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Background This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). Methods Patients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). Results The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). Conclusions This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6–12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. Clinical trial registration ClinicalTrials.gov, number NCT01379989.

Background Spatially-resolved transcriptomics has now enabled the quantification of high-throughput and transcriptome-wide gene expression in intact tissue while also retaining the spatial coordinates. Incorporating the precise spatial mapping of gene activity advances our understanding of intact tissue-specific biological processes. In order to interpret these novel spatial data types, interactive visualization tools are necessary. Results We describe spatialLIBD, an R/Bioconductor package to interactively explore spatially-resolved transcriptomics data generated with the 10x Genomics Visium platform. The package contains functions to interactively access, visualize, and inspect the observed spatial gene expression data and data-driven clusters identified with supervised or unsupervised analyses, either on the user’s computer or through a web application. Conclusions spatialLIBD is available at https://bioconductor.org/packages/spatialLIBD. It is fully compatible with SpatialExperiment and the Bioconductor ecosystem. Its functionality facilitates analyzing and interactively exploring spatially-resolved data from the Visium platform.

Este libro nos pone al día en tres grandes bloques, uno inicial donde se aborda el estado del conocimiento tanto desde la perspectiva biótica como física de la cuenca, la geología, hidrología, sedimentología y su relación con los ecosistemas y la biodiversidad acuática; los peces, su diversidad taxonómica y genética, ecología e historias de vida y los servicios ecosistémicos que brindan como recursos pesqueros. En la segunda parte se consideran los conflictos ambientales en la cuenca, desde temas como la contaminación y la modificación del hábitat; los peces introducidos (exóticos y trasplantados y la “presión” de una demanda cada vez mayor de la pesca. En la sección tercera, tras una interpretación concienzuda de los capítulos anteriores y el conocimiento de los investigadores, se hace un análisis detallado de todas las amenazas, así como las estrategias de conservación y manejo del recurso íctico. Todo ello, sienta las bases para una serie de recomendaciones para la toma de decisiones que son recogidas al final de la obra.

En este capítulo se identifican y describen los servicios ecosistémicos generados por las poblaciones de peces en la cuenca del río Magdalena. En lo concerniente a los servicios de aprovisionamiento se valora la pesca artesanal, junto con sus beneficios como el aporte al empleo y a la seguridad alimentaria, presentándose conjuntamente aspectos relacionados con servicios de abastecimiento relacionados con pesca recreativa y deportiva, recursos genéticos y piscicultura. En cuanto a los servicios de regulación y mantenimiento, se describen los aportes a la regulación en la dinámica de la red trófica y el balance de nutrientes, a la reducción de contaminantes, a la transformación de materia orgánica en los sistemas de interacción peces-hábitat, bioturbación, transporte de los nutrientes-carbón-minerales, energía y la dispersión de semillas, junto con control biológico de plagas y enfermedades tropicales. Con relación a los servicios culturales se contemplan los relacionados con interacciones físicas e intelectuales asociados con la demanda para la educación e información y conocimiento local, y aquellos asociados con interacciones espirituales y simbólicas. Se concluye que el grado de desarrollo actual del conocimiento en la cuenca subestima los servicios ecosistémicos brindados por los peces, se enfatiza en la necesidad de modificar los paradigmas de manejo tradicional y se presentan recomendaciones para propender por su materialización.

The mitochondrial ATP synthase emerges as key hub of cellular functions controlling the production of ATP, cellular signaling, and fate. It is regulated by the ATPase inhibitory factor 1 (IF1), which is highly abundant in neurons. Herein, we ablated or overexpressed IF1 in mouse neurons to show that IF1 dose defines the fraction of active/inactive enzyme in vivo, thereby controlling mitochondrial function and the production of mitochondrial reactive oxygen species (mtROS). Transcriptomic, proteomic, and metabolomic analyses indicate that IF1 dose regulates mitochondrial metabolism, synaptic function, and cognition. Ablation of IF1 impairs memory, whereas synaptic transmission and learning are enhanced by IF1 overexpression. Mechanistically, quenching the IF1-mediated increase in mtROS production in mice overexpressing IF1 reduces the increased synaptic transmission and obliterates the learning advantage afforded by the higher IF1 content. Overall, IF1 plays a key role in neuronal function by regulating the fraction of ATP synthase responsible for mitohormetic mtROS signaling.

To evaluate the effectiveness of an integrated emergency department (ED)/hospital at home (HH) medical care model in mild COVID-19 pneumonia and evaluate baseline predictors of major outcomes and potential savings. Retrospective cohort study with patients evaluated for COVID-19 pneumonia in the ED, from March 3 to April 30, 2020. All of them were discharged home and controlled by HH. The main outcomes were ED revisit and the need for deferred hospital admission (protocol failure). Outcome predictors were analyzed by simple logistic regression model (OR; 95% CI). Potential savings of this medical care model were estimated. Of the 377 patients attended in the ED, 109 were identified as having mild pneumonia and were included in the ED/HH medical care model. Median age was 50.0 years, 52.3% were males and 57.8% had Charlson index = 1. The median HH stay was 8 (IQR 3.7-11) days. COVID-19-related ED revisit was 19.2% (n = 21) within 6 days (IQR 3-12.5) after discharge from ED. Overall protocol failure (deferred hospital admission) was 6.4% (n = 7), without ICU admission. The ED/HH model provided potential cost savings of 77% compared to traditional stay, due to the costs of home care entails 23% of the expenses generated by a conventional hospital stay. 789 days of hospital stay were avoided by HH, rather than hospital admission. An innovative ED/HH model for selected patients with mild COVID-19 pneumonia is feasible, safe and effective. Less than 6.5% of patients requiring deferred hospital admission and potential savings were generated due to hospitalization.

Charcot-Marie-Tooth (CMT) disease is a neuropathy that lacks effective therapy. CMT patients show degeneration of peripheral nerves, leading to muscle weakness and loss of proprioception. Loss of mitochondrial oxidative phosphorylation proteins and enzymes of the antioxidant response accompany degeneration of nerves in skin biopsies of CMT patients. Herein, we followed a drug-repurposing approach to find drugs in a Food and Drug Administration-approved library that could prevent development of CMT disease in the Gdap1-null mouse model. We found that the antibiotic florfenicol is a mitochondrial uncoupler that prevents the production of reactive oxygen species and activates respiration in human GDAP1-knockdown neuroblastoma cells and in dorsal root ganglion neurons of Gdap1-null mice. Treatment of CMT-affected Gdap1-null mice with florfenicol has no beneficial effect in the course of the disease. However, administration of florfenicol, or the antioxidant MitoQ, to pre-symptomatic GDAP1-null mice prevented weight gain and ameliorated the motor coordination deficiencies that developed in the Gdap1-null mice. Interestingly, both florfenicol and MitoQ halted the decay in mitochondrial and redox proteins in sciatic nerves of Gdap1-null mice, supporting that oxidative damage is implicated in the etiology of the neuropathy. These findings support the development of clinical trials for translation of these drugs for treatment of CMT patients.

Objective. To analyze clinical, laboratory, and radiologic findings and final health outcomes in patients with pulmonary embolism and coronavirus disease 2019 (COVID-19). To compare them to findings and outcomes in patients with pulmonary embolism without COVID-19. Methods. Multicenter, observational, retrospective study in 4 Spanish hospital emergency departments (EDs) from January 15 to April 15, 2020. Cases were located by reviewing all ED requests for pulmonary computed tomography angiography (CTA) procedures. Clinical, laboratory, and radiologic findings; medical histories and comorbidity; risk factors; and outcomes were compared between the 2 groups of patients (with or without COVID-19). Results. A total of 399 CTAs were ordered; 88 pulmonary embolisms were diagnosed, 28 of them (32%) in patients with COVID-19. This group had more men, and a history of thromboembolic disease was more common. We found no between-group differences in clinical presentation, laboratory, or radiologic findings; nor were there differences in final outcomes. In-hospital mortality was 7% (2 cases) in patients with COVID-19 and 17% (10 cases) in patients without the virus (odds ratio for death in patients with pulmonary embolism and COVID-19, 0.38; 95% CI, 0.08-1.89). Conclusions. We found no clinically important differences in the clinical, laboratory, or radiologic findings between patients with or without COVID-19 who were treated for pulmonary embolism in our hospital EDs. Final outcomes also did not differ.

