Subchondral bone microarchitecture and failure mechanism under compression: A finite element study

Subchondral bone (SCB) microdamage is commonly observed in traumatic joint injuries and has been strongly associated with post-traumatic osteoarthritis (PTOA). Knowledge of the three-dimensional stress and strain distribution within the SCB tissue helps to understand the mechanism of SCB failure, and may lead to an improved understanding of mechanisms of PTOA initiation, prevention and treatment. In this study, we used high-resolution micro-computed tomography (µCT)-based finite element (FE) modelling of cartilage-bone to evaluate the failure mechanism and the locations of SCB tissue at high-risk of initial failure under compression. The µCT images of five cartilage-bone specimens with an average SCB thickness of 1.23 ± 0.20 mm were used to develop five µCT-based FE models. The FE models were analysed under axial compressions of approximately 30 MPa applied to the cartilage surface while the bone edges were constrained. Strain and stress-based failure criteria were then applied to evaluate the failure mechanism of the SCB tissue under excessive compression through articular cartilage. µCT-based FE models predicted two locations in the SCB at high-risk of initial failure: (1) the interface of the calcified-uncalcified cartilage due to excessive tension, and (2) the trabecular bone beneath the subchondral plate due to excessive compression. µCT-based FE models of cartilage-bone enabled us to quantify the distribution of the applied compression which was transferred through the articular cartilage to its underlying SCB, and to investigate the mechanism and the mode of SCB tissue failure. Ultimately, the results will help to understand the mechanism of injury formation in relation to PTOA.     

A Finite Element Model of the L5-S1 Functional Spinal Unit: Development and Comparison with Biomechanical Tests In Vitro

The main objective of this work is to develop a three-dimensional finite element model of the L5-S1 segment that is able to simulate its passive mobility measured in vitro . Due to their limited role in segment mobility, an isotropic linear elastic constitutive law was used for cartilage, cancellous and cortical bone. The intervertebral disk ground substance was modeled with a non-linear hyperelastic polynomial law. Fibers of the disk, as well as ligaments, were modeled with piecewise linear springs. Flexion-extension, axial rotation, and lateral bending torques were applied to the model. A comparison with the experimental results obtained on the same segment for these three major motions was conducted. The compliance of the segment subjected to pure torques was found to be similar between numerical and experimental results for all major motions. Coupled motions and translations were also similar, even in their amplitude. For lateral bending, the normal coupled motions originate from the geometry of the disk and not from the facet geometry.     

Stochastic Finite Element Analysis of Biological Systems: Comparison of a Simple Intervertebral Disc Model with Experimental Results

Statistical methods allow the effects of uncertainty to be incorporated into finite element models. This has potential benefits for the analysis of biological systems where natural variability can give rise to substantial uncertainty in both material and geometrical properties. In this study, a simple model of the intervertebral disc under compression was created and analysed as both a deterministic and a stochastic system. Factorial analysis was used to determine the important parameters to be included in the stochastic analysis. The predictions from the model were compared to experimental results from 21 sheep discs. The size and shape of the distribution of the axial deformations predicted by the model was consistent with the experimental results given that the number of model solutions far exceeded the number of experimental results. Stochastic models could be valuable in determining the range and most likely value of stress in a tissue or implant.     

A Digital Model for the Venous Junctions

The venous network in the lower limbs is composed of a considerable number of confluent junctions. Each of these singularities introduces some blood flow disturbances. Each physiological junction is unique, in terms of its geometry as well as the blood flow rate. In order to account for this great variability, we developed a numerical model based on the use of the N3S code (a software package for solving Navier-Stokes equations). To test the validity of the model, one of the numerical simulations is compared with the data obtained in the corresponding experimental configuration. The velocity measurements were carried out with an ultrasonic pulsed Doppler velocimeter. We also measured pressure differences using differential sensors. The numerical computations were then used to obtain the values of the flow variables at any point, with various geometrical and flow configurations. As far as the velocity field is concerned, a very marked three-dimensional pattern with swirls was observed. The pressure evolution was also strongly disturbed, with a non-linear decrease. All these data indicate that confluence effects cannot be neglected when evaluating pressure decreases. With a tool of this kind, it is possible to accurately predict the disturbances associated with any geometrical configuration or any flow rate.     

A Finite Element Approach for Skeletal Muscle using a Distributed Moment Model of Contraction

Abstract

The present paper describes a geometrically and physically nonlinear continuum model to study the mechanical behaviour of passive and active skeletal muscle. The contraction is described with a Huxley type model. A Distributed Moments approach is used to convert the Huxley partial differential equation in a set of ordinary differential equations. An isoparametric brick element is developed to solve the field equations numerically. Special arrangements are made to deal with the combination of highly nonlinear effects and the nearly incompressible behaviour of the muscle. For this a Natural Penalty Method (NPM) and an Enhanced Stiffness Method (ESM) are tested. Finally an example of an analysis of a contracting tibialis anterior muscle of a rat is given. The DM-method proved to be an efficient tool in the numerical solution process. The ESM showed the best performance in describing the incompressible behaviour.     

