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Supplementary Data from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance

Gastric cancer represents the third leading cause of global cancer mortality and an area of unmet clinical need. Drugs that target the DNA damage response, including ATR inhibitors (ATRi), have been proposed as novel targeted agents in gastric cancer. Here, we sought to evaluate the efficacy of ATRi in preclinical models of gastric cancer and to understand how ATRi resistance might emerge as a means to identify predictors of ATRi response. A positive selection genome-wide CRISPR-Cas9 screen identified candidate regulators of ATRi resistance in gastric cancer. Loss-of-function mutations in either SMG8 or SMG9 caused ATRi resistance by an SMG1-mediated mechanism. Although ATRi still impaired ATR/CHK1 signaling in SMG8/9-defective cells, other characteristic responses to ATRi exposure were not seen, such as changes in ATM/CHK2, γH2AX, phospho-RPA, or 53BP1 status or changes in the proportions of cells in S- or G2–M-phases of the cell cycle. Transcription/replication conflicts (TRC) elicited by ATRi exposure are a likely cause of ATRi sensitivity, and SMG8/9-defective cells exhibited a reduced level of ATRi-induced TRCs, which could contribute to ATRi resistance. These observations suggest ATRi elicits antitumor efficacy in gastric cancer but that drug resistance could emerge via alterations in the SMG8/9/1 pathway.Significance:These findings reveal how cancer cells acquire resistance to ATRi and identify pathways that could be targeted to enhance the overall effectiveness of these inhibitors.

Supplementary Table from SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance

High aluminum loading incorporation in the SBA-15 silica structure was investigated. Different Si/Al molar ratios (15, 10, and 2) were evaluated. The SBA-15 and the aluminum-containing materials (Al-SBA-15) were prepared by the “pH adjusting” method with modifications. The mesoporous structure of the materials was demonstrated by the type IV isotherms. The SBA-15 pore changed from a cylindrical to a slit-like structure in the presence of higher aluminum content. X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM) pointed out that the structural order is compromised in the presence of a higher aluminum load in the Al-SBA-15 materials, although the mesoporous structure was preserved. Higher Al loading increases the total quantity of Lewis acid sites as well as generates Brönsted acid sites. CO adsorption FTIR spectroscopy suggests aluminum incorporation into the SBA-15 and generation of acid sites. The Si-O-Al linkage in the aluminum-containing materials was corroborated by UV-Vis DRS due to the presence of a peak centered at 216 nm related to the Al-O bond, which is ascribed to four-coordinated framework aluminum in the SBA-15 structure. XPS spectra of Al 2p suggested that the Al species are less oxidized than the Al2O3 phase giving some indication of Al incorporation into the SBA-15 framework. 27Al MAS NMR results revealed that the aluminum species are in a tetrahedral oxygen coordination environment for Al-SBA-15 with Si/Al molar ratios of 15 and 10. Aluminum species in both tetrahedral and octahedral environments were evidenced for Al-SBA-15 with a Si/Al molar ratio of 2.

Resumen La Seccion de Via Aerea de la Sociedad Catalana de Anestesiologia, Reanimacion y Terapeutica del Dolor (SCARTD) presenta la actualizacion de las recomendaciones para la evaluacion y manejo de la via aerea dificil con el fin de incorporar los avances tecnicos y los cambios observados en la practica clinica desde la publicacion de la primera edicion en 2008. La metodologia elegida fue la adaptacion de 5 guias internacionales recientemente publicadas, cuyo contenido fue previamente analizado y comparado de forma estructurada, y el consenso de expertos de los 19 centros participantes. El documento final fue sometido a la valoracion de los miembros de la SCARTD y a la revision por parte de 11 expertos independientes. Estas recomendaciones estan pues sustentadas en la evidencia cientifica actualmente disponible y en un amplio acuerdo de los profesionales de su ambito de aplicacion. En esta edicion se amplia la definicion de via aerea dificil, abarcando todas las tecnicas de manejo, y se hace mayor hincapie en la valoracion de la via aerea y en la clasificacion en 3 categorias segun el potencial grado de dificultad y las consideraciones de seguridad adicionales, que guiaran la planificacion de la estrategia a seguir. La preparacion previa al manejo de la via aerea, no solo relativa al paciente y al material, sino tambien a la comunicacion e interaccion entre todos los agentes implicados, ocupa un lugar destacado en todos los escenarios incluidos en el presente documento. El texto refleja el aumento progresivo del uso de los videolaringoscopios y de los dispositivos de segunda generacion en nuestro entorno y promueve tanto su uso electivo como el uso precoz en la via aerea no prevista. Tambien recoge la creciente utilizacion de la ecografia como herramienta de apoyo en la exploracion y toma de decisiones. Se han abordado nuevos escenarios como el riesgo de broncoaspiracion y la extubacion considerada dificil. Finalmente, se trazan las lineas maestras de los programas de entrenamiento y formacion continuada en via aerea necesarios para garantizar la implementacion efectiva y segura de las recomendaciones.

The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines.

The phase diagram of Al-Li-Cu system in the Al-rich region was determined by means of first-principles calculations and statistical mechanics. The mixing enthalpies of many configurations for different lattices in the whole Al-Li-Cu system were determined by density functional theory simulations to find the stable phases in the convex hull. They were fitted with a cluster expansion to calculate the free energy of the configurations with different compositions as a function of temperature in the Al-rich region (Al content > 40 at. %) by means of Monte Carlo simulations. It was found that the ground state phases in the Al-rich part of the Al-Li-Cu phase diagram were {\alpha}-Al, {\theta}' (Al2Cu), {\delta}' (Al3Li), {\delta} (AlLi) and T1 (Al6Cu4Li3), while {\theta}'' (Al3Cu), T1' (Al2CuLi) and Al3Cu2Li were found on the lowest mixing enthalpy surfaces of their lattices and were metastable. {\alpha}-Al, {\delta} and T1 are stable phases in the whole temperature range while {\delta}' becomes metastable at very low temperature and {\theta} (Al2Cu) replaces {\theta}' as the stable phase at approximately 550 K due to the vibrational entropic contribution. In addition, the phase diagram in the Al-rich region was built and it was shown in isothermal sections from 100 K to 900 K. They were in good agreement with the limited experimental data in the literature and provided new information regarding the stability, solubility and stoichiometry of the different phases. This information is important to understand the precipitation mechanisms during high temperature aging.

Gastric cancer represents the third leading cause of global cancer mortality and an area of unmet clinical need. Drugs that target the DNA damage response, including ATR inhibitors (ATRi), have been proposed as novel targeted agents in gastric cancer. Here, we sought to evaluate the efficacy of ATRi in preclinical models of gastric cancer and to understand how ATRi resistance might emerge as a means to identify predictors of ATRi response. A positive selection genome-wide CRISPR-Cas9 screen identified candidate regulators of ATRi resistance in gastric cancer. Loss-of-function mutations in either SMG8 or SMG9 caused ATRi resistance by an SMG1-mediated mechanism. Although ATRi still impaired ATR/CHK1 signaling in SMG8/9-defective cells, other characteristic responses to ATRi exposure were not seen, such as changes in ATM/CHK2, γH2AX, phospho-RPA, or 53BP1 status or changes in the proportions of cells in S- or G2–M-phases of the cell cycle. Transcription/replication conflicts (TRC) elicited by ATRi exposure are a likely cause of ATRi sensitivity, and SMG8/9-defective cells exhibited a reduced level of ATRi-induced TRCs, which could contribute to ATRi resistance. These observations suggest ATRi elicits antitumor efficacy in gastric cancer but that drug resistance could emerge via alterations in the SMG8/9/1 pathway. Significance: These findings reveal how cancer cells acquire resistance to ATRi and identify pathways that could be targeted to enhance the overall effectiveness of these inhibitors.

BackgroundIgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions [1, 2], that share pathogenic mechanisms [1], in which B-lymphocytes are described as key cells implicated in these processes. BAFF, APRIL and BAFF-R are cytokines implicated in the development of B-lymphocytes [3, 4] and in autoimmune processes [5, 6]. In this regard, an influence of BAFF, APRIL and BAFFR polymorphisms was observed on several immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion variant for inflammatory conditions [7, 8].ObjectivesTo determine whether BAFF, APRIL and BAFFR could be used as differential biomarkers between IgAV and IgAN.MethodsBAFF rs374039502 (which colocalizes with BAFF GCTGT>A), two tag variants within APRIL (rs11552708 and rs6608) and two tag variants within BAFFR (rs7290134 and rs77874543) were genotyped in 394 Caucasian IgAV patients, 95 patients with IgAN and 832 matched healthy controls.ResultsSimilar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when BAFF, APRIL and BAFFR variants were analyzed independently (Table 1). In accordance with that, no BAFF, APRIL and BAFFR genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences were observed between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls when each when BAFF, APRIL and BAFFR genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies of APRIL and BAFFR were compared between the different comparative groups above mentioned (data not shown).Table 1.Genotype and allele frequencies of BAFF, APRIL and BAFFR in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.PolymorphismChangeData setGenotypes, % (n)Alleles, % (n)1/21/11/22/212BAFF rs374039502T/AIgAV92.1 (363)7.9 (31)0.096.1 (757)3.9 (31)IgAV with nephritis90.1 (128)9.9 (14)0.095.1 (270)4.9 (14)IgAN91.6 (87)8.4 (8)0.095.8 (182)4.2 (8)Controls91.8 (764)7.8 (65)0.4 (3)95.7 (1593)4.3 (71)APRIL rs11552708G/AIgAV78.7 (310)20.1 (79)1.3 (5)88.7 (699)11.3 (89)IgAV with nephritis81.1 (116)18.9 (27)0.090.6 (259)9.4 (27)IgAN75.8 (72)23.2 (22)1.1 (1)87.4 (166)12.6 (24)Controls78.7 (655)19.7 (164)1.6 (13)88.6 (1474)11.4 (190)APRIL rs6608C/TIgAV72.6 (286)25.4 (100)2.0 (8)85.3 (672)14.7 (116)IgAV with nephritis75.5 (108)23.1 (33)1.4 (2)87.1 (249)12.9 (37)IgAN65.3 (62)30.5 (29)4.2 (4)80.5 (153)19.5 (37)Controls71.0 (591)26.6 (221)2.4 (20)84.3 (1403)15.7 (261)BAFFR rs7290134A/GIgAV58.9 (232)35.5 (140)5.6 (22)76.6 (604)23.4 (184)IgAV with nephritis60.1 (86)32.2 (46)7.7 (11)76.2 (218)23.8 (68)IgAN57.9 (55)38.9 (37)3.2 (3)77.4 (147)22.6 (43)Controls58.7 (488)35.1 (292)6.3 (52)76.2 (1268)23.8 (396)BAFFR rs77874543G/CIgAV83.2 (328)15.5 (61)1.3 (5)91.0 (717)9.0 (71)IgAV with nephritis83.1 (118)16.9 (24)0.091.5 (260)8.5 (24)IgAN86.3 (82)13.7 (13)0.093.2 (167)6.8 (13)Controls83.7 (696)16.0 (133)0.4 (3)91.6 (1525)8.4 (139)IgAV: IgA vasculitis; IgAN: IgA nephropathy.ConclusionOur results reveal a similar BAFF, APRIL and BAFFR genetic distribution in IgAV and IgAN, suggesting that these genes could not be used as differential biomarkers between these pathologies.References[1]N Engl J Med 2013;368:2402-14;[2]Am J Kidney Dis 1988;12:373-7;[3]J Exp Med 1999;189:1747-56;[4]Nat Genet 2005;37:793-4;[5]Arthritis Res Ther 2018;20:158;[6]Arthritis Res Ther 2020;22:157;[7]Engl J Med 2017;376:1615-26;[8]Sci Rep 2018;8:8195.AcknowledgementsThis study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].Disclosure of InterestsDiana Prieto-Peña: None declared, Fernanda Genre: None declared, Sara Remuzgo Martinez: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Diego de Argila: None declared, Esther F. Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Abbvie, MSD, Jansen, and Roche, Grant/research support from: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Raquel López-Mejías: None declared

SBA-15 is a material with interesting characteristics associated with the size, order, uniformity, and pores distribution. However, the absence of acidity in SBA-15 restricts its applications as a potential acid catalyst in the industry for the large-scale production of fuels and chemicals. Mesoporous SBA-15 modified by the incorporation of heteroatomic species can be a good strategy to include acidity and prepare an efficient catalyst. In this work, we present a comparative study in the preparation of SBA-15 and Zr-SBA-15 mesoporous materials with high zirconium loads (Si/Zr ¿= ¿10, 5, and 2) using direct-synthesis and pH-adjusting approaches with a low crystallization temperature of 60 ¿°C. The materials were characterized using XRPD, HRTEM, ICP, SEM-EDS, XPS, DRS UV-VIS, FT-IR, NH3-TPD, in situ FT-IR with pyridine probe, and N2-physisorption. Characterization by ICP and SEM-EDS indicated that the Si/Zr molar ratio of Zr-materials prepared by the pH adjustment better matched the nominal values. N2-physisorption showed that the mesoporosity of the materials was preserved even at the high Zr load. XRPD and HRTEM pointed out that Zr-SBA-15 materials prepared by the pH adjustment showed a higher level of ordering in the porous network. Regardless of the synthesis approach, the presence of a higher Zr load caused a loss in the structural ordering. It must be highlighted that the high-resolution XPS spectra of Zr 3d suggested the formation of Si–O–Zr bonds giving some indication of Zr incorporation into the SBA-15 framework. The formation of Si–O–Zr linkage in the Zr-materials was also corroborated by DRS UV-VIS due to the presence of a blue shift in the absorption edge for both series of the Zr-SBA-15 materials. NH3-TPD and in-situ FT-IR spectroscopy with pyridine probe showed that the presence of Zr species introduces acidity in the SBA-15 and at higher Zr load the Brønsted acidity increased particularly for the Zr-materials prepared by pH adjustment. In conclusion, this study evidences that the pH-adjusting approach improves structural, textural, morphological, and acidic properties in SBA-15 and Zr-SBA-15 materials compared to the direct-synthesis approach.

