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Parasitic diseases are a public health problem, especially in developing countries where millions of people are affected every year. Current treatments have several drawbacks: emerging resistance to the existing drugs, lack of efficacy, and toxic side effects. Therefore, new antiparasitic drugs are urgently needed to treat and control diseases that affect human health, such as malaria, Chagas disease, leishmaniasis, amebiasis, giardiasis schistosomiasis, and filariasis, among others. Quinoxaline is a compound containing a benzene ring and a pyrazine ring. The oxidation of both pyrazine ring nitrogens allows the obtention of quinoxaline 1,4-di-N-oxides (QdNOs) derivatives. By modifying the chemical structure of these compounds, it is possible to obtain a wide variety of biological properties. This review investigated the activity of quinoxaline derivatives and QdNOs against different protozoan parasites and helminths. We also cover the structure-activity relationship (SAR) and summarize the main findings related to their mechanisms of action from published works in recent years. However, further studies are needed to determine specific molecular targets. This review aims to highlight the new development of antiparasitic drugs with better pharmacological profiles than current treatments.

Background: Patients with rheumatoid arthritis (RA) have an increased risk of SARS-CoV-2 infection due to intrinsic characteristics of the pathology and the medications used to treat it. The aim was to evaluate the incidence of and factors related to SARS-CoV-2 infection in patients with RA in Colombia. Methods: This was an observational study of patients diagnosed with RA who were treated at a health care institution in Colombia. The study evaluated whether the patients presented SARS-CoV-2 infection and other clinical variables. Variables associated with the risk of SARS-CoV-2 infection were identified. Results: A total of 2566 patients with RA were identified. They had a median age of 61.9 years, and 81.1% were women. They were mainly treated with synthetic disease-modifying antirheumatic drugs (DMARDs) (85.3%), glucocorticoids (52.2%), and biological DMARDs (26.8%). The incidence of SARS-CoV-2 infection was 5.1%, and the factors that increased the risk included treatment with synthetic DMARDs with or without biological DMARDs but with concomitant systemic glucocorticoids [odds ratio (OR): 2.18, 95% confidence interval (CI): 1.21–3.93 and OR: 1.69, 95% CI: 1.05–2.74, respectively] and receiving antidiabetic drugs (OR: 2.24, 95% CI: 1.27–3.94). A total of 20.8% of patients with COVID-19 required hospitalization and 3.8% died. Conclusion: The incidence of COVID-19 is higher among patients with RA who receive DMARDs and glucocorticoids simultaneously or who have diabetes mellitus than among patients with RA not receiving these drug combinations, which should guide treatment strategies.

We find a simple expression in complex terms for homogeneous harmonic polynomials, which we use to express the Laurent series of a harmonic function around an isolated singularity. Also, we show a residue theorem and study the orientation at isolated singularities through the use of complex dilatation, focusing on those points where orientation is not preserved nor reversed, making essential the concept of exceptional set and extending it to isolated singularities.

Objective To analyze the results of the preimplantation genetic testing for aneuploidy at the Instituto de Fertilidad Humana - Inser Bogota, Colombia, from 2016 to 2020. Methods This study is an observational, retrospective, and correlative analysis of biopsies from 319 embryos (from 54 patients) submitted to preimplantation genetic testing for aneuploidy by different molecular techniques. Results Of the 54 patients included in the study, 42 provided their own oocytes, and 12 used donated oocytes. The main indication to perform the preimplantation genetic testing was advanced maternal age. We obtained 319 embryos: Ninety-one (28.5%) euploid, 197 (61.8%) aneuploid and 31 (9.7%) with no detectable DNA. The highest rate of aneuploid embryos was found in patients over 40 years (72.7%), and the euploidy rate in patients under 35 years was 37.1%. After the transfer of euploid embryos, the rates for implantation, ongoing pregnancy, live birth, and miscarriage were 40%, 50%, 40.6%, and 0%, respectively. Older maternal age correlated with higher numbers of aneuploid embryos and lower numbers of both euploid and 5-day embryos. Conclusions There was a positive correlation between maternal age and aneuploidy rate. Complex chromosomal abnormalities were the most frequent aneuploidies, followed by mosaicism and double aneuploidies. The miscarriage rate after the transfer of euploid embryos was 0 %.

espanol?Que es hoy una produccion academica? ?Bajo que normas y estatutos se conforma un libro que se supone academico? Plantear estas preguntas es ya sumergirse en problemas propios de lo que ha quedado de la universidad moderna, de lo que es luego de haber sido victima de un lento pero constante desmantelamiento. Donde, a grandes rasgos, se remplazo el rigor de la problematizacion por la efectividad del dato; donde, frente a la complejidad del analisis, el funcionamiento de un concepto, se posiciono la estadistica, la grafica, el calculo y el porcentaje. Sustituciones que no son ajenas a los movimientos propios de una epoca, pues es claro que la epoca en la que se constituyo la universidad no es la nuestra y lo que nos va quedando son las trasformaciones que aparecen. Lo que hemos heredado del modelo de universidad moderno responde a otras necesidades, a otros reclamos, a otros intereses, que no se reducen solamente a un nuevo modo de constitucion de la universidad, sino que han modificado el estatuto del saber mismo, su legitimidad, su formacion y formulacion. EnglishWhat is an academic production today? Under which norms is made up a book that is supposed to be academic? To pose these questions is to immerse oneself in problems typical of what has remained of the modern university, of what it is after having been the victim of a slow but constant dismantling. Where, broadly speaking, the rigor of the problematization was replaced by the effectiveness of the data; where, in the face of the complexity of the analysis, the operation of a concept, the statistics, the graph, the calculation and the percentage were positioned. These substitutions are not alien to the movements of an era, since it is clear that the era in which the university was established is not ours and what we are left with are the transformations that appear. What we have inherited from the modern university model responds to other needs, other demands, other interests, which are not only reduced to a new mode of constitution of the university, but have modified the status of knowledge itself, its legitimacy, its formation and formulation

Introducción: El desarrollo de la odontología conservadora ha generado el surgimiento y evolución de los sistemas adhesivos; los procesos de adhesión dependen del material, la experiencia del operador, las características del tejido y del control de las condiciones locales. La dentinogenesis imperfecta (DI) es una condición del desarrollo del diente que afecta el tejido dentinario, en la cual se ven comprometidas tanto la dentición temporal como permanente. Objetivos: Evaluar el comportamiento mecánico de los sistemas adhesivos en dientes sanos y dientes con DI. Materiales y métodos: Se realizaron 10 pruebas de microtensión en dientes sanos y 10 pruebas de microtensión en dientes con DI; Se verificó la distribución normal de los datos con la prueba Kolmororov – Smirnof, Se utilizó la prueba t student para analizar las diferencias entre los grupos con respecto a los valores de microtensión, además se utilizó la prueba taub de Kendall para establecer correlación entre dientes y tipo de falla. Resultados: Los dientes con dentinogenesis imperfecta presentan un grado de adhesión significativamente menor con respecto a los dientes sanos. Conclusión: Los dientes con DI presentan fallas en la adhesión debido a la estructura macro y microscópica, sin embargo, presentaron cierto grado de adhesión.

