2,544 research outputs found

    Depressed Adolescents’ Pupillary Response to Peer Acceptance and Rejection: The Role of Rumination

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    Heightened emotional reactivity to peer feedback is predictive of adolescents’ depression risk. Examining variation in emotional reactivity within currently depressed adolescents may identify subgroups that struggle the most with these daily interactions. We tested whether trait rumination, which amplifies emotional reactions, explained variance in depressed adolescents’ physiological reactivity to peer feedback, hypothesizing that rumination would be associated with greater pupillary response to peer rejection and diminished response to peer acceptance. Twenty currently depressed adolescents (12–17) completed a virtual peer interaction paradigm where they received fictitious rejection and acceptance feedback. Pupillary response provided a time-sensitive index of physiological arousal. Rumination was associated with greater initial pupil dilation to both peer rejection and acceptance, and diminished late pupillary response to peer acceptance trials only. Results indicate that depressed adolescents high on trait rumination are more reactive to social feedback regardless of valence, but fail to sustain cognitive-affective load on positive feedback

    Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity in vivo and in vitro

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    Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble μ receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury

    Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

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    Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of 20through20 through 800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of 200orless,osteoporosisscreeningfollowedbytreatmentwascost−saving,resultinginlowertotalcoststhannoscreeningaswellasmoreQALYs(10.6additionalquality−adjustedlife−days).Whenassumingalendronatecostsof200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of 400 through 800,screeningandtreatmentresultedingreaterlifetimecoststhannoscreeningbutwashighlycost−effective,withICERsrangingfrom800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from 714 per QALY gained through 13,902perQALYgained.Probabilisticsensitivityanalysesrevealedthatthecost−effectivenessofosteoporosisscreeningfollowedbyalendronatetreatmentwasrobusttojointinputparameterestimatevariationatawillingness−to−paythresholdof13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of 50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

    Depicting the tree of life in museums: guiding principles from psychological research

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    The Tree of Life is revolutionizing our understanding of life on Earth, and, accordingly, evolutionary trees are increasingly important parts of exhibits on biodiversity and evolution. The authors argue that in using these trees to effectively communicate evolutionary principles, museums need to take into account research results from cognitive, developmental, and educational psychology while maintaining a focus on visitor engagement and enjoyment. Six guiding principles for depicting evolutionary trees in museum exhibits distilled from this research literature were used to evaluate five current or recent museum trees. One of the trees was then redesigned in light of the research while preserving the exhibit’s original learning goals. By attending both to traditional factors that influence museum exhibit design and to psychological research on how people understand diagrams in general and Tree of Life graphics in particular, museums can play a key role in fostering 21st century scientific literacy

    Regulation of neutrophil senescence by microRNAs

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    Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

    Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: A double-blind randomised placebo controlled 6-month trial

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    <p>Abstract</p> <p>Background</p> <p>Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50–70 years.</p> <p>Methods</p> <p>We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A<sub>1c</sub>(GHbA<sub>1c</sub>). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale.</p> <p>Results</p> <p>Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA<sub>1c </sub>(mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred.</p> <p>Conclusion</p> <p>This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN55819922</p

    Sociological and Communication-Theoretical Perspectives on the Commercialization of the Sciences

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    Both self-organization and organization are important for the further development of the sciences: the two dynamics condition and enable each other. Commercial and public considerations can interact and "interpenetrate" in historical organization; different codes of communication are then "recombined." However, self-organization in the symbolically generalized codes of communication can be expected to operate at the global level. The Triple Helix model allows for both a neo-institutional appreciation in terms of historical networks of university-industry-government relations and a neo-evolutionary interpretation in terms of three functions: (i) novelty production, (i) wealth generation, and (iii) political control. Using this model, one can appreciate both subdynamics. The mutual information in three dimensions enables us to measure the trade-off between organization and self-organization as a possible synergy. The question of optimization between commercial and public interests in the different sciences can thus be made empirical.Comment: Science & Education (forthcoming

    Spatial and nonspatial implicit motor learning in Korsakoff’s amnesia: evidence for selective deficits

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    Patients with amnesia have deficits in declarative memory but intact memory for motor and perceptual skills, which suggests that explicit memory and implicit memory are distinct. However, the evidence that implicit motor learning is intact in amnesic patients is contradictory. This study investigated implicit sequence learning in amnesic patients with Korsakoff’s syndrome (N = 20) and matched controls (N = 14), using the classical Serial Reaction Time Task and a newly developed Pattern Learning Task in which the planning and execution of the responses are more spatially demanding. Results showed that implicit motor learning occurred in both groups of participants; however, on the Pattern Learning Task, the percentage of errors did not increase in the Korsakoff group in the random test phase, which is indicative of less implicit learning. Thus, our findings show that the performance of patients with Korsakoff’s syndrome is compromised on an implicit learning task with a strong spatial response component
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