Introduction: Health professionals are asked to promote health, especially organ transplantation; however, they do not always have specific training. Objective: To analyze information about donation and organ transplantation among Spanish medical students. Method: The population under study is medical students in Spanish universities using the database of the International Donor Collaborative Project, stratified by geographic area and academic year (n = 9275). The instrument used is the attitude questionnaire for organ donation for "PCID-DTO-Ríos" transplantation, validated with an explained variance of 63.203% and α = 0.834. The Student t test was applied together with the χ2 test, complemented by an analysis of the remainders, and Fisher's exact test was applied. Results: Of the students, 74% indicate that they have received information from university professors about organ transplant. Concerning specific issues with the donation, it is notable that only 66.7% (n = 6190) know and accept the concept of brain death as the death of a person. However, only 22% consider themselves as having good information, and 35.3% indicate that their information is scarce or void. Students indicate having received information about transplant from other extra-university sources, such as television and Internet (80.9%), books and magazines (73.2%), and the press (66.9%). From the information obtained in the sociofamilial field, 60.7% have obtained information from the family and 58.1% from friends. Of this information, 9% has been negative from friends, 7.5% from family, 6% from the Internet and television, and 4% from university professors. Conclusion: Spanish medical students believe they have little information about organ transplantation and have received negative information. Sin financiación 1.066 JCR (2020) Q4, 160/162 Inmunology 0.373 SJR (2020) Q3, 260/456 Surgery No data IDR 2020 UEM

Introduction Despite sensitization of medical students toward the donation of organs, a non-negligible percentage of students are not in favor of donation. Objective To analyze the reasons of Spanish medical students who do not have a favorable attitude toward the donation of their own organs after death. Method The population under study is medical students in Spanish universities, using the database of the International Donor Collaborative Project, stratified by geographic area and academic year. The questionnaire completion was anonymous and self-administered. The study group is medical students with an unfavorable attitude toward organ donation. The assessment instrument used is a validated questionnaire of attitude toward the donation of organs for transplant, “PCID-DTO-Ríos.” The reasons against the donation are valued in the questionnaire through a question. Results Of the participants included in the PCID, students who are not in favor of organ donation were selected (n = 1899). Of them, 8.1% (n = 154) are against and 91.1% (n = 1745) are doubtful. The main reasons indicated are the fear of apparent death in 11.4% of respondents, fear of possible mutilation after donation in 11.1%, and religious reasons in 2.6%. Of those, 6.9% indicate other reasons but do not clearly specify the reasons, using words such as “fear” (2.5%) or “doubts about the process” (4.1%); 66.2% (n = 1257) indicated an “assertive refusal” (“I don't want to express my reasons”). Conclusion Twenty percent of Spanish medical students are not in favor of donating their organs and are not in favor of showing their reasons. Sin financiación 1.066 JCR (2020) Q4, 160/162 Inmunology 0.373 SJR (2020) Q3, 260/456 Surgery No data IDR 2020 UEM

BackgroundAxial spondyloarthritis (axSpA) is an inflammatory disease with detrimental effects on the health status of the individuals affected by this condition [1]. axSpA patients also exhibit high cardiovascular (CV) risk, mainly due to accelerated atherosclerosis [2]. Interestingly, the adipomyokine irisin was described to play a beneficial role in several physiological and pathophysiological processes such as inflammation, angiogenesis, oxidative stress, as well as lipid and bone metabolism [3]. However, studies on the role of irisin in CV risk in the setting of axSpA or in the pathogenesis of axSpA are limited [4].ObjectivesIn this study we evaluated the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis and CV risk in a large cohort of patients with axSpA. We also assessed its role as a marker of axSpA susceptibility and severity.Methods725 patients who fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axSpA were included in this study [5]. In these patients, the presence of subclinical atherosclerosis (plaques and/or abnormal carotid intima-media thickness values) was assessed by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A and rs1570569 G/T) were genotyped by TaqMan probes in all the patients and in 656 age, sex and ethnically-matched healthy controls. Additionally, serum irisin levels were determined by ELISA in all the patients. All analyses were performed using STATA v.11.1 statistical software, adjusting for potential confounding factors. The strength of associations is indicated as odds ratios (OR) [95% confidence intervals].ResultsLow levels of serum irisin were linked to the presence of plaques (p=0.002) and with atherogenic index values indicative of an adverse lipid profile (p=0.01). Serum irisin levels also negatively correlated with visual analogue scale (VAS) patient, VAS physician and Bath Ankylosing Spondylitis Metrology Index (BASMI) values (p2.1 (indicative of high disease activity) (OR: 1.46 [1.08-1.97], p=0.01), while the minor allele of rs16835198 (T) was less frequent in this group of patients (OR: 0.73 [0.57-0.92], p=0.01).ConclusionLow serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.References[1]Packham J. Rheumatology (Oxford). 2018;57(6):vi29-vi34.[2]Szabo SM, et al. Arthritis Rheum. 2011;63(11):3294–304.[3]Korta P, et al. Medicina (Kaunas). 2019;55(8):485.[4]Nam B, et al. Ann Rheum Dis. 2020;79:1358.[5]Sieper J, et al. Ann Rheum Dis. 2009;68(2):ii1–44.AcknowledgementsThis work was partially supported by grants from Instituto de Investigación Sanitaria IDIVAL (NVAL17/10), from the `Asociación Cántabra de Reumatología’ awarded to FG. FG and JR-G are beneficiaries of a grant funded by `Instituto de Salud Carlos III´ (ISCIII) (PI20/00059). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII, co-funded by the European Regional Development Fund. VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL18/01). RL-M is a recipient of a Miguel Servet type I programme fellowship from ISCIII, co-funded by the European Social Fund, `Investing in your future´ (grant CP16/00033).Disclosure of InterestsSara Remuzgo-Martínez: None declared, Javier Rueda-Gotor: None declared, Verónica Pulito-Cueto: None declared, Raquel López-Mejías: None declared, Alfonso Corrales: None declared, Leticia Lera-Gómez: None declared, Raquel Pérez-Fernández: None declared, Virginia Portilla: None declared, Iñigo Gonzalez-Mazon: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Rosa Expósito: None declared, Cristina Mata: None declared, Javier Llorca: None declared, Vanessa Hernández-Hernández: None declared, Carlos Rodríguez-Lozano: None declared, Nuria Barbarroja Puerto: None declared, Rafaela Ortega Castro: None declared, Esther F. Vicente-Rabaneda: None declared, Cristina Fernández-Carballido: None declared, Maria Paz Martínez-Vidal: None declared, David Castro-Corredor: None declared, Joaquín Anino-Fernández: None declared, Diana Peiteado: None declared, Chamaida Plasencia: None declared, E Galindez: None declared, María L. García Vivar: None declared, Nuria Vegas-Revenga: None declared, Irati Urionaguena: None declared, Oreste Gualillo: None declared, Juan Carlos Quevedo-Abeledo: None declared, Santos Castañeda: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD, GSK, Grant/research support from: Abbvie, MSD, Janssen, Roche, Fernanda Genre: None declared

