Brain tissue mechanics is governed by microscale relations of the tissue constituents.

Local mechanical tissue properties are a critical regulator of cell function in the central nervous system (CNS) during development and disorder. However, we still don't fully understand how the mechanical properties of individual tissue constituents, such as cell nuclei or myelin, determine tissue mechanics. Here we developed a model predicting local tissue mechanics, which induces non-affine deformations of the tissue components. Using the mouse hippocampus and cerebellum as model systems, we show that considering individual tissue components alone, as identified by immunohistochemistry, is not sufficient to reproduce the local mechanical properties of CNS tissue. Our results suggest that brain tissue shows a universal response to applied forces that depends not only on the amount and stiffness of the individual tissue constituents but also on the way how they assemble. Our model may unify current incongruences between the mechanics of soft biological tissues and the underlying constituents and facilitate the design of better biomedical materials and engineered tissues. To this end, we provide a freely-available platform to predict local tissue elasticity upon providing immunohistochemistry images and stiffness values for the constituents of the tissue.

Positive, negative and controlled durotaxis.

Cell migration is a physical process central to life. Among others, it regulates embryogenesis, tissue regeneration, and tumor growth. Therefore, understanding and controlling cell migration represent fundamental challenges in science. Specifically, the ability of cells to follow stiffness gradients, known as durotaxis, is ubiquitous across most cell types. Even so, certain cells follow positive stiffness gradients while others move along negative gradients. How the physical mechanisms involved in cell migration work to enable a wide range of durotactic responses is still poorly understood. Here, we provide a mechanistic rationale for durotaxis by integrating stochastic clutch models for cell adhesion with an active gel theory of cell migration. We show that positive and negative durotaxis found across cell types are explained by asymmetries in the cell adhesion dynamics. We rationalize durotaxis by asymmetric mechanotransduction in the cell adhesion behavior that further polarizes the intracellular retrograde flow and the protruding velocity at the cell membrane. Our theoretical framework confirms previous experimental observations and explains positive and negative durotaxis. Moreover, we show how durotaxis can be engineered to manipulate cell migration, which has important implications in biology, medicine, and bioengineering.

The nucleus acts as a ruler tailoring cell responses to spatial constraints.

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.

Mechanotransmission of haemodynamic forces by the endothelial glycocalyx in a full-scale arterial model.

The glycocalyx has been identified as a key mechano-sensor of the shear forces exerted by streaming blood onto the vascular endothelial lining. Although the biochemical reaction to the blood flow has been extensively studied, the mechanism of transmission of the haemodynamic shear forces to the endothelial transmembrane anchoring structures and, consequently, to the subcellular elements in the cytoskeleton, is still not fully understood. Here we apply a multiscale approach to elucidate how haemodynamic shear forces are transmitted to the transmembrane anchors of endothelial cells. Wall shear stress time histories, as obtained from image-based computational haemodynamics models of a carotid bifurcation, are used as a load and a continuum model is applied to obtain the mechanical response of the glycocalyx all along the cardiac cycle. The main findings of this in silico study are that: (1) the forces transmitted to the transmembrane anchors are in the range of 1-10 pN, which is in the order of magnitude reported for the different conformational states of transmembrane mechanotranductors; (2) locally, the forces transmitted to the anchors of the glycocalyx structure can be markedly different from the near-wall haemodynamic shear forces both in amplitude and frequency content. The findings of this in silico approach warrant future studies focusing on the actual forces transmitted to the transmembrane mechanotransductors, which might outperform haemodynamic descriptors of disturbed shear as localizing factors of vascular disease.

Methodology for Y Chromosome Capture: A complete genome sequence of Y chromosome using flow cytometry, laser microdissection and magnetic streptavidin-beads.

This study is a comparison of the efficiency of three technologies used for Y chromosome capture and the next-generation sequencing (NGS) technologies applied for determining its whole sequence. Our main findings disclose that streptavidin-biotin magnetic particle-based capture methodology offers better and a deeper sequence coverage for Y chromosome capture, compared to chromosome sorting and microdissection procedures. Moreover, this methodology is less time consuming and the most selective for capturing only Y chromosomal material, in contrast with other methodologies that result in considerable background material from other, non-targeted chromosomes. NGS results compared between two platforms, NextSeq 500 and SOLID 5500xl, produce the same coverage results. This is the first study to explore a methodological comparison of Y chromosome capture and genetic analysis. Our results indicate an improved strategy for Y chromosome research with applications in several scientific fields where this chromosome plays an important role, such as forensics, medical sciences, molecular anthropology and cancer sciences.

MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content.

MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH) levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

Mechanics Reveals the Biological Trigger in Wrinkly Fingers.

Fingertips wrinkle due to long exposure to water. The biological reason for this morphological change is unclear and still not fully understood. There are two main hypotheses for the underlying mechanism of fingertip wrinkling: the 'shrink' model (in which the wrinkling is driven by the contraction of the lower layers of skin, associated with the shrinking of the underlying vasculature), and the 'swell' model (in which the wrinkling is driven by the swelling of the upper layers of the skin, associated with osmosis). In reality, contraction of the lower layers of the skin and swelling of the upper layers will happen simultaneously. However, the relative importance of these two mechanisms to drive fingertip wrinkling also remains unclear. Simulating the swelling in the upper layers of skin alone, which is associated with neurological disorders, we found that wrinkles appeared above an increase of volume of [Formula: see text] Therefore, the upper layers can not exceed this swelling level in order to not contradict in vivo observations in patients with such neurological disorders. Simulating the contraction of the lower layers of the skin alone, we found that the volume have to decrease a [Formula: see text] to observe wrinkles. Furthermore, we found that the combined effect of both mechanisms leads to pronounced wrinkles even at low levels of swelling and contraction when individually they do not. This latter results indicates that the collaborative effect of both hypothesis are needed to induce wrinkles in the fingertips. Our results demonstrate how models from continuum mechanics can be successfully applied to testing hypotheses for the mechanisms that underly fingertip wrinkling, and how these effects can be quantified.

Inercia terapéutica en el manejo de pacientes con diabetes mellitus tipo 2 en el ámbito de la Atención Primaria / Therapeutic inertia in the management of type 2 diabetic patients in Primary Health Care

Objetivo. Valorar la inercia terapéutica (IT) en el manejo de los pacientes diabéticos tipo 2 (DM2) respecto al control glucémico y lipídico. Material y métodos. Se estudiaron 2 grupos de pacientes. Grupo 1: todos los pacientes mayores de 14 años con registro de DM2 hasta el 28-02-2013 y con la última determinación de HbA1c ≥ 8,5%. Grupo 2: todos los pacientes menores de 60 años con diagnóstico de DM2 realizado entre el 1-01-2011 y el 31-12-2012, sin complicaciones crónicas de la enfermedad y con la última determinación de HbA1c ≥ 6,5%. Resultados. Grupo 1: fueron incluidos 253 pacientes (13% de los DM2 registrados). La IT fue del 43% para la DM2, del 83% para el colesterol LDL y del 80% para los triglicéridos. La IT fue inferior (p = 0,037) en los pacientes con HbA1c ≥ 10%. La IT en el manejo del perfil lipídico no fue diferente dependiendo de los niveles de HbA1c. Grupo 2: fueron valorados todos los pacientes con DM2 (n = 53) que cumplían criterios de inclusión (2,7% de los casos de DM2 registrados). Porcentaje de visitas en las que se practicó IT: 55% para la DM2, 63% para el colesterol LDL y 64% para los triglicéridos. Se observó una mayor intensificación de la terapia en pacientes con HbA1c > 7,5% en 3 de las 5 visitas realizadas. Conclusiones. En ambos grupos la IT fue elevada, existiendo un infrarregistro de los motivos de la misma. Es importante mejorar la actitud y las condiciones laborales de los profesionales que atienden a la población diabética (AU)

Objective. To assess therapeutic inertia (TI) in the management of type 2 diabetic patients (DM2), as regards glycemic and lipid control. Materials and methods. Two groups of patients were studied. Group 1: All the patients were older than 14 years, diagnosed with DM2 up to 28th February 2013, and their last determination of HbA1c was ≥ 8.5%. Group 2: All patients, under 60 years old, diagnosed with DM2 between the 1st January 2011 and the 31st December 2012, with no chronic complications and their last determination of HbA1c was ≥ 6.5%. Results. Group 1: 253 patients were included (13% of DM2 diagnosed). TI was 43% for DM2, 83% for LDL cholesterol, and 80% for triglycerides. TI was lower (P = .037) in patients with HbA1c ≥ 10%. There was no difference in TI as regards the management of lipid profile depending on the HbA1c levels. Group 2: All DM2 patients (n = 53) who met inclusion criteria were assessed (2.7% of DM2 diagnosed). Percentage of visits of those patients that had TI: 55% for DM2, 63% for LDL cholesterol and 64% for triglycerides. A more intense therapy was observed in patients with HbA1c > 7.5% in 3 of the 5 visits made. Conclusions. TI in both groups was high and there is a lack of recording the reasons for this. It is important to improve the attitude of the professionals who care for the diabetic population (AU)

Microstructural quantification of collagen fiber orientations and its integration in constitutive modeling of the porcine carotid artery.

