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Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.
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Epilepsia , Microglía , Humanos , Encéfalo , Convulsiones/tratamiento farmacológicoRESUMEN
Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.
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Cyanobacterial blooms imperil the use of freshwater around the globe and present challenges for water management. Studies have suggested that blooms are trigged by high temperatures and nutrient concentrations. While the roles of nitrogen and phosphorus have long been debated, cyanobacterial dominance in phytoplankton has widely been associated with climate warming. However, studies at large geographical scales, covering diverse climate regions and lake depths, are still needed to clarify the drivers of cyanobacterial success. Here, we analyzed data from 464 lakes covering a 14,000 km north-south gradient in the Americas and three lake depth categories. We show that there were no clear trends in cyanobacterial biomass (as biovolume) along latitude or climate gradients, with the exception of lower biomass in polar climates. Phosphorus was the primary resource explaining cyanobacterial biomass in the Americas, while nitrogen was also significant but particularly relevant in very shallow lakes (< 3 m depth). Despite the assessed climatic gradient water temperature was only weakly related to cyanobacterial biomass, suggesting it is overemphasized in current discussions. Depth was critical for predicting cyanobacterial biomass, and shallow lakes proved more vulnerable to eutrophication. Among other variables analyzed, only pH was significantly related to cyanobacteria biomass, likely due to a biologically mediated positive feedback under high nutrient conditions. Solutions toward managing harmful cyanobacteria should thus consider lake morphometric characteristics and emphasize nutrient control, independently of temperature gradients, since local factors are more critical - and more amenable to controls - than global external forces.
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Cianobacterias , Biomasa , Lagos , Nutrientes , Nitrógeno , FósforoRESUMEN
The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Index (CCI), C-reactive protein (CRP), CAC (COVID-19-associated coagulopathy), defined according to the ISTH score, treatment and in-hospital events were collected. Between March and April 2020, 331 COVID-19 patients were enrolled, 72 of them (21.8%) with myocardial injury. Patients with myocardial injury showed a higher CCI score (median (interquartile range), 5 (4-7) vs. 2 (1-4), p = 0.001), higher CRP values (18.3 (9.6-25.9) mg/dL vs. 12.0 (5.4-19.4) mg/dL, p Ë 0.001) and CAC score (1 (0-2) vs. 0 (0-1), p = 0.001), and had lower use of any anticoagulant (57 patients (82.6%) vs. 229 patients (90.9%), p = 0.078), than those without. In the adjusted logistic regression, CRP, myocardial injury, CCI and CAC score were positive independent predictors of mortality, whereas anticoagulants resulted as a protective factor. Myocardial injury in COVID-19 patients is associated with inflammation and coagulopathy, resulting in a worse in-hospital prognosis. Treatment with anticoagulant agents may help to improve in-hospital outcomes.
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The increasing occurrence of cyanobacterial blooms worldwide represents an important threat for both the environment and public health. In this context, the development of risk analysis and management tools as well as sustainable and cost-effective treatment processes is essential. The research project TALGENTOX, funded by the Ibero-American Science and Technology Program for Development (CYTED-2019), aims to address this ambitious challenge in countries with different environmental and social conditions within the Ibero-American context. It is based on a multidisciplinary approach that combines ecology, water management and technology fields, and includes research groups from Chile, Colombia, Mexico, Peru and Spain. In this review, the occurrence of toxic cyanobacteria and cyanotoxins in freshwaters from these countries are summarized. The presence of cyanotoxins has been confirmed in all countries but the information is still scarce and further monitoring is required. In this regard, remote sensing or metagenomics are good alternatives at reasonable cost. The risk management of freshwaters from those countries considering the most frequent uses (consumption and recreation) has been also evaluated. Only Spain and Peru include cyanotoxins in its drinking water legislation (only MC-LR) and thus, there is a need for regulatory improvements. The development of preventive strategies like diminishing nutrient loads to aquatic systems is also required. In the same line, corrective measures are urgently needed especially in drinking waters. Advanced Oxidation Processes (AOPs) have the potential to play a major role in this scenario as they are effective for the elimination of most cyanotoxins classes. The research on the field of AOPs is herein summarized considering the cost-effectiveness, environmental character and technical applicability of such technologies. Fenton-based processes and photocatalysis using solar irradiation or LED light represent very promising alternatives given their high cost-efficiency. Further research should focus on developing stable long-term operation systems, addressing their scale-up.
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Cianobacterias , Agua Dulce , Chile , Colombia , Agua Dulce/análisis , México , Microcistinas , Perú , Gestión de Riesgos , España , Tecnología , Estados UnidosRESUMEN
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20151-x.
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Properties of semiconductors are largely defined by crystal imperfections including native defects. Van der Waals (vdW) semiconductors, a newly emerged class of materials, are no exception: defects exist even in the purest materials and strongly affect their electrical, optical, magnetic, catalytic and sensing properties. However, unlike conventional semiconductors where energy levels of defects are well documented, they are experimentally unknown in even the best studied vdW semiconductors, impeding the understanding and utilization of these materials. Here, we directly evaluate deep levels and their chemical trends in the bandgap of MoS2, WS2 and their alloys by transient spectroscopic study. One of the deep levels is found to follow the conduction band minimum of each host, attributed to the native sulfur vacancy. A switchable, DX center - like deep level has also been identified, whose energy lines up instead on a fixed level across different hosts, explaining a persistent photoconductivity above 400 K.
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Dyslipidemia and inflammation exacerbate postprandial metabolic stress in people with diabetes. Acute dietary supplementation with polyphenols shows promise in improving postprandial metabolic stress in type 2 diabetes (T2D). Cocoa is a rich source of dietary polyphenols with demonstrated cardioprotective effects in adults without diabetes. To date, the acute effects of cocoa on postprandial lipids and inflammation have received little attention in the presence of T2D. This report expands on our earlier observation that polyphenol-rich cocoa, given as a beverage with a fast-food-style, high-fat breakfast, increased postprandial high-density lipoprotein-cholesterol (HDL-C) in adults with T2D. We now test whether polyphenol-rich cocoa modulated postprandial apolipoproteins (Apo-A1, B), non-esterified fatty acids, nuclear magnetic resonance (NMR)-derived lipoprotein subclass profiles, and select biomarkers of inflammation following the same dietary challenge. We found that cocoa decreased NMR-derived concentrations of total very low-density lipoprotein and chylomicron particles and increased the concentration of total HDL particles over the 6-hour postprandial phase. Serum interleukin-18 was decreased by cocoa vs. placebo. Thus, polyphenol-rich cocoa may alleviate postprandial dyslipidemia and inflammation following a high-fat dietary challenge in adults with T2D. The study was registered at clinicaltrials.gov as NCT01886989.
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Chocolate , Diabetes Mellitus Tipo 2/metabolismo , Grasas de la Dieta , Lipoproteínas , Periodo Posprandial/efectos de los fármacos , Biomarcadores/sangre , Biomarcadores/metabolismo , Dieta Alta en Grasa , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/metabolismo , Método Doble Ciego , Femenino , Humanos , Inflamación/metabolismo , Lipoproteínas/sangre , Lipoproteínas/clasificación , Lipoproteínas/metabolismo , Masculino , Persona de Mediana Edad , Preparaciones de Plantas/farmacologíaRESUMEN
Polymeric complex coacervation occurs when two oppositely charged polyelectrolytes undergo an associative phase separation in aqueous salt solution, resulting in a polymer-dense coacervate phase and a polymer-dilute supernatant phase. This phase separation process represents a powerful way to tune polymer solutions using electrostatic attraction and is sensitive to environmental conditions such as salt concentration and valency. One area of particular research interest is using this to create nanoscale polymer assemblies, via (for example) block copolymers with coacervate-forming blocks. The key to understanding coacervate-driven assembly is the formation of the interface between the coacervate and supernatant phases and its corresponding thermodynamics. In this work, we use recent advances in coacervate simulation and theory to probe the nature of the coacervate-supernatant interface. First, we show that self-consistent field theory informed by either Monte-Carlo simulations or transfer matrix theories is capable of reproducing interfacial features present in large-scale molecular dynamics simulations. The quantitative agreement between all three methods gives us a way to efficiently explore interfacial thermodynamics. We show how salt affects the interface, and we find qualitative agreement with literature measurements of interfacial tension. We also explore the influence of neutral polymers, which we predict to drastically influence the phase behavior of coacervates. These neutral polymers can significantly alter the interfacial tension in coacervates; this has a profound effect on the design and understanding of coacervate-driven self-assembly, where the equilibrium structure is tied to interfacial properties.
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Por medio de esta revisión, se busca realizar un recuento y una explicación sobre el entorno de intercambio bibliográfico BibFrame a partir del conocimiento que ha sido diseminado, en su mayor parte, por un grupo de profesionales de la Biblioteca del Congreso de los Estados Unidos de América. En este trabajo, se muestran aspectos clave de esta iniciativa en y se enfocan cuestiones medulares de su funcionamiento como entorno ubicado en la web. Se discute su posible normalización partiendo del traslado de MARC21 a esta herramienta.
