La \uabfredda\ubb e \uaballegra\ubb impostura dell\u2019abate Vella nella Palermo settecentesca

Il saggio delinea una geniale impostura che occup\uf2 la scena palermitana di fine Settecento seguendo la ricostruzione di uno storico ottocentesco, Domenico Scin\ue0, e la sua riscrittura in un romanzo di Leonardo Sciascia. Un solo protagonista, l\u2019abate Vella, nel testo dello storico; due personaggi, il Vella e il Di Blasi, nel "Consiglio d\u2019Egitto" (1963). Scin\ue0, in uno scritto del 1824, presenta l\u2019abate Vella come un avventuriero e ripercorre l'impostura grazie alla quale egli aveva costruito dal nulla una falsa storia della Sicilia, tutta orientata a rafforzare e ampliare prerogative e diritti della monarchia contro le appropriazioni, ritenute indebite, dei grandi feudatari. Nel romanzo storicamente fedele \ue8 la ricostruzione dell\u2019impostura, rigorosamente storici e reali sono i personaggi, tutta sciasciana (nel senso che ci si ritrova l\u2019ideologia, a volte l\u2019ironia, spesso lo sconforto dell\u2019autore) \ue8 l\u2019invenzione narrativa che presiede alla scrittura dei monologhi, dei dialoghi, alla ricostruzione delle situazioni, degli ambienti che fanno da sfondo alle vicende, elementi questi ultimi necessari per costruire \uabil vero romanzesco\ubb. Alla fine, prendendo spunto dall\u2019inganno velliano, altre falsificazioni, altre imposture si materializzeranno nel romanzo: supreme quelle della storia, della scrittura, dei libri e, quindi, della letteratura; \uabtragica\ubb quella della congiura giacobina palermitana del 1795 e del suo fallimento

Passive scalar diffusion in the near field region of turbulent rectangular submerged free jets

Jets are a common way to transfer mass among fluids, or from a fluid to a surface. At moderate Reynolds numbers and low turbulent intensities the jet exhibits a Near Field Region (NFR) several diameters long. The paper presents numerical results and a theoretical model for the passive scalar diffusion of a submerged free jet in the NFR. Large Eddy Simulations (LES), in the Reynolds number range of 5000–40,000 and the Schmidt number range 1–100, are performed obtaining the passive scalar fields. Three mathematical models for the passive scalar diffusion are presented; the first one is valid in the NFR, specifically in the Undisturbed Region of Flow (URF), and the other two, obtained under the hypotheses of Tollmien and Görtler momentum spreading, are valid in the Potential Core Region (PCR). The last two models employ a turbulent Schmidt number inversely proportional to the mean velocity gradient, conclusion obtained from the LES numerical results. The self-similar solutions of the passive scalar show good agreement with the LES results. The wide range of Reynolds and Schmidt numbers investigated gives generality to the results

Three-dimensional numerical simulation of a failed coronary stent implant at different degrees of residual stenosis. Part II: Apparent viscosity and wall permeability

The influence of the degree of residual stenosis (DOR) on the hemodynamics inside coronary arteries is investigated through three-dimensional (3D) numerical simulations. The vascular wall permeability is investigated and the effect of the non-Newtonian viscosity discussed. The results agree in predicting an abrupt increase in wall permeability above 45% DOR, indicating that the implant could lead to a massive restenosis. This behavior is considered to be due to the shift of the regions involved by low and oscillatory wall shear stress (WSS), from the zone adjacent to the struts toward the center of the stent meshes

Three-dimensional numerical simulation of a failed coronary stent implant at different degrees of residual stenosis. Part I: Fluid dynamics and shear stress on the vascular wall

The influence of the degree of residual stenosis on the hemodynamics inside coronary arteries is investigated through three-dimensional (3D) numerical simulations. The present paper, which is the first of a series of two, focuses on the influence that the degree of residual stenosis (DOR) has on the fluid dynamics and the shear stresses acting on the stent and the artery wall. The pulsatile nature of the blood flow and its non-Newtonian features are taken into account. Four models of artery are investigated. The results show that the wall shear stress (WSS) increases monotonically, but not linearly, with the DOR

p53-Mediated downregulation of H ferritin promoter transcriptional efficiency via NF-Y

The tumor suppressor protein p53 triggers many of the cellular responses to DNA damage by regulating the transcription of a series of downstream target genes. p53 acts on the promoter of the target genes by interacting with the trimeric transcription factor NF-Y. H ferritin promoter activity is tightly dependent on a multiprotein complex called Bbf; on this complex NF-Y plays a major role. The aim of this work was to study the modulation of H ferritin expression levels by p53. CAT reporter assays indicate that: (i) p53 overexpression strongly downregulates the transcriptional efficiency driven by an H ferritin promoter construct containing only the NF-Y recognition sequence and that the phenomenon is reverted by p53 siRNA; (ii) the p53 C-terminal region is sufficient to elicitate this regulation and that a correct C-terminal acetylation is also required. The H ferritin promoter displays no p53-binding sites; chromatin immunoprecipitation assays indicate that p53 is recruited on this promoter by NF-Y. The p53–NF-Y interaction does not alter the NF-Y DNA-binding ability as indicated by electrophoretic mobility shift assay (EMSA) analysis. These results demonstrate that the gene coding for the H ferritin protein belongs to the family of p53-regulated genes, therefore adding a new level of complexity to the regulation of the H ferritin transcription and delineate a role for this protein in a series of cellular events triggered by p53 activation

Acute hemodynamic effects of inhaled nitric oxide, dobutamine and a combination of the two in patients with mild to moderate secondary pulmonary hypertension

INTRODUCTION: The use of low-dose dobutamine to maintain hemodynamic stability in pulmonary hypertension may have a detrimental effect on gas exchange. The aim of this study was to investigate whether inhaled nitric oxide (INO), dobutamine and a combination of the two have beneficial effects in patients with end-stage airway lung disease and pulmonary hypertension. METHOD: Hemodynamic evaluation was assessed 10 min after the administration of each drug and of their combination, in 28 candidates for lung transplantation. RESULTS: Administration of INO caused a reduction in mean pulmonary arterial pressure (MPAP), an increase in PaO(2) with a significant reduction in venous admixture effect (Q(s)/Q(t)).Dobutamine administration caused an increase in cardiac index and MPAP, with a decrease in PaO(2) as a result of a higher Q(s)/Q(t). Administration of a combination of the two drugs caused an increase in the cardiac index without MPAP modification and an increase in PaO(2) and Q(s)/Q(t). CONCLUSION: Dobutamine and INO have complementary effects on pulmonary circulation. Their association may be beneficial in the treatment of patients with mild to moderate pulmonary hypertension

Mechanisms of endothelial cell dysfunction in cystic fibrosis

Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC. CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF

Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma

Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs’ location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study)

Background Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58–85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). Conclusions The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival