9 research outputs found

    Política y persona, visión política del personalismo desde una lectura contemporánea de Emmanuel Mounier

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    Tesis de maestríaEsta investigación, “política y persona. Visión política del personalismo desde una lectura contemporánea de Emmanuel Mounier” pretende poner a disposición del lector una serie de conceptos y de autores para que puedan valorar si esta corriente filosófica responde alguna de sus expectativas; la visión que se da es una que está basada en las ciencias políticas, ya que existe poca visión global de este movimiento y se pretende contribuir a llenar ese vacío.INTRODUCCIÓN 1. El PROBLEMA DE LA PERSONA EN EL PENSAMIENTO POLITICO 2. VISION POLITICA DEL PERSONALISMO 3. BALANCE DE LA VISION POLITICA EN LA EPOCA ACTUAL 4. PERSONALIZACION Y CIUDADANIA BIBLIOGRAFÍAMaestríaMagister en Ciencia Polític

    UCT943, a next generation Plasmodium falciparum PI4K inhibitor preclinical candidate for the treatment of malaria

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    The 2-aminopyridine MMV048 was the first drug candidate inhibiting; Plasmodium; phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite life cycle, leading to the 2-aminopyrazine UCT943. The compound displayed higher asexual blood stage, transmission-blocking, and liver stage activities than MMV048 and was more potent against resistant; Plasmodium falciparum; and; Plasmodium vivax; clinical isolates. Excellent; in vitro; antiplasmodial activity translated into high efficacy in; Plasmodium berghei; and humanized; P. falciparum; NOD-; scid IL-2R; Îł; null; mouse models. The high passive permeability and high aqueous solubility of UCT943, combined with low to moderate; in vivo; intrinsic clearance, resulted in sustained exposure and high bioavailability in preclinical species. In addition, the predicted human dose for a curative single administration using monkey and dog pharmacokinetics was low, ranging from 50 to 80 mg. As a next-generation; Plasmodium; PI4K inhibitor, UCT943, based on the combined preclinical data, has the potential to form part of a single-exposure radical cure and prophylaxis (SERCaP) to treat, prevent, and block the transmission of malaria

    Our Choice\u3cem\u3e/Nuestra OpciĂłn:\u3c/em\u3e The Imperial County, California, Childhood Obesity Research Demonstration Study

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    Background: Despite recent declines among young children, obesity remains a public health burden in the United States, including among Latino/Hispanic children. The determining factors are many and are too complex to fully address with interventions that focus on single factors, such as parenting behaviors or school policies. In this article, we describe a multisector, multilevel intervention to prevent and control childhood obesity in predominantly Mexican-origin communities in Southern California, one of three sites of the CDC-funded Childhood Obesity Research Demonstration (CA-CORD) study. Methods: CA-CORD is a partnership between a university-affiliated research institute, a federally qualified health center, and a county public health department. We used formative research, advisory committee members\u27 recommendations, and previous research to inform the development of the CA-CORD project. Our theory-informed multisector, multilevel intervention targets improvements in four health behaviors: fruit, vegetable, and water consumption; physical activity; and quality sleep. Intervention partners include 1200 families, a federally qualified health center (including three clinics), 26 early care and education centers, two elementary school districts (and 20 elementary schools), three community recreation centers, and three restaurants. Intervention components in these sectors target changes in behaviors, policies, systems, and the social and physical environment. Evaluation activities include assessment of the primary outcome, BMI z-score, at baseline, 12-, and 18-months post-baseline, and sector evaluations at baseline, 12, and 24 months. Conclusions: Identifying feasible and effective strategies to prevent and control childhood obesity has the potential to effect real changes in children\u27s current and future health status

    A novel pyrazolopyridine with in vivo activity in Plasmodium berghei- and Plasmodium falciparum-infected mouse models from structure-activity relationship studies around the core of recently identified antimalarial imidazopyridazines

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    Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics profiles. The lead compounds also proved to be very potent in the parasite liver and gametocyte stages, which makes them of high interest

    Identification of a potential antimalarial drug candidate from a series of 2-aminopyrazines by optimization of aqueous solubility and potency across the parasite life cycle

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    Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2RÎł(null) mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages

    Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase

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    As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. Stemming from this series, we found that the derivative, MMV390048, lacked cross-resistance with current drugs used to treat malaria. This compound was efficacious against all Plasmodium life cycle stages, apart from late hypnozoites in the liver. Efficacy was shown in the humanized Plasmodium falciparum mouse model, and modest reductions in mouse-to-mouse transmission were achieved in the Plasmodium berghei mouse model. Experiments in monkeys revealed the ability of MMV390048 to be used for full chemoprotection. Although MMV390048 was not able to eliminate liver hypnozoites, it delayed relapse in a Plasmodium cynomolgi monkey model. Both genomic and chemoproteomic studies identified a kinase of the Plasmodium parasite, phosphatidylinositol 4-kinase, as the molecular target of MMV390048. The ability of MMV390048 to block all life cycle stages of the malaria parasite suggests that this compound should be further developed and may contribute to malaria control and eradication as part of a single-dose combination treatment

    Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase.

    No full text
    As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. Stemming from this series, we found that the derivative, MMV390048, lacked cross-resistance with current drugs used to treat malaria. This compound was efficacious against all Plasmodium life cycle stages, apart from late hypnozoites in the liver. Efficacy was shown in the humanized Plasmodium falciparum mouse model, and modest reductions in mouse-to-mouse transmission were achieved in the Plasmodium berghei mouse model. Experiments in monkeys revealed the ability of MMV390048 to be used for full chemoprotection. Although MMV390048 was not able to eliminate liver hypnozoites, it delayed relapse in a Plasmodium cynomolgi monkey model. Both genomic and chemoproteomic studies identified a kinase of the Plasmodium parasite, phosphatidylinositol 4-kinase, as the molecular target of MMV390048. The ability of MMV390048 to block all life cycle stages of the malaria parasite suggests that this compound should be further developed and may contribute to malaria control and eradication as part of a single-dose combination treatment
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