Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

BACKGROUND: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients. METHODS: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. RESULTS: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac. CONCLUSION: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs

A New Academic Quality at Work Tool (AQ@workT) to Assess the Quality of Life at Work in the Italian Academic Context

The present study provides evidence for a valid and reliable tool, the Academic Quality at Work Tool (AQ@workT), to investigate the quality of life at work in academics within the Italian university sector. The AQ@workT was developed by the QoL@Work research team, namely a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The tool is grounded in the job demands-resources model and its psychometric properties were assessed in three studies comprising a wide sample of lecturers, researchers, and professors: a pilot study (N = 120), a calibration study (N = 1084), and a validation study (N = 1481). Reliability and content, construct, and nomological validity were supported, as well as measurement invariance across work role (researchers, associate professors, and full professors) and gender. Evidence from the present study shows that the AQ@workT represents a useful and reliable tool to assist university management to enhance quality of life, to manage work-related stress, and to mitigate the potential for harm to academics, particularly during a pandemic. Future studies, such as longitudinal tests of the AQ@workT, should test predictive validity among the variables in the tool

Salmonella enterica ssp. arizonae infection in a 43-year-old Italian man with hypoglobulinemia: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p><it>Salmonella enterica </it>ssp. <it>arizonae </it>is an uncommon human pathogen with serious infections reported in immunocompromised hosts. In Europe, only a few cases have been described. Patients with this infection usually have a history of contact with reptiles or travel abroad. We present a case report of infection in a patient with hypoglobulinemia and a literature review.</p> <p>Case presentation</p> <p>We describe the case of a 43-year-old Caucasian Italian man with hypoglobulinemia who presented to our hospital with sepsis and diarrhea. A stool culture yielded <it>S. enterica </it>ssp. <it>arizonae</it>. Our patient was treated with oral ciprofloxacin and made a full recovery. We also present a review of the cases of <it>S. enterica </it>ssp. <it>arizonae </it>infections previously reported in Europe.</p> <p>Conclusions</p> <p>The majority of infections from <it>S. enterica </it>ssp. <it>arizonae </it>occur in patients who are immunocompromised. Data from the literature suggests that it may be difficult to eradicate the bacteria and thus, prolonged antibiotic courses are often used. It would be advisable for clinicians to investigate for pre-existing immune dysfunction if <it>S. enterica </it>ssp. <it>arizonae </it>is isolated. In Italy, although there have only been a few cases, the likely route of transmission remains unclear and requires further surveillance.</p

Reporting conditionals with modals

Conditionals and modals work in tandem in some instances of practical reasoning, or decision making. Consider the following example (from Kratzer 2012): a. I want to become a mayor. b. (q) I will become a mayor only if (p) I go to the pub. c. Therefore, I should go to the pub. Given what the cogniser wants (a) and the relevant circumstances (b), the conclusion that the cogniser goes to the pub comes out as necessary. Hence, the presence of the necessity modal should in (c). Indeed, given the context of (a), the necessity modal in (c) is simply a reflection of the necessity of p for q, which is overtly represented by the use of the ‘only if p, q’ construction. This chapter looks into whether indirect reports of conditionals – in particular, indirect reports which involve the use of a modal verb – are sensitive to the necessity of p for q in cases where necessity is not overtly represented in a conditional, as in ‘if p, q’ formulations. We report on two online experiments into the relation between (i) perceived necessity or sufficiency of the truth of a conditional antecedent for the truth of the consequent, and (ii) the formulation of an indirect report of a conditional with necessity or possibility modals (have to, should, could). In Experiment 1, the ‘necessity/sufficiency of p for q’ variable was manipulated by contextually altering the number of alternative antecedents (e.g. Cummins et al. 1991; Thompson 1994; Politzer 2003). It was found that modals used in indirect reports of ‘if p, q’ conditionals co-vary with the number of alternative antecedents in predictable ways. This suggests that modals used in indirect reports of ‘if p, q’ conditionals may be a diagnostic for biconditional versus material interpretations of conditionals. The aim of Experiment 2 was to find out whether the results of Experiment 1 could be replicated in contexts which lower/eliminate the believability of the conditionals. It was found that manipulating the believability variable has no reliable effect on the results

Indirect Reports in Modern Eastern Armenian

In this work we consider the distribution of complementizers in Modern Eastern Armenian. There are two complementizers: wor and t‘e. They both introduce complement clauses, but t‘e also expresses a dubitative value, implying that the speaker has doubts on the content following the complementizer. Moreover, t‘e, when embedded under verbs of saying, shifts the anchoring of indexicals, moving the anchor from the speaker – better called utterer – to the subject of the saying predicate. On the basis of this and further evidence coming from the analysis of sequence of tense and if-clauses, we will argue that the position of t‘e in the left periphery of the clause occupies a high position in the syntactic hierarchy. The aim of this work is on one hand, a better understanding of indirect reports and their syntax and, on the other, a more precise characterization of indexicals across languages

Structural and Functional Similarities between Osmotin from Nicotiana Tabacum Seeds and Human Adiponectin

Osmotin, a plant protein, specifically binds a seven transmembrane domain receptor-like protein to exert its biological activity via a RAS2/cAMP signaling pathway. The receptor protein is encoded in the gene ORE20/PHO36 and the mammalian homolog of PHO36 is a receptor for the human hormone adiponectin (ADIPOR1). Moreover it is known that the osmotin domain I can be overlapped to the β-barrel domain of adiponectin. Therefore, these observations and some already existing structural and biological data open a window on a possible use of the osmotin or of its derivative as adiponectin agonist. We have modelled the three-dimensional structure of the adiponectin trimer (ADIPOQ), and two ADIPOR1 and PHO36 receptors. Moreover, we have also modelled the following complexes: ADIPOQ/ADIPOR1, osmotin/PHO36 and osmotin/ADIPOR1. We have then shown the structural determinants of these interactions and their physico-chemical features and analyzed the related interaction residues involved in the formation of the complexes. The stability of the modelled structures and their complexes was always evaluated and controlled by molecular dynamics. On the basis of these results a 9 residues osmotin peptide was selected and its interaction with ADIPOR1 and PHO36 was modelled and analysed in term of energetic stability by molecular dynamics. To confirm in vivo the molecular modelling data, osmotin has been purified from nicotiana tabacum seeds and its nine residues peptide synthesized. We have used cultured human synovial fibroblasts that respond to adiponectin by increasing the expression of IL-6, TNF-alpha and IL-1beta via ADIPOR1. The biological effect on fibroblasts of osmotin and its peptide derivative has been found similar to that of adiponectin confirming the results found in silico

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Compositional analysis of bacterial communities in seawater, sediment, and sponges in the Misool coral reef system, Indonesia

Sponge species have been deemed high microbial abundance (HMA) or low microbial abundance (LMA) based on the composition and abundance of their microbial symbionts. In the present study, we evaluated the richness and composition of bacterial communities associated with one HMA sponge (Xestospongia testudinaria; Demospongiae: Haplosclerida: Petrosiidae), one LMA sponge (Stylissa carteri; Demospongiae: Scopalinida - Scopalinidae), and one sponge with a hitherto unknown microbial community (Aaptos suberitoides; Demospongiae: Suberitida: Suberitidae) inhabiting the Misool coral reef system in the West Papua province of Indonesia. The bacterial communities of these sponge species were also compared with seawater and sediment bacterial communities from the same coastal coral reef habitat. Using a 16S rRNA gene barcoded pyrosequencing approach, we showed that the most abundant phylum overall was Proteobacteria. The biotope (sponge species, sediment or seawater) explained almost 84% of the variation in bacterial composition with highly significant differences in composition among biotopes and a clear separation between bacterial communities from seawater and S. carteri; X. testudinaria and A. suberitoides and sediment. The Chloroflexi classes SAR202 and Anaerolineae were most abundant in A. suberitoides and X. testudinaria and both of these species shared several OTUs that were largely absent in the remaining biotopes. This suggests that A. suberitoides is a HMA sponge. Although similar, the bacterial communities of S. carteri and seawater were compositionally distinct. These results confirm compositional differences between sponge and non-sponge biotopes and between HMA and LMA sponges.publishe

Neurosphere-Derived Cells Exert a Neuroprotective Action by Changing the Ischemic Microenvironment

BACKGROUND: Neurosphere-derived cells (NC), containing neural stem cells, various progenitors and more differentiated cells, were obtained from newborn C57/BL6 mice and infused in a murine model of focal ischemia with reperfusion to investigate if: 1) they decreased ischemic injury and restored brain function; 2) they induced changes in the environment in which they are infused; 3) changes in brain environment consequent to transient ischemia were relevant for NC action. METHODOLOGY/PRINCIPAL FINDINGS: NC were infused intracerebroventricularly 4 h or 7 d after 30 min middle cerebral artery occlusion. In ischemic mice receiving cells at 4 h, impairment of open field performance was significantly improved and neuronal loss significantly reduced 7–14 d after ischemia compared to controls and to ischemic mice receiving cells at 7 d. Infusion of murine foetal fibroblast in the same experimental conditions was not effective. Assessment of infused cell distribution revealed that they migrated from the ventricle to the parenchyma, progressively decreased in number but they were observable up to 14 d. In mice receiving NC at 7 d and in sham-operated mice, few cells could be observed only at 24 h, indicating that the survival of these cells in brain tissue relates to the ischemic environment. The mRNA expression of trophic factors such as Insulin Growth Factor-1, Vascular Endothelial Growth Factor-A, Transforming Growth Factor-β1, Brain Derived Neurotrophic Factor and Stromal Derived Factor−1α, as well as microglia/macrophage activation, increased 24 h after NC infusion in ischemic mice treated at 4 h compared to sham-operated and to mice receiving cells at 7 d. CONCLUSIONS/SIGNIFICANCE: NC reduce functional impairment and neuronal damage after ischemia/reperfusion injury. Several lines of evidence indicate that the reciprocal interaction between NC and the ischemic environment is crucial for NC protective actions. Based on these results we propose that a bystander control of the ischemic environment may be the mechanism used by NC to rapidly restore acutely injured brain function