Legal and professional implications of shared care: a case study in oral anticoagulation stroke prevention therapy.

Policy initiatives and technological advances enable the use of integrated shared care models of healthcare delivery whereby the focus of care is moved from the hospital to the community, and also of models where patients take increasing responsibility for monitoring and treatment. Such shifts may or may be perceived to change professional roles and responsibilities with implications to the delivery of a professionally and legally acceptable standard of care. We focus on oral anticoagulation and stroke prevention therapy to examine some possible professional and legal implications of the increasing use of shared care

Reduced number of axonal mitochondria and tau hypophosphorylation in mouse P301L tau knockin neurons.

Expression of the frontotemporal dementia-related tau mutation, P301L, at physiological levels in adult mouse brain (KI-P301L mice) results in overt hypophosphorylation of tau and age-dependent alterations in axonal mitochondrial transport in peripheral nerves. To determine the effects of P301L tau expression in the central nervous system, we examined the kinetics of mitochondrial axonal transport and tau phosphorylation in primary cortical neurons from P301L knock-in (KI-P301L) mice. We observed a significant 50% reduction in the number of mitochondria in the axons of cortical neurons cultured from KI-P301L mice compared to wild-type neurons. Expression of murine P301L tau did not change the speed, direction of travel or likelihood of movement of mitochondria. Notably, the angle that defines the orientation of the mitochondria in the axon, and the volume of individual moving mitochondria, were significantly increased in neurons expressing P301L tau. We found that murine tau phosphorylation in KI-P301L mouse neurons was diminished and the ability of P301L tau to bind to microtubules was also reduced compared to tau in wild-type neurons. The P301L mutation did not influence the ability of murine tau to associate with membranes in cortical neurons or in adult mouse brain. We conclude that P301L tau is associated with mitochondrial changes and causes an early reduction in murine tau phosphorylation in neurons coupled with impaired microtubule binding of tau. These results support the association of mutant tau with detrimental effects on mitochondria and will be of significance for the pathogenesis of tauopathies

Infrared fixed point in quantum Einstein gravity

We performed the renormalization group analysis of the quantum Einstein gravity in the deep infrared regime for different types of extensions of the model. It is shown that an attractive infrared point exists in the broken symmetric phase of the model. It is also shown that due to the Gaussian fixed point the IR critical exponent $\nu$ of the correlation length is 1/2. However, there exists a certain extension of the model which gives finite correlation length in the broken symmetric phase. It typically appears in case of models possessing a first order phase transitions as is demonstrated on the example of the scalar field theory with a Coleman-Weinberg potential.Comment: 9 pages, 7 figures, final version, to appear in JHE

Epigenetic regulation of adult neural stem cells: implications for Alzheimer's disease.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tReviewExperimental evidence has demonstrated that several aspects of adult neural stem cells (NSCs), including their quiescence, proliferation, fate specification and differentiation, are regulated by epigenetic mechanisms. These control the expression of specific sets of genes, often including those encoding for small non-coding RNAs, indicating a complex interplay between various epigenetic factors and cellular functions.Previous studies had indicated that in addition to the neuropathology in Alzheimer's disease (AD), plasticity-related changes are observed in brain areas with ongoing neurogenesis, like the hippocampus and subventricular zone. Given the role of stem cells e.g. in hippocampal functions like cognition, and given their potential for brain repair, we here review the epigenetic mechanisms relevant for NSCs and AD etiology. Understanding the molecular mechanisms involved in the epigenetic regulation of adult NSCs will advance our knowledge on the role of adult neurogenesis in degeneration and possibly regeneration in the AD brain.Internationale Stichting Alzheimer Onderzoek (ISAO)Netherlands Organization for Scientific Research (NWO)Maastricht University Medical Centre 

Glycosaminoglycan Interactions in Murine Gammaherpesvirus-68 Infection

Glycosaminoglycans (GAGs) commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68) infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces

General practitioners' beliefs about effectiveness and intentions to prescribe smoking cessation medications: qualitative and quantitative studies

BACKGROUND: General practitioners' (GPs) negative beliefs about nicotine dependence medications may act as barriers to prescribing them. METHODS: Study1: Twenty-five GPs from 16 practices across London were interviewed in this qualitative study. Framework analysis was used to identify key themes. Study 2: A convenience sample of 367 GPs completed an internet-based survey. Path-analysis was used to examine the relations between beliefs and intentions to prescribe smoking cessation medications. RESULTS: Study 1: Whilst nicotine replacement therapy (NRT) and bupropion were generally perceived as effective and cost-effective, the effectiveness of NRT was seen as critically dependent on behavioural support for smoking cessation. This dependence appeared to be influenced by perceptions that without support smokers would neglect psychological aspects of smoking and use NRT incorrectly. GPs perceived bupropion as dangerous and were concerned about its side-effects. Study 2: GPs' beliefs had medium (NRT, f(2 )= .23) to large (bupropion, f(2)=.45; NRT without support, f(2)=.59) effects on their intentions to prescribe medications. Beliefs about effectiveness of NRT and bupropion and the perceived danger of bupropion were the key predictors of intentions to prescribe NRT and bupropion, respectively. Beliefs about neglecting psychological aspects of smoking and incorrect use had indirect effects on intentions to prescribe NRT without support, operating via beliefs about effectiveness. CONCLUSION: GPs vary in their beliefs about the effectiveness and safety of smoking cessation medications. Their intentions to prescribe these medications vary in line with these beliefs. Interventions aimed at increasing the likelihood with which GPs prescribe these medications may be more effective if they addressed these beliefs

Does dog-ownership influence seasonal patterns of neighbourhood-based walking among adults? A longitudinal study

<p>Abstract</p> <p>Background</p> <p>In general dog-owners are more physically active than non-owners, however; it is not known whether dog-ownership can influence seasonal fluctuations in physical activity. This study examines whether dog-ownership influences summer and winter patterns of neighbourhood-based walking among adults living in Calgary, Canada.</p> <p>Methods</p> <p>A cohort of adults, randomly sampled from the Calgary metropolitan area, completed postal surveys in winter and summer 2008. Both winter and summer versions of the survey included questions on dog-ownership, walking for recreation, and walking for transportation in residential neighbourhoods. <b>Participation </b>in neighbourhood-based walking was compared, among dog-owners and non-owners, and in summer and winter, using general linear modeling. <b>Stability </b>of participation in neighbourhood-based walking across summer and winter among dog-owners and non-owners was also assessed, using logistic regression.</p> <p>Results</p> <p>A total of 428 participants participated in the study, of whom 115 indicated owning dogs at the time of both surveys. Dog-owners reported more walking for recreation in their neighbourhoods than did non-owners, both in summer and in winter. Dog-owners were also more likely than non-owners to report participation in walking for recreation in their neighbourhoods, in summer as well as in winter. Dog-owners and non-owners did not differ in the amount of walking that they reported for transportation, either in summer or in winter.</p> <p>Conclusions</p> <p>By acting as cues for physical activity, dogs may help their owners remain active across seasons. Policies and programs related to dog-ownership and dog-walking, such as dog-supportive housing and dog-supportive parks, may assist in enhancing population health by promoting physical activity.</p

An Essential Role for the Proximal but Not the Distal Cytoplasmic Tail of Glycoprotein M in Murid Herpesvirus 4 Infection

Murid herpesvirus-4 (MuHV-4) provides a tractable model with which to define common, conserved features of gamma-herpesvirus biology. The multi-membrane spanning glycoprotein M (gM) is one of only 4 glycoproteins that are essential for MuHV-4 lytic replication. gM binds to gN and is thought to function mainly secondary envelopment and virion egress, for which several predicted trafficking motifs in its C-terminal cytoplasmic tail could be important. We tested the contribution of the gM cytoplasmic tail to MuHV-4 lytic replication by making recombinant viruses with varying C-terminal deletions. Removing an acidic cluster and a distal YXXΦ motif altered the capsid distribution somewhat in infected cells but had little effect on virus replication, either in vitro or in vivo. In contrast, removing a proximal YXXΦ motif as well completely prevented productive replication. gM was still expressed, but unlike its longer forms showed only limited colocalization with co-transfected gN, and in the context of whole virus appeared to support gN expression less well. We conclude that some elements of the gM cytoplasmic tail are dispensible for MuHV-4 replication, but the tail as a whole is not