Interlaboratory Coverage Test on Plant Food Bioactive Compounds and their Metabolites by Mass Spectrometry-Based Untargeted Metabolomics.

Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method

Flavanols and Anthocyanins in Cardiovascular Health: A Review of Current Evidence

Nowadays it is accepted that natural flavonoids present in fruits and plant-derived-foods are relevant, not only for technological reasons and organoleptic properties, but also because of their potential health-promoting effects, as suggested by the available experimental and epidemiological evidence. The beneficial biological effects of these food bioactives may be driven by two of their characteristic properties: their affinity for proteins and their antioxidant activity. Over the last 15 years, numerous publications have demonstrated that besides their in vitro antioxidant capacity, certain phenolic compounds, such as anthocyanins, catechins, proanthocyanidins, and other non coloured flavonoids, may regulate different signaling pathways involved in cell survival, growth and differentiation. In this review we will update the knowledge on the cardiovascular effects of anthocyanins, catechins and proanthocyanidins, as implied by the in vitro and clinical studies on these compounds. We also review the available information on the structure, distribution and bioavailability of flavanols (monomeric catechins and proanthocyanidins) and anthocyanins, data necessary in order to understand their role in reducing risk factors and preventing cardiovascular health problems through different aspects of their bioefficacy on vascular parameters (platelet agregation, atherosclerosis, blood pressure, antioxidant status, inflammation-related markers, etc.), myocardial conditions, and whole-body metabolism (serum biochemistry, lipid profile), highlighting the need for better-designed clinical studies to improve the current knowledge on the potential health benefits of these flavonoids to cardiovascular and metabolic health

HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer

Background Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems.Trial design After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment

In Vitro Models for Studying Secondary Plant Metabolite Digestion and Bioaccessibility

There is an increased interest in secondary plant metabolites, such as polyphenols and carotenoids, due to their proposed health benefits. Much attention has focused on their bioavailability, a prerequisite for further physiological functions. As human studies are time consuming, costly, and restricted by ethical concerns, in vitro models for investigating the effects of digestion on these compounds have been developed and employed to predict their release from the food matrix, bioaccessibility, and assess changes in their profiles prior to absorption. Most typically, models simulate digestion in the oral cavity, the stomach, the small intestine, and, occasionally, the large intestine. A plethora of models have been reported, the choice mostly driven by the type of phytochemical studied, whether the purpose is screening or studying under close physiological conditions, and the availability of the model systems. Unfortunately, the diversity of model conditions has hampered the ability to compare results across different studies. For example, there is substantial variability in the time of digestion, concentrations of salts, enzymes, and bile acids used, pH, the inclusion of various digestion stages; and whether chosen conditions are static (with fixed concentrations of enzymes, bile salts, digesta, and so on) or dynamic (varying concentrations of these constituents). This review presents an overview of models that have been employed to study the digestion of both lipophilic and hydrophilic phytochemicals, comparing digestive conditions in vitro and in vivo and, finally, suggests a set of parameters for static models that resemble physiological conditions

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

(Poly)phenols are a large group of compounds, found in food, beverages, dietary supplements and herbal medicines. Owing to their biological activities, absorption and metabolism of the most abundant compounds in humans are well understood. Both the chemical structure of the phenolic moiety and any attached chemical groups define whether the polyphenol is absorbed in the small intestine, or reaches the colon and is subject to extensive catabolism by colonic microbiota. Untransformed substrates may be absorbed, appearing in plasma primarily as methylated, sulfated and glucuronidated derivatives, with in some cases the unchanged substrate. Many of the catabolites are well absorbed from the colon and appear in the plasma either similarly conjugated, or as glycine conjugates, or in some cases unchanged. Although many (poly)phenol catabolites have been identified in human plasma and / or urine, the pathways from substrate to final catabolite, and the species of bacteria and enzymes involved, are still scarcely reported. While it is clear that the composition of the human gut microbiota can be modulated in vivo by supplementation with some (poly)phenol-rich commodities, such modulation is definitely not an inevitable consequence of supplementation, it depends on the treatment, length of time and on the individual metabotype, and it is not clear whether the modulation is sustained when supplementation ceases. Some catabolites have been recorded in plasma of volunteers at concentrations similar to those shown to be effective in in vitro studies suggesting that some benefit may be achieved in vivo by diets yielding such catabolites

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Llibre Blanc de la mediació a Catalunya

Projectes científics associats: IDT SGR2009-688; ONTOMEDIA CSO-2008-05536-SOCI, TSI-20501-2008-131; GCC SGR2009-221; GREL SGR2009-357; SGR2009-1328; AT CSD2007-0022; AT COST IC0801Altres ajuts: TSI-20501-2008-131Altres ajuts: COST-IC0801L'estudi que es presenta ara és fruit de gairebé dos anys de treball. Una cartografia completa de les experiències en mediació en tots els àmbits socials, de les escoles als hospitals, de les empreses als nuclis familiars, de la mediació comunitària als conflictes de consum o laborals, de la mediació penal a la mediambiental. També s'hi ha incorporat una anàlisi dels costos de la mediació i de la seva configuració jurídica. La conjunció de les fotografies en relleu i dels estudis més teòrics han fet possible la reflexió ulterior, les interpretacions crítiques i, en darrer terme, les conclusions i les recomanacions, que ens ajudaran a progressar. La mediació permet detenir l'escalada dels conflictes i sostreure'ls de la resolució judicial, per implicar les parts i fer-les protagonistes actives de les solucions a què arribin. Des del Departament de Justícia, ens interessa superar l'excessiva judicialització dels conflictes -insatisfactòria per a tothom- i promoure instruments que facilitin, de manera àgil però amb totes les garanties, la intel·ligència dels problemes i, a partir d'aquí, la fixació de les millors solucions per a les parts implicades, que elles mateixes hauran construït

Diseño, análisis y optimización del flujo de aire de un jet de textura

[ES] La empresa AITEX, en la cual el alumno está realizando prácticas en empresa, tiene una máquina BCF (Bulked Continuous Filament) parada desde hace más de un año, debido a que no disponen de una pieza necesaria que pueda soportar las exigencias de dicha máquina. Por lo que una de las tareas encomendadas en la puesta en marcha de la máquina es realizar el diseño y los estudios de esta pieza, es decir, realizar el diseño de un "JET" (boquilla a instalar dentro del kit del chorro de textura) que se acople a dicha máquina, y hacer un estudio y simulación para calcular el flujo de aire para su correcto funcionamiento, estos dos últimos procesos se realizarán mediante un software de elementos finitos. Para conseguir el objetivo, se realizará tanto el diseño del jet, como los estudios necesarios para optimizar el flujo de aire y para que esta pieza pueda soportar las temperaturas, esfuerzos y volúmenes de hilo que circularán por su interior. Como se ha nombrado anteriormente, con la ayuda del software de elementos finitos, se realizarán diferentes simulaciones para obtener el diseño más apropiado en función del flujo de aire obtenido. El funcionamiento de la máquina BCF consiste en poder hacer un hilo con mayor grosor. Después de pasar por una serie de rodillos para darle estiraje al hilo, se introducirá en un bloque donde se encontrará nuestra pieza, en el interior de nuestra pieza se le proporcionará al hilo aire a presión a través de dos conductos, consiguiendo así un aumento de tamaño, pasando de tener un hilo fino a un hilo más grueso. Por tanto, el objetivo de tener operativo el jet se realizará para poder aumentar el grosor del hilo, permitiendo así poner en marcha la línea de trabajo de estampación en alfombras, por lo que será un proyecto de gran ayuda para la empresa.[EN] The AITEX company, in which the student is doing an internship in a company, has a BCF (Bulked Continuous Filament) machine stopped for more than a year, because it does not have a necessary part that can withstand the demands of said machine. Therefore, one of the tasks entrusted to start up the machine is to design and study this part, that is, to design a "JET" (nozzle to be installed in the texture jet kit). that is attached to said machine, and make a study and simulation to calculate the air flow for its correct operation, these last two processes are carried out using finite element software. To achieve the objective, both the design of the jet will be carried out, as well as the necessary studies to optimize the air flow and so that this piece can withstand the temperatures, efforts and volumes of thread that will circulate inside it. As mentioned above, with the help of finite element software, different simulations were performed to obtain the most appropriate design based on the air flow obtained. The operation of the BCF machine consists of being able to make a thread with greater thickness. After passing through a series of rollers to stretch the yarn, it will be introduced into a block where our piece will be found, inside our piece the wire will be supplied with pressurized air through two conductors, thus achieving an increase in size, going from having a fine thread to a thicker thread. Therefore, the objective of having the jet operational will be carried out in order to increase the thickness of the thread, thus allowing to start up the line of work of stamping on carpets, so it will be a project of great help for the company.Aura Pascual, D. (2021). Diseño, análisis y optimización del flujo de aire de un jet de textura. Universitat Politècnica de València. http://hdl.handle.net/10251/174243TFG

Dual Role of Natural Killer Cells on Graft Rejection and Control of Cytomegalovirus Infection in Renal Transplantation

Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural killer (NK) cells may display alloreactive potential in case of mismatch between recipient inhibitory killer-cell immunoglobulin-like receptors (KIRs) and graft HLA class I molecules. Several studies have addressed the impact of this variable in kidney transplant with conflicting conclusions; yet, increasing evidence supports that alloantibody-mediated NK cell activation via FcγRIIIA (CD16) contributes to rejection. On the other hand, human cytomegalovirus (HCMV) infection constitutes a risk factor directly associated with the rate of graft loss and reduced host survival. The levels of HCMV-specific CD8+ T cells have been reported to predict the risk of posttransplant infection, and KIR-B haplotypes containing activating KIR genes have been related with protection. HCMV infection promotes to a variable extent an adaptive differentiation and expansion of a subset of mature NK cells, which display the CD94/NKG2C-activating receptor. Evidence supporting that adaptive NKG2C+ NK cells may contribute to control the viral infection in kidney transplant recipients has been recently obtained. The dual role of NK cells in the interrelation of HCMV infection with rejection deserves attention. Further phenotypic, functional, and genetic analyses of NK cells may provide additional insights on the pathogenesis of solid organ transplant complications, leading to the development of biomarkers with potential clinical value.The authors are supported by a coordinated research project from Fundació La Marató de TV3 (137/C/2012) and by grants from: Plan Estatal I+D Retos (SAF2013-49063-C2-1-R), Spanish Ministry of Economy and Competitiveness (MINECO, FEDER); EU FP7-MINECO Infect-ERA program (PCIN-2015-191-C02-01); FIS-FEDER PI13/00598 and 16/00617, Intensification Programs (Spanish Ministry of Health ISCIII); and RedinRen RD16/0009/0013. AM is supported by Asociación Española Contra el Cáncer (AECC). AP is supported by EU-FP7 Marie Curie Training Network (NATURIMMUN FP7-PEOPLE-2012-ITN-317013)