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Autoimmune and inflammatory diseases are highly complex, limiting treatment and the development of new therapies. Recent work has shown that cell-free DNA bound to biological microparticles is linked to systemic lupus erythematosus, a prototypic autoimmune disease. However, the heterogeneity and technical challenges associated with the study of biological particles have hindered a mechanistic understanding of their role. Our goal was to develop a well-controlled DNA-particle model system to understand how DNA-particle complexes affect cells. We first characterized the adsorption of DNA on the surface of polystyrene nanoparticles (200 nm and 2 µm) using transmission electron microscopy, dynamic light scattering, and colorimetric DNA concentration assays. We found that DNA adsorbed on the surface of nanoparticles was resistant to degradation by DNase 1. Macrophage cells incubated with the DNA-nanoparticle complexes had increased production of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). We probed two intracellular DNA sensing pathways, toll-like receptor 9 (TLR9) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), to determine how cells sense the DNA-nanoparticle complexes. We found that the cGAS-STING pathway is the primary route for the interaction between DNA-nanoparticles and macrophages. These studies provide a molecular and cellular-level understanding of DNA-nanoparticle-macrophage interactions. In addition, this work provides the mechanistic information necessary for future in vivo experiments to elucidate the role of DNA-particle interactions in autoimmune diseases, providing a unique experimental framework to develop novel therapeutic approaches.
Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , DNA , Fator de Necrose Tumoral alfa , NucleotidiltransferasesRESUMO
In this study was examined the response of carbon steel to atmospheric corrosion after one-year exposure in Valle de Aburrá, a subregion located in northwestern Colombia. The study involved the assessment of material mass loss and corrosion rate, the characterization of atmospheric aggressiveness, and the analysis of the morphology and composition of corrosion products in five different sites. Climatological and meteorological factors were assessed by testing for chloride content, sulfur dioxide levels, and time of wetness (TOW). The analysis of corrosion products was conducted using scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy. Based on corrosion rates, two sites exhibited a more aggressive environment, with a corrosivity category of C3, while the remaining sites were categorized as C2. The study confirmed the presence of lepidocrocite and goethite phases on the surface of carbon steel at all test sites. Data analysis revealed that both the TOW and the industrial activity significantly influence the corrosion of this metal.
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Blood pressure (BP) measurements obtained during a twenty-four-hour ambulatory blood pressure monitoring (24 h ABPM) have not been reliably applied to extract arterial hemodynamics. We aimed to describe the hemodynamic profiles of different hypertension (HT) subtypes derived from a new method for total arterial compliance (Ct) estimation in a large group of individuals undergoing 24 h ABPM. A cross-sectional study was conducted, which included patients with suspected HT. Cardiac output, Ct, and total peripheral resistance (TPR) were derived through a two-element Windkessel model without having a pressure waveform. Arterial hemodynamics were analyzed according to HT subtypes in 7434 individuals (5523 untreated HT and 1950 normotensive controls [N]). The individuals mean age was 46.2 ± 13.0 years; 54.8% were male, and 22.1% were obese. In isolated diastolic hypertension (IDH), the cardiac index (CI) was greater than that in normotensive (N) controls (CI: IDH vs. N mean difference 0.10 L/m/m2; CI 95% 0.08 to 0.12; p value <0.001), with no significant clinical difference in Ct. Isolated systolic hypertension (ISH) and divergent systolic-diastolic hypertension (D-SDH) had lower Ct values than nondivergent HT subtype (Ct: divergent vs. nondivergent mean difference -0.20 mL/mmHg; CI 95% -0.21 to -0.19 mL/mmHg; p value <0.001). Additionally, D-SDH displayed the highest TPR (TPR: D-SDH vs. N mean difference 169.8 dyn*s/cm-5; CI 95% 149.3 to 190.3 dyn*s/cm-5; p value <0.001). A new method is provided for the simultaneous assessment of arterial hemodynamics with 24 h ABPM as a single diagnostic tool, which allows a comprehensive assessment of arterial function for hypertension subtypes. Main hemodynamic findings in arterial HT subtypes with regard to Ct and TPR. The 24 h ABPM profile reflects the state of Ct and TPR. Younger individuals with IDH present with a normal Ct and frequently increased CO. Patients with ND-SDH maintain an adequate Ct with a higher TPR, while subjects with D-SDH present with a reduced Ct, high PP and high TPR. Finally, the ISH subtype occurs in older individuals with significantly reduced Ct, high PP and a variable TPR proportional to the degree of arterial stiffness and MAP values. There was an observed increase in PP with age in relation to the changes in Ct (see also text). SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; PP: pulse pressure; N: normotension; HT: hypertension; IDH: isolated diastolic hypertension; ND-SDH: nondivergent systole-diastolic hypertension; D-SDH: divergent systolic-diastolic hypertension; ISH: isolated systolic hypertension; Ct: total arterial compliance; TPR: total peripheral resistance; CO: cardiac output; 24 h ABPM: 24 h ambulatory blood pressure monitoring.
