Bruno Blanckeman, Patrick Modiano ou l’écriture comme un nocturne. Des noirceurs de l’Histoire aux ténèbres du Temps

Bruno Blanckeman, già autore del saggio Lire Patrick Modiano, specialista dell’opera letteraria del Premio Nobel 2014, torna ad analizzare le zone d’ombra, spettrali e perturbanti, che caratterizzano la scrittura modianesca. Patrick Modiano ou l’écriture comme un nocturne si divide in tre sezioni, precedute da un preambolo sulla fortuna critica dell’autore. La prima sezione, dal titolo «Faux-fuyants» (pp. 19-66), analizza alcuni dei motivi chiave dell’opera di Modiano, associati e declinati d..

L’incoerenza creativa nella narrativa francese contemporanea, M. Majorano (dir.)

L’incoerenza? «Un talismano contro la sorte» e una «risorsa per il romanzo». Questa la chiave di lettura che apre la miscellanea sul «disordine», stilistico e strutturale, che sembra aver invaso la narrativa francese contemporanea. «Entrare in un romanzo è come entrare in un edificio ignoto», scrive M. Majorano nel saggio introduttivo (L’incoerenza e la letteratura, pp. 9-25). Con Perec, lo studioso raccomanda «precauzione» e «spirito di osservazione» di fronte alle «sgrammaticature» dell’aut..

Matteo Majorano (a cura di), La Giostra dei sentimenti

Dal Romanticismo alla narrativa francese odierna, passando per lo sperimentalismo del Nouveau Roman: com’è cambiato, nel tempo, il nesso tra scrittura ed emotività? Come si rapportano oggi l’io-scrittore e l’io-lettore di fronte ai sentimenti? Una giostra: è questa l’immagine che dà il titolo alla raccolta di ventiquattro saggi curati da Matteo Majorano. Il suo contributo, La scrittura dei sentimenti e la speranza / L’écriture des sentiments et l’espoir (pp. 9-28), introduce gli obiettivi del..

Development of a repressible mycobacterial promoter system based on two transcriptional repressors

Tightly regulated gene expression systems represent invaluable tools for studying gene function and for the validation of drug targets in bacteria. While several regulated bacterial promoters have been characterized, few of them have been successfully used in mycobacteria. In this article we describe the development of a novel repressible promoter system effective in both fast- and slow-growing mycobacteria based on two chromosomally encoded repressors, dependent on tetracycline (TetR) and pristinamycin (Pip), respectively. This uniqueness results in high versatility and stringency. Using this method we were able to obtain an ftsZ conditional mutant in Mycobacterium smegmatis and a fadD32 conditional mutant in Mycobacterium tuberculosis, confirming their essentiality for bacterial growth in vitro. This repressible promoter system could also be exploited to regulate gene expression during M. tuberculosis intracellular growt

Development of a repressible mycobacterial promoter system based on two transcriptional repressors

Tightly regulated gene expression systems represent invaluable tools for studying gene function and for the validation of drug targets in bacteria. While several regulated bacterial promoters have been characterized, few of them have been successfully used in mycobacteria. In this article we describe the development of a novel repressible promoter system effective in both fast- and slow-growing mycobacteria based on two chromosomally encoded repressors, dependent on tetracycline (TetR) and pristinamycin (Pip), respectively. This uniqueness results in high versatility and stringency. Using this method we were able to obtain an ftsZ conditional mutant in Mycobacterium smegmatis and a fadD32 conditional mutant in Mycobacterium tuberculosis, confirming their essentiality for bacterial growth in vitro. This repressible promoter system could also be exploited to regulate gene expression during M. tuberculosis intracellular growth

Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint

Introduction: Evaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-\u3b1 blockers in psoriatic arthritis (PsA). Methods: Systemic and local disease activity indexes (disease activity score [DAS]; the Ritchie articular index [mRAI], erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular [THOMP] and joint articular [KJAI]-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml - 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a ten week period. Total SF white blood cell (WBC) counts (WBC/ \u3bcl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8/14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105. Results: At baseline, CRP and/or ESR were significantly correlated with SF-CK (IL-1\u3b2, IL-1Ra, IL-6, IL-8) and CCK (CCL2, CCL3 and CCL4). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/\u3bcl and in SF-CK (TNF-\u3b1, IL- 1\u3b2, IL-1Ra, IL-6 and IL-22). Pre- and post- IAE injections, there were significant correlations between ST markers and SF-CK (IL-1\u3b2 with CD45; IL-1\u3b2 and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3)

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and >= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p < 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p < 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p < 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay