Multilocus Sequence Typing of Commensal and EnteropathogenicEscherichia Colifrom Domestic and Wild Lagomorphs in Italy

The aim of the study was to determine the multilocus sequence types of Escherichia coli from diseased farm rabbits and apparently healthy wild lagomorphs, and the genetic relatedness among them. Fifty-five enteropathogenic E. coli from reared rabbits and 32 from wild rabbits and hares were characterised by multilocus sequence typing (MLST) according to the Michigan State University EcMLST scheme. Isolates were differentiated into 37 sequence types (STs), which were grouped into 8 clonal complexes (CCs). The most common ST was ST140 (CC31), followed by ST238 and ST119 (CC17). MLST analysis revealed 22 novel STs. Phylogenetic analyses showed a heterogeneous distribution of STs into 3 clusters of genetically related strains. The genetic relationship among STs of different origin and the detection of new, as well as previously described STs as human pathogens, indicate a widespread distribution and adaptability of particular lineages to different hosts. These findings highlight the need for further research to improve the knowledge about E. coli populations colonising the gut of lagomorphs and their zoonotic potential

Amyotrophic Lateral Sclerosis and Multiple Sclerosis Overlap: A Case Report

The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis demonstrated 3 periventricular and juxtacortical lesions, hyperintense in T2 and FLAIR sequences, and 3 liquoral immunoglobulin G (IgG) oligoclonal bands, consistent with diagnosis of primary progressive MS (PPMS). This unusual overlap of ALS and MS leads to the discussion of a hypothetical common pathological process of immunological dysfunction in these two disorders, although the role of immune response in ALS remains ambivalent and unclear

What’s the best assessment of preload after cardiac surgery?

Objective: The assessment of the role of transesophageal echocardiography and invasive tests with pulmonary modified catheter to monitor the preload indexes in patients in intensive- care-unit after cardiac coronary surgery. Materials and Methods: Between January and December 2004 24 patients (14 male, 10 female) with coronary artery disease were prospectively enrolled for preload assessment during off-pump myocardial revascularization. Pulmonary Capillary Wedge Pressure (PCWP), Left Ventricular End Diastolic Indexed Area (LVEDAI), Δ Aortic Velocity (ΔVAo), Right Ventricular End Diastolic Volume (RVEDVI) as preload indexes were evaluated. Transesophageal echocardiography and pulmonary modified catheter monitoring were performed during the preoperative period at T1 and after fluid infusion (T2). Patients were considered Responders (R) or No Responders (NR) if the Stroke Volume Index increase at T2 was >20% with respect to T1. Results: Mean T1 PCWP was similar in both groups (12.8±2.2 in R vs. 11.4±3 mmHg in NR; p=NS) and mean increase of PCWP at T2 was similar in both groups (1.5±0.3% in R vs. 1.2±3% in NR; p=NS). Mean T1 RVEDVI was similar in both groups (97.33±34 in R vs. 101±21 ml/m2 in NR; p=NS); T2 RVEDVI was similar in R and NR Groups (122.11±49 vs. 138.54±30 ml/m2; p=NS); mean T1 and T2 LVEDAI was similar in R and NR (11.2±3.5 vs. 10.2±2.3 at T1 and 14.04±3.35 vs. 14.67±2.1 cm2/m2 at T2 respectively; p=NS). Higher mean value of T1 ΔVAo (20±7% in R vs. 10±2% in NR; p=0.006) were recorded while similar mean value of T2 ΔVAo were observed (11±3% in R vs. 5±2% in NR; p=0.743). Correlation index between T1 and T2 ΔVAo (R=0.82) in R was significant (p=0.0002), while correlation index between T1 and T2 ΔVAo (R=0.11) in NR was not significant. Conclusions: Our study showed in patients soon after coronary cardiac surgery ΔVAo is the only predictor of “fluid responsiveness” and of ventricular compliance

Clinical features and lifestyle of patients with amyotrophic lateral sclerosis in Campania: brief overview of an Italian database

Background. Physical activity and occupational exposures appeared to play a relevant role in pathogenesis of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown origin. Materials and methods. We aimed to make an overview of the clinical characteristics and life - style (occupation and sport) of a population of 395 patients with ALS from campania, in southern Italy. Results. ALS onset resulted anticipated of about 11 years in industry workers, whilst the more frequent site of onset among farmers was upper limbs. compared to non-athletes, athletes, particu- larly soccer players, showed a 7 years anticipation of ALS onset, with higher mortality after 5 years. Discussion and conclusions. We suggest that subjects genetically prone to abnormal response to hy - poxia during strenuous physical activity or exposed to neurotoxic agents, such as athletes, farmers or industry workers, might present increased risk to develop ALS. Future case-control and follow-up studies on our population should be implemented to deepen the present results. Riassunto (Caratteristiche cliniche e stile di vita di pazienti con sclerosi laterale amiotrofica in Campania: breve panoramica di un database italiano). Introduzione. Attivita fisica ed esposizione professionale a sostanze tossiche sembrano svolgere un ruolo rilevante nella patogenesi della sclerosi laterale amiotrofica (SLA), una malattia neurodegenerativa di origine sconosciuta. Materiali e metodi. ci siamo proposti di effettuare una panoramica delle caratteristiche cliniche e dello stile di vita (attivita lavorativa e sport) di una popolazione di 395 pazienti affetti da SLA provenienti dalla regione campania, in Italia meridionale. Risultati. L'insorgenza della SLA e risultata anticipata di circa 11 anni nei lavoratori dell'industria, mentre il sito piu frequente di insorgenza tra i contadini era caratterizzato dagli arti superiori. Rispetto ai non- sportivi, gli sportivi, soprattutto i calciatori, hanno mostrato un'anticipazione di 7 anni nell'insorgenza della SLA, con maggiore mortalita a 5 anni. Discussione e conclusioni. Abbiamo ipotizzato che i soggetti geneticamente predisposti a risposte anomale all'ipossia durante l'attivita fisica intensa o esposti ad agenti neurotossici, come gli sportivi, gli agricoltori o i lavoratori dell'industria, possano presentare un aumen - tato rischio di sviluppare la SLA. Futuri studi caso-controllo e di follow-up sulla nostra popolazione dovrebbero essere effettuati per approfondire i risultati attuali

A multicenter randomized phase 4 trial comparing sodium picosulphate plus magnesium citrate vs. polyethylene glycol plus ascorbic acid for bowel preparation before colonoscopy. The PRECOL trial

Background: Adequate bowel preparation before colonoscopy is crucial. Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From a patient perspective, bowel preparation is the main obstacle to colonoscopy. Several low-volume bowel preparations have been formulated to provide more tolerable purgative solutions without loss of efficacy. Objectives: Investigate efficacy, safety, and tolerability of Sodium Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing diagnostic colonoscopy. Materials and methods: In this phase 4, randomized, multicenter, twoarm trial, adult outpatients received either SPMC or PEG-ASC for bowel preparation before colonoscopy. The primary aims were quality of bowel cleansing (primary endpoint scored according to Boston Bowel Preparation Scale) and patient acceptance (measured with six visual analogue scales). The study was open for treatment assignment and blinded for primary endpoint assessment. This was done independently with videotaped colonoscopies reviewed by two endoscopists unaware of study arms. A sample size of 525 patients was calculated to recognize a difference of 10% in the proportion of successes between the arms with a two-sided alpha error of 0.05 and 90% statistical power. Results: Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned to SPMC) represented the analysis population. There was no statistically significant difference in success rate according to BBPS: 94.4% with PEG-ASC and 95.7% with SPMC (P = 0.49). Acceptance and willing to repeat colonoscopy were significantly better for SPMC with all the scales. Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and SPMC, respectively (P = 0.17). Nausea and meteorism were significantly more bothersome with PEG-ASC than SPMC. There were no serious adverse events in either group. Conclusion: SPMC and PEG-ASC are not different in terms of efficacy, but SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to lowvolume PEG based purgative solutions for bowel preparation

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

A New Orbiting Deployable System for Small Satellite Observations for Ecology and Earth Observation

In this paper, we present several study cases focused on marine, oceanographic, and atmospheric environments, which would greatly benefit from the use of a deployable system for small satellite observations. As opposed to the large standard ones, small satellites have become an effective and affordable alternative access to space, owing to their lower costs, innovative design and technology, and higher revisiting times, when launched in a constellation configuration. One of the biggest challenges is created by the small satellite instrumentation working in the visible (VIS), infrared (IR), and microwave (MW) spectral ranges, for which the resolution of the acquired data depends on the physical dimension of the telescope and the antenna collecting the signal. In this respect, a deployable payload, fitting the limited size and mass imposed by the small satellite architecture, once unfolded in space, can reach performances similar to those of larger satellites. In this study, we show how ecology and Earth Observations can benefit from data acquired by small satellites, and how they can be further improved thanks to deployable payloads. We focus on DORA—Deployable Optics for Remote sensing Applications—in the VIS to TIR spectral range, and on a planned application in the MW spectral range, and we carry out a radiometric analysis to verify its performances for Earth Observation studies

A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873