Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification. In vitro, responses to GC/RA treatment were more effective in MYC-amplified cells. These effects were mediated by BRG1 and involved a reprogramming towards prodifferentiation gene expression signatures and downregulation of MYC. In MYC-amplified cells, administration of GC/RA enhanced the cell growth inhibitory effects of A/S which, in turn, accentuated the prodifferentiation features promoted by GC/RA. Finally, these treatments improved overall survival of mice orthotopically implanted with MYC-amplified, but not BRG1-mutant, cells and reduced tumor cell viability and proliferation. We propose that the combination of epigenetic treatments with retinoids and corticoids of MYC-driven lung tumors constitute a strategy for therapeutic intervention in this otherwise incurable disease

Telemedicine Strategy to Rescue CPAP Therapy in Sleep Apnea Patients with Low Treatment Adherence: A Pilot Study

Patients with sleep apnea are usually treated with continuous positive airway pressure (CPAP). This therapy is very effective if the patient's adherence is satisfactory. However, although CPAP adherence is usually acceptable during the first months of therapy, it progressively decreases, with a considerable number of patients accepting average treatment duration below the effectiveness threshold (4 h/night). Herein, our aim was to describe and evaluate a novel telemedicine strategy for rescuing CPAP treatment in patients with low adherence after several months/years of treatment. This two-week intervention includes (1) patient support using a smartphone application, phone and voice recorder messages to be answered by a nurse, and (2) daily transmission and analysis of signals from the CPAP device and potential variation of nasal pressure if required. On average, at the end of the intervention, median CPAP adherence considerably increased by 2.17 h/night (from 3.07 to 5.24 h/night). Interestingly, the procedure was able to markedly rescue CPAP adherence: the number of patients with poor adherence (<4 h/night) was considerably reduced from 38 to 7. After one month, adherence improvement was maintained (median 5.09 h/night), and only 13 patients had poor adherence (<4 h/night). This telemedicine intervention (103€ per included patient) is a cost-effective tool for substantially increasing the number of patients with CPAP adherence above the minimum threshold for achieving positive therapeutic effects

Comparative genomics uncovers unique gene turnover and evolutionary rates in a gene family involved in the detection of insect cuticular pheromones

Chemoreception is an essential process for the survival and reproduction of animals. Many of the proteins responsible for recognizing and transmitting chemical stimuli in insects are encoded by genes that are members of moderately sized multigene families. The members of the CheB family are specialized in gustatory-mediated detection of long-chain hydrocarbon pheromones in Drosophila melanogaster and play a central role in triggering and modulating mating behavior in this species. Here, we present a comprehensive comparative genomic analysis of the CheB family across 12 species of the Drosophila genus. We have identified a total of 102 new CheB genes in the genomes of these species, including a functionally divergent member previously uncharacterized in D. melanogaster. We found that, despite its relatively small repertory size, the CheB family has undergone multiple gain and loss events and various episodes of diversifying selection during the divergence of the surveyed species. Present estimates of gene turnover and coding sequence substitution rates show that this family is evolving faster than any known Drosophila chemosensory family. To date, only other insect gustatory-related genes among these families had shown evolutionary dynamics close to those observed in CheBs. Our findings reveal the high adaptive potential of molecular components of the gustatory system in insects and anticipate a key role of genes involved in this sensory modality in species adaptation and diversification

IAA : Información y actualidad astronómica (36)

Sumario : Púlsares: faros para navegantes cósmicos.-- Espectroscopía: leyendo entre líneas (II).-- Un universo acelerado.-- CIENCIA EN HISTORIAS. Margaret Burbidge.-- DECONSTRUCCIÓN Y otros ENSAYOS. Hola, soy Nikola.-- EL “MOBY DICK” DE... Cristina Rodríguez López (IAA-CSIC).-- ACTUALIDAD.-- ENTRE BASTIDORES.-- SALA LIMPIA.-- CIENCIA: PILARES E INCERTIDUMBRES. La Vía Láctea.-- AGENDA/RECOMENDADOS.--N

Telemedicine Strategy for CPAP Titration and Early Follow-up for Sleep Apnea During COVID-19 and Post-Pandemic Future.

