Topiramate in pregnancy - Preliminary experience from the UK epilepsy and pregnancy register

Objectives: Topiramate (Topamax (R)) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate.

Tuberous sclerosis complex: clinical features, diagnosis, and prevalence within Northern Ireland

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 and TSC2 genes on chromosomes 9 and 16 respectively. Diagnosis is based on clinical features but can be difficult as a result of variable phenotypic expression. With the advantage of mutation analysis in making a diagnosis of TSC, and improved identification of the associated clinical features, there have been few new data on its prevalence and on the proportion of cases due to new mutations. We have performed a retrospective epidemiological study on the prevalence of TSC, the clinical features attributed to it, and the availability of mutational analysis. We identified 73 known patients with TSC (5 deceased): 39 were female and 34 male. Ages ranged from 10 months to 69 years, with a mean age of 27 years 11 months (SD 16y 10mo). The point prevalence of TSC in our study was estimated at I out of 24 956 on the prevalence day (30 April 2004). The majority of patients (42.5%) were diagnosed at less than 15 months of age; 25% were not given a diagnosis on first developing symptoms. In all, 93.2% had epilepsy and 71.2% had a learning disability.* A mutation was identified in 95.8% of those tested (26% TSC1 and 74% TSC2). TSC2 mutations were correlated with a more severe phenotype. The new mutation rate was calculated at 64%. We conclude that the prevalence of TSC is higher than previously calculated. We recommend that all children with epilepsy be assessed for features of TSC. Larger studies will be required to assess the prevalence of mutations in each gene, and genotype-phenotype correlation.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register

Objective: To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs).

Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity

Odontoblasts form the outermost cellular layer of the dental pulp where they have been proposed to act as sensory receptor cells. Despite this suggestion, evidence supporting their direct role in mediating thermo-sensation and nociception is lacking. Transient receptor potential (TRP) ion channels directly mediate nociceptive functions, but their functional expression in human odontoblasts has yet to be elucidated. In the present study, we have examined the molecular and functional expression of thermo-sensitive TRP channels in cultured odontoblast-like cells and in native human odontoblasts obtained from healthy wisdom teeth. PCR and western blotting confirmed gene and protein expression of TRPV1, TRPA1 and TRPM8 channels. Immunohistochemistry revealed that these channels were localised to odontoblast-like cells as determined by double staining with dentin sialoprotein (DSP) antibody. In functional assays, agonists of TRPV1, TRPA1 and TRPM8 channels elicited [Ca2+]i transients that could be blocked by relevant antagonists. Application of hot and cold stimuli to the cells also evoked rises in [Ca2+]i which could be blocked by TRP-channel antagonists. Using a gene silencing approached we further confirmed a role for TRPA1 in mediating noxious cold responses in odontoblasts. We conclude that human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth. Cultured and native human odontoblasts express functional TRP channels that may play a crucial role in mediating thermal sensation in teeth.

What Happened to the ‘Development’ in Sustainable Development? Business Guidelines Two Decades After Brundtland

Over twenty years ago ‘Our Common Future’ presented a conceptualization and explanation of the concept of sustainable development. Since then numerous alternative definitions of the concept have been offered, of which at least some are exclusive to each other. At the same time, the role of business in the transition to sustainable development has increasingly received attention. Bringing these two trends in sustainable development together, this paper returns to the Brundtland version of the concept to examine to what extent the original principles of sustainable development are still embedded within key business guidelines, namely the UN Global Compact, the OECD Guidelines for Multinational Enterprises, the ICC Business Charter for Sustainable Development, the CAUX Principles, the Global Sullivan Principles and the CERES Principles. The findings suggest that these business guidelines tend to emphasize environmental rather than social aspects of sustainable development, in particular to the detriment of the original Brundtland prioritization of the needs of the poorest. Furthermore, the attention to environmental aspects stresses win-win situations and has a clear managerialist focus; whereas more conceptual environmental issues concerning systems interdependencies, critical thresholds or systemic limits to growth find little attention. The normative codes and principles targeted at the private sector thus not only add another voice to the multiple discourses on sustainable development but also contribute to a reinterpretation of the original agenda set by Brundtland towards conceptualizations of sustainable development around the needs of industrialised rather than developing countries. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment

Music, rhythm, rise time perception and developmental dyslexia: Perception of musical meter predicts reading and phonology

Introduction: Rhythm organises musical events into patterns and forms, and rhythm perception in music is usually studied by using metrical tasks. Metrical structure also plays an organisational function in the phonology of language, via speech prosody, and there is evidence for rhythmic perceptual difficulties in developmental dyslexia. Here we investigate the hypothesis that the accurate perception of musical metrical structure is related to basic auditory perception of rise time, and also to phonological and literacy development in children. Methods: A battery of behavioural tasks was devised to explore relations between musical metrical perception, auditory perception of amplitude envelope structure, phonological awareness (PA) and reading in a sample of 64 typically-developing children and children with developmental dyslexia. Results: We show that individual differences in the perception of amplitude envelope rise time are linked to musical metrical sensitivity, and that musical metrical sensitivity predicts PA and reading development, accounting for over 60% of variance in reading along with age and I.Q. Even the simplest metrical task, based on a duple metrical structure, was performed significantly more poorly by the children with dyslexia. Conclusions: The accurate perception of metrical structure may be critical for phonological development and consequently for the development of literacy. Difficulties in metrical processing are associated with basic auditory rise time processing difficulties, suggesting a primary sensory impairment in developmental dyslexia in tracking the lower-frequency modulations in the speech envelope. © 2010 Elsevier.

Age-related changes in energy efficiency of gait, activity, and participation in children with cerebral palsy

Aim
The aim of this study was to use a prospective longitudinal study to describe age-related trends in energy efficiency during gait, activity, and participation in ambulatory children with cerebral palsy (CP).

Method
Gross Motor Function Measure (GMFM), Paediatric Evaluation of Disability Inventory (PEDI), and Lifestyle Assessment Questionnaire-Cerebral Palsy (LAQ-CP) scores, and energy efficiency (oxygen cost) during gait were assessed in representative sample of 184 children (112 male; 72 female; mean age 10y 9mo; range 4–16y) with CP. Ninety-four children had unilateral spastic CP, 84 bilateral spastic CP, and six had other forms of CP. Fifty-seven were classified as Gross Motor Function Classification System (GMFCS) level I, 91 as level II, 22 as level III, and 14 as level IV). Assessments were carried out on two occasions (visit 1 and visit 2) separated by an interval of 2 years and 7 months. A total of 157 participants returned for reassessment.

Results
Significant improvements in mean raw scores for GMFM, PEDI, and LAQ-CP were recorded; however, mean raw oxygen cost deteriorated over time. Age-related trends revealed gait to be most inefficient at the age of 12 years, but GMFM scores continued to improve until the age of 13 years, and two PEDI subscales to age 14 years, before deteriorating (p<0.05). Baseline score was consistently the single greatest predictor of visit 2 score. Substantial agreement in GMFCS ratings over time was achieved (?lw=0.74–0.76).

Interpretation
These findings have implications in terms of optimal provision and delivery of services for young people with CP to maximize physical capabilities and maintain functional skills into adulthood.

Systematic review of reviews of risk factors for intracranial aneurysms

Systematic reviews of systematic reviews identify good quality reviews of earlier studies of medical conditions. This article describes a systematic review of systematic reviews performed to investigate factors that might influence the risk of rupture of an intracranial aneurysm. It exemplifies the technique of this type of research and reports the finding of a specific study. The annual incidence of subarachnoid haemorrhage resulting from the rupture of intracranial aneurysms is estimated to be nine per 100,000. A large proportion of people who have this bleed, will die or remain dependent on the care of others for some time. Reliable knowledge about the risks of subarachnoid haemorrhage in different populations will help in planning, screening and prevention strategies and in predicting the prognosis of individual patients. If the necessary data were available in the identified reviews, an estimate for the numerical relationship between a particular characteristic and the risk of subarachnoid haemorrhage was included in this report. The identification of eligible systematic reviews relied mainly on the two major bibliographic databases of the biomedical literature: PubMed and EMBASE. These were searched in 2006, using specially designed search strategies. Approximately 2,000 records were retrieved and each of these was checked carefully against the eligibility criteria for this systematic review. These criteria required that the report be a systematic review of studies assessing the risk of subarachnoid haemorrhage in patients known to have an unruptured intracranial aneurysm or of studies that had investigated the characteristics of people who experienced a subarachnoid haemorrhage without previously being known to have an unruptured aneurysm. Reports which included more than one systematic review were eligible and each of these reviews was potentially eligible. The quality of each systematic review was assessed. In this review, 16 separate reports were identified, including a total of 46 eligible systematic reviews. These brought together research studies for 24 different risk factors. This has shown that the following factors appear to be associated with a higher risk of subarachnoid haemorrhage: being a woman, older age, posterior circulation aneurysms, larger aneurysms, previous symptoms,