Electronic Structure Characterization of a Thiophene Benzo-Annulated Series of Common Building Blocks for Donor and Acceptor Compounds Studied by Gas Phase Photoelectron and Photoabsorption Synchrotron Spectroscopies.

The near-edge x-ray-absorption fine-structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS) spectra of benzo[ b]thiophene (BBT) and dibenzothiophene (DBT) in the gas phase have been measured at the carbon K-edge and sulfur LII,III-edge regions. The assignment of the spectral features has been provided by theoretical calculations based on density functional theory (DFT) and its time-dependent generalization (TDDFT) in the linear response regime. Observed trends in computed C 1s and S 2p ionization potentials (IPs) have been rationalized in terms of both the inductive effects due to the presence of S and the increased π-electrons delocalization arising from the benzo-annulation process. The analysis of the NEXAFS carbon K-edge and sulfur LII,III-edge regions provided information on both low-lying delocalized virtual π orbitals, and higher-lying localized σ*(C-S) states. The evolution of the NEXAFS carbon K-edge spectral features along the series thiophene (T) and derivatives, BBT and DBT, is informative of a stabilizing effect due to increased aromaticity. This effect is however more pronounced in going from T to BBT compared to the introduction of a second annulated phenyl ring in DBT. The nature of the most intense sulfur LII,III-edge NEXAFS spectral features is instead conserved along the series reflecting thus the localized nature of the virtual states involved in the S 2p core-excitation process.

Anaemia as a risk stratification tool for symptomatic patients referred via the two-week wait pathway for colorectal cancer.

Introduction Anaemia is associated with cancer. In 2014 a new form was introduced in our department requesting a haemoglobin (Hb) result on every two-week wait referral for suspected colorectal cancer (CRC). The aim of this study was to review the impact of this intervention. In particular, the significance of any evidence of anaemia (without additional indices) was investigated. Methods A review was conducted of 1,500 consecutive suspected CRC referrals recorded prospectively over a 10-month period. Data on demographics, referral Hb, referral criteria and outcomes were analysed. Anaemia was defined according to World Health Organization criteria (Hb <120g/l for women, Hb <130g/l for men). Results Overall, 1,015 patients were eligible for inclusion in the study. Over a third (38.2%) were documented as anaemic on referral. These patients were three times more likely to be diagnosed with CRC than non-anaemic patients (odds ratio [OR]: 3.22, 95% confidence interval [CI]: 1.87-5.57). Using a more stringent threshold (Hb <100g/l for women and <110g/l for men), they were four times more likely to have CRC (OR: 4.27, 95% CI: 2.35-7.75). Almost a quarter (23.7%) were actually anaemic at the time of referral but not referred with anaemia. In this subgroup, there was a 2.8-fold increase in risk of CRC diagnosis compared with non-anaemic patients (adjusted OR: 2.77, 95% CI: 1.55-4.95). Conclusions Nearly a quarter of patients not referred with iron deficiency anaemia had evidence of anaemia and this was still associated with a higher rate of CRC detection. A full blood count alone might help to risk stratify symptoms such as change in bowel habit in patients on urgent pathways and identify those cases most likely to benefit from invasive investigation.

Estimating the real incidence of invasive listeriosis through an integrated surveillance model in use in Lombardy (Italy, 2006-2014).

The annual incidence of listeriosis in Italy is lower (0·19-0·27 per 100 000 inhabitants per year) than in Europe (0·34-0·52 per 100 000 inhabitants per year). Since the observed incidence of listeriosis may be biased downward for underdiagnosis or under-reporting, this work aims to estimate the real incidence of listeriosis during a 9-year period in the Lombardy region, Italy. Data on listeriosis cases were collected from national mandatory notification system (MAINF) and Laboratory-based Surveillance System (LabSS). The two sources were cross-matched and capture-recapture method was applied to estimate the number of undetected cases and the real incidence of invasive listeriosis. Five hundred and eighty invasive listeriosis cases were detected by the two sources between 2006 and 2014: 50·2% were identified only via MAINF, 16·7% were recorded only via LabSS, overlaps occurred in 192 cases (33·1%). The mean annual incidence detected only by MAINF was 0·56 per 100 000 inhabitants, which rose to 0·67 per 100 000 considering also the cases detected by LabSS. The capture-recapture method allowed to estimate an incidence of 0·84 per 100 000. The high incidence of listeriosis may be due to improved sensitivity of the surveillance system, but also reflect a real increase, associated with an increased population at risk.

Study of the electronic structure of short chain oligothiophenes.

The electronic structure of short-chain thiophenes (thiophene, 2,2'-bithiophene, and 2,2':5',2″-terthiophene) in the gas phase has been investigated by combining the outcomes of Near-Edge X-ray-Absorption Fine-Structure (NEXAFS) and X-ray Photoemission Spectroscopy (XPS) at the C K-edge with those of density functional theory (DFT) calculations. The calculated NEXAFS spectra provide a comprehensive description of the main experimental features and allow their attribution. The evolution of the C1s NEXAFS spectral features is analyzed as a function of the number of thiophene rings; a tendency to stabilization for increasing chain length is found. The computation of the binding energy allows to assign the experimental XPS peaks to the different carbon sites on the basis of both the inductive effects generated by the presence of the S atom as well as of the differential aromaticity effects.

S2p core level spectroscopy of short chain oligothiophenes.

The Near-Edge X-ray-Absorption Fine-Structure (NEXAFS) and X-ray Photoemission Spectroscopy (XPS) of short-chain oligothiophenes (thiophene, 2,2'-bithiophene, and 2,2':5',2″-terthiophene) in the gas phase have been measured in the sulfur L2,3-edge region. The assignment of the spectral features is based on the relativistic two-component zeroth-order regular approximation time dependent density functional theory approach. The calculations allow us to estimate both the contribution of the spin-orbit splitting and of the molecular-field splitting to the sulfur binding energies and give results in good agreement with the experimental measurements. The deconvolution of the calculated S2p NEXAFS spectra into the two manifolds of excited states converging to the LIII and LII edges facilitates the attribution of the spectral structures. The main S2p NEXAFS features are preserved along the series both as concerns the energy positions and the nature of the transitions. This behaviour suggests that the electronic and geometrical environment of the sulfur atom in the three oligomers is relatively unaffected by the increasing chain length. This trend is also observed in the XPS spectra. The relatively simple structure of S2p NEXAFS spectra along the series reflects the localized nature of the virtual states involved in the core excitation process.

[Dynamic contrast-enhanced magnetic resonance imaging of the wrist in early arthritis]. / La risonanza magnetica dinamica del polso nella valutazione delle artriti precoci.

OBJECTIVES: MRI has been proposed as the imaging method of choice to evaluate the long-term outcome in patients with early arthritis. The role of dynamic MRI, performed at presentation, in predicting the outcome of patients with early arthritis has been addressed in the present study. METHODS: 39 patients with early arthritis, involving at least one wrist, were studied with clinical visits and laboratory investigations, every 3 months. Dynamic MRI was performed with a low-field (0.2T), extremity-dedicated machine (Artoscan, Esaote, Genova, Italy) equipped with a permanent magnet and with a dedicated hand and wrist coil. During the intravenous injection of Gd-DTPA, twenty consecutive fast images of 3 slices of the wrist were acquired. The synovial contrast enhancement ratio was calculated both as rate of early enhancement (REE) per second during the first 55" and as relative enhancement (RE) at t seconds. RESULTS: In our cohort of patients, REE and RE were significantly lower than those observed in a historical cohort of 36 patients with active rheumatoid arthritis. In univariate analysis, low RE predicted complete remission of arthritis. In multivariate analysis, fulfillment of RA criteria during follow-up was predicted by high RE. The need for immunosoppressive treatment at the end of follow-up was predicted by both low RE and high REE. CONCLUSIONS: Dynamic MRI may be used to predict several outcomes of early arthritis involving the wrist.

Drinking habits and risk of altered liver enzymes in the general population of a rural area in Southern Italy.

PURPOSE: To assess the overall drinking habits (amount and duration of alcohol intake, as well as type of alcoholic drinks consumed) and their potential for alteration of liver enzymes in a random sample of the general population aged > or =18 years of a rural area in Southern Italy. MATERIALS AND METHODS: Of the 4000 subjects selected, 3306 (82.7%) agreed to take part in the study. Of these, 41% were teetotallers (54.4% females, 26.1% males; p<0.01). A very small proportion of subjects reported > or =4 drinks/day (11.9% males, 0.8% females; p<0.01). RESULTS: Increased aspartate aminotransferase and/or alanine aminotransferase values were observed in 148 (4.5%) subjects. Hepatitis C virus positivity alone, excessive body mass index alone and alcohol intake alone were observed in 28.6, 23.8 and 18.4% of cases, respectively. After exclusion of subjects with chronic viral hepatitis infections (hepatitis B virus and/or hepatitis C virus) and adjustment for the confounding effect of age (>50 years) and body mass index (> or =25) by multiple logistic regression analysis, subjects who reported consuming >4 drinks/day were 2.4-fold (95%CI=1.1-5.2) more likely than teetotallers to have altered liver enzyme values; subjects reporting intake below this threshold were not at risk of alterations in aspartate aminotransferase/alanine aminotransferase (OR 1.4; 95%CI=0.7-2.6). CONCLUSIONS: These findings indicate that only a small proportion of the rural population studied (particularly females) can be considered as alcohol misusers. Moreover, a mild alcohol intake (< or =4 drinks/day) is not associated with alterations in aspartate aminotransferase/alanine aminotransferase levels in the absence of other factors such as hepatitis viruses and impaired body mass index.

