La lima e il testo da Ovidio a Marziale: poetica e comunicazione

In the poetic texts from the Imperial age (from exiled Ovid to Martial and Statius) the metaphor of poetic lima undergoes a deep transformation: the lima is no longer in the hands of the poet, who has polished his verses for years and years, but (often) in those of a cultivated patron, requested by the author to correct the book before publication. In the Flavian age the lima is then placed within the complex communication system of literary patronage, where it becomes an element of homage and compliment. However, the metaphor never loses its original poetological meaning: both Martial and Statius use it differently, in relation to themselves and in relation to intellectual patrons, thus subtly reaffirming their own different and higher commitment to literature

Experiencias frente a la vacunación contra la COVID-19 de los adultos mayores en un centro de salud de Chota, 2022

La presente investigación tuvo como objetivo: describir y analizar las experiencias frente a la vacunación contra la COVID-19 de los adultos mayores en un centro de salud de Chota, 2022. Método: la investigación fue cualitativa, con abordaje descriptivo. La población fue de 103 adultos mayores, quienes cumplieron los criterios de inclusión y exclusión; la muestra fue de 12 adultos mayores, siendo esta de tipo no probabilístico por conveniencia. Así mismo, para la presente investigación se tuvo la aprobación del comité de ética e investigación de la Facultad de Medicina, luego se realizó la recolección de los datos, donde se utilizó como instrumento una entrevista semiestructurada, que fue elaborada por la investigadora y validada por juicio de expertos; luego se procedió a analizar los datos mediante el método de análisis temático. Además, durante la investigación se tuvo en cuenta los principios éticos personalistas según Sgreccia. Resultados: surgieron tres categorías: 1) Atención humanizada centrada en el paciente durante la vacunación. 2) Reacciones post vacunación de la COVID-19. 3) Experiencia de seguridad y protección frente al cumplimiento de sus dosis. Conclusión: Los adultos mayores del centro de salud mental de Chota, manifestaron su experiencia con la vacunación de la COVID – 19, destacando que fue positiva a través del sentimiento de seguridad, el trato humanizado brindado por el personal de enfermería y la ausencia de reacciones adversas frente a la vacuna contra la COVID - 19. Además de la manifestación de seguridad que sienten para ellos y sus familias

Rievocando Guido Davide Neri

La morte di Guido Davide Neri, di cui quest’anno ricorre il ventennale, ha determinato la presa di coscienza – nei suoi maestri, amici, colleghi e allievi – dell’irreparabilità dell’evento, della definitività del venir meno di una voce così teoreticamente stimolante ed eclettica. Perdita tragicamente vissuta nella cerchia della sua frequentazione, ma, parallelamente, inserita nell’ampio contesto del dibattito culturale nazionale e internazionale, in cui Neri era organicamente inserito. Pare a noi, che non lo abbiamo conosciuto e gli siamo temporalmente più distanti rispetto a quanti ne hanno sinora scritto, quasi inusuale che, a un filosofo mancato da così poco tempo, sia stata consacrata una già così importante quantità di ricerche e studi. Al di là della retorica che spesso accompagna, in ambiente accademico, il ritiro dall’attività didattica o la scomparsa di un docente, e abituati alla necessità della sedimentazione storica per la messa a punto del bilancio storiografico, ci ha stupito l’intensità con cui Neri è stato ricordato e la varietà degli interventi sulla sua figura, l’insegnamento e la produzione scientifica. Se da un lato questo acuisce, in noi, il rimpianto di non averlo incrociato nel mondo, dall’altro stimola la volontà di tornare a lui, al suo pensiero, alle sue opere. Un ritorno che, non mediato dall’influenza personale, potrà certo apparire privo di taluni elementi importanti, come la testimonianza diretta o la compartecipazione a certe esperienze determinanti, ma, insieme, si potrà giovare del giusto distacco critico, trovando ora nel prezioso Fondo Guido Davide Neri, conservato presso l’Università degli Studi di Milano, la fonte privilegiata dell’accesso alla sua opera teorica. Questo, si potrebbe dire, è il fil rouge che accomuna i nostri brevi contributi, diversi per tematiche e occasione di elaborazione, ma tutti contraddistinti dall’interesse e dalla volontà di avvicinare un po’ meglio la figura di Neri: le carte dell’archivio personale per noi hanno rappresentato e rappresentano la possibilità di accedere al suo laboratorio, di scoprire da esse l’uomo e il filosofo e di dare concretezza documentaria alla dialettica tra pensiero, letture ed esperienze. Certo il lavoro da svolgere è ancora molto e solo lo scandaglio approfondito del materiale permetterà di penetrare a fondo l’officina neriana. Quello che noi qui, più limitatamente, offriamo, è soltanto un piccolo esempio di quanto di rilevante e ancora da vedere è racchiuso nei faldoni e aspetta di essere portato alla luce. Il nostro, in altre parole, vorrebbe essere un invito a ripensare Neri attraverso le carte, convinti della loro imprescindibilità ai fini della ricostruzione storico-critica del suo percorso filosofico e coscienti del loro straordinario valore intrinseco (per certi versi anche estetico). Gli interventi che presentiamo – ne siamo convinti – sono poi una ulteriore testimonianza della capacità di Neri e del suo pensiero di porsi in dialogo, anche a distanza, con una sempre nuova varietà di interlocutori

MicroRNA profiling of paediatric AML with FLT-ITD or MLL-rearrangements: Expression signatures and in vitro modulation of miR-221-3p and miR-222-3p with BRD4/HATs inhibitors.

