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Introduction This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer's disease (AD). Methods Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham). Results PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P

This article belongs to the Proceedings of The 8th International Symposium on Sensor Science This work attempts the identification of the production year, the cultivar's region and the aging method used in the elaboration of different Spanish red wines, all from the "tempranillo" grape variety. The identification of such characteristics relies on the use of a voltammetric electronic tongue (ET) system formed by modified graphite-epoxy electrodes (GEC) and metallic electrodes to collect a set of six voltammograms per sample, and different chemometric tools to accomplish the final identifications. A large sample set that included 199 different wine samples from commercial and own elaboration origin were analysed with the electronic tongue system, using the cyclic voltammetry technique and without any sample pre-treatment. To process the extremely complex and high-dimensionality generated data, a compression strategy was used for the acquired voltammograms, using discrete wavelet transform (DWT). This treatment reduced the information to ca. 10%, preserving significant features from the voltammetric signals. Compressed data was evaluated firstly by unsupervised methods, i.e., principal component analysis (PCA), without much success as it was found that such methods were unable to unravel the patterns contained within such complex data samples. Finally, the processed electrochemical information was evaluated by supervised methods to accomplish the proper identification; among those methods were linear discriminant analysis (LDA), supported vector machines (SVM) or artificial neural networks (ANN). The best results were obtained using artificial neural networks (ANNs), achieving 96.1% of correct classification for bottled year, 86.8% for elaboration region (protected designation of origin) and 98.6% for maturation type with or without use of wood barrel.

Resumen Introduccion En la actualidad no existe consenso en cuanto a la necesidad de realizar linfadenectomia axilar (LA) en los casos en que se detectan macrometastasis en el ganglio centinela (GC). En este estudio se presenta la utilidad del ganglio secundario (GS), una nueva tecnica diagnostica, como factor predictor de afectacion axilar. Metodos Se diseno un estudio observacional, retrospectivo y multicentrico con el objetivo de validar la tecnica del GS, entendido como tal el siguiente ganglio a nivel anatomico y de difusion linfogammagrafica tras el GC, como predictor de la afectacion axilar. Sobre un total de 2.273 pacientes afectas de cancer de mama se obtuvo una muestra valida de 283 pacientes a las que se habia analizado el estado del GS de forma adicional. Las variables principales del estudio fueron el estado histologico del GC, del GS y del vaciamiento axilar y se valoro la sensibilidad, especificidad y exactitud de la prueba. Resultados La prueba del GS, con GC positivo, presenta una sensibilidad del 61,1%, una especificidad del 78,7%, un valor predictivo positivo del 45,8% y un valor predictivo negativo del 87,3%, con una exactitud del 74,7%. Conclusion El estudio del GS junto con la tecnica del GC permite realizar una estadificacion mas precisa del estado axilar, en pacientes con cancer de mama, en comparacion con el estudio unico del GC.

Introduction: Currently, there is no agreement regarding if it would be necessary to perform an axillary lymph node dissection (ALND) in patients who have macrometastases in the sentinel lymph node (SLN). We studied the utility of the secondary node analysis (SN), defined as the following node after the SLN in an anatomical and lymphatic pathway, as a sign of malignant axillary involvement. Methods: An observational, retrospective and multicentre study was designed to assess the utility of the SN as a sign of axillary involvement. Among 2273 patients with breast cancer, a valid sample of 283 was obtained representing those who had the SN studied. Main end-points of our study were: the SLN, the SN and the ALND histological pattern. Sensitivity, specificity and precision of the test were also calculated. Results: SN test, in cases with positive SLN, has a sensitivity of 61.1%, a specificity of 78.7%, a positive predictive value of 45.8% and a negative predictive value of 87.3% with a precision of 74.7%. Conclusion: The study of the SN together with the technique of the SLN allows a more precise staging of the axillary involvement, in patients with breast cancer, than just the SLN technique. (C) 2017 AEC. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: studies conducted in animal models and humans suggest the presence of a dynamic equilibrium of amyloid-β (Aβ) peptide between cerebrospinal fluid (CSF) and plasma compartments. Objective: to determine whether plasma exchange (PE) with albumin replacement was able to modify Aβ concentrations in CSF and plasma as well as to improve cognition in patients with mild-moderate Alzheimer's disease (AD). Methods: in a multicenter, randomized, patient- and rater-blind, controlled, parallel-group, phase II study, 42 AD patients were assigned (1 : 1) to PE treatment or control (sham) groups. Treated patients received a maximum of 18 PE with 5% albumin (Albutein®, Grifols) with three different schedules: two PE/weekly (three weeks), one PE/weekly (six weeks), and one PE/bi- weekly (12 weeks), plus a six-month follow-up period. Plasma and CSF Aβ1-40 and Aβ1-42 levels, as well as cognitive, functional, and behavioral measures were determined. Results: CSF Aβ1-42 levels after the last PE compared to baseline were marginally higher in PE-treated group versus controls (adjusted means of variation: 75.3 versus -45.5 pg/mL; 95% CI: -19.8, 170.5 versus 135.1, 44.2; p = 0.072). Plasma Aβ1-42 levels were lower in the PE-treated group after each treatment period (p

Grape-derived polyphenols are considered to be one of the most promising ingredients for functional foods due to their health-promoting activities. We applied a HPLC-MS-based untargeted metabolomic approach in order to evaluate the impact of a functional food based on grape skin polyphenols on the urinary metabolome of healthy subjects. Thirty-one volunteers participated in two dietary crossover randomized intervention studies: with a single-dose intake (187 mL) and with a 15-day sustained consumption (twice per day, 187 mL per day in total) of a functional beverage (FB). Postprandial (4-hour) and 24-hour urine samples collected after acute consumption and on the last day of sustained FB consumption, respectively, were analysed using an untargeted HPLC-qTOF-MS approach. Multivariate modelling with subsequent application of an S-plot revealed differential mass features related to acute and prolonged consumption of FB. More than half of the mass features were shared between the two types of samples, among which several phase II metabolites of grape-derived polyphenols were identified at confidence level II. Prolonged consumption of FB was specifically reflected in urine metabolome by the presence of first-stage microbial metabolites of flavanols: hydroxyvaleric acid and hydroxyvalerolactone derivatives. Overall, several epicatechin and phenolic acid metabolites both of tissular and microbiota origin were the most representative markers of FB consumption. To our knowledge, this is one of the first studies where an untargeted LC-MS metabolomic approach has been applied in nutrition research on a grape-derived FB., This work has been supported by Spanish public grants AGL2006-14228-C03-02 and AGL2009-13906-C02-01 and the CONSOLIDER-INGENIO 2010 Programme, FUN-C-FOOD (CSD2007-063) from the Spanish Ministry of Economy and Competitiveness (MINECO), the PI13/01172 Project (Plan N de I+D+i 2013–2016) by ISCII-Subdirección General de Evaluación y Fomento de la Investigación as co-funded by FEDER (Fondo Europeo de Desarrollo Regional); the National Strategic Consortia for Technical Research Programme, in collaboration with the Bosch i Gimpera Foundation, FBG305132 and FBG305273; and Miguel Torres S.A. (Proyecto CENIT HIGEA CEN-20072003). We also thank the award of 2014SGR1566 from the Generalitat de Catalunya’s Agency AGAUR. The Juan de la Cierva postdoctoral fellowship contract from the Spanish government awarded by the Spanish Ministry to Olha Khymenets is acknowledged. Rosa Vazquez-Fresno, Rafael Llorach and Mireia Urpi-Sarda would like to thank, respectively, the FPI 2010 fellowship and the Ramon y Cajal programmes from MICINN and the European Social Funds.

Systemic lupus erithematosus (SLE) is an autoimmune disease with multiorgan involvement caused principally by vasculitis of small vessels. The gastrointestinal tract is one of the most frequently affected by SLE, with abdominal pain as the most common symptom. An early diagnosis and treatment of lupus enteritis is essential to avoid complications like hemorrhage or perforation, with up to 50 % of mortality rate. However, differential diagnosis sometimes is difficult, especially with other types of gastrointestinal diseases as digestive involvement of antiphospholipid syndrome (APS), moreover when both entities may coexist. We describe the case of a patient with both diseases that was diagnosed with lupus enteritis and treated with steroid therapy; the patient had an excellent response.

The purpose of this study was to determine whether phenolic extracts with antimicrobial activity may be considered as an alternative to the use of sulfur dioxide (SO 2) for controlling malolactic fermentation (MLF) in winemaking. Inhibition of the growth of six enological strains (Lactobacillus hilgardii CIAL-49, Lactobacillus casei CIAL-52, Lactobacillus plantarum CIAL-92, Pediococcus pentosaceus CIAL-85, Oenococcus oeni CIAL-91 and O. oeni CIAL-96) by phenolic extracts (n = 54) from different origins (spices, flowers, leaves, fruits, legumes, seeds, skins, agricultural by-products and others) was evaluated, being the survival parameter IC 50 calculated. A total of 24 extracts were found to significantly inhibit the growth of at least two of the LAB strains studied. Some of these extracts were also active against two acetic acid bacteria (Acetobacter aceti CIAL-106 and Gluconobacter oxydans CIAL-107). Transmission electron microscopy of the bacteria cells after incubation with the phenolic extract confirmed damage of the integrity of the cell membrane. Finally, to test the technological applicability of the extracts, the eucalyptus extract was added (2 g/L) to an industrially elaborated red wine, and the progress of the MLF was evaluated by means of residual content of malic acid. Addition of the extract significantly delayed the progress of both inoculated and spontaneous MLF, in comparison to the control wine (no antimicrobial agent added), although not as effective as K 2S 2O 5 (30 mg/L). These results demonstrated the potential applicability of phenolic extracts as antimicrobial agents in winemaking. © 2012 Elsevier Ltd., This work has been funded by the Spanish Ministry for Science and Innovation (AGL2006-04514, AGL2009-13361-C02-00, PRI-PIBAR-2011-1358 and CSD2007-00063 Consolider Ingenio 2010 FUN-C-FOOD Projects), and the Comunidad de Madrid (ALIBIRD P2009/AGR-1469 Project). AGR and CC are the recipients of a fellowship from the JAE-Pre Program (CSIC) and the FPI program (MICINN), respectively.

In recent years, the wine industry has become increasingly interested in the influence of the terroir characteristics on the features of a wine and, in particular, the mechanisms by which a soil influences wine quality. Among published papers on this topic, most merely describe the effect of the soil; few explain it. In this study were conducted a sensory evaluation and phenolic composition and stilbene concentration tests in order to analyze the effects of soil on wine. Significant differences were found in the results of the tests conducted on two vineyards during two consecutive harvests in 2004 and 2005. The results, in line with previous reports, show that the more fertile of the two vineyards, which was also the one with the greatest water-holding capacity, produced wines that presented significantly lower color intensity and shade, as well as lower total phenolic composition and a smaller quantity of hydroxycinnamic compounds. In 2004, these wines presented significantly higher trans-resveratrol content, due to a fungal attack that was favored by the vineyard's soil characteristics. Extreme drought conditions in 2005 had a marked impact on the characteristics of the wines, increasing wavelength measurements significantly and reducing stilbene concentrations. Finally, sensory evaluations revealed significant differences between the wines produced on the two vineyards in both years for five of the seven attributes evaluated. No significant differences were found from one year to the next between the wines produced from the same vineyard, indicating that the attributes of these wines were maintained despite markedly different vintage conditions.

The electronic and optical properties of the rutile titanium dioxide compound have been investigated experimentally by absorption measurements and theoretically by a full‐potential linearized augmented plane wave (FPLAPW) method within the local density approximation (LDA). The thin films for the absorption measurements were prepared by DC magnetron sputtering. The theoretical results for the absorption compared qualitatively well with the experimental findings. The dielectric functions and band‐structure have also been calculated, and the LDA band‐gap energy is corrected by an on‐site Coulomb potential.