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Molecular testing; Ovarian cancer Proves moleculars; Càncer d'ovaris Pruebas moleculares; Cáncer de ovarios Background The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. Patients and methods Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. Results The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. Conclusions Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation. This work was supported by funding from the AIRC [grant numbers IG 2016 – ID. 18921 and IG 2021 – ID. 25932 projects – P.I. SP and CO-2018-12367051 (Ministero della Salute) P.I SP]; Ricerca Corrente grant M2/7 from Ministero della Salute to DC, Ricerca Corrente from Ministero della Salute to SP. SM is supported by the Italian Association for Cancer Research [grant number IG-2017 n: IG19997]. MITO16A/MaNGO-OV2 trial was partially supported by Roche. AL is a recipient of a grant from the Asociación Española contra el Cáncer (AECC) [grant number INVES20095LLOP]. VS is a recipient of a grant from the Instituto de Salud Carlos III [grant number CPII19/00033] and a European grant for personalized medicine [grant number ERAPERMED 2019-215]. BP is a recipient of a grant from GOIRC. BP was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche. NC has received funding from AstraZeneca (to the institution). FP has received funding from Roche, AstraZeneca, Pfizer, Merck Sharp & Dome, Bayer, Incyte, Taiho Oncology, Janssen Cilag, Exelixis, Aileron, and Daiichi Sankyo (grants to the institution for clinical trial activities).

This paper proposes the combined use of Finite Element Modeling (FEM) and Equivalent Circuit Modeling (ECM) to describe the nonlinear electromechanical and acoustic behavior of a CMUT in an integrated circuit simulation environment. CMUT ECM lumped parameters are computed by FEM simulations. The proposed method is implemented in LTSpice, and validated by comparing ECM and FEM static, small-signal harmonic, and large-signal transient simulation results. The model was then applied to the performance assessment of the CMUT coupled to a realistic integrated transceiver configuration by computing TX efficiency and noise figure. The proposed approach allows accurate large-signal analysis of CMUTs interfaced to ultrasound front-end circuits by considering non-ideal characteristics of the system, such as the pulser nonlinearities.

Aim: Root hydraulic conductivity is one of the main factors that control water flow in the soil-plant system and ultimately affect crop irrigation requirements. This work sets out to estimate root water conductivity for three self-rooted or grafted table grape cultivars.Methods and results: We evaluated root water conductivity of the cultivars ‘Black Magic’, ‘Matilde’ and ‘Victoria’ grafted onto 1103 Paulsen rootstock or self-rooted. Measurements were performed on two-year-old table grapes grown in pots filled with pumice. Root water conductivity was determined by placing the pots in a pressure chamber and increasing pressures from 0.05 to 0.30 MPa, at intervals of 0.05 MPa. Plant growth in terms of shoot and root dry matter was also evaluated, as well as leaf and root area.Conclusion: Root water conductivity differed according to cultivar and grafting. The ‘Victoria’ cultivar had higher root water conductivity than the other two, which differed little between them. The grafted plants showed higher root water conductivity than the self-rooted plants, except the plants of the cultivar ‘Matilde’, whose root water conductivity for the grafted and self-rooted plants was almost the same. It was also observed that the higher root water conductivity in relation to cultivar and grafting changed with increasing water flux and was constant for high water flux.Significance and impact of the study: Estimation of root hydraulic conductivity helps to determine the water consumption of the cultivars investigated, whether self-rooted or grafted, as well as the amount of irrigation water to apply to vineyards.

Modern electrical network control and management architectures are based on the communication among different devices through communication protocols. Some leading features emerge as essential prerequisites for the devices to be effective in their various functions and at the same time to be security compliant. The management of economic transactions is an additional requirement emerged. The article explores the main features required for decentralized technical and economic management based on blockchain.

To avoid leg short-circuit in inverters, dead time must be introduced on leg gate signals. Dead time affects the inverter output voltage fundamental harmonic amplitude, voltage harmonic distortion and inverter efficiency by introducing additional voltage drops. In this regard, dead time effects have been widely investigated for traditional two-level three-phase voltage source inverters in the literature but not extensively for multilevel topology structures. This paper provides a detailed analysis of dead time impact on the harmonic distortion and efficiency of Cascaded H-Bridges Multilevel Inverters (CHBMIs). For this purpose, a general mathematical formulation to determine voltage drop due to dead time effects, also taking into account the adopted Multicarrier PWM strategy, has been provided and experimentally validated for a five-level three-phase CHBMI structure. As a comparison tool between expected and ideal inverter output voltage, the percentage voltage error e% is introduced. In most of the cases, e% is lower than 5%, and it starts increasing for very low amplitude modulation index or for specific working points where nonlinearities occur. Furthermore, several experimental investigations have been carried out to evaluate the CHBMI performance in terms of harmonic distortion and efficiency by changing, the values of dead time, modulation index and switching frequency for ten different multi-carried PWM strategies. Experimental results confirm the strong dependency between the dead time impact on the converter performance and the adopted Multi Carrier-PWM (MC-PWM) strategy: as a way of example, converter efficiency can be reduced from 80% to 60% when dead time is increased from 0.5 μs to 1.5 μs and Phase Shifted-PWM (PS-PWM) is adopted.

Electrical drives fed by Multilevel Inverters (MIs) are of considerable interest for traction and e-mobility applications. In detail, Cascaded H-Bridge Multilevel Inverter (CHBMI) is a promising solution for electrical drive optimization purposes in terms of efficiency, safety, integration and flexible use of energy sources. The aim of this paper is the experimental implementation of the field-oriented control strategy of Interior Permanent Magnet Synchronous Machine (IPMSM) fed by CHBMI by use of NI-SOM sbrRIO-9651 FPGA controller. This FPGA controller can be programmable in the LabVIEW programming environment with the consequent benefits of graphical programming. The paper address the acquisition of mechanical and electrical quantities necessary for closed-loop control, such as speed, position and currents, the development of their condition circuits, the control software implementation and the experimental validation. © 2022 IEEE.

The current climatic scenario requires the use of innovative solutions to increase the production of electricity from renewable energy sources. Multilevel Power Inverters are a promising solution to improve the penetration of renewable energy sources into the electrical grid. Moreover, the performance of MPIs is a function of the modulation strategy employed and of its features (modulation index and switching frequency). This paper presents an extended and experimental analysis of three-phase five-level Cascaded H-Bridges Multilevel Inverter performance in terms of efficiency and harmonic content considering several MC PWM modulation strategies. In detail, the CHBMI performance is analyzed by varying the modulation index and the switching frequency. For control purposes, the NI System On Module sbRIO-9651 control board, a dedicated FPGA-based control board for power electronics and drive applications programmable in the LabVIEW environment, is used. The paper describes the modulation strategies implementation, the test bench set-up, and the experimental investigations carried out. The results obtained in terms of Total Harmonic Distorsion (THD) and efficiency are analyzed, compared, and discussed.

Cascaded H-Bridges Multilevel Inverter (CHBMI) is a fascinating solution for optimization purposes in several application fields. The CHBMI performance optimization can be reached both with hardware and software solutions. In detail, the CHBMI performances are a function of the modulation strategy adopted and its parameters such as modulation index, switching frequency, and dead time. This paper presents performance experimental analysis on dead time effects on CHBMI performance in terms of harmonic distortion and conversion efficiency. In this analysis, two different modulation strategies have been considered and implemented. The paper focuses on modulation strategies implemented, the test bench set-up, experimental investigations, and the results comparative analysis.

Cascaded H-Bridges Multilevel Inverters are an innovative and promising solution in different application fields. This topology allows obtaining an improvement in the performance (e.g. reduced harmonic content, the low voltage stress on power components, and high efficiency) in respect to the traditional two-level inverters. In this context, the Multicarrier-PWM strategies play an important role thanks to their features. This paper presents an experimental investigation on the performance of a three-phase five-level Cascaded H-Bridge inverter by using different PWM modulation strategies. In particular, the paper is focused on the experimental validation of the main features of Multicarrier PWM taken into account by varying the modulation index and the switching frequency.

Neuroendocrine carcinoma (NEC) of the uterine cervix is less characterized than neuroendocrine neoplasms of other sites such as of the digestive system and the lung. Special AT-rich sequence-binding protein 2 (SATB2) recently emerged as a marker of well-differentiated neuroendocrine tumors of the lower gastrointestinal (GI) tract. Among NECs, SATB2 is more frequently expressed in cutaneous Merkel cell carcinoma than in NEC of other anatomical sites. In our study, we performed an immunohistochemical study of SATB2 in 16 NECs of the uterine cervix, where the expression of these markers is still undefined. SATB2 was expressed in 12/16 cervical NECs (75%), with 7/16 cases (44%) showing SATB2 positivity in ≥ 50% of cells. In 7 cervical NECs associated with a non-neuroendocrine component, the expression of SATB2 was restricted to the neuroendocrine component. SATB2 was positive in all cases that expressed CDX2 (n = 7) and TTF1 (n = 5), with no evident association with p16 and p53. Our study demonstrated that SATB2 is often expressed in NECs of the uterine cervix. This information should be taken into account when assessing the origin of a NEC.

Multilevel Power Inverters (MPIs) represent a valid solution to improve the performances of energy production systems from renewable energy sources. Furthermore, the use of novel FPGA control systems allows simplifying the implementation of multicarrier PWM techniques for MPIs with computational benefits. This paper describes the implementation of several multicarrier PWM techniques on NI-SOM sbRIO-9651 for the control of a three-phase five-level cascaded H-bridge inverter. In detail, sbRIO-9651 is a control system in the field of Power Electronics and Drives (PED) programmable in the LabVIEW graphical programming environment. The paper is focused on modulation techniques implementation, testing, and experimental validation.

Introduction In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. Objective To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. Methods Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value Results Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. Conclusion MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.

Item does not contain fulltext BACKGROUND: Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy. METHODS: We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie

Despite some populations show a wide spectrum of different BRCA pathogenic variants (PVs), particular ethnic groups carry at high frequency a single or a few recurrent PVs, usually due to a founder effect. The identification of these founder PVs, with simple molecular methods, improves BRCA1/2 testing and cancer risk assessment. In this study, we developed a rapid and reliable PCR method, coupled with capillary electrophoresis (CE) for genotyping the Italian founder BRCA1 c.4964_4982del19 (rs80359876) variant. In addition, we compared the performance of two CE platforms: (Agilent 2100 Bioanalyzer and the Experion Automated Electrophoresis system) to identify this variant. Our findings suggest that CE represents a simple and standardized diagnostic strategy for the unambiguously identification of the BRCA1 c.4964_4982del19 variant, on both germline and somatic DNA samples. The results and performance obtained by two platforms are absolutely superimposable in terms of specificity and sensitivity, as well as for their feasibility, time of analysis and costs.

The ST18 ˗497-65050 T > C polymorphisms (rs17315309) exhibit a very strong association in the pathogenesis of Pemphigus Vulgaris (PV) and could represent a new potential molecular target for the treatment of disease. The present study aimed to establish a low-cost, sensitive and reliable assay using high-resolution melting curve analysis (HRMA) on magnetic induction rotor-based platform, the Magnetic Induction Cycler (MIC) (Bio molecular Systems). HRMA assay was able to identify easily and unambiguously the c.-497-65050 T > C genotypes evaluating melting curve shape and melting temperature (Tm). The results of HRMA were validated by direct DNA sequencing. The HRMA is rapid, sensitive, low-cost and high-throughput assay to screen the rs17315309 variant and could be used in clinical diagnostic laboratories.

Background Significant alterations of the cutaneous microbiota (CM) have been recently demonstrated in bullous pemphigoid (BP). Microbiome data of both oral cavity (OM) and gut (GM) from patients affected by bullous disease are not available yet and, further consistent studies focused on the role of such microbial populations are still missing. Objective Objective: In this pilot study we characterized and compared GM, OM and CM of patients affected by pemphigus vulgaris (PV) and BP to investigate a distinctive microbiome composition in this two rare dermatological disorders. Methods High-throughput sequencing of the V1-V3 hyper-variable regions of 16S rRNA was used to compare the bacterial community composition of stool, skin and oral mucosae swabs in a cohort of PV and BP patients. A dedicated bioinformatics software coupled with in-house pipeline was implemented to analyse and compare diseases dataset. Results GM samples of both PV and BP patients were principally characterized by Firmicutes and Bacteroidetes phyla. Interestingly, the Firmicutes phylum and Staphylococcus genus were mainly represented in cutaneous samples. The diversity of phyla in oral mucosae was higher than those of gut and skin samples and, Bacteroidetes phylum was significantly underrepresented in all PV samples. Conclusion Firmicutes phylum and Staphilococcus genus were the most represented in OM and CM swabs of PV and BP microbial populations. Moreover, we argue the quantitative imbalance linked to the decrease of Bacteriodetes in the oral cavity of PV patients might be associated to disease typical fetor. To shed light on this peculiar feature further studies are still required.

Introduction Loss-of-function mutations in cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene are associated with Idiopathic Infantile Hypercalcemia (IIH) and adult kidney stone disease. The enzyme deficiency leads to an impaired vitamin D catabolism pathway, resulting in a syndrome characterized by recurrent hypercalcemia, hypercalciuria and suppressed parathyroid hormone (PTH) levels. In these patients, the genetic evaluation of CYP24A1 is an important diagnostic tool, allowing the definitive diagnosis of IIH. Methods A rapid CYP24A1 gene testing based on High Resolution Melting Analysis (HRMA) was designed in order to detect the CYP24A1 c.428_430delAAG (p.Glu143del), a recurrent IIH-associated variant. Results HRMA method was able to identify c.428_430delAAG genotypes evaluating melting curve shape and melting temperature (Tm). Heterozygous samples exhibited a typical melting profile while homozygous samples showed a specific Tm shift. Conclusions We provide evidence about application of HRMA in unambiguous genotyping of the CYP24A1 c.428_430delAAG variant, making this method useful in clinical molecular diagnostics. This approach opens the way to a helpful molecular analysis of CYP24A1 gene in IIH diagnosis, to an improved pharmacological treatment strategy and to a reduced risk of recurrent stones and worsening nephrocalcinosis.

BRCA1/2 screening in Hereditary Breast and Ovarian Syndrome (HBOC) is an essential step for effective patients’ management. Next-Generation Sequencing (NGS) can rapidly provide high throughput and reliable information about the qualitative and quantitative status of tumor-associated genes. Straightforwardly, bioinformatics methods play a key role in molecular diagnostics pipelines. BRCA1/2 genes were evaluated with our NGS workflow, coupled with Multiplex Amplicon Quantification (MAQ) and Multiplex Ligation-dependent Probe Amplification (MLPA) assays. Variant calling was performed on Amplicon Suite, while Copy Number Variant (CNV) prediction by in house and commercial CNV tools, before confirmatory MAQ/MLPA testing. The germline profile of BRCA genes revealed a unique HBOC pattern. Although variant calling analysis pinpointed heterozygote and homozygote polymorphisms on BRCA1 and BRCA2, respectively, the CNV predicted by our script suggested two conflicting interpretations: BRCA1 duplication and/or BRCA2 deletion. Our commercial software reported a BRCA1 duplication, in contrast with variant calling results. Finally, the MAQ/MLPA assays assessed a whole BRCA2 copy loss. In silico CNV analysis is a time and cost-saving procedure to powerfully identify possible Large Rearrangements using robust and efficient NGS pipelines. Our layout shows as bioinformatics algorithms alone cannot completely and correctly identify whole BRCA1/2 deletions/duplications. In particular, the complete deletion of an entire gene, like in our case, cannot be solved without alternative strategies as MLPA/MAQ. These findings support the crucial role of bioinformatics in deciphering pitfalls within NGS data analysis.