BackgroundIgA vasculitis (IgAV) and IgA nephropathy (IgAN) are inflammatory conditions that share pathogenic and molecular mechanisms [1] and may represent different outcomes of a continuous spectrum of the disease [2]. Interleukin (IL)-33 is a cytokine that exerts its biological functions by binding to its receptor, IL-1 receptor like 1 (IL-1RL1) [3]. Several lines of evidence demonstrate that genetic variants located both in IL33 and IL1RL1 genes are implicated in the increased risk of numerous immune-mediated diseases [4].ObjectivesTo determine whether IgAV and IgAN exhibit a different IL33-IL1RL1 association pattern.MethodsThree tag genetic variants within IL33 (rs3939286, rs7025417 and rs7044343) and three tag polymorphisms within IL1RL1 (rs2310173, rs13015714 and rs2058660), which cover the major variability of these loci and that were previously associated with several inflammatory diseases were genotyped in 380 Caucasian patients with IgAV, 96 patients with IgAN and 845 sex and ethnically matched healthy controls.ResultsSimilar genotype and allele frequencies were observed in the whole cohort of patients with IgAV when compared to those with IgAN when IL33-IL1RL1 genetic variants were analyzed independently (Table 1). In accordance with that, no IL33-IL1RL1 genotype or allele differences were detected between IgAV patients who developed nephritis and patients with IgAN (Table 1). Additionally, no statistically significant differences between the whole cohort of patients with IgAV and healthy controls as well as between patients with IgAN and healthy controls were observed when each IL33-IL1RL1 genetic variant was also analyzed independently (Table 1). Similar results were disclosed when haplotype frequencies were compared between the different comparative groups above mentioned (data not shown).Table 1.Genotype and allele frequencies of IL33 and IL1RL1 in the whole cohort of patients with IgAV, patients with IgAV who developed nephritis, patients with IgAN and healthy controls.PolymorphismChangeData setGenotypes, % (n)Alleles, % (n)1/21/11/22/212IL33 rs3939286C/TIgAV49.1 (186)40.9 (155)10.0 (38)69.5 (527)30.5 (231)IgAV with nephritis48.5 (66)39.7 (54)11.8 (16)68.4 (186)31.6 (86)IgAN43.8 (42)49.0 (47)7.3 (7)68.2 (131)31.8 (61)Controls49.0 (414)41.4 (350)9.6 (81)69.7 (1178)30.3 (512)IL33 rs7025417T/CIgAV68.1 (254)29.5 (110)2.4 (9)82.8 (618)17.2 (128)IgAV with nephritis69.9 (93)27.1 (36)3.0 (4)83.5 (222)16.5 (44)IgAN61.5 (59)37.5 (36)1.0 (1)80.2 (154)19.8 (38)Controls70.8 (598)25.9 (219)3.3 (28)83.7 (1415)16.3 (275)IL33 rs7044343T/CIgAV42.3 (160)42.1 (159)15.6 (59)63.4 (479)36.6 (277)IgAV with nephritis44.5 (61)39.4 (54)16.1 (22)64.2 (176)35.8 (98)IgAN40.6 (39)49.0 (47)10.4 (10)65.1 (125)34.9 (67)Controls44.5 (376)43.9 (371)11.6 (98)66.4 (1123)33.6 (567)IL1RL1 rs2310173G/TIgAV29.2 (111)46.1 (175)24.7 (94)52.2 (397)47.8 (363)IgAV with nephritis32.1 (44)43.1 (59)24.8 (34)53.6 (147)46.4 (127)IgAN20.8 (20)46.9 (45)32.3 (31)44.3 (85)55.7 (107)Controls30.2 (255)46.7 (395)23.1 (195)53.6 (905)46.4 (785)IL1RL1 rs13015714T/GIgAV56.3 (211)39.5 (148)4.3 (16)76.0 (570)24.0 (180)IgAV with nephritis61.8 (84)33.8 (46)4.4 (6)78.7 (214)21.3 (58)IgAN54.2 (52)40.6 (39)5.2 (5)74.5 (143)25.5 (49)Controls57.2 (483)37.2 (314)5.7 (48)75.7 (1280)24.3 (410)IL1RL1 rs2058660A/GIgAV56.9 (215)38.6 (146)4.5 (17)76.2 (576)23.8 (180)IgAV with nephritis62.2 (84)31.9 (43)5.9 (8)78.1 (211)21.9 (59)IgAN53.1 (51)42.7 (41)4.2 (4)74.5 (143)25.5 (49)Controls56.7 (479)37.5 (317)5.8 (49)75.4 (1275)24.6 (415)IgAV: IgA vasculitis; IgAN: IgA nephropathy.ConclusionOur results reveal that IgAV and IgAN share a similar IL33-IL1RL1 association pattern.References[1]N Engl J Med 2013;368:2402-14;[2]Am J Kidney Dis 1988;12:373-7;[3]J Immunol 2007;179:2551–5,[4]Sci Rep 2021;11:16163AcknowledgementsThis study was supported by the European Regional Development Fund (ERDF) and “Fondo de Investigaciones Sanitarias” (grant PI18/00042 and PI21/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) [grant number CM20/00006]; SR-M is supported by funds of the RETICS Program co-funded by ERDF [grant number RD16/0012/0009]; VP-C is supported by a pre-doctoral grant from IDIVAL [grant number PREVAL 18/01]; RL-M is a recipient of a Miguel Servet type II programme fellowship from the ISCIII, co-funded by ESF `Investing in your future´ [grant number CPII21/00004].Disclosure of InterestsDiana Prieto-Peña: None declared, Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda Fillloy: None declared, J. Narváez: None declared, LUIS CAMINAL MONTERO: None declared, PAZ COLLADO: None declared, Antonio Fernandez-Nebro: None declared, Gisela Díaz-Cordoves: None declared, Secundino Cigarrán: None declared, Jesús Calviño: None declared, Carmen Cobelo: None declared, Patricia Quiroga Colino: None declared, Javier Sanchez Perez: None declared, Esteban Rubio-Romero: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galíndez-Agirregoikoa: None declared, Oreste Gualillo: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche, Raquel López-Mejías: None declared

Introduction Religious factors have conditioned the attitude toward organ donation and transplantation (ODT) since the beginning of transplantation, despite the fact that most religions are in favor of transplantation. Objective To assess the impact of religious beliefs of medical students on their attitude toward ODT. Method Population under study: Medical students in Spanish universities. Study sample: Stratified by geographical area and academic course. Assessment instrument: Attitude ODT questionnaire PCID-DTO-Ríos, anonymous and self-administered. Results Of all students, 42% (n = 3907) declare themselves atheists or agnostics. The remaining 58% (n = 5368) declare themselves to be religious, the majority being Catholic (55%, n = 5102). Of the rest, 0.2% are Muslims (n = 8), 0.1% Protestants (n = 1), and the remaining 2.7% (n = 257) indicate other religious doctrines but do not want to specify it. Regarding their attitude toward ODT, those who consider themselves atheists or agnostics have a more favorable attitude than those who consider themselves religious (84% versus 76%; P < .001). Among those who follow some kind of religion, Catholics are more in favor of ODT than non-Catholics (77% vs 64%, P < .001). Note that among the religious, only 57% (n = 3050) know which religion is in favor of transplantation, while 22% (n = 1,152) consider that it has not been pronounced on the matter, 13% (n = 723) think the religion is against donation, and the remaining 8% (n = 443) do not know. Conclusion The religion professed by medical students conditions their attitude toward donation, with the atheists and agnostics being more in favor of donation. Sin financiación 0.784 JCR (2019) Q4, 155/158 Immunology, 191/210 Surgery, 24/24 Transplantation 0.363 SJR (2019) Q3, 254/451 Surgery, 27/41 Transplantation No data IDR 2019 UEM

The knowledge acquired during university education about organ donation and transplantation (ODT) decisively influences the information future health professionals transmit. This is important in ODT where the participation of the general public is essential to obtain organs. Objective To determine notions of Spanish medicine and nursing students on ODT and its relationship with attitude toward ODT. Methods and Design and design. We conducted a sociologic, multicenter, and observational study. The population for our study consisted of medical and nursing students in Spanish universities. Our database was the Collaborative International Donor Project, stratified by geographic area and academic course. A validated questionnaire (PCID-DTO-RIOS) was self-administered and completed anonymously. Our sample consisted of 9598 medical and 10,566 nursing students (99% confidence interval; precision of ±1%), stratified by geographic area and year of study. Results The completion rate for our study was 90%. Only 20% (n=3640) of students thought their notions on ODT were good; 41% (n=7531) thought their notions were normal; 36% (n=6550) thought their notions were scarce. Comparing groups, there were differences between those who believed that their notions on ODT were good (44% nursing vs 56% medical students; P < .000), and those who believed it scarce (54% nursing vs 46% medical students; P < .000). Notions on ODT were related with attitude toward the donation of one's own organs: those who considered their notions were good were more in favor then those who considered it scarce (88% vs 72%; P < .000). Conclusion Only 20% of Spanish medical and nursing students thought their notions on ODT were good. Having good knowledge is related to a favorable attitude towards ODT. Receiving specific information on the subject could improve their knowledge about ODT during their training. Sin financiación 1.066 JCR (2020) Q4, 160/162 Inmunology 0.373 SJR (2020) Q3, 260/456 Surgery No data IDR 2020 UEM

Introduction: Awareness of organ donation among Spanish doctors and medical students is very positive. However, the emerging group of professionals of non-Spanish nationality studying in Spain has not been analyzed. Objective: To analyze the differences in the attitudes toward the different types of donation among medical students, according to their nationality. Methods: The population under study is medical students in Spanish universities using the database of the International Collaborative Donor Project, stratified by geographic area and academic year. Groups under study include students of non-Spanish nationality as group 1 (n = 1570) and students of Spanish nationality as Group 2 (n = 7705). Instruments are validated questionnaires of attitude toward donation "PCID-DTO-Ríos," "PCID-DVR-Ríos," "PCID-DVH-Ríos," and "PCID-XenoTx-Ríos." Results: The attitude toward the donation of own organs after death is similar in both groups (P = .703). Non-Spaniards are 79.2% in favor compared to 79.6% of Spaniards. Living kidney donation, both unrelated (33.3% vs 29.3% in favor; P = .001) and related (91.2% vs 89, 6% in favor; P = .047), is more favorable among non-Spanish students. There are no differences regarding non-related living liver donation (29.7% vs 29.3% in favor; P = .063), but there are differences in the results for related living liver donation (94.1% vs 88%; P < .001). The attitude toward xenotransplantation of organs is similar (80.8% vs 80.8%; P = .999). Conclusions: Awareness of the donation of organs among Spanish medical students is similar to non-Spanish students studying in Spain, except the attitude toward living donation. Sin financiación 1.066 JCR (2020) Q4, 160/162 Inmunology 0.373 SJR (2020) Q3, 260/456 Surgery No data IDR 2020 UEM

Information provided by health care professionals is crucial to create a climate of social opinion. This is important in organ donation and transplantation (ODT), where the participation of the general public is essential to obtain organs. Objective To determine the attitude toward the Law of Presumed Consent (LPC) among Spanish university students and to analyze their relation with attitude toward ODT. Methods and design. The type of study was a sociologic, multicenter, observational study. The population included medical and nursing students in Spanish universities. Database of Collaborative International Donor Project was used stratified by geographic area and academic course. A validated questionnaire (Collaborative International Donor Project, organ donation and transplantation questionnaire in Spanish [PCID-DTO-RIOS]) was self-administered and completed anonymously. A sample of 9598 medical and 10,566 nursing students was analyzed (99% confidence and precision of ±1%) and stratified by geographic area and year of study. Results Completion rate was 90%. Regarding attitude toward LPC, 66% of the students were against the law, whereas 34% accepted it. Of the students surveyed, 9% considered the law as a gesture of solidarity, 25% as an effective way of not wasting organs, 48% as an abuse of power, and 18% as offenses against the family. Those students who were in favor of LPC also had a more favorable attitude toward ODT (86% vs 76%; P < .001). Comparing groups, nursing students were less in favor of LPC than medical students (32% vs 36%; P < .000). Conclusion Sixty-six percent of Spanish university medical and nursing students were against the LPC. The favorable attitude toward ODT is associated with considering the law as a gesture of solidarity or as an effective way of not wasting organs. Sin financiación 1.066 JCR (2020) Q4, 160/162 Immunology 0.373 SJR (2020) Q3, 260/456 No data IDR 2020 UEM

