Genetic mapping reveals Nfkbid as a central regulator of humoral immunity to Toxoplasma gondii.

Protective immunity to parasitic infections has been difficult to elicit by vaccines. Among parasites that evade vaccine-induced immunity is Toxoplasma gondii, which causes lethal secondary infections in chronically infected mice. Here we report that unlike susceptible C57BL/6J mice, A/J mice were highly resistant to secondary infection. To identify correlates of immunity, we utilized forward genetics to identify Nfkbid, a nuclear regulator of NF-κB that is required for B cell activation and B-1 cell development. Nfkbid-null mice ("bumble") did not generate parasite-specific IgM and lacked robust parasite-specific IgG, which correlated with defects in B-2 cell maturation and class-switch recombination. Though high-affinity antibodies were B-2 derived, transfer of B-1 cells partially rescued the immunity defects observed in bumble mice and were required for 100% vaccine efficacy in bone marrow chimeric mice. Immunity in resistant mice correlated with robust isotype class-switching in both B cell lineages, which can be fine-tuned by Nfkbid gene expression. We propose a model whereby humoral immunity to T. gondii is regulated by Nfkbid and requires B-1 and B-2 cells for full protection.

Ammonia surrogates in the synthesis of primary amines.

Primary amines are derivatives of ammonia in which one hydrogen atom is replaced by an alkyl or aryl group. Ammonia serves as the primary nitrogen source in amination reactions, and its utilization in solution or as a pure gas has witnessed notable advancements. However, the use of gaseous ammonia remains problematic in academic laboratory settings, while employing aqueous ammonia poses challenges in highly water-sensitive transformations. Consequently, the search for alternative sources of ammonia has garnered considerable attention among the organic chemistry community. This comprehensive literature review focuses on the use of ammonia surrogates in amination reactions, irrespective of the resulting intermediate. The review emphasizes the formation of the C-N bond and underscores the importance of generating intermediate products that can be readily transformed into primary amines through well-established reactions.

Gut microbes and health. / Microbiota intestinal y salud.

The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.

RISK FACTORS FOR HYPOGLYCEMIA IN INPATIENTS WITH TOTAL PARENTERAL NUTRITION AND TYPE 2 DIABETES: A POST HOC ANALYSIS OF THE INSUPAR STUDY.

Objective: Treatment of hyperglycemia with insulin is associated with increased risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients receiving total parenteral nutrition (TPN). The aim of this study was to determine the predictors of hypoglycemia in hospitalized T2DM patients receiving TPN. Methods: Post hoc analysis of the INSUPAR study, which is a prospective, open-label, multicenter clinical trial of adult inpatients with T2DM in a noncritical setting with indication for TPN. Results: The study included 161 patients; 31 patients (19.3%) had hypoglycemic events, but none of them was severe. In univariate analysis, hypoglycemia was significantly associated with the presence of diabetes with end-organ damage, duration of diabetes, use of insulin prior to admission, glycemic variability (GV), belonging to the glargine insulin group in the INSUPAR trial, mean daily grams of lipids in TPN, mean insulin per 10 grams of carbohydrates, duration of TPN, and increase in urea during TPN. Multiple logistic regression analysis showed that the presence of diabetes with end-organ damage, GV, use of glargine insulin, and TPN duration were risk factors for hypoglycemia. Conclusion: The presence of T2DM with end-organ damage complications, longer TPN duration, belonging to the glargine insulin group, and greater GV are factors associated with the risk of hypoglycemia in diabetic noncritically ill inpatients with parenteral nutrition. Abbreviations: ADA = American Diabetes Association; BMI = body mass index; CV% = coefficient of variation; DM = diabetes mellitus; GI = glargine insulin; GV = glycemic variability; ICU = intensive care unit; RI = regular insulin; T2DM = type 2 diabetes mellitus; TPN = total parenteral nutrition.

Reliability and validity of an FFQ for South American children and adolescents from the SAYCARE study.

OBJECTIVE: The purpose of this study was to analyse the reliability and validity of a semi-quantitative FFQ to assess food group consumption in South American children and adolescents. DESIGN: The SAYCARE (South American Youth/Child cARdiovascular and Environmental) study is an observational, multicentre, feasibility study performed in a sample of 3- to 18-year-old children and adolescents attending private and public schools from six South American countries. Participants answered the FFQ twice with a two-week interval and three 24-h dietary recalls. Intraclass and Spearman's correlations, weighted Cohen's kappa (κw), percentage of agreement and energy-adjusted Pearson's correlation coefficients were calculated. SETTING: Seven cities in South America (Buenos Aires, Lima, Medelin, Montevideo, Santiago, Sao Paulo and Teresina). SUBJECTS: A sample of 200 children and 244 adolescents for reliability analyses and 252 children and 244 adolescents for validity analyses were included. RESULTS: Depending on the food group, for children and adolescents, reliability analyses resulted in Spearman's coefficients from 0·47 to 0·73, intraclass correlation coefficients from 0·66 to 0·99, κw coefficients from 0·35 to 0·63, and percentage of agreement between 72·75 and 83·52 %. In the same way, validity analyses resulted in Spearman's coefficients from 0·17 to 0·37, energy-adjusted Pearson's coefficients from 0·17 to 0·61, κw coefficients from 0·09 to 0·24, and percentages of agreement between 45·79 and 67·06 %. CONCLUSION: The SAYCARE FFQ achieved reasonable reliability and slight-moderate validity for almost all food groups intakes. Accordingly, it can be used for the purpose of ranking the intake of individuals within a population.

Neuronal filopodium formation induced by the membrane glycoprotein M6a (Gpm6a) is facilitated by coronin-1a, Rac1, and p21-activated kinase 1 (Pak1).

Stress-responsive neuronal membrane glycoprotein M6a (Gpm6a) functions in neurite extension, filopodium and spine formation and synaptogenesis. The mechanisms of Gpm6a action in these processes are incompletely understood. Previously, we identified the actin regulator coronin-1a (Coro1a) as a putative Gpm6a interacting partner. Here, we used co-immunoprecipitation assays with the anti-Coro1a antibody to show that Coro1a associates with Gpm6a in rat hippocampal neurons. By immunofluorescence microscopy, we demonstrated that in hippocampal neurons Coro1a localizes in F-actin-enriched regions and some of Coro1a spots co-localize with Gpm6a labeling. Notably, the over-expression of a dominant-negative form of Coro1a as well as its down-regulation by siRNA interfered with Gpm6a-induced filopodium formation. Coro1a is known to regulate the plasma membrane translocation and activation of small GTPase Rac1. We show that Coro1a co-immunoprecipitates with Rac1 together with Gpm6a. Pharmacological inhibition of Rac1 resulted in a significant decrease in filopodium formation by Gpm6a. The same was observed upon the co-expression of Gpm6a with the inactive GDP-bound form of Rac1. In this case, the elevated membrane recruitment of GDP-bound Rac1 was detected as well. Moreover, the kinase activity of the p21-activated kinase 1 (Pak1), a main downstream effector of Rac1 that acts downstream of Coro1a, was required for Gpm6a-induced filopodium formation. Taken together, our results provide evidence that a signaling pathway including Coro1a, Rac1, and Pak1 facilitates Gpm6a-induced filopodium formation. Formation of filopodia by membrane glycoprotein M6a (Gpm6a) requires actin regulator coronin-1a (Coro1a), known to regulate plasma membrane localization and activation of Rac1 and its downstream effector Pak1. Coro1a associates with Gpm6a. Blockage of Coro1a, Rac1, or Pak1 interferes with Gpm6a-induced filopodium formation. Moreover, Gpm6a facilitates Rac1 membrane recruitment. Altogether, a mechanistic insight into the process of Gpm6a-induced neuronal filopodium formation is provided.

Executive summary of the consensus document on metabolic disorders and cardiovascular risk in patients with HIV infection.

The importance of the metabolic disorders and their impact on patients with HIV infection requires an individualized study and continuous updating. HIV patients have the same cardiovascular risk factors as the general population. The HIV infection per se increases the cardiovascular risk, and metabolic disorders caused by some antiretroviral drugs are added risk factors. For this reason, the choice of drugs with a good metabolic profile is essential. The most common metabolic disorders of HIV infected-patients (insulin resistance, diabetes, hyperlipidemia or osteopenia), as well as other factors of cardiovascular risk, such as hypertension, should also be dealt with according to guidelines similar to the general population, as well as insisting on steps to healthier lifestyles. The aim of this document is to provide a query tool for all professionals who treat HIV-patients and who may present or display any metabolic disorders listed in this document.

[Consensus statement on metabolic disorders and cardiovascular risks in patients with human immunodeficiency virus]. / Documento de consenso sobre alteraciones metabólicas y riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana.

OBJECTIVE: This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients. METHODS: This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system. RESULTS: A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated. CONCLUSIONS: These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included.

Reducing Solvent Consumption in Reductive Catalytic Fractionation through Lignin Oil Recycling.

Reductive catalytic fractionation (RCF) enables the simultaneous valorization of lignin and carbohydrates in lignocellulosic biomass through solvent-based lignin extraction, followed by depolymerization and catalytic stabilization of the extracted lignin. Process modeling has shown that the use of exogenous organic solvent in RCF is a challenge for economic and environmental feasibility, and previous works proposed that lignin oil, a mixture of lignin-derived monomers and oligomers produced by RCF, can be used as a cosolvent in RCF. Here, we further explore the potential of RCF solvent recycling with lignin oil, extending the feasible lignin oil concentration in the solvent to 100 wt %, relative to the previously demonstrated 0-19 wt % range. Solvents containing up to 80 wt % lignin oil exhibited 83-93% delignification, comparable to 83% delignification with a methanol-water mixture, and notably, using lignin oil solely as a solvent achieved 67% delignification in the absence of water. In additional experiments, applying the RCF solvent recycling approach to ten consecutive RCF reactions resulted in a final lignin oil concentration of 11 wt %, without detrimental impacts on lignin extraction, lignin oil molar mass distribution, aromatic monomer selectivity, and cellulose retention. Overall, this work further demonstrates the potential for using lignin oil as an effective cosolvent in RCF, which can reduce the burden on downstream solvent recovery.

Screening of variables affecting the selective leaching of valuable metals from waste motherboards' PCBs.

The presence of valuable and hazardous metals in waste printed circuit boards, especially, motherboards, makes their recovery necessary as implies great economic and environmental advantages and develops urban mining processes. Hence, this research is focused on the selective leaching of Cu, Pb, and Sn as base metals using nitric acid and hydrochloric acid and Au, Ag, and Pd as precious metals using thiourea and sodium thiosulfate from waste motherboards' PCBs in a sequential eco-friendly two-stage process. Previously, thiourea and sodium thiosulfate were used as leaching agents to investigate their applicability for the leaching of metals from PCBs in a single-stage process. Screening experimental design was applied to screen the variables affecting the leaching process in order to evaluate their impact on the recovery of metals and select the significant factors. The results demonstrated that base and precious metals can be leached appropriately in two consecutive stages compared to a single-stage process. Nitric acid was found to be a much more efficient agent to leach Cu and Pb in comparison with hydrochloric acid which was more suitable for the leaching of Sn. In the case of precious metals, higher amounts of Au were leached using thiourea, whereas sodium thiosulfate was able to leach more Pd. Roughly similar results were obtained for the leaching of Ag using these leaching agents. Nitric acid concentration, average particle size, temperature, and leaching time were found to be significant to maximize the leaching of Cu and Pb and minimize that for Au, Ag, and Pd in the first stage. Initial pH was the only variable influencing the second stage, in particular, Au leaching by thiourea.

S/N/O-Enriched Carbons from Polyacrylonitrile-Based Block Copolymers for Selective Separation of Gas Streams.

A series of polyacrylonitrile (PAN)-based block copolymers with poly(methyl methacrylate) (PMMA) as sacrificial bock were synthesized by atom transfer radical polymerization and used as precursors for the synthesis of porous carbons. The carbons enriched with O- and S-containing groups, introduced by controlled oxidation and sulfuration, respectively, were characterized by Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectrometry, and their surface textural properties were measured by a volumetric analyzer. We observed that the presence of sulfur tends to modify the structure of the carbons, from microporous to mesoporous, while the use of copolymers with a range of molar composition PAN/PMMA between 10/90 and 47/53 allows the obtainment of carbons with different degrees of porosity. The amount of sacrificial block only affects the morphology of carbons stabilized in oxygen, inducing their nanostructuration, but has no effect on their chemical composition. We also demonstrated their suitability for separating a typical N2/CO2 post-combustion stream.

Postnatal nitric oxide inhibition modifies neurotensin effect on ATPase activity.

We have previously showed that peptide neurotensin inhibits neuronal Na(+), K(+)-ATPase activity, an effect which involves high affinity neurotensin receptor. Nitric oxide (NO) acts as a neurotransmitter or as a neuromodulator when it is synthesized by neuronal nitric oxide synthase. Neurotensin effect on Na(+), K(+)-ATPase activity was evaluated in cortical synaptosomal membranes isolated from rats injected at 3, 4 and 5 postnatal days with saline (control) or N (ω)-nitro-L-arginine methyl esther (L-NAME), a nitric oxide synthase inhibitor. Assays were carried out at two stages: juvenile (35 days) and adult (56 days) ages. In an open field task, results recorded in juvenile rats markedly differed from those obtained in adult rats. The presence of neurotensin at 3.5 × 10(-8)-3.5 × 10(-6 )M concentration decreased 16-34% Na(+), K(+)-ATPase activity in membranes purified from control animals. At variance, the peptide failed to alter this enzyme activity in membranes obtained after L-NAME treatment. After administration of L-NAME, [(3)H]-ouabain binding to membranes isolated from adult male rats decreased 64% in the presence of 1.0 × 10(-6 )M neurotensin, a peptide concentration which only slightly decreased binding to membranes isolated from juvenile rats. It is postulated that early postnatal NO dysfunction may exert a permanent change in neurotensin system that influence later Na(+), K(+)-ATPase response to neurotensin.

Psychometric properties of 4-item questionnaire for sleep habits and time in a South American paediatric population.

OBJECTIVES: To assess the psychometric properties of 4-item questionnaire about sleep habits and time in South American children (3-10 years) and adolescents (11-18 years). MATERIAL AND METHODS: We evaluated 459 participants from seven South American cities. Two items from week and weekend days wake up time and bedtime were asked twice, with a 2-week interval. We calculated time spent in bed (subtracting wake up time from bedtime). Participants also answered the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) sleep time questionnaire. RESULTS: The questionnaire showed acceptable temporal stability in children and adolescents on total days (rho≥0.30; p<0.05). For total days, the questionnaire presented acceptable convergent validity only in children (rho from 0.48 to 0.62; p≤0.01) compared with the HELENA questionnaire. CONCLUSION: The 4-item questionnaire is a reliable and valid tool for children; however, its validity is not consistent in adolescents for sleep habits and time.

Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose.

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.

Metabolic Syndrome Among Young Health Professionals in the Multicenter Latin America Metabolic Syndrome Study.