This review aims to report on and explain the bibliographic exchange environment BibFrame taking as starting point the knowledge that has been disseminated, mainly, by a group of professionals from the Library Of Congress of the United States of America. This work shows key aspects of this initiative and focus on medular points regarding its functioning as a web environment. The work discusses the possible standardization of this environment, starting with transferring from MARC21 to this tool.
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OBJECT: A spinal epidural abscess (SEA) is rare but potentially devastating if not diagnosed early. Unfortunately, diagnostic delays and associated neurological deficits are common. The objectives of this analysis were to explore the use of a novel clinical decision guideline to screen patients who present to the emergency department (ED) with spine pain for SEA and to determine the diagnostic test characteristics of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in patients at risk for SEA. METHODS: This was a prospective, cohort analysis comparing the incidence of diagnostic delays and presence of motor deficits at the time of diagnosis before and after implementation of a novel decision guideline using risk factor assessment followed by ESR and CRP testing prior to definitive imaging. A delay was defined as either multiple ED visits or admission to a nonsurgical service without a diagnosis of SEA. A 9-month substudy was performed in all patients who presented to the ED with spine pain so that the diagnostic test characteristics of the ESR and CRP level could be defined. RESULTS: A total of 55 patients with an SEA in the 9-year control period and 31 patients with an SEA in the 5-year study period were identified. Diagnostic delays were observed in 46 (83.6%) of 55 patients before guideline implementation versus 3 (9.7%) of 31 after guideline implementation (p < 0.001). Motor deficits were present at the time of diagnosis in 45 (81.8%) of 55 patients before guideline implementation versus 6 (19.4%) of 31 after guideline implementation (p < 0.001). The sensitivity and specificity of ESR in patients with an SEA risk factor were 100% and 67%, respectively. The receiver operating characteristic curve analysis revealed better test characteristics for ESR (area under curve 0.96) than for CRP (area under curve 0.81). CONCLUSIONS: A treatment guideline incorporating risk factor assessment followed by ESR and CRP testing was highly sensitive and moderately specific in identifying ED patients with SEA. A decrease in diagnostic delays and a lower incidence of motor deficits at the time of diagnosis was observed.
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Infecciones del Sistema Nervioso Central/diagnóstico , Servicio de Urgencia en Hospital , Absceso Epidural/diagnóstico , Dolor/diagnóstico , Guías de Práctica Clínica como Asunto , Adulto , Diagnóstico Tardío , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Diquat is a bipyridyl herbicide with nephrotoxic effects. This in vitro study demonstrates a colorimetric test for detection of diquat in human urine. Urine specimens using ten concentrations of diquat herbicide solution and controls for urine and glyphosate were prepared. A two-step assay (addition of bicarbonate followed by sodium dithionite) was performed, with a resulting color change of the original solution for each specimen. Color change intensity was noted immediately and after 30 min, by gross visual inspection. A green color with concentration-dependent intensity was detected in all specimens, in which concentrations of diquat solution ranged from 0.73 to 730 mg/L. This colorimetric effect disappeared after 30 min. The sodium bicarbonate/dithionite test may be useful as a qualitative bedside technique for the detection of urinary diquat in the appropriate clinical setting.
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Colorimetría , Diquat/envenenamiento , Diquat/orina , Herbicidas/envenenamiento , Herbicidas/orina , Sistemas de Atención de Punto , Biomarcadores/orina , Ditionita/química , Humanos , Intoxicación/diagnóstico , Intoxicación/orina , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Bicarbonato de Sodio/químicaRESUMEN
The ability to target gene deletion to a specific cellular compartment via the Cre/loxP system has been a powerful tool in the analysis of broadly expressed genes. Here, we report the generation of a transgenic mouse line in which expression of Cre-recombinase is under the regulatory control of the VE-Cadherin promoter. Temporal distribution and activity of the enzyme was evaluated with two independent Cre reporter lines. Histological analysis was performed throughout development and in the adult. Recombination of lox P sites with subsequent expression of beta-galactosidase or GFP was detected as early as E7.5 in endothelial cells of the yolk sac. Progressive staining of the embryonic vasculature was noted from E8.5-13.5; however, more contiguous reporter expression was only seen by E14.5 onward in all endothelial compartments including arteries, veins, and capillaries. In addition, we found Cre activity in lymphatic endothelial cells. Unlike other endothelial-specific Cre mice, this model showed expression in the adult quiescent vasculature. Furthermore, the constitutive nature of the VE-Cadherin promoter in the adult can be advantageous for analysis of gene deletion in pathological settings.