Molecular simulations of the large conductance mechanosensitive (MscL) channel under mechanical loading

AbstractThe MscL channel is a mechanosensitive channel which is gated by membrane stress or tension. Here, we describe a series of simulations which apply simulated mechanical stress to a molecular model of the MscL channel using two methods – direct force application to the transmembrane segments, and anisotropic pressure coupling. In the latter simulations, pressures less than that equivalent to a bilayer tension of 12 dyn/cm did not cause the channel to open, while pressures in excess of this value resulted in the channel opening. These results are in approximate agreement with experimental findings

Parents’ knowledge of car safety and practices amongst school children in an urban community of Lagos, Nigeria

No fewer than 1.2 million deaths globally are attributed to road traffic crashes yearly, with low- and middleincome countries contributing disproportionately to these deaths. Children are a vulnerable road user group, and riding unrestrained is a significant risk factor for death and injury among child car passengers. This studyaimed to determine child car safety knowledge and practices among parents of children attending a private school in an urban setting in Lagos, Nigeria. A descriptive study, using observations of child car safety practices, and a survey of parental knowledge and attitudes of child car safety, were conducted simultaneously amongst children 0-10 years riding in cars to school. Data was analysed using Epi Info Version 3.5.1. A total of 127 cars were observed as children were being dropped off at school. The proportion of child passengers aged 0 - 10 years restrained by any device was 6.3%, with only 2.4% of these children being appropriately restrained for age; 19.7% of observed child passengers rode in the front seat. Awareness of car safety seats among parents was high at 85%. However, less than 40% of respondents knew the correct age to commence use of child restraints, seat belts, or front seating. The reason most cited for non-use of child restraints was unavailability (24.1%). Despite the high level of awareness about car safety seats, parental knowledge of specific child passenger safety issues and practices were poor. Targeted interventions are needed to bridge the gap between awareness, knowledge and practice in this population.Keywords: child, motor vehicle passenger, car restraints, adults, knowledge and attitude, road safet

Buckle up safely: a cluster randomised trial to evaluate the effectiveness of a pre-school based program to increase appropriate use of child restraints

BACKGROUND: Road traffic crashes for car occupants are a leading cause of death and serious injury in children from high and middle income countries globally. Correct use of appropriate child restraints can significantly reduce death and serious injury but there is a need for well powered trials to examine effectiveness of programs to increase optimal child restraint practices. The aim of this trial is to examine the effectiveness of a comprehensive intervention to increase the use of appropriate child restraints, and decrease incorrect use of child restraints in pre-school aged children traveling in cars. METHODS AND DESIGN: A cluster randomised controlled trial will be conducted, involving 28 pre-school or childcare centres in low income areas of Sydney, Australia, over one calendar year. The intervention is an educational program involving an in-service for centre staff, distribution of educational materials to parents, a parent workshop demonstrating restraint use, subsidised restraints for parents in need, and vouchers for a free restraint checking service. Blinded assessors will observe restraint use at all centres at the end of the calendar year. Data will be analysed on an intention-to-treat basis; the primary analysis will compare the proportion of each of the two outcome measures (use of appropriate restraints, and incorrect use of restraints) at each centre between intervention and control groups. Detailed process evaluation will be conducted, including examination of implementation and utilisation of various elements of the program by both centres and families. DISCUSSION: This assessor blinded cluster randomised trial is powered to provide credible evidence about the efficacy of an education and distribution program in a pre-school setting to increase appropriate use, and decrease incorrect use of child restraints. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12609000612213

Computational model of the cerebral ventricles in hydrocephalus

Understanding the mechanisms of tissue injury in hydrocephalus is important to shed light on the pathophysiology of this neurostructural disorder. To date, most of the finite element models created to study hydrocephalus have been two-dimensional (2D). This may not be adequate as the geometry of the cerebral ventricles is unique. In this study, a three-dimensional (3D) finite element model of the cerebral ventricles during hydrocephalus is presented. Results from this model show that during hydrocephalus, the periventricular regions experience the highest stress, and stress magnitude is approximately 80 times higher than the cerebral mantle. This suggests that functional deficits observed in hydrocephalic patients could therefore be more related to the damage to periventricular white matter. In addition, the stress field simulated in the tissues based on the 3D model was found to be approximately four times lower than on the 2D model.4 page(s

Unconfined compression of white matter

The porous properties of brain tissue are important for understanding normal and abnormal cerebrospinal fluid flow in the brain. In this study, a poroviscoelastic model was fitted to the stress relaxation response of white matter in unconfined compression performed under a range of low strain rates. A set of experiments was also performed on the tissue samples using a no-slip boundary condition. Results from these experiments demonstrated that the rheological response of the white matter is primarily governed by the intrinsic viscoelastic properties of the solid phase. The permeability of white matter was found to be of the order of 10⁻¹² m⁴/Ns.8 page(s

Rheological properties of anisotropic tissues at large amplitude oscillatory shear

The mechanical properties of soft biological tissues have been widely investigated over the past five decades [1–5]. Reported measurements of soft biological tissues such as the brain, spinal cord, liver and muscle vary by orders of magnitude, depending on the sample preparation, anisotropy and loading regime. Knowing the accurate mechanical properties of biological tissues is important for many applications, for example car crash testing and simulations require accurate information on how different parts of the body deform due to a combination of loads. Deformation of tissues around prosthetics and artificial limbs are critical in understanding load transfer at interfaces with the body. The recent use of Magnetic Resonance Elastography (MRE) in diagnostic imaging has resulted in a surge of interest in accurate measurements of mechanical properties of tissues [6].2 page(s

The Effects of the interthalamic adhesion position on cerebrospinal fluid dynamics in the cerebral ventricles

The interthalamic adhesion is a unique feature of the third ventricle in the brain. It differs in shape and size and its location varies between individuals. In this study, computational fluid dynamics was performed on 4 three-dimensional models of the cerebral ventricular system with the interthalamic adhesion modeled in different locations in the third ventricle. Cerebrospinal fluid (CSF) was modeled as incompressible Newtonian fluid and flow was assumed laminar. The periodic motion of CSF flow as a function of the cardiac cycle starting from diastole was prescribed as the inlet boundary condition at the foramen of Monroe. Results from this study show how the location of the interthalamic adhesion influences the pattern of pressure distribution in the cerebral ventricles. In addition, the highest CSF pressure in the third ventricle can vary by ?50% depending on the location of the interthalamic adhesion. We suggest that the interthalamic adhesion may have functional implications on the development of hydrocephalus and it is important to model this anatomical feature in future studies.4 page(s

The Mechanical properties of neonatal rat spinal cord in vitro, and comparisons with adult

A number of studies have investigated the mechanical properties of adult spinal cord under tension, however it is not known whether age has an effect on these properties. This is of interest to those aiming to understand the clinical differences between adults and children with spinal cord injury (e.g. severity and recovery), and those developing experimental or computational models for paediatric spinal cord injury. Entire spinal cords were freshly harvested from neonatal rats (14 days) and tested in vitro under uniaxial tension at a range of strain rates (0.2, 0.02, 0.002/s) to a range of strains (2%, 3.5%, 5%), with relaxation responses being recorded for 15 min. These mechanical properties were compared to previously reported data from similar experiments on adult rat spinal cords, and the peak stress and the stress after 15 min of relaxation were found to be significantly higher for spinal cords from adults than neonates (p<0.001). A non-linear viscoelastic model was developed and was observed to adequately predict the mechanical behaviour of this tissue. The model developed in this study may be of use in computational models of paediatric spinal cord. The significant differences between adult and neonatal spinal cord properties may explain the higher initial severity of spinal cord injury in children and may have implications for the development of experimental animal models for paediatric spinal cord injury, specifically for those aiming to match the injury severity with adult experimental models.6 page(s

The Effects of preconditioning strain on measured tissue properties

Characterizing the mechanical properties of soft biological tissues presents a formidable challenge. In order to ensure that the structure of the specimens is at a repeatable reference state, preconditioning is commonly performed before the actual test. However, the exact mechanisms of preconditioning remain unclear and more research on this issue needs to be undertaken so that the methods for preconditioning can be refined to reduce experimental variability. Previous studies have suggested that the choice of preconditioning strain may influence the measured properties. In this study, uniaxial tests were performed on three groups of spinal cord tissues. Two groups (Groups 1 and 2) were preconditioned at 5% strain and tested to 5% and 2% each, while the third (Group 3) was preconditioned at 2% strain and tested to 2%. The peak stress measured at 2% strain for group 3 was 0.0054±0.0035 MPa and this was significantly higher than group 2 (134%; p=0.015) and group 1 (p=0.005). However, the ratio of peak to equilibrium stress and the relaxation time were similar for both preconditioning strains. This study suggests that in future work, the preconditioning strain should be reported and the highest strain being used in the study should be used for preconditioning. This is important to allow meaningful comparison of test data within the study and also with other studies.3 page(s