Reinforcing the Recommendations for Future Research

(Poly)phenols have anti-diabetic properties that are mediated through the regulation of the main biomarkers associated with type 2 diabetes mellitus (T2DM) (fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (IR)), as well as the modulation of other metabolic, inflammatory and oxidative stress pathways. A wide range of human and pre-clinical studies supports these effects for different plant products containing mixed (poly)phenols (e.g., berries, cocoa, tea) and for some single compounds (e.g., resveratrol). We went through some of the latest human intervention trials and pre-clinical studies looking at (poly)phenols against T2DM to update the current evidence and to examine the progress in this field to achieve consistent proof of the anti-diabetic benefits of these compounds. Overall, the reported effects remain small and highly variable, and the accumulated data are still limited and contradictory, as shown by recent meta-analyses. We found newly published studies with better experimental strategies, but there were also examples of studies that still need to be improved. Herein, we highlight some of the main aspects that still need to be considered in future studies and reinforce the messages that need to be taken on board to achieve consistent evidence of the anti-diabetic effects of (poly)phenols.publishersversionpublishe

Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study

The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.This work was financially supported by the Centre for the Development of Industrial Technology (CDTI) from the Spanish Government (NEMAF project) and R.G.V., P.F-B. and M-T.G.C. are participating to the COST Action FA1403 Positive (Interindividual variation in response to consumption of plant food bioactives and determinants involved). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.[Purpose] The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease.[Methods] In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis.[Results] After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (−18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products.[Conclusions] Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.This study was supported by public funds: Projects CICYT-BFU2007-60576 and Consolider-Ingenio 2010 (CSD2007-00063, Fun-C-Food) from the Spanish Ministry of Science and Innovation (MICINN) and GERM-06-04486 (Fundación Séneca, Murcia, Spain). Dr. Tomé-Carneiro received a FPI grant from MICINN and Dr. Larrosa received a JAE-DOC contract from the Consejo Superior de Investigaciones Científicas (CSIC, Spain).Peer reviewe

A systematic review and meta-analysis of the effects of flavanol-containing tea, cocoa and apple products on body composition and blood lipids: exploring the factors responsible for variability in their efficacy

Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p &lt; 0.001), waist circumference (−0.29, p &lt; 0.001), total-cholesterol (−0.21, p &lt; 0.001), LDL-cholesterol (−0.23, p &lt; 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m2, non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders

A landscape of the Castillian Plateau during Late Pleistocene. Paleontological aspects of the Zarzamora Cave (Segovia, Spain)

En este trabajo se exponen los aspectos paleoecológicos de la cueva de la Zarzamora (Segovia, España); un yacimiento kárstico del Pleistoceno Superior, que se encuentra en la zona de transición entre la Sierra de Guadarrama y la Submeseta Norte castellana. La asociación de macrofauna sugiere un paisaje abierto, dominado por especies pastadoras, équidos (Equus ferus y Equus hydruntinus) en su mayoría, además de bovinos y rinocerontes. Entre los carnívoros destaca la hiena manchada (Crocuta crocuta) tanto por la abundancia de restos esqueléticos como por las evidencias de su presencia en la cueva (coprolitos, marcas de dientes y huesos digeridos). Además hay félidos (cf. Panthera pardus., Lynx sp.), cánidos (Canis lupus, Vulpes vulpes) y una especie de mustélido (Meles meles). La asociación de micromamíferos, tanto los taxones dominantes (Oryctolagus cuniculus, Microtus cabrerae y Microtus duodecimcostatus) como el resto de las especies identificadas, es característica de un periodo climático templado. La ausencia de especies del Pleistoceno Medio indica una edad más reciente dentro del Pleistoceno Superior. Los resultados del análisis polínico obtenido de coprolitos de hiena corroboran la existencia de un paisaje abierto con estepas, prados y pequeños bosquetes aclarados dominados por robles y encinas, además de Juniperus y taxones mesófilos.This study presents paleoecological aspects of the Zarzamora Cave karstic site (Segovia, Spain). This site is a Late Pleistocene cave deposit in a limestone outcrop that extends from the crystalline piedmont of the Sierra de Guadarrama to the Tertiary Castilian Plateau. The Zarzamora Cave is a small gallery with a NE-SW direction and approximately 1 m high, 2 m wide and around 7 m in longitudinal accessible development. The total length is still unknown due to the sediment infilling. The “keyhole shaped” section suggests that the karstic system evolved from phreatic to vadose conditions. The sedimentary infilling is around 90 cm thick and four stratigraphic units have been identified. The upper three units are made of crystalline dolomite matrix with macro and microvertebrate fossils. The lower unit is made of plastic clay with no paleontological evidence. The entrance to the Zarzamora Cave is a few meters away from the entrance of the Búho Cave. It was during the excavation of the latter in the late years of the 1980s that the entrance to the Zarzamora Cave was found. Then, the site was divided in three sectors: Búho Cave, Zarzamora Cave and Cata Exterior.Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