Background: Metabolic syndrome (MS) and its components increase the risk of a number of chronic diseases. Evidence regarding its prevalence among health professionals, particularly in Latin America, is limited. The purpose of this study was to assess the overall prevalence of MS and its components among health professionals and students from five Latin American countries. Methods: A cross-sectional multicenter study entitled LATIN America METabolic Syndrome (LATINMETS) was conducted on five groups of apparently healthy volunteer subjects. Sociodemographic factors, lifestyle variables (smoking and physical activity), anthropometric measurements (weight, height, and waist circumference), standard biochemical analyses [triglycerides, glucose, and high-density lipoprotein cholesterol (HDL-C)], and blood pressure measurements were assessed. MS was diagnosed based on internationally harmonized criteria. Associations between MS components and sociodemographic, lifestyle, and anthropometric variables were analyzed using multivariate logistic regression. Results: A total of 1,032 volunteers (n = 316-Mexico, n = 285-Colombia, n = 223-Brazil, n = 132-Paraguay, and n = 76-Argentina) were recruited. The majority of them were women (71.9%), students (55.4%), and younger than 28 years (67.2%). The overall prevalence of age-standardized MS was 15.5% (23.1% men and 12.2% women). The majority (59.3%) presented at least one MS component, mainly abdominal obesity (29.7%) and low HDL-C levels (27.5%). After adjusting for age and sex, MS and its components were positively associated with being overweight or obese. Conclusions: MS prevalence in this study was similar to that generally found among young populations in Latin-American countries. More than half of the sample had at least one MS component, suggesting that preventive measures and treatments aimed at achieving low-risk health status are essential in this population.

Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial.

BACKGROUND: There is no established insulin regimen in T2DM patients receiving parenteral nutrition. AIMS: To compare the effectiveness (metabolic control) and safety of two insulin regimens in patients with diabetes receiving TPN. DESIGN: Prospective, open-label, multicenter, clinical trial on adult inpatients with type 2 diabetes on a non-critical setting with indication for TPN. Patients were randomized on one of these two regimens: 100% of RI on TPN or 50% of Regular insulin added to TPN bag and 50% subcutaneous GI. Data were analyzed according to intention-to-treat principle. RESULTS: 81 patients were on RI and 80 on GI. No differences were observed in neither average total daily dose of insulin, programmed or correction, nor in capillary mean blood glucose during TPN infusion (165.3 ± 35.4 in RI vs 172.5 ± 43.6 mg/dL in GI; p = 0.25). Mean capillary glucose was significantly lower in the GI group within two days after TPN interruption (160.3 ± 45.1 in RI vs 141.7 ± 43.8 mg/dL in GI; p = 0.024). The percentage of capillary glucose above 180 mg/dL was similar in both groups. The rate of capillary glucose ≤70 mg/dL, the number of hypoglycemic episodes per 100 days of TPN, and the percentage of patients with non-severe hypoglycemia were significantly higher on GI group. No severe hypoglycemia was detected. No differences were observed in length of stay, infectious complications, or hospital mortality. CONCLUSION: Effectiveness of both regimens was similar. GI group achieved better metabolic control after TPN interruption but non-severe hypoglycemia rate was higher in the GI group. CLINICAL TRIAL REGISTRY: This trial is registered at clinicaltrials.gov as NCT02706119.

[Notes on the cost-effectiveness of nutritional therapy with oral supplementation in the integral recovery of the patient with MRD]. / Apuntes sobre el coste-efectividad de la terapia nutricional con suplementación oral en la recuperación integral del paciente con DRE.

INTRODUCTION: The efficient management of health services requires obtaining the highest level of health possible with the available resources. The health economy has developed in recent years under the pressure of a more demanding population, older and with more comorbidities, in an environment of limited resources and greater financing difficulties. The Economics of Nutrition was born as a new discipline that addresses aspects related to the role of economics and nutrition in the health of healthy and sick populations. The economic analyzes are part of the evaluation tools for health interventions. Cost-effectiveness studies are the most frequently used. Cost-effectiveness studies have shown that the use of oral nutritional supplements offer clinical advantages for undernourished patients (reduction of morbidity and mortality) and economic benefits for the system (reduction of hospital stay, lower re-entry rates and cost savings). Oral nutritional supplementation in the integral recovery of the patient with malnutrition related to the disease is cost effective.

INTRODUCCIÓN: La gestión eficiente de los servicios sanitarios obliga a obtener el máximo nivel de salud posible con los recursos disponibles. La economía de la salud se ha desarrollado en los últimos años ante la presión de una población más demandante, de más edad y con más comorbilidades en un entorno de recursos limitados y mayores dificultades de financiación. La economía de la nutrición nace como una nueva disciplina que atiende aspectos relacionados con el papel de la economía y la nutrición en la salud de las poblaciones sanas y enfermas. Los análisis económicos forman parte de las herramientas de evaluación de las intervenciones sanitarias. Los estudios de coste-efectividad "los más frecuentemente utilizados" han demostrado que la utilización de los suplementos nutricional orales ofrece ventajas clínicas para los pacientes desnutridos (reducción de morbimortalidad) y económicas para el sistema (reducción de estancia hospitalaria, menores tasas de reingresos y ahorros de costes). La suplementación nutricional oral en la recuperación integral del paciente con desnutrición relacionada con la enfermedad es coste-efectiva.

Adsorption of an anionic dye (Congo red) from aqueous solutions by pine bark.

Pinus pinaster bark, an abundant by-product from the timber industry, has been studied as a potential low-cost adsorbent for the removal of Congo red (CR) dye from wastewaters. Surface morphological and physico-chemical characteristics of pine bark were analysed using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), determination of the point of zero charge (pHPZC) and elemental analysis. Assays were performed to determine the wavelength for the maximum absorbance and the stability with time of CR solutions depending on concentration and/or pH, which resulted to be a very significant parameter. Adsorption studies were conducted on batch mode to study the effect of contact time (till 7 days), pH (2-9), adsorbent dosage (1-10 g L-1) and temperature (25-60 °C). The bark adsorption capacity at equilibrium varied between 0.3 and 1.6 mg g-1 and the equilibrium adsorption percentage between 23.4 and 100% depending on adsorbent dosage, temperature and pH at an initial CR concentration of 5 mg L-1. Kinetic data for the removal of CR by pine bark were best fitted by the pseudo-second-order kinetic model. The equilibrium data fitted well with the Freundlich model. Thermodynamic analysis indicated that the adsorption process is exothermic and spontaneous.

Optimization of the Extraction of Bioactive Compounds from Walnut (Juglans major 209 x Juglans regia) Leaves: Antioxidant Capacity and Phenolic Profile.

This work studies the extraction of phenolic compounds from walnut leaves of the hybrid Juglans major 209 x Juglans regia based on extract antioxidant capacity. Once the solid/liquid ratio was selected (1/10 g/mL), by means of a Box-Benkhen experimental design, the influence of temperature (25-75 °C), time (30-120 min), and aqueous ethanol concentration (10-90%) on extraction yield and ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) antioxidant activities were analyzed. In all cases, the quadratic effect of % EtOH was the most significant, followed by the linear effect of temperature and, for most of the responses, the effect of time was almost negligible. Response surface analysis allowed to select the optimal extraction conditions: 75 °C, 120 min and 50% ethanol, which led to the following extract properties: extraction yield, 30.17%; FRAP, 1468 nmol ascorbic acid equivalents (AAE)/mg extract d.b.; DPPH, 1.318 mmol Trolox equivalents (TRE)/g extract d.b.; DPPH EC50, 0.11 mg/mL; ABTS, 1.256 mmol TRE/g extract (on dry basis) and ABTS EC50, 0.985 mg/mL. Quercetin 3-ß-D-glucoside, neochlorogenic acid, and chlorogenic acid, in this order, were the main compounds identified in this extract by ultra-performance liquid chromatography coupled with electrospray ionization and time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS), with various potential applications that support this valorization alternative for walnut leaves.