An Oral Antioxidant Formulation Delaying and Potentially Reversing

This is the final published version. It first appeared at http://clinmedlibrary.com/articles/ijdcr/ijdcr-2-023.php?jid=ijdcr.Background: The majority of dogs with diabetes mellitus develop blinding mature cataracts through the action of the enzyme aldose reductase producing sorbitol with osmotic action drawing water into the lens thus causing opacification. Here we evaluate the use of OcuGLO™ a formulation including the aldose reductase inhibitor alpha lipoic acid, grapeseed extract, carotenoids, omega-3-fatty acids, and coenzyme Q10 in the prevention of canine diabetic cataract in a prospective placebo-controlled double-masked study. Materials and methods: Dogs with diabetes mellitus but as yet without the development of blinding diabetic cataracts were given either OcuGLO™ or a placebo containing antioxidant vitamins. Dogs were examined monthly and their degree of lens opacification documented photographically using a Genesis D fundus camera at +10D. Time to progression of lens opacification was documented and compared between the OcuGLO™ group and the placebo group, using Kaplan Meier survival curve statistics Results: Mean time without change in lens opacification was 278 ± 184 days with OcuGLO Rx™ and 77 ± 40 days in the placebo group this difference being statistically significant at p=0.0005. Twelve of 15 dogs taking the placebo developed significantly increased lens opacification while 5 of 15 dogs taking OcuGLO Rx™ developed significant cataract. of these five dogs four animals did not receive daily OcuGLO Rx™ as directed due to unrelated concurrent illness or owner non-compliance. The remaining dog progressed despite Ocu-GLO Rx™ administration. In two dogs, diabetic cataract was reversed with regained vision on Ocu-GLO Rx™. Discussion: This small preliminary study demonstrates that oral Ocu-GLO Rx™ has beneficial effects in delaying cataract formation in dogs with diabetes mellitus. We look forward to further studies with larger case populations but note that the statistical significance reached between placebo and supplement-treated group, even with a small study population, demonstrates the efficacy of this commercially available dietary supplement

Briefing: UK Ministry of Defence Force Protection Engineering Programme

The Defence Science and Technology Laboratory sponsored, QinetiQ-led Force Protection Engineering Research Programme has two main strands, applied and underpinning research. The underpinning strand is led by Blastech Ltd. One focus of this research is into the response of geomaterials to threat loading. The programme on locally won fill is split into four main characterisation strands: high-stress (GPa) static pressure–volume; medium-rate pressure–volume (split Hopkinson bar); high-rate (flyer plate) pressure–volume; and unifying modelling research at the University of Sheffield, which has focused on developing a high-quality dataset for locally won fill in low and medium strain rates. With the test apparatus at Sheffield well-controlled tests can be conducted at both high strain rate and pseudo-static rates up to stress levels of 1 GPa. The University of Cambridge has focused on using one-dimensional shock experiments to examine high-rate pressure–volume relationships. Both establishments are examining the effect of moisture content and starting density on emergent rate effects. Blastech Ltd has been undertaking carefully controlled fragment impact experiments, within the dataspace developed by the Universities of Sheffield and Cambridge. The data from experiments are unified by the QinetiQ-led modelling team, to predict material behaviour and to derive a scalable locally won fill model for use in any situation

Demyelination and axonal preservation in a transgenic mouse model of Pelizaeus-Merzbacher disease

It is widely thought that demyelination contributes to the degeneration of axons and, in combination with acute inflammatory injury, is responsible for progressive axonal loss and persistent clinical disability in inflammatory demyelinating disease. In this study we sought to characterize the relationship between demyelination, inflammation and axonal transport changes using a Plp1-transgenic mouse model of Pelizaeus-Merzbacher disease. In the optic pathway of this non-immune mediated model of demyelination, myelin loss progresses from the optic nerve head towards the brain, over a period of months. Axonal transport is functionally perturbed at sites associated with local inflammation and 'damaged' myelin. Surprisingly, where demyelination is complete, naked axons appear well preserved despite a significant reduction of axonal transport. Our results suggest that neuroinflammation and/or oligodendrocyte dysfunction are more deleterious for axonal health than demyelination per se, at least in the short ter

Temporal variations in English Populations of a forest insect pest, the green spruce aphid (Elatobium abietinum), associated with the North Atlantic Oscillation and global warming

Based on an exceptionally long modern ecological dataset (41 years), it has been possible to show that warm weather in England associated with a positive North Atlantic Oscillation (NAO) index causes the spring migration of the green spruce aphid (Elatobium abietinum), a pest species of spruce trees (Picea) to start earlier, continue for longer and contain more aphids. An upward trend in the NAO index during the period 1966-2006 is associated with an increasing population size of E. abietinum. It is important to understand the mechanisms behind the population fluctuations, because this aphid causes considerable damage to Picea plantations. Present day weather associated fluctuations in forest insect pests may be useful analogues in understanding past pest outbreaks in forests

Why don't they accept Non-Invasive Ventilation? : Insight into the interpersonal perspectives of patients with MND.

"Objectives. Although non-invasive ventilation (NIV) can benefit survival and quality of life, it is rejected by a substantial proportion of people with motor neurone disease (MND). The aim of this study was to understand why some MND patients decline or withdraw from NIV. Method. Nine patients withMND(male = 7, mean age = 67 years) participated in this study. These patients, from a cohort of 35 patients who were offered NIV treatment to support respiratory muscle weakness, did not participate in NIV treatment when it was clinically appropriate. Semi-structured interviews and interpretative phenomenological analysis (IPA) were employed to explore these patient’s experience of MND and their thoughts and understanding of NIV treatment. Results. Using IPA, four themes were identified: preservation of the self, negative perceptions of NIV, negative experience with health care services, and not needing NIV. Further analysis identified the fundamental issue to be the maintenance of perceived self, which was interpreted to consist of the sense of autonomy, dignity, and quality of life. Conclusions. The findings indicate psychological reasons for disengagement with NIV. The threat to the self, the sense of loss of control, and negative views of NIV resulting from anxiety were more important to these patients than prolonging life in its current form. These findings suggest the importance of understanding the psychological dimension involved in decision-making regarding uptake of NIV and a need for sensitive holistic evaluation if NIV is declined.

Complementary hydro-mechanical coupled finite/discrete element and microseismic modelling to predict hydraulic fracture propagation in tight shale reservoirs

This paper presents a novel approach to predict the propagation of hydraulic fractures in tight shale reservoirs. Many hydraulic fracture modelling schemes assume that the fracture direction is pre-seeded in the problem domain discretization. This is a severe limitation as the reservoir often contains large numbers of pre-existing fractures that strongly influence the direction of the propagating fracture. To circumvent these shortcomings a new fracture modelling treatment is proposed where the introduction of discrete fracture surfaces is based on new and dynamically updated geometrical entities rather than the topology of the underlying spatial discretization. Hydraulic fracturing is an inherently coupled engineering problem with interactions between fluid flow and fracturing when the stress state of the reservoir rock attains a failure criterion. This work follows a staggered hydro-mechanical coupled finite/discrete element approach to capture the key interplay between fluid pressure and fracture growth. In field practice the fracture growth is hidden from the design engineer and microseismicity is often used to infer hydraulic fracture lengths and directions. Microsesimic output can also be computed from changes of the effective stress in the geomechanical model and compared against field microseismicity. A number of hydraulic fracture numerical examples are presented to illustrate the new technology

Peptidyl-prolyl cis-trans isomerases (immunophilins) and their roles in parasite biochemistry, host-parasite interaction and antiparasitic drug action.

Immunophilin is the collective name given to the cyclophilin and FK506-binding protein (FKBP) families. As the name suggests, these include the major binding proteins of certain immunosuppressive drugs: cyclophilins for the cyclic peptide cyclosporin A and FKBPs for the macrolactones FK506 and rapamycin. Both families, although dissimilar in sequence, possess peptidyl-prolyl <i>cis-trans</i> isomerase activity in vitro and can play roles in protein folding and transport, RNA splicing and the regulation of multiprotein complexes in cells. In addition to enzymic activity, many immunophilins act as molecular chaperones. This property may be conferred by the isomerase domain and/or by additional domains. Recent years have seen a great increase in the number of known immunophilin genes in parasitic protozoa and helminths and in many cases their products have been characterized biochemically and their temporal and spatial expression patterns have been examined. Some of these genes represent novel types: one example is a <i>Toxoplasma gondii</i> gene encoding a protein with both cyclophilin and FKBP domains. Likely roles in protein folding and oligomerisation, RNA splicing and sexual differentiation have been suggested for parasite immunophilins. In addition, unexpected roles in parasite virulence (Mip FKBP of <i>Trypanosoma cruzi</i>) and host immuno-modulation (e.g. 18-kDa cyclophilin of <i>Toxoplasma gondii</i>) have been established. Furthermore, in view of the potent antiparasitic activities of cyclosporins, macrolactones and nonimmunosuppressive derivatives of these compounds, immunophilins may mediate drug action and/or may themselves represent potential drug targets. Investigation of the mechanisms of action of these agents may lead to the design of potent and selective antimalarial and other antiparasitic drugs. This review discusses the properties of immunophilins in parasites and the 'animal model' <i>Caenorhabditis elegans</i> and relates these to our understanding of the roles of these proteins in cellular biochemistry, host-parasite interaction and the antiparasitic mechanisms of the drugs that bind to them

Sustainability appraisal: Jack of all trades, master of none?

Sustainable development is a commonly quoted goal for decision making and supports a large number of other discourses. Sustainability appraisal has a stated goal of supporting decision making for sustainable development. We suggest that the inherent flexibility of sustainability appraisal facilitates outcomes that often do not adhere to the three goals enshrined in most definitions of sustainable development: economic growth, environmental protection and enhancement, and the wellbeing of the human population. Current practice is for sustainable development to be disenfranchised through the interpretation of sustainability, whereby the best alternative is good enough even when unsustainable. Practitioners must carefully and transparently review the frameworks applied during sustainability appraisal to ensure that outcomes will meet the three goals, rather than focusing on a discourse that emphasises one or more goals at the expense of the other(s)