Exploring the muscle architecture effect on the mechanical behaviour of mouse rotator cuff muscles.

Incorporating detailed muscle architecture aspects into computational models can enable researchers to gain deeper insights into the complexity of muscle function, movement, and performance. In this study, we employed histological, multiphoton image processing, and finite element method techniques to characterise the mechanical dependency on the architectural behaviour of supraspinatus and infraspinatus mouse muscles. While mechanical tests revealed a stiffer passive behaviour in the supraspinatus muscle, the collagen content was found to be two times higher in the infraspinatus. This effect was unveiled by analysing the alignment of fibres during muscle stretch with the 3D models and the parameters obtained in the fitting. Therefore, a strong dependence of muscle behaviour, both active and passive, was found on fibre orientation rather than collagen content.

A numerical investigation of changes in lens shape during accommodation.

The purpose of this study was to investigate how the mechanical properties and geometry of the lens influence the changes in lens shape during accommodation. To do so, ex vivo stretching tests of the isolated lens were simulated via finite element analysis. In these tests, the lens is stretched from the accommodated state to the non-accommodated state. Several key characteristics of the lens were studied: the stiffness gradient of the lens material, the distribution of the capsule thickness, the mechanical properties of the capsule and the material comprising the lens, nucleus and cortex, and the influence of two different age-related lens geometries (17 and 29 y/o subjects). To determine the effects on the changes in lens shape during accommodation, changes in the anterior and posterior radius, the lens and nucleus thicknesses and the equatorial lens diameter were analysed. The results suggest that multiple factors exert statistically significant influences on how the lens changes its shape, but two factors predominate over the rest: the stiffness ratio between the nucleus and cortex and the stiffness of the capsule, specifically the posterior surface.

[Patient safety in psychiatric hospitalization - What incidents are reported and managed?] / Qué se notifica y gestiona en seguridad del paciente en hospitalización psiquiátrica.

INTRODUCTION: Reporting and management systems monitoring patient safety incidents (PSIs) facilitate the understanding of mechanisms of action and allow work on improvement activities to minimise their occurrence. In our country, little is known about the adverse effects of healthcare during psychiatric hospitalisation (PH). The aim of this study is to determine the occurrence and characteristics of the PSIs, as well as the improvement actions resulting from them, in the PH services being offered at the Parc Sanitari Sant Joan de Deu (an institution specialized in mental healthcare). MATERIAL AND METHOD: An observational, descriptive, and cross-sectional study was conducted, covering the period 2013-2016. Analysis was made of the PSIs reported in the following areas of PH: acute and sub-acute (ASA), and medium and long-term stay (MLS). The following variables were identified: number, type and level of harm resulting from the PSIs, professional category of the person declaring the PSI, method of analysis used to investigate the PSI, and improvement actions generated by those PSIs that required either root-cause analysis or audit reports. The chi-squared test was used for statistical purposes when comparing percentages. RESULTS: A total of 2,940 PSIs were reported. The frequency in ASA was significantly higher (7.1 per 1,000 stays) than in MLS (5.3). Almost all (97.6%) of the incidents were related to falls, aggressive and/or disturbed behaviour, mind-altering drugs, self-harm, medication, dangerous objects, and patients escaping. PSIs recording moderate or severe harm were similar in the 2 different areas (16.5% in ASA vs. 14.2% in MLS). A small percentage (1.02%) of the PSIs resulted in root cause analysis or audit reporting, due to their severity, and from those incidents, 56 improvement actions were generated. CONCLUSIONS: PH demonstrates its own characteristics with regard to the type of PSIs and differs from general hospitalisation. Reporting of PSIs is higher in ASA than in MLS, although the level of harm experienced by the patients is similar. There is a clear understanding of reporting in PH, demonstrated by the steady increase in the numbers declared and also highlights the high level of awareness of the nursing staff.

Oxidative stress prediction: A preliminary approach using a response surface based technique.

A response surface was built to predict the lipid peroxidation level, generated in an iron-ascorbate in vitro model, of any organ, which is correlated with the oxidative stress injury in biological membranes. Oxidative stress studies are numerous, usually performed on laboratory animals. However, ethical concerns require validated methods to reduce the use of laboratory animals. The response surface described here is a validated method to replace animals. Tissue samples of rabbit liver, kidney, heart, skeletal muscle and brain were oxidized with different concentrations of FeCl3 (0.1 to 8mM) and ascorbate (0.1mM), during different periods of time (0 to 90min) at 37°C. Experimental data obtained, with lipid content and antioxidant activity of each organ, allowed constructing a multidimensional surface capable of predicting, by interpolation, the lipid peroxidation level of any organ defined by its antioxidant activity and fat content, when exposed to different oxidant conditions. To check the predictive potential of the technique, two more experiments were carried out. First, in vitro oxidation data from lung tissue were collected. Second, the antioxidant capacity of kidney homogenates was modified by adding melatonin. Then, the response surface generated could predict lipid peroxidation levels produced in these new situations. The potential of this technique could be reinforced using collaborative databases to reduce the number of animals in experimental procedures.

Predicting muscle fatigue: a response surface approximation based on proper generalized decomposition technique.

A novel technique is proposed to predict force reduction in skeletal muscle due to fatigue under the influence of electrical stimulus parameters and muscle physiological characteristics. Twelve New Zealand white rabbits were divided in four groups ([Formula: see text]) to obtain the active force evolution of in vitro Extensor Digitorum Longus muscles for an hour of repeated contractions under different electrical stimulation patterns. Left and right muscles were tested, and a total of 24 samples were used to construct a response surface based in the proper generalized decomposition. After the response surface development, one additional rabbit was used to check the predictive potential of the technique. This multidimensional surface takes into account not only the decay of the maximum repeated peak force, but also the shape evolution of each contraction, muscle weight, electrical input signal and stimulation protocol. This new approach of the fatigue simulation challenge allows to predict, inside the multispace surface generated, the muscle response considering other stimulation patterns, different tissue weight, etc.

Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction.

On Using Model Populations to Determine Mechanical Properties of Skeletal Muscle. Application to Concentric Contraction Simulation.

In the field of computational biomechanics, the experimental evaluation of the material properties is crucial for the development of computational models that closely reproduce real organ systems. When simulations of muscle tissue are concerned, stress/strain relations for both passive and active behavior are required. These experimental relations usually exhibit certain variability. In this study, a set of material parameters involved in a 3D skeletal muscle model are determined by using a system biology approach in which the parameters are randomly varied leading to a population of models. Using a set of experimental results from an animal model, a subset of the entire population of models was selected. This reduced population predicted the mechanical response within the window of experimental observations. Hence, a range of model parameters, instead of a single set of them, was determined. Rat Tibialis Anterior muscle was selected for this study. Muscles ([Formula: see text]) were activated through the sciatic nerve and during contraction the tissue pulled a weight fixed to the distal tendon (concentric contraction). Three different weights 1, 2 and 3 N were used and the time course of muscle stretch was analyzed obtaining values of (mean [Formula: see text] standard deviation): [Formula: see text], [Formula: see text] and [Formula: see text] respectively. A paired two-sided sign rank test showed significant differences between the muscle response for the three weights ([Formula: see text]). This study shows that the Monte Carlo method could be used for determine muscle characteristic parameters considering the variability of the experimental population.

Determination of passive viscoelastic response of the abdominal muscle and related constitutive modeling: stress-relaxation behavior.

In this paper, the authors investigate the passive viscoelastic properties of rabbit abdominal wall. In vitro strain relaxation tests were performed in the oblique muscle (in two perpendicular directions), the rectus abdominis and the linea alba in the longitudinal direction. Based on experimental data, a model for the viscoelastic mechanical properties of this tissue is presented here. In particular, we used a 3D non-linear viscoelastic model to fit data sets obtained from tissue of the rabbit abdominal wall. Uniaxial relaxation tests were carried out for samples obtained from the abdominal wall. The experimental results clearly demonstrate the anisotropy and nonlinearity of the abdominal tissue. The stress relaxation was higher in the transverse direction (closer to muscle fibers) with an average value of the final stress ratio of 48%, than in the longitudinal direction with around 56% of this ratio for the oblique muscle. These tests, at several stretch levels, presented a different behavior depending on the region where the tissue sample was located. There was no dependence between the stress relaxation ratio and the stretch level for the oblique muscles in their longitudinal or transverse directions (p>0.01). In contrast, for rectus abdominis and linea alba a dependence between the stress relaxation ratio and stretch level was found. Our study revealed an increase in the stress relaxation ratio for the rectus abdominis (p<0.01) and a decrease for the linea alba with higher stretch levels (p<0.01). Overall good predictions ε<0.115 were obtained with the model proposed for the oblique muscle (no dependence on the stretch level) and to reproduce the non-linear viscoelastic response of rectus abdominis and linea alba.

On simulating sustained isometric muscle fatigue: a phenomenological model considering different fiber metabolisms.

The present study shows a new computational FEM technique to simulate the evolution of the mechanical response of 3D muscle models subjected to fatigue. In an attempt to obtain very realistic models, parameters needed to adjust the mathematical formulation were obtained from in vivo experimental tests. The fatigue contractile properties of three different rat muscles (Tibialis Anterior, Extensor Digitorium Longus and Soleus) subjected to sustained maximal isometric contraction were determined. Experiments were conducted on three groups [Formula: see text] of male Wistar rats [Formula: see text] using a protocol previously developed by the authors for short tetanic contractions. The muscles were subjected to an electrical stimulus to achieve tetanic contraction during 10 s. The parameters obtained for each muscle were incorporated into a finite strain formulation for simulating active and passive behavior of muscles with different fiber metabolisms. The results show the potential of the model to predict muscle fatigue under high-frequency stimulation and the 3D distribution of mechanical variables such as stresses and strains.

A 3D electro-mechanical continuum model for simulating skeletal muscle contraction.

A thermodynamically consistent three-dimensional electro-mechanical continuum model for simulating skeletal muscle contraction is presented. Active and passive responses are accounted for by means of a decoupled strain energy function into passive and active contributions. The active force is obtained as the maximum tetanic force penalized by two functions that consider the external stimulus frequency and the overlap between actin and myosin filaments. Passive response is modelled by a transversely isotropic strain energy function. The robustness of the model is analyzed by means of finite element simulations that reproduce the one-dimensional isometric, concentric and eccentric contractions in a simplified model of a muscle. The model has also been implemented to reproduce isometric and concentric contractions on a three-dimensional finite element model of the rat tibialis anterior (TA) muscle. The finite element model was obtained from magnetic resonance imaging and the preferential directions associated with the collagen and muscular fibres were considered. The proposed model was able to reproduce the observed experimental response of the active force generated by the isolated rat TA muscle during isometric and concentric contractions. In addition, the predicted force-velocity relationship is in good agreement with experimental data reported for the fast-twitch extensor digitorum longus (e.d.l) muscle of male rats.

Variations in tendon stiffness due to diets with different glycotoxins affect mechanical properties in the muscle-tendon unit.

Passive elastic behavior of tendon tissue from rats subjected to different dietary treatments was characterized. For that purpose, twenty-four weanling Wistar rats (41.02 ± 0.16 g) were randomly distributed into four groups. During 88 days each group was fed on different diets: control diet and diets containing advanced glycation end products (AGEs) from glucose-lysine model system, from bread crust and bread dough, respectively. After the trial animals were sacrificed and tendon samples were extracted and tested mechanically to fracture in a uniaxial tensile test machine. A transversely-hyperelastic model was formulated based on stress-strain relationships and its parameters were fit to the experimental data using the Levenberg-Marquardt optimization algorithm. Material parameters were incorporated in a finite element model to study different stress-strain distributions in a muscle-tendon unit. Results show higher strains and stresses in the muscle belly when properties of a stiffer tendon associated with a diet rich in AGEs are included in the model. A real increase in this mechanical response of the tissue could imply possible pain in joint mobility.

A 3D active-passive numerical skeletal muscle model incorporating initial tissue strains. Validation with experimental results on rat tibialis anterior muscle.

This paper presents a three-dimensional finite element model of skeletal muscle and its validation incorporating inital tissue strains. A constitutive relation was determined by using a convex free strain energy function (SEF) where active and passive response contributions were obtained fitting experimental data from the rat tibialis anterior (TA) muscle. The passive and active finite strains response was modelled within the framework of continuum mechanics by a quasi-incompressible transversely isotropic material formulation. Magnetic resonance images (MRI) were obtained to reconstruct the external geometry of the TA. This geometry includes initial strains also taken into account in the numerical model. The numerical results show excellent agreement with the experimental results when comparing reaction force-extension curves both in passive and active tests. The proposed constitutive model for the muscle is implemented in a subroutine in the commercial finite element software package ABAQUS.

Influencia del concentrado de plaquetas sobre la reconstrucción de defectos de cartílago articular en la rodilla de cordero / Influence of concentrated platelets on the reconstruction of cartilage defects in the lamb knee joint

Objetivo. Analizar el efecto de las plaquetas sobre el crecimiento de cartílago en los defectos articulares provocados en la rodilla ovina. Material y método. Se provocó un defecto de 4mm de diámetro y 3mm de profundidad en la tróclea femoral de ambas rodillas en corderos macho de 6 meses de edad. La distribución de los grupos fue: grupo A (n=6): el defecto de la rodilla derecha se rellenó con concentrado de plaquetas 5min después de ser activado con ClCa. Grupo B (n=6): el defecto se rellenó con colágeno y plaquetas. Material y método. Las plaquetas se obtuvieron por centrifugación de 10ml de sangre arterial obtenida de cada animal antes de la cirugía. En los defectos de la rodilla izquierda no se administraron plaquetas. Las ovejas fueron sacrificadas 10 semanas después de la cirugía. Se realizaron estudios macro y microscópicos. Resultados. En el grupo A, se observó cartílago hialino en 4 de los defectos de la rodilla derecha a las 10 semanas de la cirugía. Ninguno de los defectos de la rodilla izquierda mostró crecimiento de cartílago hialino. En el grupo B, no se observó cartílago hialino en nigún defecto. No obstante, todos los defectos presentaron mejor celularidad condral y menor fibrosis en los defectos tratados con plaquetas que en los no tratados. Conclusiones. Esta técnica para la reconstrucción con plaquetas de defectos articulares de oveja ha mostrado en nuestro estudio resultados esperanzadores que empeoran combinadas con un andamiaje de colágeno (AU)

Objective. To study the influence of platelets on cartilage growth in articular defects in the sheep knee. Material and methods. Male Rasa Aragonesa sheep (6 months) were operated under general anaesthesia. A 4mm diameter and 3mm deep defect was made in the femoral trochlea in both knees. The right knee defect was filled with platelet concentrate 5min after being activated with ClCa in group A (n=6), and similarly activated platelets + collagen scaffold in group B (n=6). Platelets were obtained by centrifuging 10ml arterial blood from the sheep prior to the surgical procedure. The left knee defect was not filled. The sheep were sacrificed 10 weeks after surgery. Macroscopic and microscopic studies were performed. Results. In group A, hyaline cartilage was observed in the right knee defect at the end of the experiment in four cases. None of the defects of the left knees showed hyaline cartilage growth. In group B, hyaline cartilage was not observed in any right knee defect. However, in group B, all sheep showed better chondral cellularity and regeneration and lower fibrosis in the defects treated with platelets than in non-treated ones. Conclusions. This technique for articular defect reconstruction with platelets has shown satisfactory results in our study. However, collagen scaffolds may decrease this positive effect (AU)

Active response of skeletal muscle: in vivo experimental results and model formulation.

The contractile properties of the tibial anterior (TA) of Wistar rats were measured by means of a multipurpose testing machine. The muscle was isolated from the connective tissues, preserving the proximal insertion. The distal tendon was transected and fixed to the machine actuator. The leg was inmobilised using a pin drilled through the femoral condyle. In this way the force response was studied in vivo at different constant lengths for some voltages and frequencies. Mathematical functions are proposed for adjusting the force-length, force-frequency and force-time relations. The model includes a novel formulation for the depression response during muscle tetanisation.

Monitoring in vivo load transmission through an external fixator.

This work presents a portable non-invasive external fixator to assess and monitor fracture healing in real time. To evaluate the potential of this fixator, a transverse osteotomy was performed in the tibia of six adult sheep (mean age 3+/-0.5 years and weight 63+/-5 kg). The fractures were stabilized by a specially designed unilateral external fixator, which was instrumented by means of a set of strain gauges. Strains in the external surface of the fixator were monitored during all the healing process. A wireless, remote monitoring of the implant was developed through a specially designed external telemetric device. The strain gauges were arranged in two different half-bridge Wheatstone configurations, allowing easy post-processing of the signal. Thus, bending loads were measured in two planes of the external fixator acting as a load cell. The load through the fixator was evaluated for the gait cycle during all the healing process. Full weight bearing of the injured leg was observed from the beginning. The load transmission mechanism in the fixator was quite similar in all operated tibias and radiographic images showed a successful healing in all animals. Although the fixator has only been tested in an animal model, after further testing this system may have clinical potential.

Passive nonlinear elastic behaviour of skeletal muscle: experimental results and model formulation.

The goal of this study was to characterize the passive elastic behaviour of muscle and tendon tissues of rat tibialis anterior. For that purpose, tissue samples from 3 month old female Wistar rats (210+/-11g) were mechanically tested in vitro. Moreover, an in vivo device was developed to measure the muscle-tendon unit response to increasing load. Mechanical tests, consisting of uniaxial loading along the longitudinal axis of tendon and muscle strips, revealed the nonlinear mechanical behaviour of these tissues. A material model was formulated and its parameters fit to the experimental data using the Levenberg-Marquardt optimization algorithm. The fit goodness was assessed and R(2) values close to 1 and very low epsilon values were obtained. The passive behaviour of a future finite element model of a muscle-tendon unit will be validated against the in vivo passive extension tests by comparing the reaction force-extension curves.

An experimental study of the mouse skin behaviour: damage and inelastic aspects.

Samples of male and female mice skin were tested under monotonic and cyclic loading to mechanically characterize the tissue for large deformations. Cyclic tests have shown a typical Mullins effect widely known for elastomers and other soft tissues. No statistical difference was found in the maximum stretch of the sample after the fifth loading cycle for male (1.26 +/- 0.035) and female (1.18 +/- 0.083). However, larger dispersion was obtained for the maximum stress for both genders, 0.61 +/- 0.16 MPa for male and 0.78 +/- 0.32 MPa for female. Results show the presence of inelastic strain and stress softening in the skin at large deformations. They also have shown how stress softening and residual strain change with the magnitude of the applied load. Good correlation was observed between the residual strain and the maximum strain previously attained by the sample during loading for all samples. However, the correlation was different between genders.

[Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in ischemic vascular disease]. / Polimorfismo C677T del gen de la metilentetrahidrofolato reductasa (MTHFR) en la patología isquémica vascular.

AIM: Genetic and metabolism of C677T methylenetetrahydrofolate reductase (MTHFR) mutation and its relationship with ischemic vascular disease are revised. DEVELOPMENT: Homocygotes for C677T MTHFR mutation, 10-15% of general population, develop a thermolabil variant of the MTHFR enzyme which has a reduced functional activity. Because of this lower activity, is more likely for these patients to have mild hyperhomocysteinemia, a potential vascular risk factor, through their lives. A correct intake of folates and group B vitamins can help to compensate this genetic trend caused by the mutation. CONCLUSION: Molecular finding of C677T MTHFR mutation allow us to identify a part of population with a potential risk factor for ischemic vascular disease, with the advantage that is an easily revertible factor by modulation of the diet.

Polimorfismo C677T del gen de la metilentetrahidrofolato reductasa (MTHFR) en la patología isquémica vascular / Methylenetetrahydrofolate reductase (mthfr) c677t polymorphism in ischemic vascular disease

Objetivo. Se analizan las características genéticas y metabólicasde la mutación C677T del gen de la metilentetrahidrofolatoreductasa (MTHFR) y su relación con la enfermedad isquémicavascular a través de una revisión de la bibliografía. Desarrollo.Los homocigotos para la mutación C677T MTHFR, que constituyenel 10-15% de la población general, desarrollan una variedadtermolábil de la enzima MTHFR con una actividad funcional reducida,que hace que tengan una tendencia sostenida a lo largo de suvida a padecer hiperhomocisteinemia moderada, que es candidataa ser un factor de riesgo vascular. El aporte adecuado de folatos yvitaminas del grupo B contribuye a revertir el condicionamientogenético que sobre el metabolismo de los folatos y de la metioninadetermina la mutación. Conclusión. La determinación molecularde la mutación C677T MTHFR permitirá identificar a un gruponotable de la población con tendencia a desarrollar un factor deriesgo potencial y fácilmente prevenible

Aim. Genetic and metabolism of C677T methylenetetrahydrofolate reductase (MTHFR) mutation and its relationshipwith ischemic vascular disease are revised. Development. Homocygotes for C677T MTHFR mutation, 10-15% of generalpopulation, develop a thermolabil variant of the MTHFR enzyme which has a reduced functional activity. Because of thislower activity, is more likely for these patients to have mild hyperhomocysteinemia, a potential vascular risk factor, throughtheir lives. A correct intake of folates and group B vitamins can help to compensate this genetic trend caused by the mutation.Conclusion. Molecular finding of C677T MTHFR mutation allow us to identify a part of population with a potential risk factorfor ischemic vascular disease, with the advantage that is an easily revertible factor by modulation of the diet

[Prevalence of methylenetetrahydrofolate reductase C677T mutation among patients with acute ischemic cerebrovascular disease in Aragon]. / Prevalencia de la mutación C677T del gen de la metilentetrahidrofolato reductasa en pacientes con patología isquémica cerebrovascular aguda en la Comunidad Autónoma Aragonesa.

BACKGROUND: Mutation C677T of the methylenetetrahydrofolate reductase (MTHFR) is the main cause of mild hyperhomocysteinemia. Hyperhomocysteinemia is a recognized risk factor for aterothrombosis. MTHFR C677T patients have higher levels of homocysteine in absence of dietary folates. METHODS: Retrospective study over data from patients studied for MTHFR C677T diagnosed of ischemic stroke (IS) younger 50 or older 50 without classic vascular risk factors or with familiar or personal history suggesting thrombophilia in a period of 3 years. MTHFR C677T was screened in 90 healthy blood donors as a control group. Computer database was used for descriptive statistics. RESULTS: Blood samples from 99 patients and from 90 donors (control). Mean age: 44.3 with Standard deviation (SD) 13.9 years in IS group and 39.1 with SD 8.3 years in control group. We found 19 (19.19%) homozygotes for MTHFR C677T in IS group and 14 (15.55%) in control group. CONCLUSIONS: Homozygosis for MTHFR C667T is more frequent in the IS group than in the control one, although there is no significant differences. Anyway, we suggest that, because of the high prevalence of the mutation MTHFR C677T found, screening should be made in the thombophilia studies, so that we could find patients with a risk factor that could be lowered by folates in the diet.