Proof-of-concept study demonstrating the pathogenicity of affinity-purified IgG antibodies directed to domain I of β2-glycoprotein I in a mouse model of anti-phospholipid antibody-induced thrombosis.

IgG aPL against domain I of β2-glycoprotein I (β2GPI) [anti-DI (aDI)] is associated with the pathogenesis of APS, an autoimmune disease defined by thrombosis and pregnancy morbidity. To date, however, no study has demonstrated direct pathogenicity of IgG aDI in vivo. In this proof-of-concept study, we designed a novel system to affinity purify polyclonal aDI aPL in order to assess its prothrombotic ability in a well-characterized mouse microcirculation model for APS

Unexplored olive cultivars from the Valencian Community (Spain): some chemical characteristics as a valorization strategy

[EN] The olive processing industry has till date been dominated by a small group of cultivars, leading to the possibility of some olive cultivars becoming extinct in the near future. In this study, we determined the composition of some chemical components in the olive oils from 31 minor olive cultivars of the Valencian Community. Our main aim was to identify suitable cultivars, which could produce differentiated olive oils, thus aiming towards their valorization. The average oil content of minor olive cultivars was found to be good, with some of them reporting approximately 60% (dry basis). On average, the total phenolic content was 229mg kg(-1), with cv. Mas Blanc reporting the highest content (570mg kg(-1)). Among the various tocopherols found in olives, -tocopherol was the main constituent, with a maximum concentration of 290.6mg kg(-1). Linoleic acid was the main polyunsaturated fatty acid and varied between 3.4% (cv. Del Pomet) and 16.9% (cv. Blanqueta Enguera). Special attention needs to be paid to the composition of sterols, since some olive oils exceeded the limits established for some sterols by the current European legislation. Some of the cultivars studied were highly productive, and originated differentiated olive oils with a rich composition of antioxidants and essential fatty acids. In some cases, these beneficial compounds were higher than those of commercial oils obtained from the most common cultivars worldwide. These results could contribute to the commercial exploitation of some of the studied cultivars.Salazar-García, DC.; Malheiro, R.; Pereira, JA.; López- Cortés, I. (2019). Unexplored olive cultivars from the Valencian Community (Spain): some chemical characteristics as a valorization strategy. European Food Research and Technology. 245(2):325-334. https://doi.org/10.1007/s00217-018-3164-7S3253342452Avidan B, Birger R, Abed-El-Hadi F, Salmon O, Hekster O, Friedman Y, Lavee S (2011) Adopting vigorous olive cultivars to high density hedgerow cultivation by soil applications of uniconazole, a gibberellin synthesis inhibitor. Span J Agric Res 9:821–830Barranco D, Rallo L (2000) Olive cultivars in Spain. HortTechnology 10:107–110Navero DB (2000) World catalogue of olive varieties. International Olive Oil Council, MadridBorges TH, Pereira JA, Cabrera-Vique C, Lara L, Oliveira AF, Seiquer I (2017) Characterization of Arbequina virgin olive oils produced in different regions of Brazil and Spain: physicochemical properties, oxidative stability and fatty acid profile. Food Chem 215:454–462Laroussi-Mezghani S, Le Dréau Y, Molinet J, Hammami M, Grati-Kamoun N, Artaud J (2016) Biodiversity of Tunisian virgin olive oils: varietal origin classification according to their minor compounds. Eur Food Res Technol 242:1087–1099Kosma I, Vavoura M, Kontakos S, Karabagias I, Kontominas M, Apostolos K, Badeka A (2016) Characterization and classification of extra virgin olive oil from five less well-known Greek olive cultivars. J Am Oil Chem Soc 93:837–848Reboredo-Rodríguez P, González-Barreiro C, Cancho-Grande B, Valli E, Bendini A, Toschi TG, Simal-Gandara J (2016) Characterization of virgin olive oils produced with autochthonous Galician varieties. Food Chem 212:162–171Kyçyk O, Aguillera MP, Gaforio JJ, Jiménez A, Beltrán G (2016) Sterol composition of virgin olive oil of forty-three olive cultivars from the World Collection Olive Germplasm Bank of Cordoba. J Sci Food Agric 96:4143–4150Ruiz-Domínguez ML, Raigón MD, Prohens J (2013) Diversity for olive oil composition in a collection of varieties from the region of Valencia (Spain). Food Res Int 54:1941–1949Mateos R, Dominguez MM, Espartero JL, Cert A (2003) Antioxidant effect of phenolic compounds, α-tocopherol, and other minor components in virgin olive oil. J Agric Food Chem 51:7170–7175Hermoso M, Uceda M, García A, Morales B, Frias ML, Fernández A (1991) Elaboración de Aceite de Calidad. Consejeria de Agricultura y Pesca, SevillaMalheiro R, Rodrigues N, Bissaro C, Leimann F, Casal S, Ramalhosa E, Pereira JA (2017) Improvement of sensorial and volatile profiles of olive oil by addition of olive leaves. Eur J Lipid Sci Technol 119:1700177Commission Delegated Regulation (EU) 2016/2095 amending Regulation (EEC) No 2568/91 on the characteristics of olive oil and olive-residue oil and on the relevant methods of analysis. Off J Eur Union L:326Slover HT, Thompson RH, Merola GV (1983) Tocopherol and sterol determination by capillary gas chromatography. J Am Oil Chem Soc 60:1524–1528Sousa A, Casal S, Malheiro R, Lamas H, Bento A, Pereira JA (2015) Aromatized olive oil: Influence of flavouring in quality, composition, stability, antioxidants, and antiradical potential. LWT Food Sci Technol 60:22–28Limón P, Malheiro R, Casal S, Acién-Fernández FG, Fernández-Sevilla JM, Rodrigues N, Cruz R, Bermejo R, Pereira JA (2015) Improvement of stability and carotenoids fraction of virgin olive oil by addition of microalgae Scenedesmus almeriensis extracts. Food Chem 175:203–211Motilva MJ, Tovar MJ, Romero MP, Alegre S, Girona J (2000) Influence of regulated deficit irrigation strategies applied to olive trees (Arbequina cultivar) on oil yield and oil composition during the fruit ripening period. J Sci Food Agric 80:2037–2043Palese AM, Nuzzo V, Favati F, Pietrafesa A, Celano G, Xiloyannis C (2010) Effects of water deficit on the vegetative response, yield and oil quality of olive trees (Olive europaea L., cv Coratina) grown under intensive cultivation. Sci Hortic 125:222–229Allalout A, Krichèn D, Methenni K, Taamalli A, Oueslati I, Daoud D, Zarrouk M (2009) Characterization of virgin olive oil from Super Intensive Spanish and Greek varieties grown in northern Tunisia. Sci Hortic 120:77–83Simopoulos AP, DiNicolantonio JJ (2016) The importance of a balanced ω-6 to ω-3 ratio in the prevention and management of obesity. Open Heart 3:e000385Marongui B, Özcan MM, Rosa A, Dessi MA, Piras A, AlJuhaimi F (2015) Monitoring of the fatty acid compositions of some olive oils. Riv Ital Sostanze Grasse 92:39–42Paiva-Martins F, Kiritsakis A (2017) Olive fruit and olive oil composition and their functionalcompounds. In: Kiritsakis A, Shahidi F (eds) Olives and olive oil as functional foods. Bioactivity, chemistry and processing. Wiley, Hoboken, pp 81–116Shahzad N, Khan W, Shadab MD, Ali A, Saluja SS, Sharma S, Al-Allaf FA, Abduljaleel Z, Ibrahim IAA (2017) Phytosterols as a natural anticancer agent: current status and future perspective. Biomed Pharmacol 88:786–794Covas MI, Ruiz-Gutiérrez V, de la Torre R, Kafatos A, Lamuela-Raventós RM, Osada J, Owen RW, Visioli F (2006) Minor components of olive oil: evidence to date of health benefits in humans. Nutr Rev 64:S20–S30Pirodi M, Albini A, Fabiani R, Giovannelli L, Luceri C, Natella F, Rosignoli P, Rossi T, Taticchi A, Servili M, Galli F (2017) Nutrigenomics of extra-virgin olive oil: a review. Biofactors 43:17–41Franco MN, Galeano-Díaz T, Sánchez J, De Miguel C, Martín-Vertedor D (2014) Total phenolic compounds and tocopherols profiles of seven olive oil varieties grown in the South-West of Spain. J Oleo Sci 63:115–125Aparicio R, Roda L, Albi MA, Gutiérrez F (1999) Effect of various compounds on virgin olive oil stability measured by Rancimat. J Agric Food Chem 47:4150–4155Bullota S, Celano M, Lepore SM, Montalcini T, Pujia A, Russo D (2014) Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases. J Transl Med 12:1–9Krychene D, Salvador MD, Fregapane G (2015) Stability of virgin olive oil phenolic compounds during long-term storage (18 months) at temperatures of 5–50 °C. J Agric Food Chem 63:6779–6786Aparicio-Ruiz R, García-González DL, Oliver-Pozo C, Tena N, Morales MT, Aparicio A (2016) Phenolic profile of virgin olive oils with and without sensory defects: oils with non-oxidative defects exhibit a considerable concentration of phenols. Eur J Lipid Sci Technol 118:299–307Yorulmaz A, Poyrazoğlu ES, Özcan MM, Tekin A (2012) Phenolic profiles of Turkish olives and olive oils. Eur J Lipid Sci Technol 14:1083–1093Arslan A, Özcan MM (2011) Phenolic profile and antioxidant activity of olive fruits of the Turkish variety “Sarıulak” from different locations. Grasas Aceites 64:453–461Dağdelen A, Tümen G, Özcan MM, Dündar E (2013) Phenolics profiles of olive fruits (Olea europaea L.) and oils from Ayvalık, Domat and Gemlik varieties at different ripening stages. Food Chem 136:41–45Malheiro R, Rodrigues N, Pereira JA (2015). In: Boskou D (ed) Olive and olive oil bioactive constituents. AOCS Press, UrbanaCriado MN, Morelló JR, Motilva MJ, Romero MP (2004) Effect of growing area on pigment and phenolic fractions of virgin olive oils of the Arbequina variety in Spain. J Am Oil Chem Soc 81:633–640Gómez-Rico A, Fregapane G, Salvador MD (2008) Effect of cultivar and ripening on minor components in Spanish olive fruits and their corresponding virgin olive oils. 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Higher Education, Employability and Transitions to the Labour Market

Este libro incluye conferencias de una Conferencia Europea, celebrada el 7 y 8 de septiembre 2017, en la Universidad de Sevilla. Fue organizada por el Proyecto EMPLOY – Enhancing the Employability of Non-traditional Students in Higher Education” (noviembre 2014 – ovtubre 2017). El proyecto fue financiado por el Programa Erasmus Plus, KA2 Higher Education, Strategic Partnership (Ref.: 2014-1-UK01-KA203-001842).Erasmus Plus Programme, KA2 Higher Education, Strategic Partnership Ref.: 2014-1-UK01-KA203-00184

Defective glucose and lipid metabolism in rheumatoid arthritis is determined by chronic inflammation in metabolic tissues.

Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA

'Atherothrombosis-associated microRNAs in Antiphospholipid syndrome and Systemic Lupus Erythematosus patients'.

MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors. Gene and protein expression of miRNA biogenesis-related molecules were also reduced. Accordingly, more than 75% of identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a and -125a were low, while miR-146a and miR-155 appeared elevated. Altered microRNAs' expression was linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies deregulated microRNAs expression, and decreased miRNA biogenesis-related proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis, significantly altered in neutrophils of APS and SLE patients, is associated to their atherothrombotic status, further modulated by specific autoantibodies

Advanced Breast Cancer Guidelines in Latin America: Assessment, Adaptation, and Implementation of Fifth Advanced Breast Cancer Consensus Guidelines

PURPOSEAs the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access.METHODSSixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed.RESULTSLatin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent.CONCLUSIONDespite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region