KCNQ/M currents in sensory neurons: Significance for pain therapy

Neuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents [I-K(M)] play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 subunits, the molecular correlates of I-K(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. I-K(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 muM) and XE991 (IC50, 0.26 muM) and enhanced by retigabine (10 muM). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that I-K(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target

In vitro and In vivo Characterisation of Piroxicam-Loaded Dika Wax Lipospheres

Purpose: To formulate piroxicam-loaded lipospheres and evaluate their in vitro and in vivo properties.Method: Piroxicam-loaded lipospheres were prepared by hot  homogenization technique using dika wax and Phospholipon® 90G (1:1, 1:2 and 2:1) as the lipid matrix. Characterisation, based on particle sizeand morphology, pH, drug content and encapsulation efficiency, were carried out on the lipospheres. In vitro release was evaluated in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties of the piroxicam-loaded lipospheres were studied using healthy, adult Wistar rats.Result: Photomicrographs revealed spherical particles in the range of 1.66 – 3.56 ìm. The results also indicated that lipospheres formulated with lipid matrix 1:1 and containing 0.25 % piroxicam had the highest encapsulation efficiency of 84 %. In vitro release data showed that lipospheres formulated with lipid matrix having higher concentration of dika wax exhibited the fastest drug release of drug with maximum release time between 60 - 70 min. The lipospheres exhibited good anti-inflammatoryproperties with 58.6 % oedema inhibition at 5 h. Piroxicam-loaded liposheres had an ulcer index of zero while, the reference (plain piroxicam) had an ulcer index of 15.00 ± 1.23 (p < 0.05).Conclusion: Piroxicam lipospheres formulated with a mixture of dika wax and phospholipid exhibited good in vitro and in vivo properties.Keywords: Dika wax, Lipospheres, Piroxicam, Phospholipid, Ulcerogenicity, Anti-inflammator

Recent Progress in Neutron Star Theory

This review contains chapters discussing: Energy density fluctionals of nuclear matter, Many-body theory of nucleon matter, Hadronic and quark matter, Mixtures of phases in dense matter, Neutron star observations and predictions.Comment: 33 pages +13 figs., Ann. Rev. Nucl. & Part. Science, 200

Cats, comics and Knausgård : promoting student reading at a UK academic library with a leisure reading collection

This case study describes the creation of a leisure reading collection in the Clifford Whitworth library at the University of Salford. It briefly surveys existing literature on leisure reading collections and looks at the growing interest among UK academic libraries in recreational reading. It considers the reasons for promoting reading as a leisure activity to students and describes the processes of selecting, purchasing and marketing the collection at Salford. It also considers possible future developments for the collection and the evaluation of the library’s attempts to encourage a culture of reading amongst Salford students. The positive response to the collection suggests the development of leisure reading is a worthwhile activity for academic libraries to focus on and the study contains useful information for others who are interested in creating a similar collection

Evaluation of turbulence closure models under spilling and plunging breakers in the surf zone

Turbulence closure models are evaluated for application to spilling and plunging breakers in the surf zone using open source computational fluid dynamics software. A new library of turbulence models for application to multiphase flows has been developed and is assessed for numerical efficiency and accuracy by comparing against existing laboratory data for surface elevation, velocity and turbulent kinetic energy profiles. Out of the models considered, it was found that, overall, the best model is the nonlinear k - ϵ model. The model is also shown to exhibit different turbulent characteristics between the different breaker types, consistent with experimental data

Extracellular matrix: a new player in memory maintenance and psychiatric disorders

How the brain performs higher cognitive functions such as learning and memory is traditionally studied by investigating how neurons work. However, over the past two decades, evidence has accumulated which suggests that components of the extracellular matrix contribute to the storing of information through learning processes. Thus, matrix regulation – either changes in the protein composition of the perineural network surrounding neurons or cleavage of this network by specific metalloproteases – could be relevant to the many psychiatric disorders that are shaped by previous experiences, i.e. by learning and plasticity. This includes disorders which are a direct consequence of past experiences and ones where previous experiences constitute a risk factor. Psychotherapy is one of the first-line treatments for most psychiatric conditions, and involves learning and plasticity. Here, we review selected publications pertaining to experience dependence in psychiatric conditions and summarise evidence of roles for the extracellular matrix in learning and memory. We then suggest how control of the extracellular matrix could be leveraged for innovative treatments and, more generally, discuss possible aetiological effects of extracellular matrix alterations in psychiatric disorders

Resource use data by patient report or hospital records: Do they agree?

Background: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. Conclusions: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysi

The wavelet-NARMAX representation : a hybrid model structure combining polynomial models with multiresolution wavelet decompositions

A new hybrid model structure combing polynomial models with multiresolution wavelet decompositions is introduced for nonlinear system identification. Polynomial models play an important role in approximation theory, and have been extensively used in linear and nonlinear system identification. Wavelet decompositions, in which the basis functions have the property of localization in both time and frequency, outperform many other approximation schemes and offer a flexible solution for approximating arbitrary functions. Although wavelet representations can approximate even severe nonlinearities in a given signal very well, the advantage of these representations can be lost when wavelets are used to capture linear or low-order nonlinear behaviour in a signal. In order to sufficiently utilise the global property of polynomials and the local property of wavelet representations simultaneously, in this study polynomial models and wavelet decompositions are combined together in a parallel structure to represent nonlinear input-output systems. As a special form of the NARMAX model, this hybrid model structure will be referred to as the WAvelet-NARMAX model, or simply WANARMAX. Generally, such a WANARMAX representation for an input-output system might involve a large number of basis functions and therefore a great number of model terms. Experience reveals that only a small number of these model terms are significant to the system output. A new fast orthogonal least squares algorithm, called the matching pursuit orthogonal least squares (MPOLS) algorithm, is also introduced in this study to determine which terms should be included in the final model

Stages of development and injury: an epidemiological survey of young children presenting to an emergency department

<p><b>Background:</b> The aim of our study was to use a local (Glasgow, west of Scotland) version of a Canadian injury surveillance programme (CHIRPP) to investigate the relationship between the developmental stage of young (pre-school) children, using age as a proxy, and the occurrence (incidence, nature, mechanism and location) of injuries presenting to a Scottish hospital emergency department, in an attempt to replicate the findings of a recent study in Kingston, Canada.</p> <p><b>Methods:</b> We used the Glasgow CHIRPP data to perform two types of analyses. First, we calculated injury rates for that part of the hospital catchment area for which reasonably accurate population denominators were available. Second, we examined detailed injury patterns, in terms of the circumstances, mechanisms, location and types of injury. We compared our findings with those of the Kingston researchers.</p> <p><b>Results:</b> A total of 17,793 injury records for children aged up to 7 years were identified over the period 1997–99. For 1997–2001, 6,188 were used to calculate rates in the west of the city only. Average annual age specific rates per 1000 children were highest in both males and females aged 12–35 months. Apart from the higher rates in Glasgow, the pattern of injuries, in terms of breakdown factors, mechanism, location, context, and nature of injury, were similar in Glasgow and Kingston.</p> <p><b>Conclusion:</b> We replicated in Glasgow, UK, the findings of a Canadian study demonstrating a correlation between the pattern of childhood injuries and developmental stage. Future research should take account of the need to enhance statistical power and explore the interaction between age and potential confounding variables such as socio-economic deprivation. Our findings highlight the importance of designing injury prevention interventions that are appropriate for specific stages of development in children.</p&gt

Fano 3-folds in P2xP2 format, Tom and Jerry

We study Q-factorial terminal Fano 3-folds whose equations are modelled on those of the Segre embedding of P^2xP^2. These lie in codimension 4 in their total anticanonical embedding and have Picard rank 2. They fit into the current state of classification in three different ways. Some families arise as unprojections of degenerations of complete intersections, where the generic unprojection is a known prime Fano 3-fold in codimension 3; these are new, and an analysis of their Gorenstein projections reveals yet other new families. Others represent the "second Tom" unprojection families already known in codimension 4, and we show that every such family contains one of our models. Yet others have no easy Gorenstein projection analysis at all, so prove the existence of Fano components on their Hilbert scheme