PET/CT (Positron Emission Tomography/Computed Tomography) is widely used in nodal and metastatic staging of lung cancer patients.To analyze PET/CT detection of metastatic disease in patients with lung cancer.We reviewed retrospectively F18Fluorodeoxyglucose PET/CT scans performed between December 2008 and December 2013. We selected 143 patients aged 30 to 92 years (63% males) with confirmed lung cancer referred for staging, with no previous treatment. We reviewed whole body PET/CT and brain magnetic resonance images. SUVmax (Standardized Uptake Value maximum) of primary pulmonary lesion, hilar/mediastinal nodes, and distant metastases were calculated.Histological types encountered were adenocarcinoma in 55%, squamous-cell in 15%, small-cell in 8%, large-cell in 6% and adeno-squamous in 2%. In 22 cases (15%) histology was not available. Nodal involvement was observed in 60% of patients (44% hilar and 48% mediastinal). Skip metastases (mediastinal involvement without hilum involvement) were encountered in 17% of cases, and were significantly more common among high uptake lung tumors (p0.01). Best SUVmax cut-off for node involvement was 4.4 for hilum and 4.0 for mediastinum (sensibility: 86.4%, specificity: 99.8%). Sixty six patients (46.2%) showed distant metastases on PET/CT. The most common metastases were osseous in 22%, adrenal in 16%, hepatic in14%, pulmonary in 14% and cerebral in 12%. PET/CT detected a second unexpected synchronic cancer in eight patients (6%).PET/CT is accurate for nodal staging using an uptake index as SUVmax. Distant metastases are common, especially in bone, adrenal glands and liver.

This article documents the addition of 268 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Alburnoidesbipunctatus, Chamaeropshumilis, Chlidoniashybrida, Cyperuspapyrus, Fusariumgraminearum, Loxigillabarbadensis, Macrobrachiumrosenbergii, Odontesthesbonariensis, Pelteobagrusvachelli, Posidoniaoceanica, Potamotrygonmotoro, Rhamdia quelen, Sarotherodonmelanotheron heudelotii, Sibiraeaangustata, Takifugurubripes, Tarentolamauritanica, Trimmatostroma sp. and Wallagoattu. These loci were cross-tested on the following species: Alburnoides fasciatus, Alburnoides kubanicus, Alburnoides maculatus, Alburnoides ohridanus, Alburnoides prespensis, Alburnoides rossicus, Alburnoides strymonicus, Alburnoides thessalicus, Alburnoides tzanevi, Carassius carassius, Fusarium asiaticum, Leucaspius delineatus, Loxigilla noctis dominica, Pelecus cultratus, Phoenix canariensis, Potamotrygon falkneri, Trachycarpus fortune and Vimba vimba.

The turbot ( Scophthalmus maximus ) is a highly appreciated European aquaculture species. As farming of turbot is growing as an aqua culture enterprise, the identification of genetic regions responsible for economically import ant traits might be importance for future aquaculture of turbot. The sex-determining systems of fish appear to be at a primitive stage of evolution and display an amazing diversity, includi ng male heterogametic, female heterogametic, and temperature dependent systems. F emales of this species reach commercial size 4-6 months before than males, thus the interes t of industry in obtaining all-female populations. Neither mitotic nor meiotic chromosome s have shown sex-associated heteromorphisms in turbot, but the main sex determi ning region of turbot was identified after a detailed QTL and marker association analysis. Her e we describe the construction and characterization of a bacterial artificial chromoso me (BAC) library from turbot and the identification of clones containing genes related t o the sex determining region and to the gonadal differentiation process. The BAC library wa s constructed from the genomic DNA of a highly inbred individual using the vector pIndigo BAC536. The large, high-quality inserts showed a size of at least 100 kb and

Ponencia presentada en el II Seminário Ibérico "Mudança Global na Península Ibérica. Uma visão integrada" celebrado en Lisboa (Portugal) del 4 al 5 de septiembre de 2010, La proximidad geográfica de dos especies del género Abies (A. alba y A. pinsapo) en la Península Ibérica, con evidentes divergencias ecológicas y taxonómicas, constituye a día de hoy un enigma biogeográfico y paleobotánico aún sin resolver. En la actualidad, A. alba se localiza exclusivamente en cuadrante Nororiental de la península (Pirineos) exhibiendo un patrón fisiográfico de bosque templado; y A. pinsapo ocupa tan sólo la fracción occidental de las Cordilleras Béticas (Sur peninsular) bajo condiciones climáticas de estacionalidad mediterránea.

A phytogeographic approach of Abies alba Mill. populations in the Spanish side of the Pyrenees Range is provided. The methodology is based on >Species distribution models> (SDMs) and palaeopalynological Quaternary records from Pyrenees. Articulating the results derived from the SDMs (topo-climatic perspective), and a review of the Quaternary fossil record (climate and anthropic approach), we try to build a historical understanding of the dynamics of these forests. Both tools reveal that Abies alba only occupy a small proportion of their potential distribution range (30%) and offer geographic evidence demonstrating that these populations had a wider altitudinal distribution in the past. We suggest the use of SDMs to reinforce assumptions about the Quaternary distribution of the Iberian Abies alba forest, and to locate refugia for the long-term persistence., Este trabajo se ha visto beneficiado por la financiación de los siguientes proyectos: Programa Consolider TCP-CSD2007-00058 (Programa de Investigación en Tecnologías para la valoración y conservación del Patrimonio Cultural) y HAR2008-06477-C03-03/HIST (Plan Nacional de I+D+i, Ministerio de Educación y Ciencia).

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Short- and long-term actions of the steroids corticosterone, progesterone, and ecdysterone were analyzed upon excitability of crayfish retinular cells. The three hormones showed short-term actions, particularly during photoreceptor dark adaptation; effects were found to be dependent on the hour of the day. Corticosterone and progesterone had similar effects, i.e., resembled dark-adapted conditions; ecdysterone actions were opposite and resembled light adaptation. Long-term effects were opposed to short-term effects in all cases. Possible mechanisms underlying these effects are discussed.

The electromagnetic radiation emitted when a beam of electrons crosses a periodic stratified medium with a constant velocity is discussed. The treatment is valid for radiation wavelengths of the order of the period of the structure, particularly when Bragg reflections can take place. It accounts globally for the /hacek C/erenkov emission, the resonant transition radiation, and the Bragg resonances.

Obstructive anuria does not necessarily show a marked dilatation of the urinary tract on evaluation with imaging techniques. A case with acute renal failure of this type is presented. We discuss why this condition is caused and how diagnosis can be made quickly. Likewise, we discuss the length of time we can defer renal diversion before rupture of the collecting system supervenes and, consequently, urinary extravasation.

Analysis of the morphological and genetic differences in the skin response to injury between Turbot and Brill. info:eu-repo/semantics/publishedVersion

Background: The open-label, single-arm, multicenter ORZORA trial (NCT02476968) evaluated the efficacy and safety of maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSR OC) who had tumor BRCA mutations (BRCAm) of germline (g) or somatic (s) origin or non-BRCA homologous recombination repair mutations (HRRm) and were in response to their most recent platinum-based chemotherapy after ≥2 lines of treatment. Methods: Patients received maintenance olaparib capsules (400mg twice daily) until disease progression. Prospective central testing at screening determined tumor BRCAm status and subsequent testing determined gBRCAm or sBRCAm status. Patients with predefined non-BRCA HRRm were assigned to an exploratory cohort. The co-primary endpoints were investigator-assessed progression-free survival (PFS; modified Response Evaluation Criteria in Solid Tumors v1.1) in BRCAm and sBRCAm cohorts. Secondary endpoints included health-related quality of life (HRQoL) and tolerability. Results: 177 patients received olaparib. At the primary data cut-off (17 April 2020), the median follow-up for PFS in the BRCAm cohort was 22.3months. The median PFS (95% CI) in BRCAm, sBRCAm, gBRCAm and non-BRCA HRRm cohorts was 18.0 (14.3-22.1), 16.6 (12.4-22.2), 19.3 (14.3-27.6) and 16.4 (10.9-19.3) months, respectively. Most patients with BRCAm reported improvements (21.8%) or no change (68.7%) in HRQoL and the safety profile was as expected. Conclusions: Maintenance olaparib had similar clinical activity in PSR OC patients with sBRCAm and those with any BRCAm. Activity was also observed in patients with a non-BRCA HRRm. ORZORA further supports use of maintenance olaparib in all patients with BRCA-mutated, including sBRCA-mutated, PSR OC.