Che cosa è stato l’Illuminismo: rivoluzione della mente o rivoluzione culturale dell’Antico Regime?

After the fall of the Berlin Wall in 1989, international studies in historiography gave way to a strong process of critical reassessment. In the same way, the historiography of Enlightenment is currently undergoing a rapid and decisive transformation similar to that which occurred in the West after World War II. The Anglo-Saxon world is certainly at the forefront of this process and even, it seems, guides its destiny: especially the US, where the monumental works of Jonathan Israel provide an example worthy of attention. This paper, nonetheless, aims to discuss Israel’s research hypotheses, reductively founded on the primacy of the history of philosophy and on the idea of a so-called Radical Enlightenment dominated by the thought and ideas of Spinoza, in contrast with thirty years of research on the history of culture conducted by major scholars in every part of the world, and in Italy in particular. A history of culture that has long been able to innovate and produce research hypotheses open to the future: from human rights to cultural practices, from constitutionalism to the relationship between art and politics as recognised by the nascent public opinion

Il problema Rousseau e i diritti dell’uomo. La pratica politica dei diritti tra natura e cultura, individuo e comunità, «stato di pura natura» e società civile

Jean-Jacques Rousseau padre nobile dei diritti dell’uomo e della politica dei moderni? Recentemente è stata attribuita al grande ginevrino e alla sua opera di romanziere dallo straordinario successo la qualifica di protagonista della creazione, in Europa, di una nuova mentalità empatica tra gli esseri umani, l’humus che avrebbe favorito l’affermazione del linguaggio dei diritti nel corso della seconda metà del Settecento. Lo si è definito gran divulgatore e persino – con qualche forzatura e i..

Synthesis and characterization of electrospun sorbent for the solid-phase extraction of fluoroquinolones in human plasma and their UHPLC-PDA determination

In this work we investigated the synthesis and the characterization of electrospun polyacrylonitrile (PAN) and polymethyl methacrylate (PMMA) stabilized in air, made in a 5:1 ratio, used as sorbent for the solid-phase extraction of fluoroquinolones in plasma samples and the following quantification in UHPLC-PDA. Preliminary analyses of viscosity were carried out on the polymer solution to be sure about the electrospinability. Characterizations were performed on the electrospun membrane to evaluate the morphology (SEM scanning electron microscopy and AFM atomic force microscopy), the thermal degradation behavior (TGA thermogravimetric analysis), the porosity and the surface area (BET, Brunauer Emmett Teller), and the quantitative and qualitative distribution of atomic structures (FTIR infrared analysis in Fourier transform and EDX Energy Dispersive X-ray analysis). A solid-phase extraction method was developed by studying parameters such as the amount of sorbent and the pH of the sample. Finally, a UHPLC-PDA method for the analysis of fluoroquinolones was developed and validated in accordance with the guidelines and successfully applied. The use of the prepared sorbent combined with UHPLC-PDA has allowed the development of a method whose strengths are its speed, accuracy, sensitivity, and high recoveries. In this work we investigated the synthesis and the characterization of electrospun polyacrylonitrile (PAN) and polymethyl methacrylate (PMMA) stabilized in air, made in a 5:1 ratio, used as sorbent for the solid-phase extraction of fluoroquinolones in plasma samples and the following quantification in UHPLC-PDA. Preliminary analyses of viscosity were carried out on the polymer solution to be sure about the electrospinability. Characterizations were performed on the electrospun membrane to evaluate the morphology (SEM scanning electron microscopy and AFM atomic force microscopy), the thermal degradation behavior (TGA thermogravimetric analysis), the porosity and the surface area (BET, Brunauer Emmett Teller), and the quantitative and qualitative distribution of atomic structures (FTIR infrared analysis in Fourier transform and EDX Energy Dispersive X-ray analysis). A solid-phase extraction method was developed by studying parameters such as the amount of sorbent and the pH of the sample. Finally, a UHPLC-PDA method for the analysis of fluoroquinolones was developed and validated in accordance with the guidelines and successfully applied. The use of the prepared sorbent combined with UHPLC-PDA has allowed the development of a method whose strengths are its speed, accuracy, sensitivity, and high recoveries

An Expanded Peripheral T Cell Population to a Cytotoxic T Lymphocyte (Ctl)-Defined, Melanocyte-Specific Antigen in Metastatic Melanoma Patients Impacts on Generation of Peptide-Specific Ctls but Does Not Overcome Tumor Escape from Immune Surveillance in Metastatic Lesions

It is not known if immune response to T cell–defined human histocompatibility leukocyte antigen (HLA) class I–restricted melanoma antigens leads to an expanded peripheral pool of T cells in all patients, affects cytotoxic T lymphocyte (CTL) generation, and correlates with anti-tumor response in metastatic lesions. To this end, a limiting dilution analysis technique was developed that allowed us to evaluate the same frequency of peptide-specific T cells as by staining T cells with HLA–peptide tetrameric complexes. In four out of nine patients, Melan-A/Mart-127–35–specific CTL precursors (CTLp) were ≥1/2,000 peripheral blood lymphocytes and found mostly or only in the CD45RO+ memory T cell subset. In the remaining five patients, a low (<1/40,000) peptide-specific CTLp frequency was measured, and the precursors were only in the CD45RA+ naive T cell subset. Evaluation of CTL effector frequency after bulk culture indicated that peptide-specific CTLs could be activated in all patients by using professional antigen-presenting cells as dendritic cells, but CTLp frequency determined the kinetics of generation of specificity and the final number of effectors as evaluated by both limiting dilution analysis and staining with HLA-A*0201–Melan-A/Mart-1 tetrameric complexes. Immunohistochemical analysis of 26 neoplastic lesions from the nine patients indicated absence of tumor regression in most instances, even in patients with an expanded peripheral T cell pool to Melan-A/Mart-1 and whose neoplastic lesions contained a high frequency of tetramer-positive Melan-A/Mart-1–specific T cells. Furthermore, frequent lack of a “brisk” or “nonbrisk” CD3+CD8+ T cell infiltrate or reduced/absent Melan-A/Mart-1 expression in several lesions and lack of HLA class I antigens were found in some instances. Thus, expansion of peripheral immune repertoire to Melan-A/Mart-1 takes place in some metastatic patients and leads to enhanced CTL induction after antigen-presenting cell–mediated selection, but, in most metastatic lesions, it does not overcome tumor escape from immune surveillance

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome

Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS).Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist.Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated.Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9 +/- 3.1 vs MILR 226 +/- 4.0, P=0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P=0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P=0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P=0.015), posthepatectomy liver failure (0.6% vs 4.3%, P=0.008), and bile leaks (2.2% vs 6.4%, P=0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P=0.002) and day 3 (3.1% vs 11.4%, P&lt;0.001); hospital stay was significantly shorter (5.8 +/- 1.9 vs 7.5 +/- 1.7, P&lt;0.001). There was no significant difference in overall survival and disease-free survival.Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible

The Tempered Polymerization of Human Neuroserpin

Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation