758 research outputs found

    PUK2 TREATMENT PERSISTENCE OF OXYBUTYNIN XL AND TOLTERODINE IR IN A REAL-WORLD CLINICAL PRACTICE SETTING: DATA FROM THE UNITED KINGDOM

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    Affective Influences without Approach-Avoidance Actions: On the Congruence Between Valence and Stimulus-Response Mappings

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    The valence of stimuli can influence performance in the spatial stimulus–response compatibility task, but this observation could arise from the process of selecting responses or selecting stimulus–response mappings. The response-selection account proposes that spatial compatible and incompatible keypress responses serve as approaching and avoiding actions to a valenced target. The mapping-selection account suggests that there is congruence between stimulus valence and stimulus–response mappings; positive-compatible/negative-incompatible is more congruent than negative-compatible/positive-incompatible. Whereas affective valence was part of the target stimuli to which participants responded in previous studies, the present study isolated affective valence from the target by presenting an additional mapping cue separately from the target, so that spatially compatible and incompatible keypress responses could no longer serve as approaching and avoiding actions to valenced target stimuli. The present results revealed that responses were still faster when positive and negative mapping cues were assigned to the spatially compatible and incompatible mappings than when the assignment was reversed. The finding supports the mapping-selection account, indicating that positive and negative cues influence performance without approach–avoidance actions to valenced stimuli. The experiment provides important implications as to how tasks are represented and are dependent on affective processing

    Phase transitions in biological membranes

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    Native membranes of biological cells display melting transitions of their lipids at a temperature of 10-20 degrees below body temperature. Such transitions can be observed in various bacterial cells, in nerves, in cancer cells, but also in lung surfactant. It seems as if the presence of transitions slightly below physiological temperature is a generic property of most cells. They are important because they influence many physical properties of the membranes. At the transition temperature, membranes display a larger permeability that is accompanied by ion-channel-like phenomena even in the complete absence of proteins. Membranes are softer, which implies that phenomena such as endocytosis and exocytosis are facilitated. Mechanical signal propagation phenomena related to nerve pulses are strongly enhanced. The position of transitions can be affected by changes in temperature, pressure, pH and salt concentration or by the presence of anesthetics. Thus, even at physiological temperature, these transitions are of relevance. There position and thereby the physical properties of the membrane can be controlled by changes in the intensive thermodynamic variables. Here, we review some of the experimental findings and the thermodynamics that describes the control of the membrane function.Comment: 23 pages, 15 figure

    Analgesia e sedação durante a instalação do cateter central de inserção periférica em neonatos

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    Objetivou-se caracterizar as estratégias de analgesia e sedação em neonatos submetidos à instalação do cateter central de inserção periférica (CCIP) e relacioná-las ao número de punções venosas, duração do procedimento e posicionamento da ponta do cateter. Estudo transversal com coleta prospectiva de dados, realizado em uma unidade de cuidados intensivos neonatais de um hospital privado na cidade de São Paulo, no período de 31 de agosto de 2010 a 01 de julho de 2011, em que foram avaliadas 254 inserções do CCIP. A adoção de estratégias analgésicas ou sedativas ocorreu em 88 (34,6%) instalações do cateter e não esteve relacionada ao número de punções venosas, duração do procedimento ou posicionamento da ponta do cateter. As estratégias mais frequentes foram a administração endovenosa de midazolam em 47 (18,5%) e fentanil em 19 (7,3%) inserções do cateter. Recomenda-se maior adoção de estratégias analgésicas antes, durante e após o procedimento

    Blood Levels of Macrophage Migration Inhibitory Factor after Successful Resuscitation from Cardiac Arrest

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    Introduction: Ischemia-reperfusion injury following cardiopulmonary resuscitation (CPR) is associated with a systemic inflammatory response, resulting in post-resuscitation disease. In the present study we investigated the response of the pleiotropic inflammatory cytokine macrophage migration inhibitory factor (MIF) to CPR in patients admitted to the hospital after out-of-hospital cardiac arrest (OHCA). To describe the magnitude of MIF release, we compared the blood levels from CPR patients with those obtained in healthy volunteers and with an aged- and gender-matched group of patient

    Impact Factor: outdated artefact or stepping-stone to journal certification?

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    A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

    Multipotent Basal Stem Cells, Maintained in Localized Proximal Niches, Support Directed Long-Ranging Epithelial Flows in Human Prostates

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    Sporadic mitochondrial DNA mutations serve as clonal marks providing access to the identity and lineage potential of stem cells within human tissues. By combining quantitative clonal mapping with 3D reconstruction of adult human prostates, we show that multipotent basal stem cells, confined to discrete niches in juxta-urethral ducts, generate bipotent basal progenitors in directed epithelial migration streams. Basal progenitors are then dispersed throughout the entire glandular network, dividing and differentiating to replenish the loss of apoptotic luminal cells. Rare lineage-restricted luminal stem cells, and their progeny, are confined to proximal ducts and provide only minor contribution to epithelial homeostasis. In situ cell capture from clonal maps identified delta homolog 1 (DLK1) enrichment of basal stem cells, which was validated in functional spheroid assays. This study establishes significant insights into niche organization and function of prostate stem and progenitor cells, with implications for disease.This work was supported by grants from The Royal College of Surgeons of England and a Cancer Research UK Clinician Scientist Fellowship (C10169/A12173). This work was also supported by the Wellcome Trust (grant 098357/Z/12/Z to B.D.S. and grant 110326/Z/15/Z to E.H.). E.H. is funded by a Junior Research Fellowship from Trinity College, Cambridge, a Sir Henry Wellcome Fellowship from the Wellcome Trust and acknowledges the Bettencourt-Schueller Young Researcher Prize for support. L.C.G., D.M.T., and R.W.T. are supported by the Wellcome Trust Centre Strategic Award (096919/Z/11/Z). R.W.T. is also supported by the Medical Research Council (MRC) Centre for Neuromuscular Diseases (G0601943), the Lily Foundation, and the UK National Health Service (NHS) Highly Specialised “Rare Mitochondrial Disorders of Adults and Children” Service. L.C.G. and D.M.T. receive support from the Newcastle University Centre for Ageing and Vitality funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the Engineering and Physical Sciences Research Council (EPSRC), the Economic and Social Research Council (ESRC), and MRC as part of the cross-council Lifelong Health and Wellbeing Initiative

    LDLR Expression and Localization Are Altered in Mouse and Human Cell Culture Models of Alzheimer's Disease

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    Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common form of dementia. The major molecular risk factor for late-onset AD is expression of the ε-4 allele of apolipoprotein E (apoE), the major cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR) has the highest affinity for apoE and plays an important role in brain cholesterol metabolism.Using RT-PCR and western blotting techniques we found that over-expression of APP caused increases in both LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to H4 controls. Furthermore, immunohistochemical experiments showed aberrant localization of LDLR in H4-APP neuroglioma cells, Aβ-treated primary neurons, and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent staining of LDLR and of γ- and α-tubulin showed a change in LDLR localization preferentially away from the plasma membrane that was paralleled by and likely the result of a disruption of the microtubule-organizing center and associated microtubule network.These data suggest that increased APP expression and Aβ exposure alters microtubule function, leading to reduced transport of LDLR to the plasma membrane. Consequent deleterious effects on apoE uptake and function will have implications for AD pathogenesis and/or progression
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