Editorial: Physiological computing of social cognition, volume II

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Subtipado molecular del cáncer de mama masculino con PAM50: Correlación con el subtipaje inmunohistoquímico y estudio de supervivencia.

Introducción: El cáncer de mama masculino es una enfermedad rara aún poco conocida, que principalmente corresponde a subtipo luminal usando la clasificación molecular subrogada a inmunohistoquímica. En este estudio, se evalúa por primera vez la correlación entre los subtipos moleculares basados en un panel inmunohistoquímico de seis marcadores y el obtenido mediante la firma PAM50 en el cáncer de mama masculino, así como la evolución clínica de los diferentes subtipos encontrados. Material y métodos: Se recogieron 67 muestras quirúrgicas de cáncer de mama masculino invasivo de cuatro diferentes Servicios de Anatomía Patológica. La tinción inmunohistoquímica se realizó sobre tissue-microarrays, con un panel de seis marcadores (RE, RP, Her2, Ki67, CK 5-6 y EGFR). Los subtipos de PAM50 se determinaron mediante nCounter Analysis System. Se estudió la asociación entre los subtipos obtenidos mediante inmunohistoquímica y los determinados por PAM50, así como la supervivencia global y la supervivencia libre de enfermedad en los diferentes subtipos de cada clasificación. Resultados: La distribución de los subtipos moleculares tumorales según PAM50 fue: 60% luminal B, 30% luminal A y 10% Her2-enriched. Sólo uno de los tumores Her2-enriched también fue detectado por inmunohistoquímica y tratado con trastuzumab. No se obtuvo ningún tumor de subtipo basal-like. Utilizando la clasificación inmunohistoquímica, 51% de los tumores fueron luminal B, 43% luminal A, 3,5% triple negativo y 1,5% Her2-positivo. Las características clínico-patológicas no difirieron significativamente entre los subtipos inmunohistoquímicos y PAM50. Se observó una supervivencia global menor en los tumores Her2-enriched comparados con los luminales. Conclusión: El cáncer de mama masculino es principalmente una enfermedad genómica luminal con un predominio del subtipo luminal B. Además, se observaron casos de pacientes Her2-negativos por inmunohistoquímica, pero de perfil Her2-enriched por PAM50, con peor evolución clínica comparado con el subtipo luminal, que podrían haberse beneficiado de terapia anti-Her2.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Brief Report: CYP27B1 rs10877012 T Allele Was Linked to Non-AIDS Progression in ART-Naïve HIV-Infected Patients: A Retrospective Study.