Resumen Objetivo Estudiar la concordancia entre los grados de satisfaccion de los pacientes y sus familiares (ambos pertenecientes a un mismo nucleo familiar) en cuanto a los cuidados y atenciones proporcionados durante su estancia en la UCI. Diseno Estudio transversal, observacional, descriptivo y prospectivo durante 5 meses. Ambito UCI del Hospital Universitario Marques de Valdecilla de Santander. Sujetos Pacientes mayores de 18 anos con estancia mayor de 24 h que fueron dados de alta de la UCI durante el periodo de estudio y familiares de dichos pacientes. Intervencion Instrumento: cuestionario FS-ICU 34 para evaluar la satisfaccion de los familiares de pacientes ingresados en la UCI y adaptacion de dicho cuestionario para el paciente. Se determina el grado de concordancia mediante el indice de kappa ponderado para muestras pareadas. Resultados Se analizaron todos los cuestionarios procedentes de un mismo nucleo familiar, obteniendose un total de 148 pares de cuestionarios (296 encuestas). Se obtuvieron indices kappa que oscilaron entre 0,278 y 0,558, lo que indica grados de concordancia entre debiles y moderados. Conclusiones Los familiares de los pacientes ingresados en la UCI no pueden ser considerados unos representantes adecuados, al menos para el subgrupo de pacientes competentes. En estos casos debemos acudir a esos pacientes para conocer de primera mano sus sentimientos, percepciones y vivencias durante su estancia en la UCI. Solo cuando los pacientes no estan en condiciones de participar activamente en el proceso asistencial debemos acudir a sus familias.

Objective To study the agreement between the level of satisfaction of patients and their families referred to the care and attention received during admission to the ICU. Design A prospective, 5-month observational and descriptive study was carried out. Setting ICU of Marques de Valdecilla University Hospital, Santander (Spain). Subjects Adult patients with an ICU stay longer than 24 h, who were discharged to the ward during the period of the study, and their relatives. Intervention Instrument: FS-ICU 34 for assessing family satisfaction, and an adaptation of the FS-ICU 34 for patients. The Cohen kappa index was calculated to assess agreement between answers. Results An analysis was made of the questionnaires from one same family unit, obtaining 148 pairs of surveys (296 questionnaires). The kappa index ranged between 0.278 and 0.558, which is indicative of mild to moderate agreement. Conclusions The families of patients admitted to the ICU cannot be regarded as good proxies, at least for competent patients. In such cases, we must refer to these patients in order to obtain first hand information on their feelings, perceptions and experiences during admission to the ICU. Only when patients are unable to actively participate in the care process should their relatives be consulted.

// Marta Jessica Llorca-Cardenosa 1, * , Tania Fleitas 1, * , Maider Ibarrola-Villava 1 , Maria Pena-Chilet 1 , Cristina Mongort 2 , Carolina Martinez-Ciarpaglini 2 , Lara Navarro 2 , Valentina Gambardella 1 , Josefa Castillo 1 , Susana Rosello 1 , Samuel Navarro 2 , Gloria Ribas 1 , Andres Cervantes 1 1 Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain 2 Department of Pathology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain * These authors contributed equally to this work Correspondence to: Gloria Ribas, email: gribas@incliva.es Andres Cervantes, email: andres.cervantes@uv.es Keywords: RUNX3, ARID1A, gastric cancer, gene methylation, immune microenvironment Received: June 16, 2016 Accepted: August 15, 2016 Published: August 23, 2016 ABSTRACT Gastric cancer (GC) pathogenesis involves genetic, epigenetic and environmental factors. Epigenetic alterations, such as DNA methylation are considered pivotal in the inactivation of tumor-related genes. We assessed a methylation panel of 5 genes to study their association to GC progression and microsatellite instability (MSI), and studied the role of RUNX3 in GC pathogenesis and the tumor immune microenvironment. The methylation status of 47 promoter-CpG islands was studied through MALDI-TOF mass spectrometry analysis in 35 Microsatellite stable (MSS) GC, 26 MSI, and 18 cancer-free samples (CFS), and 6 MSS GC and 4 MSI GC cell lines. We also studied RUNX3 expression by immunohistochemistry (IHC) in 40 samples, and validated differences in methylation levels between tumor, normal, and immune tissue in 14 additional samples. Unsupervised hierarchical clustering of methylation levels revealed no distinct subgroups between MSI and MSS samples or cell lines. CFSs clustered together showing higher levels of RUNX3 methylation compared to GC samples. RUNX3 showed protein silencing in cancer and normal mucosa, compared to inflammatory peritumoural infiltrate in almost all cases, showing a non-lymphocytic predominant pattern and being correlated with epigenetic silencing. Our results show aberrant promoter’s methylation in APC, CDH1, CDKN2A, MLH1 and RUNX3 associated with GC, as well as a non-lymphocytic predominant infiltrate with high expression of RUNX3 . Deep study of RUNX3 inflammation signaling could help in understanding inflammation and immune activation in the tumor microenvironment.

The involvement of health professionals from their training period is important for the promotion of living liver donation. There are data that indicate that the awareness of living donation is lower in areas with high rates of deceased donation. Objective To analyze the attitude toward living liver donation among Spanish medical students, according to donation rates of their regions. Method Population under study: Medical students in Spanish universities. Database of the Collaborative International Donor Project, stratified by geographic area and academic course. The completion was anonymous and self-administered. Groups under study: group 1 (n = 1136): students in universities of regions with >50 donors per million population (pmp); group 2 (n = 2018): students in region universities with 50 donors pmp. Thus, in group 1, a total of 88% (n = 1002) of students are in favor compared with 91% (n = 1831) of group 2 (P=.02). The psychosocial profile of each study group about their attitude toward living related liver donation is analyzed. There is a similar profile between the 2 groups, although there are differences in some variables such as age, a belief that one might need a transplant, family discussion about donation and transplantation, discussion with friends about donation and transplantation, and knowing about a donor. Conclusions The awareness of living related donation among Spanish medical students is greater among the regions with lower organ donation rates. Sin financiación 0.784 JCR (2019) Q4, 155/158 Immunology, 191/210 Surgery, 24/24 Transplantation 0.363 SJR (2019) Q3, 254/451 Surgery, 27/41 Transplantation No data IDR 2019 UEM

Methanation reactions of CO and CO2 to Substitute Natural Gas (SNG) through hydrogenation process is a long-established method, but recently, the scientific interest is receiving growing interest as a practical method for carbon dioxide reduction and a tool for renewable energy storage. In this work, the methanation of CO and CO2 mixture was investigated over Ni catalysts supported on Al2O3, Y2O3, MgO and CeO2 metal oxides. Catalysts with different Ni content (7-35 wt.%) were synthesized by the solution combustion synthesis (SCS) and characterized by N2 physisorption, XRD, H2-TPR, CO2-TPD, XPS, UV-Vis DRS, and TEM. Methanation activity tests ((H2-CO2)/(CO+CO2)=3) were carried out at atmospheric pressure varying temperature (TSET=250-600 °C) and space velocity (GHSV=10,000-50,000 h-1). Stability tests over 200 h of time-on-stream were also performed.