WiththeacutefirstwaveoftheCOVID-19pandemicover,1thelongwaitinglistforsleeptestsforOSAmanagementhasbeenfurtherincreased.2,3ThenewpreventivehealthmeasuresagainstCovid-19implythatpatientsgotothehealthcentersaslittleaspossible,whichiswhyitisnecessarytoimplementandstartupatelematicworkflowwithhomestudiestoguaranteesleeptests,4especiallyCPAPtitration.5-8WeaimedtotestanewtelematicworkflowtodeliverCPAPtherapytoOSApatientsandtoevaluateitintermsofCPAPcompliance,costs,residualevents,symptomsandsatisfactionofpatients.Theusualtitrationstrategyhasthefollo-wingsteps.Thepatientisscheduledtothedaytime-hospitalforinformation,andeducationalandpracticaltrainingsessionwiththedevice(45min).Then,ourCPAPequipmentisdeliveredtohim/herforhometitration(tobereturnedthenextday),thedataisdownloaded,andafixedpressureisprescribed.Iftheregistra-tionisincorrect,thetitrationisrepeatedanotherday.Finally,thepatientisscheduledbytheservicecompanyprovidingCPAPequip-mentthatinformsagainhowtheequipmentworks,selectsafinalmaskfortreatment,andgiveashortpracticalsessionoftheCPAPuse

Implementación de la evaluación de la competencia de aprendizaje y responsabilidad en el ámbito de la formación práctica de la farmacia galénica

Este trabajo es un resumen de tres comunicaciones presentadas por el GIDTF en el VIII Congreso Internacional de Docencia Universitaria e Innovación (CIDUI), en Tarragona los días 2, 3, y 4 de julio de 2014Projecte: 2013PID-UB/009Hemos introducido, en el ámbito de la docencia de la Farmacia Galénica/Tecnología Farmacéutica del Grado de Farmacia, una innovación docente que consiste en implementar la evaluación de la competencia transversal Capacidad de aprendizaje y responsabilidad, asociándola a la formación práctica dispensada en un conjunto de asignaturas. Se presenta la estrategia globalmente empleada para este fin en las seis asignaturas implicadas así como los instrumentos expresamente diseñados. En el caso de dos asignaturas obligatorias de mención, se examina el beneficio de la realización de una evaluación compartida alumno/profesor (coevaluación) de las prácticas de laboratorio y de la competencia asociada, comparando los resultados de una coevaluación obligatoria frente a los obtenidos mediante coevaluación voluntaria. También se aportan evidencias sobre la validación de los instrumentos de evaluación. La evaluación compartida alumnos/profesores de las prácticas mediante los instrumentos propuestos, nos ha permitido garantizar la validez del proceso y de las calificaciones. La participación obligatoria de los alumnos en el proceso de evaluación resulta beneficiosa para evaluar con seriedad y relevancia dicha competencia, ayudando finalmente a cumplir los objetivos docentes propuestos.Código del proyecto: 2013PID-UB/00

Validación del proceso y de los instrumentos de evaluación de la competencia "Capacidad de aprendizaje y responsabilidad" en el ámbito de la formación práctica en farmacia galénica

