Changes in Cerebral Oxidative Metabolism during Neonatal Seizures Following Hypoxic-Ischemic Brain Injury.

Seizures are common following hypoxic-ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain; however, the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system, we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO]) and hemodynamics during recurrent neonatal seizures following hypoxic-ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude-integrated electroencephalogram. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean electroencephalogram voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism

What is Asset-Based Community Development and how might it improve the health of people with long-term conditions? A realist synthesis

Abstract Background Asset Based Community Development (ABCD) appears to be a promising way to supporting people with long-term health problems but there is currently a lack of evidence to support this approach. Methods Taking a realist approach, a review and concept-mapping exercise of ABCD approaches to improve health were conducted with a view to providing a better understanding about these approaches, how they work, and who they work for. Results 29 papers were deemed relevant and included in the review. The realist synthesis and concept mapping helped identify concepts most commonly associated with ABCD but found no papers focussed on LTCs and thus no evidence that this approach improves health outcomes for people with LTCs. Conclusions Whilst there is a lack of clarity about how to implement ABCD or how to evaluate it, this paper offers a clearer theoretical framework about the essential ingredients needed to activate ABCD

Reactive Oxygen Species Modulate the Barrier Function of the Human Glomerular Endothelial Glycocalyx

Reactive oxygen species (ROS) play a key role in the pathogenesis of proteinuria in glomerular diseases like diabetic nephropathy. Glomerular endothelial cell (GEnC) glycocalyx covers the luminal aspect of the glomerular capillary wall and makes an important contribution to the glomerular barrier. ROS are known to depolymerise glycosaminoglycan (GAG) chains of proteoglycans, which are crucial for the barrier function of GEnC glycocalyx. The aim of this study is to investigate the direct effects of ROS on the structure and function of GEnC glycocalyx using conditionally immortalised human GEnC. ROS were generated by exogenous hydrogen peroxide. Biosynthesis and cleavage of GAG chains was analyzed by radiolabelling (S35 and 3H-glucosamine). GAG chains were quantified on GEnC surface and in the cell supernatant using liquid chromatography and immunofluorescence techniques. Barrier properties were estimated by measuring trans-endothelial passage of albumin. ROS caused a significant loss of WGA lectin and heparan sulphate staining from the surface of GEnC. This lead to an increase in trans-endothelial albumin passage. The latter could be inhibited by catalase and superoxide dismutase. The effect of ROS on GEnC was not mediated via the GAG biosynthetic pathway. Quantification of radiolabelled GAG fractions in the supernatant confirmed that ROS directly caused shedding of HS GAG. This finding is clinically relevant and suggests a mechanism by which ROS may cause proteinuria in clinical conditions associated with high oxidative stress. © 2013 Singh et al.published_or_final_versio

Oxidized polyethylene films for orienting polar molecules for linear dichroism spectroscopy

Stretched polyethylene (PE) films have been used to orient small molecules for decades by depositing solutions on their surface and allowing the solvent to evaporate leaving the analyte absorbed on the polymer film. However, the non-polar hydrophobic nature of PE is an obstacle to aligning polar molecules and biological samples. In this work PE film was treated with oxygen plasma in order to increase surface hydrophilicity. Different treatment conditions were evaluated using contact angle measurement and X-ray photoelectron spectroscopy. Treated PE (PEOX) films are shown to be able to align molecules of different polarities including progesterone, 1-pyrenecarboxaldehyde, 4′,6-diamidino-2-phenylindole (DAPI) and anthracene. The degree of alignment of each molecule was studied by running series of linear dichroism (LD) experiments and the polarizations of electronic transition moments were determined. For the first time optimal conditions (such as stretching factor and concentration of the sample) for stretched film LD were determined. PEOX aligning ability was compared to that of normal PE films. Progesterone showed a slightly better alignment on PEOX than PE. 1-Pyrenecarboxaldehyde oriented differently on the two different films which enabled transition moment assignment for this low symmetry molecule. DAPI (which does not align on PE) aligned well on PEOX and enabled us to obtain better LD data than had previously been collected with polyvinyl alcohol. Anthracene alignment and formation of dimers and higher order structures were studied in much more detail than previously possible, showing a variety of assemblies on PE and PEOX films

Position Reconstruction in Drift Chambers operated with Xe, CO2 (15%)

We present measurements of position and angular resolution of drift chambers operated with a Xe,CO$_2$(15%) mixture. The results are compared to Monte Carlo simulations and important systematic effects, in particular the dispersive nature of the absorption of transition radiation and non-linearities, are discussed. The measurements were carried out with prototype drift chambers of the ALICE Transition Radiation Detector, but our findings can be generalized to other drift chambers with similar geometry, where the electron drift is perpendicular to the wire planes.Comment: 30 pages, 18 figure

Participation in voluntary and community organisations in the United Kingdom and the influences on the self-management of long-term conditions

Voluntary and community organisations (VCOs) have health benefits for those who attend and are viewed as having the potential to support long-term condition management. However, existing community-level understandings of participation do not explain the involvement with VCOs at an individual level, or the nature of support, which may elicit health benefits. Framing active participation as ‘doing and experiencing’, the aim of this qualitative study was to explore why people with long-term vascular conditions join VCOs, maintain their membership and what prevents participation. Twenty participants, self-diagnosed as having diabetes, chronic heart disease or chronic kidney disease, were purposefully sampled and recruited from a range of VCOs in the North West of England identified from a mapping of local organisations. In semi-structured interviews, we explored the nature of their participation. Analysis was thematic and iterative involving a continual reflection on the data. People gave various reasons for joining groups. These included health and well-being, the need for social contact and pursuing a particular hobby. Barriers to participation included temporal and spatial barriers and those associated with group dynamics. Members maintained their membership on the basis of an identity and sense of belonging to the group, developing close relationships within it and the availability of support and trust. Participants joined community groups often in response to a health-related event. Our findings demonstrate the ways in which the social contact associated with continued participation in VCOs is seen as helping with long-term condition management. Interventions designed at improving chronic illness management might usefully consider the role of VCOs

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes

Ceramics studio to podiatry clinic: The impact of multi-media resources in the teaching of practical skills across diverse disciplines

This paper draws on the experiences of students from two vastly different disciplines to both explore the theoretical background supporting the use of multimedia resources to teach practical skills and provide a qualitative evaluation of student perceptions and experiences of using bespoke resources. Within ceramics and podiatry, practical skills are traditionally taught via an apprenticeship model within small groups. We explore the practical and pedagogic benefits of developing bespoke multimedia resources to teach practical skills, identifying common themes from these disparate discipline areas. Student focus groups revealed that, practically, the opportunity for repeated viewing at convenient times promoted less reliance on lecturers and better preparation prior to practical demonstrations. Pedagogically, time for reflection and sense making underpinned an increase in confidence which in turn led to increased creativity. The student voice was also used to identify recommendations and challenges driving future change

Space charge in drift chambers operated with the Xe,CO2(15%) mixture

Using prototype modules of the ALICE Transition Radiation Detector we investigate space charge effects and the dependence of the pion rejection performance on the incident angle of the ionizing particle. The average pulse height distributions in the drift chambers operated with the Xe,CO2(15%) mixture provide quantitative information on the gas gain reduction due to space charge accumulating during the drift of the primary ionization. Our results demonstrate that the pion rejection performance of a TRD is better for tracks which are not at normal incidence to the anode wires. We present detailed simulations of detector signals, which reproduce the measurements and lend strong support to our interpretation of the measurements in terms of space charge effects.Comment: 18 pages, 10 figures, accepted for publication in Nucl.Instrum.Meth. A. Data files available at http://www-alice.gsi.de/tr