Synergic Effect of α

Cervical cancer is the second leading cause of death among Mexican women. The treatment with cis-diamminedichloroplatinum (II) (CDDP) has some serious side effects. Alpha-mangostin (α-M), has a protective effect against CDDP-induced nephrotoxicity, as well as antioxidant, antitumor, and anti-inflammatory properties. Hence, we explored the in vitro and in vivo effect of α-M on human cervical cancer cell proliferation when combined with CDDP. In vitro, The cytotoxic effect of α-M and/or CDDP was measured by the 3-(3,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium assay. Meanwhile, apoptosis, reactive oxygen species (ROS) production, and the cell cycle were determined with flow cytometry. For α-M+CDDP treatment, both a coincubation and preincubation scheme were employed. In vivo, xenotransplantation was performed in female athymic BALB/c (nu/nu) mice, and then tumor volume and body weight were measured weekly, whereas α-M interfered with the antiproliferative activity of CDDP in the coincubation scheme, with preincubation with α-M+CDDP showing significantly greater cytotoxicity than CDDP or α-M alone, significantly inhibiting average tumor volume and preventing nephrotoxicity. This effect was accompanied by increased apoptosis and ROS production by HeLa cervical cancer cells, as well as an arrest in the cell cycle. These results suggest that α-M may be useful as a neoadjuvant agent in cervical cancer therapy

¿Quién quiere ser millonario? El concurso como herramienta alternativa de evaluación

Los concursos son una técnica de gamificación que, a través de una dinámica generalmente incremental y competitiva, tratan de favorecer la motivación de los estudiantes y estimular su aprendizaje haciéndolo más atractivo. El contexto de los concursos permite no solo desarrollar competencias técnicas y transversales con su aplicación, sino también plantear formas alternativas de evaluación de contenidos que pueden ser de aplicación en asignaturas de distinta tipología. En este artículo se presenta una experiencia docente en la que el famoso concurso ¿Quién quiere ser millonario? ha sido utilizado como actividad de evaluación alternativa a los exámenes parciales en la asignatura Sistemas de Comunicación en Edificios del cuarto curso del grado en Ingeniería Eléctrica. Para ello, se han implementado dos versiones o modalidades de este concurso: una modalidad on-line donde los estudiantes participaban desde sus casas y una modalidad presencial, donde los estudiantes eran evaluados en el aula ordinaria. El desarrollo de esta actividad durante los dos últimos cursos académicos permite constatar que esta metodología es adecuada para la evaluación de contenidos fundamentales.Contests constitute a gaming technique which, by means of competitive and increasing dynamics, try to boost motivation in students and stimulate their learning progress by making it more attractive. The different types of contests would allow not only to develop technical and cross-curricular competences when applied but also to contemplate alternative ways of content assessment that might be applied in different subjects. This article presents a teaching experience where the famous contest Who wants to be a millionaire has been used as an assessment alternative tool to midterms tests in the subject Communications systems in buildings in the fourth year of the Electrical Engineering bachelor ´s degree. For this matter, two different versions of the contest have been implemented: the online version where students participate from home and the face-to-face version where all the students are assessed in the classroom. The development of this activity during the last two academic courses allows us to confirm that this methodology is suitable to assess essential contents

El impacto de la obesidad sobre el lipidoma cardíaco y sus consecuencias en el daño cardíaco en ratas obesas

To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Methods: Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. Results: HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. Conclusions: These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levelsThis work was supported by funds from the Sociedad Española de Arteriosclerosis (Basic Research Award 2015), from Plan Estatal I+D+I 2013-2016: PI15/01060 and SAF2016-81063. The study was cofunded by Fondo Europeo de Desarrollo Regional (FEDER), a way to build Europ

Pharmacogenomics of prostaglandin and leukotriene receptors

Los antecedentes genéticos individuales junto con los efectos ambientales se cree que están detrás de muchas enfermedades complejas. Una serie de variantes genéticas, principalmente los SNPs (single nucleotide polymorphisms), han demostrado estar asociados con diferentes patologías y afecciones inflamatorias, que representan potenciales dianas terapéuticas. Las prostaglandinas (PTGs) y leucotrienos (LTs) son eicosanoides derivados del ácido araquidónico y relacionados con ácidos grasos poliinsaturados participan tanto en la homeostasis normal y en condiciones inflamatorias. Estos mediadores lípidos bioactivos son sintetizados a través de dos grandes vías enzimáticas multipaso: PTGs por la ciclooxigenasa y la lipooxigenasa DE 5 LTS. Los principales efectos fisiológicos de PTGs incluyen vasodilatación y la fuga vascular (PTGE2); la maduración de los mastocitos, eosinófilos, y reacciones alérgicas (PTGD2); vascular y la contracción del músculo liso de las vías respiratorias (PTGF2), e inhibición de la agregación plaquetaria (PTGI2). LTB4 está principalmente involucrado en el reclutamiento de los neutrófilos, fuga vascular y en la función de la barrera epitelial, mientras que cisteinil LTs (CysLTs) (LTC4, LTD4 y LTE4) inducen la broncoconstricción y extravasación de neutrófilos, y también participar en la fuga vascular. PTGs y LTs ejercen sus funciones biológicas mediante su unión a receptores afines, que pertenecen a las siete transmembranas acopladas a proteínas G, la superfamilia de receptores. Los SNPs en genes que codifican estos receptores pueden influir en su funcionalidad, ya que tienen un papel en la susceptibilidad a las enfermedades y la respuesta al tratamiento de los medicamentos. En esta revisión resumimos los SNPs en PTGs y receptores de LTs y su relevancia en enfermedades humanas. También ofrecemos información sobre la expresión génica. Por último, podemos especular sobre la dirección futura de este tema.Individual genetic background together with environmental effects are thought to be behind many human complex diseases. A number of genetic variants, mainly single nucleotide polymorphisms (SNPs), have been shown to be associated with various pathological and inflammatory conditions, representing potential therapeutic targets. Prostaglandins (PTGs) and leukotrienes (LTs) are eicosanoids derived from arachidonic acid and related polyunsaturated fatty acids that participate in both normal homeostasis and inflammatory conditions. These bioactive lipid mediators are synthesized through two major multistep enzymatic pathways: PTGs by cyclooxygenase and LTs by 5-lipoxygenase. The main physiological effects of PTGs include vasodilation and vascular leakage (PTGE2); mast cell maturation, eosinophil recruitment, and allergic responses (PTGD2); vascular and respiratory smooth muscle contraction (PTGF2), and inhibition of platelet aggregation (PTGI2). LTB4 is mainly involved in neutrophil recruitment, vascular leakage, and epithelial barrier function, whereas cysteinyl LTs (CysLTs) (LTC4, LTD4, and LTE4) induce bronchoconstriction and neutrophil extravasation, and also participate in vascular leakage. PTGs and LTs exert their biological functions by binding to cognate receptors, which belong to the seven transmembrane, G protein-coupled receptor superfamily. SNPs in genes encoding these receptors may influence their functionality and have a role in disease susceptibility and drug treatment response. In this review we summarize SNPs in PTGs and LTs receptors and their relevance in human diseases. We also provide information on gene expression. Finally, we speculate on future directions for this topic.Trabajo patrocinado por: Programa Miguel Servet. Ref CP14/00034, para José Antonio Cornejo García Ministerio de Economía y Competitividad y Instituto Nacional de Salud Carlos III y Fondos FEDER. Programa Sara Borrell. Ref. CD14/00242, para James R. Perkins Ministerio de Economía y Competitividad e Instituto Nacional de Salud Carlos III y Fondos FEDER. Becas FISPI12/02247, FISPI13/02598 y FISPI15/00726 Servicio Público de Salud de Andalucía. Beca PI-0279-2012 Junta de Extremadura y Fondos FEDER. Beca GR15026peerReviewe

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats

We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10−6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role

Clonal chromosomal mosaicism and loss of chromosome Y in men are risk factors for SARS-CoV-2 vulnerability in the elderly

* SCOURGE Cohort Group Javier Abellan15,16; René Acosta-Isaac17; Jose María Aguado18,19,20,21; Carlos Aguilar22; Sergio Aguilera-Albesa23,24; Abdolah Ahmadi Sabbagh25; Jorge Alba26; Sergiu Albu27,28,29; Karla A.M. Alcalá-Gallardo30; Julia Alcoba-Florez31; Sergio Alcolea Batres32; Holmes Rafael AlgarinLara33,34; Virginia Almadana35; Kelliane A. Medeiros36,37; Julia Almeida38,39; Berta Almoguera40,3; María R. Alonso41; Nuria Alvarez41; Rodolfo Alvarez-Sala Walther32; Yady Álvarez-Benítez33,34; Felipe Álvarez-Navia42,43; Katiusse A. dos Santos44; Álvaro Andreu-Bernabeu45,20; Maria Rosa Antonijoan46; Eleno Martínez-Aquino47; Eunate Arana-Arri48,49; Carlos Aranda50,51; Celso Arango45,52,20; Carolina Araque53,54; Nathalia K. Araujo55; Ana C. Arcanjo56,57,58; Ana Arnaiz59,60; Francisco Arnalich Fernández61; María J. Arranz62; José Ramon Arribas Lopez61; Maria-Jesus Artiga63; Yubelly Avello-Malaver64; Carmen Ayuso40,3; Belén Ballina Martín25; Raúl C. BaptistaRosas65,66,67; Ana María Baldion64; Andrea Barranco-Díaz34; María Barreda- Sánchez68,69; Viviana Barrera-Penagos64; Moncef Belhassen-Garcia70,43; David Bernal-Bello71; Enrique Bernal68; Joao F. Bezerra72; Marcos A.C. Bezerra73; Natalia Blanca-López74; Rafael Blancas75; Lucía Boix-Palop76; Alberto Borobia77; Elsa Bravo78; María Brion79,80; Óscar Brochado-Kith81; Ramón Brugada82,83,80,84; Matilde Bustos85; Alfonso Cabello86; Alejandro Cáceres4,5; Juan J. Caceres-Agra87; Esther Calbo76; Enrique J. Calderón88,6,89; Shirley Camacho90; Francisco C. Ceballos81; Yolanda Cañadas51; Cristina Carbonell42,43; Servando Cardona-Huerta91; Maria Sanchez Carpintero50,51; Carlos Carpio Segura32; José Antonio Carrillo-Avila92; Marcela C. Campos56; Carlos Casasnovas93,94,3; Luis Castano48,95,3,96,97; Carlos F. Castaño50,51; Jose E. Castelao98; Aranzazu Castellano Candalija99; María A. Castillo90; Walter G. ChavesSantiago100,54; Sylena Chiquillo-Gómez33,34; Marco A. Cid-Lopez30; Oscar CienfuegosJimenez91; Rosa Conde-Vicente101; Gabriela C.R. Cunha102; M. Lourdes Cordero-Lorenzana103; Dolores Corella104,105; Almudena Corrales106,107; Jose L. Cortes-Sanchez91,108; Marta Corton40,3; Karla S.C. Souza109; Fabiola T.C. Silva56; Raquel Cruz8,3,9,10; Luisa Cuesta110; Nathali A.C. Tavares111; Maria C.C. Carvalho112; David Dalmau62,76; Raquel C.S. Dantas-Komatsu113; M. Teresa Darnaude114; Raimundo de Andrés115; Carmen de Juan116; Juan De la Cruz Troca117,118,6; Carmen de la Horra89; Ana B. de la Hoz48; Alba De Martino-Rodríguez119,120; Marina S. Cruz121; Julianna Lys de Sousa Alves Neri122; Victor del Campo-Pérez123; Juan Delgado-Cuesta124; Aranzazu Diaz de Bustamante114; Anderson Díaz-Pérez34; Beatriz Dietl76; Silvia Diz-de Almeida3,10; Manoella do Monte Alves125,126; Elena Domínguez-Garrido127; Lidia S. Rosa128; Andre D. Luchessi129; Jose Echave-Sustaeta130; Rocío Eiros131; César O. EncisoOlivera53,54; Gabriela Escudero132; Pedro Pablo España133; Gladys Mercedes Estigarribia Sanabria134; María Carmen Fariñas59,60,135; Ramón Fernández59,136; Lidia FernandezCaballero40,3; Ana Fernández-Cruz137; Silvia Fernández Ferrero25; Yolanda Fernández Martínez25; María J. Fernandez-Nestosa138; Uxía Fernández-Robelo139; Amanda FernándezRodríguez81; Marta Fernández-Sampedro59,135,60; Ruth Fernández40,3; Tania Fernández-Villa140; Carmen Fernéndez Capitán99; Antonio Augusto F. Carioca141; Patricia Flores-Pérez142; Lácides Fuenmayor-Hernández34; Marta Fuertes Núñez25; Victoria Fumadó143; Ignacio Gadea144; Lidia Gagliardi50,51; Manuela Gago-Domínguez13,9; Natalia Gallego11; Cristina Galoppo145; Ana García-Soidán146; Carlos Garcia Cerrada15,16; Aitor García-de-Vicuña48,95; Josefina GarciaGarcía68; Irene García-García77; Carmen García-Ibarbia59,135,60; Andrés C. García-Montero147; Leticia García50,51; Mercedes García50,51; María Carmen García Torrejón148,16; Inés García40,3; Elisa García-Vázquez68; Emiliano Garza-Frias91; Angela Gentile145; Belén Gil-Fournier149; Jéssica N.G. de Araújo150; Mario Gómez-Duque100,54; Javier