HIV/AIDS progression is linked to vitamin D, which is regulated by several key cytochromes P450 (CYP). Single nucleotide polymorphisms (SNPs) in CYP genes influence vitamin D metabolism and serum levels. The objective of this study was to evaluate the association between CYP SNPs and the clinical AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. We performed a retrospective study in 661 ART-naïve HIV-infected patients who were stratified by their AIDS progression pattern [181 long-term nonprogressors (LTNPs), 332 moderate progressors, and 148 rapid progressors (RPs)]. Four CYP SNPs (CYP2R1 rs10500804, CYP2R1 rs1993116, CYP27B1 rs10877012, and CYP24A1 rs6013897) were genotyped using Agena Bioscience's MassARRAY platform. Correction for multiple testing was performed using the false discovery rate (Benjamini-Hochberg procedure). The adjusted regression showed a significant association only for CYP27B1 rs10877012 SNP. When analyzing all HIV patients, the rs10877012 T allele was protective against AIDS progression (ordinal outcome) under the dominant [adjusted odds ratio (aOR) = 0.69; P = 0.021) and additive (aOR) = 0.75; P = 0.025] inheritance models. When analyzing LTNPs versus RPs, the rs10877012 T allele also showed a significant protective association under the dominant (aOR = 0.45; P = 0.004) and additive (aOR = 0.54; P = 0.008) inheritance models. P values remained significant after correcting by multiple comparisons only for the comparison of LTNPs versus RPs (extreme phenotypes). The CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients. The rs10877012 SNP seems to have an impact on the clinical AIDS progression, possibly modifying vitamin D levels, which could be relevant for the pathogenesis of HIV infection.This work has been (partially) funded by the RD16/0025/0019 and RD16CIII/0002/0002, projects as part of Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (2013-2016) and cofinanced by Instituto de Salud Carlos III (ISCIII-Subdirección General de Evaluación) and Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT17/0015/0042, Fondo de Investigación Sanitaria (FIS) (grant number PI16/01863, PI17/01115, PI17CIII/00003), EPIICAL Project and Comunidad de Madrid (B2017/BMD-3703). CIBER-BBN is an initiative funded by the VINational R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, the Consolider Program, and CIBER Actions and financed by ISCIII with assistance from the European Regional Development Fund. This work has been supported partially by a EUROPARTNER: Strengthening and spreading international partnership activities of the Faculty of Biology and Environmental Protection for interdisciplinary research and innovation of the University of Lodz Programme: NAWA International Academic Partnership Programme. This article/publication is based upon work from COST Action CA 17140 "Cancer Nanomedicine from the Bench to the Bedside" supported by COST (European Cooperation in Science and Technology). AFR and MAJS are supported by “Instituto de Salud Carlos III” [grant number CP14/0010and CP17CIII/00007, respectivelly].Programa de Investigación de la Consejería de Sanidad de la Comunidad de Madrid to JLJ.S

Urinary Nitric Oxide Levels Are Associated with Blood Pressure, Fruit and Vegetable Intake and Total Polyphenol Excretion in Adolescents from the SI! Program.

Nitric oxide (NO) is important to cardiovascular health (CVH), and its bioavailability could be regulated by the antioxidant effect of polyphenols, improving endothelial function and consequently blood pressure (BP). However, scant research has been carried out on NO and CVH correlates in adolescent populations. Therefore, our aim was to investigate the association between NO and the CVH status and other health factors in adolescents. NO, total polyphenol excretion (TPE), anthropometric measurements, BP, blood lipid profile, blood glucose, diet, physical activity, and smoking status were recorded, while CVH score was classified as ideal, intermediate, and poor. Negative associations were observed between NO and body mass index, body fat percentage, BP, and triglycerides; and positive associations between NO and skeletal muscle percentage, HDL-cholesterol, fruit and vegetable intake, and TPE was observed. To capture more complex interactions among different factors, multiple linear regression was performed, obtaining a significant association between NO and fruit and vegetable intake (β = 0.175), TPE (β = 0.225), and systolic BP (β = -0.235). We conclude that urinary NO levels are positively associated with the consumption of fruits and vegetables rich in antioxidants such as polyphenols and negatively associated with systolic BP.The SI! Program for Secondary Schools trial was supported by the SHE Foundation, the la Caixa Foundation (LCF/PR/CE16/10700001), the Fundació la Marató de TV3 (grant number 369/C/2016). Support was also provided by the Ministerio de Ciencia, Innovación y Universidades (PID2020-114022RB-I00), CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades (AEI/FEDER, UE), and Generalitat de Catalunya. RF-J is a recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria- Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund/European Social Fund a way to make Europe/Investing in your future. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). GS-B was the recipient of grant LCF/PR/MS19/12220001 funded by la Caixa Foundation (ID 100010434). AT-R is a Serra Húnter fellow. EL-S was a FI-SDUR (EMC/3345/2020) fellowship from the Generalitat de Catalunya. JM-G was a postgraduate fellow of the Ministerio de Ciencia e Innovación of Spain at the Residencia de Estudiantes (2020–ongoing).S

Paleoenvironmental evolution of Laguna Seca lake (Sierra Nevada, southern Iberia) since the Late Glacial

Comunicación oral en XXI INQUA Congress. Rome (Italy). 14-20th july 2023Laguna Seca lake at 2259 masl has provided the longest alpine sedimentary record in southern Iberia, registering the last ~18 kyr in a ~14-meter-long sediment core. The oldest part of the sedimentary record represents a phase of subaerial debris flows and a small glacier/nivation hollow. The sediment characteristics abruptly changed at ~15.7 cal kyr BP, when a lake environment was established. A multi-proxy approach (magnetic susceptibility, organic geochemical analyses in bulk sediment, XRF core scanner data, and algae identification) has allowed the characterization of three different environmental phases in this lake. Deep lake conditions are identified from ~15.7 to ~10.6 cal kyr BP, agreeing with overall increasing precipitation in southern Iberia coinciding with augmenting summer insolation. This part of the record is characterized by grey lutites with high total organic carbon (TOC) content, high algae productivity, high vascular plant inputs (high C/N ratio) from the catchment and low Fe/S ratio, suggesting low oxygen conditions in the water-sediment interphase. Between ~10.6 and 8.2-8.0 cal kyr BP higher TOC and low Fe/S ratio are also recorded as well as higher algae content and low C/N ratio suggesting high aquatic production and more algae contribution to the local organic matter pool. This period registered the highest lake levels agreeing with summer insolation maximum and highest precipitation in southern Iberia. An abrupt lowering of the lake level is recorded after 8.0 cal kyr BP in the area. This is deduced by the decrease in TOC and algae in the sediments and more siliciclastic contribution from the catchment basin, evidenced by a high increase in siliciclastic elements (Si, Al, K, Ti, among others), with increased oxic conditions in the water-sediment interphase pointed out by the high increase in Fe/S ratio. Additionally, a potential increase in north African aeolian inputs (rich in Fe cations and Fe compounds) can be interpreted for the Middle and Late Holocene, evidenced by high Fe/Al values. This environmental change agrees with an aridification trend previously observed in the southern Iberian Peninsula

Reconstruction of Past Environment and Climate Using Wetland Sediment Records from the Sierra Nevada

Understanding the effects of climate change and human activities on fragile mountain ecosystems is necessary to successfully managing these environments under future climate scenarios (e.g., global warming, enhanced aridity). This can be done through the study of paleoecological records, which can provide long paleoenvironmental databases containing information on how ecosystems reacted to climate change and human disturbances before the historical record. These studies can be particularly interesting when focusing on especially warm and/or dry past climatic phases. Biotic (pollen, charcoal) and abiotic (physical, geochemistry) analyses from wetland sediment records from the Sierra Nevada, southern Spain record changes in vegetation, fire history and lake sedimentation since ~11,700 years (cal yr BP). This multiproxy paleoecological study indicates that maxima in temperature and humidity occurred in the area in the Early and Middle Holocene, with a peak in precipitation between ~10,500 and 7000 cal yr BP. This is deduced by maxima in water runoff, the highest abundance of tree species and algae and high total organic carbon values recorded in the alpine wetland’s sedimentary records of the Sierra Nevada during that time period. In the last 7000 cal yr BP, and especially after a transition period between ~7000 and 5000 cal yr BP, a progressive aridification process took place, indicated by the decrease in tree species and the increase in xerophytic herbs in this region and a reduction in water runoff evidenced by the decrease in detritic input in the wetland sedimentary records. An increasing trend in Saharan dust deposition in the Sierra Nevada wetlands is also recorded through inorganic geochemical proxies, probably due to a coetaneous loss of vegetation cover in North Africa. The process of progressive aridification during the Middle and Late Holocene was interrupted by millennial-scale climatic oscillations and several periods of relative humid/droughty conditions and warm/cold periods have been identified in different temperature and/or precipitation proxies. Enhanced human impact has been observed in the Sierra Nevada in the last ~3000 cal yr BP through the increase in fires, grazing, cultivation, atmospheric pollution as well as reforestation by Pinus and the massive cultivation of Olea at lower altitudes.This study was supported by projects CGL2013-47038-R and CGL2017-85415-R funded by Ministerio de Economía y Competitividad of Spain and Fondo Europeo de Desarrollo Regional FEDER; Séneca Project 20788/PI/18; Junta de Andalucía I+D+i Junta de Andalucía 2020 Retos P-20-00059, FEDER Project B-RNM-144-UGR18, UGR-FEDER B-RNM-144-UGR18 Proyectos I + D + i del Programa Operativo FEDER 2018 and the research group RNM-190 (Junta de Andalucía). M.J.R.R. acknowledges the postdoctoral funding provided by the European Commission/H2020 (ERC-2017-ADG, project number 788616). J.C. acknowledges the postdoctoral funding provided by the Academy of Finland (project number 316702). A.G.-A. acknowledges the Ramón y Cajal fellowship RYC-2015-18966 provided by the Ministerio de Economía y Competitividad of the Spanish Government. M.R.G. acknowledges funding by the Juan de la Cierva-Incorporación program in the University of Granada (IJCI-2017-33755) from Secretaría de Estado de I+D+i, Spain. RSA acknowledges several travel grants from Northern Arizona University to support this work

Prevalence and correlates of cardiovascular health among early adolescents enrolled in the SI! Program in Spain: a cross-sectional analysis.

The Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria (PI19/01704) and the European Regional Development Fund/European Social Fund ("A way to make Europe"/"Investing in your future"), the Fundació la Marató de TV3 (369/C/2016), the ‘la Caixa’ Foundation (LCF/PR/CE16/10700001 and LCF/PR/MS19/12220001), the Ministerio de Ciencia e Innovación (AGL2016–75329-R), the Generalitat de Catalunya, and the SHE Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Rationale and design of the school-based SI! Program to face obesity and promote health among Spanish adolescents: A cluster-randomized controlled trial

Unhealthy habits in adolescents are increasing at an alarming rate. The school offers a promising environment in which to implement effective preventive strategies to improve adolescents' lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based health-promotion intervention aimed at all stages of compulsory education in Spain. We present the study design of the SI! Program for Secondary Schools, targeting adolescents aged 12 to 16 years. Aim: The main goal of this study is to evaluate the impact of the SI! Program educational intervention on adolescent lifestyle behaviors and health parameters. Methods: The study was designed as a cluster-randomized controlled intervention trial and enrolled 1326 adolescents from 24 public secondary schools in Spain, together with their parents/caregivers. Schools and their students were randomly assigned to the intervention group (the SI! curriculum-based educational program over 2 or 4 academic years) or to the control group (usual curriculum). The primary endpoint will be the change from baseline at 2-year and 4-year follow-up in the composite Ideal Cardiovascular Health (ICH) score, consisting of four health behaviors (body mass index, dietary habits, physical activity, and smoking) and three health factors (blood pressure, total cholesterol, and glucose). Secondary endpoints will include 2-year and 4-year changes from baseline in ICH score subcomponents, the Fuster-BEWAT health scale, adiposity markers (waist circumference and body composition), polyphenol and carotenoid intake, and emotion management. Discussion: The overarching goal of the SI! Program is to instill healthy behaviors in children and adolescents that can be sustained into adulthood. The SI! Program for Secondary School is a comprehensive health-promotion intervention targeting 12-16-year-old adolescents and their immediate environment. The present study addresses the optimal timing and impact of the educational intervention on health in adolescence

Clinical Validation of a 3-Dimensional Ultrafast Cardiac Magnetic Resonance Protocol Including Single Breath-Hold 3-Dimensional Sequences

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold. Background: CMR is the reference tool for cardiac imaging but is time-consuming. Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences. Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE. Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in less than 1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort. (J Am Coll Cardiol Img 2021;14:1742–1754)Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose

Myocardial Edema After Ischemia/Reperfusion Is Not Stable and Follows a Bimodal Pattern Imaging and Histological Tissue Characterization

Background: It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon. Objectives: This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion. Methods: The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls. Results: In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h. Conclusions: Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion