4,459 research outputs found

    Self-reported cognitive function in a large international cohort of people with multiple sclerosis: associations with lifestyle and other factors

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    Background and Purpose: We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS).Methods: This study was a cross-sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log-binomial regression.Results: The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0-43.0) using the least-specific definition to 11.6% (95% confidence interval, 10.3-12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega-3 supplements were inversely associated with PCI.Conclusions: Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS

    Production of Medical Radioisotopes with High Specific Activity in Photonuclear Reactions with γ\gamma Beams of High Intensity and Large Brilliance

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    We study the production of radioisotopes for nuclear medicine in (γ,xn+yp)(\gamma,x{\rm n}+y{\rm p}) photonuclear reactions or (γ,γ\gamma,\gamma') photoexcitation reactions with high flux [(1013101510^{13}-10^{15})γ\gamma/s], small diameter (100μ\sim (100 \, \mum)2)^2 and small band width (ΔE/E103104\Delta E/E \approx 10^{-3}-10^{-4}) γ\gamma beams produced by Compton back-scattering of laser light from relativistic brilliant electron beams. We compare them to (ion,xxn+y + yp) reactions with (ion=p,d,α\alpha) from particle accelerators like cyclotrons and (n,γ\gamma) or (n,f) reactions from nuclear reactors. For photonuclear reactions with a narrow γ\gamma beam the energy deposition in the target can be managed by using a stack of thin target foils or wires, hence avoiding direct stopping of the Compton and pair electrons (positrons). (γ,γ)(\gamma,\gamma') isomer production via specially selected γ\gamma cascades allows to produce high specific activity in multiple excitations, where no back-pumping of the isomer to the ground state occurs. We discuss in detail many specific radioisotopes for diagnostics and therapy applications. Photonuclear reactions with γ\gamma beams allow to produce certain radioisotopes, e.g. 47^{47}Sc, 44^{44}Ti, 67^{67}Cu, 103^{103}Pd, 117m^{117m}Sn, 169^{169}Er, 195m^{195m}Pt or 225^{225}Ac, with higher specific activity and/or more economically than with classical methods. This will open the way for completely new clinical applications of radioisotopes. For example 195m^{195m}Pt could be used to verify the patient's response to chemotherapy with platinum compounds before a complete treatment is performed. Also innovative isotopes like 47^{47}Sc, 67^{67}Cu and 225^{225}Ac could be produced for the first time in sufficient quantities for large-scale application in targeted radionuclide therapy.Comment: submitted to Appl. Phys.

    The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

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    During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

    Arduous implementation: Does the Normalisation Process Model explain why it's so difficult to embed decision support technologies for patients in routine clinical practice

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    Background: decision support technologies (DSTs, also known as decision aids) help patients and professionals take part in collaborative decision-making processes. Trials have shown favorable impacts on patient knowledge, satisfaction, decisional conflict and confidence. However, they have not become routinely embedded in health care settings. Few studies have approached this issue using a theoretical framework. We explained problems of implementing DSTs using the Normalization Process Model, a conceptual model that focuses attention on how complex interventions become routinely embedded in practice.Methods: the Normalization Process Model was used as the basis of conceptual analysis of the outcomes of previous primary research and reviews. Using a virtual working environment we applied the model and its main concepts to examine: the 'workability' of DSTs in professional-patient interactions; how DSTs affect knowledge relations between their users; how DSTs impact on users' skills and performance; and the impact of DSTs on the allocation of organizational resources.Results: conceptual analysis using the Normalization Process Model provided insight on implementation problems for DSTs in routine settings. Current research focuses mainly on the interactional workability of these technologies, but factors related to divisions of labor and health care, and the organizational contexts in which DSTs are used, are poorly described and understood.Conclusion: the model successfully provided a framework for helping to identify factors that promote and inhibit the implementation of DSTs in healthcare and gave us insights into factors influencing the introduction of new technologies into contexts where negotiations are characterized by asymmetries of power and knowledge. Future research and development on the deployment of DSTs needs to take a more holistic approach and give emphasis to the structural conditions and social norms in which these technologies are enacte

    Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

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    Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

    Twenty Years of SUGRA

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    A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late

    Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

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    INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years
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