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Background: Enhancing self-management in health care through digital tools is a promising strategy to empower patients with type 2 diabetes (T2D) to improve self-care., Objective: This study evaluates whether the Greenhabit (mobile health [mHealth]) behavioral treatment enhances T2D outcomes compared with standard care., Methods: A 12-week, parallel, single-blind randomized controlled trial was conducted with 123 participants (62/123, 50%, female; mean age 58.25 years, SD 9.46 years) recently diagnosed with T2D. Participants were recruited face-to-face from primary care centers in Barcelona, Spain, between July 2021 and March 2022. They were randomly assigned to 1 of 2 groups: (1) an intervention group (n=61) instructed to use the Greenhabit mobile app alongside standard care, or (2) a control group (n=62) who received advice on maintaining a healthy diet and followed standard care. The Greenhabit app incorporates serious gaming technology. Participants received daily messages and challenges focused on promoting a healthy lifestyle, including nutrition, exercise, relaxation, a positive mindset, and a supportive social environment. The app encouraged participants to set weekly goals and awarded points for completing challenges. Data on nutrition, anthropometrics, and blood and urine samples were collected at baseline, 6 weeks, and 12 weeks. Questionnaires assessing quality of life, work-life balance, and social environment were administered at baseline and during the final visit. The primary outcomes were HbA1c and fasting plasma glucose (FPG). Repeated-measures analysis of variance was used to compare changes over time (baseline to 6 weeks and baseline to 12 weeks) between the 2 intervention groups. Analysis of covariance was performed to evaluate changes at 6 and 12 weeks, adjusted for baseline levels of each variable. Multiple contrasts were corrected using a Bonferroni post hoc test., Results: Both groups showed significant reductions in HbA1c after 6 and 12 weeks (mean change in the intervention group [n=50] -0.4%, P<.001 vs -0.3% in the control group [n=53], P=.001) and in FPG after 6 weeks (mean change in the intervention group -5.3 mg/dL, P=.01 vs control group -5.8 mg/dL, P=.01). At 12 weeks, the intervention group also showed significant reductions in systolic and diastolic blood pressures (mean change -4.5, P=.049 and -2.4 mmHg, P=.03, respectively), body weight (mean change -0.8 kg, P=.03), BMI (mean change -0.3 kg/m2, P=.03), waist circumference (mean change -1.0 cm, P=.046), and triglyceride concentration (mean change -20.0 mg/dL, P=.03). There was also a significant increase in high-density lipoprotein-cholesterol concentrations (mean change 2 mg/dL, P=.049). Finally, improvements were noted in 3 out of the 5 elements of balance: positivity, social environment, and work-life balance., Conclusions: The 12-week intervention with the Greenhabit behavioral treatment mHealth app showed beneficial effects on T2D outcomes and reduced the burden of cardiovascular risk factors. Although larger studies are warranted, these results suggest that mHealth apps can be a promising tool for improving T2D self-management., Trial Registration: ISRCTN Registry ISRCTN13456652; http://www.isrctn.com/ISRCTN13456652., (©Ana Maria Ruiz-Leon, Rosa Casas, Sara Castro-Barquero, Sofia Alfaro-González, Petia Radeva, Emilio Sacanella, Francesc Casanovas-Garriga, Ainhoa Pérez-Gesalí, Ramon Estruch. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.01.2025.)

Cardiovascular risk factors begin in childhood and track into adulthood, increasing the possibility of impaired cardiometabolic health. Adopting healthy dietary patterns can help curb childhood obesity, a worrisome epidemic problem at present. In the era of personalized nutrition, dietary recommendations should be adapted to different stages of life, including children (older than 3 years) and adolescents. Hereby, we present an updated version of the Mediterranean Lifestyle Pyramid addressed to children and adolescents, wihich may be used as a prevention tool by health professionals, teachers, and stakeholders. This pyramid arises from a consensus position between participants in a forum on Mediterranean Food Cultures with international experts. During this meeting, after reviewing all literature published, a consensus was reached on the new Medieterranean Lifestyle Pyramid for kids including details such as labels of the pyramid, position of foods, servings, type of foods, and healthy lifestyle habits. All components of the pyramid are supported by the most recent scientifically sound research and are based upon top-level evidence in nutritional sciences. Fruit, vegetables, legumes, nuts, wholegrains, and EVOO continue to be at the basis of the pyramid, but the importance of an adequate intake of fish, dairy products, and meat during these particular ages, when body and brain development occurs, is also considered. The promotion of physical activity, adequate sleep and good emotional health are emphasized, as well as the consumption of seasonal and local products, and overall sustainability. Improving dietary habits in early stages of life should increase health in adulthood and reduce future incidence of non-communicable chronic diseases. The Mediterranean Diet and its graphic representation in the Lifestyle Pyramid should be a health-fostering tool not only for adults and children, but also for the entire planet because it promotes the diversity of species, respect for the earth, and the local economy. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED: Not applicable STATEMENT OF SIGNIFICANCE: A new Mediterranean lifestyle pyramid is addressed to children and adolescents, as well as health professionals, teachers, and stakeholders. Fruit, vegetables, legumes, nuts, wholegrain cereals, and extra-virgin olive oil continue to be a crucial part of the pyramid, but the importance of adequate intake of fish, dairy products, and meat in these early ages, when body and brain development occurs, is also emphasized., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emilio Ros reports a relationship with Alexion Pharmaceuticals Inc that includes: speaking and lecture fees and travel reimbursement. Emilio Ros reports a relationship with California Walnuts that includes: travel reimbursement. Emilio Ros reports a relationship with Spanish Arteriosclerotic Society that includes: speaking and lecture fees. Emilio Ros reports a relationship with International Nut and Dried Fruit Council that includes: travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ramon Estruch reports administrative support was provided by Fundacion Dieta Mediterranea, Barcelona (Spain). Ramon Estruch reports a relationship with Carlos III Health Institute that includes: funding grants. Ramon Estruch reports a relationship with European Comission, Brussells, Belgium that includes: funding grants. Ramon Estruch reports a relationship with National Institute of Health, Bethesda, USA that includes: funding grants. Ramon Estruch reports a relationship with Cerveza y Salud, Madrid, Spain that includes: consulting or advisory. Ramon Estruch reports a relationship with Dallant Laboratories, Spain that includes: consulting or advisory. Ramon Estruch reports a relationship with Wine and Culinary International Forum, Barcelona (Spain) that includes: speaking and lecture fees. Ramon Estruch reports a relationship with Grand-Fountain Laboratories, Spain that includes: funding grants. Ramon Estruch reports a relationship with Karolinska Institute, Menarini Laboratories, Sweeden that includes: travel reimbursement. Ramon Estruch reports a relationship with Iberoamerican Foundation for Nutrition that includes: travel reimbursement. Ramon Estruch reports a relationship with Italian Pavilion, EXPO DUBAI 2020 that includes: travel reimbursement. Ramon Estruch reports a relationship with Vatican City that includes: travel reimbursement. Ramon Estruch reports a relationship with Fundacion de Investigación sobre Vino y Nutricion, Vilafranca (Spain)pain) that includes: funding grants and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Rosa M Lamuela-Raventos reports a relationship with Carlos III Health Institute that includes: funding grants. Rosa M Lamuela-Raventos reports a relationship with European Comission, Brussells, Belgium that includes: funding grants. Rosa M Lamuela-Raventos reports a relationship with National Institute of Health, Bethesda, USA that includes: funding grants. Rosa M Lamuela-Raventos reports a relationship with Ecoveritas SA, Spain that includes: non-financial support. Rosa M Lamuela-Raventos reports a relationship with Cerveza y Salud, Madrid, Spain that includes: funding grants. Rosa M Lamuela-Raventos reports a relationship with UNIDECO SA that includes: consulting or advisory. Rosa M Lamuela-Raventos reports a relationship with Wine in Moderation, Brussels that includes: travel reimbursement. Rosa M Lamuela-Raventos reports a relationship with ADVENTIA SA, Spain that includes: travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Andrea Vania reports a relationship with Italian Society of Human Nutrition that includes: travel reimbursement. Javier Fontecha reports a relationship with Spanish Ministry of Science, Innovation and Universities that includes: funding grants. Sara Castro-Barquero reports a relationship with Alfonso Martín Escudero Foundation that includes: employment. Ana Maria Ruiz-Leon reports a relationship with Fundacion Dieta Mediterranean, Barcelona, Spain that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aedes aegypti is of great public health concern because of its vectorial capacity to transmit various arboviruses such as Zika, yellow fever, dengue, and chikungunya. In California, its expanding geographic distribution has been unrestrained. This urgently calls for innovative tools such as the use of sterile insect technique (SIT) to strengthen invasive Aedes control. This study aimed to determine the efficacy of combining an SIT application into integrated vector management (IVM) strategies in invasive Aedes control in the West Valley region of southern California. A total of 25 Aedes hotspots, grouped into two cohorts-sites that received SIT treatment only ( n = 9) and sites that received both SIT and In2Care ® Mosquito Stations ( n = 16)-were selected for this study. Biweekly, X-ray irradiated male Ae. aegypti mosquitoes were released between April and November 2024. Data from weekly BG Sentinel-2 traps were utilized to compare the mosquito densities between the pre-intervention (2023) and intervention (2024) periods for both cohorts. In addition, a subset of samples ( n = 50) of irradiated male mosquitoes were placed in a separate cage with freshly emerged unirradiated female mosquitoes to evaluate the level of sterility of the eggs from these mosquitoes. Aedes -related service requests made by the District's residents were also compared between the pre-intervention and intervention periods to indirectly determine the effect of optimizing the control strategies on overall mosquito problems. A total of 106,608 sterile male Ae. aegypti were released between April and November 2024. The cohort with the SIT only application showed a 44% reduction in the number of female Ae. aegypti per trap-night during the intervention period compared with the pre-intervention period. At sites with In2Care Mosquito Stations that also received SIT treatment, the mosquito density dropped by 65% during the intervention period compared with the pre-intervention period. The number of Aedes -related service requests during the intervention year ( n = 367) was 45% lower than the pre-intervention year ( n = 656). Over 99.6% eggs collected from female mosquitoes mated with irradiated males did not hatch, indicating a high level of sterility of the irradiated males utilized for our SIT application. Here, we demonstrated the potential of SIT when combined with IVM strategies such as In2Care ® Mosquito Stations, offering a holistic approach to reducing the public health risks associated with Aedes -borne diseases.