El yacimiento kárstico del Pleistoceno Superior de la Cueva del Camino en el Calvero de la Higuera (Pinilla del Valle, Madrid)

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

¿Qué parásito soy?: aprendizaje lúdico de la Parasitología mediante el empleo de pistas e imágenes

La Parasitología emplea muchos conceptos, nombres, taxonomía e imágenes que complican el aprendizaje. Desarrollaremos una actividad basada en el juego para relacionar conceptos e imágenes, al tiempo que los alumnos evalúan su evolución de aprendizaje. La actividad se desarrollará en una página web

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses

peer-reviewedUnderstanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed

Assessment of Subjective Well-Being in a Cohort of University Students and Staff Members: Association with Physical Activity and Outdoor Leisure Time during the COVID-19 Pandemic

Time spent outdoors and physical activity (PA) promote mental health. To confirm this relationship in the aftermath of COVID-19 lockdowns, we explored individual levels of anxiety, depression, stress and subjective well-being (SWB) in a cohort of academic students and staff members and tested their association with sport practice, PA at leisure time and time spent outdoors. Our cross-sectional study collected data during the COVID-19 outbreak (April–May 2021) on 939 students and on 238 employees, who completed an online survey on sociodemographic and lifestyle features, depression, anxiety, stress, and SWB. Results showed that the students exhibited higher levels of anxiety, depression, and stress, and lower levels of SWB (p < 0.001 for all domains) compared to the staff members. Correlation analysis confirmed that PA and time spent in nature were associated to high mental health scores among staff and, more consistently, among students. Finally, mediation analyses indicated that the time spent in nature, social relationships, and levels of energy play a mediator role in the relationship between sport practice and SWB. Our evidence reinforces the protective role of time spent in nature in improving mental health, and provides support for policymakers to make appropriate choices for a better management of COVID-19 pandemic consequencesP.P. was funded by Life Quality Research Centre—UIDP/04748/2020, a program financially supported by FCT—Fundação para a Ciência e Tecnolo-gia/Ministério da Educação e Ciência.Peer reviewe

Predictores de riesgo en una cohorte española con cardiolaminopatías. Registro REDLAMINA

[Abstract] Introduction and objectives. According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and ≥ 2 risk factors: male sex, left ventricular ejection fraction (LVEF) < 45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. Methods. The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age ≥ 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. Results. We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF < 45% (P = .001) and NSVT (P < .001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF < 45% (P < .001). Conclusions. In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF < 45%. Therefore, female carriers of missense variants with either NSVT or LVEF < 45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis.[Resumen] Introducción y objetivos. Según las guías de muerte súbita, se debe considerar un desfibrilador automático implantable (DAI) para los pacientes con miocardiopatía dilatada debida a variantes en el gen de la lamina (LMNA) con al menos 2 factores: varones, fracción de eyección del ventrículo izquierdo (FEVI) < 45%, taquicardia ventricular no sostenida (TVNS) y variantes no missense. Nuestro objetivo es describir las características clínicas de una cohorte española de pacientes con cardiolaminopatías (registro REDLAMINA) y evaluar los criterios de riesgo vigentes. Métodos. Se evaluó la relación entre factores de riesgo y eventos cardiovasculares en una cohorte de 140 portadores de variantes en LMNA (54 probandos, 86 familiares, edad ≥ 16 años). Se consideró: a) evento arrítmico mayor (EAM) si hubo descarga apropiada del DAI o muerte súbita, y b) muerte por insuficiencia cardiaca, incluidos los trasplantes. Resultados. Se identificaron 11 variantes nuevas y 21 previamente publicadas. La FEVI < 45% (p = 0,001) y la TVNS (p < 0,001) se relacionaron con los EAM, pero no el sexo o el tipo de variante (missense frente a no missense). La FEVI < 45% (p < 0,001) fue el único factor relacionado con la muerte por insuficiencia cardiaca. Conclusiones. En el registro REDLAMINA, los únicos 2 predictores asociados con EAM fueron la TVNS y la FEVI < 45%. No se debería considerar grupo de bajo riesgo a las portadoras de variantes missense con TVNS o FEVI < 45%. Es importante individualizar la estratificación del riesgo de los portadores de variantes missense en LMNA, porque no todas tienen el mismo pronóstico.This study received a grant from the Proyecto de investigación de la Sección de Insuficiencia Cardiaca 2017 from the Spanish Society of Cardiology and grants from the Instituto de Salud Carlos III (ISCIII) [PI14/0967, PI15/01551, AC16/0014] and ERA-CVD Joint Transnational Call 2016 (Genprovic). Grants from the ISCIII and the Ministerio de Economía y Competitividad de España (Spanish Department of Economy and Competitiveness) are supported by the Plan Estatal de I+D+i 2013-2016: Fondo Europeo de Desarrollo Regional (FEDER) “Una forma de hacer Europa”