Effect of undersized drilling on the stability of immediate tapered implants in the anterior maxillary sector. A randomized clinical trial.

BACKGROUND: To evaluate the effect of undersized drilling on the primary and secondary stability of immediate implants placed in the anterior maxilla. MATERIAL AND METHODS: A comparative randomized clinical trial was carried out in 30 healthy adults. Thirty tapered implants, 16 involving conventional drilling and 14 undersized drilling, were placed immediately after anterior maxillary tooth removal. Insertion torque and implant stability assessed by resonance frequency analysis (RFA) were evaluated at three different timepoints: at implant placement and 6 and 12 weeks post-implantation. The results were compared using parametric statistical tests. RESULTS: All implants showed adequate stability during follow-up. At implant placement, the undersized drilling group exhibited greater insertion torque values than the conventional drilling group, but stability assessed by RFA showed greater mean values in the conventional group. After 6 and 12 weeks of follow-up, both groups showed improved stability, though the RFA values remained comparatively higher in the conventional group. The differences were not statistically significant. CONCLUSIONS: Based on the results obtained, undersized drilling does not appear to afford significantly improved stability of immediate implants placed in the anterior zone of the maxilla during the osseointegration period.

Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.

OBJECTIVES: To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage. METHODS: A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation. An interactive model-based simulation tool was developed in R (Shiny and R Markdown). Cmax/MIC ratio, time above MIC and AUC/MIC were used for optimizing amikacin initial dose recommendation. Probabilities of reaching targets were calculated for the dosage proposed. RESULTS: A one-compartment model with first-order linear elimination best described the 873 amikacin plasma concentrations available from 294 subjects (model development and external validation groups). Estimated amikacin population pharmacokinetic parameters were CL (L/h) = 0.525 + 4.78 × (CKD-EPI/98) × (0.77 × vancomycin) and V (L) = 26.3 × (albumin/2.9)-0.51 × [1 + 0.006 × (weight - 70)], where CKD-EPI is calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. AMKdose is a useful interactive model-based application for a priori optimization of amikacin dosage, using individual patient and microbiological information together with predefined pharmacokinetic/pharmacodynamic (PKPD) targets. CONCLUSIONS: Serum albumin, total bodyweight, estimated glomerular filtration rate (using the CKD-EPI equation) and co-medication with vancomycin showed a significant impact on amikacin pharmacokinetics. A powerful interactive initial dose-finding tool has been developed and is freely available online. AMKdose could be useful for guiding initial amikacin dose selection before any individual pharmacokinetic information is available.

Vaginal neutrophils eliminate sperm by trogocytosis.

STUDY QUESTION: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm? SUMMARY ANSWER: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs). WHAT IS KNOWN ALREADY: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis. STUDY DESIGN, SIZE, DURATION: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response. PARTICIPANTS/MATERIALS, SETTING, METHODS: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA). MAIN RESULTS AND THE ROLE OF CHANCE: We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown. WIDER IMPLICATIONS OF THE FINDINGS: Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility. STUDY FUNDING/COMPETING INTEREST(S): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests.

A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease.

AIMS: Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. METHODS: A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. RESULTS: In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI: 0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999). CONCLUSION: This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects.

Room-Temperature Spin Hall Effect in Graphene/MoS2 van der Waals Heterostructures.

Graphene is an excellent material for long-distance spin transport but allows little spin manipulation. Transition-metal dichalcogenides imprint their strong spin-orbit coupling into graphene via the proximity effect, and it has been predicted that efficient spin-to-charge conversion due to spin Hall and Rashba-Edelstein effects could be achieved. Here, by combining Hall probes with ferromagnetic electrodes, we unambiguously demonstrate experimentally the spin Hall effect in graphene induced by MoS2 proximity and for varying temperatures up to room temperature. The fact that spin transport and the spin Hall effect occur in different parts of the same material gives rise to a hitherto unreported efficiency for the spin-to-charge voltage output. Additionally, for a single graphene/MoS2 heterostructure-based device, we evidence a superimposed spin-to-charge current conversion that can be indistinguishably associated with either the proximity-induced Rashba-Edelstein effect in graphene or the spin Hall effect in MoS2. By a comparison of our results to theoretical calculations, the latter scenario is found to be the most plausible one. Our findings pave the way toward the combination of spin information transport and spin-to-charge conversion in two-dimensional materials, opening exciting opportunities in a variety of future spintronic applications.

Large Multidirectional Spin-to-Charge Conversion in Low-Symmetry Semimetal MoTe2 at Room Temperature.

Efficient and versatile spin-to-charge current conversion is crucial for the development of spintronic applications, which strongly rely on the ability to electrically generate and detect spin currents. In this context, the spin Hall effect has been widely studied in heavy metals with strong spin-orbit coupling. While the high crystal symmetry in these materials limits the conversion to the orthogonal configuration, unusual configurations are expected in low-symmetry transition-metal dichalcogenide semimetals, which could add flexibility to the electrical injection and detection of pure spin currents. Here, we report the observation of spin-to-charge conversion in MoTe2 flakes, which are stacked in graphene lateral spin valves. We detect two distinct contributions arising from the conversion of two different spin orientations. In addition to the conventional conversion where the spin polarization is orthogonal to the charge current, we also detect a conversion where the spin polarization and the charge current are parallel. Both contributions, which could arise either from bulk spin Hall effect or surface Edelstein effect, show large efficiencies comparable to the best spin Hall metals and topological insulators. Our finding enables the simultaneous conversion of spin currents with any in-plane spin polarization in one single experimental configuration.

Influence of Relativistic Effects on the Contact Formation of Transition Metals.

Our analysis of the contact formation processes undergone by Au, Ag, and Cu nanojunctions reveals that the distance at which the two closest atoms on a pair of opposing electrodes jump into contact is, on average, 2 times longer for Au than either Ag or Cu. This suggests the existence of a longer-range interaction between those two atoms in the case of Au, a result of the significant relativistic energy contributions to the electronic structure of this metal, as confirmed by ab initio calculations. Once in the contact regime, the differences between Au, Ag, and Cu are subtle, and the conductance of single-atom contacts for metals of similar chemical valence is mostly determined by geometry and coordination.

Activities, bioavailability, and metabolism of lipids from structural membranes and oils: Promising research on mild cognitive impairment.

Concomitant with increased lifespan, large segments of the population are experiencing cognitive decline, which might progress to Alzheimer's disease (AD). Currently, there is no cure for AD and, once the neurodegenerative disorders are established, patients use pharmacologic therapy to slow the progression of the symptoms and require appropriate care to manage their condition. The preclinical stage of neural degeneration that progress through mild cognitive impairment (MCI) before the onset of AD is when it might be possible to introduce behavioral changes and pharma-nutritional interventions that modify the risk factors of MCI conversion to AD. Some food components accumulate in brain tissues, where they play essential roles. Among them, polar lipids, omega 3 fatty acids, and carotenoids appear to work additively or synergistically. Therefore, there is an opportunity to formulate nutraceuticals/functional foods to slow the progression of MCI. In this paper, we review the biochemical bases and recent interventions with bioactive lipids-rich formulations. Based on accumulated evidence, we propose that appropriate large-scale trials are warranted.

The Experience of Implementing Urban HEART Barcelona: a Tool for Action.

Urban Health Equity Assessment and Response Tool (HEART) is a tool developed by the World Health Organization whose objective is to provide evidence on urban health inequalities so as to help to decide the best interventions aimed to promote urban health equity. The aim of this paper is to describe the experience of implementing Urban HEART in Barcelona city, both the adaptation of Urban HEART to the city of Barcelona, its use as a means of identifying and monitoring health inequalities among city neighbourhoods, and the difficulties and barriers encountered throughout the process. Although ASPB public health technicians participated in the Urban HEART Advisory Group, had large experience in health inequalities analysis and research and showed interest in implementing the tool, it was not until 2015, when the city council was governed by a new left-wing party for which reducing health inequalities was a priority that Urban HEART could be used. A provisional matrix was developed, including both health and health determinant indicators, which allowed to show how some neighbourhoods in the city systematically fare worse for most of the indicators while others systematically fare better. It also allowed to identify 18 neighbourhoods-those which fared worse in most indicators-which were considered a priority for intervention, which entered the Health in the Barcelona Neighbourhoods programme and the Neighbourhoods Plan. This provisional version was reviewed and improved by the Urban HEART Barcelona Working Group. Technicians with experience in public health and/or in indicator and database management were asked to indicate suitability and relevance from a list of potential indicators. The definitive Urban HEART Barcelona version included 15 indicators from the five Urban HEART domains and improved the previous version in several requirements. Several barriers were encountered, such as having to estimate indicators in scarcely populated areas or finding adequate indicators for the physical context domain. In conclusion, the Urban HEART tool allowed to identify urban inequalities in the city of Barcelona and to include health inequalities in the public debate. It also allowed to reinforce the community health programme Health in the Barcelona Neighbourhoods as well as other city programmes aimed at reducing health inequalities. A strong political will is essential to place health inequalities in the political agenda and implement policies to tackle them.

Therapy with ombitasvir/paritaprevir/ritonavir plus dasabuvir is effective and safe for the treatment of genotypes 1 and 4 hepatitis C virus (HCV) infection in patients with severe renal impairment: A multicentre experience.

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.

Interplay of Chiral and Helical States in a Quantum Spin Hall Insulator Lateral Junction.

We study the electronic transport across an electrostatically gated lateral junction in a HgTe quantum well, a canonical 2D topological insulator, with and without an applied magnetic field. We control the carrier density inside and outside a junction region independently and hence tune the number and nature of 1D edge modes propagating in each of those regions. Outside the bulk gap, the magnetic field drives the system to the quantum Hall regime, and chiral states propagate at the edge. In this regime, we observe fractional plateaus that reflect the equilibration between 1D chiral modes across the junction. As the carrier density approaches zero in the central region and at moderate fields, we observe oscillations in the resistance that we attribute to Fabry-Perot interference in the helical states, enabled by the broken time reversal symmetry. At higher fields, those oscillations disappear, in agreement with the expected absence of helical states when band inversion is lifted.

Effect of High and Low Flexibility Levels on Physical Fitness and Neuromuscular Properties in Professional Soccer Players.

This study aimed to analyse the impact of high and low flexibility levels of hamstring and quadriceps muscles on physical fitness and neuromuscular properties in professional soccer players. 62 male professional soccer players participated in this study and performed 2 instrumented flexibility tests (passive straight leg raise [PSLR] and quadriceps flexibility [QF]). Anaerobic performance was assessed using countermovement jump (CMJ), Abalakov vertical jump, 20-m sprint, and Balsom agility test. A k-means cluster analysis was performed to identify a cut-off value of hamstring and quadriceps flexibility and classify players as high hamstring flexibility (HHF) and low hamstring flexibility (LHF) or high quadriceps flexibility (HQF) and low quadriceps flexibility (LQF), respectively, according to the PSLR and QF performances. The LQF players performed better than HQF on CMJ (p=0.042, ES: 0.64) and Balsom agility test (p=0.029, ES: 0.68). In addition, LQF showed higher muscular stiffness than HQF players (p=0.002, ES: 0.88). There were no significant differences between HHF and LHF groups. When pooling the HQF and LQF players' data, the Pearson's correlation showed significant moderate positive association between muscular stiffness and QF (r=0.516, p<0.001). These results support the rationale that baseline stiffness is likely to influence athletic performance rather than flexibility level in soccer players.

Anosognosia in Alzheimer disease: Prevalence, associated factors, and influence on disease progression. / Anosognosia en la enfermedad de Alzheimer: prevalencia, factores asociados e influencia en la evolución de la enfermedad.

INTRODUCTION: Anosognosia is a frequent symptom in Alzheimer disease (AD). The objective of this article is to describe prevalence of this condition at time of diagnosis and analyse any predisposing factors and their influence on disease progression. METHODS: Observational, prospective, and analytical multi-centre study in an outpatient setting. Patients recently diagnosed with AD (NINCDS-ADRDA criteria) were included. Each patient underwent two cognitive, functional, and neuropsychiatric assessments separated by an interval of 18 months. The Clinical Insight Rating Scale was employed as a measure of anosognosia (CIR, scored 0-8). Progression was defined as an increase in the Clinical Dementia Rating Scale-sum of boxes of more than 2.5 points. The predictor variables were analysed using binary logistic regression. RESULTS: The study included 127 patients, and 94 completed both assessments. Of the total, 31.5% displayed severe anosognosia (CIR 7-8); 39.4%, altered level of consciousness (CIR 3-6); and 29.1%, normal awareness (CIR 0-2). The median baseline CIR in this cohort was 4 (Q1-Q3: 1-7), and at 18 months, 6 (Q1-Q3: 3-8), P<.001. Advanced age (odds ratio (OR) 2.43; CI 95%:1.14-5.19), lower educational level (OR 2.15; CI 95%:1.01-4.58), and more marked neuropsychiatric symptoms (OR 2.66; CI 95%:1.23-5.74) were predictor variables of anosognosia. Baseline CIR was similar in the groups with and without significant clinical progression. CONCLUSIONS: The large majority of patients with AD at the time of diagnosis showed significant anosognosia, and this condition was associated with advanced age, lower educational level, and more marked behavioural symptoms. Our results did not show that anosognosia had an effect on the initial clinical progression of AD after diagnosis.

Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps. / Administración segura de medicamentos intravenosos en pediatría: 5 años de experiencia de una Unidad de Cuidados Intensivos Pediátricos con bombas de infusión inteligentes.

OBJECTIVES: To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. DESIGN: Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. SETTING: A tertiary level hospital pediatric intensive care unit. PARTICIPANTS: Infusions delivered with infusion pumps in all pediatric intensive care unit patients. INTERVENTIONS: Design of a drug library with safety limits for all intravenous drugs prescribed. MAIN VARIABLES: Users' compliance with drug library as well as number and type of errors prevented were analyzed. RESULTS: Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. CONCLUSIONS: Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process.

The Kondo effect in ferromagnetic atomic contacts.

Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk, electronic conduction in these materials takes place mainly through the s and p electrons, whereas the magnetic moments are mostly in the narrow d-electron bands, where they tend to align. This general picture may change at the nanoscale because electrons at the surfaces of materials experience interactions that differ from those in the bulk. Here we show direct evidence for such changes: electronic transport in atomic-scale contacts of pure ferromagnets (iron, cobalt and nickel), despite their strong bulk ferromagnetism, unexpectedly reveal Kondo physics, that is, the screening of local magnetic moments by the conduction electrons below a characteristic temperature. The Kondo effect creates a sharp resonance at the Fermi energy, affecting the electrical properties of the system; this appears as a Fano-Kondo resonance in the conductance characteristics as observed in other artificial nanostructures. The study of hundreds of contacts shows material-dependent log-normal distributions of the resonance width that arise naturally from Kondo theory. These resonances broaden and disappear with increasing temperature, also as in standard Kondo systems. Our observations, supported by calculations, imply that coordination changes can significantly modify magnetism at the nanoscale. Therefore, in addition to standard micromagnetic physics, strong electronic correlations along with atomic-scale geometry need to be considered when investigating the magnetic properties of magnetic nanostructures.

Benefits of plasma rich in growth factors (PRGF) in skin photodamage: clinical response and histological assessment.

Skin ageing is characterized by small and fine wrinkles, roughness, laxity, and pigmentation as a result of epidermal thinning, collagen degradation, dermal atrophy, and fewer fibroblasts. Plasma rich in growth factors (PRGF) is an autologous plasma preparation enriched in proteins obtained from patient's own blood aimed at accelerating tissue repair and regeneration. To evaluate the benefits of PRGF in skin photodamage, 10 healthy volunteers were treated with three consecutive intradermal injections of PRGF in the facial area. Clinical outcomes and histological analysis were performed. A statistically significant increase in the epidermis and papillary dermis thickness was seen after PRGF treatment (p < 0.001). Skin thickening was observed in all patients studied, being more intense in the group of patients with photodamage (p < 0.001). After PRGF treatment, a reduction of the average area fraction of solar elastosis was observed in patients with clinical and histological signs of skin photodamage (p < 0.05).No changeswere observed in the number of CD31, XIIIa factor, cKit, CD10, nor p53-positive cells. The improvement score after PRGF use was 0.75 (9/12) for the group of patients with signs of skin photodamage. Intradermal PRGF infiltration appears to be an effective treatment for the photodamaged skin.

Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study.

BACKGROUND AND AIMS: Several studies have demonstrated a relationship between increased serum uric acid (SUA) concentrations and the prevalence of metabolic syndrome (MetS) in the oriental population. However, to the best of our knowledge, the association between SUA and MetS has never been investigated in elderly European individuals at high cardiovascular risk. The aim of this study was to conduct a cross-sectional and prospective evaluation of the associations between SUA concentrations and the MetS in elderly individuals at high cardiovascular risk. METHODS AND RESULTS: Men and women (55-80 years of age) from different PREDIMED (Prevención con DIeta MEDiterránea) recruiting centers were studied. Baseline cross-sectional (n = 4417) and prospective assessments (n = 1511) were performed. MetS was defined in accordance with the updated harmonized criteria. Anthropometric measurements and biochemical determinations were assessed at baseline and yearly during follow-up. Unadjusted and adjusted regression models were fitted to assess the risk of MetS and its components according to the levels of baseline SUA. Participants in the highest baseline sex-adjusted SUA quartile showed an increased prevalence of MetS than those in the lowest quartile, even after adjusting for potential confounders (odd ratio (OR): 2.3 (95% confidence interval (CI), 1.8-2.8); P < 0.001). Participants in the highest baseline sex-adjusted SUA quartile presented a higher incidence of new-onset MetS than those in the lowest quartile (hazard ratios (HR): 1.4 (95% CI, 1.1-1.9); P < 0.001). Participants initially free at baseline of hypertriglyceridemia (HR: 1.9 (1.6-2.4); P < 0.001), low high-density lipoprotein (HDL)-cholesterol (HR: 1.4 (1.1-1.7); P = 0.002), and hypertension components of MetS (HR: 2.0 (1.2-3.3); P = 0.008) and who were in the upper quartile of SUA had a significantly higher risk of developing these MetS components during follow-up. CONCLUSIONS: Elevated SUA concentrations are significantly associated with the development of MetS.

Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial.

BACKGROUND AND AIM: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. METHODS AND RESULTS: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57-9.10). CONCLUSIONS: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.