Il contributo si sofferma, nella prima parte, sulla valorizzazione del patrimonio cartografico storico della valle dell’Amaseno (situata tra le province di Latina e Frosinone nella Regione Lazio) attraverso un archivio digitale realizzato con l’ausilio delle nuove tecnologie di informazione geografica al fine di permettere una razionale fruizione e gestione della documentazione storica in maniera strutturata e interattiva. Nello specifico il progetto è finalizzato a censire, digitalizzare, Georeferenziare e decodificare il materiale cartografico storico alla luce del differente contesto politico, socio-economico e culturale che ha influenzato la produzione cartografica, garantendo la creazione di un catalogo informatizzato in grado di gestire informazioni complesse. La seconda parte si concentra sulla rappresentazione del confine attraverso la fonte cartografica storica, uno strumento che permette di comprendere e analizzare la complessità culturale dei territori attraverso un’ottica diacronica e al tempo stesso sincronica, volta alla ricostruzione dei processi storico-territoriali di lungo periodo.

Il dibattito storiografico degli ultimi anni ha spesso avuto quale oggetto la costruzione della frontiera mediterranea, in una prospettiva multidisciplinare e di lunga durata. Le dinamiche che regolamentano il passaggio o il controllo della frontiera sono infatti tutt’ora al centro delle politiche europee sulla gestione dei flussi migratori, e la Sicilia – oggi come in passato – è indubbiamente una delle aree geografiche più esposte e maggiormente coinvolte dal fenomeno. All’inizio del XVI secolo alcuni cambiamenti politici posero l’isola al centro di una fortissima pressione militare. Se già Alla fine del Trecento era diventato sempre più gravoso fronteggiare le scorrerie della pirateria, fu indubbiamente a partire dalla seconda metà del secolo successivo - e in particolar modo a seguito dell’avanzato degli Ottomani nell’area occidentale del Mediterraneo – che si dovette investire in termini umani e materiali nella costruzione di una frontiera capace di arginare le minacce di possibili incursioni nemiche. La necessità di contrastare gli attacchi provenienti tanto dal levante, quanto dai centri nordafricani, diede avvio alla progettazione e alla realizzazione di un sistema di architettura bastionata per sostituire le ormai fatiscenti difese medievali, notevolmente insufficienti dinanzi all’emergere di un nuovo modo di far la guerra. La presente proposta, lungi dal voler aggiungere consistenza ai risultati finora acquisiti sull’argomento, si prefigge di valorizzarne gli aspetti salienti impiegando strumenti e prospettive peculiari del digitale. Rivedere sotto quest’ottica la «pianura liquida», com’è stata talvolta definita la frontiera mediterranea, offre la possibilità di creare un modello per migliorare la nostra comprensione della Sicilia come base strategica indispensabile per garantirsi il collegamento/controllo di chilometri di terra e di mare. Il modello sarà costruito mediante l’analisi di grandi quantitativi di dati facilmente desumibili dalla mole di scritti già prodotti su quest’argomento e nella successiva trasposizione in un database; sarà possibile estrarre i dati con un algoritmo scelto, attraverso l’uso del data mining - ossia la possibilità di utilizzare tecniche per eseguire un’analisi matematica sul database. Per una migliore rappresentazione grafica dei risultati ottenuti verrà simulato il modello all’interno di carte geografiche sfruttando la tecnologia GIS; a questo proposito il database dovrà essere implementato dalla geo-localizzazione di alcuni oggetti al suo interno

In the last decade, high-density olive planting systems have been developed to facilitate less costly mechanical harvesting and pruning by using straddle harvesters. High-density orchards allow faster production since the first crop of fruit starts a few years after planting. In high-density orchards the control of tree size is essential. It is possible to control the vigour and size of the tree by selecting suitable cultivars, by choosing rootstocks capable of controlling scion vigour and, finally, by applying deficit irrigation to reduce plant vegetative growth. Knowledge of tree water requirements is needed for precise irrigation scheduling. In this study, the dwarfing capacity of two Leccino clones, Leccino Dwarf (LD) showing low vigour, and Leccino Minerva (LM) highly vigorous, was investigated under two water regimens, well-watered ( T 100 ) and water deficit ( T 50 ). We analysed growth rates, dry matter production, gas exchanges and water relations of one-year-old plants of Leccino Dwarf (LD) and Leccino Minerva (LM), grown in pots in open fields. The two genotypes showed significant differences in vigour, demonstrated by measuring the trunk diameter, shoot length and leaf area; values were significantly lower in clone LD. Stem water potential, photosynthesis and stomatal conductance were similar in both genotypes under a well-watered regime; they decreased when subjected to water deficit with values significantly lower in LM clone during the summer months, indicating physiological differences among clones and that LD adapts better to water deficit.

