Web-based physiotherapy for people affected by multiple sclerosis: a single blind, randomized controlled feasibility study

Objective: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. Design: Multi-centre, randomized controlled, feasibility study. Setting: Three multiple sclerosis out-patient centres. Participants: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4–6.5). Interventions: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy (n = 45; intervention) or a sheet of exercises (n = 45; active comparator). Outcome measures: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists. Results: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%–63% and 53%–71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial. Conclusion: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al

Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements

A considerable number of genes that code for AU-rich mRNAs including cytokines, growth factors, transcriptional factors, and certain receptors are involved in both chronic inflammation and cancer. Overexpression of these genes is affected by aberrations or by prolonged activation of several signaling pathways. AU-rich elements (ARE) are important cis-acting short sequences in the 3′UTR that mediate recognition of an array of RNA-binding proteins and affect mRNA stability and translation. This review addresses the cellular and molecular mechanisms that are common between inflammation and cancer and that also govern ARE-mediated post-transcriptional control. The first part examines the role of the ARE-genes in inflammation and cancer and sequence characteristics of AU-rich elements. The second part addresses the common signaling pathways in inflammation and cancer that regulate the ARE-mediated pathways and how their deregulations affect ARE-gene regulation and disease outcome

An expanding culture of control? The municipal administrative sanctions Act in Belgium

This article provides an in-depth study of the Act on Municipal Administrative Sanctions 1999 (MAS), which is the first major piece of legislation regulating antisocial behaviour in Belgium. MAS provides municipalities with an instrument to sanction antisocial behaviour and conduct perceived to disturb public order. The article uses Garland’s(2001) thesisonthecultureofcontroltoanalysewhetherMAShasledtoincreasedgovernmentcontrol and the exclusion of significant groups of the population. The research is based on a multiple case study in which the application of MAS was analysed over a 25-year period of security policies in Belgium (1985–2010). The Act’s implementation was studied in the two Belgian cities of Antwerp and Liège in order to consider the influence of the Flemish government and the Walloon government, respectively, in this policy area. The article uses insights from this comparison to revisit the culture of control thesis and its limitations in understanding the political competition that exists over the formulation of policies on antisocial behaviour. Effective Protection of Fundamental Rights in a pluralist worl