The awareness of organ donation among health professionals is important at the time of transplant promotion. In this sense, the training and awareness of the professionals in training is fundamental. Objective To analyze the differences in the attitude toward organ donation and the factors that condition it among medical students of regions with donation rates >50 donors per million population (pmp) with respect to those with rates 50 donors pmp. Group 2 (n = 2018): university students in regions with 50 donors pmp and with

Somatic mutation analysis represents a useful tool in selecting personalized therapy. The aim of our study was to determine the presence of common genetic events affecting actionable oncogenes using a MassARRAY technology in patients with advanced solid tumors who were potential candidates for target-based therapies. The analysis of 238 mutations across 19 oncogenes was performed in 197 formalin-fixed paraffin-embedded samples of different tumors using the OncoCarta Panel v1.0 (Sequenom Hamburg, Germany). Of the 197 specimens, 97 (49.2%) presented at least one mutation. Forty-nine different oncogenic mutations in 16 genes were detected. Mutations in KRAS and PIK3CA were detected in 40/97 (41.2%) and 30/97 (30.9%) patients respectively. Thirty-one patients (32.0%) had mutations in two genes, 20 of them (64.5%) initially diagnosed with colorectal cancer. The co-occurrence of mutation involved mainly KRAS, PIK3CA, KIT and RET. Mutation profiles were validated using a customized panel and the Junior Next-Generation Sequencing technology (GS-Junior 454, Roche). Twenty-eight patients participated in early clinical trials or received specific treatments according to the molecular characterization (28.0%). MassARRAY technology is a rapid and effective method for identifying key cancer-driving mutations across a large number of samples, which allows for a more appropriate selection for personalized therapies.

Introduction Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice. Objective To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes. Material and Methods Type of study: A sociological, interdisciplinary, observational and multicentre study in Spain. Study population: Students enrolled on the medical degree in Spain (n = 34 000). Sample size: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID-XenoTx RIOS) which was self-administered and completed anonymously. Results A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005). Conclusions Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre-clinical xenotransplantation programme and new healthcare centres.

To evaluate, by means of a meta-analysis, the effect of normal saline on mortality in intensive care patients, when compared with the use of balanced crystalloids.Published controlled clinical trials, randomised and sequential prospective studies in time, evaluating the mortality when physiological saline was used in patients admitted to intensive care units. Electronic search was performed in Medline, Embase, Cochrane Library, ISI Proceedings, and Web of Science, as well as a manual search of selected references. An independent evaluation was performed by 2 investigators. Discrepancies were resolved by consensus in the working group. Contingency tables were performed, and the OR with confidence intervals of each study were obtained. Heterogeneity was assessed by IA total of 8 articles were selected for the meta-analysis of mortality, which included a total of 20,684 patients. A significant association was observed between the use of saline and mortality in intensive care patients (OR 1.0972; 95% CI 1.0049-1.1979), when compared to the use of balanced crystalloids. No statistical evidence of publication bias (Egger, P=.5349) was found. In the sensitivity analysis, none of the studies substantially modified the overall outcome if it was eliminated from the meta-analysis.There may be an increase in mortality associated with the use of saline in patients admitted to intensive care when comparing with the use of balanced crystalloids.

Objective: To analyze the level of understanding of the brain death concept among medical students in universities in Spain. Methods: This cross-sectional sociological, interdisciplinary, and multicenter study was performed on 9598 medical students in Spain. The sample was stratified by geographical area and academic year. A previously validated self-reported measure of brain death knowledge (questionnaire Proyecto Colaborativo Internacional Donante sobre la Donación y Transplante de Organos) was completed anonymously by students. Results: Respondents completed 9275 surveys for a completion rate of 95.7%. Of those, 67% (n = 6190) of the respondents understood the brain death concept. Of the rest, 28% (n = 2652) did not know what it meant, and the remaining 5% (n = 433) believed that it did not mean that the patient was dead. The variables related to a correct understanding of the concept were: (1) being older ( P < .001), (2) studying at a public university ( P < .001), (3) year of medical school ( P < .001), (4) studying at one of the universities in the south of Spain ( P = .003), (5) having discussed donation and transplantation with the family ( P < .001), (6) having spoken to friends about the matter ( P < .001), (7) a partner’s favorable attitude toward donation and transplantation ( P < .001), and (8) religious beliefs ( P < .001). Conclusions: Sixty-seven percent of medical students know the concept of brain death, and knowledge improved as they advanced in their degree.

Resumen Objetivo Conocer el grado de satisfaccion de los familiares de los pacientes dados de alta de la UCI y el del propio paciente. Diseno Estudio transversal, observacional, descriptivo y prospectivo durante 5 meses. Ambito UCI del Hospital Universitario Marques de Valdecilla de Santander. Sujetos Familiares y pacientes que fueron dados de alta de la UCI durante ese periodo. Intervencion Instrumento: encuesta Family Satisfaction Intensive Care Unit (FS-ICU 34) para familiares de pacientes ingresados en UCI (que sobrevivieron o no) y adaptacion de la FS-ICU en cuanto a cuidados se refiere, para el propio paciente. Resultados Se obtuvieron un total de 385 encuestas, 192 de familiares de supervivientes, 31 de familiares de fallecidos y 162 de pacientes. La mayor parte de los familiares encuestados estaban satisfechos con los cuidados recibidos y el proceso de decisiones (supervivientes: 83,46 ± 11,83 y 79,42 ± 13,58, respectivamente; fallecidos: 80,41 ± 17,27 y 79,61 ± 16,93, respectivamente). Los pacientes encuestados estaban muy satisfechos con los cuidados recibidos (84,71 ± 12,85). Conclusiones El grado de satisfaccion de los familiares y de los propios pacientes ingresados en la UCI es elevado. Aun asi, existen varios puntos que deberian ser mejorados, como el ambiente de la sala de espera y el ambiente propio de la UCI en cuanto a ruido, intimidad e iluminacion se refiere, asi como algunos aspectos del proceso de toma de decisiones, entre ellos la esperanza suministrada acerca de la recuperacion de su familiar.

Medical students represent a new generation of medical thought, and if they have a favourable attitude towards organ donation this will greatly encourage its promotion. OBJECTIVE: To analyse the attitude of medical students in Spanish universities towards the donation of their own organs and to determine the factors affecting this attitude. MATERIAL AND METHODS: Type of study: A sociological, interdisciplinary, multicentre, and observational study in Spain. STUDY POPULATION: Students studying a degree in medicine enrolled in Spain (n = 34,000). SAMPLE SIZE: A sample of 9598 students (confidence of 99% and precision of ±1%), stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ donation and transplantation (PCID-DTO RIOS) was self-administered and completed anonymously. RESULTS: The questionnaire completion rate was 95.7% (n = 9.275). 80% were in favour of donation, 2% against and 18% were undecided. The following main variables were related to a favourable attitude: being of the female sex (Odds Ratio = 1.739); being in the sixth year of the degree (OR = 2.506); knowing a donor (OR = 1.346); having spoken about the subject with one's family (OR = 2.132) and friends (OR = 1.333); having a family circle that is in favour, more specifically, having a father (OR = 1.841), mother (OR = 2.538) or partner in favour (OR = 2.192); being a blood donor (OR = 2.824); acceptance of the mutilation of the body if it were necessary (OR = 2.958); and being an atheist or an agnostic (OR = 1.766). CONCLUSIONS: Spanish medical students generally have a favourable attitude towards organ donation, although 20% are not in favour. Sin financiación 2.554 JCR (2019) Q1, 2/20 Ethnic Studies; Q2, 67/193 Public, Environmental & Occupational Health 0.688 SJR (2019) Q1, 105/468 Arts and Humanities (miscellaneous), 42/1093 Cultural Studies; Q2, 184/559 Public Health, Environmental and Occupational Health No data IDR 2019 UEM

Telomere length has been associated with the development of cancer. Studies have shown that shorter telomere length may be related to a decreased risk of cutaneous melanoma. Furthermore, deregulation of the telomere-maintaining gene complexes , has been related to this oncogenic process. Some variants in these genes seem to be correlated with a change in telomerase expression. We examined the effect of 10 single nucleotide polymorphisms (SNPs) in the TERT gene (encoding telomerase), one SNP in the related TERT-CLPTM1L locus and one SNP in the TRF1 gene with telomere length, and its influence on melanoma risk in 970 Spanish cases and 733 Spanish controls. Genotypes were determined using KASP technology, and telomere length was measured by quantitative polymerase chain reaction (PCR) on DNA extracted from peripheral blood leucocytes. Our results demonstrate that shorter telomere length is associated with a decreased risk of melanoma in our population (global p -value, 2.69 × 10 −11 ), which may be caused by a diminution of proliferative potential of nevi (melanoma precursor cells). We also obtained significant results when we tested the association between rs401681 variant ( TERT-CLPTM1L locus ) with melanoma risk (Odds ratio, OR; 95% confidence interval, CI = 1.24 (1.08–1.43); p -value, 3 × 10 −3 ). This is the largest telomere-related study undertaken in a Spanish population to date. Furthermore, this study represents a comprehensive analysis of some of the most relevant telomere pathway genes in relation to cutaneous melanoma susceptibility.

Poster presentado al 18th Meeting of the European Society for Pigment Cell Research Lisbon, Portugal | 9–12 September 2013. Abstract publicado en: Pigment Cell & Melanoma Research 26(5): E1-E31

GENIRA [Gender in Rheumatoid Arthritis (RA)] is a comprehensive project aimed at studying gender differences in RA patients and how these differences impact on these patient outcomes. We are now reporting such data. Seventy RA patients of each gender were cross-sectionally evaluated following a preestablished protocol. Univariate and multivariate analyses focused in the different gender-associated comorbidity profiles and how they impact in the quality of life and disability of RA patients as assessed by the SF-36 and the Modified Health Assessment Questionnaire (M-HAQ), respectively. Both groups were comparable regarding their main demographic and clinical features. Different comorbidity profiles were found in both genders, with higher frequencies of diabetes mellitus, peptic ulcer, ischemic heart disease, smoking and chronic obstructive pulmonary disease among men and of depression and osteoporosis among women. The M-HAQ was lower in women than in men (0.89 ± 2.6 vs 0.22 ± 0.9, p = 0.04) as there were some sub-scales of the SF-36 [mental health (63.7 ± 22.0 vs 71.8 ± 21.1; p = 0.02), general health (41.3 ± 21.7 vs 50.0 ± 24.3; p = 0.02), physical functioning (PF) (57.7 ± 22.1 vs 67.3 ± 22.7; p = 0.01) and the physical summary component (PSC) (39.3 ± 8.9 vs 42.4 ± 9.3, p = 0.04)]. Multivariate analysis indicated the independent association between depression and osteoporosis rather than gender with the M-HAQ, PSC and PF and of only depression with the MH and GH. Women with RA present significantly worse disability and QOL outcomes than men; these differences can be explained by female gender-associated comorbidities such as depression and osteoporosis rather than gender per se.

To study the agreement between the level of satisfaction of patients and their families referred to the care and attention received during admission to the ICU.A prospective, 5-month observational and descriptive study was carried out.ICU of Marqués de Valdecilla University Hospital, Santander (Spain).Adult patients with an ICU stay longer than 24h, who were discharged to the ward during the period of the study, and their relatives.Instrument: FS-ICU 34 for assessing family satisfaction, and an adaptation of the FS-ICU 34 for patients. The Cohen kappa index was calculated to assess agreement between answers.An analysis was made of the questionnaires from one same family unit, obtaining 148 pairs of surveys (296 questionnaires). The kappa index ranged between 0.278-0.558, which is indicative of mild to moderate agreement.The families of patients admitted to the ICU cannot be regarded as good proxies, at least for competent patients. In such cases, we must refer to these patients in order to obtain first hand information on their feelings, perceptions and experiences during admission to the ICU. Only when patients are unable to actively participate in the care process should their relatives be consulted.

Objectives: To estimate the percentage of adherence to highly-active antiretroviral therapy (HAART) in Spanish observational studies and to identify the variables associated with adherence. Methods: Seven electronic databases were used to locate the studies. Six inclusion criteria were established. Two coders codified the variables independently. Intercoder reliability was calculated. Publication bias was analyzed through the Begg, Egger and Trim and Fill tests. Homogeneity was evaluated using the Q test and the l² index. A random effects model was assumed to estimate both the overall percentage of adherence and to explain heterogeneity. Results: This meta-analysis included 23 observational studies, yielding a total of 34 adherence estimates. The sample was composed of 9,931 HIV-positive individuals (72% men) older than 18 years under treatment with HAART. The percentage of patients adhering to an intake of >90% of the prescribed antiretroviral drugs was 55%. Wide heterogeneity was detected (I²=91.20; 95%CI: 88.75-93.13). Adherence was mainly measured using a single strategy (47.8%), the most widely used being self-report (48.7%). In the univariate analysis, the following factors were significant: infection stages A (β=0.68, p 200 copies/ml (β=-0.41, p