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Monitorização Ambulatorial da Pressão Arterial , Hipertensão , Humanos , Masculino , Idoso , Adulto , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Hipertensão/diagnóstico , Pressão Sanguínea , HemodinâmicaRESUMO
OBJECTIVE: To propose and validate a new method for estimating cardiac output based on the total arterial compliance (Ct) formula that does not need an arterial waveform and to apply it to brachial oscillometric blood pressure measurements (OBPMs). METHODS: One hundred subjects with normal heart anatomy and function were included. Reference values for cardiac output were measured with echocardiography, and Ct was calculated with a two-element Windkessel model. Then, a statistical model of arterial compliance (Ce) was used to estimate cardiac output. Finally, the measured and estimated cardiac output values were compared for accuracy and reproducibility. RESULTS: The model was derived from the data of 70 subjects and prospectively tested with the data from the remaining 30 individuals. The mean age of the whole group was 43.4 ± 12.8 years, with 46% women. The average blood pressure (BP) was 107.1/65.0 ± 15.0/9.6 mmHg and the average heart rate was 67.7 ± 11.4 beats/min. The average Ct was 1.39 ± 0.27 mL/mmHg and the average cardiac output was 5.5 ± 1.0 L/min. The mean difference in the cardiac output estimated by the proposed methodology vs. that measured by Doppler echocardiography was 0.022 L/min with an SD of 0.626 L/min. The intraclass correlation coefficient was 0.93, and the percentage error was 19%. CONCLUSION: Cardiac output could be reliably and noninvasively obtained with brachial OBPMs through a novel method for estimating Ct without the need for an arterial waveform. The new method could identify hemodynamic factors that explain BP values in an ambulatory care setting.
Assuntos
Artéria Braquial , Adulto , Pressão Sanguínea , Artéria Braquial/diagnóstico por imagem , Débito Cardíaco , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oscilometria , Reprodutibilidade dos TestesRESUMO
Growth factor independence-1 (GFI1) and GFI1B are closely related, yet differentially expressed transcriptional repressors with nearly identical DNA binding domains. GFI1 is upregulated in the earliest thymocyte precursors, while GFI1B expression is restricted to T lymphopoiesis stages coincident with activation. Transgenic expression of GFI1 potentiates T-cell activation, while forced GFI1B expression decreases activation. Both mice and humans with mutant Gfi1 display lymphoid abnormalities. Here we describe autoregulation of Gfi1 in primary mouse thymocytes and a human T-cell line. GFI1 binding to cis-element sequences conserved between rat, mouse and human Gfi1 mediates direct and potent transcriptional repression. In addition, dramatic regulation of Gfi1 can also be mediated by GFI1B. These data provide the first example of a gene directly targeted by GFI1 and GFI1B. Moreover, they support a role for auto- and trans-regulation of Gfi1 by GFI1 and GFI1B in maintaining the normal expression patterns of Gfi1, and suggest that GFI1B may indirectly affect T-cell activation through repression of Gfi1.
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Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Linfócitos T/metabolismo , Timo/metabolismo , Fatores de Transcrição , Transcrição Gênica , Animais , Sequência de Bases , Linhagem Celular , Células Cultivadas , Sequência Conservada/genética , DNA/genética , DNA/metabolismo , Humanos , Células Jurkat , Camundongos , Dados de Sequência Molecular , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas Repressoras/genética , Elementos de Resposta/genética , Homologia de Sequência do Ácido Nucleico , Timo/citologiaRESUMO
In developing countries, education to health-care professionals is a cornerstone in the battle against neglected tropical diseases (NTD). Studies evaluating the level of knowledge of medical students in clinical and socio-demographic aspects of NTD are lacking. Therefore, a cross-sectional study was conducted among students from a 7 year-curriculum medical school in Peru to assess their knowledge of NTD by using a pilot survey comprised by two blocks of 10 short questions. Block I consisted of socio-demographic and epidemiological questions whereas block II included clinical vignettes. Each correct answer had the value of 1 point. Out of 597 responders (response rate: 68.4%), 583 were considered to have valid surveys (male:female ratio: 1:1.01; mean age 21 years, SD ± 2.42). Total knowledge showed a raising trend through the 7-year curriculum. Clinical knowledge seemed to improve towards the end of medical school whereas socio-demographic and epidemiological concepts only showed progress the first 4 years of medical school, remaining static for the rest of the curricular years (p = 0.66). Higher mean scores in socio-demographic and epidemiological knowledge compared to clinical knowledge were seen in the first two years (p<0.001) whereas the last three years showed higher scores in clinical knowledge (p<0.001). In conclusion, students from this private medical school gained substantial knowledge in NTD throughout the career which seems to be related to improvement in clinical knowledge rather than to socio-demographic and epidemiological concepts. This study assures the feasibility of measuring the level of knowledge of NTD in medical students and stresses the importance of evaluating education on NTD as it may need more emphasis in epidemiological concepts, especially at developing countries such as Peru where many people are affected by these preventable and treatable diseases.
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Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/patologia , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/patologia , Competência Profissional , Estudantes de Medicina , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Peru , Inquéritos e Questionários , Clima Tropical , Adulto JovemRESUMO
Resumen Introducción. En todos los procesos químicos se requiere de un medio de reacción o solvente, y dichos solventes orgánicos son altamente volátiles por lo que son contaminantes de la atmósfera, y se requieren nuevos métodos, procesos y otro tipo de solventes que minimice dicha contaminación, y los líquidos iónicos están resultando ser una gran alternativa a dicho problema. Objetivo. Sintetizar líquidos iónicos a base del imidazol con aniones tanto inorgánicos como orgánicos y evaluar su potencial aplicación como catalizadores en reacciones importantes de síntesis orgánicas, como la síntesis asimétrica, específicamente la condensación aldolica. Materiales y métodos. El metil imidazol (99%), 1-bromobutano (97%), prolina (98%), KOH (97%), acetato de etilo, etanol, grado reactivo, fueron suministrados por Sigma Chemical Co. Se utilizó el metil imidazol; para la síntesis de líquido iónico base el bromuro de butil-metil-imidazol, [Bmim][Br]; los demás líquidos iónicos se obtienen por reacción de metátesis, para obtener el hidroxi de butil-metil-imidazol, [Bmim][OH], y el prolinato de butil-metil-imidazol, [Bmim][Pro]; estos líquidos fueron utilizados como catalizadores en la reacción de síntesis asimétrica como la condensación aldolica. Resultados. Se realizó una condensación aldolica clásica, p-nitrobenzalhedido con ciclohexanona para probar los líquidos iónicos sintetizados como catalizadores, y al comparar los resultados obtenidos con métodos convencionales se observan ventajas, como altos rendimientos y alta selectividad en menor tiempo de reacción. Conclusiones. En condiciones muy suaves de reacción, se logró reutilizar hasta 6 veces el líquido iónico como catalizador de la reacción sin perder las ventajas mencionadas, lo que lo hace un sistema sostenible.
Abstract Introduction. In all chemical processes, a reaction medium or solvent is required, and such organic solvents are highly volatile so they are pollutants to the atmosphere, and new methods, processes and other solvents are required to minimize the contamination, and Ionic liquids are proving to be a great alternative to such problem. Objective. Synthesize imidazole based ionic liquids with both inorganic and organic anions and evaluate their potential application as catalysts in important reactions of organic synthesis, such as asymmetric synthesis, specifically in asymmetric aldol reaction. Materials and Methods. Methyl imidazole (99%), 1-bromobutane (97%), proline (98%), KOH (97%), Ethyl acetate, ethanol, reagent grade were supplied by Sigma Chemical Co. It was used the methyl imidazol for the synthesis of the ionic liquid butyl methyl imidazole bromide, [Bmim] [Br], and the other ionic liquids were obtained by metathesis reaction from such ionic liquid, to obtain the butyl methyl imidazole hydroxy [Bmim] [OH], and the butyl methyl imidazole prolinate, [Bmim] [Pro]. These ionic liquids were used as catalysts in the asymmetric aldol reaction. Results. A classical aldol reaction, p-nitrobenzaldehyde with cyclohexanone was performed to test the ionic liquids synthesized as catalysts, and when comparing the results obtained with conventional methods, advantages were observed, such as high yields and high selectivity in less time reaction. Conclusions. Under very mild reaction conditions, it was possible to reuse up to 6 times the ionic liquid as a reaction catalyst without losing the mentioned advantages, which makes it a sustainable system.