OBJECTIVE: In active ulcerative colitis (UC), magnetic resonance imaging (MRI) with ferumoxil, a superparamagnetic oral contrast agent, accurately evaluates, in our experience, the increased wall thickness and frequently shows a stronger perivisceral fat signal intensity (PFSI). The aim of our study was to evaluate the clinical significance of these MRI findings in active UC. METHODS: Twenty-four consecutive patients affected by moderate pancolitis were enrolled. At entry, each patient underwent MRI with ferumoxil to evaluate wall thickness and PFSI. Two groups of patients were individuated: group A (increased PFSI) and group B (normal PFSI). After obtaining remission, the number of relapses and, at each flare-up, the clinical activity index (CAI) were evaluated in all patients in a 2-yr follow-up period. The mean CAI was calculated at the end of the follow-up in each patient. Where there was colectomy, a complete histological examination of the colon was performed. RESULTS: PFSI was increased in 16 patients (group A) and was normal in the remainder (group B). There was a significant difference of wall thickness, number of relapses/yr, and mean CAI between the two groups of patients. No difference was observed with regard the duration of disease. Six patients of group A and no patient of group B underwent colectomy. The histological evaluation showed an increased thickness of the entire colonic wall with significant changes of the perivisceral fat structures. CONCLUSIONS: An increased PFSI on MRI identifies a group of UC patients with an increased wall thickness, significantly higher than that observed in patients with normal PFSI and seems to be related to a poor prognosis.

OBJECTIVE: The introduction of new oral contrast agents that enhance image quality has increased the importance of magnetic resonance imaging (MRI) in the management of ulcerative colitis. The aim of our study was to investigate the usefulness of a new negative superparamagnetic oral contrast (ferumoxil) alone or in association with gadolinium i.v. in the assessment of the disease. METHODS: Twenty-eight patients with clinically active ulcerative colitis and 10 control subjects entered the study. In each patient a clinical, endoscopic, histological, and MRI evaluation was performed. In particular, in 14 patients affected by ulcerative colitis (group A) and in five controls, magnetic resonance images were acquired 1 h after the oral administration of 900 ml of ferumoxil, while the remaining 14 patients (group B) and five controls were submitted to double-contrast MRI (ferumoxil and gadolinium). In both groups, wall thickness, length of affected bowel segments, and, in group B, also percent contrast enhancement were calculated. RESULTS: The comparison of endoscopic and MRI extent of disease was statistically significant. Wall thickness and, in group B, also percent contrast enhancement were significantly correlated with clinical and endoscopic activities. In each group wall thickness was significantly different in the activity phases of the disease. CONCLUSIONS: MRI with negative superparamagnetic oral contrast is comparable to endoscopy in the assessment of ulcerative colitis. The double-contrast imaging does not provide more information than single oral contrast, so we concluded that the latter is preferable in the follow-up of the disease and in patients unable or with a poor compliance to undergo endoscopy.

The identification of cirrhotic patients with low life expectancy is an open clinical problem. Hypocholesterolemia is frequently found in severe chronic hepatic insufficiency because the liver is the most active site of cholesterol metabolism, but poor information is available on its precise prognostic value. We evaluated the prognostic role of hypocholesterolemia in patients with advanced liver cirrhosis.Serial serum cholesterol concentrations of 34 patients with virus-induced cirrhosis, from the first appearance of Child-Pugh class C to death, were considered. To compare survival functions, we established three base-line cholesterol cut-off points (150, 125, and 100 mg/dl) and stratified patients into groups A and B, with base-line cholesterol levels lower and higher than each cut-off value, respectively.Cholesterolemia decreased progressively in all patients. At the 100 mg/dl cut-off point all group-A patients died within 17 months, whereas 75% of group-B patients were alive at 24 months (P0.0001). Moreover, cholesterolemia was significantly correlated with cholinesterase, indirect bilirubin, and total bilirubin at entry time and immediately before death. No correlation was observed between cholesterol and these variables when stratified for the Child-Pugh score.Base-line serum cholesterol levels lower than 100 mg/dl identify a subgroup of Child-C cirrhotic patients with high mortality risk within a 2-year follow-up. The prognostic importance of cholesterolemia may also be deduced by the significant correlation with other well-established indicators of survival.

Aims: Tests were carried out to assess the effects of early defoliation, cluster thinning and cluster cutting on the basic and nutritional composition of musts and wines of Vitis vinifera L. cv. Montepulciano.Methods and results: Both production and quality variables of the musts were evaluated. Antioxidant activity was determined on berries and on wines, as were the phenol and anthocyanin concentrations. The wines were compared by sensory evaluation. The results attested to a positive effect of the treatments on grape composition and on antioxidant activity in the berries.Conclusions: The tested treatments (DP = early defoliation; D3 = cluster thinning 30 %; D5 = cluster thinning 50 %; T3 = cluster cutting 30 %; T5 = cluster cutting 50%) increased both the soluble solids and the pH of the musts and enhanced the nutritional quality (based on antioxidant concentration) of both the grapes and the wine.Significance and impact of the study: The adopted techniques may be useful in cases in which yield control is required and/or the composition of the musts and wines needs to be modified based on the concentration of sugars in the berries. However, the variable response of the vines to the various techniques suggests that each cultural practice be evaluated in relation to specific oenological objectives.

Aims: To investigate the petroleum hydrocarbon (HC)-degrading potential of indigenous micro-organisms in a sandy Mediterranean coast, accidentally contaminated with petroleum-derived HCs. Methods and Results: Using culturable methods, a population of Gram-positive n-alkane degraders was detected in the contaminated soil. Five isolates, identified as one Nocardia, two Rhodococcus and two Gordonia strains, were able to degrade medium- and long-chain n-alkanes up to C36 as assessed by growth assays and gas chromatography-mass spectrometry analysis. Diverging alkane hydroxylase-encoding genes (alkB) were detected by PCR, using degenerated primers, in all the strains; multiple sequences were obtained from the Nocardia strain, while only one alkB gene was detected in the Rhodococcus and Gordonia strains. The majority of the alkB sequences were related to Rhodococcus alkB2, but none was identical to it. Conclusions: Actinomycetes might have a key role in bioremediation of n-alkane-contaminated sites under dry, resource-limited conditions, such as those found in the Mediterranean shorelines. Significance and Impact of the Study: To our knowledge, this is the first study on the bioremediation potential in Mediterranean contaminated beaches.

Background & Aims: The endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) inhibit cancer cell proliferation by acting at cannabinoid receptors (CBRs). We studied (1) the levels of endocannabinoids, cannabinoid CB 1 and CB 2 receptors, and fatty acid amide hydrolase (FAAH, which catalyzes endocannabinoid hydrolysis) in colorectal carcinomas (CRC), adenomatous polyps, and neighboring healthy mucosa; and (2) the effects of endocannabinoids, and of inhibitors of their inactivation, on human CRC cell proliferation. Methods: Tissues were obtained from 21 patients by biopsy during colonoscopy. Endocannabinoids were measured by liquid chromatography-mass spectrometry (LC-MS). CB 1 , CB 2 , and FAAH expression were analyzed by RT-PCR and Western immunoblotting. CRC cell lines (CaCo-2 and DLD-1) were used to test antiproliferative effects. Results: All tissues and cells analyzed contain anandamide, 2-AG, CBRs, and FAAH. The levels of the endocannabinoids are 3- and 2-fold higher in adenomas and CRCs than normal mucosa. Anandamide, 2-AG, and the CBR agonist HU-210 potently inhibit CaCo-2 cell proliferation. This effect is blocked by the CB 1 antagonist SR141716A, but not by the CB 2 antagonist SR144528, and is mimicked by CB 1 -selective, but not CB 2 -selective, agonists. In DLD-1 cells, both CB 1 and CB 2 receptors mediate inhibition of proliferation. Inhibitors of endocannabinoid inactivation enhance CaCo-2 cell endocannabinoid levels and block cell proliferation, this effect being antagonized by SR141716A. CaCo-2 cell differentiation into noninvasive cells results in increased FAAH expression, lower endocannabinoid levels, and no responsiveness to cannabinoids. Conclusions: Endocannabinoid levels are enhanced in transformed colon mucosa cells possibly to counteract proliferation via CBRs. Inhibitors of endocannabinoid inactivation may prove useful anticancer agents.

Aims: The molecular diversity of 25 strains of rhizobia, isolated in Sicily from root nodules of the Mediterranean shrubby legume Spanish broom (Spartium junceum L.), is presented in relation to the known rhizobial reference strains. Methods and Results: Our approach to the study of the S. junceum rhizobial diversity combined the information given by the 16S and the intergenic spacer (IGS) 16S–23S rDNA polymorphic region by obtaining them in a single polymerase chain reaction (PCR) step. The PCR fragment size of the S. junceum isolates was 2400–2500 bp and that of the reference strains varied from 2400 in Bradyrhizobium strains to 2800 in Sinorhizobium strains. Inter- and intrageneric length variability was found among the reference strains. Restriction fragment length polymorphisms (RFLP) analysis allowed us to identify eight genotypes among the S. junceum rhizobia that were clustered into two groups, both related to the Bradyrhizobium lineage. Sequencing of representative strains of the two clusters confirmed these data. The 16S–IGS PCR–RFLP approach, when applied to rhizobial reference strains, allowed very close species (i.e. Rhizobium leguminosarum/R. tropici) to be separated with any of the three enzymes used; however, cluster analysis revealed inconsistencies with the 16S-based phylogenesis of rhizobia. Conclusions: Rhizobia nodulating S. junceum in the Mediterranean region belong to the Bradyrhizobium lineage. Our results confirm the resolution power of the 16S–23S rDNA in distinguishing among rhizobia genera and species, as well as the usefulness of the PCR–RFLP method applied to the entire 16S–IGS region for a rapid tracking of the known relatives of new isolates. Significance and Impact of the Study: The present paper is, to our knowledge, the first report on rhizobia nodulating a Mediterranean wild woody legume.

Data on allergy in ulcerative colitis (UC) have led to conflicting conclusions without proving any causal association. In this report we have investigated the presence of allergy and its possible relation with chronic colonic inflammation in patients with UC.Fifty UC patients underwent clinical, endoscopic, and histologic evaluations. The allergologic study included family/personal history; prick/patch exposition to airborne, food, and contact allergens; total serum IgE; and quantification of eosinophils in peripheral blood and intestinal mucosa. Diagnosis of rhinitis, conjunctivitis, and asthma was confirmed by specific provocation tests. Fifty healthy subjects were studied as control group.A higher prevalence of allergic symptoms was found in patients (56%) and their first-degree relatives (52%) than in controls (18% and 26%) (P0.0001; P = 0.008). In patients skin tests showed increased rates of immediate (54%) and delayed-type (20%) hypersensitivity compared with controls (30% and 6%) (P= 0.01; P= 0.03). Diagnosis of allergic IgE-mediated disease was made in 19 cases and 6 controls (P= 0.01), and allergic contact dermatitis in 10 and 3, respectively (P= 0.03). IgE levels were higher in UC patients than in controls (P=0.02). No dose-response relationship was found between degree of colonic tissue eosinophilia and clinical. endoscopic, and histologic disease severity. The degree of colonic tissue eosinophilia was higher in the presence of skin reactivity to food allergens.UC patients frequently show several markers of allergy. In particular, our data suggest an association between ulcerative colitis, tissue eosinophilia, and type-I allergy.

The study correlated reslts of spleen size measurement performed on the planar spleen scintigraphy performed with 99mTc- Sulphur (Re) Coll