An in vitro spinal cord injury model to screen neuroregenerative materials

Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, safety, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofibre meshes (±poly-lysine + laminin coating) within injury sites using a lightweight construct. Patterns of nanotopography induced outgrowth/alignment of astrocytes and neurons in the in vitro model were strikingly similar to that induced by comparable materials in related studies in vivo. This highlights the value of our model in providing biologically-relevant readouts of the regeneration-promoting capacity of synthetic bridges within the complex environment of spinal cord lesions. Our approach can serve as a prototype to develop versatile bio-screening systems to identify materials/combinatorial strategies for regenerative medicine, whilst reducing live animal experimentation.EPSRC Doctoral Training Centre in regenerative medicine (EP/F500491/1

Development and Analysis of an Adverse Outcome Pathway Network for Human Neurotoxicity

An adverse outcome pathway (AOP) network is an attempt to represent the complexity of systems toxicology. This study illustrates how an AOP network can be derived and analysed in terms of its topological features to guide research and support chemical risk assessment. A four-step workflow describing general design principles and applied design principles were established and implemented. An AOP network linking nine linear AOPs was mapped and made available in AOPXplorer. The resultant AOP network was modelled and analysed in terms of its topological features, including level of degree, eccentricity and betweenness centrality. Several well connected KEs were identified, and cell injury/death was established as the most hyperlinked KE across the network. The derived network expands the utility of linear AOPs to better understand signalling pathways involved in developmental and adult/aging neurotoxicity. The results provide a solid basis to guide the development of in vitro test method batteries, as well as further quantitative modelling of key events (KEs) and key event relationships (KERs) in the AOP network, with an eventual aim to support hazard characterisation and chemical risk assessment

GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.

Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. NG2-expressing oligodendrocyte precursor cells (NG2 cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2 cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2 cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. Conversely, blockade of GABA catabolism or GABA uptake reduced NG2 cell numbers and increased the formation of mature oligodendrocytes both in control and hypoxic mice. Our results indicate that GABAergic signaling regulates NG2 cell differentiation and proliferation in vivo, and suggest that its perturbation is a key factor in DWMI

Review Article mHealth in Sub-Saharan Africa

Mobile phone penetration rates have reached 63% in sub-Saharan Africa (SSA) and are projected to pass 70% by 2013. In SSA, millions of people who never used traditional landlines now use mobile phones on a regular basis. Mobile health, or mHealth, is the utilization of short messaging service (SMS), wireless data transmission, voice calling, and smartphone applications to transmit health-related information or direct care. This systematic review analyzes and summarizes key articles from the current body of peer-reviewed literature on PubMed on the topic of mHealth in SSA. Studies included in the review demonstrate that mHealth can improve and reduce the cost of patient monitoring, medication adherence, and healthcare worker communication, especially in rural areas. mHealth has also shown initial promise in emergency and disaster response, helping standardize, store, analyze, and share patient information. Challenges for mHealth implementation in SSA include operating costs, knowledge, infrastructure, and policy among many others. Further studies of the effectiveness of mHealth interventions are being hindered by similar factors as well as a lack of standardization in study design. Overall, the current evidence is not strong enough to warrant large-scale implementation of existing mHealth interventions in SSA, but rapid progress of both infrastructure and mHealth-related research in the region could justify scale-up of the most promising programs in the near future

mHealth in Sub-Saharan Africa

Mobile phone penetration rates have reached 63% in sub-Saharan Africa (SSA) and are projected to pass 70% by 2013. In SSA, millions of people who never used traditional landlines now use mobile phones on a regular basis. Mobile health, or mHealth, is the utilization of short messaging service (SMS), wireless data transmission, voice calling, and smartphone applications to transmit health-related information or direct care. This systematic review analyzes and summarizes key articles from the current body of peer-reviewed literature on PubMed on the topic of mHealth in SSA. Studies included in the review demonstrate that mHealth can improve and reduce the cost of patient monitoring, medication adherence, and healthcare worker communication, especially in rural areas. mHealth has also shown initial promise in emergency and disaster response, helping standardize, store, analyze, and share patient information. Challenges for mHealth implementation in SSA include operating costs, knowledge, infrastructure, and policy among many others. Further studies of the effectiveness of mHealth interventions are being hindered by similar factors as well as a lack of standardization in study design. Overall, the current evidence is not strong enough to warrant large-scale implementation of existing mHealth interventions in SSA, but rapid progress of both infrastructure and mHealth-related research in the region could justify scale-up of the most promising programs in the near future

Barriers to utilization of pre-hospital emergency medical services among residents in Libreville, Gabon: A qualitative study

Introduction: In 2002, the West-African nation of Gabon established an emergency medical system (EMS), Service d’Aide Médicale Urgente (SAMU), in Libreville, yet few people access it. Our objective was to describe Libreville residents’ knowledge and attitudes toward the SAMU in an effort to understand why this service is underutilized. Methods: Qualitative interviews consisting of nine open-ended questions were conducted on a convenience sample of twenty patients, three visitors and two patient/visitor dyads at the Jeanne Ebori Hospital Emergency Centre in October 2009. Eligible subjects arrived in vehicles other than the SAMU and were ill enough to require hospital admission. Exclusion criteria were: under 21 years old, unable to speak French, or medically unstable. A bilingual team member audio-recorded the interviews in French and transcribed them into English. Investigators organized text into codes, then into themes and theoretical constructs. Intercoder agreement was excellent. Data were collected until theoretical saturation was achieved. Results: Analysis of data revealed no difference in response between patients and visitors. People underused SAMU because of financial costs, lack of awareness of the program, use of traditional modes of transportation, infrastructure flaws, perceived response times and other misconceptions. Conclusion: We identified remediable barriers to EMS (SAMU) access in Libreville, Gabon: lack of awareness, misperceptions, established alternatives, and cost. Interventions and future investigations designed to increase EMS utilization in Gabon should target these four areas