related changes in both Ts65Dn and 2N mice. Relative to 2N mice, Ts65Dn mice showed consistent increases in Aβ40, insoluble phospho-Tau, and neurofilament light protein. These changes were correlated with deficits in learning and memory.DiscussionThese data have implications for planning future experiments aimed at preventing disease-related phenotypes and biomarkers. Interventions should be planned to address specific manifestations using treatments and treatment durations adequate to engage targets to prevent the emergence of phenotypes

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience

IntroductionPeptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.MethodologyWe retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.ResultsA total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.ConclusionThe study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly

T Lymphocytes Promote the Antiviral and Inflammatory Responses of Airway Epithelial Cells

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV)

Numerical and experimental study

2009/2010Fluid structure interaction (FSI) is one of fundamental phenomena encountered everywhere in nature or in industrial systems as well as one of the most studied and the most challenging topics in the fluid mechanics. Its research presents the core objective of this dissertation, along with experimental study of artificial heart devices. Better understanding of FSI could turn the still unexploited phenomenon into a powerful tool for resolving wealthy of multi-physics problems. Recently computational fluid dynamics community has been putting enormous efforts to uncover, make clear and answer yet numerous issues related to this developing topic. In addition, the FSI is often followed by the vortex formation, one more phenomena that could be both powerful driving force as well as distracting, disturbing occurrence. Consequently, this dissertation will begin with addressing some open issues related to the fluid-structure interaction associated with the simple system made of movable rigid leaflet and an unsteady viscous fluid flow. Such two-dimensional model, even if it appears extremely simple, is able to produce fairly rich flow features which deserve careful analytical and accurate numerical solution. Thus, we have performed a significant number of numerical experiments with the objective to uncover the role of the structure inertia in the overall behavior of the fluid-leaflet system, under the different flow recurrences. For that purpose, we have constructed a strong-coupling code and resolved the fluid and structure dynamics simultaneously, paying particular care of solution accuracy around the moving boundary. The complex problem of large fluid deformation in response to the rapid structure movements has been resolved by the time-dependent conformal mapping, exclusively developed for this specific physical arrangement. The numerical findings, even if theoretical in nature, allowed for the classification and characterization of body’s and fluid dynamics in functionality of different structure inertia and Strouhal numbers, which have been used as free parameters in all numerical experiments. The study is completed by a brief analysis of the more realistic system of actual prosthetic heart valves. Besides many problems that follow the performance of mechanical heart valve prosthesis, the complications related to the complex blood-leaflet interaction are a key factor. The intraventricular flow is characterized by large vortical structures, without significant turbulence, in a smooth circulatory pattern that, in presence of pathological conditions or mechanical devices, could be disturbed. Thus, among the criteria for the assessment of mitral valve functionality and mechanical valve design are the proper vortical features inside the left ventricle. Until nowadays the standard mechanical valves, designed originally for the aortic replacement and without exceptions symmetrical, have never satisfied the regularity of natural vortical dynamics. Thus, we have been motivated to investigate the flow features downstream of asymmetrical prototypes, exclusively designed for the mitral replacement with attempt to better mimic the natural intraventricular flow. Experimental outcomes allowed for preliminary conclusions that the break of symmetry in the novel prosthesis creates the asymmetrical vortical flow in the left ventricle, which is more similar to the natural one, although the concept introduced by this prototype has to undergo deeper testing and careful improvements before querying in the real hearts.XXIII Ciclo198

Electrochemical bromination of peracetylated glycals

Bromination of glycals with tribromides formed in situ from bromine and different bromide salts in dichloromethane (DCM) or acetonitrile (AN) was found to give predominantly the products of anti addition of bromine from the C-6 side in high yields. The same selectivity, which was much higher compared to bromination with bromine alone, was achieved in bromination of these substrates by anodic generation of bromine from the same salts