Duchenne and Becker muscular dystrophy: Cellular mechanisms, image analysis, and computational models: A review.

The muscle is the principal tissue that is capable to transform potential energy into kinetic energy. This process is due to the transformation of chemical energy into mechanical energy to enhance the movements and all the daily activities. However, muscular tissues can be affected by some pathologies associated with genetic alterations that affect the expression of proteins. As the muscle is a highly organized structure in which most of the signaling pathways and proteins are related to one another, pathologies may overlap. Duchenne muscular dystrophy (DMD) is one of the most severe muscle pathologies triggering degeneration and muscle necrosis. Several mathematical models have been developed to predict muscle response to different scenarios and pathologies. The aim of this review is to describe DMD and Becker muscular dystrophy in terms of cellular behavior and molecular disorders and to present an overview of the computational models implemented to understand muscle behavior with the aim of improving regenerative therapy.

Occupational therapy and cooking: A scoping review and future directions.

BACKGROUND: Occupational therapy (OT) has historically used cooking as an intervention and assessment approach across settings. Current practices in OT and the emergence of the multidisciplinary field of culinary medicine highlight the relationship between cooking and health. AIMS/OBJECTIVES: To map the current literature on OT and cooking and to identify key factors that may facilitate collaboration within culinary medicine. MATERIALS AND METHODS: We conducted a scoping review using the Joanna Briggs Institute methodology to identify primary contexts and clinical settings. Publications were analysed using framework thematic analysis to identify OT themes and roles. RESULTS: A total of 56 studies met the criteria for inclusion. The majority of studies (n = 29, 53%) represented home/community settings and brain injury was the largest clinical group (n = 15, 27%). Primary themes related to person (n = 47, 43%), occupation (n = 30 (28%), environment (n = 19, 17%), and psychosocial wellbeing (n = 13, 12%). The primary OT role identified was that of interventionist (n = 48, 86%). CONCLUSIONS/SIGNIFICANCE: OT's holistic practice places cooking within a larger context that can help identify and overcome the barriers to participation. Findings support multiple pathways in which OT can contribute to cooking initiatives for health promotion and potentially expand OT practice in population health.

Finite element analysis of the influence of interdigitation pattern and collagen fibers on the mechanical behavior of the midpalatal suture.

The midpalatal suture (MPS) corresponds to the tissue that joins the two maxillary bones. Understanding the mechanical behavior of this tissue is of particular interest to those patients who require orthodontic treatments such as Rapid Maxillary Expansion (RME). The objective of this research was to observe the influence of interdigitation and collagen fibers on the mechanical response of MPS. To this end, a finite element analysis in two-dimensional models of the bone-suture-bone interface was performed considering the characteristics of the MPS. The geometry of the suture was modeled with 4 different levels of interdigitation: null, moderate, scalloped and fractal. The influence of collagen fibers, aligned transversely along the suture, was considered by incorporating linked structures of the bone fronts. According to the results, the factor that has the greatest impact on the magnitude and distribution of stresses is the interdigitation degree. A higher level of interdigitation produces an increase in tissue stiffness and a lower influence of collagen fibers on the mechanical response of the tissue. Therefore, this research contributes to the understanding of the MPS biomechanics by providing information that may be useful to health staff when evaluating the feasibility of procedures such as RME.

Computational model of articular cartilage regeneration induced by scaffold implantation in vivo.

Computational models allow to explain phenomena that cannot be observed through an animal model, such as the strain and stress states which can highly influence regeneration of the tissue. For this purpose, we have developed a simulation tool to determine the mechanical conditions provided by the polymeric scaffold. The computational model considered the articular cartilage, the subchondral bone, and the scaffold. All materials were modeled as poroelastic, and the cartilage had linear-elastic oriented collagen fibers. This model was able to explain the remodeling process that subchondral bone goes through, and how the scaffold allowed the conditions for cartilage regeneration. These results suggest that the use of scaffolds might lead the cartilaginous tissue growth in vivo by providing a better mechanical environment. Moreover, the developed computational model demonstrated to be useful as a tool prior experimental in vivo studies, by predicting the possible outcome of newly proposed treatments allowing to discard approaches that might not bring good results.

Simulation of the electrical stimulation of the rat brain using sleep frequencies: A finite element modeling approach.

A realistic rat brain model was used to simulate current density and electric field distributions under frequencies characteristic of sleeping states (0.8, 5, and 12 Hz). Two anode-electrode setups were simulated: plate vs. screws-anode, both with a cephalic cathode. Our simulations showed that these frequencies have limited impact on electric field and current density; however, the highest frequency evidenced higher values for both variables. The type of electrode setup had a greater effect on current distribution and induced fields. In that sense, the screws setup resulted in higher values of the modeled variables. The numeric results obtained are within the range of available data for rodent models using the finite elements method. These modeled effects should be analyzed regarding anatomical consequences (depth of penetration of the currents) and purpose of the experiment (i.e., entrainment of brain oscillations) in the context of sleep research.

Tandem catalysts for the selective hydrogenation of butadiene with hydrogen generated from the decomposition of formic acid.

We report for the first time the selective hydrogenation of 1,3-butadiene to butene using formic acid as the hydrogen source with 1 wt% Pd/carbon in a continuous flow reactor. The catalytic results show that the selectivity is even higher when formic acid is used compared to gas hydrogen.

Biomechanical behavior of an alveolar graft under maxillary therapies.

Cleft lip and palate is a congenital defect that affects the oral cavity. Depending on its severity, alveolar graft surgery and maxillary orthopedic therapies must be carried out as a part of the treatment. It is widely accepted that the therapies should be performed before grafting. Nevertheless, some authors have suggested that mechanical stimuli such as those from the maxillary therapies could improve the success rate of the graft. The aim of this study is to computationally determine the effect of maxillary therapies loads on the biomechanical response of an alveolar graft with different degrees of ossification. We also explore how the transverse width of the cleft affects the graft behavior and compare results with a non-cleft skull. Results suggest that stresses increase within the graft as it ossifies and are greater if maxillary expansion therapy is applied. This has consequences in the bone remodeling processes that are necessary for the graft osseointegration. Maxillary orthopedic therapies after graft surgery could be considered as a part of the treatment since they seem to act as a positive extra stimulus that can benefit the graft.

Simulation of pandemics in real cities: enhanced and accurate digital laboratories.

This study develops a modelling framework for simulating the spread of infectious diseases within real cities. Digital copies of Birmingham (UK) and Bogotá (Colombia) are generated, reproducing their urban environment, infrastructure and population. The digital inhabitants have the same statistical features of the real population. Their motion is a combination of predictable trips (commute to work, school, etc.) and random walks (shopping, leisure, etc.). Millions of individuals, their encounters and the spread of the disease are simulated by means of high-performance computing and massively parallel algorithms for several months and a time resolution of 1 minute. Simulations accurately reproduce the COVID-19 data for Birmingham and Bogotá both before and during the lockdown. The model has only one adjustable parameter calculable in the early stages of the pandemic. Policymakers can use our digital cities as virtual laboratories for testing, predicting and comparing the effects of policies aimed at containing epidemics.

Bacillus thuringiensis Cry1Ac toxin and protoxin do not provoke acute or chronic cytotoxicity on macrophages and leukocytes.

The bioinsecticidal Cry1Ac proteins (protoxin and toxin) are potent immunogens that can activate macrophages by inducing upregulation of costimulatory molecules, pro-inflammatory cytokines, and mitogen-activated protein kinase (MAPK) signaling pathways. Besides, by the oral route, Cry1Ac toxin is mildly allergenic and induces intestinal lymphoid hyperplasia in mice. Given the potential utility of Cry1Ac protoxin as an adjuvant, as well as the human consumption of Cry1Ac toxin in transgenic crops, it is necessary to more deeply evaluate the toxicological potential of these proteins in mammalian immune cells. Here, were used in vitro evaluations in leukocyte and macrophage cell lines to test the potential toxicity of various doses of Cry1Ac proteins, by means of Alamar Blue, MTT, Annexin V, and JC1 assays. Our results indicated that neither Cry1Ac protoxin nor toxin elicited acute toxic effects, after monitoring the cell activity for 4, 8, 10, and 24 h of exposure. By flow cytometry and confocal microscopy analysis, it was observed that neither Cry1Ac toxin nor protoxin generated mitochondrial damage or depolarization or induced apoptosis or necrosis. In conclusion, despite their immunostimulatory effects, it was demonstrated that Cry1Ac proteins did not have cytotoxic effects, even at high concentrations, in primary leukocytes or macrophages or cell lines.

Contribution to the reproductive ecology of Notoscopelus resplendens (Richardson, 1845) (Myctophidae) in the Central-Eastern Atlantic.

Notoscopelus resplendens is an abundant myctophid in the region of the Central-Eastern Atlantic. As with a majority of other myctophid species, this species performs vertical migration, playing a key role in the oceanic food web and in carbon sequestration. We examined the reproductive biology of N. resplendens based on 579 specimens caught between 1997 and 2002 off the Canary Islands. We found that the maximum standard length (SL) was lower than the size reported by other authors. The sex ratio was not different from 1:1. The average size at first maturity (L50) was higher in females (60.34 mm SL) than in males (56.61 mm SL). The gonadosomatic index (GSI) at 50% sexual maturity in females was higher than that in males. The reproductive activity was observed from January to April, while from May onwards, the majority of fish caught were in the process of maturation. The macroscopic scale of maturation was validated through the histological analysis of the ovarian development. The batch fecundity was related to the standard length, with an average of 1068.69 ± 369.84 eggs/spawn. These first data obtained for N. resplendens indicated that it is a batch spawner with asynchronous ovarian development.

Influence of interdigitation and expander type in the mechanical response of the midpalatal suture during maxillary expansion.

BACKGROUND AND OBJECTIVE: The orthopedic Maxillary Expansion (ME) procedure is used for treating the transverse maxillary deficiency. This pathology consists in a smaller transverse dimension in the maxilla and leads to malocclusion. The treatment takes advantage of the existence of the midpalatal suture (MPS), which corresponds to the junction at the palatine bones of its horizontal portions. The technique employs a device, conventionally a palatal expander attached to the posterior teeth, to separate the two maxillary bones in the MPS. The objective of this study was to analyze, using the Finite Element Method, the biomechanical behavior of the MPS when an expansion is applied. METHODS: A Computer Tomography image of the maxilla was reconstructed, the suture geometry was modeled with different interdigitation levels and types of hyrax devices. A total of 12 geometric models (three levels for interdigitation and four types of hyrax devices) were prepared and analyzed taking into account the chewing forces and the expansion displacement. For each case, maximum principal stresses on the maxilla (bone), and equivalent stresses on the expander device (stainless steel) were observed. In the MPS, maximum principal stresses and directional displacement were evaluated. RESULTS: The results showed that the interdigitation does not have an important influence on the deformation behavior of the maxilla but it affects the stress distribution. In addition, the type of expander device and anchorage have a direct relationship with the treatment effectiveness; larger deformation in the expansion direction was obtained with skeletal when compared to dental anchorage. CONCLUSIONS: A study that allows a better understanding of the oral biomechanics during the application of ME was presented. To our knowledge, it is the first study based on computational simulations that takes into account bone structures, like maxilla and part of the skull, to analyze the interdigitation influence on the MPS behavior when exposed to a ME.

Capacitively coupled electrical stimulation of rat chondroepiphysis explants: A histomorphometric analysis.

The growth plate is a cartilaginous layer present from the gestation period until the end of puberty where it ossifies joining diaphysis and epiphysis. During this period several endocrine, autocrine, and paracrine processes within the growth plate are carried out by chondrocytes; therefore, a disruption in cellular functions may lead to pathologies affecting bone development. It is known that electric fields impact the growth plate; however, parameters such as stimulation time and electric field intensity are not well documented. Accordingly, this study presents a histomorphometrical framework to assess the effect of electric fields on chondroepiphysis explants. Bones were stimulated with 3.5 and 7 mV/cm, and for each electric field two exposure times were tested for 30 days (30 min and 1 h). Results evidenced that electric fields increased the hypertrophic zones compared with controls. In addition, a stimulation of 3.5 mV/cm applied for 1 h preserved the columnar cell density and its orientation. Moreover, a pre-hypertrophy differentiation in the center of the chondroepiphysis was observed when explants were stimulated during 1 h with both electric fields. These findings allow the understanding of the effect of electrical stimulation over growth plate organization and how the stimulation modifies chondrocytes morphophysiology.

Genes coding for transporters showed a rapid and sharp increase in their expression in response to lead, in the aquatic fern (Salvinia minima Baker).

Salvinia minima was assessed for its ability to accumulate lead (Pb) by exposing it to concentrations of 40µM Pb(NO3)2 during 24h. At the same time, the expression levels were quantified, of four genes coding for transporters: SmABCC (ABCC-MRP), SmATPase (ATPase-P3A), SmNhaD (Type-Na+/H+) and SmABCG (ABCG-WBC). In the absence of lead, S. minima had very low expression of those genes, when plants were exposed to the metal however, those genes showed a rapid (in just three hours or less) and sharp increase (up to 60 times) in their expression, particularly the SmNhaD (Type-Na+/H+) gene. This sharp increase in expression levels of the genes studied, occurred at the same time that the plant accumulated the highest content of lead in its tissues. The first two genes, are apparently implicated in detoxification and lead accumulation mechanisms, while the other two genes are apparently involved in maintaining cell balance (homeostatic control) and membrane integrity. Our results confirmed that S. minima is efficient for phytoremediation of water bodies contaminated by lead, as it is efficient in accumulating this metal in its tissues (bioconcentration factor; BCF) values greater than 1000, in short times of exposure. More importantly, our data on the expression profiles of four genes coding for transporters, represent a first sight scenario of the molecular basis for understanding the different mechanism of detoxification, apparently present in this aquatic fern.

Mechanobiological modeling of endochondral ossification: an experimental and computational analysis.

Long bone formation starts early during embryonic development through a process known as endochondral ossification. This is a highly regulated mechanism that involves several mechanical and biochemical factors. Because long bone development is an extremely complex process, it is unclear how biochemical regulation is affected when dynamic loads are applied, and also how the combination of mechanical and biochemical factors affect the shape acquired by the bone during early development. In this study, we develop a mechanobiological model combining: (1) a reaction-diffusion system to describe the biochemical process and (2) a poroelastic model to determine the stresses and fluid flow due to loading. We simulate endochondral ossification and the change in long bone shapes during embryonic stages. The mathematical model is based on a multiscale framework, which consisted in computing the evolution of the negative feedback loop between Ihh/PTHrP and the diffusion of VEGF molecule (on the order of days) and dynamic loading (on the order of seconds). We compare our morphological predictions with the femurs of embryonic mice. The results obtained from the model demonstrate that pattern formation of Ihh, PTHrP and VEGF predict the development of the main structures within long bones such as the primary ossification center, the bone collar, the growth fronts and the cartilaginous epiphysis. Additionally, our results suggest high load pressures and frequencies alter biochemical diffusion and cartilage formation. Our model incorporates the biochemical and mechanical stimuli and their interaction that influence endochondral ossification during embryonic growth. The mechanobiochemical framework allows us to probe the effects of molecular events and mechanical loading on development of bone.

Cellular scale model of growth plate: An in silico model of chondrocyte hypertrophy.

The growth plate is the responsible for longitudinal bone growth. It is a cartilaginous structure formed by chondrocytes that are continuously undergoing a differentiation process that starts with a highly proliferative state, followed by cellular hypertrophy, and finally tissue ossification. Within the growth plate chondrocytes display a characteristic columnar organization that potentiates longitudinal growth. Both chondrocyte organization and hypertrophy are highly regulated processes influenced by biochemical and mechanical stimuli. These processes have been studied mainly using in vivo models, although there are few computational approaches focused on the rate of ossification rather than events at cellular level. Here, we developed a model of cellular behavior integrating biochemical and structural factors in a single column of cells in the growth plate. In our model proliferation and hypertrophy were controlled by biochemical regulatory loop formed between Ihh and PTHrP (modeled as a set of reaction-diffusion equations), while cell growth was controlled by mechanical loading. We also examined the effects of static loading. The model reproduced the proliferation and hypertrophy of chondrocytes in organized columns. This model constitutes a first step towards the development of mechanobiological models that can be used to study biochemical interactions during endochondral ossification.

Cellular automata model for human articular chondrocytes migration, proliferation and cell death: An in vitro validation.

Articular cartilage is characterized by low cell density of only one cell type, chondrocytes, and has limited self-healing properties. When articular cartilage is affected by traumatic injuries, a therapeutic strategy such as autologous chondrocyte implantation is usually proposed for its treatment. This approach requires in vitro chondrocyte expansion to yield high cell number for cell transplantation. To improve the efficiency of this procedure, it is necessary to assess cell dynamics such as migration, proliferation and cell death during culture. Computational models such as cellular automata can be used to simulate cell dynamics in order to enhance the result of cell culture procedures. This methodology has been implemented for several cell types; however, an experimental validation is required for each one. For this reason, in this research a cellular automata model, based on random-walk theory, was devised in order to predict articular chondrocyte behavior in monolayer culture during cell expansion. Results demonstrated that the cellular automata model corresponded to cell dynamics and computed-accurate quantitative results. Moreover, it was possible to observe that cell dynamics depend on weighted probabilities derived from experimental data and cell behavior varies according to the cell culture period. Thus, depending on whether cells were just seeded or proliferated exponentially, culture time probabilities differed in percentages in the CA model. Furthermore, in the experimental assessment a decreased chondrocyte proliferation was observed along with increased passage number. This approach is expected to having other uses as in enhancing articular cartilage therapies based on tissue engineering and regenerative medicine.

Flat bones and sutures formation in the human cranial vault during prenatal development and infancy: A computational model.

The processes of flat bones growth, sutures formation and interdigitation in the human calvaria are controlled by a complex interaction between genetic, biochemical and environmental factors that regulate bone formation and resorption during prenatal development and infancy. Despite previous experimental evidence accounting for the role of the main biochemical factors acting on these processes, the underlying mechanisms controlling them are still unknown. Therefore, we propose a mathematical model of the processes of flat bone and suture formation, taking into account several biological events. First, we model the growth of the flat bones and the formation of sutures and fontanels as a reaction diffusion system between two proteins: TGF-ß2 and TGF-ß3. The former is expressed by osteoblasts and allows adjacent mesenchymal cells differentiation on the bone fronts of each flat bone. The latter is expressed by mesenchymal cells at the sutures and inhibits their differentiation into osteoblasts at the bone fronts. Suture interdigitation is modelled using a system of reaction diffusion equations that develops spatio-temporal patterns of bone formation and resorption by means of two molecules (Wnt and Sclerostin) which control mesenchymal cells differentiation into osteoblasts at these sites. The results of the computer simulations predict flat bone growth from ossification centers, sutures and fontanels formation as well as bone formation and resorption events along the sutures, giving rise to interdigitated patterns. These stages were modelled and solved by the finite elements method. The simulation results agree with the morphological characteristics of calvarial bones and sutures throughout human prenatal development and infancy.

Modeling cell adhesion and proliferation: a cellular-automata based approach.

BACKGROUND: Cell adhesion is a process that involves the interaction between the cell membrane and another surface, either a cell or a substrate. Unlike experimental tests, computer models can simulate processes and study the result of experiments in a shorter time and lower costs. One of the tools used to simulate biological processes is the cellular automata, which is a dynamic system that is discrete both in space and time. METHOD: This work describes a computer model based on cellular automata for the adhesion process and cell proliferation to predict the behavior of a cell population in suspension and adhered to a substrate. The values of the simulated system were obtained through experimental tests on fibroblast monolayer cultures. RESULTS: The results allow us to estimate the cells settling time in culture as well as the adhesion and proliferation time. The change in the cells morphology as the adhesion over the contact surface progress was also observed. The formation of the initial link between cell and the substrate of the adhesion was observed after 100 min where the cell on the substrate retains its spherical morphology during the simulation. The cellular automata model developed is, however, a simplified representation of the steps in the adhesion process and the subsequent proliferation. CONCLUSION: A combined framework of experimental and computational simulation based on cellular automata was proposed to represent the fibroblast adhesion on substrates and changes in a macro-scale observed in the cell during the adhesion process. The approach showed to be simple and efficient.

Growth plate stress distribution implications during bone development: a simple framework computational approach.

Mechanical stimuli play a significant role in the process of long bone development as evidenced by clinical observations and in vivo studies. Up to now approaches to understand stimuli characteristics have been limited to the first stages of epiphyseal development. Furthermore, growth plate mechanical behavior has not been widely studied. In order to better understand mechanical influences on bone growth, we used Carter and Wong biomechanical approximation to analyze growth plate mechanical behavior, and explore stress patterns for different morphological stages of the growth plate. To the best of our knowledge this work is the first attempt to study stress distribution on growth plate during different possible stages of bone development, from gestation to adolescence. Stress distribution analysis on the epiphysis and growth plate was performed using axisymmetric (3D) finite element analysis in a simplified generic epiphyseal geometry using a linear elastic model as the first approximation. We took into account different growth plate locations, morphologies and widths, as well as different epiphyseal developmental stages. We found stress distribution during bone development established osteogenic index patterns that seem to influence locally epiphyseal structures growth and coincide with growth plate histological arrangement.

Removal of the antibiotic metronidazole by adsorption on various carbon materials from aqueous phase.

The adsorption of the antibiotic metronidazole (MNZ) on activated carbon (F400), activated carbon cloth (ACF), mesoporous activated carbon (CMK-3), and carbon nanotubes (MWCNT) was investigated in this work. The effect of the adsorbent-adsorbate interactions as well as the operating conditions (ionic strength, solution pH, temperature, chemical modification of the adsorbents by HNO3 treatment, and water matrix) on the adsorption capacity were analyzed to substantiate the adsorption mechanism. The adsorption capacity markedly varied as function of the carbon material, decreasing in the following order: F400>ACF>F400-HNO3>CMK-3>MWCNT>MWCNT-HNO3, and depended not only on their surface area and pore size distribution, but also on their chemical nature. The adsorption of MNZ was influenced by the solution pH, but was not significantly affected by the ionic strength and temperature. The adsorption of MNZ was enhanced when the MNZ solutions were prepared using wastewater. Therefore, the electrolytes present in the wastewater cooperated rather than competed with the MNZ molecules for the adsorption sites. Desorption equilibrium data of MNZ on all carbon materials demonstrated that the adsorption was reversible corroborating the weakness of the adsorbent-adsorbate interactions.