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Summary Background The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the composition of the gut microbiome has been correlated to prognosis and evolution of advanced melanoma and proposed as a biomarker for immune checkpoint therapy. Objectives We investigated the gut fungal and bacterial compositions in early-stage melanoma and correlated microbial profiles with histopathological features. Methods Sequencing of bacterial 16S rRNA and the fungal internal transcribed spacer region was performed on faecal samples of patients with stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from patients with metastatic melanoma was also carried out. Results We found a combination of gut fungal and bacterial profiles significantly discriminating patients with melanoma from controls. In patients with melanoma, we observed an abundance of Prevotella copri and yeasts belonging to the order Saccharomycetales. We found that the bacterial and fungal community correlated to melanoma invasiveness, whereas the specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial communities in patients with stage I and II melanoma were different in structure and richer than those from patients with metastatic melanoma. Conclusions The composition of the gut microbiota in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced-stage melanoma, through direct or indirect immunomodulation.

Background Triage is the crucial point for overall emergency department (ED) management. Its purpose is to quickly and safely identify among the many patients arriving those who need rapid medical evaluation [1]. Present triage systems are based on symptomatic assessment and clinical impression to assess patient severity on admission to the ED. Some clinical tools that are widely validated in practice, such as ECG, could be implemented in triage to improve the stratification activity of the system [2]. Purpose To evaluate whether the use of ECG can improve nursing triage prediction for patients admitted to the ED for symptoms related to suspected cardiac pathology. Methods A prospective observational single-centered study was conducted. All patients who visited the ED for chest pain, syncope, dyspnoea or palpitation and underwent ECG at the time of triage were considered. The study was conducted by a pool of nurses who had previously received special training in ECG reading. Background characteristics, comorbidities and clinical conditions were recorded for each enrolled patient. In addition, the priority level assigned according to the application of the 5-level Manchester Triage System (1 to 5) and the level of priority after ECG performance (1 to 5) were recorded. The study outcome was composite: the presence of a major cardiac event within 6 weeks after triage, a cardiogenic syncope, the presence of a pulmonary embolism or aortic dissection, or an arrhythmia requiring specific emergency therapy [3]. The priority level assigned in triage and the priority level given after performing the ECG were compared by analysis of the receiver operating characteristic. Results A total of 1,211 patients were included in the study. Of these, 62.4% (756/1,211) presented chest pain, 13.8% (167/1,211) syncope, 18.2% (221/1,211) palpitation and 5.5% (67/1,211) dyspnoea. Overall, 10.5% (127/1,211) had a positive outcome. The concordance between triage nurses and cardiologists in detecting pathological and non-pathological ECGs presented a Cohen's kappa of 0.821 (p Conclusions The use of ECG in triage can be a simple and safe tool that improves the assessment of the patient's priority when presenting to the ED for a cardiac symptom. The presence of a good diagnostic concordance and a good improvement in discriminatory ability may support the implementation of ECG in nursing triage. Funding Acknowledgement Type of funding sources: None.

We report the use of microfluidics to functionalize suspended reduced graphene oxide flakes through the addition of aryl radical, generated in situ by reaction between aryl amines and isopentyl nitrite. Microfluidic enabled a tight control of temperature, reaction times and stoichiometric ratios, making it possible to tune the growth of oligomers on the surface of the flakes, which in turn affects the interactions of the functional material with the surrounding environment. The results suggest that shear stress phenomena within the reactor may play a role in the chemistry of graphene materials, by providing a constant driving force towards exfoliation of the layered structures. Scale up of the functionalization process is also reported, along with the grafting of dyes based on squaric acid cores. Photophysical characterization of the dye-modified flakes proves that the microfluidic approach is a viable method towards the development of new materials with tailored properties.

Due to the increasingly widespread diffusion of lasers in many scientific and technological fields, the engineering and the fabrication of systems able to protect either human eyes or delicate equipment from laser radiation damage is nowadays attracting lots of interest in the scientific community. In this work, the optical limiting properties of fulleropyrrolidine, gold nanoparticles and hybrid systems in solution and in a polycarbonate matrix are investigated using a continuous wave laser at 514 nm, by optical limiting, Z-scan and temporal response measurements. The comparison of the results, obtained with different techniques, has allowed us to show that thermal effects account for most of the nonlinear response in gold nanoparticles and in the hybrid system; moreover, the latter exhibits a lower nonlinear threshold and a faster response compared to the former. This paper provides a contribution to the engineering of efficient protection devices in the continuous wave regime.

Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn’s Disease. In previous studies, we have shown that Nod2−/− mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3− regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2−/− mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3− cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3− proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms.

Metal-free stereoselective additions of activated nucleophiles to s-nitrostyrenes were investigated under continuous-flow conditions in microreactors, in the presence of a chiral bifunctional catalyst. Optimization of the experimental setup gave excellent enantioselectivities (up to 85% e.e.) and higher productivities if compared to the flask syntheses. The potential of this flow chemistry approach was demonstrated by the successful synthesis of an advanced intermediate for the preparation of the GABAB receptor agonist Baclofen.

Through a cycloaddition reaction, fullerene (C60) was derivatized with a novel organic compound 5‐(benzo[b]thiophen‐3‐yl)pyridine‐3‐carbaldehyde to form the processable and stable 3‐(benzo[b]thiophene‐3yl)‐5‐fullero‐1‐methylpyrrolidinepyridine (BTFP) compound. BTFP exhibits close similarities to phenyl‐C61‐butyric‐acid‐methyl‐ester (PCBM) in terms of first reduction potential values (−0.62 and −0.61 V vs. Ag/AgCl, for BTFP and PCBM, respectively) and lowest occupied molecular orbital (LUMO) energy level values (3.93 eV in both cases). In chloroform, BTFP exhibits a bathochromic shift in the λ max of BTFP (λ max,BTFP=290 nm and λ max,PCBM=260 nm), owing to the grafted benzo[b]thiophene‐3‐yl)pyridine moiety. Despite the similarity in LUMO (3.93 eV) energy values, BTFP and PCBM differ in their luminescence‐quenching ability. The bathochromic shift in the λ max of BTFP (relative to PCMB) is likely to contribute to improved light absorption of a suitable donor for photovoltaic applications.

Background Plant seeds possess a complex microbiota which may play a crucial rolein a plethora of mechanisms, such as preservation, germination, seedling development, plant growth and health. In particular, seed endophytic microbiota is gaining more and more consideration due to the fact that it may be vertically transmitted to ensure individual competitive advantages. The Citrusspecies, including C.limon,areone of the most economically important evergreen fruit crops in the world. Objectives i)Identification and characterization ofmicrobial isolates from Citrus limon L. Burm. F. seed endosphere. ii) Structure of Citrus limon L. Burm. F. seed endosphytic microbiota. Methods -Surface-sterilization of Citrus limon L. Burm. F. seeds. - Strain isolation and phylogenetic characterization by 16S rDNA sequence. - Next Generation Sequence Technology analysis (NGS) of metagenomic DNA by pyrosequencing of 16S rDNA. - Fluorescence In Situ Hybridization coupled with Confocal Laser Scanning Microscopy (FISH-CLSM). Conclusions Culture-dependent analysis allowed the isolation of several Staphylococcus spp. and fungi belonging to genera Aspergillus, Quambalaria and Efibula from surface-sterilized seeds. These results weresupported by the detection of bacterial cells and micro–colonies in seed cryosections by FISH-CLSM. In fact, this finding highlighted the presence of Firmicutes and other bacteria colonizing intercellular spaces. NGS-basedcharacterization using metagenomic DNA from surface-sterilized seeds is being carried out in order to elucidatethe microbiota structure. Culture-dependent approaches allowed the isolation of several bacterial strains belonging to the genus Staphylococcus and several fungal strains belonging to the genera Aspergillus, Quambalaria and Efibulafrom seed endosphere. These results were supported by the detection of bacterial cells and micro–colonies in seed cryosections by FISH-CLSM. In particular, this analysis highlighted the presence of Firmicutes and other bacteria colonizing intercellular spaces. NGS-based characterization using metagenomic DNA from surface-sterilized seeds is being carried out in order to elucidate the microbiota structure.

The synthesis of a new class of robust squaraine dyes, colloquially named 1,2-hemisquarimines (1,2-HSQiMs), through the microwave-assisted condensation of aniline derivatives with the 1,2-squaraine core is reported. In CH3CN, 1,2-HSQiMs show a broad absorption band with a high extinction coefficient and a maximum at around λ=530 nm, as well as an emission band centered at about λ=574 nm, that are pH dependent. Protonation of the imine nitrogen causes a redshift of both absorption and emission maxima, with a concomitant increase in the lifetime of the emitting excited state. Encapsulation of the chromophore into a cucurbit[7]uril host revealed fluorescence enhancement and increased photostability in water. The redox characteristics of 1,2-HSQiMs indicate that charge injection into TiO2 is possible; this opens up promising perspectives for their use as photosensitizers for solar energy conversion.

The study of the microbiota is a subject of considerable and growing interest since it is drawing new important perspectives in the life sciences concerning the functional relationships between metazoans and microbial cells. In fact, it has already shown that the endogenous microbial community affects various physiological activities of multicellular organisms. The coelomic cavity of echinoderms contains a fluid in which coelomocytes are reported to exert immune functions like phagocytosis, opsonization and production of antimicrobial agents against marine bacteria [1, 2]. However, up to day nothing is known about the endogenous bacterial population of coelomic fluid. We focused on this issue, and, to this aim, both bacterial culture-dependent and –independent approaches were adopted. By the former approach, we isolated 8 distinct Gram-negative marine bacterial strains identified for their 16S rDNA sequence. Interestingly, almost all isolated strains show a considerable extracellular hydrolytic activity. Moreover, one of them exerts antimicrobial effect against Gram-negative bacteria, including most of the other strains isolated from the coelomic fluid. Finally, molecular investigation on metagenomic DNA composition is currently ongoing using Next Generation Sequence Technology. This study not only suggests insights on functional interaction between sea urchin and marine microorganisms, but also could provide a novel source of biochemical diversity for the production of bioactive compounds and enzymes that can find biotechnological applications. 1. Remziye Deveci et al. (2015). Journal of Morphology 276(5):583-8 2. Stabili L et al. (1996). Comp Biochem Physiol B Biochem Mol Biol 113(3):639-44

The most invalidating and life-threatening complication in Hirschsprung’s disease patients (HSCR) is Hirschsprung’s disease-associated enterocolitis (HAEC). The mechanisms underlying enterocolitis have not been identified. The limited knowledge of the role of intestinal microflora is in part due to the complexity of the intestinal microbiome and to the limitation of cultivation-based technologies, given that less than 25% of the intestinal bacterial species can be cultured. We used amplified ribosomal DNA restriction analysis (ARDRA) with four different restriction enzymes to study variations of microflora composition of the stools of a selected HSCR patient in different clinical conditions (acute phase vs. remission). We assessed a total of 15 stool specimens belonging to the same 3-year-old male patient suffering from HSCR, which were harvested during 4 HAEC episodes and remission phases. Restriction analysis showed that HAEC episodes seem to cluster together at ARDRA analysis, thus suggesting a sort of predisposing bacterial community for HAEC development and the need for a microflora equilibrium to maintain wellness. This approach proved to be effective, useful and powerful in assessing microflora dynamics and indicated that the differences in microflora associated with acute HAEC or remission are likely to result from a combination of disease activity and different antibiotic therapies. ARDRA proved to be useful in discriminating disease versus remission. Our findings indicated that HAEC results from a change in the equilibrium between bacterial species or from altered discrimination of harmless from harmful microorganisms, challenging the definition of pathogenic and non-pathogenic species. Based on these results, we propose ARDRA as a rapid inexpensive tool to assess microflora dynamics during HAEC episodes.

In the attempt to improve optical limiting of cw lasers by exploiting the thermo-optic effect exhibited by gold nanostructures, we investigated two coupled systems consisting of either gold nanoparticles (AuNPs) or gold-silica core-shell (AuNSs), both functionalized with a thiolated-fulleropyrrolidine (C 60 Py). We measured the optical limiting behavior under cw illumination at 514 and 647 nm, resonant with the surface plasmon resonance at around 520 of AuNPs and at 650 nm of AuNSs, respectively. Temporal response analysis shows the variation of transmitted irradiance in a 300 milliseconds time interval, corresponding to the blinking time of the human eye. Comparing the present results we those previously obtained for AuNPs1 we demonstrate an improvement of the response of functionalized nanoparticles (AuNPs- C 60 Py) with respect to bare AuNPs.

For this study we consulted the Bone Marrow Donors' Registry of Lombardy (Italy) and analyzed 43937 HLA-A,B phenotypes and 13922 HLA-A,B,DR phenotypes. We estimated the HLA-A,B and HLA-A,B,DR haplotype frequencies via the maximum-likelihood method. We analyzed the genetic structure of the 11 provinces of Lombardy by means of Principal Component Analysis and Correspondence Analysis, and estimated the variety of the different haplotypes at provincial level and the percentage of unique phenotypes at village level. We found 11189 different HLA-A,B phenotypes, 661 different HLA-A,B haplotypes and more than 4000 different HLA-A,B,DR haplotypes. We identified 20 villages, in Western Lombardy, very rich in unique/rare phenotypes. Here we report a formula which allows the identification of a putative donor matched for two haplotypes with a recipient. This result may be of great importance for the genetic study of the population of Lombardy and, even more, for bone marrow transplantation programs.

The antioxidant and pro-oxidant capacity of catecholamines (CA) and related compounds were analyzed using the oxygen radical absorbance capacity (ORAC) assay. In the assay 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH), a peroxyl radical generator, ROO*; H2O2-Cu2+, mainly a hydroxyl radical generator, *OH; and Cu2+ a transition metal were used. The antioxidant effect of CA and its related compounds were in the order: neurotransmitters: dopamine (DA), norepinephrine (NE) > metabolites > amino acid precursors as measured by using AAPH. The antioxidant effect of CA and related compounds as measured by using AAPH were linearly correlated with concentration, while the antioxidant effect of CA in scavenging *OH produced by H2O2-Cu2+ increased proportionally to concentration at low concentration, but after reaching a maximum declined with increasing concentration. In the presence of Cu2+, CA acted as pro-oxidant. Glutathione (GSH) acted as a pro-oxidant when H2O2-Cu2+ or when Cu2+ alone was used as an oxidant and showed much higher pro-oxidant effect than DA, which could have relevance in the vulnerability of dopaminergic neurons to oxidative stress in the aging and aging related diseases. The antioxidant capacity of CA and many related compounds seems to be correlated with the numbers of hydroxyl groups and their position on the benzoic ring. The O-methylation and sulfate conjugation of the hydroxyl substitution inactivates both the antioxidant and pro-oxidant activities of CA. Our results show that oxidative stress induced by low (5 microM) or high (300 microM) doses H2O2 in pheochromocytoma PC12 cells significantly up-regulate the activity of Mg-dependent neutral sphingomyelinase (Sase), and significantly decreased GSH.

The effect of black tea polyphenols on 1,2-dimethylhydrazine (DMH)-induced oxidative DNA damage in rat colon mucosa has been investigated. Fischer 344 rats were treated orally with thearubigin (TR) or theafulvin (TFu) for 10 days (40 mg/kg), injected ip with DMH (20 mg/kg) or saline and sacrificed 24 hr after DMH administration. The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured in colonic mucosa DNA and expressed as a ratio relative to 2'-deoxyguanosine (2dG). Control rat mucosa had 8-OHdG values of 1.12 +/- 0.14/10(5) dG (mean +/- SEM, n=11), whereas DMH-treated rats significantly higher values (1.52 +/- 0.14/10(5) dG, n=26, P0.05). Pretreatment of rats with TR had significantly inhibited DMH-induced oxidative DNA damage 0.99 +/- 0.09/10(5) dG, n=10, P0.05) and a similar, although less marked, effect was observed with TFu (1.15 +/- 0.19/10(5), n=9, P=0.06). These findings confirm that DMH causes oxidative DNA damage in the colon mucosa of rats and demonstrate that this effect is prevented by the consumption of complex polyphenols from black tea.

We investigated in the rat the role of the Apc gene, which is mutated in familial adenomatous polyposis and sporadic colon cancer in the process leading from normal colonic mucosa to aberrant crypt foci (ACF) and finally to adenomas and adenocarcinomas. We analysed mutations in exon 15 of the rat Apc gene using in vitro synthesized protein assay in 66 ACF and in 28 colon tumours induced by azoxymethane. No Apc mutations were found in ACF, whereas five mutations were found in the tumours. The data suggest that mutations of the Apc gene are associated with the transition from ACF to adenoma and adenocarcinoma and not from normal mucosa to ACF.

Contains fulltext : 88878.pdf (Publisher’s version ) (Closed access) In this study, we present evidence of differential Th17 responses in human monocyte-derived dendritic cells exposed to the pathogenic Candida albicans or the nonpathogenic Saccharomyces cerevisiae. We use different forms of the microorganisms, cells, hyphae, and spores, as a toolbox to dissect the role of surface mannan in the fungal immune response. In contrast to the S. cerevisiae yeast cell-induced Th1 response, dendritic cells stimulated with spores or C. albicans hyphae induce cellular responses shifted toward Th17 differentiation. The differential recognition of specific mannan structures is the master regulator of the discrimination between harmful and harmless fungi. The switch between spores and yeast is crucial for the commensalism of S. cerevisiae and depends on the use of a different receptor repertoire. Understanding the role of cell wall recognition during infection might lead to understanding the boundaries between safety and pathogenicity.

A 49-year-old operated for aortic coartaction patient presented with thoracic and ascending aortic aneurysm. He was asymptomatic. Angio-magnetic resonance nuclear scan and angiography revealed an ascending aortic aneurysm (5.2 cm), bicuspid aortic valve, 6-cm proximal descending aortic pseudoaneurysm at the site of the previous operation with involvement of the left subclavian artery. Restenosis at the original site of coarctation and aortic arch hypoplasia distally to the brachiocefalic trunk was also found. The operation performed was a "modified Bentall - De Bono". The pseudoaneurysm was not accessible through median sternotomy due to the massive lung adhesions following the previous surgery. The left common carotid artery was explanted from the aortic arch and connected with a graft to the ascending aortic conduit. A proximal neck suitable for landing zone of the endovascular stent-graft was then established. The postoperative course was uneventful. After two weeks, the patient was readmitted. The exclusion of the thoracic descending aortic pseudoaneurysm by endovascular implantation of the stent-graft prosthesis was performed. The left subclavian artery was excluded because left vertebral artery was closed. The patient did not develop hand claudicatio. The procedure was successful.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Microarrays represent a powerful tool for studies of diet-gene interactions. Their use is, however, associated with a number of technical challenges and potential pitfalls. The cost of microarrays continues to drop but is still comparatively high. This, coupled with the complex logistical issues associated with performing nutritional microarray studies, often means that compromises have to be made in the number and type of samples analysed. Additionally, technical variations between array platforms and analytical procedures will almost inevitably lead to differences in the transcriptional responses observed. Consequently, conflicting data may be produced, important effects may be missed and/or false leads generated (e.g. apparent patterns of differential gene regulation that ultimately prove to be incorrect or not significant). This is likely to be particularly true in the field of nutrition, in which we expect that many dietary bioactive agents at nutritionally relevant concentrations will elicit subtle changes in gene transcription that may be critically important in biological terms but will be difficult to detect reliably. Thus, great care should always be taken in designing and executing microarray studies. This article seeks to provide an overview of both the main practical and theoretical considerations in microarray use that represent potential sources of technical variation and error. Wherever possible, recommendations are made on what we propose to be the best approach. The overall aims are to provide a basic framework of advice for researchers who are new to the use of microarrays and to promote a discussion of standardisation and best practice in the field. © The Authors 2005.

Mutations of the APC gene are reported to occur frequently in sporadic colorectal adenomas and adenocarcinomas. We studied APC gene mutations in cases of human sporadic colorectal cancer in order to evaluate their correlation with pathologic characteristics and clinical prognosis.Most of the mutations of the APC gene (95%) are nonsense or frame shift mutations, encoding for truncated APC proteins. For this reason, mutation detection of the APC gene was performed using the in vitro synthesized protein (IVSP) assay, analysing the region between nucleotide 2058 and nucleotide 5079 of the gene, containing the mutation cluster region.Out of 58 cases of colorectal cancer, 29 presented a mutated form of APC (mutation frequency 50%). We did not find a statistically significant correlation between APC gene mutation and age, sex, localization of the primary tumour, grading, Crohn-like lymphoid reaction or presence of residual adenoma. Tumours with low invasivity (Dukes' stages A and B) were less frequently mutated (12/27, 44.5%) than tumours of Dukes' stage C (15 out of 21, 71.4%), which developed macroscopically secondary metastasis with variable latency after surgery. Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C).These data suggest that more aggressive Dukes' stage D tumours develop metastasis by means of an unknown mechanism, independent of APC mutation.

DNA damage has recently attracted much attention because of its supposed relationship with processes such as ageing and carcinogenesisl.

The putative tumour suppressor gene FHIT (fragile histidine triad) spans the common fragile site FRA3B, which is highly susceptible to breaks and deletions induced by genotoxic agents. Tumours associated with exposure to carcinogens, such as colorectal adenocarcinomas, should be particularly susceptible to alterations in the FHIT gene. We studied the frequency of FHIT alterations and their correlations with clinicopathologic features in sporadic colon carcinomas.FHIT expression was investigated by reverse transcription polymerase chain reaction in 56 primary sporadic colorectal carcinomas. The same tumours and matched normal tissues were also investigated for loss of heterozygosity by using two markers located inside the FHIT gene.Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts. Four tumours had absence or nearly undetectable levels of the normal-sized FHIT transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8. At the genomic level 46.4% (13 of 28) of the cases showed alterations involving FHIT locus. We did not find any correlation between FHIT gene alterations and clinicopathologic characteristics of the tumours.Since the FHIT gene is frequently altered, its role in the molecular pathogenesis of sporadic colon carcinoma deserves further investigation.

Background: Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. Aim of the study: In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative dammage in the rat colon mucosa. Methods: Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. Results: These results show that wine complex polyphenols and tannins induce a significant decrease (−62% for pyrimidine and −57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. Conclusions Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

The optimal aortic valve substitute in cases of active native valve endocarditis (NVE) remains controversial. This report summarizes our experience with the surgical treatment of active aortic NVE using only mechanical prostheses.Between January 1988 and January 1996, 20 patients underwent aortic valve replacement for active NVE. There were 17 men and three women. Mean age was 46.5 years (range eight to 63 years). Thirteen patients were in NYHA class IV and seven in class V. Streptococci were isolated in eight cases, while no causative micro-organism could be identified in seven patients. All operations were performed on urgent (n = 13) or emergency (n = 7) bases. A mechanical valve was implanted in all cases and radical resection of the infected tissues performed using different techniques. All patients were followed up at our institution. Two-dimensional color Doppler studies were performed one month after surgery and at six-month intervals after the first year. Transesophageal echocardiography (TEE) was performed at discharge, six months after surgery and yearly thereafter.No patient died in hospital. Mean follow up was 30.5 months, during which time three patients died, though none from endocarditis-related causes. Endocarditis recurred only one (5%). TEE demonstrated a normally functioning aortic prosthesis in 15 cases and trivial paravalvular leakage in two.Mechanical prostheses represent a safe aortic valve substitute in cases of acute native valve endocarditis. When radical resection of all the infected areas is performed, the incidence of endocarditis recurrence is acceptable. The concept that homografts are the valve substitute of choice in endocarditis cases cannot be supported by this study.

After more than 30 years since the first magnetocardiographic (MCG) recording was carried out with induction coils, MCG is now approaching the threshold of clinical use. During the last 5 years, in fact, there has been a growing interest of clinicians in this new method which provides an unrivalled accuracy for noninvasive, three-dimensional localization of intracardiac source. An increasing number of laboratories are reporting data validating the use of MCG as an effective method for preoperative localization of arrhythmogenic substrates and for planning the best catheter ablation approach for different arrhythmogenic substrates. In this article, available data from literature have been reviewed. We consider the clinical use of MCG to localize arrhythmogenic substrates in patients with Wolff-Parkinson-White syndrome and in patients with ventricular tachycardia in order to assess the state-of-the-art of the method on a large number of patients. This article also addresses some suggestions for industrial development of more compact, medically oriented MCG equipments at reasonable cost.

We describe a case of necrotizing histiocytic lymphadenitis or Kikuchi and Fujimoto disease, a rare lymphadenopathy of unknown etiology usually striking young women. It was formerly described in Japan, and subsequently in other countries and in Italy as an anatomo-clinical entity. The disease has a favourable prognosis, therefore it has to be considered differently from other lymphadenopathies with severe prognosis whose anatomo-pathological differential features were analyzed by the authors. The case here observed differs from other cases described in literature because of the presence of a perilymphadenitic component.