[Magnetic resonance imaging of the peripheral joints in psoriatic arthritis]. / La risonanza magnetica delle articolazioni periferiche nell'artrite psoriasica.

OBJECTIVE: Magnetic resonance imaging (MRI) has been widely used for the evaluation of rheumatoid arthritis (RA), with only a minority of studies considering other types of arthritis. This review is concerned with an evaluation of the MRI appearance of peripheral joints in psoriatic arthritis (PsA). METHODS: A Medline search was performed to identify all publications from the years 1985 to 2006 concerning MRI of the peripheral joints and PsA. Additional papers were retrieved by scanning the references to the Medline-listed articles. Articles written in English, French, German, and Italian were included. RESULTS: Most papers studied the hand and wrist, and only few of them were concerned with the knee, foot, temporomandibular joint, and elbow. Patients with PsA showed often, but not always, a pattern of joint inflammation which extended beyond the capsule into the extraarticular tissue. Bone oedema and erosions were less frequent than in RA. In particular, bone oedema at the entheseal junction was seen, especially in the knee. The degree of synovitis, assessed by dynamic MRI, was similar in PsA and RA. DISCUSSION: Data on MRI of the peripheral joints in PsA are scanty. Only few studies were specifically designed to evaluate the pattern of arthritis in PsA, with most information deriving from papers where different types of arthritis were considered together. An enthesis-related origin of PsA has been proposed in contrast to the primarily synovial inflammation of RA. This pathogenic interpretation is likely to be true, but does not explain all cases of PsA, and needs to be confirmed by further studies.

Composition and seasonal variation of soluble cuticular waxes in Actinidia deliciosa leaves.

This research examines the annual evolution and composition of soluble cuticular waxes of Actinidia deliciosa Chev. cv Hayward leaves. Soluble cuticular waxes of foliar blade were extracted in chloroform and analysed by GC-MS. The seasonal weighted mean of the wax coverage was about 24 microg cm(-2). The alkyl alkanoates were the main class of components (10 microg cm(-2)) followed by hydrocarbons (6 microg cm(-2)), terpenes (3 microg cm(-2)), alkanols (1 microg cm(-2)), ketones (1 microg cm(-2)), alkanoic acids (1 microg cm(-2)), alkanals (0.7 microg cm(-2)), and sterols (0.6 microg cm(-2)). The concentration of the soluble cuticular components reached a peak (43 microg cm(-2)) on the 83rd day after bud break. Different causes were proposed to explicate the seasonal evolution of the leaf waxes: biosynthesis of the waxes prevalently during rapid leaf growth; natural wax erosion and evaporation; progressive reduction in the extractability of the intracuticular free compounds due to the slow polymerization of the cutin matrix.

[Effects of a new pharmacological complex (silybin + vitamin-E + phospholipids) on some markers of the metabolic syndrome and of liver fibrosis in patients with hepatic steatosis. Preliminary study]. / Effeto di un nuovo complesso farmacologico (sillibina vitamina E+ fosfolipidi) su alcuni indicatori di sindrome metabolica e di fibrosi epatica in pazienti con epatopatia steatosica. Studio pilota.

AIM: This open preliminary pilot study was aimed to evaluate the effect of a new pharmaceutical complex (silybin+vitamin E+phospholipids - RealSIL-IBI-Lorenzini Pharmaceutical, Italy) on some parameters of metabolic syndrome and of liver fibrosis in patients with non alcoholic fatty liver disease (NAFLD) with or without the contemporaneous presence of hepatitis C virus (HCV)-related chronic hepatitis. METHODS: Eighty five patients were consecutively enrolled in the study and divided in 2 groups; the first group was represented by 59 patients affected by NAFLD, negative for other known causes of chronic liver damage (M/F= 39/20; median age and range: 44 years, 22-76, group A); the second group was represented by 26 patients (M/F=19/7; median age and range 51 years, 20-75, group B) with HCV-related chronic hepatitis associated to NAFLD. Adverse events and drop-outs were absent in all group and compliance at the study was absolute. RESULTS: This open preliminary study shows that the new compound silybin+vitamin E+ phospholipids is active, in vivo, and produces some therapeutic effects in patients with different forms of chronic liver damage. In particular, it improves insulin resistance and plasma levels of markers of liver fibrosis in patients in whom these parameters are particularly altered. CONCLUSIONS: Our data have a role of suggestion to further evaluate, through a controlled trial, a possible therapeutic use of this new compound in the management of patients with NAFLD.

Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver.

AIM: To define the characteristics of the Italian patient presenting non-alcoholic fatty liver disease. PATIENTS AND METHODS: A total of 305 patients with abnormally high plasma aminotransferase and/or gamma-glutamyl-transpeptidase levels for at least 12 months, with no known cause of chronic liver damage, were consecutively enrolled in the study. Clinical, routine biochemical and liver histology investigations were carried out in all patients. Also evaluated were: (a) oral glucose load; (b) insulinaemia and insulin-resistance using the HOMA test model; and (c) plasma endotoxaemia, total antioxidant plasma capability, tumour necrosis factor-alpha, plasma interleukin-6 and -10 levels. Malondialdehyde and 4-hydroxynonenal content were determined on liver samples from 120 patients. RESULTS: The majority of patients were young overweight or obese males, with dyslipidaemia (20-60%), diabetes (10.5%), hyperinsulinaemia (40%), hyperferritinaemia (35%). Endotoxaemia was negative in all patients and cytokines were only sporadically altered. Total antioxidant plasma capability was decreased in 38.4% of the patients. Eighty percent of the cases had histological steatosis with a mild degree of inflammation and fibrosis. Seven patients had cirrhosis. Lipid peroxidation markers were increased in 90% of the cases, inversely correlated with fibrosis. Even if at univariate analysis, age, ferritin and tissue 4-hydroxynonenal were independent factors of steatosis (P < 0.01), and insulin, HOMA and ferritin of inflammation and fibrosis (P < 0.01), at multivariate analysis no single factor was found to be an independent predictor of hepatic lesions. CONCLUSIONS: The typical Italian patient with non-alcoholic fatty liver disease is a young male, obese, not diabetic, with a variable incidence of dyslipidaemia and hyperinsulinaemia. Only liver biopsy may define the type of liver damage.

New sesquiterpene derivatives from the sponge Dysidea species with a selective inhibitor profile against human phospholipase A2 and other leukocyte functions.

Two new sesquiterpene cyclopentenones, dysidenones A and B (2, 3), and a new sesquiterpene aminoquinone, dysidine (4), all containing the same rearranged drimane skeleton, have been isolated from a Dysidea sp. sponge, along with bolinaquinone (1). The structures were established from 2D NMR data. Bolinaquinone (1), dysidine (4), and a 1:1 mixture of dysidenones A and B (2, 3) significantly inhibited human synovial phospholipase A2 (PLA2) at 10 microM. Compound 4, which shows an IC50 value of 2.0 microM, exerts a higher potency and selectivity toward this enzyme than the reference inhibitor manoalide. In addition, all of these compounds modulated at 10 microM other human leukocyte functions such as the degranulation process measured as elastase release and the superoxide production measured by chemiluminescence.

Dysidotronic acid, a new sesquiterpenoid, inhibits cytokine production and the expression of nitric oxide synthase.

In a previous study, we reported a new bioactive sesquiterpenoid, named dysidotronic acid, to be a potent, selective human synovial phospholipase A(2) inhibitor. Dysidotronic acid is a novel, non-complex manoalide analogue lacking the pyranofuranone ring. We now investigate the effect of this compound on cytokine, nitric oxide and prostanoid generation on the mouse macrophage cell line RAW 264.7, where it showed a dose-dependent inhibition with inhibitory concentration 50% values in the micromolar range. This effect was also confirmed in the mouse air pouch injected with zymosan. Dysidotronic acid inhibited the production of tumor necrosis factor alpha and interleukin-1 beta as well as the production of nitric oxide, prostaglandin E(2) and leukotriene B(4). Decreased nitric oxide generation was the consequence of inhibition of the expression of nitric oxide synthase, whereas PGE(2) and LTB(4) reduction was due to inhibition of arachidonic acid bioavailability through a direct inhibitory effect of dysodotronic acid on secretory phospholipase A(2).

Callipeltin A, a cyclic depsipeptide inhibitor of the cardiac sodium-calcium exchanger and positive inotropic agent.

Callipeltin A, a cyclic depsipeptide from the New Caledonian Lithistida sponge Callipelta sp., is a macrocyclic lactone containing four amino acids in the L configuration, Ala, Leu, Thr (2 residues); one (Arg) in the D configuration; two N-methyl amino acids, N-MeAla and N-MeGln; a methoxy tyrosine, a 3, 4-dimethyl-l-glutamine; and a 4-amino-7-guanidino-2,3 dihydroxypentanoic acid (AGDHE), formally derived from L-Arg. In cardiac sarcolemmal vesicles Callipeltin A induces a powerful (IC(50) = 0.85 microM) and selective inhibition of the Na(+)/Ca(2+) exchanger. In electrically driven guinea-pig atria, at concentrations ranging between 0.7 and 2.5 microM, Callipeltin A induces a positive inotropic effect, which at the highest concentrations is accompanied by a rise in resting tension. It is suggested that the positive inotropic effect is linked to the inhibition of the Na(+)/Ca(2+) exchanger and that Callipeltin A may be an useful tool to study the role of the cardiac Na(+)/Ca(2+) exchanger in physiological and pathological conditions.

New isomalabaricane derivatives from a new species of Jaspis sponge collected at the Vanuatu islands.

Six new cytotoxic isomalabaricane-type triterpenoids and nortriterpenoids with a 3alpha-acetoxy group were isolated, along with the known globostellatic acids B (1) and C (2), from the marine sponge Jaspis sp. collected at Vanuatu Island. The structures were determined by 2D NMR data and by comparison with spectral data of known related compounds.

Ab initio study on the photochemical isomerization of furan derivatives

The photochemical isomerization reactions of furan, 2-methylfuran, 2-trimethylsilylfuran, and furan-2-carbonitrile were studied using ab initio methods. The results are in agreement with the previously reported data obtained through semiempirical methods. In particular, the sensitized irradiation of furan derivatives populates the first excited triplet state of the furan, and this triplet state can evolve only through O-Ca cleavage. The selection of the bond to be broken can depend on energetic factors (furan-2-carbonitrile) or on kinetic factors (2-methylfuran, 2-trimethylsilylfuran). The direct irradiation of furan derivatives populates the singlet excited state and leads to a conversion into the Dewar isomer or into the corresponding triplet state through the usual intersystem crossing procedure. The efficiency of these processes determines the presence or the absence of isomerized furan derivatives in the reaction mixtures.

The photochemical behavior of colchicone and thiocolchicone.

The irradiation of colchicone 5 led to the formation of lumicolchicone 7. The same reaction cannot be obtained by using thiocolchicone 6 as substrate. Transient absorption spectroscopy of colchicone and beta-lumicolchicone showed that probably the photoisomerization occurred on colchicone in its first excited singlet state. The spectroscopic data are in agreement with the hypothesis that lumicolchicone was generated in the ground state from the S1 state of colchicone without the presence of any intermediate. Semiempirical calculations on colchicone and thiocolchicone showed that the highest single occupied molecular orbital and the lowest unoccupied molecular orbital of the singlet excited colchicone can give a disrotatory ring closure to 7, while thiocolchicone cannot give the same type of process.

Singlet oxygen mediated degradation of Klason lignin.

After some results concerning photochemical generated singlet oxygen on lignins from steam explosion, the reactions of chemically generated singlet oxygen with Klason lignins from pine and beech are described. Singlet oxygen was produced through the reaction of hydrogen peroxide with sodium hypochlorite. The degradation of lignin was followed by uv spectroscopy and gel permeation chromatography. Extensive degradation of the lignins was observed when 20 mg of Klason lignin was treated with 1 ml of 30% hydrogen peroxide and 8.56 ml of 1.093 M sodium hypochlorite. In the uv spectra registered after the treatment with singlet oxygen the absorptions typical of lignin (210-220 nm and 250-280 nm) were completely absent. The gpc analysis of lignin after a treatment with 0.1 ml of hydrogen peroxide and 0.86 ml of sodium hypochlorite showed a clear reduction of signals due to the lignin and a shift to lower molecular weight. The potential use of this procedure in the bleaching procedure was tested by using recycled paper. A maximum reduction of 51% in the amount of lignin in this paper was observed.

New jaspamide derivatives from the marine sponge Jaspis splendans collected in Vanuatu.

Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical structures were determined from 1D and 2D NMR studies and MS data. These two compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines with IC50 values in the microg/mL range.