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There is evidence that an imbalance of extracellular purine levels may be associated with increased cardiovascular risk. Platelets play a pivotal role in vascular homeostasis and thrombosis and are important source of purine nucleotides and nucleosides. Hydrolysis of nucleotides ATP and ADP is regulated by two ectonucleotidases, triphosphate diphosphohydrolase-1 (NTPDase-1/CD39) and ecto-5’-nucleotidase (ecto-5’-NT/CD73). CD39 enzyme is expressed on the endothelium, circulating blood cells, and smooth muscle cells; there is evidence that changes in CD39 expression and activity affects the potential thrombogenic of a tissue. Gender difference in the cardiovascular risk has been extensively observed; however, while the age-dependent difference in the prevalence of cardiovascular events between men and women has been attributed to the loss of the protective effect of estrogens in the postmenopausal period, the physiological mechanism behind gender disparity is still unclear. Here, we evaluated comparatively male and female rat platelet reactivity and considered the possible role of CD39 at the basis of difference observed. We found a reduced in vitro response to ADP (1–30 µM) of female compared to male platelets, associated to increased platelet CD39 expression and activity. Platelet response to ADP was strongly increased by incubation (10 min) with the CD39 inhibitor, ARL67156 (100 µM), while male platelet response was unaffected. Rat treatment with clopidogrel (30 mg/kg, per os) inhibited ex vivo platelet aggregation. Bleeding time was prolonged in female compared to male. Taken together, our results suggest that platelet ATPase and ADPase activity might be a reliable predictor of platelet reactivity.

Androgen levels inversely correlate with the incidence, susceptibility and severity of asthma. However, whether male sex hormones such as 5α-dihydrotestosterone (DHT) have beneficial effects on asthma symptoms and/or could affect asthma susceptibility have not been investigated. DHT administration to female mice, during the sensitization phase, abrogates the sex bias in bronchial hyperreactivity. This effect correlates with inhibition of leukotriene biosynthesis in the lung. DHT significantly inhibits also other asthma-like features such as airway hyperplasia and mucus production in sensitized female mice. Conversely, DHT does not affect plasma IgE levels as well as CD3+CD4+ IL-4+ cell and IgE+c-Kit+ cell infiltration within the lung but prevents pulmonary mast cell activation. The in vitro study on RBL‐2H3 cells confirms that DHT inhibits mast cell degranulation. In conclusion, our data demonstrate that immunomodulatory effects of DHT on mast cell activation prevent the translation of allergen sensitization into clinical manifestation of asthma. © 2020 Androgen levels inversely correlate with the incidence, susceptibility and severity of asthma. However, whether male sex hormones such as 5α-dihydrotestosterone (DHT) have beneficial effects on asthma symptoms and/or could affect asthma susceptibility have not been investigated. DHT administration to female mice, during the sensitization phase, abrogates the sex bias in bronchial hyperreactivity. This effect correlates with inhibition of leukotriene biosynthesis in the lung. DHT significantly inhibits also other asthma-like features such as airway hyperplasia and mucus production in sensitized female mice. Conversely, DHT does not affect plasma IgE levels as well as CD3+CD4+ IL-4+ cell and IgE+c-Kit+ cell infiltration within the lung but prevents pulmonary mast cell activation. The in vitro study on RBL‐2H3 cells confirms that DHT inhibits mast cell degranulation. In conclusion, our data demonstrate that immunomodulatory effects of DHT on mast cell activation prevent the translation of allergen sensitization into clinical manifestation of asthma.

The perinatal depression is one of the leading pathologies in the world causing disabilities and represents an important public health problem. Since 2003, the Center for Behavioral Sciences and Mental Health (Istituto Superiore di Sanità - ISS) has promoted studies and research on the mental health of women, children, partners and family in the perinatal period, leading to the realization of a structured program adopted in many Italian services. In this article, we describe the feasibility and effectiveness of the perinatal mental health approach in Italian health services and discuss the progress and new challenges.

We assess how rising exports of US liquefied natural gas affect the convergence of natural gas prices worldwide. Our results may have implications for the development of future LNG export capacity in Canada., Nous évaluons les répercussions de la hausse des exportations américaines de gaz naturel liquéfié sur la convergence des prix du gaz naturel à l’échelle mondiale. Nos résultats pourraient avoir des implications pour le développement d’une éventuelle capacité d’exportation de GNL au Canada.

