1,720,976 research outputs found

    Aromatase and regulation of the estrogen‐to‐androgen ratio in synovial tissue inflammation: common pathway in both sexes

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    Sex hormones play an active role in inflammatory responses, with androgens being anti-inflammatory, whereas estrogens have both pro-and anti-inflammatory effects. In rheumatoid arthritis (RA) patients, low levels of androgens and high levels of estrone are found in the synovial fluid. Aromatase is the key enzyme for the conversion of androgens into estrogens. Proinflammatory cytokines stimulate aromatase activity so that the inflammatory milieu can induce conversion of androgens to estrogens. Moreover, testosterone inhibits aromatase activity. As local androgen levels are low in RA, this can contribute to high aromatase activity in the synovium. Importantly, aromatase-converted estrogens are converted into proproliferative and proinflammatory 16-hydroxylated estrogens. A hormone involved in aromatase activity is vitamin D, which downregulates aromatase in human RA macrophages. Collectively, evidence suggests a key role of aromatase in sex hormone balance during chronic inflammation and points to the importance of vitamin D as a possible new tool for aromatase modulation

    Serum cytokines and steroidal hormones in polymyalgia rheumatica and elderly-onset rheumatoid arthritis

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    Background: Polymyalgia rheumatica (PMR) may create some difficulties in the differential diagnosis of elderly-onset rheumatoid arthritis (EORA) and of EORA with PMR-like onset (EORA/PMR). Aim: To investigate possible differences between three groups of patients, with regard to serum levels of inflammatory cytokines and steroidal hormones at baseline and after 1 month of treatment with glucocorticoids (prednisone 7.5-12.5 mg/day). Patients and methods: 14 patients with PMR, 15 with EORA and 14 with EORA/PMR, as well as 15 healthy, matched controls were analysed. Tumour necrosis factor alpha (TNF alpha), interleukin (IL)6, IL1 receptor antagonist (IL1Ra), cortisol, dehydroepiandrosterone sulphate (DHEAS) and 17-hydroxy-progesterone (PRG) were evaluated. Results: Serum levels of both TNF alpha and IL6 were significantly higher in all three groups of patients than in controls (p < 0.01). Serum IL6 levels were significantly higher in patients with both PMR and EORA/PMR than in patients with EORA (p < 0.05). IL1Ra serum levels were significantly higher in patients with EORA than in controls (p < 0.001) and in patients with PMR and EORA/PMR (p < 0.05). DHEAS was significantly lower in patients with EORA/PMR than in those with EORA (p < 0.05). PRG was significantly higher in all patient groups (p < 0.05). After glucocorticoid treatment, serum TNF alpha and IL6 levels significantly decreased in all patient groups; IL1Ra significantly increased in patients with PMR and in those with EORA/PMR; cortisol, DHEAS, and PRG significantly decreased in patients with PMR and in those with EORA/PMR (p < 0.05). Conclusions: Different cytokine and steroidal hormone patterns suggest that patients with PMR and those with EORA/PMR seem to be have a more intensive inflammatory reaction and are more efficient responders to glucocorticoid treatment than patients with EORA

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    β2 adrenergic receptor desensitization through chronic stimulation of Natural Killer cells

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    Stress is a ubiquitous phenomenon that impacts the health of populations across all social strata. While acute stress can be beneficial, chronic stress elevates the risk for various diseases. A major part of the body’s stress response operates through the Sympathetic-Adrenal-Medullary (SAM) axis, leading to the release of epinephrine. This stress mediator can impact the immune system and alter the immune defense response. Natural Killer (NK) cells play a critical role in early immune responses, defending against pathogens and malignant cells. During stressful situations, NK cells are recruited to the blood circulation within minutes. The expression of adrenergic receptors, particularly β2 adrenergic receptors (β2AR), renders them sensitive to epinephrine. This study analyzed the response of NK cells to acute and chronic β2AR stimulation. We confirmed that acute β2AR stimulation inhibits NK cell functions in vitro. Epinephrine showed potent inhibitory effects, suppressing the activation of NK cells independent of the activation signal. The β2AR stimulation reduced NK cell adhesion, IFNγ secretion, degranulation, and cytotoxicity. We could show that β2AR stimulation effectively blocked the LFA-1 activity and led to the detachment from its ligand ICAM-1. The effect was rescued through the addition of Propranolol, a beta blocker, or ADRB2 knock out implicating LFA-1 inhibition as critical role for NK cell mobilization. The metabolic analysis revealed that β2AR agonists influenced the metabolic profile upon NK cell activation, leading to a prolonged glycolysis activity displayed by Seahorse ECAR values. In contrast, chronic β2AR stimulation nullified NK cell inhibition. After five days of β2AR treatment, NK cells were no longer responsive to a β2AR agonist. Chronic β2AR stimulation did not alter protein translation but led to receptor phosphorylation through the PKA feedback loop, initiating a G-protein switch and receptor desensitization. The β2AR treatment with long-acting β2 agonist (LABA) Indacaterol and epinephrine displayed different properties. While epinephrine inhibited NK cells only transiently as long as the β2AR agonist was abundant, Indacaterol could not be washed away and continuously stimulated the receptor. For this reason, a single LABA treatment was sufficient to induce NK cell desensitization. However, peripheral NK cells from LABA-treated patients remained responsive to epinephrine. They did not exhibit inhibition but showed an overall correlation in NK cell fitness with asthma severity. Taken together, the transient, inhibitory effect of epinephrine indicate that the hormone plays a crucial role in NK cell recruitment during acute stressful situations while repeated β2AR stimulation leads to desensitization

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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