Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing

Antiviral resistance; Solid organ transplant; Next-generation sequencingResistencia a los antivirales; Trasplante de órganos sólidos; Secuenciación de próxima generaciónResistència als antivirals; Trasplantament d'òrgans sòlids; Seqüenciació de pròxima generacióOBJETIVES: The aim of this study was to identify CMV drug resistance mutations (DRM) in solid organ transplant (SOT) recipients with suspected resistance comparing next-generation sequencing (NGS) with Sanger sequencing and assessing risk factors and the clinical impact of resistance. METHODS: Using Sanger sequencing as the reference method, we prospectively assessed the ability of NGS to detect CMV DRM in the UL97 and UL54 genes in a nationwide observational study from September 2013 to August 2016. RESULTS: Among 44 patients recruited, 14 DRM were detected by Sanger in 12 patients (27%) and 20 DRM were detected by NGS, in 16 (36%). NGS confirmed all the DRM detected by Sanger. The additional six mutations detected by NGS were present in <20% of the sequenced population, being located in the UL97 gene and conferring high-level resistance to ganciclovir. The presence of DRM by NGS was associated with lung transplantation (p = 0.050), the administration of prophylaxis (p = 0.039), a higher mean time between transplantation and suspicion of resistance (p = 0.038) and longer antiviral treatment duration before suspicion (p = 0.024). However, the latter was the only factor independently associated with the presence of DRM by NGS in the multivariate analysis (OR 2.24, 95% CI 1.03 to 4.87). CONCLUSIONS: NGS showed a higher yield than Sanger sequencing for detecting CMV resistance mutations in SOT recipients. The presence of DRM detected by NGS was independently associated with longer antiviral treatment.The present study was funded by Agency for Health Technology Assessment and Research and Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (PS12/02131 and PI17/02150) and by the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, FI-DGR 2017, Grant No. 00794), which is supported by the Secretaria d'Universitats i Recerca (Economy and Knowledge Department, Generalitat de Catalunya), and co-funded by the European Social Fund and by Fundacio Marato TV3 project (201824). The study sponsor had no role in the collection, analysis, or interpretation of the data

Revisión bibliográfica de implantología bucofacial del año 2007

Se expone una revisión de la literatura científica publicada en revistas indexadas durante el año 2007 sobre Implantología Bucofacial. La escasez de tiempo de que disponen los profesionales para consultar las múltiples fuentes de información, ha motivado a los autores a resumir los artículos publicados y clasificarlos en los siguientes apartados: generalidades, pacientes especiales, superficies y diseños, tejidos blandos, implantes inmediatos, carga inmediata, complicaciones, elevación sinusal, técnicas avanzadas, plasma rico en plaquetas y factores de crecimiento, cirugía guiada, cirugía mínimamente invasiva y miniimplantes, con la intención de facilitar una puesta al día

Dense matter with eXTP

In this White Paper we present the potential of the Enhanced X-ray Timing and Polarimetry (eXTP) mission for determining the nature of dense matter; neutron star cores host an extreme density regime which cannot be replicated in a terrestrial laboratory. The tightest statistical constraints on the dense matter equation of state will come from pulse profile modelling of accretion-powered pulsars, burst oscillation sources, and rotation-powered pulsars. Additional constraints will derive from spin measurements, burst spectra, and properties of the accretion flows in the vicinity of the neutron star. Under development by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Science, the eXTP mission is expected to be launched in the mid 2020s.Comment: Accepted for publication on Sci. China Phys. Mech. Astron. (2019

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study

Background. We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. Methods. From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. Results. The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered ?high risk? for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid?related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. Conclusions. The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid?related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1(3 release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Low growth resilience to drought is related to future mortality risk in trees

Severe droughts have the potential to reduce forest productivity and trigger tree mortality. Most trees face several drought events during their life and therefore resilience to dry conditions may be crucial to long-term survival. We assessed how growth resilience to severe droughts, including its components resistance and recovery, is related to the ability to survive future droughts by using a tree-ring database of surviving and now-dead trees from 118 sites (22 species, >3,500 trees). We found that, across the variety of regions and species sampled, trees that died during water shortages were less resilient to previous non-lethal droughts, relative to coexisting surviving trees of the same species. In angiosperms, drought-related mortality risk is associated with lower resistance (low capacity to reduce impact of the initial drought), while it is related to reduced recovery (low capacity to attain pre-drought growth rates) in gymnosperms. The different resilience strategies in these two taxonomic groups open new avenues to improve our understanding and prediction of drought-induced mortality.Fil: DeSoto, Lucía. Consejo Superior de Investigaciones Científicas; España. Universidad de Coimbra; PortugalFil: Cailleret, Maxime. Eidgenössische Technische Hochschule Züric; Suiza. Université Aix-marseille; Francia. Swiss Federal Institute for Forest, Snow and Landscape Research; SuizaFil: Sterck, Frank. University of Agriculture Wageningen; Países BajosFil: Jansen, Steven. Universitat Ulm; AlemaniaFil: Kramer, Koen. University of Agriculture Wageningen; Países Bajos. Land Life Company; Países BajosFil: Robert, Elisabeth M. R.. Creaf; España. Vrije Unviversiteit Brussel; Bélgica. Royal Museum for Central Africa; BélgicaFil: Aakala, Tuomas. University of Helsinki; FinlandiaFil: Amoroso, Mariano Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural. - Universidad Nacional de Rio Negro. Instituto de Investigaciones en Recursos Naturales, Agroecología y Desarrollo Rural; ArgentinaFil: Bigler, Christof. Eidgenössische Technische Hochschule Züric; SuizaFil: Camarero, J. Julio. Consejo Superior de Investigaciones Científicas; EspañaFil: Čufar, Katarina. University 0f Ljubljana; EsloveniaFil: Gea Izquierdo, Guillermo. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria; EspañaFil: Gillner, Sten. Technische Universität Dresden; AlemaniaFil: Haavik, Laurel J.. Servicio Forestal de los Estados Unidos; Estados UnidosFil: Hereş, Ana Maria. Basque Centre For Climate Change; España. Transilvania University of Brasov; RumaniaFil: Kane, Jeffrey M.. Humboldt State University; Estados UnidosFil: Kharuk, Vyacheslav I.. Siberian Federal University; Rusia. Siberian Division of the Russian Academy of Sciences; RusiaFil: Kitzberger, Thomas. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Klein, Tamir. Weizmann Institute of Science; IsraelFil: Levanič, Tom. Slovenian Forestry Institute; EsloveniaFil: Linares, Juan C.. Universidad Pablo de Olavide; EspañaFil: Mäkinen, Harri. Natural Resources Institute Finland; FinlandiaFil: Oberhuber, Walter. Universidad de Innsbruck; AustriaFil: Papadopoulos, Andreas. Geoponiko Panepistimion Athinon; GreciaFil: Rohner, Brigitte. Eidgenössische Technische Hochschule Zürich; Suiza. Swiss Federal Institute for Forest, Snow and Landscape Research; SuizaFil: Sangüesa Barreda, Gabriel. Universidad de Valladolid; EspañaFil: Stojanovic, Dejan B.. University of Novi Sad; SerbiaFil: Suarez, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Villalba, Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Martínez Vilalta, Jordi. Universitat Autònoma de Barcelona; España. Creaf; Españ

Twitter as a Tool for Teaching and Communicating Microbiology: The #microMOOCSEM Initiative

Online social networks are increasingly used by the population on a daily basis. They are considered a powerful tool for science communication and their potential as educational tools is emerging. However, their usefulness in academic practice is still a matter of debate. Here, we present the results of our pioneering experience teaching a full Basic Microbiology course via Twitter (#microMOOCSEM), consisting of 28 lessons of 40-45 minutes duration each, at a tweet per minute rate during 10 weeks. Lessons were prepared by 30 different lecturers, covering most basic areas in Microbiology and some monographic topics of general interest (malaria, HIV, tuberculosis, etc.). Data analysis on the impact and acceptance of the course were largely affirmative, promoting a 330% enhancement in the followers and a >350-fold increase of the number of visits per month to the Twitter account of the host institution, the Spanish Society for Microbiology. Almost one third of the course followers were located overseas. Our study indicates that Massive Online Open Courses (MOOC) via Twitter are highly dynamic, interactive, and accessible to great audiences, providing a valuable tool for social learning and communicating science. This strategy attracts the interest of students towards particular topics in the field, efficiently complementing customary academic activities, especially in multidisciplinary areas like Microbiology.Versión del edito

Forest and woodland replacement patterns following drought-related mortality

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern post drought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services.Peer reviewe

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period