Validation of Normal Human Bronchial Epithelial Cells as a Model for Influenza A Infections in Human Distal Trachea

Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that α2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic.     

A Theoretical Model for Utilizing Mammalian Pharmacology and Safety Data to Prioritize Potential Impacts of Human Pharmaceuticals to Fish

Due to the potential for long-term, low-level exposure of environmental species to pharmaceuticals in the environment, concerns over chronic ecotoxicity have been raised. Pharmaceuticals typically have specific enzyme and receptor-based modes of action, which are extensively studied in mammals during drug development. A survey of the literature demonstrated that there is conservation of many enzyme/receptor systems between mammalian and teleost systems. Based on this conservation of enzyme/receptor systems across teleost species, a model has been developed to utilize the information from mammalian pharmacology and toxicology studies to evaluate the potential for chronic receptor mediated responses in fish. In this model, a measured human therapeutic plasma concentration (H_TPC) is compared to a predicted steady state plasma concentration (F_SSPC) in fish, and an effect ratio (ER = H_TPC/F_SSPC) is computed. The lower the ER, the greater the potential for a pharmacological response in fish. Data collection and model validation will strengthen the applicability of this approach as a viable tool for prioritizing research initiatives that examine the potential impact of pharmaceuticals on fish.     

A Model of the Structural and Functional Development of the Normal Human Fetal Left Ventricle Based on a Global Growth Law

The purpose of this research is to study the growth of the normal human left ventricle (LV) during the fetal period from 14 to 40 weeks of gestation. A new constitutive law for the active myocardium describing the mechanical properties of the active muscle during the whole cardiac cycle has been proposed. The LV model is a thick-walled, incompressible, hyperelastic cylinder, with families of helicoidal fibers running on cylindrical surfaces [1] . Based on the works of Lin and Taber [2] done on the embryonic chick heart, we use for the human fetal heart a growth law in which the growth rate depends on the wall stresses. The parameters of the growth law are adapted to agree with sizes and volumes inferred from two dimensional ultrasound measurements performed on 18 human fetuses. Then calculations are performed to extrapolate the cardiac performance during normal growth of the fetal LV. The results presented support the idea that a growth law in which the growth rate depends linearly on the mean wall stresses averaged through the space and during whole cardiac cycle, is adapted to the normal human fetal LV development.     

A Novel Culture Model for Human Pluripotent Stem Cell Propagation on Gelatin in Placenta-conditioned Media

The propagation of human pluripotent stem cells (hPSCs) in conditioned medium derived from human cells in feeder-free culture conditions has been of interest. Nevertheless, an ideal humanized ex vivo feeder-free propagation method for hPSCs has not been developed; currently, additional exogenous substrates including basic fibroblast growth factor (bFGF), a master hPSC-sustaining factor, is added to all of culture media and synthetic substrata such as Matrigel or laminin are used in all feeder-free cultures. Recently, our group developed a simple and efficient protocol for the propagation of hPSCs using only conditioned media derived from the human placenta on a gelatin-coated dish without additional exogenous supplementation or synthetic substrata specific to hPSCs. This protocol has not been reported previously and might enable researchers to propagate hPSCs efficiently in humanized culture conditions. Additionally, this model obviates hPSC contamination risks by animal products such as viruses or unknown proteins. Furthermore, this system facilitates easy mass production of hPSCs using the gelatin coating, which is simple to handle, dramatically decreases the overall costs of ex vivo hPSC maintenance.     

Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

Virologica Sinica - Human papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to...     

Expressed Emotion,Human Agency,and Schizophrenia: Toward a New Model for the EE-Relapse Association

Although there is a clear statistical association between expressed emotion (EE) and schizophrenic relapse, our understanding of the mechanisms underlying this relationship is underdeveloped. This study tested a theoretical model in which caregivers’ perceptions of their ill relative’s agency underlie the EE-relapse association. To evaluate this model, we completed qualitative and quantitative analyses of narratives provided by individuals caring for a relative with schizophrenia. The results indicate that high-EE caregivers perceive the expression of symptoms as stemming from their ill relative’s agency more frequently than low-EE caregivers. This was true for both high-EE-criticism and high-EE-emotional overinvolvement caregivers. High-EE and low-EE caregivers did not differ in their perceptions of the role of their ill relative’s agency with regard to the control of symptoms. The findings suggest that EE may be a proxy risk factor for caregivers’ perceptions of their ill relative’s agency.

