Characterization by length heterogeneity (LH)-PCR of a hydrogen-producing community obtained in dark fermentation using coastal lake sediment as an inoculum

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Proteomic Analysis of Sera from Common Variable Immunodeficiency Patients Undergoing Replacement Intravenous Immunoglobulin Therapy

Common variable immunodeficiency is the most common form of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment of these patients. By using a differential proteomic approach based on 2D-DIGE, we examined serum samples from normal donors and from matched, naive, and immunoglobulin-treated patients. The results highlighted regulated expression of serum proteins in naive patients. Among the identified proteins, clusterin/ApoJ serum levels were lower in naive patients, compared to normal subjects. This finding was validated in a wider collection of samples from newly enrolled patients. The establishment of a cellular system, based on a human hepatocyte cell line HuH7, allowed to ascertain a potential role in the regulation of CLU gene expression by immunoglobulins

Function and dysfunction of the PI system in membrane trafficking

The phosphoinositides (PIs) function as efficient and finely tuned switches that control the assembly–disassembly cycles of complex molecular machineries with key roles in membrane trafficking. This important role of the PIs is mainly due to their versatile nature, which is in turn determined by their fast metabolic interconversions. PIs can be tightly regulated both spatially and temporally through the many PI kinases (PIKs) and phosphatases that are distributed throughout the different intracellular compartments. In spite of the enormous progress made in the past 20 years towards the definition of the molecular details of PI–protein interactions and of the regulatory mechanisms of the individual PIKs and phosphatases, important issues concerning the general principles of the organisation of the PI system and the coordination of the different PI-metabolising enzymes remain to be addressed. The answers should come from applying a systems biology approach to the study of the PI system, through the integration of analyses of the protein interaction data of the PI enzymes and the PI targets with those of the ‘phenomes' of the genetic diseases that involve these PI-metabolising enzymes

Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid--short Radiotherapy--rectum 3rd trial).

BACKGROUND: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. METHODS/DESIGN: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500-825 mg/m2/bid), on days 1-21, or (b) capecitabine as above plus VPA (oral daily day -14 to 21, with an intra-patient titration for a target serum level of 50-100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power.Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-Histones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. DISCUSSION: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT.EudraCT Number: 2012-002831-28. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01898104

Critical role of bevacizumab scheduling in combination with pre-surgical chemo-radiotherapy in MRI-defined high-risk locally advanced rectal cancer: Results of the BRANCH trial.

BACKGROUND: We have previously shown that an intensified preoperative regimen including oxaliplatin plus raltitrexed and 5-fluorouracil/folinic acid (OXATOM/FUFA) during preoperative pelvic radiotherapy produced promising results in locally advanced rectal cancer (LARC). Preclinical evidence suggests that the scheduling of bevacizumab may be crucial to optimize its combination with chemo-radiotherapy. PATIENTS AND METHODS: This non-randomized, non-comparative, phase II study was conducted in MRI-defined high-risk LARC. Patients received three biweekly cycles of OXATOM/FUFA during RT. Bevacizumab was given 2 weeks before the start of chemo-radiotherapy, and on the same day of chemotherapy for 3 cycles (concomitant-schedule A) or 4 days prior to the first and second cycle of chemotherapy (sequential-schedule B). Primary end point was pathological complete tumor regression (TRG1) rate. RESULTS: The accrual for the concomitant-schedule was early terminated because the number of TRG1 (2 out of 16 patients) was statistically inconsistent with the hypothesis of activity (30%) to be tested. Conversely, the endpoint was reached with the sequential-schedule and the final TRG1 rate among 46 enrolled patients was 50% (95% CI 35%-65%). Neutropenia was the most common grade ≥ 3 toxicity with both schedules, but it was less pronounced with the sequential than concomitant-schedule (30% vs. 44%). Postoperative complications occurred in 8/15 (53%) and 13/46 (28%) patients in schedule A and B, respectively. At 5 year follow-up the probability of PFS and OS was 80% (95%CI, 66%-89%) and 85% (95%CI, 69%-93%), respectively, for the sequential-schedule. CONCLUSIONS: These results highlights the relevance of bevacizumab scheduling to optimize its combination with preoperative chemo-radiotherapy in the management of LARC.The study was a no-profit trial partially supported by research grants from the Italian Ministry of Health to A. Avallone (RF-2009-1539464) and to A. Budillon (RF- 2011-02346914)

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age>65 years, antiviral treatment and for severe disease, lactate dehydrogenase >300 mg/dL

Produzione di bio-idrogeno attraverso l'auto-fermentazione di rifiuti vegetali: dall'analisi della diversità microbica all'arricchimento della comunità microbica indigena fermentante

Alternative production chains are called for to reduce the dependence on fossil fuel, to mitigate climate change and to redirect the current production processes towards natural closed ecological cycles. In this context, microbial dark fermentation is a promising way to produce H2 from organic waste contributing to solve two related emergencies: waste disposal and renewable clean energy production. The aim of this study was to asses an innovative approach for fermentative H2 production from common domestic organic waste: the analysis and improvement of the ability to produce H2 of indigenous microbial communities. For this purpose the following objectives were pursued: 1. to explore the feasibility of H2 production by mesophilic self-fermentation of vegetable waste without pretreatment or added nutrients and to improve the process by controlling operative parameters; 2. to screen microbial diversity of the waste in order to isolate and identify potential H2-producers and to characterize the fermentation metabolism of isolates using glucose as nutrient source and optimization parameter; 3. to perform bioaugmentation of the indigenous microbial community in order to improve the H2 production by self-fermentation. To this purpose pure culture and bacterial consortium of three new strains, isolated and enriched from the same waste, were inoculated. The effects of the bioaugmentation in terms of H2 production were investigated, hydrolysis and fermentation pathways were also analyzed. Moreover, the three single strains were characterized for their ability to produce H2 on different sugars, key products of the hydrolysis of cellulose and hemicelluloses.Nell’ottica di ridurre la dipendenza dai combustibili fossili, di mitigare i cambiamenti climatici e di ridirigere gli attuali processi produttivi verso cicli chiusi simili a quelli naturali è necessario sviluppare filiere produttive sostenibili. La dark fermentation è attualmente considerata il più promettente processo biologico per la produzione di H2 in quanto essa offre un duplice vantaggio: generare un vettore energetico “pulito” e utilizzare biomasse residuali abbattendo i costi economici ed ambientali del loro smaltimento. Nel presente lavoro è stato adottato un approccio innovativo per la produzione di H2 da rifiuti vegetali: l’analisi ed il miglioramento delle capacità di produrre H2 della comunità indigena del rifiuto vegetale. In particolare sono stati perseguiti i seguenti obiettivi: 1. la dimostrazione della fattibilità del processo di produzione di H2 per auto-fermentazione di rifiuti vegetali in assenza di pretrattamenti o aggiunta di nutrienti e il miglioramento del processo tramite il controllo dei parametri operativi; 2. lo screening della diversità microbica della comunità indigena del rifiuto allo scopo di identificare, selezionare e caratterizzare metabolicamente i ceppi batterici H2-produttori utilizzando il glucosio come fonte nutritiva e parametro di ottimizzazione; 3. l’incremento della produzione di H2 dell’auto-fermentazione tramite Bioaugmentation. Tre nuovi H2-produttori sono stati selezionati e testati individualmente sul rifiuto e le performances produttive comparate con quelle ottenute tramite l’utilizzo di un consorzio batterico composto dai tre microorganismi. Un ulteriore obiettivo è stata la caratterizzazione del metabolismo fermentativo e delle rese dei tre ceppi sui principali prodotti di idrolisi dei rifiuti vegetali.Dottorato di ricerca in Ecologia e gestione delle risorse biologich