Resumen En este trabajo se presenta una estrategia de regulación robusta de los ácidos grasos volátiles (AGV) en un proceso de digestión anaerobia. La estrategia propuesta es una ley de control por retroalimentación no lineal obtenida por linealización entrada-salida que permite alcanzar el objetivo de control a pesar de errores de modelado (incertidumbres en la cinética de las reacciones) y las restricciones del actuador. Los experimentos fueron conducidos con un reactor anaerobio piloto de lecho fijo y flujo ascendente (UAFBR) con volumen activo de 0,947 m3, completamente equipado, utilizado para el tratamiento de aguas residuales provenientes de una destilería de vino en Narbonne, Francia. Con el objetivo de validar los modelos utilizados, resultados simulados y experimentales, son presentados y discutidos los parámetros de desempeño del controlador bajo los modelos AM2 y ADM1 (tiempo de subida, tiempo de establecimiento, sobre impulso y error en estado estacionario) obtenidos de las simulaciones numéricas, que prueban la eficiencia y aplicabilidad de la estrategia de control propuesta. Abstract In this article a robust regulation strategy of volatile fatty acids is proposed by an anaerobic digestion process. The proposed strategy is a control law via nonlinear feedback obtained by input-output linearization that allows the completion of the control goals despite the modeling errors (uncertainties in the kinetics of the reactions) and the actuator restrictions. The experiments were conducted with an pilot fixed anaerobic reactor and ascending flow (UAFBR) with an active volume of 0.947 m3 fully equipped, used for the treatment of residual waters coming from a wine distillery in Narbonne, France. With the goal of validating the models used, simulated and experimental results are presented and discussed. The performance parameters of the controller under the AM2 and ADM1 models (up time, establishment time, over-impulse and stationary state error) obtained from the numeric simulations that prove the efficiency and applicability of the proposed control strategy. Resumo Neste trabalho, apresenta-se uma estratégia de regulação robusta dos ácidos graxos voláteis (AGV) em um processo de digestão anaeróbia. A estratégia proposta é uma lei de controle por retroalimentação não linear obtida por linearização entrada-saída que permite atingir o objetivo de controle apesar de erros de modelagem (incertezas na cinética das reações) e das restrições do acionador. As experiências foram conduzidas com um reator anaeróbio-piloto de leito fixo e fluxo ascendente (UAFBR) com volume ativo de 0,947 m3, completamente equipado, utilizado para tratar águas residuais provenientes de uma destilaria de vinho em Narbonne, França. Com o objetivo de validar os modelos utilizados, resultados simulados e experimentais, são apresentados e discutidos os parâmetros de desempenho do controlador sob os modelos AM2 e ADM1 (tempo de subida, tempo de estabelecimento, sobre impulso e erro de estado estacionário) obtidos das simulações numéricas, que provam a eficiência e a aplicabilidade da estratégia de controle proposta.

The current therapy for the treatment of leishmaniasis is unsatisfactory because it has multiple side effects, and resistance has been reported among the parasites that cause these diseases. Numerous efforts have been made to develop new candidates for vaccines. In recent years, particles of biodegradable polymers have been proposed as vehicles to transport and protect antigens, proteins, drugs and vaccines. In this work, the oil/water (o/w) single emulsion-solvent evaporation technique was used to prepare PLGA biodegradable particles. The encapsulation of two hypothetical proteins from Leishmania panamensis was performed to validate the proposed method. For this validation, different concentrations (50, 100, 150, 200, 250, 500, and 750 μg/ml) of both proteins were encapsulated into PLGA particles, and the particle sizes and shapes were evaluated by optical microscopy and scanning electron microscopy (SEM), respectively. The release of proteins was confirmed by SDS-PAGE and Western blot analyses. The integrity of both proteins was conserved, and they were released from day one until day 15, with a maximum amount of 46 ± 4.25% for the LpanUA.27.1260 protein and 26.19 ± 3.41% for LpanUA.22.1860. Additionally, the protective efficacy of one of these encapsulated proteins was evaluated in vivo using BALB/c mice infected with L. panamensis. Therefore, the encapsulation of proteins is presented here as an excellent alternative to evaluate the antigenicity of proteins from parasites of medical importance such as L. panamensis.

Las grandes tecnologías que tiene al alcance el ser humano, ha generado una nueva revolución en las grandes industrias, las cuales quieren satisfacer a la población. El semillero de investigación robótica e impresión 3d se propuso a innovar y crear un robot domótico que cumpla con esta labor, ya que en la actualidad el ritmo de vida es muy sofocante y lleno de actividades rutinarias en las casas o apartamentos. El beneficio que tiene un robot domótico es ayudar a las labores cotidianas, específicamente, de jardinero y mayordomo para este caso. Los resultados que se han adquirido brindan una disminución de labores domésticas, con el beneficio de la automa- tización mediante cámaras, sensores y extremidades, siendo controlado de forma inalámbrica.

Let the function $$\varphi $$ be holomorphic in the unit disk $${\mathbb {D}}$$ of the complex plane $${\mathbb {C}}$$ and let $$\varphi ({\mathbb {D}})\subset {\mathbb {D}}$$ . We study the global behavior, the structure of the level sets and the singular points of the function $$\begin{aligned} \mu (z):=(1-|\varphi (z)|^2)/(1-|z|^2). \end{aligned}$$ In particular we show that $$\mu $$ is subharmonic and that the sets $$ \{z\in {\mathbb {D}} : \mu (z)

Diagnosis of leishmaniasis based on antibodies detection represents a challenge due to cross-reaction of sera with other infectious agents, which co-exist in endemic areas of Leishmania sp, especially patients with Trypanosoma cruzi. This work is aimed at searching for immunogenic proteins in sera from patients with cutaneous and mucosal leishmaniasis that may be potential candidates for the development of diagnostic tests and/or vaccines that help control the infection. Total protein extracts of L. panamensis promastigotes were put in contact with sera from patients with cutaneous and mucosal leishmaniasis (immunoblots). Immunoreactive proteins were identified by mass spectrometry and bioinformatics tools. 81 proteins were identified. One of these was uniquely recognized by the sera from patients with ML but not from sera from either CL or Chagas disease patients. MS analysis of this band pointed to the putative leishmanial 3-oxoacyl-(Acylcarrierprotein) reductase.

Let the function $$\varphi $$ be holomorphic in the unit disk $${\mathbb {D}}$$ of the complex plane $${\mathbb {C}}$$ and let $$\varphi ({\mathbb {D}})\subset {\mathbb {D}}$$ . We study the level sets and the critical points of the hyperbolic derivative of $$\varphi $$ , $$\begin{aligned} |D_{\varphi }(z)|:=\frac{(1-|z|^2)|\varphi '(z)|}{1-|\varphi (z)|^2}. \end{aligned}$$ In particular, we show how the Schwarzian derivative of $$\varphi $$ reveals the nature of the critical points.

Aptamers are single-stranded DNA or RNA sequences of 20–80 nucleotides that interact with different targets such as: proteins, ions, viruses, or toxins, through non-covalent interactions and their unique three-dimensional conformation. They are obtained in vitro by the systematic evolution of ligands by exponential enrichment (SELEX). Because of their ability of target recognition with high specificity and affinity, aptamers are usually compared to antibodies. However, they present many advantages that make them promising molecules for the development of new methods for the diagnosis and treatment of human diseases. In medical parasitology, aptamers also represent an attractive alternative for the implementation of new parasite detection methods, easy to apply in endemic regions. The aim of this study was to describe the current advances in the development of diagnostic tests based on aptamers in parasitology. For this, articles were selected following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with specific inclusion and exclusion criteria. The 26 resulting articles deal with the use of aptamers for the detection of six important protozoa that affect human health. This systematic review clearly demonstrates the specificity, sensitivity and selectivity of aptamers and aptasensors, that certainly will soon become standard methods in medical parasitology.

In eukaryotic cells, nuclear cleavage and polyadenylation of mRNA precursors (pre-mRNA) generate functional protein encoding transcripts that can be exported to the cytoplasm and translated. Nevertheless, in protozoan parasites that cause intestinal infections in humans, the current knowledge on mRNA 3′-end formation is limited. We performed a genomic survey in Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum databases and predicted that polyadenylation machineries are generally well conserved in these pathogens. Notably, most parasites have the 25 kDa subunit of the heterotetrameric CFIm (CFIm25), the 77 kDa subunit of the heterohexameric CPSF (CPSF73) and the poly(A) polymerase (PAP), which are essential proteins for poly(A) site selection, RNA cleavage and poly(A) tail synthesis. However, several differences exist that may be useful to develop new methods to control these pathogens. Taking E. histolytica as a study model, we focused on the EhCFIm25 protein, because it is the unique subunit of CFIm in this pathogen, whereas active CFIm in humans is formed by two 25 kDa subunits interacting with two larger subunits. Human and parasite CFIm25 proteins only share 32% identity but they have a similar three-dimensional folding. Interestingly, trophozoites loose virulence and are induced to death when EhCFIm25 expression is silenced, which denotes the relevance of this protein for E. histolytica control. To assess this hypothesis, we obtained RNA aptamers that specifically recognize EhCFIm25 by using the SELEX (systematic evolution of ligands by exponential enrichment) procedure and showed that their ingestion by phagocytosis dramatically reduces trophozoites proliferation. Moreover, RNA-protein binding and molecular modeling assays allowed us to identify that the GUUG motif is the binding site of EhCFIm25, while it is the UGUA sequence for the human protein. All these observations led us to propose that aptamers targeting specific parasite proteins, alone or in combination with the conventional treatment, could represent a new tool for controlling the development of amoebiasis and other challenging parasitic diseases.

Messenger RNA 3′-end polyadenylation is an important regulator of gene expression in eukaryotic cells. In our search for new ways of treating parasitic infectious diseases, we looked at whether or not alterations in polyadenylation might control the survival of Entamoeba histolytica (the agent of amoebiasis in humans). We used molecular biology and computational tools to characterize the mRNA cleavage factor EhCFIm25, which is essential for polyadenylation in E. histolytica. By using a strategy based on the systematic evolution of ligands by exponential enrichment, we identified single-stranded RNA aptamers that target EhCFIm25. The results of RNA-protein binding assays showed that EhCFIm25 binds to the GUUG motif in vitro, which differs from the UGUA motif bound by the homologous human protein. Accordingly, docking experiments and molecular dynamic simulations confirmed that interaction with GUUG stabilizes EhCFIm25. Incubating E. histolytica trophozoites with selected aptamers inhibited parasite proliferation and rapidly led to cell death. Overall, our data indicate that targeting EhCFIm25 is an effective way of limiting the growth of E. histolytica in vitro. The present study is the first to have highlighted the potential value of RNA aptamers for controlling this human pathogen.

Este es un articulo de estudio de caso sobre las herramientas de gestion e interaccion con las instituciones publicas y de acercamiento con la poblacion joven, desarrollado en la universidad Distrital Francisco Jose de Caldas en el ano 2017. Metodologia: Se desarrolla un metodo mixto con un componente cualitativo por medio de entrevistas semiestructuradas a actores involucrados en temas de juventud, tecnologia y administracion publica. El componente cuantitativo se desarrolla mediante un cuestionario de 36 preguntas aplicado a 417 jovenes vinculados a los procesos adelantados por la administracion para este sector poblacional. Resultados: En el analisis se distinguen tres factores sobresalientes; el costo-beneficio, la resistencia cultural y las condiciones de contratacion estatal, como la existencia de voluntad politica y los requisitos burocraticos para la implementacion, asociada al costo beneficios. Ademas, los factores de accesibilidad, seguridad, diseno, usabilidad, inversion y gestion humana se calificaron como altamente importantes con 90% de favorabilidad promedio en las encuestas. Conclusion: Los factores de accesibilidad, seguridad, diseno, usabilidad, inversion y gestion humana, son sinergicos e importantes para el exito de la implementacion de las plataformas virtuales. La relacion costo-beneficio, la cultura, la voluntad politica y los requerimientos burocraticos son factores adicionales que deben tenerse en cuenta cuando las implementaciones tecnologicas se desarrollan con las instituciones gubernamentales. Limitaciones: La implementacion de herramientas e-government esta sujeta a las disposiciones dictadas por leyes nacionales que aun no se actualizan para adoptar sistemas tecnologicos en sus procesos. Originalidad: Refuerza las bases para la implementacion de estrategias de e-government en las administraciones locales con respaldo estadistico de alta confiabilidad.

The 25 kDa subunit of the Clevage Factor Im (CFIm25) is an essential factor for messenger RNA polyadenylation in human cells. Therefore, here we investigated whether the homologous protein of Entamoeba histolytica, the protozoan responsible for human amoebiasis, might be considered as a biochemical target for parasite control. Trophozoites were cultured with bacterial double-stranded RNA molecules targeting the EhCFIm25 gene, and inhibition of mRNA and protein expression was confirmed by RT-PCR and Western blot assays, respectively. EhCFIm25 silencing was associated with a significant acceleration of cell proliferation and cell death. Moreover, trophozoites appeared as larger and multinucleated cells. These morphological changes were accompanied by a reduced mobility, and erythrophagocytosis was significantly diminished. Lastly, the knockdown of EhCFIm25 affected the poly(A) site selection in two reporter genes and revealed that EhCFIm25 stimulates the utilization of downstream poly(A) sites in E. histolytica mRNA. Overall, our data confirm that targeting the polyadenylation process represents an interesting strategy for controlling parasites, including E. histolytica. To our best knowledge, the present study is the first to have revealed the relevance of the cleavage factor CFIm25 as a biochemical target in parasites.