This study presents a novel system for diagnosing and evaluating soccer performance using wearable inertial sensors integrated into players' insoles. Designed to meet the needs of professional podiatrists and sports practitioners, the system focuses on three key soccer-related movements: passing, shooting, and changes of direction (CoDs). The system leverages low-power IMU sensors, Bluetooth Low Energy (BLE) communication, and a cloud-based architecture to enable real-time data analysis and performance feedback. Data were collected from nine professional players from the SD Huesca women's team during controlled tests, and bespoke algorithms were developed to process kinematic data for precise event detection. Results indicate high accuracy rates for detecting ball-striking events and CoDs, with improvements in algorithm performance achieved through adaptive thresholds and ensemble neural network models. Compared to existing systems, this approach significantly reduces costs and enhances practicality by minimizing the number of sensors required while ensuring real-time evaluation capabilities. However, the study is limited by a small sample size, which restricts generalizability. Future research will aim to expand the dataset, include diverse sports, and integrate additional sensors for broader applications. This system offers a valuable tool for injury prevention, player rehabilitation, and performance optimization in professional soccer, bridging technical advancements with practical applications in sports science.

The objective was to determine whether gravity support for the left arm of right-handed participants would increase left arm use during a three-dimensional (3-D) reaching task in virtual reality. Twelve healthy control participants each completed 630 reaching movements broken into six blocks. The majority of targets were placed close to the midsagittal plane at three heights, and participants were free to use either limb when reaching for targets. The hand had to stay in the target for a prescribed dwell time before the target disappeared. For all reaching tasks within a block, the left arm gravity support was set to either 0% or 75% of full arm support. The blocks also varied in the dwell time (2, 4, or 6 s). The order of blocks was balanced across participants in terms of gravity support level and dwell time. Electromyogram (EMG) level in the left medial deltoid decreased with increasing gravity support ( P < 0.001) and was higher for higher targets compared to lower targets ( P < 0.001). The odds of using the left arm were 1.95 times higher with gravity support compared to no support ( P < 0.001). With gravity support, we expected greater shifts toward the left arm in tasks that were more energetically demanding. This was not the case, as the increased use was evenly distributed across all target heights, and use decreased or remained unchanged with increasing dwell time. Results are discussed relative to current models of limb choice and the potential use of robotic gravity support to overcome learned nonuse in stroke patients. NEW & NOTEWORTHY We have shown that gravity support from a robotic exoskeleton increases use of the left arm of right-handed healthy participants. Prior work has shown similar results when movements of one arm are amplified in a virtual environment. The advantage of this approach is the potential to apply the intervention during functional task practice outside of the VR environment or during performance of actual activities of daily living (ADL).