Informe del proyecto 2014PID-UB/050 llevado a cabo por el Grupo de Innovación Docente Consolidado de Tecnología Farmacéutica GIDTF-2013Se presentan los avances del Grupo de Innovación Docente de Tecnología Farmacéutica (GIDTF) en su línea de actuación relativa a la estrategia de desarrollo gradual y de evaluación de la competencia de aprendizaje y responsabilidad, trabajada en las prácticas de laboratorio de las asignaturas del ámbito de la Farmacia Galénica/Tecnología Farmacéutica que se imparte en 1º, 3º, 4º y 5º del Grado de Farmacia y en módulos de postgrado del Título de Especialista de Farmacia Industrial y Galénica (TEFIG). Se confirma que la evaluación compartida alumnos/profesores de las prácticas mediante los instrumentos propuestos, permite garantizar la validez del proceso y de las calificaciones de las prácticas y de la competencia asociada. La participación de los alumnos en el proceso de evaluación resulta beneficiosa para validar los instrumentos de evaluación diseñados para este fin, ayudando finalmente a cumplir los objetivos docentes propuestos

Intermittent hypoxia increases kidney tumor vascularization in a murine model of sleep apnea

We investigate the effects of intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), on renal cancer progression in an animal and cell model. An in vivo mouse model (Balb/c, n = 50) of kidney cancer was used to assess the effect of IH on tumor growth, metastatic capacity, angiogenesis and tumor immune response. An in vitro model tested the effect of IH on RENCA cells, macrophages and endothelial cells. Tumor growth, metastatic capacity, circulating vascular endothelial growth factor (VEGF) and content of endothelial cells, tumor associated macrophages and their phenotype were assessed in the tumor. In vitro, VEGF cell expression was quantified.Although IH did not boost tumor growth, it significantly increased endothelial cells (p = 0.001) and circulating VEGF (p<0.001) in the in vivo model. Macrophages exposed to IH in vitro increased VEGF expression, whereas RENCA cells and endothelial cells did not. These findings are in keeping with previous clinical data suggesting that OSA has no effect on kidney cancer size and that the association observed between OSA and higher Fuhrman grade of renal cell carcinoma may be mediated though a proangiogenic process, with a key role of macrophages

IAA : Información y actualidad astronómica (38)

Sumario : La importancia del cielo oscuro.-- Viajes en el tiempo.-- CIENCIA EN HISTORIAS. Vera Rubin, la madre de la materia oscura.-- DECONSTRUCCIÓN Y otros ENSAYOS. Astrología amorosa para escépticos.-- EL “MOBY DICK” DE... Miguel Ángel Pérez Torres (IAA).-- ACTUALIDAD.-- ENTRE BASTIDORES.-- SALA LIMPIA.-- CIENCIA: PILARES E INCERTIDUMBRES. El origen de la vida.-- RECOMENDADOS.N

Transcultural adaptation and validation of the ' Hip and Knee ' questionnaire into Spanish

BACKGROUND: The purpose of the present study is to translate and validate the 'Hip and Knee Outcomes Questionnaire', developed in English, into Spanish. The 'Hip and Knee Outcomes Questionnaire is a questionnaire planned to evaluate the impact in quality of life of any problem related to the human musculoskeletal system. 10 scientific associations developed it. METHODS: The questionnaire underwent a validated translation/retro-translation process. Patients undergoing primary knee arthroplasty, before and six months postoperative, tested the final version in Spanish. Psychometric properties of feasibility, reliability, validity and sensitivity to change were assessed. Convergent validity with SF-36 and WOMAC questionnaires was evaluated. RESULTS: 316 patients were included. Feasibility: a high number of missing items in questions 3, 4 and 5 were observed. The number of patients with a missing item was 171 (51.35%) in the preoperative visit and 139 (44.0%) at the postoperative. Internal validity: revision of coefficients in the item-rest correlation recommended removing question 6 during the preoperative visit (coefficient <0.20). Convergent validity: coefficients of correlation with WOMAC and SF-36 scales confirm the questionnaire's validity. Sensitivity to change: statistically significant differences were found between the mean scores of the first visit compared to the postoperative. CONCLUSION: The proposed translation to Spanish of the 'Hip and Knee Questionnaire' is found to be reliable, valid and sensible to changes produced at the clinical practice of patients undergoing primary knee arthroplasty. However, some changes at the completion instructions are recommended. LEVEL OF EVIDENCE: Level I. Prognostic study