216 research outputs found

    I negozi collegati nel diritto societario

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    The aim of the research is to analyse the connections between agreements under Company law and the study of legal consequences of such bonds. The research is organized in three main sections. The first part is dedicated to reconstruct the theories of linked contracts and economic operations. It emerges the tendency of the legislator to legislate hypothesis of linked contracts in Business Law in order to achieve more certainty in business transactions. The second section is concentrated over hypothesis of linked contracts in Company Law provided by the legislature. It is therefore analysed the relationship between Company’s Agreements and Shareholders' Agreements, the relationship between Cooperative’s Agreement and Agreements with its own shareholders, the leveraged buy-out operations, the regulation of funding in relation to a specific transaction and the payment for share capital secured in Limited Liability Partnerships (In Italian Company's Law defined as «società a responsabilità limitata»). The third part concentrates on the analysis of a series of court judgements regarding hypothesis of linked contracts created pursuant to the power of autonomy of the parties: the connection between a Company’s Agreement and the agreement to sell a property to the same company; the connection between a Company’s Agreement and a contract between the company and his own shareholder; the connection between a Company’s Agreement and the stipulation of a shared property agreement with a shareholder. The analysis proceeds by focusing on three situations in which the connection is set up in a way to circumvent the law: in the first it is violated the rule to protect the integrity of the share capital, in the second the proper fulfilment of taxes and in the third one the pre-emption clause. The conclusions point out the characteristics of linked contracts in Company Law

    Francesco Petrarca: a work, a novel

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    This article aims to propose the need to approach Francesco Petrarca's Opera Omnia as a single text, fragmented into different individual works. I will demonstrate that its unity is not in extratextual, historical or biographical elements, but in the same poetic form, since the coherence that governs the structure is above all artistic. Moreover, such a form has to be read and considered as a novel. To define this text and justify the proposed choice, I will resort to the teaching of some renowned theorists and critics of contemporary literature because it is the poet himself who allows to refer to his work from an ever-new present. If it is true that Petrarca is a classical author, since he places himself in that rhetorical and poetic tradition, from there he addresses not only his contemporaries, but also ad posteros, which makes it possible to consider him ancient as well as contemporary, and as such it is possible to analyze him. In addition, if it is true that a classic is an author whose work never finishes saying what it has to say, the passage of time cannot be a penalty, but a resource with which his word lives in a constant present and that is why it is possible to read under a current hermeneutic lens.El presente artículo quiere proponer la necesidad de enfocar la Opera Omnia de Francesco Petrarca como un texto único, fragmentado en diferentes obras individuales. Demostraré que su unidad no demora en elementos extratextuales, históricos o biográficos, sino en la misma forma poética, ya que la coherencia que rige la estructura no es, sino artística. Más aún, que dicha forma tiene que ser leída y considerada como una novela. Para definir este texto y justificar la elección propuesta, recurriré a la enseñanza de unos renombrados teóricos y críticos de la literatura de la contemporaneidad porque es el mismo poeta quien permite referirse a su obra desde un presente siempre nuevo. Si es cierto que Petrarca es un autor clásico, ya que se coloca en aquella tradición retórica y poética, de allí se dirige no solo a sus contemporáneos, sino también ad posteros, y esto significa que es posible considerarlo antiguo a la vez que contemporáneo, y como tal es posible analizarlo. Además, si es cierto que clásico es aquel autor cuya obra nunca acaba de decir lo que tiene que decir, el paso del tiempo no puede ser una penalización, sino un recurso con el que su palabra vive en un presente constante y que por ello es posible leer bajo una óptica hermenéutica actual

    Clinical recrudescence of chronic untreated P. malariae infection after BNT162b2 CoVID-19 vaccine

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    We described a case of clinical reactivation of chronic P. malariae infection following CoVID-19 vaccination with BNT162b2 (Pifzer-Biontech CoVID-19 vaccine) in a 48-year old Italian man.The patient came to our attention for fever of unknown origin show a quartan pattern (every third day) associated to splenomegaly, the onset of the fever occurred one month after CoVID-19 vaccination with BNT162b2. P. malariae was diagnosed using Carestart™ malaria rapid test and Polymerase-Chain Reaction. Post-vaccine transient reduction of immune reactivity is described in literature, although the mechanism is unknown

    Pneumocystosis as a Complication of H1N1 Influenza A Infection in an HIV-Positive Patient on Effective cART

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    H1N1 influenza A virus can affect the immune system, causing lymphopenia. This might be of great concern for HIV individuals undergoing effective antireroviral therapy (cART). We report the first confirmed case of H1N1-induced AIDS and Pneumocystis jiroveci pneumonia in an HIV-positive woman on effective cART since 2006

    Chlorpromazine and amitriptyline are substrates and inhibitors of the acrb multidrug efflux pump

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    Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors. However, their mode of action is poorly under-stood. Exposure of Salmonella enterica serovar Typhimurium and Escherichia coli to chlorpromazine selected for mutations within genes encoding RamR and MarR, regu-lators of the multidrug tripartite efflux pump AcrAB-TolC. Further experiments with S. Typhimurium containing AcrB D408A (a nonfunctional efflux pump) and chlor-promazine or amitriptyline resulted in the reversion of the mutant acrB allele to the wild type. Together, this suggests these drugs are AcrB efflux substrates. Subsequent docking studies with AcrB from S. Typhimurium and E. coli, followed by molecular dynamics simulations and free energy calculations showed that chlorpromazine and amitriptyline bind at the hydrophobic trap, a preferred binding site for substrates and inhibitors within the distal binding pocket of AcrB. Based on these simulations, we suggest that chlorpromazine and amitriptyline inhibit AcrB-mediated efflux by in-terfering with substrate binding. Our findings provide evidence that these drugs are substrates and inhibitors of AcrB, yielding molecular details of their mechanism of action and informing drug discovery of new efflux inhibitors. IMPORTANCE Efflux pumps of the resistance nodulation-cell division (RND) super-family are major contributors to multidrug resistance for most of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acineto-bacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. The development of inhibitors of these pumps would be highly desirable; how-ever, several issues have thus far hindered all efforts at designing new efflux in-hibitory compounds devoid of adverse effects. An alternative route to de novo design relies on the use of marketed drugs, for which side effects on human health have been already assessed. In this work, we provide experimental evidence that the antipsychotic drugs chlorpromazine and amitriptyline are inhibi-tors of the AcrB transporter, the engine of the major RND efflux pumps in Escherichia coli and Salmonella enterica serovar Typhimurium. Furthermore, in silico calculations have provided a molecular-level picture of the inhibition mechanism, allowing rationalization of experimental data and paving the way for similar studies with other classes of marketed compounds

    HIV Drugs Inhibit Transfer of Plasmids Carrying Extended-Spectrum β-Lactamase and Carbapenemase Genes

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    More and more bacterial infections are becoming resistant to antibiotics. This has made treatment of many infections very difficult. One of the reasons this is such a large problem is that bacteria are able to share their genetic material with other bacteria, and these shared genes often include resistance to a variety of antibiotics, including some of our drugs of last resort. We are addressing this problem by using a fluorescence-based system to search for drugs that will stop bacteria from sharing resistance genes. We uncovered a new role for two drugs used to treat HIV and show that they are able to prevent the sharing of two different types of resistance genes in two unique bacterial strains. This work lays the foundation for future work to reduce the prevalence of resistant infections.Antimicrobial-resistant (AMR) infections pose a serious risk to human and animal health. A major factor contributing to this global crisis is the sharing of resistance genes between different bacteria via plasmids. The WHO lists Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, producing extended-spectrum β-lactamases (ESBL) and carbapenemases as “critical” priorities for new drug development. These resistance genes are most often shared via plasmid transfer. However, finding methods to prevent resistance gene sharing has been hampered by the lack of screening systems for medium-/high-throughput approaches. Here, we have used an ESBL-producing plasmid, pCT, and a carbapenemase-producing plasmid, pKpQIL, in two different Gram-negative bacteria, E. coli and K. pneumoniae. Using these critical resistance-pathogen combinations, we developed an assay using fluorescent proteins, flow cytometry, and confocal microscopy to assess plasmid transmission inhibition within bacterial populations in a medium-throughput manner. Three compounds with some reports of antiplasmid properties were tested; chlorpromazine reduced transmission of both plasmids and linoleic acid reduced transmission of pCT. We screened the Prestwick library of over 1,200 FDA-approved drugs/compounds. From this, we found two nucleoside analogue drugs used to treat HIV, abacavir and azidothymidine (AZT), which reduced plasmid transmission (AZT, e.g., at 0.25 μg/ml reduced pCT transmission in E. coli by 83.3% and pKpQIL transmission in K. pneumoniae by 80.8% compared to untreated controls). Plasmid transmission was reduced by concentrations of the drugs which are below peak serum concentrations and are achievable in the gastrointestinal tract. These drugs could be used to decolonize humans, animals, or the environment from AMR plasmids

    Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia - challenges, strengths, and opportunities in a global health emergency.

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    Aims- The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia. Methods- This was an observational study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients\u2019 medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO 2 /FiO 2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome. Results- A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth \u201cboosted mixed model\u201d included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example. Conclusion- This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels
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