Rationale
Hypericum perforatum
, popularly called St. John’s wort (SJW), is a medicinal plant mainly used as antidepressant with a favorable safety profile than standard antidepressants. Some studies ...have also documented other SJW bioactivities, including pain modulation.
Objectives
The aim of this study was to demonstrate the capability of SJW to relieve nitric oxide (NO)-induced nociceptive hypersensitivity and identify the effective component.
Methods
Nociceptive hypersensitivity induced by administration of the NO donors nitroglycerin (GTN) and sodium nitroprusside (SNP) was assessed by cold and hot plate tests. The cellular pathways and molecular targets involved were investigated by Western blotting.
Results
GTN and SNP produced a prolonged allodynia and hyperalgesia in mice. A single oral administration of low doses of an SJW dried extract or purified hypericin reversed the NO donor-induced nociceptive behavior whereas hyperforin and flavoinoids were ineffective. Investigating into the cellular pathways involved, an increased CREB and STAT1 phosphorylation, and activation of NF-κB were detected within PAG and thalamus following NO donors’ administration. These cellular events were prevented by SJW or hypericin. Since hypericin showed PKC blocking properties, a role of PKC as an upstream modulator of these transcription factors was hypothesized. NO donors increased expression and phosphorylation of protein kinase C (PKC) γ and ε isoforms, molecular events prevented by SJW or hypericin.
Conclusions
SJW reversed NO-induced nociceptive hypersensitivity through the blockade of a supraspinal signaling pathway involving a PKC-dependent CREB, STAT1 and NF-κB activation due to presence of hypericin. These data indicate SJW/hypericin as a therapeutic perspective for pain treatment.
: Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. ...In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with ≥80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD.
Plasma and urine glycosaminoglycans (GAGs) are long, linear sulfated polysaccharides that have been proposed as potential noninvasive biomarkers for several diseases. However, owing to the analytical ...complexity associated with the measurement of GAG concentration and disaccharide composition (the so-called GAGome), a reference study of the normal healthy GAGome is currently missing. Here, we prospectively enrolled 308 healthy adults and analyzed their free GAGomes in urine and plasma using a standardized ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry method together with comprehensive demographic and blood chemistry biomarker data. Of 25 blood chemistry biomarkers, we mainly observed weak correlations between the free GAGome and creatinine in urine and hemoglobin or erythrocyte counts in plasma. We found a higher free GAGome concentration – but not a more diverse composition - in males. Partitioned by gender, we also established reference intervals for all detectable free GAGome features in urine and plasma. Finally, we carried out a transference analysis in healthy individuals from two distinct geographical sites, including data from the Lifelines Cohort Study, which validated the reference intervals in urine. Our study is the first large-scale determination of normal free GAGomes reference intervals in plasma and urine and represents a critical resource for future physiology and biomarker research.
This paper contributes to the issue of political deception by exploring the role of self-deception in democratic politics. Within politics, deception of the people is actually very often produced by ...the self-deception of political leaders and officials, which is then supplemented by mechanisms of self-deception of the public itself. That self-deception, rather than simply straightforward deception, is a significant obstacle to truth and transparency in democratic politics is often hinted at by political scientists and historians but never properly pursued. And yet it should be, for which one of them is the case has important normative implications. This paper briefly presents the notion of self-deception and offers some reasons to take its presence in politics seriously. It also counters possible objections to doing so. Different kinds of political self-deception are presented and illustrated through historical examples so as to provide a clear typology and make the case for self-deception in politics stronger.
The investigation of the alloy composition is a key point for studying archaeological and historical metal artefacts. Portable X-ray fluorescence is the most commonly used technique to perform ...non-invasive alloy analysis. Nevertheless, quantitative results are usually not reliable when metal surface is covered by either corrosion or patination layers. In such cases, micro samples, representative of the bulk alloy, have to be taken. Shavings samples are a good compromise between representativeness and degree of invasiveness when the purpose of the analysis is to obtain accurate quantitative data. This work aims at evaluating and comparing accuracy and precision of X-ray Fluorescence quantitative data obtained by performing analysis on the surface and on shavings of certified reference materials. Results point out that quantitative data obtained from surface and shavings samples have comparable accuracy and precision if a suitable calibration model using certified reference materials in the same form, i.e. surface or shavings, is applied. Repeatability tests were also carried out using the same certified reference materials. Results proved repeatable within 5% for all the detected elements. Uncertainties are slightly higher for shavings with respect to surface measurements. Two case studies concerning an archaeological and a Renaissance bronze artefacts are also discussed.
Display omitted
•Set up of an analytical protocol for XRF quantitative analysis of ancient bronzes.•Two calibration models, based on shavings and surface measurements, were compared.•Both models showed similar values of accuracy and precision.•Quantitative data repeatability is slightly higher for surfaces than for shavings.•Analyses of ancient bronzes are as repeatable as those of CRMs, except for lead.
An algorithm to determine the quality of electrocardiograms (ECGs) can enable inexperienced nurses and paramedics to record ECGs of sufficient diagnostic quality. Previously, we proposed an algorithm ...for determining if ECG recordings are of acceptable quality, which was entered in the PhysioNet Challenge 2011. In the present work, we propose an improved two-step algorithm, which first rejects ECGs with macroscopic errors (signal absent, large voltage shifts or saturation) and subsequently quantifies the noise (baseline, powerline or muscular noise) on a continuous scale. The performance of the improved algorithm was evaluated using the PhysioNet Challenge database (1500 ECGs rated by humans for signal quality). We achieved a classification accuracy of 92.3% on the training set and 90.0% on the test set. The improved algorithm is capable of detecting ECGs with macroscopic errors and giving the user a score of the overall quality. This allows the user to assess the degree of noise and decide if it is acceptable depending on the purpose of the recording.
In this paper, we examine the similarities and the differences between two global problems, the coronavirus pandemic and climate change, and the extent to which the experience with the COVID-19 ...pandemic can be of use for tackling climate change. We show that both problems share the same microeconomic foundations, involving an overprovision of a global public bad. In addition, they entail externalities whose correction comes at very high economic and social costs. We leverage on a well-established problem such as climate change that has been studied for several years now, to highlight the common traits with the COVID-19 pandemic, but also important differences. The COVID-19 crisis is itself a reality check for climate policy, international governance and prevention in general. Indeed, the COVID-19 pandemic is a mock laboratory of climate change, where the time scale of unfolding events is reduced from decades to days. While the former is often measured in days, weeks, months, years, the latter is measured in years, decades, and centuries.
Efficiency Versus Equality in Bargaining Galeotti, Fabio; Montero, Maria; Poulsen, Anders
Journal of the European Economic Association,
12/2019, Letnik:
17, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract We consider how the outcome of bargaining varies with changes in the trade-off between equality, efficiency, and total-earnings maximization. We observe that subjects avoid an equal-earning ...outcome if it is Pareto inefficient; a large proportion of bargaining pairs avoids an equal and Pareto efficient outcome in favor of one giving unequal and total-earnings maximizing payoffs, and this proportion increases when unequal outcomes imply larger earnings to one of the players, even though this also implies higher inequality; finally, we document a compromise effect that violates the independence of irrelevant alternatives condition.
This report presents an intriguing case of a mineralized lesion resembling calcinosis circumscripta observed in the caudal peduncle of a wels catfish, housed in a public aquarium in northern Italy. ...The investigation encompasses a comprehensive analysis of various aspects, including clinical presentation, diagnostic imaging, as well as gross and microscopic pathology, and immunohistochemistry. Histopathology, in particular, highlighted a severe focally extensive granulomatous reaction, confirmed by dense histiocytic inflammatory infiltrates and the massive presence of multinucleated foreign body type giant cells localized around lakes and aggregates of mineralized material. Moreover, the usefulness and limitations of immunohistochemistry and special stains in characterizing fish tissues and cell types are highlighted. Although reported in elasmobranchs and sturgeons, to our knowledge, this is the first description of calcinosis circumscripta in teleost fish and it offers valuable insights into the understanding of similar pathologies in aquatic organisms.
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