Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro

<p>Abstract</p> <p>Background</p> <p>The application of mechanical insults to the spinal cord results in profound cellular and molecular changes, including the induction of neuronal cell death and altered gene expression profiles. Previous studies have described alterations in gene expression following spinal cord injury, but the specificity of this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile stresses on cultured spinal cord cells from E15 Sprague-Dawley rats, using the FX3000^®Flexercell Strain Unit. We examined cell morphology and viability over a 72 hour time course. Microarray analysis of gene expression was performed using the Affymetrix GeneChip System^®, where categorization of identified genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. Changes in expression of 12 genes were validated with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to "apoptosis" and 17 genes related to "response to stimulus". KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis.</p> <p>Conclusions</p> <p>We have demonstrated that spinal cord cells undergo cell death in response to cyclic tensile stresses, which were dose- and time-dependent. In addition, we have identified the up regulation of various genes, in particular of the MAPK pathway, which may be involved in this cellular response. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.</p

Effect of training and sudden detraining on the patellar tendon and its enthesis in rats

<p>Abstract</p> <p>Background</p> <p>Different conditions may alter tendon characteristics. Clinical evidence suggests that tendon injuries are more frequent in athletes that change type, intensity and duration of training. Aim of the study was the assessment of training and especially detraining on the patellar tendon (PT) and its enthesis.</p> <p>Methods</p> <p>27 male adult Sprague-Dawley rats were divided into 3 groups: 20 rats were trained on a treadmill for 10 weeks. Of these, 10 rats were euthanized immediately after training (trained group), and 10 were caged without exercise for 4 weeks before being euthanized (de-trained group). The remaining 7 rats were used as controls (untrained rats). PT insertion, structure (collagen fiber organization and proteoglycan, PG, content), PT thickness, enthesis area, and subchondral bone volume at the enthesis were measured by histomorphometry and microtomography.</p> <p>Results</p> <p>Both PG content and collagen fiber organization were significantly lower in untrained and detrained animals than in trained ones (<it>p </it>< 0.05 and <it>p </it>< 0.0001). In the detrained group, fiber organization and PG content were worse than that of the untrained groups and the untrained group showed a significantly higher score than the detrained group (<it>p </it>< 0.05). In the trained group, the PT was significantly thicker than in untrained group (<it>p </it>< 0.05). No significant differences in the enthesis area and subchondral bone volume among the three groups were seen.</p> <p>Conclusions</p> <p>Moderate exercise exerts a protective effect on the PT structure while sudden discontinuation of physical activity has a negative effect on tendons. The present results suggest that after a period of sudden de-training (such as after an injury) physical activity should be restarted with caution and with appropriate rehabilitation programs.</p

Effect of Strain Magnitude on the Tissue Properties of Engineered Cardiovascular Constructs

Mechanical loading is a powerful regulator of tissue properties in engineered cardiovascular tissues. To ultimately regulate the biochemical processes, it is essential to quantify the effect of mechanical loading on the properties of engineered cardiovascular constructs. In this study the Flexercell FX-4000T (Flexcell Int. Corp., USA) straining system was modified to simultaneously apply various strain magnitudes to individual samples during one experiment. In addition, porous polyglycolic acid (PGA) scaffolds, coated with poly-4-hydroxybutyrate (P4HB), were partially embedded in a silicone layer to allow long-term uniaxial cyclic mechanical straining of cardiovascular engineered constructs. The constructs were subjected to two different strain magnitudes and showed differences in biochemical properties, mechanical properties and organization of the microstructure compared to the unstrained constructs. The results suggest that when the tissues are exposed to prolonged mechanical stimulation, the production of collagen with a higher fraction of crosslinks is induced. However, straining with a large strain magnitude resulted in a negative effect on the mechanical properties of the tissue. In addition, dynamic straining induced a different alignment of cells and collagen in the superficial layers compared to the deeper layers of the construct. The presented model system can be used to systematically optimize culture protocols for engineered cardiovascular tissues

Learning technology and disability-overcoming barriers to inclusion: evidence from a multicountry study

The paper uses data from a 15-country study to discuss the factors which affect the use of Information and communication technologies (ICT) learning technologies by disabled people and consequently their access to education. Significant differences were found both between and within countries: income and language were the main factors affecting availability. Thus the greatest availability was in the higher income English speaking countries and the richer European countries. The main barriers to technology use included cost, lack of funding and lack of information. A particular disparity in technology access was found between the English speaking European population and Aboriginal speakers of indigenous languages in Australia, with considerably greater access by the former than the latter group. A number of recommendations are presented to increase access to learning and assistive technologies by disabled people. They include encouragement for developers to produce free of charge (minority language) technologies, research on more effective provision of technologies and personal assistance, assistive technology centres in all learning institutions, simple funding mechanisms and a fund to support technology provision in the poorer countries

Why a successful task substitution in glaucoma care could not be transferred from a hospital setting to a primary care setting: A qualitative study

Background: Healthcare systems are challenged by a demand that exceeds available resources. One policy to meet this challenge is task substitution-transferring tasks to other professions and settings. Our study aimed to explore stakeholders' perceived feasibility of transferring hospital-based monitoring of stable glaucoma patients to primary care optometrists.Methods: A case study was undertaken in the Rotterdam Eye Hospital (REH) using semi-structured interviews and document reviews. They were inductively analysed using three implementation related theoretical perspectives: sociological theories on professionalism, management theories, and applied political analysis.Results: Currently it is not feasible to use primary care optometrists as substitutes for optometrists and ophthalmic technicians working in a hospital-based gl

Restoring the orangutan in a Whole- or Half-Earth context

Various global-scale proposals exist to reduce the loss of biological diversity. These include the Half-Earth and Whole-Earth visions that respectively seek to set aside half the planet for wildlife conservation or to diversify conservation practices fundamentally and change the economic systems that determine environmental harm. Here we assess these visions in the specific context of Bornean orangutans Pongo pygmaeus and their conservation. Using an expert-led process we explored three scenarios over a 10-year time frame: continuation of Current Conditions, a Half-Earth approach and a Whole-Earth approach. In addition, we examined a 100-year population recovery scenario assuming 0% offtake of Bornean orangutans. Current Conditions were predicted to result in a population c. 73% of its current size by 2032. Half-Earth was judged comparatively easy to achieve and predicted to result in an orangutan population of c. 87% of its current size by 2032. Whole-Earth was anticipated to lead to greater forest loss and ape killing, resulting in a prediction of c. 44% of the current orangutan population for 2032. Finally, under the recovery scenario, populations could be c. 148% of their current size by 2122. Although we acknowledge uncertainties in all of these predictions, we conclude that the Half-Earth and Whole-Earth visions operate along different timelines, with the implementation of Whole-Earth requiring too much time to benefit orangutans. None of the theorized proposals provided a complete solution, so drawing elements from each will be required. We provide recommendations for equitable outcomes

Significant loss of mitochondrial diversity within the last century due to extinction of peripheral populations in eastern gorillas

Species and populations are disappearing at an alarming rate as a direct result of human activities. Loss of genetic diversity associated with population decline directly impacts species' long-term survival. Therefore, preserving genetic diversity is of considerable conservation importance. However, to assist in conservation efforts, it is important to understand how genetic diversity is spatially distributed and how it changes due to anthropogenic pressures. In this study, we use historical museum and modern faecal samples of two critically endangered eastern gorilla taxa, Grauer's (Gorilla beringei graueri) and mountain gorillas (Gorilla beringei beringei), to directly infer temporal changes in genetic diversity within the last century. Using over 100 complete mitochondrial genomes, we observe a significant decline in haplotype and nucleotide diversity in Grauer's gorillas. By including historical samples from now extinct populations we show that this decline can be attributed to the loss of peripheral populations rather than a decrease in genetic diversity within the core range of the species. By directly quantifying genetic changes in the recent past, our study shows that human activities have severely impacted eastern gorilla genetic diversity within only four to five generations. This rapid loss calls for dedicated conservation actions, which should include preservation of the remaining peripheral populations.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis