130 research outputs found

    Respuesta fisiológica y química de clones de Ulmus minor susceptibles y resistentes a la grafiosis tras la inoculación con Ophiostoma novo-ulmi

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    Los motivos por los que algunos genotipos de Ulmus minor Mill. resisten más que otros a la infección con el hongo patógeno Ophiostoma novo-ulmi son aun desconocida. Con el objetivo de evaluar si la resis- tencia a la enfermedad de la grafiosis está relacionada con la posesión de ciertos rasgos fisiológicos o quí- micos, se compararon clones de U. minor resistentes y susceptibles a la grafiosis, antes y después de la ino- culación con O. novo-ulmi . Se midieron el potencial hídrico, las tasas de respiración y fotosíntesis foliar, y la conductividad hidráulica de ramas terminales y su composición química mediante espectroscopía de infrarrojo (FT-IR). La inoculación con el hongo produjo un aumento en la proporción de vasos emboliza- dos, de modo que a los 21 días la conductividad hidráulica era solo un 20% de la conductividad máxima en los clones susceptibles. Como consecuencia, el potencial hídrico y la fotosíntesis disminuyeron entor- no a un 100-200% en relación a los controles en los clones susceptibles mientras que no hubo reducciones significativas en los resistentes. Además, los clones mostraron una composición química de sus ramas di- ferente. Por ejemplo, en los árboles inoculados con agua utilizados como control, el pico de absorción en la región del espectro infrarrojo relacionado con la suberina fue más alto en los clones resistentes que en los susceptibles.Estos resultados sugieren que el perfil químico más defensivo de los clones resistentes les permite mantener la funcionalidad fisiológica tras la inoculación con O. novo-ulmi prácticamente inalterada, en comparación con los clones más susceptibles

    Assessment of oxidative damage to proteins and DNA in urine of newborn infants by a validated UPLC-MS/MS approach

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    The assessment of oxidative stress is highly relevant in clinical Perinatology as it is associated to adverse outcomes in newborn infants. This study summarizes results from the validation of an Ultra Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) method for the simultaneous quantification of the urinary concentrations of a set of endogenous biomarkers, capable to provide a valid snapshot of the oxidative stress status applicable in human clinical trials, especially in the field of Perinatology. The set of analytes included are phenylalanine (Phe), para-tyrosine (p-Tyr), ortho-tyrosine (o-Tyr), meta-tyrosine (m-Tyr), 3-NO2-tyrosine (3NO 2-Tyr), 3-Cl-tyrosine (3Cl-Tyr), 2′-deoxyguanosine (2dG) and 8-hydroxy-2′-deoxyguanosine (8OHdG). Following the FDA-based guidelines, appropriate levels of accuracy and precision, as well as adequate levels of sensitivity with limits of detection (LODs) in the low nanomolar (nmol/L) range were confirmed after method validation. The validity of the proposed UPLC-MS/MS method was assessed by analysing urine samples from a clinical trial in extremely low birth weight (ELBW) infants randomized to be resuscitated with two different initial inspiratory fractions of oxygen

    Crosstalk Between LXR and Caveolin-1 Signaling Supports Cholesterol Efflux and Anti-Inflammatory Pathways in Macrophages

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    © 2021 Ramírez, Torrecilla-Parra, Pardo-Marqués, de-Frutos, Pérez-García, Tabraue, de la Rosa, Martín-Rodriguez, Díaz-Sarmiento, Nuñez, Orizaola, Través, Camps, Boscá and Castrillo.Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis.We thank MINECO FPI predoctoral fellowship granted to MCO (BES-2015-075339). Experimental work was supported by grants from Ministerio de Ciencia, Investigación y Universidades, y Fondo Europeo de Desarrollo Regional (FEDER) Grant REF: PID2019-104284RB-I00/AEI/10.13039/501100011033 (to AC) and support from Networks of Excellence from MINECO (Nuclear Receptors in Cancer, Metabolism and Inflammation [NuRCaMeIn] SAF2017-90604-REDT to AC. Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional (to LB). Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación Proyectos de I+D+i Retos Investigación 2018 (RTI2018-095061-B-I00); TALENTO Grant from Madrid Government, Spain (2017-T1/BMD-5333); Consejería de Ciencia, Universidades e Innovación Comunidad de Madrid, Spain (PEJD-2018-POST/BMD-8900 and PEDJ-2018-AI/BDM-9724) to CMR