Resumo Introdução. Todos os processos químicos requerem um meio de reação ou solvente, tais solventes orgânicos são altamente voláteis, é assim que são os poluentes principais da atmosfera, porem precisa-se de novos métodos, processos e outros solventes para minimizar a contaminação, por isso, os líquidos iónicos estão provando para ser uma ótima alternativa para esse problema. Objetivo. A sínteses dos líquidos iónicos com base em imidazol e usando ânions inorgânicos e orgânicos e avaliar sua potencial aplicação como catalisadores em reações importantes em síntese orgânica, tais como a síntese assimétrica, especificamente a condensação aldólica. Materiais e Métodos. O imidazol metil (99%), 1-bromobutano (97%), prolina (98%), KOH (97%), acetato de etila e etanol no grau de reagente, foram fornecidos pelo Sigma Chemical Co. O metila-imidazol foi utilizado para a síntese baseado no líquido iónico brometo de metil-butil-imidazo-, [BMIM] [Br], Os outros líquidos iónicos são obtidos por reação de metátese, para se obter o hidroxi de butil-metil-imidazol, [BMIM][OH], e prolinato de butil-metil-imidazol, [BMIM][Pro], estes líquidos foram usadas como catalisadores na reação de síntese assimétrica, como a condensação aldólica. Resultados. Foi realizada uma condensação aldólica clássica usando p-nitrobenzaldeído com a cicloexanona para testar os líquidos iónicos sintetizados como catalisador, ao comparar os resultados obtidos com os métodos convencionais darão vantagens, tais como rendimentos elevados e alta seletividade é observada no tempo de reação mais rápido. Conclusões. Nas condições muito suave de reação, foi possível reutilizar até 6 vezes o líquido iónico como catalisador da reação, sem perder as vantagens mencionadas, tornando-se um sistema sustentável.
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Compilamos y analizamos los datos de observaciones realizadas entre los años 2001 y 2013 en tres sectores a lo largo del cauce del río La Vieja, ubicado en el valle geográfico del río Cauca, Colombia. Describimos los datos espacial y temporalmente, enfocándonos en identificar patrones de composición y abundancia de especies. Registramos 28 especies de aves acuáticas en 33 transectos, siendo 22 especies observadas en más del 50 % de los transectos. Las diferencias en el número de especies por transecto no fueron significativas entre los tres sectores del río. Sin embargo, dos análisis de agrupamiento, considerando tanto los datos de presencia/ausencia como de abundancia, indicaron que la composición de especies presenta estructura espacial a lo largo del río. En contraste, aunque las observaciones se realizaron durante más de diez años no se encontró evidencia de cambios temporales en la composición de especies. No obstante, algunas especies mostraron tendencias de aumento o disminución en su frecuencia. Presentamos el nuevo registro de una especie (Chloroceryle aenea) para la región. A pesar de que el paisaje asociado al río La Vieja ha sufrido un gran impacto antropogénico, aún conserva una diversidad significativa de aves acuáticas que pueden servir para aportar valor a los planes de conservación en la zona.
We compiled and analyzed data gathered from observations during the period 2001-2013 in three sectors along La Vieja river, located in the Cauca river valley, Colombia. We describe spatial and temporal aspects of such dataset, focusing in indentify patterns of species' composition and abundance. We recorded 28 waterbird species in 33 transects, being 22 species observed in more than 50 % of these transects. The species richness among transects did not shows significant differences. However, two cluster analyses, considering both presence/absence and abundance data, showed that there is spatial structure in the species composition along the river. In contrast, although observations were conducted during more than ten years there is no evidence of temporal changes in species composition. Still, some species showed increase or decrease trends in their frequency. We present a new record for one species (Chloroceryle aenea) for the region. Despite that the landscape surrounding La Vieja river have faced a high anthropogenic impact, the river still presents a significant diversity of waterbirds, which could add value to the conservation plans in the zone.
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En Colombia existen diversas poblaciones en zonas aisladas que no tienen acceso a servicios de salud especializados, entre ellos salud mental. La telemedicina es una herramienta que permite proporcionar estos servicios, llevando medicina especializada a un menor costo y similar calidad a través de tecnologías de la información y las comunicaciones. Como una solución a esta problemática se propuso la estructuración de un protocolo de teleconsulta psiquiátrica y la implementación de una aplicación web, con el fin de proveer servicios de diagnóstico y control a pacientes con incidencia de enfermedades mentales. Para la realización de este proyecto se analizaron lineamientos clínicos y operacionales en servicios de telepsiquiatría, se realizó un análisis de algunas patologías de interés, se hizo un desarrollo del proceso de ingeniería de software, y por último se diseñó una evaluación técnica y clínica de la aplicación para así obtener una retroalimentación del sistema.
Colombia had are several isolated populations in areas without access to specialized health services, much less on mental health. Telemedicine is a tool that allows to provide these services, bringing specialized medicine at lower costs and similar quality through information and communication technologies. As a solution to this problem, a psychiatric tele-consultation protocol and the implementation of a web application was proposed in order to provide diagnosis and follow up to patients with mental diseases. For the development of this project; clinical and operational guidelines in Telepsychiatry services were reviewed, diseases of interest were analyzed, a software engineering process was implemented, and finally a clinical and technical evaluation were designed in order to have a feedback for the system.