Gómez-Arrue119,120; Luis Gómez Carrera32; María Gómez García151; Ángela Gómez Sacristán152; Juan R. González4,5,6,14; Anna González-Neira41; Beatriz González Álvarez119,120; Fernan Gonzalez Bernaldo de Quirós153; Rafaela González-Montelongo154; Javier González-Peñas45,20,52; Manuel Gonzalez-Sagrado101; Hugo Gonzalo Benito155; Oscar Gorgojo-Galindo156; Miguel Górgolas86; Florencia Guaragna145; Jessica G. Chaux54; Encarna Guillen-Navarro68,157,158,159; Beatriz Guillen-Guio106; Pablo Guisado-Vasco130; Luz D. Gutierrez-Castañeda160,54; Juan F. Gutiérrez-Bautista161; Sara HeiliFrades162; Rafael H. Jacomo163; Estefania Hernandez164; Cristina Hernández Moro25; Luis D. Hernandez-Ortega165,166; Guillermo Hernández-Pérez42; Rebeca Hernández-Vaquero167; Belen Herraez41; M. Teresa Herranz68; María Herrera50,51; María José Herrero168,169; Antonio HerreroGonzalez170; Juan P. Horcajada171,172,28,173; Natale Imaz-Ayo48; Maider IntxaustiUrrutibeaskoa174; Antonio Íñigo-Campos154; María Íñiguez175; Rubén Jara68; Ángel Jiménez50,51; Ignacio Jiménez-Alfaro176; Pilar Jiménez161; María A. Jimenez-Sousa81; Iolanda Jordan177,178,6; Rocío Laguna-Goya179,180; Daniel Laorden32; María Lasa-Lazaro179,180; María Claudia Lattig90,181; Ailen Lauriente145; Anabel Liger Borja182; Lucía Llanos183; Amparo López-Bernús42,43; Miguel It is made available under a CC-BY-NC-ND 4.0 International license . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. medRxiv preprint doi: https://doi.org/10.1101/2020.04.19.20071357; this version posted February 18, 2022. The copyright holder for this preprint López de Heredia3 ; Esther Lopez-Garcia117,118,6,184; Eduardo López Granados185,186,3; Rosario Lopez-Rodriguez40,3; Miguel A. López-Ruz187,188,189; Leonardo Lorente190; José M. LorenzoSalazar154; José E. Lozano191; María Lozano-Espinosa182; Ignacio Mahillo192,193,107; Esther Mancebo179,180; Carmen Mar133; Cristina Marcelo Calvo99; Alba Marcos-Delgado194; Miguel Marcos42,43; Alicia Marín Candon77; Pablo Mariscal Aguilar32; Laura Martin-Pedraza74; Marta Martin-Fernandez195; Caridad Martín-López182; José-Ángel Martín-Oterino42,43; María Dolores Martín196; Vicente Martín194,6; María M. Martín197; María Martín-Vicente81; Amalia Martinez198; Óscar Martínez-González75; Ricardo Martínez164; Pedro Martinez-Paz155; Covadonga M. DiazCaneja45,52,20; Oscar Martinez-Nieto64,181; Iciar Martinez-Lopez199,200; Michel F. MartinezResendez91; Silvia Martínez59,135; Juan José Martinez94,3; Angel Martinez-Perez201; Andrea Martínez-Ramas40,3; Violeta Martínez Robles25; Laura Marzal40,3; Juliana F. Mazzeu202,203,204; Francisco J. Medrano88,6,89; Xose M. Meijome205,206; Natalia Mejuto-Montero207; Ingrid Mendes3 ; Alice L. Duarte109; Ana Méndez-Echevarria208; Humberto Mendoza Charris78,34; Eleuterio Merayo Macías209; Fátima Mercadillo210; Arieh R. Mercado-Sesma165,166; Pablo Minguez40,3; Elena Molina-Roldán211; Antonio J J. Molina194; Juan José Montoya164; Susana M.T. Pinho36,212,213; Patricia Moreira-Escriche116; Xenia Morelos-Arnedo78,34; Rocío Moreno3 ; Victor Moreno Cuerda15,16; Antonio Moreno-Docón68; Junior Moreno-Escalante34; Alberto Moreno Fernández99; Patricia Muñoz García214,107,20; Pablo Neira145; Julian Nevado3,11,12; Israel NietoGañán146; Vivian N. Silbiger129; Rocio Nuñez- Torres41; Antònia Obrador-Hevia215,216; J. Gonzalo Ocejo-Vinyals59,135; Virginia Olivar145; Silviene F. Oliveira56,217,204,218; Lorena Ondo40,3; Alberto Orfao38,39; Eva Ortega-Paino63; Luis Ortega219; Rocio Ortiz-Lopez91; Fernando Ortiz-Flores59,135; José A. Oteo26,175; Manuel Pacheco164; Fredy Javier Pacheco-Miranda34; Irene Padilla Conejo25; Sonia Panadero-Fajardo92; Mara Parellada45,52,20; Roberto Pariente-Rodríguez146; Vicente Friaza6,89; Estela Paz-Artal179,180,220; Germán Peces-Barba221,107; Miguel S. Pedromingo Kus222; Celia Perales144; Ney P.C. Santos223; Genilson P. Guegel224; Perez Maria Jazmin145; Alexandra Perez82,80; Patricia Pérez-Matute175; César Pérez225; Gustavo