Cytoskeletal regulation of inflammation and its impact on skin blistering disease epidermolysis bullosa acquisita

Actin remodelling proteins regulate cytoskeletal cell responses and are important in both innate and adaptive immunity. These responses play a major role in providing a fine balance in a cascade of biological events that results in either protective acute inflammation or chronic inflammation that leads to a host of diseases including autoimmune inflammation mediated epidermolysis bullosa acquisita (EBA). This review describes the role of the actin cytoskeleton and in particular the actin remodelling protein called Flightless I (Flii) in regulating cellular inflammatory responses and its subsequent effect on the autoimmune skin blistering disease EBA. It also outlines the potential of an antibody based therapy for decreasing Flii expression in vivo to ameliorate the symptoms associated with EBA.Zlatko Kopecki, Ralf J. Ludwig and Allison J. Cowi

Effect of packing on nasal mucosa of sheep

The effects of packing with ribbon gauze and neuropatties on the nasal mucosa was assessed using sheep as an animal model. Fourteen sheep either underwent ribbon gauze or neuropattie nasal packing. Trauma to nasal mucosa caused by ribbon gauze and neuropatties was compared to mucosa on the lateral aspect of the middle turbinate which was not in contact with any packing. This tissue was used as a control. Ribbon gauze packing resulted in significant loss of 68 per cent of the ciliated surface of the mucosa when compared with the control group with a 15 per cent loss of ciliated surface (p < 0.005). Neuropattie packing also resulted in significant loss of 50 per cent of the ciliated surface of the mucosa when compared with the control group (p < 0.005). There was no significant difference in loss of ciliated mucosa in the specimens packed with ribbon gauze or neuropatties (p = 0.25). Nasal packing results in a significant mucosal injury with loss of cilia. This may influence the mucociliary clearance of the nose in the post-operative healing phase. Pre-operative nasal packing should be used circumspectly and if possible avoided.Chi-kee Leslie Shaw, Robert B. Dymock, Allison Cowin and Peter-John Wormal

Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

The closest elastic tensor of arbitrary symmetry to an elasticity tensor of lower symmetry

The closest tensors of higher symmetry classes are derived in explicit form for a given elasticity tensor of arbitrary symmetry. The mathematical problem is to minimize the elastic length or distance between the given tensor and the closest elasticity tensor of the specified symmetry. Solutions are presented for three distance functions, with particular attention to the Riemannian and log-Euclidean distances. These yield solutions that are invariant under inversion, i.e., the same whether elastic stiffness or compliance are considered. The Frobenius distance function, which corresponds to common notions of Euclidean length, is not invariant although it is simple to apply using projection operators. A complete description of the Euclidean projection method is presented. The three metrics are considered at a level of detail far greater than heretofore, as we develop the general framework to best fit a given set of moduli onto higher elastic symmetries. The procedures for finding the closest elasticity tensor are illustrated by application to a set of 21 moduli with no underlying symmetry.Comment: 48 pages, 1 figur

Performance evaluation of novel square-bordered position-sensitive silicon detectors with four-corner readout

We report on a recently developed novel type of large area (62 mm x 62 mm) position sensitive silicon detector with four-corner readout. It consists of a square-shaped ion-implanted resistive anode framed by additional low-resistivity strips with resistances smaller than the anode surface resistance by a factor of 2. The detector position linearity, position resolution, and energy resolution were measured with alpha-particles and heavy ions. In-beam experimental results reveal a position resolution below 1 mm (FWHM) and a very good non-linearity of less than 1% (rms). The energy resolution determined from 228Th alpha source measurements is around 2% (FWHM).Comment: 13 pages, 10 figures, submitted to Nucl. Instr. and Meth.

Multiscale Bone Remodelling with Spatial P Systems

Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as our shape-based one already resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Understanding presentations of children with fever to a Sydney emergency department

Background: Fever is a common childhood illness resulting in a potentially high number of presentations to local Emergency Departments (ED). This paper describes the characteristics of these presentations of children, including initial and subsequent diagnosis, disposition from ED and seasonal variations, to inform nursing and other health professionals working within these departments. Methods: The study was conducted at a metropolitan hospital in Sydney, using existing data collected by emergency staff. Data for a 12-month period were extracted from the existing database of all ED presentations. Results: This study demonstrated that the age of the majority of febrile child presentations varied between 13 months and 24 months (53%), and the number of ED visits doubled during the winter months (33%). Most of the child presentations to ED in this study were not urgent (68%). Viral illness, upper respiratory tract infections, and urinary tract infections accounted for 14.9 % of all the ED presentations, with most being discharged to home. Conclusion: This study confirms the continuing pattern of inappropriate presentations to EDs of children with fever. Public education campaigns are needed to reduce these presentations

Lifting the silver flakes: the pathogenesis and management of chronic plaque psoriasis

Psoriasis is a common chronic inflammatory skin condition in which patients suffer from mild to chronic plaque skin plaques. The disease manifests through an excessive inflammatory response in the skin due to complex interactions between different genetic and environmental factors. Psoriasis can affect the physical, emotional, and psychosocial well-being of patients, and currently there is no cure with treatments focusing primarily on the use of anti-inflammatory agents to control disease symptoms. Traditional anti-inflammatory agents can cause immunosuppression and adverse systemic effects. Further understanding of the disease has led to current areas of research aiming at the development of selective molecular targets to suppress the pathogenic immune responses.Heng T. Chong, Zlatko Kopecki, and Allison J. Cowi