Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Capital gains from player transfers as a value creation tool: some evidence from European listed football clubs

PurposeThis article explores the value creation process from player sales in football to understand if the related capital gains correspond to significant increases in the stock value of selling companies. In addition, it aims to detect any potential drivers for higher (or slower) abnormal stock returns.Design/methodology/approachThe authors analyze all the capital gains of the Italian and Portuguese listed football companies (the only ones for which, based on their annual reports, it was possible to trace the net book value for each player sold and, consequently, if any, the related capital gain) from 2012 to 2020 and use event study analysis to calculate the abnormal returns of the football companies' stocks. Moreover, the authors use a multiple linear regression model to identify the factors affecting investors' reactions and value creation process intensity.FindingsThe results show that, on average, the capital gains from player transfers in football are positive income components and produce statistically significant higher abnormal returns. In addition, the authors identified some relevant drivers related to their intensity which could guide the choices of corporate executives regarding future disposals of the multi-year performance rights of players in the roster.Research limitations/implicationsThis study considers only Italian and Portuguese football listed companies. It would be helpful to consider some of the companies from other countries which are also outstanding from the sports perspective, but, in practice, it was not possible due to the impossibility to trace the net book value of the single footballers sold in those clubs' public financial disclosure.Practical implicationsThe value relevance of the capital gains from player trading activities should increase their importance, creating cascade effects on several activities generating value for football clubs (youth sector management, player scouting, technical improvement of the players). In addition, financial data show that the capital gains from player transfers are a basic income of European football clubs nowadays. Their executives consider these operations recurrent and continually search for more valuable transfers. Hence, it is reasonable to think that they (will) choose the players to sell considering both sports and financial aspects.Originality/valueTo the best of the authors' knowledge, this is the first study exploring the effects of capital gains from player trading activities on professional football clubs' stock value. The results obtained are even more relevant if one considers the importance these income components have in the profit formula of professional football clubs nowadays, also because of the negative repercussions caused by the recent COVID-19 pandemic

One Year of Lung Ultrasound in Children with SARS-CoV-2 Admitted to a Tertiary Referral Children's Hospital: A Retrospective Study during 2020-2021

During the COVID-19 pandemic, the lung ultrasound (LU) turned out to be a pivotal tool to study the lung involvement in the adult population, but the same was not well evaluated in children. We detected the LU patterns through an integrated approach with clinical-laboratory features in children hospitalized for COVID-19 in relation to the temporal trend of the Italian epidemic. We conducted a retrospective study which took place at a pediatric tertiary hospital from 15 March 2020 to 15 March 2021. We compared the characteristics of the initial phase of the first COVID-19 year-in the spring and summer (15 March-30 September 2020)-and those of the second phase-in the autumn and winter (1 October 2020-15 March 2021). Twenty-eight patients were studied both in the first and in the second phase of the first COVID-19 year. The disease severity score (DSS) was significantly greater in the second phase (p = 0.015). In the second phase of the first COVID-19 year, we detected a more significant occurrence of the following LU features than in the first phase: the irregular pleural line (85.71% vs. 60.71%; p = 0.035), the B-lines (89.29% vs. 60%; p = 0.003) and the several but non-coalescent B-lines (89.29% vs. 60%; p = 0.003). The LU score correlated significantly with the DSS, with a moderate relationship (r = 0.51, p < 0.001). The combined clinical, laboratory and ultrasound approaches might be essential in the evaluation of pulmonary involvement in children affected by COVID-19 during different periods of the pandemic

Triple canonical covers of varieties of minimal degree.

In this article we study pluriregular varieties X of general type with base-point-free canonical bundle whose canonical morphism has degree 3 and maps X onto a variety of minimal degree Y. We carry out our study from two different perspectives. First we study in Section 2 and Section 3 the canonical ring of X describing completely the degrees of its minimal generators. We apply this to the study of the projective normality of the images of the pluricanonical morphisms of X. Our study of the canonical ring of X also shows that, if the dimension of X is greater than or equal to 3, there does not exist a converse to a theorem of M. Green that bounds the degree of the generators of the canonical ring of X. This is in sharp contrast with the situation in dimension 2 where such converse exists, as proved by the authors in a previous work. Second, we study in Section 4, the structure of the canonical morphism of X. We use this to show among other things the nonexistence of some a priori plausible examples of triple canonical covers of varieties of minimal degree. We also characterize the targets of flat canonical covers of varieties of minimal degree. Some of the results of Section 4 are more general and apply to varieties X which are not necessarily regular, and to targets Y that are scrolls which are not of minimal degree

The Long Pentraxin PTX3 Controls Klebsiella Pneumoniae Severe Infection

Klebsiella pneumoniae is a common pathogen in human sepsis. The emergence of multidrug-resistant K. pneumoniae strains represents a major clinical challenge in nosocomial and community acquired infections. The long pentraxin PTX3, a key component of humoral innate immunity, is involved in resistance to selected pathogens by promoting opsonophagocytosis. We investigated the relevance of PTX3 in innate immunity against K. pneumoniae infections using Ptx3-/- mice and mouse models of severe K. pneumoniae infections. Local and systemic PTX3 expression was induced following K. pneumoniae pulmonary infection, in association with the up-regulation of TNF-α and IL-1β. PTX3 deficiency in mice was associated with higher bacterial burden and mortality, release of pro-inflammatory cytokines as well as IL-10 in the lung and systemically. The analysis of the mechanisms responsible of PTX3-dependent control of K. pneumoniae infection revealed that PTX3 did not interact with K. pneumoniae, or promote opsonophagocytosis. The comparison of susceptibility of wild-type, Ptx3-/-, C3-/- and Ptx3-/-/C3-/- mice to the infection showed that PTX3 acted in a complement-independent manner. Lung histopathological analysis showed more severe lesions in Ptx3-/- mice with fibrinosuppurative, necrotizing and haemorrhagic bronchopneumonia, associated with increased fibrin deposition in the lung and circulating fibrinogen consumption. These findings indicate that PTX3 contributes to the control of K. pneumoniae infection by modulating inflammatory responses and tissue damage. Thus, this study emphasizes the relevance of the role of PTX3 as regulator of inflammation and orchestrator of tissue repair in innate responses to infections

The Minnesota living with heart failure questionnaire: comparison of different factor structures

BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is one of the most widely used health-related quality of life questionnaires for patients with heart failure (HF). It provides scores for two dimensions, physical and emotional, and a total score. However, there are some concerns about its factor structure and alternatives have been proposed, some including a third factor representing a social dimension. The objectives of the present study were to analyze the internal structure of the MLHFQ and the unidimensionality of the total score, and to compare the different factor structures proposed. METHODS: The MLHFQ was given to 2565 patients with HF. The structural validity of the questionnaire was assessed by confirmatory factor analysis (CFA), and Rasch analysis. These two approaches were also applied to the alternative structures proposed. RESULTS: The CFA results for the hypothesized model of two latent factors and the Rasch analysis confirmed the adequacy of the physical and emotional scales. Rasch analysis for the total score showed only two problematic items. The results of the CFA for other two-factor structures proposed were not better than the results for the original structure. The Rasch analyses applied to the different social factors yielded the best results for Munyombwe’s social dimension, composed of six items. CONCLUSIONS: Our results support the validity of using the MLHFQ physical, emotional and total scores in patients with HF, for clinical practice and research. In addition, they confirmed the existence of a third factor, and we recommend the use of Munyombwe’s social factor