Age, Origin and Functional Study of the Prevalent LDLR Mutation Causing Familial Hypercholesterolaemia in Gran Canaria

The p.(Tyr400_Phe402del) mutation in the LDL receptor (LDLR) gene is the most frequent cause of familial hypercholesterolaemia (FH) in Gran Canaria. The aim of this study was to determine the age and origin of this prevalent founder mutation and to explore its functional consequences. For this purpose, we obtained the haplotypic information of 14 microsatellite loci surrounding the mutation in one homozygous individual and 11 unrelated heterozygous family trios. Eight different mutation carrier haplotypes were identified, which were estimated to originate from a common ancestral haplotype 387 (110–1572) years ago. This estimation suggests that this mutation happened after the Spanish colonisation of the Canary Islands, which took place during the fifteenth century. Comprehensive functional studies of this mutation showed that the expressed LDL receptor was retained in the endoplasmic reticulum, preventing its migration to the cell surface, thus allowing us to classify this LDLR mutation as a class 2a, defective, pathogenic variant.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII): PI20/00846, INT21/00032 (RMS), CM19/00116 (AMGL) with the participation of the European Union through European Regional Development Funds (“A way to make Europe”), the Fundación Canaria del Instituto de Investigaciones Sanitarias de Canarias (FCIISC): PIFIISC20/16 and the Fundación Mapfre Guanarteme (Beca Investigación 2020). NMS was supported by a María Zambrano Fellowship funded by the Spanish Ministry of Universities within the “Next Generation EU” scheme

Impact of Covid-19 pandemic on patients with immune thrombocytopaenia

Background and Objectives: The aim of this study was to determine the impact of the COVID-19 pandemic on the lives of patients with immune thrombocytopaenia (ITP) treated at our hospital. Materials and Methods: The study was conducted in the Community of Madrid, which has the highest number of COVID-19 cases in Spain. We included 143 adult patients with ITP (130 with chronic ITP, 8 with persistent ITP, and 5 with newly diagnosed ITP). We conducted a telephone survey to collect the data and created a registry. Materials and Methods: Overall, 24 patients presented symptoms suggestive of COVID-19, which was confirmed by RT-PCR in 8 cases. The cumulative incidence of confirmed SARS-CoV-2 infection was higher in the patients with ITP than in the Madrid population. There were no differences in the disease incidence or clinical course of infection in the patients treated with immunosuppressants. Almost all of the patients reported adherence to the prescribed treatment, although 49.2% of the hospital visits were either cancelled or postponed, 17.2% because of the patients’ fear of coming to the centre. Nearly half of the cohort was considered vulnerable, and 17% had been granted a dependency or disability benefit. Conclusions: COVID-19 had a major impact on the psychosocial, occupational, and quality of care of patients with ITP.This study was supported by FIS-Fondos FEDER PI19/00631 and PI19/00772 and by the Platelet Disorder Support Associatio

Chemical-proteomics Identify Peroxiredoxin-1 as an Actionable Target in Triple-negative Breast Cancer

Triple-negative breast cancer (TNBC) is difficult to treat; therefore, the development of drugs directed against its oncogenic vulnerabilities is a desirable goal. Herein, we report the antitumor effects of CM728, a novel quinone-fused oxazepine, against this malignancy. CM728 potently inhibited TNBC cell viability and decreased the growth of MDA-MB-231-induced orthotopic tumors. Furthermore, CM728 exerted a strong synergistic antiproliferative effect with docetaxel in vitro and this combination was more effective than the individual treatments in vivo. Chemical proteomic approaches revealed that CM728 bound to peroxiredoxin-1 (Prdx1), thereby inducing its oxidation. Molecular docking corroborated these findings. CM728 induced oxidative stress and a multi-signal response, including JNK/p38 MAPK activation and STAT3 inhibition. Interestingly, Prdx1 downregulation mimicked these effects. Finally, CM728 led to DNA damage, cell cycle blockage at the S and G2/M phases, and the activation of caspase-dependent apoptosis. Taken together, our results identify a novel compound with antitumoral properties against TNBC. In addition, we describe the mechanism of action of this drug and provide a rationale for the use of Prdx1 inhibitors, such as CM728, alone or in combination with other drugs, for the treatment of TNBC.This project was supported by Centro Atlántico del Medicamento S.A. (CEAMED), CDTI [IDI-20111517], ACIISI [EATIC2017010006], Universidad de Las Palmas de Gran Canaria, Cabildo Insular de Gran Canaria, Fundación del Instituto Canario de Investigación del Cáncer (FICIC), and Miguel Ángel Rodríguez Cardenes. E. Spínola-Lasso is the recipient of a predoctoral fellowship from the Agencia Canaria de Investigación, Innovación y Sociedad de la Información de la Consejería de Economía, Conocimiento y Empleo y por el Fondo Social Europeo (FSE) Programa Operativo Integrado de Canarias 2014-2020, Eje 3 Tema Prioritario 74 (85%) [TESIS2020010081]. J.C. Montero was funded by the Instituto de Salud Carlos III through the Miguel Servet Program [CP12/03073 and CPII17/00015] and received research support from the same institution [PI15/00684 and PI18/00796]. A. Pandiella received funding from the Ministry of Economy and Competitiveness of Spain [BFU2015-71371-R and PID2020-115605RB-I00], Instituto de Salud Carlos III through CIBERONC, Junta de Castilla y León [CSI146P20], CRIS Cancer Foundation, ACMUMA, UCCTA, ALMOM, and the European Community through the Regional Development Funding Program (FEDER)

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Theoretical analysis of urban runoff pollutographs: identification of characterization variables and impact

This research presents a novel methodology to determine runoffwater retention volumes thatallow the design of storage tanks for storm sewer overflows. It is based on the use of theStormwater Management Model (SWMM) to generate hydrographs and runoffpollutographs ofafictional urban basin. Three pollutants (TS, BOD5and TN) are simulated for a given set of rainsand the values taken by a proposed set of characterization variables for the pollutographsobtained are analysed. Correlation and determination coefficients that exist between thedifferent variables are analysed while also performing a multivariate characterization using PCAand cluster analysis. In the case study presented, using IDF curves of the studied city, aprobability of occurrence (Tr) is assigned to the values taken by the proposed characterizationvariables. To assess the impact and identify the most unfavourable pollutographs within the setof selected rains, impact evaluation variables (IEV?s) are established, based on the proposedcharacterization variables and by simulating the discharge to a receiving water body (river withinitial concentration and constantflow). Finally, a storm sewer overflow is simulated, deriving amaximumflow for purification, and dimensioning retention tanks for different fractions of thetotal volume of runoffto control the maximum values of a specific IEV impact evaluationvariable. Taking a design return period Trssd?10 years, the results obtained in the study casewere 146.50 m3/ha imp for a 100% retention of the total runoffvolume and 117.20 m3/ha impfor an 80% retentio

Diario de Campo: Boletín Interno de los investigadores del área de Antropología. 97 (2008) abril. Diario de Campo

Imágenes del mundo nahua en el acervo de la Tototeca "Nacho López" de la CDI por Xilonen Luna Ruiz y Margarita Sosa Suárez. - El nagualismo en época prehispánica y colonial por Roberto Martínez González. - Aspectos para la práctica pericial por Roberto Martínez González. – Cristianos ortodoxos y maronitas en Yucatán por Iván Frannco. - Conformación, desarrollo, reorganización y actualización del acervo hemerográfico de la Biblioteca Nacional de Antropología e Historia por Angélica Hernández Pérez y Teresa Serrano Espinosa. - Los haberes del patrimonio cultural material e inmaterial, voces permitidas por María del Carmen Lechuga García y Marisol Salas Díaz. - Etnografía, epistemología y el proyecto de una antropología teóricamente dialógica por Johannes Neurath. - Maíz, Naturaleza y Cultura por Cristina Barros. - Henrietta Yurchenco (1916-2007). Uno de sus días, como un sueño musical por Benjamín Muratalla. - Etnografía de los confines: Andanzas de Anne Chapman por Francisco Barriga Puente. - Arqueología y antropología de las religiones por Druzo Mardonado Jiménez. - Conceptos, imágenes y representaciones de la salud y la enfermedad en México. Siglos XIX y XX por José Luis Juárez López. - Ciudad de pueblos. La macrocomunidad de Milpa Alta en la ciudad de México por Hilario Topete. - Las mujeres en Mesoamérica prehispánica por Gabriela Frinee Mateos Flores. - Mujeres en el arte popular. de promesas, traiciones, monstruos y celebridades por Martha Monzón. - Suplemento 47. El mundo nahua: parentesco y ritualidad

La evaluación colegiada de las competencias básicas en la Comunidad Autónoma de Canarias : hacia un modelo de escuela inclusiva y sostenible

Precede al título: Educación Primaria y Educación Secundaria ObligatoriaLa Ley Orgánica de Educación (LOE) introduce el concepto de «competencias básicas» como eje articulador del currículo, conectando de pleno con las reflexiones y las estrategias que se están desarrollando en otros sistemas educativos internacionales a la luz del informe Delors (1996), el documento DeSeCo (Definición y Selección de Competencias fundamentales) elaborado por la OCDE, de las evaluaciones PISA (Programa para la Evaluación Internacional del Alumnado), etc. Esta propuesta centra el foco en la dimensión formativa de la «evaluación», aspecto inacabado con la LOGSE (Ley Orgánica General del Sistema Educativo), a pesar de los esfuerzos realizados en esa dirección. Trabajar en las aulas para la consecución de las «competencias básicas» lleva ineludiblemente al problema de cómo evaluarlas de forma colegiada —cuando la propia ordenación del sistema educativo fragmenta cada una de las enseñanzas en diferentes áreas o materias— y de cómo emplear la información que proporciona esta labor para hacer valer el sentido formativo y regulador que debe tener la evaluación de las competencias básicas.Consejería de Educación y Universidades. Dirección General de Ordenación, Innovación y Promoción Educativa; Avda. Buenos Aires, 5; 38071 Tenerife; Tel. +34922592592; Fax +34922592570; [email protected]

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV

The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations