Abdominal aortic aneurysm volume and relative intraluminal thrombus volume might be auxiliary predictors of rupture-an observational cross-sectional study.

Objectives: The study aimed to identify differences and compare anatomical and biomechanical features between elective and ruptured abdominal aortic aneurysms (AAAs). Methods: Data (clinical, anatomical, and biomechanical) of 98 patients with AAA, 75 (76.53%) asymptomatic (Group aAAA) and 23 (23.46%) ruptured AAA (Group rAAA), were prospectively collected and analyzed. Anatomical, morphological, and biomechanical imaging markers like peak wall stress (PWS) and rupture risk equivalent diameter (RRED), comorbid conditions, and demographics were compared between the groups. Biomechanical features were assessed by analysis of Digital Imaging and Communication in Medicine images by A4clinics (Vascops), and anatomical features were assessed by 3Surgery (Trimensio). Binary and multiple logistic regression analysis were used and adjusted for confounders. Accuracy was assessed using receiving operative characteristic (ROC) curve analysis. Results: In a multivariable model, including gender and age as confounder variables, maximal aneurysm diameter [MAD, odds ratio (OR) = 1.063], relative intraluminal thrombus (rILT, OR = 1.039), and total aneurysm volume (TAV, OR = 1.006) continued to be significant predictors of AAA rupture with PWS (OR = 1.010) and RRED (OR = 1.031). Area under the ROC curve values and correct classification (cc) for the same parameters and the model that combines MAD, TAV, and rILT were measured: MAD (0.790, cc = 75%), PWS (0.713, cc = 73%), RRED (0.717, cc = 55%), TAV (0.756, cc = 79%), rILT (0.656, cc = 60%), and MAD + TAV + rILT (0.797, cc = 82%). Conclusion: Based on our results, in addition to MAD, other important predictors of rupture that might be used during aneurysm surveillance are TAV and rILT. Biomechanical parameters (PWS, RRED) as valuable predictors should be assessed in prospective clinical trials. Similar studies on AAA smaller than 55 mm in diameter, even difficult to organize, would be of even greater clinical value.

Abrupt Deterioration of COVID-19 Patients and Spreading of SARS COV-2 Virions in the Lungs.

A unique feature of COVID-19 interstitial pneumonia is an abrupt progression to respiratory failure. Our calculation shows that this abrupt deteriorate may be caused by a sudden shift in the spread of virus-laden bioaerosols through the airways to many different regions of the lungs from the initial site of infection.

Comparison of Surgisis, Vypro II and TiMesh in contaminated and clean field.

PURPOSE: The study aimed to evaluate the histologic properties and infection resistance of three different mesh materials in a rat model. METHODS: Each mesh, in both infectious (n = 96) and non-infectious groups (n = 270), was positioned both in sublay (preperitoneally) and onlay (subcutaneously) locations. Properties of the biological (Surgisis; Cook Surgical), composite, partially resorbing (Vypro II mesh; Ethicon) and non-resorbing (TiMesh; GFE Medizintechnik GmbH) mesh were evaluated and compared. Animals were killed at 7, 21 and 90 days after implantation. The following parameters were evaluated to assess the host response to the mesh material: inflammation, vascularization, fibrosis, collagen formation, Ki67, and a foreign body reaction by granuloma formation (FBG). RESULTS: Surgisis mesh produced more pronounced inflammation and cell proliferation, and less intense granuloma formation, as well as fibrosis, compared to the other two groups. When the infected materials were examined, we found signs of local infection to be more often present in Surgisis group of animals. CONCLUSIONS: In the presence of bacterial contamination, no benefits were observed in the use of the Surgisis prosthesis over the use of TiMesh and Vypro II.

Smeared multiscale finite element model for electrophysiology and ionic transport in biological tissue.

Basic functions of living organisms are governed by the nervous system through bidirectional signals transmitted from the brain to neural networks. These signals are similar to electrical waves. In electrophysiology the goal is to study the electrical properties of biological cells and tissues, and the transmission of signals. From a physics perspective, there exists a field of electrical potential within the living body, the nervous system, extracellular space and cells. Electrophysiological problems can be investigated experimentally and also theoretically by developing appropriate mathematical or computational models. Due to the enormous complexity of biological systems, it would be almost impossible to establish a detailed computational model of the electrical field, even for only a single organ (e.g. heart), including the entirety of cells comprising the neural network. In order to make computational models feasible for practical applications, we here introduce the concept of smeared fields, which represents a generalization of the previously formulated multiscale smeared methodology for mass transport in blood vessels, lymph, and tissue. We demonstrate the accuracy of the smeared finite element computational models for the electric field in numerical examples. The electrical field is further coupled with ionic mass transport within tissue composed of interstitial spaces extracellularly and by cytoplasm and organelles intracellularly. The proposed methodology, which couples electrophysiology and molecular ionic transport, is applicable to a variety of biological systems.

Expression of vitamin D receptors in the superior cervical ganglia of rats.

We investigated the role of vitamin D in the sympathetic nervous system including the distribution of vitamin D receptors (VDR), 1α-hydroxylase and 24-hydroxylase (CYP24) in neuronal subpopulations and satellite glia in the superior cervical ganglia (SCGs) of rats using immunohistochemistry. VDR immunoreactivity was observed in the cytoplasm and nucleus of nearly all neurons in the SCG. Intensity of VDR fluorescence was significantly greater in the cytoplasm of neuropeptide Y (NPY) negative somata compared to NPY positive neurons. Immunoreactivity for 1α-hydroxylase also was observed in the cytoplasm of all neurons of the SCG, but the intensity of fluorescence was less in the nuclei. To the contrary, the immunoreactivity for CYP24 was stronger in the nuclei, although it was present at lower intensity also in the cytoplasm of neurons. VDR and 1α-hydroxylase immunofluorescence was observed in many non-neuron cells, except satellite glial cells, which exhibited weak CYP24 immunofluorescence. Expression of VDRs and key metabolizing enzymes indicated the importance of vitamin D in the autonomic nervous system and the ability of sympathetic neurons to activate and deactivate vitamin D for its autocrine and paracrine roles.

Isoflurane post-conditioning influences myocardial infarct healing in rats.

Isoflurane post-conditioning causes an early increase in cardiac progenitor cells; however, during the chronic phase of infarct healing, the number was smaller compared to control, which suggests a positive effect on infarct scar maturity. Myofibroblasts participate in early phase infarct contraction, but their number is small in a mature scar. We investigated whether isoflurane post-conditioning stimulates differentiation of progenitor cells to myofibroblasts and to verify our hypothesis that isoflurane post-conditioning improves maturation of a myocardial scar. Ischemia was induced for 30 min in female rats. From the last 5 min of ischemia until 10 min into reperfusion, the isoflurane group received 1.5% isoflurane, while the control group received only an air-oxygen mixture. Infarct area was analyzed using immunohistochemistry. During the subacute phase of infarct healing, the number of myofibroblasts was greater in isoflurane-treated animals than in the control group. During the chronic phase of infarct healing, post-conditioned animals exhibited fewer myofibroblasts compared to control animals, even those derived from progenitor cells, i.e., α-smooth actin-nestin positive cells. In addition, isoflurane post-conditioning resulted in higher percentage of mature blood vessels compared to control animals. The myocardium of the isoflurane treated animals exhibited more myofibroblasts in granulation tissue compared to control animals. The smaller number of myofibroblasts together with the greater number of mature blood vessels during the chronic phase of healing demonstrated faster healing of the infarct area of isoflurane-treated animals compared to control animals.

Regional aerosol deposition in the human airways: The SimInhale benchmark case and a critical assessment of in silico methods.

Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future.

The influence of sex and gonadectomy on hepatic and brain fatty acid composition, lipogenesis and ß-oxidation.

The aim of this study was to investigate the influence of sex and castration of rats on liver and brain fatty acid profile and liver mRNA expression of genes involved in lipogenesis and ß-oxidation. Castration significantly increased body weight and liver index and decreased serum triglyceride content in the female rats. The fatty acid composition of the liver tissue was influenced by sex and castration. Male rats had higher content of C16:0, C18:1n7, C18:2n6 and C22:5n3, while female rats had higher content of C18:0, C20:4n6 and C22:6n3. Castration of male rats decreased differences caused by sex for C18:2n6, C20:4n6 and C22:6n3. Values for C16:1n7 were higher in the castrated male rats in comparison with all other groups. Liver phospholipids showed a distribution of fatty acids similar to the total lipids. Brain total lipids and phospholipids were not influenced by sex or castration. Castration increased ∆6D gene expression in both the sexes, while ∆5D and ∆9D increased in females and males respectively. Gonadectomy increased expression of the FASN gene in the females and decreased CPT1 and ACOX1 gene expression in the liver tissue of male rats. The observed results of lipid peroxidation, measured by TBARS, were the lowest in the intact females in comparison with all other groups. In conclusion, sex strongly influences both SFA and PUFA in liver tissue, and castration decreases these differences only for PUFA. Castration also influences the expression of the genes involved in lipid metabolism differently in male and female rats, with an increase in lipogenic genes in female rats and a decrease in key genes for mitochondrial and peroxisomal ß-oxidation in male rats.

Does the presence of an unerupted lower third molar influence the risk of mandibular angle and condylar fractures?

It has been suggested that unerupted lower third molars (M3) increase the fragility of the mandibular angle and simultaneously decrease the risk of condylar fracture. However, it is unknown whether this applies regardless of the direction and point of impact of the traumatic force. The aim of this study was to investigate the impact of an unerupted M3 on the fragility of the angle and condyle in terms of a force acting from different directions and affecting different regions of the mandible. Computed tomography scans of a human mandible and finite element methodology were used to obtain two three-dimensional models: a model with, and the other without an unerupted M3. A force of 2000N was applied to three different regions of the models: the symphysis, ipsilateral body, and contralateral body, respectively. When the force was applied to the mandibular body, the results revealed increased angle fragility in cases with unerupted M3. When the force was applied to the symphysis, the condyle region showed higher fragility, irrespective of the presence of an unerupted M3. In summary, fragility of the angle and condyle regions depends on the presence of an unerupted M3 and on the direction and point of impact of the force.

Middle and inner ear modelling: from microCT images to 3D reconstruction and coupling of models.

We present finite element (FE) modeling approaches of ear mechanics including 3-dimensional (3D) reconstruction of the human middle and inner ear. Specifically, we demonstrate a semi-automatic methodology for the 3D reconstruction of the inner ear structures, a FE harmonic response model of the middle ear to predict the stapes footplate frequency response, a 2D FE slice model of the cochlea for the coupled response at the micromechanical level for either acoustic or electrical excitation and a coupled FE middle ear model with a simplified cochlea box model to simulate the basilar membrane velocity in response to acoustic excitation. The proposed methodologies are validated against experimental and literature data and the results are in good agreement.

Assessment of Knee Cartilage Stress Distribution and Deformation Using Motion Capture System and Wearable Sensors for Force Ratio Detection.

Knowledge about the knee cartilage deformation ratio as well as the knee cartilage stress distribution is of particular importance in clinical studies due to the fact that these represent some of the basic indicators of cartilage state and that they also provide information about joint cartilage wear so medical doctors can predict when it is necessary to perform surgery on a patient. In this research, we apply various kinds of sensors such as a system of infrared cameras and reflective markers, three-axis accelerometer, and force plate. The fluorescent marker and accelerometers are placed on the patient's hip, knee, and ankle, respectively. During a normal walk we are recording the space position of markers, acceleration, and ground reaction force by force plate. Measured data are included in the biomechanical model of the knee joint. Geometry for this model is defined from CT images. This model includes the impact of ground reaction forces, contact force between femur and tibia, patient body weight, ligaments, and muscle forces. The boundary conditions are created for the finite element method in order to noninvasively determine the cartilage stress distribution.

Assessment of association between genetic variants in microRNA genes hsa-miR-499, hsa-miR-196a2 and hsa-miR-27a and prostate cancer risk in Serbian population.

Due to their potentially functional significance, genetic variants within microRNA genes have been recognized as candidates for cancer-related genetic biomarkers. Among the most extensively studied so far are rs3746444, rs11614913 and rs895819. Nevertheless, only few previous studies in Asian population analyzed the association of rs3746444 and rs11614913 with prostate cancer (PCa) risk, while rs895819 was not evaluated in relation to this issue. The aim of this study was to assess the possible association between these genetic variants and PCa risk and progression in Serbian population. 355 samples of peripheral blood were obtained from the patients with PCa and 353 samples from patients with benign prostatic hyperplasia (BPH). 312 volunteers derived from general population who gave samples of buccal swabs were included in the control group. Genotyping of rs3746444, rs11614913 and rs895819 was performed by using PCR-RFLP method, HRM analysis and allele-specific PCR, respectively. Allelic and genotypic associations were evaluated by unconditional linear (for serum PSA level in PCa patients) and logistic regression method with adjustment for age. Minor allele C of rs895819 was found to be associated with the increased risk of developing PCa under dominant (P=0.035; OR=1.38, 95%CI 1.02-1.86) and overdominant (P=0.04; OR=1.37, 95%CI 1.01-1.85) genetic model. Same genetic variant was found to be associated with the clinical stage of localized PCa, as well as with the presence of distant metastases. Allele G of rs3746444 was also shown to be associated with the decreased risk of PCa progression. According to our data, rs3746444 qualifies for a genetic variant potentially associated with PCa aggressiveness in Serbian population. Furthermore, our study provided the first evidence of association between rs895819 and PCa risk, as well as for its genetic association with the presence of distant metastases among PCa patients.

Mechanical weakening of devitalized teeth: three-dimensional Finite Element Analysis and prediction of tooth fracture.

AIM: To determine to which extent cavity preparation and each step of dentine removal in the process of root canal treatment (access cavity preparation and root canal enlargement) both individually and jointly contribute to the weakening of the tooth. METHODS: Numerical analysis using finite element method (FEM) of separate and combined influence of two-surface Class II preparation and root canal treatment was undertaken to evaluate the decrease in tooth strength. The influence of the two stages in root canal treatment, access cavity preparation and root canal enlargement, was also analysed separately and jointly. After each of these phases, the crown was restored with composite resin, and the FEA was performed only on restored teeth. To estimate the influence of all these procedures on tooth fracture resistance numerically, a Failure Index based on the maximum principal stress criterion (MPCS) was applied. Compressive and tensile stresses were analysed separately and corresponding Failure Indices were calculated. RESULTS: A two-surface resin composite restoration weakened the tooth by 23.25%. Nevertheless, the Failure Indices showed that this tooth was not likely to fracture even under high occlusal stress (710N). However, after access cavity preparation, the Failure Indices reached the point where, under high occlusal force that may occur in the posterior area, a tooth fracture occurred. The enlargement of root canals had an additional, but relatively small impact on tooth weakening, making the tooth even more susceptible to fracture. The combined influence of both cavity preparation and root canal enlargement led to weakening of 62.6% under a load of 710N, ultimately causing tooth fracture. CONCLUSION: The combined finite element method and the maximum principal stress analysis gave insight into the fracture mechanisms of teeth with two-surface composite restorations followed by root canal preparation. Removal of tooth tissue, despite its subsequent restoration with dental materials, weakened the tooth by changing the stress intensity and distribution through tooth structures. Access cavity preparation had the greatest influence on tooth strength whilst canal enlargement did not contribute to this process substantially.

Tissue fatty acid composition and estimated ∆ desaturase activity after castration in chicken broilers fed with linseed or sunflower oil.

The aims of this study were to investigate the influence of the short-term addition of sunflower and linseed oil and castration on fatty acid composition and desaturation indexes in chicken broilers. Forty-eight male Ross 308 chicken broilers were supplemented with 5% of sunflower or linseed oil. The four experimental groups were linseed oil supplementation and castration (LC), linseed oil without castration (LN), sunflower oil and castration (SC) and sunflower oil without castration (SN). There was no significant influence of castration or oil supplement on live weights, weight gain, feed intake or feed conversion. Castration resulted in an increase in polyunsaturated fatty acids (PUFA), total n3, n6, measured desaturation indexes and a decrease in the saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) content of abdominal fat. In breast muscle, castration increased PUFA and 18:3n3 values, while in the liver tissue, castration did not influence the parameters measured. Linseed oil supplementation significantly increased 18:3n3, n3 long chain polyunsaturated fatty acids (LC PUFA), total n3 and decreased total n6, n6/n3 ratio, and 20:4n6 content. Values for 20:4n6 were the highest in SC and the lowest in the LC group. Linseed oil also significantly decreased ∆5 and ∆4 desaturation indexes in the thighs and ∆5 and ∆5, 6 in abdominal fat and the liver. These results suggest that short-term supplementation of basal diet with 5% of linseed oil could significantly increase n3 LC PUFA and decrease n6/n3 ratio content in the edible tissues of chicken broilers, without adverse effects on growth performance. Meanwhile, castration only improved fatty acid profile in abdominal fat, which is not nutritionally important. The interactions observed between basal diet, supplemented oil, sex hormones and other non-nutritional factors must be elucidated in future trials in order to correctly predict the nutritional value of linseed-fed poultry.

Radiosensitization by gold nanoparticles

Recent years brought increasing use of gold nano particles (GNP) as a model platform for interaction of irradiation and GNPs aiming radiosensitization. Endocytosis seems to be one of the major pathways for cellular uptake of GNPs. Internalization mechanism of GNPs is likely receptor-mediated endocytosis, influenced by GNP size, shape, its coating and surface charging. Many showed that DNA damage can occur as a consequence of metal-enhanced production of low energy electrons, Auger electrons and alike. Kilovoltage radiotherapy (RT) carries significantly higher dose enhancement factor (DEF) that is observed with megavoltage irradiations, the latter usually been at the order of 1.1-1.2. Higher gold concentrations seem to carry higher risk of toxicity, while with lower concentrations the DEF can be reduced. Adding a chemotherapeutic agent could increase level of enhancement. Clinical trials are eagerly awaited with a promise of gaining more knowledge deemed necessary for more successful transition to widespread clinical practice (AU)

Radiosensitization by gold nanoparticles.

Recent years brought increasing use of gold nano particles (GNP) as a model platform for interaction of irradiation and GNPs aiming radiosensitization. Endocytosis seems to be one of the major pathways for cellular uptake of GNPs. Internalization mechanism of GNPs is likely receptor-mediated endocytosis, influenced by GNP size, shape, its coating and surface charging. Many showed that DNA damage can occur as a consequence of metal-enhanced production of low energy electrons, Auger electrons and alike. Kilovoltage radiotherapy (RT) carries significantly higher dose enhancement factor (DEF) that is observed with megavoltage irradiations, the latter usually been at the order of 1.1-1.2. Higher gold concentrations seem to carry higher risk of toxicity, while with lower concentrations the DEF can be reduced. Adding a chemotherapeutic agent could increase level of enhancement. Clinical trials are eagerly awaited with a promise of gaining more knowledge deemed necessary for more successful transition to widespread clinical practice.

The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles.

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.

Patient specific multiscale modelling for plaque formation and progression.

We present a three-dimensional model of plaque formation and progression that was tested in a set of patients who underwent coronary Computed Tomography angiography (CTA) for anginal symptoms. The 3D blood flow is described by the Navier-Stokes equations, 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 Lipoprotein (LDL) transports in lumen of the vessel and through the vessel tissue (which has a mass consumption term) are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. A full three-dimensional model was created. Furthermore, features potentially affecting plaque growth, such as patient risk score, circulating biomarkers, localization and composition of the initial plaque, and coronary vasodilating capability were also investigated. The proof of concept of the model effectiveness was assessed 6 months after the baseline evaluation.