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In situ fenestration of stent-graft represents a potential option for the treatment of aortic diseases in patients unsuitable for standard endovascular repair. The best fenestration strategy to restore perfusion of collateral vessels after their coverage by an endograft depends mainly on the anatomical area. Several tools are employed as fenestration devices, including needles, radiofrequency probes, and laser systems, used in conjunction with other instrumentation to provide enough support and stability during the procedure. In this systematic review, the approaches to reach the correct fenestration site both in human, animal, and in in vitro environments are described and discussed, highlighting advantages and limitations. Both commercial and dedicated solutions for the intraoperative modification of the fabric material are reported as well. The clinical interest in this procedure has so far encouraged researchers to develop and refine both methods and tools to solve the current limitations of this technique, intending to extend the indications for endovascular treatment to a broader range of patients.

Modern and contemporary art materials are generally prone to irreversible colour changes upon exposure to light and oxidizing agents. Graphene can be produced in thin large sheets, blocks ultraviolet light, and is impermeable to oxygen, moisture and corrosive agents; therefore, it has the potential to be used as a transparent layer for the protection of art objects in museums, during storage and transportation. Here we show that a single-layer or multilayer graphene veil, produced by chemical vapour deposition, can be deposited over artworks to protect them efficiently against colour fading, with a protection factor of up to 70%. We also show that this process is reversible since the graphene protective layer can be removed using a soft rubber eraser without causing any damage to the artwork. We have also explored a complementary contactless graphene-based route for colour protection that is based on the deposition of graphene on picture framing glass for use when the direct application of graphene is not feasible due to surface roughness or artwork fragility. Overall, the present results are a proof of concept of the potential use of graphene as an effective and removable protective advanced material to prevent colour fading in artworks.

Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pyloriinfection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.

Malignant mesothelioma (MM) is an aggressive malignancy, highly resistant to current medical and surgical therapies, whose tumor cells characteristically show a high level of aneuploidy and genomic instability. We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. Thr/Tyr kinase (TTK)/monopolar spindle 1 kinase (Mps-1) is a kinase of the spindle assembly checkpoint that controls cell division and cell fate. CFI-402257 is a novel, selective inhibitor of Mps-1 with antineoplastic activity. We found that CFI-402257 suppresses MM growth. We found that Mps-1 is overexpressed in MM and that its expression correlates with poor patients’ outcome. In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe. In vivo, CFI-402257 reduced MM growth in an orthotopic, syngeneic model, when used as a single agent, and more so when used in combination with cisplatin+pemetrexed, the current standard of care. Our preclinical findings indicate that CFI-402257 is a promising novel therapeutic agent to improve the efficacy of the current chemotherapeutic regimens for MM patients.

Germline BAP1mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1mutations were professionally exposed to asbestos. We hypothesized that germline BAP1mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1+/-mouse model, we found that, compared with their wild-type littermates, BAP1+/-mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1+/-mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild-type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1mutations, possibly via alterations of the inflammatory response.

Si descrive una serie di casi nei quali il sintomo più rilevante era la presenza di “mento addormentato” (Numb Chin Syndrome, NCS) correlato a infezioni odontogene e lesioni cistiche. Questa neuropatia del nervo alveolare è caratterizzata da ipoestesia o parestesia del labbro inferiore e del mento.

Sedimentation is the most common and effectively practiced method of urban drainage control in terms of operating installations and duration of service. Assessing the percentage of suspended solids removed after a given detention time is essential for both design and management purposes. In previous experimental studies by some of the authors, the expression of iso-removal curves (i.e. representing the water depth where a given percentage of suspended solids is removed after a given detention time in a sedimentation column) has been demonstrated to depend on two parameters which describe particle settling velocity and occulation factor. This study proposes an investigation of the influence of some hydrological and pollutant aggregate information of the sampled events on both parameters. The Multi-Objective (EPR-MOGA) and Multi-Case Strategy (MCS-EPR) variants of the Evolutionary Polynomial Regression (EPR) are originally used as data-mining strategies. Results are proved to be consistent with previous findings in the field and some indications are drawn for relevant practical applicability and future studies. [ABSTRACT FROM AUTHOR]

Obiettivo dello studio è osservare il management di una leucoplachia con displasia lieve-moderata del bordo della lingua in un periodo di 15 anni.

In letteratura non sono riportati casi di pazienti affetti da carcinoma squamoso orale non sottoposti a terapia chirurgica o radio-chemioterapia. Presentiamo qui di seguito un caso non sottoposto a terapia, con follow-up di 32 mesi.

An electrochemical study of several molecules has been carried out, using novel graphene‐modified screen printed electrodes (GN‐SPEs). Different analytical parameters have been optimized, as: the graphene concentration for a homogeneous coating of the electrode surfaces, the scan rates and the potential window for the electrochemical detection of potassium ferricyanide, catechol, hexaammineruthenium(III) chloride, sodium hexachloroiridate‐(III) hydrate, dopamine, epinephrine, L‐tyrosine, 3,4‐dihydroxyphenylacetic acid (DOPAC), ascorbic acid, uric acid, 4‐acetamidophenol (acetaminophen), NADH, H2O2, caffeic acid, guanine, and serotonin (5‐HT) hydrochloride. In addition, different experimental conditions were tested, especially the solvents used to obtain a stable graphene nanoribbon dispersion. Among these various analytes, especially good results were obtained with NADH which was detected at an applied potential of +0.44 V, vs.Ag/AgCl, compared to the +0.55 V at pristine SWCNT paste electrodes, [7]), and with a detection limit (of 200 µM), good sensitivity (1.70 µA/mM mm2), and good reproducibility (RSD% ranging from 3 to 20 for different SPEs used for each single point of calibration plot). Also dopamine, has been successfully detected at GN‐ SPEs even in the presence of an electrochemical interfering compound. Results for dopamine showed a good detection limit (of 4 µM), sensitivity (17.70 µA/mM mm2) and reproducibility (RSD% ranging from 7 to 20 for different SPEs used for each single point of calibration plot).

Hepatitis C virus (HCV) re-infection after liver transplantation (LT) is characterized by an accelerated disease progression in recent years with unclear mechanisms. We evaluate the relationship between progression of liver fibrosis and histological necro-inflammation in HCV recipients, according to age of transplant. Fifty-five patients transplanted (1993-2002) for HCV liver disease, were included in the study. Recipients were retrospectively stratified in three different age of transplant, of 40 months each: group 1) from January 1993 to May 1996; group 2) from June 1996 to august 1999; group 3) from September 1999 to December 2002. Grading(necro-inflammation) and staging(fibrosis) scores were evaluated in liver biopsies at 1, 2 and 3 years from LT (Ishak classification). For all age of transplant the main factor associated with fibrosis progression, was gradingscore (p < 0.05). However mean stagingscore for each point of gradingincreased from 0.3 ± 0.2 in older LT to 0.7 ± 0.5 in newer ones (p 0.01). In conclusion in HCV-LT patients (1) liver fibrosis is strictly associated to histological necro-inflammation; (2) the proportion of this relationship has been changing in recent years since newer LT patients, show an increased amount of fibrosis in comparison with the older ones, for similar gradingscore.

There is increasing evidence that proteins normally involved in the cell cycle play a role in the regulation of neuronal apoptotic death following various insults. However, it is not clear if the same mechanisms regulate cell death of oligodendrocytes as well. In this study, we investigated the mechanism of ceramide-induced apoptosis in primary rat oligodendrocytes. We show that ceramide treatment initiates a cascade of biochemical events involving cell cycle regulatory proteins. Although at the time of induction of cell death the oligodendrocytes are postmitotic, activation of c-myc and translocation of Cdc25A into the nucleus can be demonstrated. Of particular interest are the findings of the up-regulation of PCNA and down-regulation of p21WAF1/CIP1protein, an inhibitor of cell-cycle progression. The current results show that activation of regulatory cell-cycle proteins at the oligodendrocytes G1-S checkpoint may constitute a crucial step of the death pathway of oligodendrocytes.

The local cytokine response to uropathogenic phenotype Escherichia coliKBC211 infection exhibits characteristics of both TH1 and TH2 profiles. Interleukin (IL)-6, MIP-2, IL-12, IL-18, and tumor necrosis factor-alpha (TNF-?) are expressed, but IL-4, IL-5, and IL-10 are also present at low levels. This is clearly a complex response that should be explored more fully. The relative contributions of the bladder epithelium and other cells of the bladder wall should also be determined. Epithelial cytokine responses may be considerable, and because these cells are the first to encounter the pathogen, they will be of great importance in the immune response to pathogenic E. coli.