Novel therapeutic strategies are needed for paediatric patients affected by Acute Myeloid Leukaemia (AML), particularly for those at high-risk for relapse. MicroRNAs (miRs) have been extensively studied as biomarkers in cancer and haematological disorders, and their expression has been correlated to the presence of recurrent molecular abnormalities, expression of oncogenes, as well as to prognosis/clinical outcome. In the present study, expression signatures of different miRs related both to presence of myeloid/lymphoid or mixed-lineage leukaemia 1 and Fms like tyrosine kinase 3 internal tandem duplications rearrangements and to the clinical outcome of paediatric patients with AML were identified. Notably, miR-221-3p and miR-222-3p resulted as a possible relapse-risk related miR. Thus, miR-221-3p and miR-222-3p expression modulation was investigated by using a Bromodomain‑containing protein 4 (BRD4) inhibitor (JQ1) and a natural compound that acts as histone acetyl transferase inhibitor (curcumin), alone or in association, in order to decrease acetylation of histone tails and potentiate the effect of BRD4 inhibition. JQ1 modulates miR-221-3p and miR-222-3p expression in AML with a synergic effect when associated with curcumin. Moreover, changes were observed in the expression of CDKN1B, a known target of miR-221-3p and miR-222-3p, increase in apoptosis and downregulation of miR-221-3p and miR-222-3p expression in CD34+ AML primary cells. Altogether, these findings suggested that several miRs expression signatures at diagnosis may be used for risk stratification and as relapse prediction biomarkers in paediatric AML outlining that epigenetic drugs, could represent a novel therapeutic strategy for high-risk paediatric patients with AML. For these epigenetic drugs, additional research for enhancing activity, bioavailability and safety is needed

Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders

The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset

The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study

Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCγ receptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q<0.1), but not in arms in which patients did not receive doxorubicin (i.e., the rituximab-cyclophosphamide-vincristine-prednisone and rituximab-fludarabine-mitoxantrone arms). The impact of MLH1 on time to treatment failure was independent after adjusting for the Follicular Lymphoma International Prognostic Index and other potential confounding variables by multivariate analysis. These data indicate that MLH1 genotype is a predictor of failure to benefit from rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone treatment in advanced follicular lymphoma and confirm that FCGR2A and FCGR3A polymorphisms have no impact when follicular lymphoma is treated with rituximab plus chemotherapy (clinicaltrials.gov identifier: NCT00774826)

Nonpegylated liposomal doxorubicin combination regimen in patients with diffuse large B-cell lymphoma and cardiac comorbidity. Results of the HEART01 phase II trial conducted by the Fondazione Italiana Linfomi

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76\ua0years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF <50% (12%). Based on the intent to treat analysis, overall response rate was 72%, including 28 patients in complete remission (complete remission rate, 56%), and 8 in partial remission (16%). At the end of treatment, grades 3 to 4 cardiac events were observed in 6 patients. No significant modifications from baseline values of LVEF were observed during treatment and follow-up. Nonpegylated liposomal doxorubicin instead of doxorubicin in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is a feasible option for patients with diffuse large B-cell lymphoma presenting with concomitant cardiac disorders

Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1-negative clonal disorder, which belongs to the myelodysplastic/myeloproliferative group. This disease is characterized by recurrent somatic mutations in SETBP1, ASXL1 and ETNK1 genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive genomic characterization of aCML we applied a high-throughput sequencing strategy to 43 aCML samples, including both whole-exome and RNA-sequencing data. Our dataset identifies ASXL1, SETBP1, and ETNK1 as the most frequently mutated genes with a total of 43.2%, 29.7 and 16.2%, respectively. We characterized the clonal architecture of 7 aCML patients by means of colony assays and targeted resequencing. The results indicate that ETNK1 variants occur early in the clonal evolution history of aCML, while SETBP1 mutations often represent a late event. The presence of actionable mutations conferred both ex vivo and in vivo sensitivity to specific inhibitors with evidence of strong in vitro synergism in case of multiple targeting. In one patient, a clinical response was obtained. Stratification based on RNA-sequencing identified two different populations in terms of overall survival, and differential gene expression analysis identified 38 significantly overexpressed genes in the worse outcome group. Three genes correctly classified patients for overall survival

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions