Early progression as a predictor of survival in marginal zone lymphomas: An analysis from the FIL-NF10 study

Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome inMZL and identifies a high-risk population

The importance of a taste. A comparative study on wild food plant consumption in twenty-one local communities in Italy

A comparative food ethnobotanical study was carried out in twenty-one local communities in Italy, fourteen of which were located in Northern Italy, one in Central Italy, one in Sardinia, and four in Southern Italy. 549 informants were asked to name and describe food uses of wild botanicals they currently gather and consume. Data showed that gathering, processing and consuming wild food plants are still important activities in all the selected areas. A few botanicals were quoted and cited in multiple areas, demonstrating that there are ethnobotanical contact points among the various Italian regions (Asparagus acutifolius, Reichardia picroides, Cichorium intybus, Foeniculum vulgare, Sambucus nigra, Silene vulgaris, Taraxacum officinale, Urtica dioica, Sonchus and Valerianella spp.). One taxon (Borago officinalis) in particular was found to be among the most quoted taxa in both the Southern and the Northern Italian sites

Circulating miR-320b and miR-483-5p levels are associated with COVID-19 in-hospital mortality

none28noThe stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.restrictedGiuliani, Angelica; Matacchione, Giulia; Ramini, Deborah; Di Rosa, Mirko; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Monsurrò, Vladia; Recchioni, Rina; Marcheselli, Fiorella; Marchegiani, Francesca; Piacenza, Francesco; Cardelli, Maurizio; Galeazzi, Roberta; Pomponio, Giovanni; Ferrarini, Alessia; Gabrielli, Armando; Baroni, Silvia Svegliati; Moretti, Marco; Sarzani, Riccardo; Giordano, Piero; Cherubini, Antonio; Corsonello, Andrea; Antonicelli, Roberto; Procopio, Antonio Domenico; Ferracin, Manuela; Bonafè, Massimiliano; Lattanzio, Fabrizia; Olivieri, FabiolaGiuliani, Angelica; Matacchione, Giulia; Ramini, Deborah; Di Rosa, Mirko; Bonfigli, Anna Rita; Sabbatinelli, Jacopo; Monsurrò, Vladia; Recchioni, Rina; Marcheselli, Fiorella; Marchegiani, Francesca; Piacenza, Francesco; Cardelli, Maurizio; Galeazzi, Roberta; Pomponio, Giovanni; Ferrarini, Alessia; Gabrielli, Armando; Baroni, Silvia Svegliati; Moretti, Marco; Sarzani, Riccardo; Giordano, Piero; Cherubini, Antonio; Corsonello, Andrea; Antonicelli, Roberto; Procopio, Antonio Domenico; Ferracin, Manuela; Bonafè, Massimiliano; Lattanzio, Fabrizia; Olivieri, Fabiol

Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

Purpose: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. Methods: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. Results: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard vs experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). Conclusion: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative

Modelli in vitro per lo studio dell'ecologia microbica del sistema gastro intestinale

Il crescente interesse della comunità scientifica sul microbiota intestinale e sul ruolo che svolge nell’interazione con l’ospite ha accelerato l’evoluzione di sistemi alternativi allo studio in vivo su animali. Questi sistemi riguardano fermentatori in vitro capaci di simulare, a seconda del modello, aree distinte del tratto digestivo. I modelli in vitro sono un potente strumento necessario per comprendere l'impatto della dieta sul microbiota intestinale, in particolare, le colture continue a multi-stadi consentono di eseguire studi a lungo termine, per valutare eventuali perturbazioni del microbiota in condizioni di stato stazionario. Le recenti modifiche come l’immobilizzazione del microbiota fecale, il movimento peristaltico, l’aggiunta di mucina e la capacità di eseguire trattamenti in parallelo hanno migliorato la capacità di questi strumenti di avvicinarci sempre più alla realtà umana in vivo. Questi strumenti, partendo da culture pure, miste o da campioni fecali, ci aiutano nella comprensione dei fenomeni di interazione che avvengano nel tratto digestivo del nostro organismo. In questa tesi discuto i modelli più utilizzati, associati ad applicazioni che li vedono coinvolti nella comprensione del ruolo dei polifenoli, prebiotici e nell’uso di farmaci. L’introduzione iniziale ha l’obbiettivo di dare un quadro generale sulla composizione del microbiota nelle principali aree dell’apparato gastrointestinale

Novel antifouling agent zinc pyrithione: determination, acute toxicity and bioaccumulation in marine mussels (Mytilus galloprovincialis)

Anti-fouling biocide zinc pyrithione (ZnPT) and its biological fate have received little attention because this compound was assumed not to be persistent in marine ecosystems.We developed an analytical procedure that proved to be efficient and very sensitive in extracting ZnPT and its main secondary products, zinc and ionized PT‾, from both seawater and biological samples, namely in gills and digestive gland of the bioindicator species Mytilus galloprovincialis. Short-term experiments were carried out to investigate ZnPT toxicity and bioaccumulation. The effects on survival and the tissue bioaccumulation of ZnPT and its secondary products were studied on adult mussels from a natural population, collected inside the harbour area of Porto Santo Stefano (Italy) and exposed to sublethal doses of the biocide up to 7 days.ZnPT was shown to be persistent in experimental seawater in the short term. A basal level of ZnPT and ionized PT‾ was detected in mussels, indicating that ZnPT availability in the sampling site is already high enough to induce a detectable accumulation in individuals of the native population. ZnPT rapidly accumulated in tissues of the exposed mussels, proportionately to both exposure concentration and time, identifying the gills and the digestive gland as important targets in the biological path of the contaminants.Even though the 7day-LC50 = 8.27 µM established here appears high with respect to reported ZnPT environmental concentrations, our results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed

Bioaccumulation of PGEs and other traffic-related metals in populations of the small mammal Apodemus sylvaticus

The accumulation of the platinum group elements (PGEs), Pd, Pt, Rh, and other heavy metals (Cd, Cr, Cu, Mn, Ni, Pb, Zn) in the wood mouse Apodemus sylvaticus was investigated in relation to environmental availability, comparing levels in the commonly used target tissues, the liver and kidney, to hair responses. In particular the research aimed to evaluate the suitability of a non-destructive hair-based biomonitoring approach and the responsiveness of PGEs as tracers for the environmental hazard assessment of pollutants linked to traffic in intensively anthropized areas.The four populations considered, inhabiting an urban, a suburban, an agricultural and a reference site, respectively, were shown to be capable of characterizing the differently polluted areas. In particular, multivariate analysis showed a significant correlation between metal levels in tissues and soils. Animals from both the urban and suburban sites, compared to those from the reference site, showed higher levels of those elements (PGEs, Cd, Cr, Ni, Pb and Zn), the availability of which is likely to be related to road traffic. On the contrary, Mn and Cu characterized the animals from the agricultural site. Even though the detected metal concentrations in tissues did not exceed the LOAEL levels, stress indices such as the PGE, Cd and Pb kidney/liver ratios and the kidney/body weight ratios were found to be altered.Significant correlations were established between hair and both internal tissues and soils, for non-essential metals PGE, Cd, Ni and Pb, and also for biologically essential Zn, the level of which was high in urban soils. Hair proved to be a suitable non-invasive tool for monitoring metal exposure responses in small mammals

Novel antifouling agent zinc pyrithione: stress induction and genotoxicity on marine mussel Mytilus galloprovincialis

The anti-fouling biocide zinc pyrithione (ZnPT) was recently demonstrated to be more persistent than expected in the coastal environment, and to have a potential for bioaccumulation. We investigated the occurrence of adverse effects in the marine mussel Mytilus galloprovincialis when exposed to non-lethal concentrations of the contaminant (0.2 and 0.4 µM ZnPT), through the use of a battery of biomarkers from the molecular to the individual level. In particular, the expression of HSP27, HSP60, HSP70 and the presence of genotoxic damage were investigated in the gills and digestive gland of mussels by means of Western Blot and TUNEL procedures, respectively. In addition, a stress on stress response test was performed in order to highlight a possible general stress conditions in the exposed bivalves.A concentration of 0.2 µM ZnPT was found sufficient to trigger a marked stress response in gills and digestive gland, and a dose-dependent HSP expression was highlighted. Moreover, at the tested concentrations, ZnPT was found able to induce genotoxic effects, as demonstrated by an amplified DNA fragmentation (up to +37% of TUNEL positive cells in comparison to the control group) and by an increased frequency of apoptotic cells (up to +5%) in the tissues of the exposed mussels. In addition, the stress on stress response test demonstrated a heavily decreased tolerance to anoxic conditions in mussels exposed to the higher tested concentration of the biocide (LT50 = 5.4 days) compared to the control individuals (LT50 = 10.7 days). Multivariate analyses highlighted a strong correspondence between the observed biological effects in M. galloprovincialis, HSP over-expression and DNA damage in the gills and digestive gland, and the bioaccumulation levels of the biocide.Data presented here indicate the need for further investigations on the ZnPT effects on the key species of marine coastal communities, with the aim of obtaining the necessary information for a sound risk assessment of the impact of this new antifoulant on marine ecosystems

Effetti a breve e lungo terminedel biocida antifouling zinco piritione sulpolichete marino Dinophilus gyrociliatus

Il biocida zinco piritione (ZnPT) è uno degli additivi più utilizzati nelle vernici antivegetative applicate alle imbarcazioni. Si è voluto studiarne gli efetti a breve e a lungo termine sul polichete marino Dinophilus gyrociliatus, tipico degli habitat costieri e possibile target non voluto del biocida.Oltre a test di tossicità acuta (96 h LC50 = 7,77 nM al buio e 11,52 nM in condizioni di luce) sono stati allestiti “Life Table Response Experiments” (LTRE), per valutare gli efetti su ciclo biologico e demograia del polichete.Concentrazioni nanomolari dell’inquinante (0,5 and 1,0 nM), già riscontrabili in natura in alcuni ambiti portuali europei, hanno mostrato di avere efetti su sopravvivenza e riproduzione, ma anche a livello di popolazione, alterando alcuni dei principali indici demograici, quali l’aspettativa di vita e0 (ino a –33 % rispetto al controllo), il tasso netto d’accrescimento R0 (ino a –63 %) e il tasso di crescita della popolazione λ (ino a –9 %), importante indicatore della fitness biologica di una popolazione.Il sospetto di efetti sul potenziale di crescita di D. gyrociliatus suggerisce la pericolosità del biocida per questa ed altre specie aini e il rischio di alterazione della biodiversità nell’ambiente marino costiero, imponendo la necessità di una più ampia valutazione degli efetti cronici dell’utilizzo su larga scala di questo biocida nelle pratiche antifouling