Orientación psicosocial y apoyo al adulto mayor que asiste al Hospital Nacional Pedro de Bethancourt, Asociación Probienestar del paciente diabético y Asociación de Jubilados de Sacatepéquez, Antigua Guatemala.

Posibilitar orientación psicosocial y apoyo al adulto mayor que asiste al Hospital Hermano Pedro de ¬Betancourt, Asociación Probienestar del Paciente Diabético y Asociación de Jubilados y Pensionados de Sacatepéquez”, El Ejercicio Profesional Supervisado se llevó a cabo en la aldea de San Felipe de Jesús de Antigua Guatemala, con el objetivo de proporcionar herramientas psicológicas que posibilitaran al adulto mayor, reflexionar acerca del proceso de vida, en especial del proceso de envejecimiento, para que fuera capaz de encontrar el sentido de vida aún en circunstancias de sufrimiento y contribuir de esta manera a mejorar su Salud Mental. Desarrolló los subprogramas de: servicio, docencia e investigación. El subprograma de servicio, brindó atención clínica de casos, tanto de forma individual como grupal. Se realizaron entrevistas, historias clínicas, en las que se registró la información de forma confidencial, que permitió recopilar los datos más relevantes de la problemática. En el subprograma de docencia, se impartieron talleres y charlas, de forma participativa, en el cual se dieron a conocer diversos temas como: el sufrimiento, estrés, la culpa, motivación, trastornos del sueño, la familia, sentido de vida, autoestima, autorrealización, el significado de la muerte, entre otros. Temas que se desarrollaron a lo largo del Ejercicio Profesional Supervisado y que fueron de mucha ayuda para las personas con las que se trabajó. En el subprograma de investigación, se tomó como base la observación, se consideró de suma importancia trabajar el tema “Factores que ocasionan la falta de sentido de vida en el adulto mayor”. El tipo de investigación que se llevó a cabo fue descriptivo, esta permitió sustentar el trabajo que se llevó a cabo durante el Ejercicio Profesional Supervisado. Se aplicó un cuestionario sobre el sufrimiento, para conocer los factores que ocasionaron este tipo de sentimientos y provocaron escasos deseos de seguir viviendo. Se analizó la información y se estableció que, el mayor sufrimiento para el adulto mayor es la dificultad de relación y convivencia con los hijos. La falta de sentido de vida es provocada por el sentimiento de soledad que posee el adulto mayor luego de la partida de los hijos del hogar o la muerte de su pareja

Abordaje de los desafíos metodológicos presentes en la formulación y evaluación de un proyecto socioproductivo en la comunidad Colonia la Libertad, Upala, Costa Rica, 2018

La presente investigación se ha desarrollado en la comunidad rural Colonia la Libertad, distrito Aguas Claras, cantón Upala, provincia Alajuela, Costa Rica, 2018. Con la finalidad de elaborar un estudio de factibilidad para instalación de una Planta Procesadora y Comercializadora de Carne de Pollo, la cual sería gestionada a través de la Cooperativa de Productores Agropecuarios y Servicios Múltiples de Colonia Libertad de Upala (Coopeliberteños R.L.). Este proyecto busca a través del trabajo cooperativo desarrollar un proyecto socioproductivo como mecanismo de producción y comercialización que represente una fuente de ingresos para las personas asociadas a Coopeliberteños R.L.Facultad de Humanidades y Ciencias de la Educació

Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 μM were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. © 2009 Elsevier Ltd. All rights reserved

Expansion of a specific plasmodium falciparum PfMDR1 Haplotype in southeast Asia with increased substrate transport

Artemisinin-based combination therapies (ACTs) have been vital in reducing malaria mortality rates since the 2000s. Their efficacy, however, is threatened by the emergence and spread of artemisinin resistance in Southeast Asia. The Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) transporter plays a central role in parasite resistance to ACT partner drugs through gene copy number variations (CNV) and/or single nucleotide polymorphisms (SNPs). Using genomic epidemiology, we show that multiple pfmdr1 copies encoding the N86 and 184F haplotype are prevalent across Southeast Asia. Applying genome editing tools on the Southeast Asian Dd2 strain and using a surrogate assay to measure transporter activity in infected red blood cells, we demonstrate that parasites harboring multicopy N86/184F PfMDR1 have a higher Fluo-4 transport capacity compared with those expressing the wild-type N86/Y184 haplotype. Multicopy N86/184F PfMDR1 is also associated with decreased parasite susceptibility to lumefantrine. These findings provide evidence of the geographic selection and expansion of specific multicopy PfMDR1 haplotypes associated with multidrug resistance in Southeast Asia.IMPORTANCE Global efforts to eliminate malaria depend on the continued success of artemisinin-based combination therapies (ACTs) that target Plasmodium asexual blood-stage parasites. Resistance to ACTs, however, has emerged, creating the need to define the underlying mechanisms. Mutations in the P. falciparum multidrug resistance protein 1 (PfMDR1) transporter constitute an important determinant of resistance. Applying gene editing tools combined with an analysis of a public database containing thousands of parasite genomes, we show geographic selection and expansion of a pfmdr1 gene amplification encoding the N86/184F haplotype in Southeast Asia. Parasites expressing this PfMDR1 variant possess a higher transport capacity that modulates their responses to antimalarials. These data could help tailor and optimize antimalarial drug usage in different regions where malaria is endemic by taking into account the regional prevalence of pfmdr1 polymorphisms.This work was funded by Portuguese National funds through the Foundation for Science and Technology (FCT) (project UIDB/50026/2020 and UIDP/50026/2020; fellowships PD/BD/127826/2016 to C.C., SFRH/BD/129769/2017 to M.S., SFRH/BD/145427/2019 to V.B., SFRH/BD/131540/2017 to R.S.P., and IF/00143/2015/CP1294/CT0001 to P.E.F. and contract funding to M.I.V. provided through DL 57/2016 [CRP]); by the projects NORTE-01-0145-FEDER-000013, NORTE-01-0145-FEDER-000023, and NORTE 01-0145-FEDER-028178, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the Euro pean Regional Development Fund (ERDF); by the Institute Merieux through “Starting” Mérieux Research Grant 2016 to M.I.V.; by the ESCMID to P.E.F. and by the NIH R01 AI109023 and R37AI50234 to D.A.F.info:eu-repo/semantics/publishedVersio

Chloroquine Clinical Failures in P. falciparum Malaria Are Associated with Mutant Pfmdr-1, Not Pfcrt in Madagascar

Molecular studies have demonstrated that mutations in the Plasmodium falciparum chloroquine resistance transporter gene (Pfcrt) play a major role in chloroquine resistance, while mutations in P. falciparum multidrug resistance gene (Pfmdr-1) act as modulator. In Madagascar, the high rate of chloroquine treatment failure (44%) appears disconnected from the overall level of in vitro CQ susceptibility (prevalence of CQ-resistant parasites <5%) or Pfcrt mutant isolates (<1%), strongly contrasting with sub-Saharan African countries. Previous studies showed a high frequency of Pfmdr-1 mutant parasites (>60% of isolates), but did not explore their association with P. falciparum chloroquine resistance. To document the association of Pfmdr-1 alleles with chloroquine resistance in Madagascar, 249 P. falciparum samples collected from patients enrolled in a chloroquine in vivo efficacy study were genotyped in Pfcrt/Pfmdr-1 genes as well as the estimation of the Pfmdr-1 copy number. Except 2 isolates, all samples displayed a wild-type Pfcrt allele without Pfmdr-1 amplification. Chloroquine treatment failures were significantly associated with Pfmdr-1 86Y mutant codon (OR = 4.6). The cumulative incidence of recurrence of patients carrying the Pfmdr-1 86Y mutation at day 0 (21 days) was shorter than patients carrying Pfmdr-1 86N wild type codon (28 days). In an independent set of 90 selected isolates, in vitro susceptibility to chloroquine was not associated with Pfmdr-1 polymorphisms. Analysis of two microsatellites flanking Pfmdr-1 allele showed that mutations occurred on multiple genetic backgrounds. In Madagascar, Pfmdr-1 polymorphism is associated with late chloroquine clinical failures and unrelated with in vitro susceptibility or Pfcrt genotype. These results highlight the limits of the current in vitro tests routinely used to monitor CQ drug resistance in this unique context. Gaining insight about the mechanisms that regulate polymorphism in Pfmdr1 remains important, particularly regarding the evolution and spread of Pfmdr-1 alleles in P. falciparum populations under changing drug pressure which may have important consequences in terms of antimalarial use management

Antimalarial Exposure Delays Plasmodium falciparum Intra-Erythrocytic Cycle and Drives Drug Transporter Genes Expression

BACKGROUND: Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold. CONCLUSIONS/SIGNIFICANCE: Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug

In vitro selection of Plasmodium falciparum drug-resistant parasite lines

The in vitro selection of antimicrobial resistance in important pathogens can provide critical information on the genetic basis of drug resistance, and such information can be used to predict, anticipate and even contain the spread of resistance in clinical practice. For instance, the discovery of the role of pfmdr1 in mefloquine resistance in malaria parasites resulted from in vitro studies. However, the in vitro selection of resistance is difficult, challenging and time consuming. In this review, we discuss the key parameters that impact on the efficiency of the in vitro selection of resistance, and propose strategies to improve and streamline this process

Chloroquine Susceptibility and Reversibility in a Plasmodium falciparum Genetic Cross

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT), are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 × Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the Southeast Asiaderived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute with the pfcrt and pfmdr1 loci to influence CQR levels. Chemoreversal via a wide range of chemical structures operates through a direct pfcrt-based mechanism. Direct inhibition of parasite growth by these reversal agents is influenced by pfcrt mutations and additional loci. Direct labeling of purified recombinant PfMDR1 protein with a highly specific photoaffinity CQ analogue, and lack of competition for photolabeling by VP, supports our QTL predictions. We find no evidence that pfmdr1 copy number affects CQ response in the progeny, however, inheritance patterns indicate that an allele-specific interaction between pfmdr1 and pfcrt is part of the complex genetic background of CQR