82 research outputs found

    Protocol for the saMS trial (supportive adjustment for multiple sclerosis): a randomized controlled trial comparing cognitive behavioral therapy to supportive listening for adjustment to multiple sclerosis

    Get PDF
    BackgroundMultiple Sclerosis (MS) is an incurable, chronic, potentially progressive and unpredictable disease of the central nervous system. The disease produces a range of unpleasant and debilitating symptoms, which can have a profound impact including disrupting activities of daily living, employment, income, relationships, social and leisure activities, and life goals. Adjusting to the illness is therefore particularly challenging. This trial tests the effectiveness of a cognitive behavioural intervention compared to supportive listening to assist adjustment in the early stages of MS.MethodsThis is a two arm randomized multi-centre parallel group controlled trial. 122 consenting participants who meet eligibility criteria will be randomly allocated to receive either Cognitive Behavioral Therapy or Supportive Listening. Eight one hour sessions of therapy (delivered over a period of 10 weeks) will be delivered by general nurses trained in both treatments. Self-report questionnaire data will be collected at baseline (0 weeks), mid-therapy (week 5 of therapy), post-therapy (15 weeks) and at six months (26 weeks) and twelve months (52 weeks) follow-up. Primary outcomes are distress and MS-related social and role impairment at twelve month follow-up. Analysis will also consider predictors and mechanisms of change during therapy. In-depth interviews to examine participants’ experiences of the interventions will be conducted with a purposively sampled sub-set of the trial participants. An economic analysis will also take place. DiscussionThis trial is distinctive in its aims in that it aids adjustment to MS in a broad sense. It is not a treatment specifically for depression. Use of nurses as therapists makes the interventions potentially viable in terms of being rolled out in the NHS. The trial benefits from incorporating patient input in the development and evaluation stages. The trial will provide important information about the efficacy, cost-effectiveness and acceptability of the interventions as well as mechanisms of psychosocial adjustment.Trial registrationCurrent Controlled Trials ISRCTN91377356<br/

    Targeting of proteins and protein analogs to metal-chelating lipid vesicles

    Get PDF
    NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. This investigation demonstrates that new metal-chelating lipids formed into mixed vesicles can bind to a variety histidine-rich ligands through metal coordination. Our results show the feasibility of metal-chelating lipids as a method for targeting histidine-rich compounds to lipid interfaces. Interesting metal chelating lipid materials for protein orientation studies, matching the surface distribution of surface residues, protein drug delivery, and for two-dimensional protein crystallization could be made with chelating-lipids. Engineered proteins containing a histidine "tag" or proteins with natural surface histidine residues are easily targeted to the interface using metal binding. Both metal binding and histidine-rich ligand binding were investigated with mixed metal-chelating lipid vesicles. New metal-chelating lipids containing an iminodiacetate (IDA) chelating-moiety were formed into mixed vesicles and shown to bind transition metal ions through the lipid headgroup. Metal binding was characterized through calorimetry, freeze-etch microscopy, light scattering, ESR, and fluorescence studies. Fluorescently-labeled lipids containing iminodiacetate showed a large change in the fluorescence emission spectra upon metal binding, behavior which has proven useful for a vesicle-based metal sensor. Metal-loaded vesicles bound a model protein specifically through surface-accessible histidines, as shown using ESR studies. Equilibrium binding measurements showed at least an order of magnitude increase in binding affinity of the protein for the membrane when metal was present. The association constants determined through isothermal titration calorimetry for a model bivalent histidine compound binding to metal-chelating lipid bilayers were of the order of [...], while monovalent binding constants were of the order [...]. Lipid re-organization upon ligand binding was probed with model histidine compounds and histidine polymers using fluorescently-labeled metal-chelating lipid vesicles. The ability of lipids to form multivalent ligand-lipid complexes was investigated using the formation of lipid excimers, as demonstrated by fluorescence measurements of the E/M intensity ratio. Histidine content of model compounds determines the magnitude of the effect on the fluorescence emission spectra. Histidine polymers showed a larger increase of the E/M ratio than the smaller bivalent or monovalent compounds. Combining equilibrium binding results obtained with model complexes and results from fluorescence experiments, studies with metal-chelating vesicles support multivalent coordination and reorganization of the lipids by histidine-rich ligands

    Metal-Induced Dispersion of Lipid Aggregates: A Simple, Selective, and Sensitive Fluorescent Metal Ion Sensor

    No full text
    A new metal ion sensor capable of detecting nanomolar concentrations (< 1 ppb) of Cu^(2+) is made from mixed vesicles of a novel pyrene‐labeled metal‐chelating ligand and distearoyl phosphatidylcholine. When copper is added, the fluorescence monomer intensity emitted at 377 nm greatly increases, while the intensity of light emitted at 470 nm decreases. This effect is probably due to the dispersal of the fluorescent lipid throughout the matrix upon metal binding and is depicted schematically below

    Specific Protein Attachment to Artificial Membranes via Coordination to Lipid-Bound Copper(II)

    No full text
    A versatile and convenient method for targeting proteins to lipid assemblies using metal ion coordination is described. Mixed lipid bilayers and Langmuir monolayers containing a metal-chelating lipid and divalent copper ions are shown to bind protein via surface-accessible histidine residues. Cu^(2+) chelated by iminodiacetate (IDA) in the headgroup serves as an affinity ligand to target the protein to the interface. The compact, uncharged Cu^(2+)-IDA headgroup can be incorporated into lipid assemblies without disrupting the lipid packing. Surface pressure-area isotherms of DSPC monolayers containing 5 mol % of IDA-lipid show that Cu^(2+) enhances the rate and extent of myoglobin association with the interface. Myoglobin binds to small unilamellar vesicles containing 2% Cu^(2+)-IDA lipid (48% DSPC and 50% cholesterol) at least an order of magnitude more tightly than to vesicles without metal or loaded with Ca^(2+). The Cu^(2+)-IDA lipid more than doubles the amount of protein targeted to the interface. Cu^(2+) ESR parameters g_∥ and A_∥, measured for liposomes with native and DEPC-modified myoglobin, support coordination of surface histidine side chains to Cu^(2+) as the binding interaction

    Metal-Induced Dispersion of Lipid Aggregates: A Simple, Selective, and Sensitive Fluorescent Metal Ion Sensor

    No full text
    A new metal ion sensor capable of detecting nanomolar concentrations (< 1 ppb) of Cu^(2+) is made from mixed vesicles of a novel pyrene‐labeled metal‐chelating ligand and distearoyl phosphatidylcholine. When copper is added, the fluorescence monomer intensity emitted at 377 nm greatly increases, while the intensity of light emitted at 470 nm decreases. This effect is probably due to the dispersal of the fluorescent lipid throughout the matrix upon metal binding and is depicted schematically below

    Specific Protein Attachment to Artificial Membranes via Coordination to Lipid-Bound Copper(II)

    No full text
    A versatile and convenient method for targeting proteins to lipid assemblies using metal ion coordination is described. Mixed lipid bilayers and Langmuir monolayers containing a metal-chelating lipid and divalent copper ions are shown to bind protein via surface-accessible histidine residues. Cu^(2+) chelated by iminodiacetate (IDA) in the headgroup serves as an affinity ligand to target the protein to the interface. The compact, uncharged Cu^(2+)-IDA headgroup can be incorporated into lipid assemblies without disrupting the lipid packing. Surface pressure-area isotherms of DSPC monolayers containing 5 mol % of IDA-lipid show that Cu^(2+) enhances the rate and extent of myoglobin association with the interface. Myoglobin binds to small unilamellar vesicles containing 2% Cu^(2+)-IDA lipid (48% DSPC and 50% cholesterol) at least an order of magnitude more tightly than to vesicles without metal or loaded with Ca^(2+). The Cu^(2+)-IDA lipid more than doubles the amount of protein targeted to the interface. Cu^(2+) ESR parameters g_∥ and A_∥, measured for liposomes with native and DEPC-modified myoglobin, support coordination of surface histidine side chains to Cu^(2+) as the binding interaction
    corecore