BACKGROUND: Mechanical characteristics of vascular tissue may play a role in different arterial pathologies, which, amongst others, requires robust constitutive descriptions to capture the vessel wall's anisotropic and non-linear properties.Specifically, the complex 3D network of collagen and its interaction with other structural elements has a dominating effect of arterial properties at higher stress levels.The aim of this study is to collect quantitative collagen organization as well as mechanical properties to facilitate structural constitutive models for the porcine carotid artery.This helps the understanding of the mechanics of swine carotid arteries, being a standard in clinical hypothesis testing, in endovascular preclinical trials for example. METHOD: Porcine common carotid arteries (n=10) were harvested and used to (i) characterize the collagen fiber organization with polarized light microscopy, and (ii) the biaxial mechanical properties by inflation testing.The collagen organization was quantified by the Bingham orientation density function (ODF), which in turn was integrated in a structural constitutive model of the vessel wall.A one-layered and thick-walled model was used to estimate mechanical constitutive parameters by least-square fitting the recorded in vitro inflation test results.Finally, uniaxial data published elsewhere were used to validate the mean collagen organization described by the Bingham ODF. RESULTS: Thick collagen fibers, i.e.the most mechanically relevant structure, in the common carotid artery are dispersed around the circumferential direction.In addition, almost all samples showed two distinct families of collagen fibers at different elevation, but not azimuthal, angles.Collagen fiber organization could be accurately represented by the Bingham ODF (κ1,2,3=[13.5,0.0,25.2] and κ1,2,3=[14.7,0.0,26.6]; average error of about 5%), and their integration into a structural constitutive model captured the inflation characteristics of individual carotid artery samples.Specifically, only four mechanical parameters were required to reasonably (average error from 14% to 38%) cover the experimental data over a wide range of axial and circumferential stretches.However, it was critical to account for fibrilar links between thick collagen fibers.Finally, the mean Bingham ODF provide also good approximation to uniaxial experimental data. CONCLUSIONS: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, the collagen fiber orientations measured from polarized light microscopy, alone, seem to be insufficient structural information. Alternatively, a larger dispersion of collagen fiber orientations, that is likely to arise from analyzing larger wall sections, could have had a similar effect, i.e. could have avoided coupling amongst thick collagen fibers. STATEMENT OF SIGNIFICANCE: The applied structural constitutive model, based on individually measured collagen orientation densities, was able to capture the biaxial and uniaxial properties of the common carotid artery. Since the model required coupling amongst thick collagen fibers, an effective orientation density that accounts for cross-links between the main collagen fibers has been porposed. The model provides a good approximation to the experimental data.

Computational modeling of acute myocardial infarction.

Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.

The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict fractional flow reserve without adenosine?) multicenter study.

OBJECTIVE: Functional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations. OBJECTIVE: We sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa-NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa. METHODS: We conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30-70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa-NTG and FFR were measured. RESULTS: 283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa-NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa-NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84-0.92, P < 0.001) and 0.94 (95% CI: 0.92-0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa-NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa-NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa-NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis. CONCLUSION: The cutoff value of acute Pd/Pa-NTG > 0.88 has a high NPV meaning adenosine-FFR can be avoided in almost half of lesions.

[Therapeutic inertia in the management of type 2 diabetic patients in Primary Health Care]. / Inercia terapéutica en el manejo de pacientes con diabetes mellitus tipo 2 en el ámbito de la Atención Primaria.

OBJECTIVE: To assess therapeutic inertia (TI) in the management of type 2 diabetic patients (DM2), as regards glycemic and lipid control. MATERIALS AND METHODS: Two groups of patients were studied. Group 1: All the patients were older than 14 years, diagnosed with DM2 up to 28th February 2013, and their last determination of HbA1c was ≥ 8.5%. Group 2: All patients, under 60 years old, diagnosed with DM2 between the 1st January 2011 and the 31st December 2012, with no chronic complications and their last determination of HbA1c was ≥ 6.5%. RESULTS: Group 1: 253 patients were included (13% of DM2 diagnosed). TI was 43% for DM2, 83% for LDL cholesterol, and 80% for triglycerides. TI was lower (P=.037) in patients with HbA1c ≥ 10%. There was no difference in TI as regards the management of lipid profile depending on the HbA1c levels. Group 2: All DM2 patients (n=53) who met inclusion criteria were assessed (2.7% of DM2 diagnosed). Percentage of visits of those patients that had TI: 55% for DM2, 63% for LDL cholesterol and 64% for triglycerides. A more intense therapy was observed in patients with HbA1c>7.5% in 3 of the 5 visits made. CONCLUSIONS: TI in both groups was high and there is a lack of recording the reasons for this. It is important to improve the attitude of the professionals who care for the diabetic population.

A theoretical model of the endothelial cell morphology due to different waveforms.

Endothelial cells are key units in the regulatory biological process of blood vessels. They represent an interface to transmit variations on the fluid dynamic changes. They are able to adapt its cytoskeleton, by means of microtubules reorientation and F-actin reorganization, due to new mechanical environments. Moreover, they are responsible for initiating a huge cascade of biological processes, such as the release of endothelins (ET-1), in charge of the constriction of the vessel and growth factors such as TGF-ß and PDGF. Although a huge efforts have been made in the experimental characterization and description of these two issues the computational modeling has not gained such an attention. In this work we study the 3D remodeling of endothelial cells based on the main features of blood flow. In particular we study how different oscillatory shear index and the time average wall shear stresses modify the endothelial cell shape. We found our model fitted the experimental works presented before in in vitro studies. We also include our model within a computational fluid dynamics simulation of a carotid artery to evaluate endothelial cell shape index which is a key predictor of atheroma plaque formation. Moreover, our approach can be coupled with models of collagen and smooth muscle cell growth, where remodeling and the associated release of chemical substance are involved.

Computational model of collagen turnover in carotid arteries during hypertension.

It is well known that biological tissues adapt their properties because of different mechanical and chemical stimuli. The goal of this work is to study the collagen turnover in the arterial tissue of hypertensive patients through a coupled computational mechano-chemical model. Although it has been widely studied experimentally, computational models dealing with the mechano-chemical approach are not. The present approach can be extended easily to study other aspects of bone remodeling or collagen degradation in heart diseases. The model can be divided into three different stages. First, we study the smooth muscle cell synthesis of different biological substances due to over-stretching during hypertension. Next, we study the mass-transport of these substances along the arterial wall. The last step is to compute the turnover of collagen based on the amount of these substances in the arterial wall which interact with each other to modify the turnover rate of collagen. We simulate this process in a finite element model of a real human carotid artery. The final results show the well-known stiffening of the arterial wall due to the increase in the collagen content.

Production patterns of packaging waste categories generated at typical Mediterranean residential building worksites.

The construction sector is responsible for around 28% of the total waste volume generated in Europe, which exceeds the amount of household waste. This has led to an increase of different research studies focusing on construction waste quantification. However, within the research studies made, packaging waste has been analyzed to a limited extent. This article focuses on the packaging waste stream generated in the construction sector. To this purpose current on-site waste packaging management has been assessed by monitoring ten Mediterranean residential building works. The findings of the experimental data collection revealed that the incentive measures implemented by the construction company to improve on-site waste sorting failed to achieve the intended purpose, showing low segregation ratios. Subsequently, through an analytical study the generation patterns for packaging waste are established, leading to the identification of the prevailing kinds of packaging and the products responsible for their generation. Results indicate that plastic waste generation maintains a constant trend throughout the whole construction process, while cardboard becomes predominant towards the end of the construction works with switches and sockets from the electricity stage. Understanding the production patterns of packaging waste will be beneficial for adapting waste management strategies to the identified patterns for the specific nature of packaging waste within the context of construction worksites.

A structural approach including the behavior of collagen cross-links to model patient-specific human carotid arteries.

In this work the mechanical response of the carotid arterial wall is studied. Some limitations of previous models of the arterial wall are overcomed and variability of the fitting problem is reduced. We review some experimental data from the literature and provide a constitutive model to characterize such data. A strain energy function is introduced including the behavior of cross-links between the main collagen fibers. With this function we are able to fit experimental data including information about the microstructure that previous models were not able to do. To demonstrate the applicability of the proposed model a patient-specific carotid artery geometry is reconstructed and simulated in a finite element framework, providing a microstructural description of the arterial wall. Our results qualitatively and quantitatively describe the experimental findings given in the literature fitting macroscopic mechanical tests and improving the features of previously developed models.

Dissemination of hepatocellular carcinoma in subcutaeous tissue after fine needle aspiration cytology (FNAC).

The hepatocellular carcinoma (HCC) is the fifth most frequent tumor in the world, and the third cause of death related to cancer. Histological samples obtained from diseased liver likely to have HCC are currently prescribed in selected patients in whose imaging studies and tumor markers are not sufficient for the diagnosis. In recent years, a risk of tumoral seeding along needle tract of FNAC to obtain histological samples has been reported. We present a case of tumor implantation of HCC cells in the needle tract, a year and four months after a percutaneous fine needle aspiration cytology (FNAC).

Validation of a cheap and simple nondestructive method for obtaining AFLPs and DNA sequences (mitochondrial and nuclear) in amphibians.

The use of nondestructive methods for obtaining DNA from amphibians (e.g. buccal swabs) allows genetic studies to be performed without affecting the survival of the studied individuals. In this study, we compared two methods of nondestructive DNA sampling, buccal swabs and interdigital membrane or toe-clipping, in several amphibian species of different size: Rhinella spinulosa, R. atacamensis, six species of the genus Telmatobius and Pleurodema thaul. We evaluated the integrity of the DNA extracted by sequencing fragments of mitochondrial and nuclear genes and by generating amplified fragment length polymorphisms markers (AFLPs). In all cases, we obtained an adequate amount of DNA (mean range 55-298 ng/µL). We obtained identical DNA sequences from buccal swab and interdigital membrane/toe-clip for all individuals. The differences in the coding of AFLP markers between the tissues were similar to those reported for replicas of the same type of sample in similar analyses in other species of amphibians. In conclusion, the use of buccal swabs is a trustworthy and inexpensive method to obtain DNA for mitochondrial and nuclear sequencing and AFLP analyses. Given the types of markers evaluated, buccal swabs may be used for phylogenetic, phylogeographic and population genetic studies, even in small amphibians (<33 mm).

Anisotropic microsphere-based approach to damage in soft fibered tissue.

An anisotropic damage model for soft fibered tissue is presented in this paper, using a multi-scale scheme and focusing on the directionally dependent behavior of these materials. For this purpose, a micro-structural or, more precisely, a microsphere-based approach is used to model the contribution of the fibers. The link between micro-structural contribution and macroscopic response is achieved by means of computational homogenization, involving numerical integration over the surface of the unit sphere. In order to deal with the distribution of the fibrils within the fiber, a von Mises probability function is incorporated, and the mechanical (phenomenological) behavior of the fibrils is defined by an exponential-type model. We will restrict ourselves to affine deformations of the network, neglecting any cross-link between fibrils and sliding between fibers and the surrounding ground matrix. Damage in the fiber bundles is introduced through a thermodynamic formulation, which is directly included in the hyperelastic model. When the fibers are stretched far from their natural state, they become damaged. The damage increases gradually due to the progressive failure of the fibrils that make up such a structure. This model has been implemented in a finite element code, and different boundary value problems are solved and discussed herein in order to test the model features. Finally, a clinical application with the material behavior obtained from actual experimental data is also presented.

Mujer de 18 años con metahemoglobinemia tras utilización de crema anestésica tópica / An 18 year old female with methaemoglinaemia after using EMLA(R) topical anaesthetic cream

La metahemoglobinemia es una entidad poco frecuente, cuyo diagnóstico se basa en la aparición de niveles elevados de metahemoglobina en sangre, tanto en adultos como en niños. Es una de las causas importantes de cianosis, y en ocasiones la severidad de su presentación puede requerir el ingreso en Unidades de Cuidado Intensivo. Las causas pueden ser adquiridas o congénitas, siendo ésta última debida a mutación en el gen de la hemoglobina reductasa dependiente de NADPH. La forma adquirida o metahemoglobinemia tóxica se produce cuando los hematíes son expuestos a sustancias químicas oxidantes que aumentan la producción de metahemoglobina, sobrepasando los mecanismos reductores de protección que actúan normalmente. Se presenta el caso de una mujer de 18 años, con cuadro de cianosis de aparición súbita diagnosticada de metahemoglobinemia tóxica tras utilización de crema anestésica tópica EMLA(R) (mezcla de anestésicos locales, lidocaína y prilocaína(AU)

Methaemoglobinaemia is a very uncommon disorder, with its diagnosis being based on the appearance of high levels of methaemoglobin in the blood, both in adults and children. It is an important cause of cyanosis, and occasionally its severity of its presentation may require admission to an Intensive Care Unit. It may be acquired or hereditary; the latter being due to a mutation of the NADPH-dependent haemoglobin reductase gene. The acquired form or toxic methaemoglobinaemia is produced when red cells are exposed to oxidising chemicals that increase methaemoglobin production, overwhelming the regulatory mechanisms that function normally (AU)