Perez-de-Nanclares48,95; Felipe Pérez-García226,227; Patricia Perez228; Luis A. Pérez-Jurado1,2,3; M. Elena Pérez-Tomás68; Teresa Perucho229; Lisbeth A. Pichardo25; Adriana P. Ribeiro36,37,213; Mel·lina Pinsach-Abuin82,80; Luz Adriana Pinzón100,54; Jeane F.P. Medeiros230; Guillermo Pita41; Francesc Pla-Junca231,3; Laura Planas-Serra94,3; Ericka N. Pompa-Mera232; Gloria L. Porras-Hurtado164; Aurora Pujol94,3,233; María Eugenia Quevedo Chávez33,34; Maria Angeles Quijada46,234; Inés Quintela8 ; Soraya Ramiro León149; Pedro Rascado Sedes235; Joana F.R. Nunes56; Delia Recalde119,120; Emma Recio-Fernández175; Salvador Resino81; Renata R. Sousa213,236; Carlos S. RivadeneiraChamorro54; Diana Roa-Agudelo64; Montserrat Robelo Pardo235; Marianne R. Fernandes223,237; María A. Rodriguez-Hernandez85; Agustí Rodriguez-Palmero238,94; Emilio Rodríguez-Ruiz235,9; Marilyn Johanna Rodriguez54; Fernando Rodriguez-Artalejo117,118,6,184; Marena RodríguezFerrer34; Carlos Rodriguez-Gallego239,240; José A. Rodriguez-Garcia25; Belén Rodríguez Maya15; Antonio Rodriguez-Nicolas161; German Ezequiel Rodriguez Novoa145; Paula A. RodriguezUrrego64; Federico Rojo241,242; Andrea Romero-Coronado34; Rubén Morilla89,243; Filomeno Rondón García25; Antonio Rosales-Castillo244; Cladelis Rubio245; María Rubio Olivera50,51; Francisco Ruiz-Cabello161,188,246; Eva Ruiz-Casares229; Juan J. Ruiz-Cubillan59,135; Javier RuizHornillos247,51,248; Montserrat Ruiz94,3; Pablo Ryan249,250,251; Hector D. Salamanca53,54; Lorena Salazar-García90; Giorgina Gabriela Salgueiro Origlia 99; Anna Sangil76; Olga SánchezPernaute252; Pedro-Luis Sánchez131,43; Antonio J. Sánchez López253; Clara Sánchez-Pablo131; María Concepción Sánchez Prados32; Javier Sánchez Real25; Jorge Sánchez Redondo15,254; Cristina Sancho- Sainz174; Esther Sande255; Arnoldo Santos225; Agatha Schlüter94,3; Sonia Segovia231,256,257; Alex Serra-Llovich62; Fernando Sevil Puras22; Marta Sevilla Porras3,11; Miguel A. Sicolo258,259; Cristina Silván Fuentes3 ; Vitor M.S. Moraes260; Vanessa S. Souza102; Jordi SoléViolán261,107; José Manuel Soria201; Jose V. Sorlí104,105; Nayara S. Silva262; Juan Carlos Souto17; John J. Sprockel100,54; José Javier Suárez-Rama8 ; David A. Suarez-Zamora64; Xiana TaboadaFraga207; Eduardo Tamayo263,156; Alvaro Tamayo-Velasco264; Juan Carlos TaracidoFernandez170; Romero H.T. Vasconcelos111; Carlos Tellería119,120; Thássia M.T. Carratto260; Jair Antonio Tenorio Castaño3,11,12; Alejandro Teper145; Izabel M.T. Araujo109; Juan Torres-Macho265; Lilian Torres-Tobar266; Ronald P. Torres Gutiérrez222; Jesús Troya249; Miguel Urioste210; Juan Valencia-Ramos267; Agustín Valido35,268; Juan Pablo Vargas Gallo269,270; Belén Varón271; Tomas Vega272; Santiago Velasco-Quirce273; Valentina Vélez-Santamaría93,94; Virginia Víctor50,51; Julia Vidán Estévez25; Gabriela V. Silva109; Miriam Vieitez-Santiago59,135; Carlos Vilches274; Lavinia Villalobos25; Felipe Villar221; Judit Villar-Garcia275,276,277; Cristina Villaverde3,40; Pablo VillosladaBlanco175; Ana Virseda-Berdices81; Tatiana X. Costa278; Zuleima Yáñez34; Antonio Zapatero Gaviria279; Ruth Zarate280; Sandra Zazo241; Carlos Flores106,107,154; José A. Riancho59,60,135; Augusto Rojas-Martinez281; Pablo Lapunzina3,11,12; Ángel Carracedo3,8,9,10,13The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome events (CME) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (CME and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, CME and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.The authors acknowledge support from the Catalan Department of Economy and Knowledge (SGR2017/1974, SGR2017/801) and the Spanish Ministry of Science “Programa de Excelencia María de Maeztu” (MDM-2014-0370) and “Centro de Excelencia Severo Ochoa” (CEX2018-000806-S), the Fondo Europeo de Desarrollo Regional, UE (RTI2018-100789-B-I00) and the Estonian Research Council (PUT1660). Authors also receive support from the Generalitat de Catalunya through the CERCA Program.N

The Caldera. No. 14

El Instituto Caldas decidió implementar este año el Sistema de Gestión de la Calidad, asumiendo como principal objetivo mejorar permanentemente el servicio educativo que ofrecemos y cumplir con las expectativas de padres de familia y estudiantes. Para llevar a cabo este propósito, contamos con el apoyo incondicional de la UNAB y de toda la comunidad educativa, quienes de manera activa participaron en cada una de las actividades programadas para el logro de este objetivo. Este proceso nos permitió conocer nuestras fortalezas y áreas de oportunidad, basados en evidencias; información a partir de la cual se inicia el mejoramiento institucional.Entrevista a: Claudia Lucía Salazar Jaimes; Por Consuelo Parra Rodríguez…04 Tendencias educativas: Pedagogía por proyectos; Por Gisela Afanador Díaz…10 Celta: University of Cambridge; Por Oscar Mauricio Ortíz Delgado…16 Project Free Time; Por Freddy Augusto López…18 Reloj Solar: Un merecido reconocimiento a tan significativa labor…19 Una visita muy esperada; Por Grace Jurado Daza…20 Biblioteca Escolar Caldas: Con un antes y un después todos podemos hacer la diferencia; Por Freddy Quitián Fino…22 XIII Simposio Estudiantil: Liderazgo y contexto social; Por Natalia Franco y Leidy Villamizar (Estudiantes de 11B) …23 Concurso Intercolegiado de Ortografía; Por Natalia Franco y Leidy Villamizar (Estudiantes de 11B) …24 Asofacaldas…25 Soy autónomo, soy caldista TV; Por Abelardo Carreño Gómez…28 Galería…30The Caldas Institute decided to implement the Quality Management System this year, assuming the main objective of permanently improving the educational service we offer and meeting the expectations of parents and students. To carry out this purpose, we have the unconditional support of UNAB and the entire educational community, who actively participated in each of the activities programmed to achieve this objective. This process will get us to know our strengths and areas of opportunity, based on evidence; information from which institutional improvement begins

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

BACKGROUND: Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services.Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. METHODS/DESIGN: This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. DISCUSSION: This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01484223 [http://ClinicalTrials.gov].S

Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes