The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly and its prevalence is set to increase rapidly in coming decades. However, there are as yet no available drugs that can halt or even stabilize disease progression. One of the main pathological features of AD is the presence in the brain of senile plaques mainly composed of aggregated β amyloid (Aβ), a derivative of the longer amyloid precursor protein (APP). The amyloid hypothesis proposes that the accumulation of Aβ within neural tissue is the initial event that triggers the disease. Here we review research efforts that have attempted to inhibit the generation of the Aβ peptide through modulation of the activity of the proteolytic secretases that act on APP and discuss whether this is a viable therapeutic strategy for treating AD.<p></p> Alzheimer's disease (AD) is the most common form of dementia in the elderly but as yet there are no drugs that can halt the progression of this disease. In a theory called the ‘amyloid hypothesis’, researchers have proposed that the accumulation of a small protein fragment called beta amyloid or Aβ within brain tissue is the event which triggers Alzheimer's disease. Aβ is a derivative of the longer amyloid precursor protein (APP). Here we review research efforts that have attempted to inhibit the generation of Aβ through modulation of proteins called secretases which cut APP into Aβ. Author edits made on: 20 May 2015

Moving Healthcare Professionals Programme:embedding the promotion of physical activity in healthcare curricula

The benefits of physical activity to health are widely extolled, particularly in relation to the prevention and management of disease. However, few undergraduate healthcare curricula make space to specifically teach physical activity promotion. The professional standards of accrediting bodies ensure that public health and health promotion are embedded in pre-registration degree programmes but there is no standardised approach to covering physical activity. The national Moving Healthcare Professionals Programme (MHPP) is designed to support UK healthcare professionals and educators to gain knowledge and skills that would enable physical activity to be included within routine care to facilitate better patient outcomes

Targeted protein delivery: carbodiimide crosslinking influences protein release from microparticles incorporated within collagen scaffolds

open access articleTissue engineering response may be tailored via controlled, sustained release of active agents from protein-loaded degradable microparticles incorporated directly within three-dimensional (3D) ice-templated collagen scaffolds. However, the effects of covalent crosslinking during scaffold preparation on the availability and release of protein from the incorporated microparticles have not been explored. Here, we load 3D ice-templated collagen scaffolds with controlled additions of poly-(DL-lactide-co-glycolide) microparticles. We probe the effects of subsequent N-(3-dimethylaminopropyl)- N0-ethylcarbodiimide hydrochloride crosslinking on protein release, using microparticles with different internal protein distributions. Fluorescein isothiocyanate labelled bovine serum albumin is used as a model protein drug. The scaffolds display a homogeneous microparticle distribution, and a reduction in pore size and percolation diameter with increased microparticle addition, although these values did not fall below those reported as necessary for cell invasion. The protein distribution within the microparticles, near the surface or more deeply located within the microparticles, was important in determining the release profile and effect of crosslinking, as the surface was affected by the carbodiimide crosslinking reaction applied to the scaffold. Crosslinking of microparticles with a high proportion of protein at the surface caused both a reduction and delay in protein release. Protein located within the bulk of the microparticles, was protected from the crosslinking reaction and no delay in the overall release profile was seen

The influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites.

This study investigates the influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites. Three different silanes (mercaptopropyl trimethoxy silane (MPTMS), aminopropyl trimethoxy silane (APTMS) and aminopropyltriethoxy silane (APTES)) were applied to HA substrates in order to study the effect of head group (which binds to the polymer) and tail group (which binds to the surface hydroxyl groups in HA). A composite of hydroxyapatite (HA) and poly(d,l lactide-co-glycolide (50:50)) (PLGA) was investigated. The influence of concentration, the reaction time, drying temperature and substrate surface on silanisation was examined. TGA was used to detect the degree of silanisation. HA with MPTMS (1wt.% MPTMS with reaction time of 1h) was used as filler in PLGA-30wt.% HA composites for an in-vitro degradation study carried out in PBS. In addition, the mechanical properties of the composites were studied. Silanisation affects the properties of the composite by improving the bonding at the interface and hence it was found to influence the plastic mechanical properties rather than the elastic mechanical properties or the degradation profile of the composite.The authors are grateful to Riverside Medical Group for the funding.This is the accepted manuscript for a paper published in Materials Science and Engineering: C Volume 48, 1 March 2015, Pages 642–650, doi: 10.1016/j.msec.2014.12.05

MicroCT analysis of connectivity in porous structures: optimising data acquisition and analytical methods in the context of tissue engineering

Micro-computed X-Ray Tomography (MicroCT) is one of the most powerful techniques available for the three dimensional characterisation of complex multi-phase or porous microarchitectures. The imaging and analysis of porous networks are of particular interest in tissue engineering due to the ability to predict various large-scale cellular phenomena through the micro-scale characterisation of the structure. However, optimising the parameters for MicroCT data capture and analyses requires a careful balance of feature resolution and computational constraints whilst ensuring that a structurally representative section is imaged and analysed. In this work, artificial datasets were used to evaluate the validity of current analytical methods by considering the effect of noise and pixel size arising from the data capture, and intrinsic structural anisotropy and heterogeneity. A novel ‘segmented percolation method’ was developed to exclude the effect of anomalous, non-representative features within the datasets, allowing for scale-invariant structural parameters to be obtained consistently and without manual intervention for the first time. Finally, an in-depth assessment of the imaging and analytical procedures are presented by considering percolation events such as micro-particle filtration and cell sieving within the context of tissue engineering. Along with the novel guidelines established for general pixel size selection for MicroCT, we also report our determination of 3 µm as the definitive pixel size for use in analysing connectivity for tissue engineering applications.MN was sponsored by Geitslich Pharma AG and the Gates Cambridge Trus

STARTING KINDERGARTEN: TRANSITION ISSUES FOR CHILDREN WITH SPECIAL NEEDS

To investigate issues in transition to kindergarten for children with special needs, we explored several sources of information (peer‐reviewed literature, government websites, parent surveys, and interviews with professionals). We found that administrative issues like lack of integration and the evaluation of services available to children and families, and parent support issues like promoting advocacy were recurring themes in all sources. Although some barriers are very clear, more systematic research is needed to identify factors facilitating successful adjustment to kindergarten among children with special needs. Key words: school entry, disability, school adjustment, special education Désirant étudier les problèmes de transition à la maternelle chez les enfants ayant des besoins particuliers, les auteures ont exploré plusieurs sources d’information (publications évaluées par les pairs, sites Web gouvernementaux, sondages auprès de parents et entrevues avec des professionnels). Les auteures ont découvert que les problèmes administratifs, comme le manque d’intégration et l’évaluation des services offerts aux enfants et aux familles, et les problèmes reliés au soutien des parents, notamment la défense de leurs droits, étaient des thèmes récurrents dans toutes les sources. Bien que certains obstacles soient très clairement décrits, il faudrait une recherche plus systématique pour identifier les facteurs qui favorisent l’adaptation des enfants ayant des besoins spéciaux à la maternelle. Mots clés : entrée à l’école, déficience, adaptation scolaire, éducation de l’enfance en difficulté

Crosslinking Collagen Constructs: Achieving Cellular Selectivity Through Modifications of Physical and Chemical Properties

Collagen-based constructs have emerged in recent years as ideal candidates for tissue engineering implants. For many biomedical applications, collagen is crosslinked in order to improve the strength, stiffness and stability of the construct. However, the crosslinking process may also result in unintended changes to cell viability, adhesion or proliferation on the treated structures. This review provides a brief overview of some of both the most commonly used and novel crosslinkers used with collagen, and suggests a framework by which crosslinking methods can be compared and selected for a given tissue engineering application