The organization of the actin cytoskeleton is essential for several cellular processes. Here we report the characterization of a Saccharomyces cerevisiae novel gene, SDA1, encoding a highly conserved protein, which is essential for cell viability and is localized in the nucleus. Depletion or inactivation of Sda1 cause cell cycle arrest in G(1) by blocking both budding and DNA replication, without loss of viability. Furthermore, sda1-1 temperature-sensitive mutant cells arrest at the non-permissive temperature mostly without detectable structures of polymerized actin, although a normal actin protein level is maintained, indicating that Sda1 is required for proper organization of the actin cytoskeleton. To our knowledge, this is the first mutation shown to cause such a phenotype. Recovery of Sda1 activity restores proper assembly of actin structures, as well as budding and DNA replication. Furthermore we show that direct actin perturbation, either in sda1-1 or in cdc28-13 cells released from G(1) block, prevents recovery of budding and DNA replication. We also show that the block in G(1) caused by loss of Sda1 function is independent of Swe1. Altogether our results suggest that disruption of F-actin structure can block cell cycle progression in G(1) and that Sda1 is involved in the control of the actin cytoskeleton.

OBJECTIVE: To evaluate the efficacy of a combination of topical corticosteroids with topical antimycotic drugs in the therapy of atrophic‐erosive forms of oral lichen planus (OLP).

Triflate salts of Mg(II), Zn(II), and Cu(II) in liquid, low weight poly(ethylene glycol) dimethyl ether (PEGM(400)) to determine their conductivity and to ascertain their possible use as electrolyte media, have been studied. Their liquid structures have been studied by energy-dispersive X-ray diffraction. By this technique, the cation geometrical coordination has been determined. Furthermore, the local structure of the bivalent cations has been singled out by application of the difference method to isomorphic solutions. We found that the investigated cations have an octahedral coordination, with the exception of Cu, which displays two apical bonds longer than the planar ones. We also found that the polymer chain is coordinated to the cations Mg and Zn through the oxygen atoms of the polymer units 1, 5, and 9.

p300 is a nuclear phosphoprotein likely to be involved in the control of cell growth. Here we show that SV40 large T antigen (Tag) forms a specific complex with p300. In various Tag‐expressing cell lines, the affinity of Tag for p300 was restricted to a newly identified unphosphorylated but ubiquitinated form of the protein. Further, Tag did not associate with p300 in an SV40 Tag‐producing cell line (REV2) in which the original transformed phenotype (SV52) is reverted. Biochemical studies demonstrate that both the phosphorylation and the ubiquitination profile of p300 are altered in REV2 with respect to the wild‐type fully transformed SV52 parental cells, wherein Tag‐p300 complexes are readily detected. In contrast to Tag, the adenovirus early expression product E1a interacts with both phosphorylated and unphosphorylated forms of p300. In addition, when REV2 cells were infected with adenovirus, E1a‐p300 complexes were detected, suggesting that the p300 expressed in REV2 has lost the affinity for Tag, but not for E1a. We then compared the ability of Tag and E1a to affect the transcription levels of the cAMP‐responsive promoter (CRE), which is modulated in vivo by p300, in REV2 cells. We found that Tag repressed the CRE promoter in all of the cell lines in which Tag‐p300 complexes were detected, but not in REV2 cells. In contrast, E1a efficiently inhibited CRE‐directed transcription in this cell line. The data thus indicate that the different specificities exhibited by Tag and E1a towards the various forms of p300 are reflected in vivo as a difference in the ability of these viral oncoproteins to modulate the expression of CRE‐containing genes.

In the framework of the EU programme for systematic sequencing of the Saccharomyces cerevisiaegenome we determined the sequence of a 9359 bp fragment of the right arm of chromosome VII. Five open reading frames (ORFs) of at least 300 nucleotides were found in this region. YGR267c encodes a protein with significant similarity to the enzyme GTP‐cyclohydrolase I, that controls the first step in the biosynthetic pathway leading to various pterins and shows a high degree of sequence conservation from bacteria to mammals. We have recently demonstrated (Nardese et al., 1996) that YGR267c corresponds to the FOL2gene, previously localized in the same chromosomal region by genetic mapping. The protein deduced from YGR270w belongs to the superfamily of putative ATPases associated with diverse cellular activities. It corresponds to the YTA7gene, a member of a set of yeast genes coding for putative ATPases with high similarity to constituents of the 26S protease. The three ORFs YGR266w, YGR268c and YGR269w encode putative products of unknown function, with neither significant similarity to proteins in databases nor recognizable domains. YGR268c and YGR269w are partially overlapping ORFs: YGR268c seems to correspond to a real gene, whereas YGR269w is probably a fortuitous ORF. The sequence has been entered in the EMBL data library under Accession Number Y07893. © 1998 John Wiley & Sons, Ltd.

Anti-myeloperoxidase (anti-MPO) antibodies were detected in 34 of 88 (38%) patients with type 1 diabetes mellitus but in only 3 of 55 (5.7%) healthy subjects and in 4 of 20 patients with autoimmune disease. Specificity of anti-MPO antibodies was assessed by MPO inhibition studies. No relationship was found between the occurrence of anti-MPO and anti-thyroperoxidase antibodies. Levels of soluble intercellular adhesion molecule 1 (ICAM-1) were found to be higher in anti-MPO antibodypositive (n=28, 508±126 ng/ml) than in anti-MPO antibody-negative (n=58, 438±140 ng/ml;P<0.05) patients. A state of chronic neutrophil activation has been described in diabetes mellitus. As anti-MPO antibodies can stimulate neutrophils to damage endothelial cells in systemic vasculitis, this suggests that a similar mechanism may be operative in the development of diabetic angiopathy.

Some cetyltrialkylammonium tribromide salts have been studied in the solid phase using Raman spectroscopy and energy dispersive X-ray diffraction. The first technique detected the presence of asymmetric tribromides while the latter technique revealed the degree of asymmetry of the tribromide units (difference in the bond lengths between external and central Br atoms), by application of a subtraction method. In this method the spectra of the corresponding monobromide salts were recorded and differences between tribromide and monobromide curves isolated the tribromide contributions. The existence of asymmetrical and symmetrical tribromide ions has been established and the degree of asymmetry was then correlated to the steric hindrance and electronegativity of the ammonium substituents. The values of the Br–Br bond distances have been deduced; the most asymmetric tribromide has Br–Br distances at 2.38 and 2.66 Å, while the symmetric tribromide has both Br–Br bond lengths equal to 2.52 Å. A linear geometry is confirmed for the tribromide ions.

The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication and for late viral gene expression, but the role of the SV40 small-t antigen in these processes is still unclear. We have previously demonstrated that small t inhibits SV40 DNA replication in vitro. In this study, we investigated the effect of small t on SV40 replication in cultured cells. CV1 monkey cell infection experiments indicated that mutant viruses that lack small t replicate less efficiently than the wild-type virus. We next microinjected CV1 cells with SV40 DNA with and without purified small-t protein and analyzed viral DNA replication efficiency by Southern blotting. Replication of either wild-type SV40 or small-t deletion mutant DNA was increased three- to fivefold in cells coinjected with purified small t. Thus, in contrast to our in vitro observation, small t stimulated viral DNA replication in vivo. This result suggests that small t has cellular effects that are not detectable in a reconstituted in vitro replication system. We also found that small t stimulated progression of permissive monkey cells--but not of nonpermissive rodent cells--from G0-G1 to the S phase of the cell cycle, possibly leading to an optimal intracellular environment for viral replication.

The pharmacodynamic effects of FCE20700, a new PGE2 derivative, have been investigated in 6 healthy volunteers given single intragastric (i.g.) and intraduodenal (i.d.) doses of 1 and 2 mg and placebo, according to a double-blind, within — subjects design. For 30–270 min following i.g. administration the effect of FCE20700 on peptone-stimulated gastric acid secretion (AS) was assessed by i.g. titration, and serum gastrin (G) levels were also determined. For the same period after i.d. dosing the effect of the compound on pentagastrin-stimulated AS and on mucoproteins and bicarbonate content in the gastric juice was measured. Blood pressure (BP), heart rate and possible side-effects were monitored. Following i.g. administration there was a moderate, dose-related, significant inhibition of AS; significant inhibition of G levels was observed only after the highest dose. After i.d. administration there was a very modest through dose-related and significant inhibition of AS; a brief maximal increase in mucoproteins and in bicarbonate levels was apparent after the 1 mg dose. After i.d. but not after i.g. administration of 2 mg there was a modest but significant decrease in BP. No side-effects of clinical relevance were reported. The results appear to suggest a major activity of FCE20700 on cytoprotection rather than in inhibiting gastric acid secretion. The observed change in BP may indicate that after i.d. administration there will be some systemic effects of FCE20700.

The lethal effects occurring in neonatal (<24-h-old) BALB/c mice after challenge with 25 mg of lipopolysaccharide (LPS) per kg of body weight were significantly counteracted by pretreatment with recombinant interleukin-10 (rIL-10; 25 or 50 ng/mouse). Concordantly, blockage of endogenous IL-10 with the SXC1 monoclonal antibody increased LPS-induced mortality. Both IL-10 and SXC1 modulated the release of tumor necrosis factor alpha (TNF-alpha) so that, relative to controls, peak TNF-alpha values after LPS challenge were decreased by rIL-10 and increased by anti-IL-10.

A group of 30 independent mutants of Saccharomyces cerevisiae, resistant to the respiratory inhibitor antimycin A, was investigated from a genetical and biochemical point of view. All the mutants can be grouped into two nuclear loci: AMY1 maps on the VII chromosome, between leu 1 and trp 5; AMY2 is close to its centromere on either chromosome XVIII or XIX. Both genes do not affect mitochondrial structures or functions.

The aim of this study was to examine the ability of Pseudomonas aeruginosa components to induce release of cytokines from human leukocytes. Human whole-blood cultures were incubated with several concentrations of purified P. aeruginosa products, including porins, exomucopolysaccharide, lipopolysaccharide, and toxin A. Supernatants were assayed for tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) activities. All of the P. aeruginosa components except toxin A were able to stimulate the release of both cytokines. On a weight basis, porins were as effective as lipopolysaccharide and significantly more effective than exomucopolysaccharide in inducing IL-6 release (P < 0.05). Moreover, porins were more potent than either exomucopolysaccharide or lipopolysaccharide in inducing TNF-alpha release (P < 0.05). Further experiments using isolated leukocytes suggested that monocytes were the cell population predominantly responsible for the production of both cytokines. These data indicate that P. aeruginosa porins are able to induce significant cytokine production. These components may be responsible for the chronically overactive inflammatory response associated with persistent lung infection in cystic fibrosis patients.

In the framework of the EU programme for systematic sequencing of the Saccharomyces cerevisiae genome we determined the sequence of a 9359 bp fragment of the right arm of chromosome VII. Five open reading frames (ORFs) of at least 300 nucleotides were found in this region. YGR267c encodes a protein with significant similarity to the enzyme GTP-cyclohydrolase I, that controls the first step in the biosynthetic pathway leading to various pterins and shows a high degree of sequence conservation from bacteria to mammals. We have recently demonstrated (Nardese et al., 1996) that YGR267c corresponds to the FOL2 gene, previously localized in the same chromosomal region by genetic mapping. The protein deduced from YGR270w belongs to the superfamily of putative ATPases associated with diverse cellular activities. It corresponds to the YTA7 gene, a member of a set of yeast genes coding for putative ATPases with high similarity to constituents of the 26S protease. The three ORFs YGR266w, YGR268c and YGR269w encode putative products of unknown function, with neither significant similarity to proteins in databases nor recognizable domains. YGR268c and YGR269w are partially overlapping ORFs: YGR268c seems to correspond to a real gene, whereas YGR269w is probably a fortuitous ORF. The sequence has been entered in the EMBL data library under Accession Number Y07893. © 1998 John Wiley & Sons, Ltd.

The association between the level of class I major histocompatibility (MHC) antigen expression and the tumorigenic phenotype was determined for cells from a series of 15 lines of adenovirus type 2 (Ad2)-, Ad12-, and simian virus 40 (SV40)-transformed hamster cells and 16 lines of cells established from hamster tumors induced by SV40 mutants. These cells range from nontumorigenic to highly tumorigenic in both syngeneic and allogeneic adult hamsters. The Ad2-transformed cells--cells that were nontumorigenic in syngeneic adult hamsters--expressed either high levels or low levels of class I MHC antigens. The SV40-transformed cells--cells transformed in vitro that produced tumors with equal efficiency in both syngeneic and allogeneic adult hamsters--or cells derived from SV40-induced tumors expressed very high levels of class I MHC antigens. The Ad12-transformed cells uniformly expressed low levels of class I MHC antigens; these cells produced tumors 200- to 1,000-fold less efficiently in allogeneic adult hamsters than in syngeneic adult hamsters and produced tumors with about the same efficiency in immunoimmature newborns and immunocompetent syngeneic adult hamsters. We conclude that the expression of either high levels or low levels of class I MHC antigens is, at most, a minor factor in the differences observed among these adenovirus- and SV40-transformed cells in their tumor-inducing capacity in naive, immunocompetent hamsters.