Aedes aegypti is fast spreading across California, with over 300 cities within 22 central and southern counties being infested since its introduction in 2013. Due to its cryptic breeding habitats, control efforts have not been successful so far. This calls for innovative tools such as sterile insect technique (SIT) to reinforce the existing integrated pest management (IPM). Here, we assessed fitness, survivorship, and dose response of X-ray irradiated male Ae. aegypti in California. Locally acquired Ae. aegypti eggs were hatched and reared in temperature-controlled laboratory setting at the West Valley Mosquito and Vector Control District in Ontario, California. Freshly emerged adult male mosquitoes were manually separated using motor-operated aspirators and treated with X-ray radiation at different dosage (42-60 Gy). Dose response of irradiated males was analyzed and induced sterility determined. Survivorship of males treated with different X-ray doses was compared. Fecundity of females that mated with irradiated males at different X-ray doses was generally comparable. Overall, induced sterility increased with higher X-ray doses. Nulliparous females that mated with male Ae. aegypti treated with 55-60 Gy laid eggs with over 99% sterility. Non-irradiated male mosquitoes had higher survivorship (mean = 0.78; P = 0.0331) than irradiated mosquitoes (mean range = 0.50-0.65). The competitiveness index of irradiated males decreased with increasing X-ray treatment doses, 1.14 at 55 Gy and 0.49 at 60 Gy, and this difference was significant (P < 0.01). Irradiated males showed high survivorship and competitiveness-key for the anticipated SIT application for the control of invasive Ae. aegypti in California., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Anastrepha ludens (Mexican fruit-fly) is a highly polyphagous fruit fly species (Tephritidae) attacking wild and commercial fruit from Mexico to Panama. Here we report on a recent habitat and host range expansion as A. ludens lately started to attack apples (Malus domestica) in Mexico, a phenomenon likely influenced by global warming. We document natural infestations in apple-growing regions in the States of Nuevo León and Hidalgo, Mexico where A. ludens has started to attack the cultivars 'Golden Delicious', 'Rayada' and 'Criolla'. No infestations were found in the apple-growing region of Zacatlán, Puebla. To determine apple cultivar susceptibility to the attack of this emerging pest, we ran forced infestation assays in enclosed fruit-bearing branches in all three apple-growing regions and studied the metabolome of all fruit. A clear pattern emerged indicating that the cultivar 'Golden Delicious' was the most susceptible, with 'Criolla' exhibiting complete resistance in one location (Puebla). Although A. ludens can develop in this new host, development rates (egg-adult) and adult emergence were affected when compared with the performance in the natural host 'Marsh' grapefruit. Warmer temperatures and specific secondary metabolites of some apple cultivars are likely contributing to the territorial and host expansion of A. ludens., Competing Interests: Competing interests The authors declare no competing interests. Ethics declarations The authors declare that only insects were used and that special care was taken to only use the necessary amount. Grower approval for apple collections We worked in commercial apple orchards with a commercially significant pest. We obtained verbal permissions from all orchard owners under a gentleman´s agreements as that is the local custom. Growers or their administrators supervised our work in all cases. No official permissions were needed also in the case of the fruit fly pest., (© 2024. The Author(s).)

Mosquito Sterile Insect Technique (SIT) programs can be developed in smaller agencies through synchronization of the colony development to take advantage of the natural male early emergence. This paper examined key aspects of Ae. aegypti colony synchronization work, including egg hatching, larval development, and adult emergence to produce sufficient numbers of adult male mosquitoes within a specific timeframe for irradiation and release. Our data indicated that a relatively low percentage of males are required for colony propagation. Additional results highlighted that fresher Ae. aegypti eggs could yield as high as a 93 % hatching success than older eggs when placed under vacuum pressure in yeast infused water for 1.5 h. Eggs that were one-month old hatched (93 %) better than older eggs (0-32 %). A higher egg density in the hatching flask was correlated to a lower hatch rate, and higher larval density was related to unsynchronized pupae and delayed adult emergence. By keeping Ae. aegypti larvae at reasonable density, over 95 % of adults emerged on the first two days of emergence - indicating a high synchronicity. A standardized colony maintenance protocol therefore renders a synchronized larval development and adult male emergence which are critical in SIT programs., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The IMPACT BCN trial-a parallel-group randomized clinical trial where 1221 pregnant women at high risk for small-for-gestational age (SGA) newborns were randomly allocated at 19- to 23-week gestation into three groups: Mediterranean diet, Mindfulness-based Stress reduction or non-intervention-has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion., Material and Methods: Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8-week Stress reduction program adapted for pregnancy, consisting of weekly 2.5-h and one full-day sessions. Non-intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36-week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion., Results: While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non-intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99-28.09] in Mediterranean diet and 20.44 [5.13-81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups., Conclusions: Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Background: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed., Objectives: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women., Methods: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods., Results: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (β: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively)., Conclusions: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Metabolic syndrome (MetS) in adolescence is a risk factor for future cardiovascular disease. The chronic inflammation associated with MetS can be attenuated by the anti-inflammatory effect of polyphenols. We aimed to evaluate total urinary polyphenols as a biomarker of anti-inflammatory diets and their effect on MetS in adolescents., Methods: In this retrospective analysis of a longitudinal cohort study, the relationship between total polyphenol excretion (TPE) in urine, the inflammatory potential of the diet measured through the Children's Dietary Inflammatory Index (C-DII), and the presence of metabolic syndrome was evaluated. The study population consisted of adolescents enrolled in the SI! Program for Secondary Schools trial, who had completed all the study forms and provided urine samples at baseline and at the two-year follow-up. Multivariate linear regression and multinominal logistic regression models were generated to evaluate the relationship of changes in TPE with changes in the C-DII score and changes in MetS status, respectively. An analysis of the ROC curve was performed to assess the potential of TPE as a biomarker of an anti-inflammatory diet., Results: This study included 662 adolescents, 51.2% were males, and 48.8% were females, with a mean age of 12 (0.38) years at baseline. The relationship between changes in TPE and changes in the C-DII score was stratified by sex with a p-value <0.001 for the interaction. TPE and C-DII were inversely associated in males (-0.13 mg GAE/g creatinine [-0.26; -0.01] per 1-SD increase, p-value = 0.037). In addition, an increase in changes in TPE levels were associated with a reversal in MetS status in all adolescents (1.30 [1.27; 1.34] per 1-SD increase, p-value<0.001). The ROC curve showed that urinary TPE levels can predict dietary inflammatory potential with an AUC = 0.793 (0.725; 0.863) in males., Conclusion: Polyphenols excreted in urine are a potential biomarker of anti-inflammatory diets in males and are associated with a reversal of MetS status in adolescents., Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT03504059, https://clinicaltrials.gov/study/NCT03504059., Competing Interests: Conflict of interest R.M.L-R reports receiving lecture fees from Cerveceros de España and receiving lecture fees and travel support from Adventia, Unideco, and Idilia Foods SL. RE reports grants from Fundación Dieta Mediterránea, Spain and Cerveza y Salud, Spain. Also, personal fees for given lectures from Brewers of Europe, Belgium, Fundación Cerveza y Salud, Spain, Pernaud-Ricard, Mexico, Instituto Cervantes, Alburquerque, USA; Instituto Cervantes, Milan, Italy, Instituto Cervantes, Tokyo, Japan, Lilly Laboratories, Spain, and Wine and Culinary International Forum, Spain, and non-financial support to organize a National Congress on Nutrition. Also feeding trials with products from Grand Fountain and Uriach Laboratories, Spain. The other authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: We investigated whether structured maternal lifestyle interventions based on Mediterranean diet or stress reduction influence fetal-infant neurodevelopment detected by detailed fetal neurosonography and Ages and Stages Questionnaires 3rd edition (ASQ) at 12 months old., Methods: This was a secondary analysis of a randomized clinical trial (2017-2020), including 1,221 singleton pregnancies at high risk for small-for-gestational age. Participants were randomized into three groups at 19-23 weeks' gestation: Mediterranean diet intervention, stress reduction program, or usual care. A detailed neurosonography was performed on 881 participants at mean (SD) 33.4 (1.1) weeks' gestation. Neurosonographic measurements were done offline. ASQ was performed on 276 infants at 1 year of corrected age., Results: Biparietal diameter was similar among study groups. Mediterranean diet group fetuses had deeper insula (26.80 [1.68] versus 26.63 [1.75], mm, p = 0.02) and longer corpus callosum (42.98 [2.44] versus 42.62 [2.27], mm, p = 0.04), with a lower rate of suboptimal score infants in ASQ problem-solving domain (6.2 vs. 16.3%, p = 0.03). Stress reduction group fetuses had deeper insula (26.90 [1.75] versus 26.63 [1.75], mm, p = 0.04) and lower rates of suboptimal score infants in ASQ fine motor domain (4.3 vs. 12.8%, p = 0.04), compared to usual care group fetuses., Conclusion: Maternal structured intervention during pregnancy of the trial has the potential to modify offspring's neurodevelopment., (© 2024 S. Karger AG, Basel.)

Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac disorder characterized by the gradual replacement of cardiomyocytes with fibrous and adipose tissue, leading to ventricular wall thinning, chamber dilation, arrhythmias, and sudden cardiac death. Despite advances in treatment, disease management remains challenging. Animal models, particularly mice and zebrafish, have become invaluable tools for understanding AC's pathophysiology and testing potential therapies. Mice models, although useful for scientific research, cannot fully replicate the complexity of the human AC. However, they have provided valuable insights into gene involvement, signalling pathways, and disease progression. Zebrafish offer a promising alternative to mammalian models, despite the phylogenetic distance, due to their economic and genetic advantages. By combining animal models with in vitro studies, researchers can comprehensively understand AC, paving the way for more effective treatments and interventions for patients and improving their quality of life and prognosis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m 2 , harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (βadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown., Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data., Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001)., Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Objective: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up., Methods: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact., Results: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %., Conclusions: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters., Competing Interests: Declaration of competing interest J.S.-S. reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation and Instituto Danone, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, the California Almond Board of California, Pistachio Growers and Borges S.A; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone Spain; Serving in the Board of Danone Institute International. D·C. reported receiving grants from Instituto de Salud Carlos III. R.E. reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Meditarránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; nonfinancial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. The rest of the authors have declared that no competing interests exist. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: A Mediterranean diet has positive effects on the brain in mid-older adults; however, there is scarce information on pregnant individuals. We aimed to evaluate the effect of a structured Mediterranean diet intervention on the cortical structure of the maternal brain during pregnancy., Methods: This study was a secondary analysis of the IMPACT BCN, a randomized clinical trial with 1221 high-risk pregnant women randomly allocated into three groups at 19-23 weeks of gestation: Mediterranean diet intervention, a mindfulness-based stress reduction program, or usual care. Maternal brain magnetic resonance imaging was performed during the third trimester of pregnancy in a random subgroup of participants. For this study, data from the Mediterranean diet and usual groups were analyzed. Maternal dietary intake, adherence to the Mediterranean diet and metabolite biomarkers were evaluated using a food frequency questionnaire, a 17-item dietary screener and plasma/urine samples, respectively., Results: The cluster-wise analysis showed that the Mediterranean diet group participants ( n = 34) had significantly larger surface areas in the right precuneus (90%CI: <0.0001-0.0004, p < 0.001) and left superior parietal (90%CI: 0.026-0.033, p = 0.03) lobules compared to the usual care group participants ( n = 37). A larger right precuneus area was associated with high improvements in adherence to the Mediterranean diet, a high intake of walnuts and high concentrations of urinary hydroxytyrosol. A larger left superior parietal area was associated with a high intake of walnuts and high concentrations of urinary hydroxytyrosol., Conclusions: The promotion of a Mediterranean diet during pregnancy has a significant effect on maternal brain structure.

Objective: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD)., Methods: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models., Results: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption., Conclusions: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The human mitochondrial DNA polymerase gamma is a holoenzyme, involved in mitochondrial DNA (mtDNA) replication and maintenance, composed of a catalytic subunit (POLG) and a dimeric accessory subunit (POLG2) conferring processivity. Mutations in POLG or POLG2 cause POLG-related diseases in humans, leading to a subset of Mendelian-inherited mitochondrial disorders characterized by mtDNA depletion (MDD) or accumulation of multiple deletions, presenting multi-organ defects and often leading to premature death at a young age. Considering the paucity of POLG2 models, we have generated a stable zebrafish polg2 mutant line (polg2 ia304 ) by CRISPR/Cas9 technology, carrying a 10-nucleotide deletion with frameshift mutation and premature stop codon. Zebrafish polg2 homozygous mutants present slower development and decreased viability compared to wild type siblings, dying before the juvenile stage. Mutants display a set of POLG-related phenotypes comparable to the symptoms of human patients affected by POLG-related diseases, including remarkable MDD, altered mitochondrial network and dynamics, and reduced mitochondrial respiration. Histological analyses detected morphological alterations in high-energy demanding tissues, along with a significant disorganization of skeletal muscle fibres. Consistent with the last finding, locomotor assays highlighted a decreased larval motility. Of note, treatment with the Clofilium tosylate drug, previously shown to be effective in POLG models, could partially rescue MDD in Polg2 mutant animals. Altogether, our results point at zebrafish as an effective model to study the etiopathology of human POLG-related disorders linked to POLG2, and a suitable platform to screen the efficacy of POLG-directed drugs in POLG2-associated forms., (© 2024. The Author(s).)

Background: Promoting physical activity (PA) and healthy feeding (HF) is crucial to address the alarming increase in obesity rates in developing countries. Leveraging mobile phones for behavior change communication to encourage infant PA and promote HF is particularly significant within the Mexican context., Objective: This study aims to explore the effectiveness and feasibility of mHealth interventions aimed at promoting PA and HF among primary caregivers (PCs) of Mexican children under the age of 5 years. Additionally, the study aims to disseminate insights gained from intervention implementation amidst the COVID-19 pandemic and assess the potential of behavior change mHealth interventions on a broader population scale., Methods: NUTRES, an mHealth intervention, underwent an effectiveness-implementation hybrid trial. Over 36 weeks, participants in the intervention group (IG), totaling 230 individuals, received approximately 108 SMS text messages tailored to their children's age. These messages covered topics such as PA and HF and emphasized the significance of proper child nutrition amidst the COVID-19 pandemic. NUTRES participants were recruited from both urban and rural health units across 2 states in Mexico. Given the COVID-19 context, both baseline and follow-up surveys were conducted via mobile or fixed telephone. The evaluation of effectiveness and implementation used a mixed methods approach. Qualitative analysis delved into participants' experiences with NUTRES and various implementation indicators, including acceptance, relevance, and coverage. Grounded theory was used for coding and analysis. Furthermore, difference-in-differences regression models were used to discern disparities between groups (comparison group [CG] versus IG) concerning knowledge and practices pertaining to infant PA and HF., Results: Of the total 494 PCs enrolled in NUTRES, 334 persisted until the end of the study, accounting for 67.6% (334/494) participation across both groups. A majority of PCs (43/141, 30.5%, always; and 97/141, 68.8%, sometimes) used the SMS text message information. Satisfaction and acceptability toward NUTRES were notably high, reaching 98% (96/98), with respondents expressing that NUTRES was "good," "useful," and "helpful" for enhancing child nutrition. Significant differences after the intervention were observed in PA knowledge, with social interaction favored (CG: 8/135, 5.9% vs IG: 20/137, 14.6%; P=.048), as well as in HF practice knowledge. Notably, sweetened beverage consumption, associated with the development of chronic diseases, showed divergence (CG: 92/157, 58.6% vs IG: 110/145, 75.9%; P=.003). In the difference-in-differences model, a notable increase of 0.03 in knowledge regarding the benefits of PA was observed (CG: mean 0.13, SD 0.10 vs IG: mean 0.16, SD 0.11; P=.02). PCs expressed feeling accompanied and supported, particularly amidst the disruption of routine health care services during the COVID-19 pandemic., Conclusions: While NUTRES exhibited a restricted impact on targeted knowledge and behaviors, the SMS text messages functioned effectively as both a reminder and a source of new knowledge for PCs of Mexican children under 5 years of age. The key lessons learned were as follows: mHealth intervention strategies can effectively maintain communication with individuals during emergencies, such as the COVID-19 pandemic; methodological and implementation barriers can constrain the effectiveness of mHealth interventions; and using mixed methods approaches ensures the complementary nature of results. The findings contribute valuable evidence regarding the opportunities and constraints associated with using mobile phones to enhance knowledge and practices concerning PA and HF among PCs of children under 5 years old., Trial Registration: ClinicalTrials.gov NCT04250896; https://clinicaltrials.gov/ct2/show/NCT04250896., (©Ana Lilia Lozada-Tequeanes, Florence L Théodore, Edith Kim-Herrera, Armando García-Guerra, Amado D Quezada-Sánchez, Rocio Alvarado-Casas, Anabelle Bonvecchio. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 09.04.2024.)

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort., Methods: Participants ( n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology., Results: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted β = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women ( β = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008)., Conclusions: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

Objectives: Several studies suggest that moderate wine consumption, particularly red wine, may have benefits for cardiovascular health. Red wine contains a variety of bioactive compounds, including polyphenols like phenolic acids, which have demonstrated anti-inflammatory effects in experimental models. The aim of this study was to assess the anti-inflammatory properties of wine, measured as urinary tartaric acid, a new biomarker of wine consumption., Design, Settings, and Participants: One-year longitudinal study that included 217 participants from the PREDIMED trial., Measurements: Plasma inflammatory biomarkers and urinary tartaric acid were analyzed using xMAP technology and high-performance liquid chromatography, respectively. Multivariable regression analyses were performed to assess the relationship between variations over 1-year in urinary tartaric acid concentrations and 1-year changes in serum inflammatory molecules, including adhesion cell molecules, interleukine-6, tumour necrosis factor alpha, and monocyte chemotactic protein 1. Three categories were built according to tertiles of 1-y changes in urinary tartaric acid., Results: Using a ROC curve, urinary tartaric acid was corroborated as a reliable biomarker of wine consumption (AUC = 0.818 (95% CI: 0.76; 0.87). In the continuous analysis, participants with higher increases in tartaric acid significantly reduced their concentrations in soluble vascular adhesion molecule (sVCAM-1) after 1-year of follow-up (-0.20 (-0.38; -9,93) ng/mL per 1-SD increment, p-value = 0.031). Moreover, tertiles 2 and 3 of 1-year changes in tartaric acid presented a significant reduction in soluble intercellular cell adhesion molecule (sICAM-1) as compared to tertile 1 (-0.31 (-0.52; -0.10) ng/mL, p-value = 0.014 and -0.29 (-0.52; -0.07) ng/mL, p-value = 0.023, respectively). Participants in the third tertile also exhibited a reduced concentration of sVCAM-1 compared to those in the first tertile (-0.31 (-0.55; -0.06) ng/mL, p-value = 0.035)., Conclusions: Our findings suggest that wine consumption is associated with lower levels of inflammation due to the anti-inflammatory properties of wine compounds., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Vitamin B12 is an essential nutrient that is involved in numerous physiological processes, and its deficiency can lead to various complications, including neurological and haematological disorders. Some studies have suggested that vitamin B12 may have anti-inflammatory effects, but the mechanisms underlying this relationship are not yet fully understood. We investigated the relationship between circulating vitamin B12 and inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP). The association of peripheral levels of vitamin B12 with IL-6 and CRP was assessed in 136 human samples from a high cardiovascular risk population. To corroborate the results from the human trial, the analysis was replicated in naturally aged mice., Results: Individuals with higher serum levels of vitamin B12 showed lower concentrations of IL-6 and CRP after adjustment for potential confounders, and an inverse association was also found between serum IL-6 and vitamin B12 levels in naturally aged mice., Conclusion: Circulating vitamin B12 was inversely associated with IL-6 and CRP in humans and with IL-6 in mice, suggesting that it may exert an anti-inflammatory effect through modulation of these pro-inflammatory molecules. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Scope: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk., Methods and Results: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores., Conclusions: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed "pale", disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/β-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-β pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/β-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/β-catenin signalling cascade., (© 2023. The Author(s).)

Background: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment., Objective: This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development., Study Design: This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes., Results: When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm 3 ; standard deviation, 23.92 cm 3 vs 294.01 cm 3 ; standard deviation, 26.29 cm 3 ; P=.04), corpus callosum (mean, 1.16 cm 3 ; standard deviation, 0.19 cm 3 vs 1.26 cm 3 ; standard deviation, 0.22 cm 3 ; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm 3 vs 46.60; standard deviation, 4.69 cm 3 ; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m 3 vs 1.79; standard deviation, 0.30 cm 3 ; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01)., Conclusion: Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce., Objective: To characterize in detail patients reporting DHRs to APs., Methods: We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches., Results: Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P = .005 and P = .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P = .0002 and P = .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required., Conclusions: Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Vitamin B 12 plays a crucial role in cognition, but its effect might be regulated by the presence of other micronutrients, such as folate. The aim was to evaluate the effects of vitamin B 12 on cognitive performance according to adherence to the Mediterranean diet, and whether the Mediterranean diet also results in increased folate or vitamin B12 levels., Methods: This is a cohort study nested in a randomized controlled clinical trial performed in Hospital Clinic in Barcelona, Spain. A total of 170 participants of the PREDIMED trial (Barcelona - Hospital Clinic site) aged 55-80 years at high cardiovascular risk were included. Adherence to the Mediterranean diet was assessed using a validated 14-item questionnaire, memory function was evaluated with a battery of neuropsychological tests and serum vitamin B 12 and folate were determined using an automated electrochemiluminiscence immunoassay system., Results: In the multivariable adjusted linear regression model, serum vitamin B 12 concentration presented a significant correlation with memory function (r 2  = 0.57; P = 0.028) in participants with high adherence to the Mediterranean diet whereas the correlation was weak and inverse for those who presented a low adherence to the Mediterranean diet (r 2  = 0.37, P = 0.731). Mediterranean diet adherence showed a positive association with serum folate, but not with serum vitamin B 12 ., Conclusions: In an older Mediterranean population at high cardiovascular risk, changes in serum vitamin B 12 correlate with better memory function only in the context of a high adherence to the Mediterranean pattern, suggesting that the effects of vitamin B 12 goes further than a mere nutritional requirement., Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of the 11 participating centres. The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639 (https://www.isrctn.com/ISRCTN35739639)., Competing Interests: Conflicts of interest E.R. reports grants, personal fees, non-financial support and other from the California Walnut Commission while the study was carried out; grants, personal fees, non-financial support and other from Alexion; and personal fees and other from Amarin, outside the submitted work. R.M.L.-R. reports personal fees from Cerveceros de España, personal fees, and other from Adventia, Wine in Moderation, UNIDECO, and Ecoveritas S.A., outside the submitted work. R.E. reports grants from the Fundación Dieta Mediterránea (Spain), and Cerveza y Salud (Spain), and personal fees for given lectures from Brewers of Europe (Belgium), the Fundación Cerveza y Salud (Spain), Pernaud-Ricard (Mexico), Instituto Cervantes (Alburquerque, USA), Instituto Cervantes (Milan, Italy), Instituto Cervantes (Tokyo, Japan), Lilly Laboratories (Spain), and the Wine and Culinary International Forum (Spain), as well as non-financial support for the organization of a National Congress on Nutrition and feeding trials with products from Grand Fountain and Uriach Laboratories (Spain). Data described in the manuscript, code book, and analytic code will be made available upon request pending and approval to the PREDIMED trial Steering Committee, only to external researchers for studies following the project purposes., (Copyright © 2023. Published by Elsevier Ltd.)

Aims: To test, for the first time in latent autoimmune diabetes in adults (LADA), the effects of autoantigen-specific immunotherapy by intralymphatic administration of aluminium-formulated recombinant human glutamic acid decarboxylase 65 (GAD-alum); specifically, to test if this treatment is safe, to test whether it induces a strong immunological response akin to a similar protocol in type 1 diabetes and to look for associations with preserved beta-cell function., Materials and Methods: Three GAD-alum injections, 4 μg each, were administered 1 month apart into an inguinal lymph node in 14 people with newly diagnosed LADA (age 30-62 years) presenting with high levels of antibodies against glutamic acid decarboxylase (GADA). Adverse effects, immunological variables and beta-cell function were monitored, with detailed measurements at 5 and 12 months from baseline., Results: Clinical adverse effects were minor and transient and measured laboratory variables were unaffected. All participants completed the study. Treatment raised levels of GADA, elicited strong effects on reactivity of peripheral blood mononuclear cells to GAD and raised cytokine/chemokine levels. Beta-cell function appeared stable preferentially in the seven participants carrying human leukocyte antigen (HLA) haplotypes DR3DQ2, as assessed by C-peptide glucagon tests (P < 0.05 vs. seven non-carriers)., Conclusion: Intralymphatic treatment with GAD-alum in LADA is without clinical or other safety concerns over a 12-month period. As in a similar protocol used in type 1 diabetes, treatment exerts a strong immunological impact and is compatible with protection of beta-cell function preferentially in HLA-DR3DQ2 LADA patients. These findings pave the way for a randomized controlled trial in this important subgroup of LADA patients., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoroughly tested through methodologically rigorous studies that minimize the risk of reverse causality.

Background: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk., Methods: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring., Results: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HR adj (95%CI): 1.01 (1.00, 1.03)) and BMI (HR adj : 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk., Conclusions: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19., Trial Registration: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 )., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Importance: Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition., Objective: To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition., Design, Setting, and Participants: The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points., Intervention: Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion., Main Outcomes and Measures: The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses)., Results: A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, -0.94% [95% CI, -1.19 to -0.69]; 3 years, -0.38% [95% CI, -0.64 to -0.12] and visceral fat storage after 1 year, -126 g [95% CI, -179 to -73.3 g]; 3 years, -70.4 g [95% CI, -126 to -15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95% CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition., Conclusions and Relevance: The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points., Trial Registration: isrctn.org Identifier: ISRCTN89898870.

The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject of several recent reviews. Furthermore, comprehensive reviews about COVID-19 therapeutic have been also published. Therefore, we do not delve into details on these topics; instead we direct the readers to those other reviews. To avoid confusions with what we know about proteins from other coronaviruses, we exclusively report findings that have been experimentally confirmed in SARS-CoV-2. We have identified host mechanisms that appear to be the primary targets of SARS-CoV-2 proteins, including gene expression and immune response pathways such as ribosome translation, JAK/STAT, RIG-1/MDA5 and NF-kβ pathways. Additionally, we emphasize the multiple functions exhibited by SARS-CoV-2 proteins, along with the limited information available for some of these proteins. Our aim with this review is to assist researchers and contribute to the ongoing comprehension of SARS-CoV-2's pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Justo Arevalo, Castillo-Chávez, Uribe Calampa, Zapata Sifuentes, Huallpa, Landa Bianchi, Garavito-Salini Casas, Quiñones Aguilar and Pineda Chavarría.)

Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability., Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use., Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome., Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models., Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO 2 eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced., Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection., Trial Registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870., Competing Interests: Declaration of competing interest This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 and the AICO/2021/347 grants from the Generalitat Valenciana; the SEMERGEN grant. J.S-S is partially supported by ICREA under the ICREA Academia programme. C.B. was granted by Juan de la Cierva grant. P.M.G. was granted by the Specialist Postdoctoral program of the Consejería de Salud y Familias, Junta de Andalucía (Spain). None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication. J.S.-S. reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation and Instituto Danone, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, the California Almond Board of California, Pistachio Growers and Borges S.A; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone Spain; Serving in the Board of Danone Institute International. D.C. reported receiving grants from Instituto de Salud Carlos III. R.E. reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Meditarránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. The rest of the authors have declared that no competing interests exist. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients., Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders., Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n  = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p  < 0.001), magnesium (0% vs. 7.6%, p  = 0.001), iron (24.5% vs. 74.1%, p  < 0.001), and vitamin B9 (0% vs. 29.8%, p  < 0.001), vitamin C (0% vs. 1.9%, p  = 0.033), and vitamin D (61.5% vs. 92.8%, p  < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet., Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies., Competing Interests: RE reports grants from the Fundación Dieta Mediterránea (Spain), and Cerveza y Salud (Spain), and personal fees for given lectures from Brewers of Europe (Belgium), the Fundación Cerveza y Salud (Spain), Pernaud-Ricard (Mexico), Instituto Cervantes (Alburquerque, United States), Instituto Cervantes (Milan, Italy), Instituto Cervantes (Tokyo, Japan), Lilly Laboratories (Spain), and the Wine and Culinary International Forum (Spain), as well as nonfinancial support for the organization of a National Congress on Nutrition and feeding trials with products from Grand Fountain and Uriach Laboratories (Spain). EG reports, during the conduct of the study, grants from La Caixa Foundation, grants from Cerebra Foundation for the Brain Injured Child, and grants from AGAUR. AN reports personal fees from La Caixa Foundation (Doctoral INPhINIT – RETAINING, fellowship LCF/BQ/DR19/11740018), during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Castro-Barquero, Larroya, Crispi, Estruch, Nakaki, Paules, Ruiz-León, Sacanella, Freitas, Youssef, Benitez, Casas, Genero, Gomez, Casanovas-Garriga, Gratacós, Casas and Crovetto.)

Importance: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and childhood neurodevelopment., Objective: To test the hypothesis that structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (MBSR) during pregnancy improve child neurodevelopment at age 2 years., Design, Setting, and Participants: This was a prespecified analysis of the parallel-group Improving Mothers for a Better Prenatal Care Trial Barcelona (IMPACT BCN) randomized clinical trial, which was conducted at a university hospital in Barcelona, Spain, from February 2017 to March 2020. A total of 1221 singleton pregnancies (19 to 23 weeks' gestation) with high risk of delivering newborns who were small for gestational age were randomly allocated into 3 groups: a Mediterranean diet intervention, an MBSR program, or usual care. A postnatal evaluation with the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III), was performed. Data were analyzed from July to November 2022., Interventions: Participants in the Mediterranean diet group received monthly individual and group educational sessions and free provision of extra virgin olive oil and walnuts. Those in the stress reduction group underwent an 8-week MBSR program adapted for pregnancy. Individuals in the usual care group received pregnancy care per institutional protocols., Main Outcomes and Measures: Neurodevelopment in children was assessed by Bayley-III at 24 months of corrected postnatal age., Results: A total of 626 children (293 [46.8%] female and 333 [53.2%] male) participated at a mean (SD) age of 24.8 (2.9) months. No differences were observed in the baseline characteristics between intervention groups. Compared with children from the usual care group, children in the Mediterranean diet group had higher scores in the cognitive domain (β, 5.02; 95% CI, 1.52-8.53; P = .005) and social-emotional domain (β, 5.15; 95% CI, 1.18-9.12; P = .01), whereas children from the stress reduction group had higher scores in the social-emotional domain (β, 4.75; 95% CI, 0.54-8.85; P = .02)., Conclusions and Relevance: In this prespecified analysis of a randomized clinical trial, maternal structured lifestyle interventions during pregnancy based on a Mediterranean diet or MBSR significantly improved child neurodevelopmental outcomes at age 2 years., Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

Background: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function., Objective: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk., Methods: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as <1, ≥1 to <3, ≥3 to <7, and ≥7 servings/wk (1 serving=30 g). Multivariable-adjusted linear regression models were fitted to assess associations between baseline nut consumption and 2-y cognitive changes., Results: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend <0.001). Compared with participants consuming <1 serving/wk of nuts, those categorized as consuming ≥3 to <7 and ≥7 servings/wk showed more favorable changes in general cognitive performance (β z-score [95% CI] = 0.06 [0.00,0.12] and 0.13 [0.06,0.20], respectively). No significant changes were observed in the multivariable-adjusted models for other cognitive domains assessed., Conclusion: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.

Background and Aims: Hybridization is a common and important force in plant evolution. One of its outcomes is introgression - the transfer of small genomic regions from one taxon to another by hybridization and repeated backcrossing. This process is believed to be common in glacial refugia, where range expansions and contractions can lead to cycles of sympatry and isolation, creating conditions for extensive hybridization and introgression. Polyploidization is another genome-wide process with a major influence on plant evolution. Both hybridization and polyploidization can have complex effects on plant evolution. However, these effects are often difficult to understand in recently evolved species complexes., Methods: We combined flow cytometry, analyses of transcriptomic sequences and pollen tube growth assays to investigate the consequences of polyploidization, hybridization and introgression on the recent evolution of several Erysimum (Brassicaceae) species from the South of the Iberian Peninsula, a well-known glacial refugium. This species complex differentiated in the last 2 million years, and its evolution has been hypothesized to be determined mainly by polyploidization, interspecific hybridization and introgression., Key Results: Our results support a scenario of widespread hybridization involving both extant and 'ghost' taxa. Several taxa studied here, most notably those with purple corollas, are polyploids, probably of allopolyploid origin. Moreover, hybridization in this group might be an ongoing phenomenon, as pre-zygotic barriers appeared weak in many cases., Conclusions: The evolution of Erysimum spp. has been determined by hybridization to a large extent. Species with purple (polyploids) and yellow flowers (mostly diploid) exhibit a strong signature of introgression in their genomes, indicating that hybridization occurred regardless of colour and across ploidy levels. Although the adaptive value of such genomic exchanges remains unclear, our results demonstrate the significance of hybridization for plant diversification, which should be taken into account when studying plant evolution., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

GAD-alum given into lymph nodes to Type 1 diabetes (T1D) patients participating in a multicenter, randomized, placebo-controlled double-blind study seemed to have a positive effect for patients with DR3DQ2 haplotype, who showed better preservation of C-peptide than the placebo group. Here we compared the immunomodulatory effect of GAD-alum administered into lymph nodes of patients with T1D versus placebo with focus on patients with DR3DQ2 haplotype., Methods: GAD autoantibodies, GADA subclasses, GAD 65 -induced cytokine secretion (Luminex panel) and proliferation of peripheral mononuclear cells were analyzed in T1D patients (n=109) who received either three intra-lymphatic injections (one month apart) with 4 µg GAD-alum and oral vitamin D supplementation (2000 IE daily for 120 days), or placebo., Results: Higher GADA, GADA subclasses, GAD 65 -induced proliferation and cytokine secretion was observed in actively treated patients after the second injection of GAD-alum compared to the placebo group. Following the second injection of GAD-alum, actively treated subjects with DR3DQ2 haplotype had higher GAD 65 -induced secretion of several cytokine (IL4, IL5, IL7, IL10, IL13, IFNγ, GM-CSF and MIP1β) and proliferation compared to treated individuals without DR3DQ2. Stratification of samples from GAD-alum treated patients according to C-peptide preservation at 15 months revealed that "good responder" individuals with better preservation of C-peptide secretion, independently of the HLA haplotype, had increased GAD 65 -induced proliferation and IL13 secretion at 3 months, and a 2,5-fold increase of IL5 and IL10 as compared to "poor responders". The second dose of GAD-alum also induced a more pronounced cytokine secretion in "good responders" with DR3DQ2, compared to few "good responders" without DR3DQ2 haplotype., Conclusion: Patients with DR3DQ2 haplotype had a distinct early cellular immune response to GAD-alum injections into the lymph node, and predominant GAD 65 -induced IL13 secretion and proliferation that seems to be associated with a better clinical outcome. If confirmed in the ongoing larger randomized double-blind placebo-controlled clinical trial (DIAGNODE-3), including only patients carrying DR3DQ2 haplotype, these results might be used as early surrogate markers for clinical efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Puente-Marin, Dietrich, Achenbach, Barcenilla, Ludvigsson and Casas.)

Scope: Excessive visceral adipose tissue (VAT) is associated with higher secretion of pro-inflammatory molecules, contributing to systemic inflammation and obesity-related metabolic disturbances., Methods and Results: This prospective analysis includes 117 overweight/obese adults (55-75 years) from the PREDIMED-Plus study. Fourteen inflammatory markers and adipokines are measured using a Bio-Plex assay with multiplex technology: insulin, glucagon, IL-6, visfatin, ghrelin, GLP-1, TNF-α, MCP-1, PAI-1, resistin, C-peptide, leptin, adipsin, and adiponectin. Participants are categorized into tertiles according to changes in VAT after 1-year of follow-up, determined by dual-energy X-Ray absorptiometry. Participants allocate in tertile 3, which represent an increase of VAT content after 1-year of follow-up compared to tertile 1, show significant differences in insulin (T3 vs T1, fully adjusted model: p = 0.037, p for trend 0.042), PAI-1 (fully adjusted model: p = 0.05, p for trend 0.06), c-peptide (fully adjusted model: p = 0.037, p for trend 0.042), and TNF-α (fully adjusted model p = 0.037, p for trend 0.042)., Conclusion: The results evidence that a reduction in VAT is associated with clinical improvements in several inflammatory and adiposity markers, mainly in insulin, c-peptide, and PAI-1 levels, and these improvements may contribute to a reduction in cardiometabolic disturbances observe in obesity., (© 2022 Wiley-VCH GmbH.)

Anastrepha spp. (Diptera: Tephritidae) infestations cause significant economic losses in commercial fruit production worldwide. However, some plants quickly counteract the insertion of eggs by females by generating neoplasia and hindering eclosion, as is the case for Persea americana Mill., cv. Hass (Hass avocados). We followed a combined transcriptomics/metabolomics approach to identify the molecular mechanisms triggered by Hass avocados to detect and react to the oviposition of the pestiferous Anastrepha ludens (Loew). We evaluated two conditions: fruit damaged using a sterile pin (pin) and fruit oviposited by A. ludens females (ovi). We evaluated both of the conditions in a time course experiment covering five sampling points: without treatment (day 0), 20 min after the treatment (day 1), and days 3, 6, and 9 after the treatment. We identified 288 differentially expressed genes related to the treatments. Oviposition (and possibly bacteria on the eggs' surface) induces a plant hypersensitive response (HR), triggering a chitin receptor, producing an oxidative burst, and synthesizing phytoalexins. We also observed a process of cell wall modification and polyphenols biosynthesis, which could lead to polymerization in the neoplastic tissue surrounding the eggs.

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity., Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown., Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04])., Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity., Clinical Trial Registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paz-Graniel, Fitó, Ros, Buil-Cosiales, Corella, Babio, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Vázquez, Daimiel, García-Gavilán, Toledo, Nishi, Sorlí, Castañer, García-Ríos, García de la Hera, Barón-López, Ruiz-Canela, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Fernández-García, Vázquez-Ruiz, Fernández-Carrión, Goday, Peña-Orihuela, Compañ-Gabucio, Schröder, Martínez-Gonzalez and Salas-Salvadó.)

Regulatory T cells are an important component of the immune system that plays a key role in maintaining homeostasis. Identification of distinct regulatory T cell subsets is essential to understand their function. Mass cytometry or CyTOF is a technology that enables the simultaneous measurement of up to 50 markers in single cells by using antibodies tagged with heavy metals, which are then detected with time-of-flight mass spectrometry. This chapter describes a mass cytometry approach for phenotypic characterization of regulatory T cells and determination of their master transcription factor Foxp3., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults., Design: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial., Setting: Community-dwelling, free-living participants in PREDIMED-Plus trial., Participants: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome., Intervention: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations., Measurements: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk., Results: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12))., Conclusions: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks., Competing Interests: Fernandez-Aranda acknowledges consulting fees from Novo Nordisk and Wiley as EIC for the European Eat Dis Rev. He has also received honoraria for lectures and support for travel/meetings from Novo Nordisk. He discloses his honorary participation in the Data Safety Monitoring Board or Advisory Board of Sustain-Consortium-Germany. Emilio Ros has received honoraria for presentations and support for attending meetings/travel from the California Walnut Commission, Alexion and the Spanish Atherosclerosis Society. He has also received consulting fees from Alexion. He participates in the Data Safety Monitoring Board or Advisory Board of the PREDIMED-Plus Clinical Trial. Ramon Estruch has received research grants from Instituto de Salud Carlos III, Madrid, Spain. He has received honoraria for presentations from Fundacion Cerveza y Salud, Spain; Instituto Cervantes, Albuquerque, USA; Instituto Cervantes, Milan, Italy; Instituto Cervantes, Tokyo, Japan; Fundacion Bosch i Gimpera, Spain; Wine and Culinary International Forum; Pernaud Richart; Mexico; Fundacion Dieta Mediterranea, Barcelona, Spain. He has received support for travel or meetings or conference organization from ERAB, Belgium, Brewers of Europe, Belgium, and Sociedad Española de Nutrición (SEN). He has served on the Advisory Board of Cerveza y Salud, Spain. Jordi Salas-Salvadó reported receiving consulting fees from Eroski Foundation. He has also received grants and support for attending meetings/travel from Nut and Dried Fruit Foundation. He is an honorary Member of the International Advisory Board of the Project “Effect of cashew nut supplementation on glycemic status and lipid profile in type 2 diabetes subjects”, Member of the Scientific Advisory Committee of the European PEGASO project (Personalized Guidance Services for Optimizing lifestyle management in teenagers through awareness, motivation and engagement) and Member of the Scientific Committee of Danone Institute International. He received personal fees for serving as a Member of the Institute Danone Advisory Board. Sangeetha Shyam has received consulting fees from Abbott Sdn Bhd. Stephanie K. Nishi is a volunteer member of Plant-Based Canada, a non-profit organization. Other authors (Jesús Francisco García-Gavilán, Indira Paz-Graniel, José J Gaforio4 Miguel Ángel Martínez-González, Dolores Corella, J. Alfredo Martínez, Ángel M. Alonso-Gómez, Julia Wärnberg, Jesús Vioque, Dora Romaguera, José López-Miranda, Francisco J Tinahones, José Lapetra, J. Luís Serra-Majem, Aurora Bueno-Cavanillas, Josep A. Tur, Vicente Martín Sánchez, Xavier Pintó, Pilar Matía-Martín, Josep Vidal, María del Mar Alcarria, Lidia Daimiel, Óscar García Regata, Rafael Perez Araluce, Eva M Asensio, Olga Castañer, Antonio Garcia-Rios, Alejandro Oncina-Cánovas, Cristina Bouzas, M. Angeles Zulet, Elena Rayó, Rosa Casas1,16,17, Sandra Martin-Pelaez, Lucas Tojal-Sierra, Bernal-López MR, Silvia Carlos, Jose V.Sorlí, Albert Goday, Patricia J. Peña-Orihuela, Ana Pastor-Morel, Sonia Eguaras, María Dolors Zomeño, Miguel Delgado-Rodríguez, Nancy Babio, and Montserrat Fitó) declared no potential conflict of interest.