An Attempt to Improve Stance Mechanics of Trans-Tibial Amputee Gait by the Design of a Modular Ankle Joint Prosthetic

Background: A-priori research shows that trans-tibial (TT) amputees display poor gait parameters when walking with low-cost ankle-foot prosthetics (here referred to as baseline AFP’s). This has drastic implications for the amputee populations in the developing world specifically, as they have limited access to advanced prosthetic technologies. Low-cost AFP’s are unable to adequately replicate natural stance mechanics, and reliance on these devices results in increased energy expenditure, osteoarthritis and lower-limb joint deterioration. Methodology: This project details the design of a novel ankle joint prosthetic (AJP) that serves as an attachment to baseline AFP’s, with the aim of facilitating better stance mechanics via the restoration of ankle joint mechanisms. The work is presented in three core sections: Part 1 explains the rationale as to why adequately replicating natural stance mechanics is an appropriate need; Part 2 presents the design of the modular low-cost AJP that utilises only simple mechanical elements; and Part 3 presents the experimental quantification of the impact the AJP has on stance mechanics of a baseline AFP (Otto Bock 1D10) in a simulation of the TT amputee walking gait cycle, via the use of three able-bodied participants and a pseudo-prosthesis. Results: The results indicate that the AJP significantly improves the stance mechanics of the baseline AFP. During forefoot rollover a stable joint moment and an increase in joint range of motion (RoM) was observed, yielding a decrease in ankle stiffness. During initial weight acceptance of early stance, an increase in joint RoM displays the restoration of controlled plantarflexion, which indicates an improved transition from heelstrike to footflat. This is a critical mechanism that facilitates stability control during weight acceptance, and the results suggest that the designed AJP is performing better in this regard than its closest functional competitor. However, equipment errors limited the ability to accurately report on ankle stiffness of this phase. Conclusions: Overall the final conclusions are that the designed AJP improves rollover shapes of the baseline AFP, eases phase transitions, and facilitates stability control and forward tibial progression. In combination with the low cost price (±50 USD), its ease of assembly and modular design, the AJP is thus a preferable option for low-income amputees in developing countries. Finally, there is significant evidence of functional and mechanical reliability, and therefore testing of the device can progress to a clinical study involving amputee participants

De paradox van een maakbare natuur – ingebakken en omstreden : betekenis culturele identiteit voor draagvlak natuurbeleid en –beheer

This essay explores the diverse forms of social engagement with nature, against the background of cultural identity. Cultural identity, used here as an umbrella term for the connections people feel with their environment, is a factor in the local nature conservation initiatives taken by people and businesses. Conversely, for some groups in society the landscape can represent a cultural identity with which they have no affinity at all. The report is based on a literature study and aims to contribute tothe public debate on the objectives of nature policy. This is illustrated by a few examples of innovative forms of public engagement with nature. A broad public debate that emphasises engagement with nature (whatever idea of nature that might be) and respect for everyone’s opinions is essential, not only to ensure that nature policy commands widespread support, but also to inspire cultural identity with nature

Exendin-4 Improves Glycemic Control, Ameliorates Brain and Pancreatic Pathologies, and Extends Survival in a Mouse Model of Huntington's Disease

OBJECTIVE—The aim of this study was to find an effective treatment for the genetic form of diabetes that is present in some Huntington's disease patients and in Huntington's disease mouse models. Huntington's disease is a neurodegenerative disorder caused by a polyglutamine expansion within the huntingtin protein. Huntington's disease patients exhibit neuronal dysfunction/degeneration, chorea, and progressive weight loss. Additionally, they suffer from abnormalities in energy metabolism affecting both the brain and periphery. Similarly to Huntington's disease patients, mice expressing the mutated human huntingtin protein also exhibit neurodegenerative changes, motor dysfunction, perturbed energy metabolism, and elevated blood glucose levels

AAV Vector-Mediated Overexpression of CB1 Cannabinoid Receptor in Pyramidal Neurons of the Hippocampus Protects against Seizure-Induced Excitoxicity

The CB1 cannabinoid receptor is the most abundant G-protein coupled receptor in the brain and a key regulator of neuronal excitability. There is strong evidence that CB1 receptor on glutamatergic hippocampal neurons is beneficial to alleviate epileptiform seizures in mouse and man. Therefore, we hypothesized that experimentally increased CB1 gene dosage in principal neurons would have therapeutic effects in kainic acid (KA)-induced hippocampal pathogenesis. Here, we show that virus-mediated conditional overexpression of CB1 receptor in pyramidal and mossy cells of the hippocampus is neuroprotective and moderates convulsions in the acute KA seizure model in mice. We introduce a recombinant adeno-associated virus (AAV) genome with a short stop element flanked by loxP sites, for highly efficient attenuation of transgene expression on the transcriptional level. The presence of Cre-recombinase is strictly necessary for expression of reporter proteins or CB1 receptor in vitro and in vivo. Transgenic CB1 receptor immunoreactivity is targeted to glutamatergic neurons after stereotaxic delivery of AAV to the dorsal hippocampus of the driver mice NEX-cre. Increased CB1 receptor protein levels in hippocampal lysates of AAV-treated Cre-mice is paralleled by enhanced cannabinoid-induced G-protein activation. KA-induced seizure severity and mortality is reduced in CB1 receptor overexpressors compared with AAV-treated control animals. Neuronal damage in the hippocampal CA3 field is specifically absent from AAV-treated Cre-transgenics, but evident throughout cortical areas of both treatment groups. Our data provide further evidence for a role of increased CB1 signaling in pyramidal hippocampal neurons as a safeguard against the adverse effects of excessive excitatory network activity

Nonviral Approaches for Neuronal Delivery of Nucleic Acids

The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cost of large-scale formulation. Nonviral vectors are an attractive alternative in that they offer improved safety profiles compared to viruses, are less expensive to produce, and can be targeted to specific neuronal subpopulations. However, most nonviral vectors suffer from significantly lower transfection efficiencies than neurotropic viruses, severely limiting their utility in neuron-targeted delivery applications. To realize the potential of nonviral delivery technology in neurons, vectors must be designed to overcome a series of extra- and intracellular barriers. In this article, we describe the challenges preventing successful nonviral delivery of nucleic acids to neurons and review strategies aimed at overcoming these challenges