    Stable nitrogen isotopes in coastal macroalgae: geographic and anthropogenic variability

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    Proyectos ANILE (CTM2009-08396 and CTM2010-08804-E) del Plan Nacional de I+D+i y RADIALES del Instituto Español de Oceanografía (IEO). I.G.V. recibió un contrato FPI del Ministerio de Economía y CompetividadGrowing human population add to the natural nitrogen loads to coastal waters. As the excess nitrogen is readily incorporated in new biomass anthropogenic and natural nitrogen sources may be traced by the measurement of stable nitrogen isotopes (δ15N). In this study δ15N was determined in two species of macroalgae (Ascophyllum nodosum and Fucus vesiculosus), and in nitrate and ammonium to determine the relative importance of anthropogenic versus natural sources of nitrogen along the coast of NW Spain. Both algal species and nitrogen sources showed similar isotopic enrichment for a given site, but algal δ15N was not related to either inorganic nitrogen concentrations or δ15N in the water samples. The latter suggests that inorganic nitrogen inputs are variable and do not always leave an isotopic trace in macroalgae. However, a significant linear decrease in macroalgal δ15N along the coast is consistent with the differential effect of upwelling. Besides this geographic variability, the influence of anthropogenic nitrogen sources is evidenced by higher δ15N in macroalgae from rias and estuaries compared to those from open coastal areas and in areas with more than 15x103 inhabitants in the watershed. These results indicate that, in contrast with other studies, macroalgal δ15Nis not simply related to either inorganic nitrogen concentrations or human population size but depends on other factors as the upwelling or the efficiency of local waste treatment systems.Plan nacional I+D+i, IEOPreprint3,258

    Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy

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    BACKGROUND: Cancer therapy-induced cardiomyopathy (CCM) is associated with cumulative drug exposures and preexisting cardiovascular disorders. These parameters incompletely account for substantial interindividual susceptibility to CCM. We hypothesized that rare variants in cardiomyopathy genes contribute to CCM. METHODS: We studied 213 patients with CCM from 3 cohorts: retrospectively recruited adults with diverse cancers (n=99), prospectively phenotyped adults with breast cancer (n=73), and prospectively phenotyped children with acute myeloid leukemia (n=41). Cardiomyopathy genes, including 9 prespecified genes, were sequenced. The prevalence of rare variants was compared between CCM cohorts and The Cancer Genome Atlas participants (n=2053), healthy volunteers (n=445), and an ancestry-matched reference population. Clinical characteristics and outcomes were assessed and stratified by genotypes. A prevalent CCM genotype was modeled in anthracycline-treated mice. RESULTS: CCM was diagnosed 0.4 to 9 years after chemotherapy; 90% of these patients received anthracyclines. Adult patients with CCM had cardiovascular risk factors similar to the US population. Among 9 prioritized genes, patients with CCM had more rare protein-altering variants than comparative cohorts ( P≤1.98e-04). Titin-truncating variants (TTNtvs) predominated, occurring in 7.5% of patients with CCM versus 1.1% of The Cancer Genome Atlas participants ( P=7.36e-08), 0.7% of healthy volunteers ( P=3.42e-06), and 0.6% of the reference population ( P=5.87e-14). Adult patients who had CCM with TTNtvs experienced more heart failure and atrial fibrillation ( P=0.003) and impaired myocardial recovery ( P=0.03) than those without. Consistent with human data, anthracycline-treated TTNtv mice and isolated TTNtv cardiomyocytes showed sustained contractile dysfunction unlike wild-type ( P=0.0004 and P<0.002, respectively). CONCLUSIONS: Unrecognized rare variants in cardiomyopathy-associated genes, particularly TTNtvs, increased the risk for CCM in children and adults, and adverse cardiac events in adults. Genotype, along with cumulative chemotherapy dosage and traditional cardiovascular risk factors, improves the identification of patients who have cancer at highest risk for CCM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01173341; AAML1031; NCT01371981.This work was supported in part by grants from the Instituto de Salud Carlos III (ISCIII) (PI15/01551, PI17/01941 and CB16/11/00432 to P.G-P. and L.A-P.), the Spanish Ministry of Economy and Competitiveness (SAF2015-71863-REDT to P.G-P.), the John S. LaDue Memorial Fellowship at Harvard Medical School (Y.K.), Wellcome Trust (107469/Z/15/Z to J.S.W.), Medical Research Council (intramural awards to S.A.C. and J.S.W; MR/M003191/1 to U.T), National Institute for Health Research Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London (P.J.B., S.A.C., J.S.W.), National Institute for Health Research Biomedical Research Centre at Imperial College London Healthcare National Health Service Trust and Imperial College London (D.O.R., S.A.C., S.P., J.S.W.), Sir Henry Wellcome Postdoctoral Fellowship (C.N.T.), Rosetrees and Stoneygate Imperial College Research Fellowship (N.W.), Fondation Leducq (S.A.C., C.E.S., J.G.S.), Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health (UK; HICF-R6-373; S.A.C., P.J.B., J.S. W.), the British Heart Foundation (NH/17/1/32725 to D.O.R.; SP/10/10/28431 to S.A.C), Alex’s Lemonade Stand Foundation (K.G.), National Institutes of Health (R.A.: U01CA097452, R01CA133881, and U01CA097452; Z.A.: R01 HL126797; B.K.: R01 HL118018 and K23-HL095661; J.G.S. and C.E.S.: 5R01HL080494, R01HL084553), and the Howard Hughes Medical Institute (C.E.S.). The Universitario Puerta de Hierro and Virgen de la Arrixaca Hospitals are members of the European Reference Network on Rare and Complex Diseases of the Heart (Guard-Heart; http://guard-heart.ern-net.eu). This publication includes independent research commissioned by the Health Innovation Challenge Fund (HICF), a parallel funding partnership between the Department of Health and Wellcome Trust. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe”.S

    Salud de los trabajadores

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    Actividad f&iacute;sica y su relaci&oacute;n con los factores de riesgo cardiovascular de carteros chilenosAn&aacute;lisis de resultados: riesgos psicosociales en el trabajo Suceso-Istas 21 en Cesfam Quell&oacute;nAusentismo laboral por enfermedades oftalmol&oacute;gicas, Chile 2009Brote de diarreas por norovirus, posterremoto-tsunami, Constituci&oacute;n, Regi&oacute;n del MauleCalidad de vida en profesionales de la salud p&uacute;blica chilenaCaracterizaci&oacute;n del reposo laboral en personal del SSMN durante el primer semestre de 2010Concentraci&oacute;n de nicotina en pelo en trabajadores no fumadores expuestos a humo de tabaco ambientalCondiciones de trabajo y bienestar/malestar docente en profesores de ense&ntilde;anza media de SantiagoDisfunci&oacute;n auditiva inducida por exposici&oacute;n a xilenoErgonom&iacute;a aplicada al estudio del s&iacute;ndrome de dolor lumbar en el trabajoEstimaci&oacute;n de la frecuencia de factores de riesgo cardiovascular en trabajadores de una empresa mineraExposici&oacute;n a plaguicidas inhibidores de la acetilcolinesterasa en Colombia, 2006-2009Factores de riesgo y da&ntilde;os de salud en conductores de una empresa peruana de transporte terrestre, 2009Las consecuencias de la cultura en salud y seguridad ocupacional en una empresa mineraPercepci&oacute;n de cambios en la pr&aacute;ctica m&eacute;dica y estrategias de afrontamientoPercepci&oacute;n de la calidad de vida en la Universidad del Biob&iacute;oPesos m&aacute;ximos aceptables para tareas de levantamiento manual de carga en poblaci&oacute;n laboral femeninaRiesgo coronario en trabajadores mineros seg&uacute;n la funci&oacute;n de Framingham adaptada para la poblaci&oacute;n chilenaTrastornos emocionales y riesgo cardiovascular en trabajadores de la salu

    Allergic Rhinitis and its Impact on Asthma (ARIA) Guidelines - 2016 Revision

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    BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment
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