Tuscany Sangiovese grape juice imparts cardioprotection by regulating gene expression of cardioprotective C-type natriuretic peptide.

PURPOSE: A regular intake of red grape juice has cardioprotective properties, but its role on the modulation of natriuretic peptides (NPs), in particular of C-type NP (CNP), has not yet been proven. The aims were to evaluate: (1) in vivo the effects of long-term intake of Tuscany Sangiovese grape juice (SGJ) on the NPs system in a mouse model of myocardial infarction (MI); (2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; (3) the activation of CNP/NPR-B/NPR-C in healthy human subjects after 7 days' SGJ regular intake. METHODS: (1) C57BL/6J male and female mice (n = 33) were randomly subdivided into: SHAM (n = 7), MI (n = 15) and MI fed for 4 weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200 µl/per day) (MI + SGJ, n = 11). Echocardiography and histological analyses were performed. Myocardial NPs transcriptional profile was investigated by Real-Time PCR. (2) MCEC-1 were treated for 24 h with a pool of SGJ small RNAs and cell viability under 24 h exposure to H2O2 was evaluated by MTT assay. (3) Human blood samples were collected from seven subjects before and after the 7 days' intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood. RESULTS: Our experimental data, obtained in a multimodal pipeline, suggest that the long-term intake of SGJ promotes an adaptive response of the myocardium to the ischemic microenvironment through the modulation of the cardiac CNP/NPR-B/NPR-C system. CONCLUSIONS: Our results open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.

Shewanella algae infection in Italy: report of 3 years' evaluation along the coast of the northern Adriatic Sea.

Shewanella algae are Gram-negative, nonfermentative, motile bacilli, classified in the genus Shewanella in 1985. These environmental bacteria are occasionally identified in human infections, with a relatively strong association with exposure to seawater during warm seasons. This report describes a case series of 17 patients with infection correlated to S. algae in the coastal area of Romagna, Italy, from 2013 to 2016. The types of infection included otitis, pneumonia, sepsis and soft tissue (wound). Exposure to the marine environment during hot months was confirmed in 12 of 17 patients. An apparent correlation between increased severity of infection and patient age was also observed.

First report of sepsis due to Catabacter hongkongensis in an Italian patient.

The first isolation of Catabacter hongkongensis in Italy is reported. Pleomorphic Gram-positive rods were grown in blood cultures from samples obtained from a 55-year-old patient admitted to the intensive care unit with sepsis after he experienced massive thoracic and abdominal trauma. The identification was obtained by amplification and sequencing of the 16S rRNA gene.

An averaging technique for the P300 spatial distribution.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and Images". OBJECTIVES: The main objectives of the paper regard the analysis of amplitude spatial distribution of the P300 evoked potential over a scalp of a particular subject and finding an averaged spatial distribution template for that subject. This template, which may differ for two different subjects, can help in getting a more accurate P300 detection for all BCIs that inherently use spatial filtering to detect P300 signal. Finally, the proposed averaging technique for a particular subject obtains an averaged spatial distribution template through only several epochs, which makes the proposed averaging technique fast and possible to use without applying any prior training data as in case of data enhancement technique. METHODS: The method used in the proposed framework for the averaging of spatial distribution of P300 evoked potentials is based on the statistical properties of independent components (ICs). These components are obtained by using independent component analysis (ICA) from different target epochs. RESULTS: This paper gives a novel averaging technique for the spatial distribution of P300 evoked potentials, which is based on the P300 signals obtained from different target epochs using the ICA algorithm. Such a technique provides a more reliable P300 spatial distribution for a subject of interest, which can be used either for an improved spatial selection of ICs, or more accurate P300 detection and extraction. In addition, the experiments demonstrate that the values of spatial intensity computed by the proposed technique for P300 signal converge after only several target epochs for each electrode allocation. Such a speed of convergence allows the proposed algorithm to easily adapt to a subject of interest without any additional artificial data preparation prior the algorithm execution such in case of data enhancement technique. CONCLUSION: The proposed technique averages the P300 spatial distribution for a particular subject over all electrode allocations. First, the technique combines P300-like components obtained by the ICA run within a target epoch in order to obtainan averaged P300 spatial distribution. Second, the technique averages spatial distributions of P300 signals obtained from different target epochs in order to get the final averaged template. Such an template can be useful for any BCI technique where spatial selection is used to detect evoked potentials.

Dipyridamole-induced C-type natriuretic peptide mRNA overexpression in a minipig model of pacing-induced left ventricular dysfunction.

Dipyridamole (DP) restores ischemic tissue blood flow stimulating angiogenesis in eNOS-dependent pathways. C-type natriuretic peptide (CNP) is expected to mimic the migration-stimulatory effect of NO via a cGMP-dependent mechanism. Aim of this study was to assess the role of concomitant treatment with DP on CNP levels in blood and myocardial tissue of minipigs with left ventricular dysfunction (LVD) induced by pacing at 200bpm in the right ventricular apex. Minipigs with DP therapy (DP+, n=4) or placebo (DP-, n=4) and controls (C-SHAM, n=4) underwent 2D-EchoDoppler examination and blood collection before and after 4 weeks of pacing, when cardiac tissue was collected. Histological/immunohistochemical analyses were performed. CNP levels were determined by radioimmunoassay; cardiac CNP, BNP, natriuretic receptors expression by Real-Time PCR. After pacing, cardiac parameters resulted less impaired in DP+ compared to DP-. Histological sections presented normal morphology while the arteriolar density resulted: C-SHAM: 9.0±1.2; DP-: 4.9±0.3; DP+: 6.5±0.6number/mm(2); C-SHAM vs DP- and DP+ p=0.004, p=0.04, respectively. CNP mRNA resulted lower in DP- compared to C-SHAM and DP+ as well as NPR-B (p=0.011, DP- vs DP+). Both NPR-A/NPR-C mRNA expressions were significantly (p<0.001) lower both in DP- and DP+ compared to C-SHAM. BNP mRNA was higher in LVD. CNP plasma levels showed a similar trend with respect to gene expression (C-SHAM: 30.5±15; DP-: 18.6±5.5; DP+: 21.2±4.7pg/ml). These data suggest that DP may serve as a preconditioning agent to increase the protective CNP-mediated endocrine response in LVD. This response, mediated by its specific receptor NPR-B, may offer new insights into molecular targets for treatment of LVD.

Cold perception and gene expression differ in Olea europaea seed coat and embryo during drupe cold acclimation.

FAD2 and FAD7 desaturases are involved in cold acclimation of olive (Olea europaea) mesocarp. There is no research information available on cold acclimation of seeds during mesocarp cold acclimation or on differences in the cold response of the seed coat and embryo. How FAD2 and FAD7 affect seed coat and embryo cold responses is unknown. Osmotin positively affects cold acclimation in olive tree vegetative organs, but its role in the seeds requires investigation. OeFAD2.1, OeFAD2.2, OeFAD7 and Oeosmotin were investigated before and after mesocarp acclimation by transcriptomic, lipidomic and immunolabelling analyses, and cytosolic calcium concentration ([Ca(2+)](cyt)) signalling, F-actin changes and seed development were investigated by epifluorescence/histological analyses. Transient [Ca(2+)](cyt) rises and F-actin disassembly were found in cold-shocked protoplasts from the seed coat, but not from the embryo. The thickness of the outer endosperm cuticle increased during drupe exposure to lowering of temperature, whereas the embryo protoderm always lacked cuticle. OeFAD2 transcription increased in both the embryo and seed coat in the cold-acclimated drupe, but linoleic acid (i.e. the product of FAD2 activity) increased solely in the seed coat. Osmotin was immunodetected in the seed coat and endosperm of the cold-acclimated drupe, and not in the embryo. The results show cold responsiveness in the seed coat and cold tolerance in the embryo. We propose a role for the seed coat in maintaining embryo cold tolerance by increasing endosperm cutinization through FAD2 and osmotin activities.

Pharmacokinetics of TH-302: a hypoxically activated prodrug of bromo-isophosphoramide mustard in mice, rats, dogs and monkeys.

PURPOSE: To characterize the pharmacokinetics of the prodrug, TH-302, and its active metabolite, bromo-IPM (Br-IPM), in nonclinical species. METHODS: TH-302 was administered in single oral, intraperitoneal and intravenous bolus doses to mice, rats, dogs and monkeys as well as in acute and chronic safety studies in rats and dogs as a 30-min intravenous infusion given once a week for 3 weeks. Assessments were made using liquid chromatography-tandem mass spectrometry. RESULTS: TH-302 was extensively distributed with high systemic clearance exceeding hepatic plasma flow in all species studied, resulting in half-lives ranging between 8 min (mice) and over 4 h (rats). In rats, TH-302 exhibited linear kinetics following intravenous administration and good oral bioavailability. In acute and chronic safety studies, there was no accumulation of TH-302 following once weekly dosing for 3 weeks in the rat and dog. Br-IPM plasma concentrations were a small fraction of the TH-302 plasma concentrations with significantly smaller percentages present in dogs than in rats. Allometric scaling predicted that the systemic clearance and steady-state volume of distribution in humans would be 38.8 l/h/m(2) and 34.3 l/m(2), respectively, resulting in a terminal elimination half-life of about 36 min. These values were similar to those observed in patients with solid tumors (27.1 l/h/m(2), 23.5 l/m(2) and 47 min). CONCLUSIONS: TH-302 exhibited good safety, efficacy and pharmacokinetic properties in nonclinical species, translating into favorable properties in humans.

A micro-PET/CT approach using O-(2-[18F]fluoroethyl)-L-tyrosine in an experimental animal model of F98 glioma for BNCT.

The present study focuses on a micro-PET/CT application to be used for experimental Boron Neutron Capture Therapy (BNCT), which integrates, in the same frame, micro-CT derived anatomy and PET radiotracer distribution. Preliminary results have demonstrated that (18)F-fluoroethyl-tyrosine (FET)/PET allows the identification of the extent of cerebral lesions in F98 tumor bearing rat. Neutron autoradiography and α-spectrometry on axial tissues slices confirmed the tumor localization and extraction, after the administration of fructose-boronophenylalanine (BPA). Therefore, FET-PET approach can be used to assess the transport, the net influx, and the accumulation of FET, as an aromatic amino acid analog of BPA, in experimental animal model. Coregistered micro-CT images allowed the accurate morphological localization of the radiotracer distribution and its potential use for experimental BNCT.

Cold affects the transcription of fatty acid desaturases and oil quality in the fruit of Olea europaea L. genotypes with different cold hardiness.

The olive tree lacks dormancy and is low temperature sensitive, with differences in cold tolerance and oil quality among genotypes. The oil is produced in the drupe, and the unsaturated fatty acids contribute to its quality. The aim of the present research was to investigate the relationship among development, cold response, expression of fatty acid desaturase (FAD) genes, and unsaturated fatty acid composition in drupes belonging to genotypes differing in leaf cold tolerance, but producing good oil (i.e. the non-hardy Moraiolo, the semi-hardy Frantoio, and the hardy Canino). In all genotypes, cold sensitivity, evaluated by cold-induced transient increases in cytosolic calcium, was high in the epi-mesocarp cells before oil body formation, and decreased during oil biogenesis. However, genotype-dependent differences in cold sensitivity appeared at the end of oil production. Genotype-dependent differences in FAD2.1, FAD2.2, FAD6, and FAD7 expression levels occurred in the epi-mesocarp cells during the oleogenic period. However, FAD2.1 and FAD7 were always the highest in the first part of this period. FAD2.2 and FAD7 increased after cold applications during oleogenesis, independently of the genotype. Unsaturated fatty acids increased in the drupes of the non-hardy genotype, but not in those of the hardy one, after cold exposure at the time of the highest FAD transcription. The results show a direct relationship between FAD expression and lipid desaturation in the drupes of the cold-sensitive genotype, and an inverse relationship in those of the cold-resistant genotype, suggesting that drupe cold acclimation requires a fine FAD post-transcriptional regulation. Hypotheses relating FAD desaturation to storage and membrane lipids, and genotype cold hardiness are discussed.

A ruptured right sinus of Valsalva diverticled aneurysm: echocardiographic diagnosis and surgical repair.

Aneurysms of sinus of Valsava (SV) are uncommon heart lesions resulting from either a congenital deficiency or an acquired degeneration of the aortic wall. Usually these lesions are asymptomatic and incidentally diagnosed by echocardiography. Therefore when rupture occurs, they might require a prompt surgical operation. We report the case of a 58-year-old man who suddenly developed chest pain. On physical examination a new finding of sistodyastolic murmur was detected. On two-dimensional echocardiography was evidenced an aneurysm of the right SV ruptured in the right atrium. The patient was submitted to urgent surgery. Surgical aneurysm exclusion was achieved through a double access either transaortic and trans-right atrium approach. The right SV was obliterated by suturing a dacron patch on the aortic site while complete exclusion of the aneurysm expanding in the right atrium, was acquired through the right atrium itself, by 5/0 continous prolene suture line. The postoperative course was uneventful and the patient was discharged on 6th postoperative day. Transesophageal echocardiography represent the gold standard technique to assess this disease and to plan the adequate surgical treatment. The management of an asymptomatic, non ruptured aneurysm is not clear, however surgery is advisable when the aneurysm is complicated by rupture with an acceptably low operative risk and good long-term outcome.

Automatic screening of obstructive sleep apnea from the ECG based on empirical mode decomposition and wavelet analysis.

This study analyses two different methods to detect obstructive sleep apnea (OSA) during sleep time based only on the ECG signal. OSA is a common sleep disorder caused by repetitive occlusions of the upper airways, which produces a characteristic pattern on the ECG. ECG features, such as the heart rate variability (HRV) and the QRS peak area, contain information suitable for making a fast, non-invasive and simple screening of sleep apnea. Fifty recordings freely available on Physionet have been included in this analysis, subdivided in a training and in a testing set. We investigated the possibility of using the recently proposed method of empirical mode decomposition (EMD) for this application, comparing the results with the ones obtained through the well-established wavelet analysis (WA). By these decomposition techniques, several features have been extracted from the ECG signal and complemented with a series of standard HRV time domain measures. The best performing feature subset, selected through a sequential feature selection (SFS) method, was used as the input of linear and quadratic discriminant classifiers. In this way we were able to classify the signals on a minute-by-minute basis as apneic or nonapneic with different best-subset sizes, obtaining an accuracy up to 89% with WA and 85% with EMD. Furthermore, 100% correct discrimination of apneic patients from normal subjects was achieved independently of the feature extractor. Finally, the same procedure was repeated by pooling features from standard HRV time domain, EMD and WA together in order to investigate if the two decomposition techniques could provide complementary features. The obtained accuracy was 89%, similarly to the one achieved using only Wavelet analysis as the feature extractor; however, some complementary features in EMD and WA are evident.

Sleep staging classification based on HRV: time-variant analysis.

An algorithm to evaluate the sleep macrostructure based on heart rate fluctuations from ECG signal is presented. This algorithm is an attempt to evaluate the sleep quality out of sleep centers. The algorithm is made up by a) a time-variant autoregressive model used as feature extractor and b) a hidden Markov model used as classifier. Characteristics coming from the joint probability of HRV features were used to fed the HMM. 17 full polysomnography recordings from healthy subjects were used in the current analysis. When compared to Wake-NREM-REM given by experts, the automatic classifier achieved a total accuracy of 78.21+/-6.44% and a kappa index of 0.41+/-.1085 using two features and a total accuracy of 79.43+/-8.83% and kappa index of 0.42+/-.1493 using three features.

Automatic detection of sleep macrostructure based on bed sensors.

This study analyses the spectral components of the heart rate fluctuations of a new contact-less technology for sleep evaluation. Both heart beat interval (HBI) and movement activity were extracted from the multichannel ballistocardiographic (BCG) measurements, based on Emfit sensor foils placed into bed mattress. Powers spectral densities (PSD) of HBI have been compared with the ones obtained from the standard ECG during sleep stage 2. In addition, spectral features obtained from the contact-less technology and standard ECG has been used to automatically classify the sleep macrostructure through a time-varying autoregressive model and a Hidden Markov Model. Whole night recordings from six subjects were analyzed in this study. Spectral components did not show significant differences between the two measurements. Further, contactless technology achieved a total accuracy of 83 % and kappa index of 0.42, while standard ECG achieved an accuracy of 84 % and kappa index of 0.43 when compared to clinical sleep staging from polysomnography.

Analysis of heart rate variability to predict patient age in a healthy population.

OBJECTIVES: To estimate age of healthy subjects by means of the heart rate variability (HRV) parameters thus assessing the potentiality of HRV indexes as a biomarker of age. METHODS: Long-term indexes of HRV in time domain, frequency domain and non-linear parameters were computed on 24-hour recordings in a dataset of 63 healthy subjects (age range 20-76 years old). Then, as interbeat dynamics markedly change with age, showing a reduced HRV in older subjects, we tried to capture age-related influence on HRV by principal component analysis and to predict the subject age by means of a feedforward neural network. RESULTS: The network provides good prediction of patient age, even if a slight overestimation in the younger subjects and a slight underestimation in the older ones were observed. In addition, the important contribution of non-linear indexes to prediction is underlined. CONCLUSIONS: HRV as a predictor of age may lead to the definition of a new biomarker of aging.

Direct investigation of orbital ordering in a colossal magnetoresistance manganite by means of X-ray linear dichroism at the Mn L edge.

We have investigated for the first time the orbital ordering in a three-dimensional colossal magnetoresistance manganite, namely La(7/8)Sr(1/8)MnO3, by applying soft X-ray linear dichroism (XLD) to the Mn L edge. We found that the cooperative Jahn-Teller distorted orthorhombic phase, which is present at a temperature of 240 K, is probably accompanied by a predominantly cross type (x2 - z2)/(y2 - z2) orbital ordering. This result is discussed in the light of different exchange interaction models.

Electronic structure of A- and B-site doped lanthanum manganites: a combined X-ray spectroscopic study.

The electronic properties of a series of colossal magnetoresistance (CMR) compounds, namely LaMnO3, La(1-x)Ba(x)(MnO3 (0.2 < or = x < or = 0.55), La(0.76)Ba(0.24)Mn(0.84)Co(0.16)O3, and La(0.76)Ba(0.24)Mn(0.78)Ni(0.22)O3, have been investigated in a detailed spectroscopic study. A combination of X-ray photoelectron spectroscopy (XPS), X-ray emission spectroscopy (XES), X-ray absorption spectroscopy (XAS), and resonant inelastic X-ray scattering (RIXS) was used to reveal a detailed picture of the electronic structure in the presence of Ba, Co, and Ni doping in different concentrations. The results are compared with available theory. The valence band of La(1-x)()Ba(x)MnO3 (0 < or = x < or = 0.55) is dominated by La 5p, Mn 3d, and O 2p states, and strong hybridization between Mn 3d and O 2p states is present over the whole range of Ba concentrations. Co-doping at the Mn site leads to an increased occupancy of the e(g) states near the Fermi energy and an increase in the XPS valence band intensity between 0.5 and 5 eV, whereas the Ni-doped sample shows a lower density of occupied states near the Fermi energy. The Ni d states are located in a band spanning the energy range of 1.5-5 eV. XAS spectra indicate that the hole doping leads to mixed Mn 3d-O 2p states. Furthermore, RIXS at the Mn L edge has been used to probe d-d transitions and charge-transfer excitations in La(1-x)Ba(x)MnO3.

[4 + 2] cycloadditions of nitroalkenes in water. Highly asymmetric synthesis of functionalized nitronates.

The [4 + 2] cycloadditions of (E)-2-aryl-1-cyano-1-nitroalkenes 1 with achiral and enantiopure vinyl ethers 2 and 3 carried out in sole water are reported. These reactions occur in a heterogeneous phase under mild conditions and are fast and highly stereoselective. By using (-)-N,N-dicyclohexyl-(1S)-isoborneol-10-sulfonamide as a chiral auxiliary, the cycloadditions are totally asymmetric. The face selectivity is discussed in terms of the shape of the chiral auxiliary and the reactive conformation of vinyl ether.

An approach to the design of reinforcement functions in real world, agent-based applications.

The success of any reinforcement learning (RL) application is in large part due to the design of an appropriate reinforcement function. A methodological framework to support the design of reinforcement functions has not been defined yet, and this critical and often underestimated activity is left to the ability of the RL application designer. We propose an approach to support reinforcement function design in RL applications concerning learning behaviors for autonomous agents. We define some dimensions along which we can describe reinforcement functions; we consider the distribution of reinforcement values, their coherence and their matching with the designer's perspective. We give hints to define measures that objectively describe the reinforcement function; we discuss the trade-offs that should be considered to improve learning and we introduce the dimensions along which this improvement can be expected. The approach we are presenting is general enough to be adopted in a large number of RL projects. We show how to apply it in the design of learning classifier systems (LCS) applications. We consider a simple, but quite complete case study in evolutionary robotics, and we discuss reinforcement function design issues in this sample context.

Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas.

The effect of hyperthermia on the accumulation of technetium-99m-labeled liposomes was studied in feline sarcomas. Each cat received two separate injections of liposomes. The first was used to quantify the amount of technetium-99m-labeled liposomes within the tumor under normothermic conditions. The second injection was made at the beginning of a 60-min hyperthermia procedure. Planar scintigraphy was used to measure the activity of technetium-99m-labeled liposomes within the tumor at predetermined times up to 18 h after injection. Regions of interest were drawn for the tumor, lungs, liver, kidney, and aorta. Counts in the regions of interest were decay corrected. Counts/pixel in the tumor under normothermic and hyperthermic conditions were normalized to aorta counts/pixel. A total of 16 cats were eligible for the study. In two of the 16 cats, incomplete count data precluded analysis. In the remaining 14 cats, hyperthermia resulted in a significant increase in liposome accumulation in the tumor (P = 0.001). Tumor volume ranged from 1.2 to 236.2 cm3, and thermal dose ranged from 2.0 to 243.3 CEM43CT90 (equivalent time that the 10th percentile temperature was equal to 43 degrees C). There was not a relationship between either tumor volume or hyperthermia dose on the magnitude of increased liposome accumulation, suggesting that this method has application across a range of tumor volumes and degrees of heatibility.