Evolutionary Medicine: A Powerful Tool for Improving Human Health

Modern evolutionary research has much to contribute to medical research and health care practices. Conversely, evolutionary biologists are tapping into the rapidly expanding databases of medical genomic information to further their research. These two fields, which have historically functioned in almost complete isolation, are finding mutual benefit in the exchange of information. The long-term benefits of this synthesis of two major areas of research include improved health care. Recently, efforts to catalyze this relationship have brought together evolutionary biologists, medical practitioners, anthropologists, and ethicists to lay the groundwork for further collaboration and exploration. The range of overlap is surprisingly broad and potentially invaluable.     

A Kinetic Model for Human Platelet Survival with Long-Lasting Time-Activity Curves

A model is presented that allows for the interpretation of the time course of the level of radiolabeled platelets in terms of platelet survival times, rate constant for removal from circulation, pooling time in an extra pool, the rate at which platelets re-enter circulation from the extra-pool, and the size of the plasma pool and extra-pools. The tenets of the model are that: (1) platelets leave the circulation at a rate proportional to their number per unit volume; (2) of the leaving platelets, a fraction b goes into a pool from which they return into circulation after a pooling time and another fraction (1 - b) is irreversibly destroyed; (3) the platelets in the extra-pool do not “queue up”, and thus the distribution function describing the probability of return is exponential; and (4) the time activity curve of the radiolabeled platelets can be described by the sum of two exponentials. Under steady state conditions, curve fitting allows determination of the constants determining the time activity curve (the respective amplitudes and rate constants of the two exponentials); mean pooling time; relative pool size; and survival time of platelets. The model is applied to data collected from patients over a period from 10 days following reinjection of autologous radiolabeled platelets.     

Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions

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Human endogenous retroviruses, hormones and APOBEC3G: A connection to explore in schizophrenia

Human endogenous retroviruses (HERVs) represent the footprints of previous retroviral infections. They are integrated within the human germ line and constitute approximately 7% of our genome. They have the potential to harm, given their capacity to alter the cellular metabolism, and could be involved in various pathological processes such as systemic lupus erythematosus or multiple sclerosis. In this respect it has been found that the stimulation of HERVs genome expression was observed after a steroid hormone treatment, stating the first evidence that an enhanced expression of the HERVs genome by hormones may be involved in the etiology of breast cancer. There is now increasing evidence that HERVs may in fact be involved in the etiology of schizophrenia, a disorder characterized by heterogeneous presence of positive, negative and cognitive symptoms that affect all aspects of mental activity, with a first peak incidence for males and females in the decade 15-24 and a second peak at age 55-64 for females, both periods characterized by two moments of significant hormonal changes. In connection with genetic aspects, several studies suggest a linkage between chromosome 22 (22q) and schizophrenia, being different genes of this chromosomal region reported as candidate genes for association with the disorder. Likewise, in a closely region of these genes, on 22q13, is located a gene named APOBEC3G, a potent intrinsic inhibitor of retroviral replication that also includes some HERVs. We propose that hormonal changes that coincide with two peak incidences in schizophrenia produce an enhancement in the expression of some HERV families implicated in the etiopathology of the disorder. The expression of HERVs is followed by a defective action of APOBEC3G that avoids carry out its function, that is, the inhibition of retroviral replication. This altered process might play a critical role in the etiopathogenesis of schizophrenia.     

Sentinel Human Health Indicators: A Model for Assessing Human Health Status of Vulnerable Communities

The presence of toxic substances in the Great Lakes (GL) continues to be a significant concern. Eleven of the most persistent and ubiquitous substances were identified as “critical Great Lakes pollutants” by the International Joint Commission (IJC). In some areas of the GL these toxic substances bioaccumulate in sediment and organisms, biomagnify in food webs, and persist at high levels. The Agency for Toxic Substances and Disease Registry (ATSDR) Great Lakes Human Health Effects Research Program (GLHHERP) characterizes contaminant exposures via GL fish consumption and investigates the potential for short- and long-term adverse health effects. The program has identified a set of eight indicators to determine risk. The GLHHERP findings indicate: (1) vulnerable populations are still being exposed to persistent toxic substances (2) body burden levels are two to four times higher than in the general U.S. population, (3) women and minorities are less knowledgeable about fish advisories than other segments of the population, (4) the presence of neurodevelopmental deficits in newborns, and cognitive deficits in children and adults, and (5) disturbances in reproductive parameters have been demonstrated in adults. The public health implications of these findings and the need for intervention strategies are discussed.