Lipid mediators (LM) encompass pro-inflammatory prostaglandins (PG) and leukotrienes (LT) but also specialized pro-resolving mediators (SPM) which display pivotal bioactivities in health and disease. Pharmacological intervention with inflammatory disorders such as osteoarthritis and rheumatoid arthritis commonly employs anti-inflammatory drugs that can suppress PG and LT formation, which however, possess limited effectiveness and side effects. Here, we report on the discovery and characterization of the two novel benzoxanthene lignans 1 and 2 that modulate select LM biosynthetic enzymes enabling the switch from pro-inflammatory LT to SPM biosynthesis as potential pharmacological strategy to intervene with inflammation. In cell-free assays, compound 1 and 2 inhibit microsomal prostaglandin E2 synthase-1 and leukotriene C4 synthase (IC50 ∼ 0.6–3.4 µM) and potently interfere with 5-lipoxygenase (5-LOX), the key enzyme in LT biosynthesis (IC50 = 0.04 and 0.09 µM). In human neutrophils, monocytes and M1 and M2 macrophages, compound 1 and 2 efficiently suppress LT biosynthesis (IC50

A guide to long-term thinking: how to envision the far future of Earth. We live on a planet careening toward environmental collapse that will be largely brought about by our own actions. And yet we struggle to grasp the scale of the crisis, barely able to imagine the effects of climate change just ten years from now, let alone the multi-millennial timescales of Earth's past and future life span. In this book, Vincent Ialenti offers a guide for envisioning the planet's far future—to become, as he terms it, more skilled deep time reckoners. The challenge, he says, is to learn to inhabit a longer now. Ialenti takes on two overlapping crises: the Anthropocene, our current moment of human-caused environmental transformation; and the deflation of expertise—today's popular mockery and institutional erosion of expert authority. The second crisis, he argues, is worsening the effects of the first. Hearing out scientific experts who study a wider time span than a Facebook timeline is key to tackling our planet's emergency. Astrophysicists, geologists, historians, evolutionary biologists, climatologists, archaeologists, and others can teach us the art of long-termism. For a case study in long-term thinking, Ialenti turns to Finland's nuclear waste repository “Safety Case” experts. These scientists forecast far future glaciations, climate changes, earthquakes, and more, over the coming tens of thousands—or even hundreds of thousands or millions—of years. They are not pop culture “futurists” but data-driven, disciplined technical experts, using the power of patterns to construct detailed scenarios and quantitative models of the far future. This is the kind of time literacy we need if we are to survive the Anthropocene.

The specific "outcome-oriented" pattern of the emotional intelligence (EI) should be considered of capital importance for teenagers in order to promote mental health. Nevertheless it is rarely evaluated because a specific tool, useful for routinely use, is not available. In this paper the authors describe the effectiveness of a new approach of public health to improve the EI "outcome-oriented", by a specific index.A comparison of two samples: experimental (i.e. applying the program) vs control group, without randomization.12 classes belonging to 3 different schools.A sample of 276 students, 146 (53%) belonging to the experimental classes.A program of 20 meetings, once a week, based on the handbook Intervento psicoeducativo per la promozione del benessere psicologico e dell'intelligenza emotiva nelle scuole (Psycho-educational intervention for promoting psychological well-being and emotional intelligence at school) in order to stimulate a "peer to peer student approach".Index of emotional intelligence (15 items), inventory idea questionnaire (19 items), learning ability questionnaire (6 items).Nonparametric tests were used.The authors found significant statistical differences at the conclusion of the study for all considered measures.The results show a remarkable and positive impact of the approach above all on the "outcome-oriented" EI. Significant results were also observed about the indicator concerning irrational beliefs. The same significant results were found about learning abilities (goal definition, problem-solving and communication skills). The main limit is the study design (lack of randomization). Further evaluation is needed.

What happened, in the years leading up to Valentine’s Day 2014, that made a canister of nuclear waste burst open and spew out fire underground at a US facility for the long-term disposal of radioac...

As surgeons have become more adept and midterm to long-term results have demonstrated improved patient outcomes, the indications for reverse total shoulder arthroplasty (RTSA) have expanded. This study compares the clinical outcomes and complication rates between patients 65 years and younger and patients 70 years and older undergoing RTSA.A retrospective analysis of a prospectively collected cohort with minimum 2-year follow-up was performed at a single institution. Patient demographic data, American Shoulder and Elbow Surgeons (ASES) score, range of motion, patient satisfaction, notching, and complication rates were analyzed.There were 32 patients (57 ± 4.9 years old) in the 65 years and younger group, whereas 50 patients (76 ± 4.9 years old) were in the 70 years and older group. The mean follow-up time was 3 years (range, 2-8 years). There were no significant differences in preoperative, postoperative, or change in ASES scores between the younger and older groups. Postoperatively, the younger cohort achieved a higher degree (mean) of forward flexion (133° vs. 117°), abduction (127° vs. 110°), and external rotation (40° vs. 27°) (P .05). The average improvement in forward flexion and external rotation was also found to be larger in the younger cohort (P .05). The younger and older groups had comparable complication rates, notching rates, and overall satisfaction rates.Patient-reported outcomes scores and complication rates after RTSA of patients aged 65 years and younger were similar to those of patients aged 70 years and older. However, younger patients were able to achieve increased postoperative range of motion.

In this paper, the structure of locally finite groups of infinite rank whose subgroups of infinite rank are permutable in a subgroup of finite index is investigated.

Nimesulide is a relatively selective cyclooxygenase (COX) -2 inhibitor, non-steroidal anti-inflammatory drug; it has been discovered in 1971 and firstly commercialized in Italy in 1985. There is much evidence that the pharmacological profile of nimesulide is peculiar and not shared with the other COX-2 selective inhibitors, suggesting that other molecular mechanisms besides inhibition of COX-2 derived prostaglandins are involved. Similarly, experimental data suggest that the gastrointestinal safety of nimesulide cannot be ascribed only to a COX-1 sparing effect. On the inflammatory process, the efficacy of nimesulide is dependent upon a wide spectrum of actions, due to the combination of effects on immune and non–immune cells. Early data demonstrated a central role for cyclic AMP (cAMP) in the anti-inflammatory effect of nimesulide; more recently, we have shown the involvement of the pathway ecto-5’-nucleotidase/adenosine A2A receptor. To date, the molecular mechanism(s) that confers uniqueness to nimesulide have not yet been defined. To go inside the mechanism of action of an existing drug, such as nimesulide, would be helpful to refine its therapeutic use but also to identify new targets for novel therapeutic anti-inflammatory approach. Here, we focus on accumulated evidence for a peculiar pharmacological profile of nimesulide.

Adenosine is the final product of ATP metabolism, mainly derived from the action of 5’- nucleotidase cleavage of AMP. Cellular production of adenosine is greatly enhanced in inflamed tissues, ischemic tissues and under hypoxia, where ATP is released from damaged cells. Much evidence has been accumulated on adenosine antinflammatory effects mediated through A2A receptor activation; A2A adenosine receptor has also been shown to play a role in matrix deposition and wound healing in a damaged tissue, contributing to dermal tissue protection and repair. Fibroblast growth factor-2 (FGF-2) is a powerful mitogen for fibroblast; it is expressed by several inflammatory cell types and plays a pivotal role in angiogenesis, wound healing, gastric ulcer protection. Human recombinant FGF-2 has shown to have antinflammatory effects. The purpose of the present work was to investigate on the antinflammatory effect of systemic administration of the adenosine A2A agonist, 2-p-(2- Carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride hydrate (CGS21680), in the rat model of carrageenan-induced paw edema. We found that CGS21680 inhibits inflammation induced by carrageenan injection into the rat paw and this effect is associated to the local reduction of cytokine levels and dermal increase of FGF-2 expression. Our results suggest that FGF-2 might be involved in the antinflammatory and tissue protective effect due to A2Areceptor activation.

When an extremely influential leader leaves behind little documentation of his work and ideas, memories of the man fill the gap for surviving colleagues.

Rotator cuff tears are among the most prevalent musculotendinous injuries treated by orthopedic surgeons. Outcomes following attempted surgical repair are highly dependent on tear size and muscle quality. It is the aim of this review to outline the natural history of rotator cuff muscle degeneration

Il presente studio ha avuto come obiettivo la valutazione dei cambiamenti, durante l’arco dei quattro anni di formazione, di un gruppo di 20 allievi di una scuola di specializzazione in psicoterapia di orientamento cognitivo. I dati del gruppo sperimentale sono stati confrontati con quelli di un gruppo di controllo. Entrambi i gruppi hanno redatto, all’inizio e al termine della formazione, un’autocaratterizzazione, strumento che permette di comprendere la prospettiva con la quale un individuo costruisce la propria realta con modalita di cambiamento in continuo divenire. Alle autocaratterizzazioni e stata applicata l’analisi del contenuto, definita da Berelson come capace di descrivere in modo obiettivo, sistematico e quantitativo il contenuto manifesto della comunicazione. E stato adottato un protocollo che ha definito le procedure seguite, il manuale dei codici interpretativi e la griglia di codifica. Ogni autocaratterizzazione e stata analizzata da un gruppo di analisti con meccanismi di controllo delle decodifiche soggettive. Per verificare se ai soggetti siano accaduti, nell’arco temporale preso in considerazione, eventi che possano aver inciso sull’assetto cognitivo e stato somministrato il Questionario sugli Avvenimenti della Vita (QAV).I risultati della ricerca attestano variazioni significative tra gruppo sperimentale e gruppo di controllo. Gli allievi, dopo quattro anni di formazione, ritengono che gli altri riconoscano in loro una maggiore capacita di spiegare comportamenti e atteggiamenti degli altri, una maggiore capacita autoriflessiva, un senso di soddisfazione per il completamento del proprio percorso formativo e quindi l’assunzione di un ruolo professionale.

In this paper, we study the behavior of locally finite groups of infinite rank whose proper subgroups of infinite rank have one of the three following properties, which are generalizations of permutability: S-permutability, semipermutability and S-semipermutability. In particular, it is proved that if G is a locally finite group of infinite rank whose proper subgroups of infinite rank are S-permutable (resp. semipermutable), then G is locally nilpotent (resp. all subgroups are semipermutable). For locally finite groups whose proper subgroups of infinite rank are S-semipermutable, the same statement can be proved only for groups with min-p for every prime p. A counterexample is given for the general case.

Some classes of finitely generated hyperabelian groups defined in terms of semipermutability and S-semipermutability are studied in the paper. The classification of finitely generated hyperabelian groups all of whose finite quotients are PST-groups recently obtained by Robinson is behind our results. An alternative proof of such a classification is also included in the paper.