Reflexiones sobre un tema polémico : la resolución de problemas

online resource (54 p.)Libro ElectrónicoUno de los aspectos más importantes de la enseñanza de la Matemática , donde es mayor el índice de fracaso de los estudiantes, es el de la resolución de problemas. Es por ello que, desde hace algún tiempo, figura como una de las principales líneas de investigación didáctica. Así pues, tal como muestra la vasta bibliografía al respecto, un importante número de investigadores en los últimos decenios, han presentado sus propuestas de intervención pedagógica para modificar la situación de manera positiva y afrontar el reto que representa el enseñar y aprender a resolver problemas matemáticos. En estos estudios, se considera la resolución de problemas como una tarea compleja en la que intervienen múltiples variables - de tarea, de contexto, estratégicas, personales, y otras – las cuales tienen impacto sobre el proceso de resolución de problemas.La resolución de problemas: un reto para la educación matemática contemporánea. 4 ¿Cómo favorecer el desarrollo el desarrollo de habilidades en la resolución de problemas?. 19 Algunas consideraciones de interés sobre la incidencia de las matemáticas y las ciencias en la resolución de problemas. 25 Las técnicas participativas, el trabajo grupal y la resolución de problemas. 40 ¿Cómo evaluar la resolución de problemas en clases? 4

NATIONAL EXAM OF NURSING IN CHILE: THE IMPORTANCE AND CHALLENGES

http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-95532011000100004&lng=es&nrm=isoSi bien la evaluación de la calidad de la formación de los egresados, a través de un examen nacional, es una realidad reciente en Chile, la experiencia internacional es amplia y variada. Este artículo da a conocer la necesidad y trascendencia de aplicar algún tipo de medición de competencias en egresados de carreras de enfermería, las características de las evaluaciones que realizan algunos países que las han implementado; así como las políticas y organizaciones que regulan su aplicación. También describe la experiencia de aplicación de un examen nacional en el área de la salud en Chile, como es el caso de medicina y enfermería

Functional Analyses Reveal Extensive RRE Plasticity in Primary HIV-1 Sequences Selected under Selective Pressure

HIV-1 Rev response element (RRE) is a functional region of viral RNA lying immediately downstream to the junction of gp120 and gp41 in the env coding sequence. The RRE is essential for HIV replication and binds with the Rev protein to facilitate the export of viral mRNA from nucleus to cytoplasm. It has been suggested that changes in the predicted secondary structure of primary RRE sequences impact the function of the RREs; however, functional assays have not yet been performed. The aim of this study was to characterize the genetic, structural and functional variation in the RRE primary sequences selected in vivo by Enfuvirtide pressure. Multiple RRE variants were obtained from viruses isolated from patients who failed an Enfuvirtide-containing regimen. Different alterations were observed in the predicted RRE secondary structures, with the abrogation of the primary Rev binding site in one of the variants. In spite of this, most of the RRE variants were able to bind Rev and promote the cytoplasmic export of the viral mRNAs with equivalent efficiency in a cell-based assay. Only RRE45 and RRE40-45 showed an impaired ability to bind Rev in a gel-shift binding assay. Unexpectedly, this impairment was not reflected in functional capacity when RNA export was evaluated using a reporter assay, or during virus replication in lymphoid cells, suggesting that in vivo the RRE would be highly malleable. The Rev-RRE functionality is unaffected in RRE variants selected in patients failing an ENF-containing regimen. Our data show that the current understanding of the Rev-RRE complex structure does not suffice and fails to rationally predict the function of naturally occurring RRE mutants. Therefore, this data should be taken into account in the development of antiviral agents that target the RRE-Rev complex

Remodeling the bladder tumor immune microenvironment by mycobacterial species with changes in their cell envelope composition

Intravesical BCG instillation after bladder tumor resection is the standard treatment for non-muscle invasive bladder cancer; however, it is not always effective and frequently has undesirable side effects. Therefore, new strategies that improve the clinical management of patients are urgently needed. This study aimed to comprehensively evaluate the bladder tumor immune microenvironment profile after intravesical treatment with a panel of mycobacteria with variation in their cell envelope composition and its impact on survival using an orthotopic murine model to identify more effective and safer therapeutic strategies. tumor-bearing mice were intravesically treated with a panel of BCG and M. brumae cultured under different conditions. Untreated tumor-bearing mice and healthy mice were also included as controls. After mycobacterial treatments, the infiltrating immune cell populations in the bladder were analysed by flow cytometry. We provide evidence that mycobacterial treatment triggered a strong immune infiltration into the bladder, with BCG inducing higher global absolute infiltration than M. brumae. The induced global immune microenvironment was strikingly different between the two mycobacterial species, affecting both innate and adaptive immunity. Compared with M. brumae, BCG treated mice exhibited a more robust infiltration of CD4 + and CD8 + T-cells skewed toward an effector memory phenotype, with higher frequencies of NKT cells, neutrophils/gMDSCs and monocytes, especially the inflammatory subset, and higher CD4 + T/CD4 + T and CD8 + T/CD4 + T ratios. Conversely, M. brumae treatment triggered higher proportions of total activated immune cells and activated CD4 + and CD8 + T cells and lower ratios of CD4 + T cells/CD4 + T, CD8 + T cells/CD4 + T and inflammatory/reparative monocytes. Notably, the mycobacterial cell envelope composition in M. brumae had a strong impact on the immune microenvironment, shaping the B and myeloid cell compartment and T-cell maturation profile and thus improving survival. Overall, we demonstrate that the bladder immune microenvironment induced by mycobacterial treatment is species specific and shaped by mycobacterial cell envelope composition. Therefore, the global bladder immune microenvironment can be remodelled, improving the quality of infiltrating immune cells, the balance between inflammatory and regulatory/suppressive responses and increasing survival

Impact of Long-Term Cryopreservation on Blood Immune Cell Markers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome : Implications for Biomarker Discovery

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex neuroimmune disorder characterized by numerous symptoms of unknown etiology. The ME/CFS immune markers reported so far have failed to generate a clinical consensus, perhaps partly due to the limitations of biospecimen biobanking. To address this issue, we performed a comparative analysis of the impact of long-term biobanking on previously identified immune markers and also explored additional potential immune markers linked to infection in ME/CFS. A correlation analysis of marker cryostability across immune cell subsets based on flow cytometry immunophenotyping of fresh blood and frozen PBMC samples collected from individuals with ME/CFS (n = 18) and matched healthy controls (n = 18) was performed. The functionality of biobanked samples was assessed on the basis of cytokine production assay after stimulation of frozen PBMCs. T cell markers defining Treg subsets and the expression of surface glycoprotein CD56 in T cells and the frequency of the effector CD8 T cells, together with CD57 expression in NK cells, appeared unaltered by biobanking. By contrast, NK cell markers CD25 and CD69 were notably increased, and NKp46 expression markedly reduced, by long-term cryopreservation and thawing. Further exploration of Treg and NK cell subsets failed to identify significant differences between ME/CFS patients and healthy controls in terms of biobanked PBMCs. Our findings show that some of the previously identified immune markers in T and NK cell subsets become unstable after cell biobanking, thus limiting their use in further immunophenotyping studies for ME/CFS. These data are potentially relevant for future multisite intervention studies and cooperative projects for biomarker discovery using ME/CFS biobanked samples. Further studies are needed to develop novel tools for the assessment of biomarker stability in cryopreserved immune cells from people with ME/CFS

The HR2 polymorphism N140I in the HIV-1 gp41 combined with the HR1 V38A mutation is associated with a less cytopathic phenotype

<p>Abstract</p> <p>Background</p> <p>Resistance to the fusion inhibitor enfuvirtide (ENF) is achieved by changes in the gp41 subunit of the HIV envelope glycoprotein (Env). Specific ENF-associated mutational pathways correlate with immunological recovery, even after virological failure, suggesting that the acquisition of ENF resistance alters gp41 pathogenicity. To test this hypothesis, we have characterized the expression, fusion capability, induction of CD4⁺T cell loss and single CD4⁺T cell death of 48 gp41 proteins derived from three patients displaying different amino acids (N, T or I) at position 140 that developed a V38A mutation after ENF-based treatment.</p> <p>Results</p> <p>In all cases, intra-patient comparison of Env isolated pre- or post-treatment showed comparable values of expression and fusogenic capacity. Furthermore, Env with either N or T at position 140 induced comparable losses of CD4⁺T-cells, irrespective of the residue present at position 38. Conversely, Env acquiring the V38A mutation in a 140I background induced a significantly reduced loss of CD4⁺T cells and lower single-cell death than did their baseline controls. No altered ability to induce single-cell death was observed in the other clones.</p> <p>Conclusions</p> <p>Overall, primary gp41 proteins with both V38A and N140I changes showed a reduced ability to induce single cell death and deplete CD4⁺T cells, despite maintaining fusion activity. The specificity of this phenotype highlights the relevance of the genetic context to the cytopathic capacity of Env and the role of ENF-resistance mutations in modulating viral pathogenicity <it>in vivo</it>, further supporting the hypothesis that gp41 is a critical mediator of HIV pathogenesis.</p

Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo

A complex link exists between HIV-1 and autophagy, and discordant results have been reported in different in vitro models regarding the way HIV and autophagy modulate each other. Despite this, there is very limited knowledge about the interplay between HIV and autophagy in vivo in lymphoid tissue, due in part by the lack of cell models that recapitulate the in vivo setting. Here, we evaluate the interrelationship between HIV and autophagy using human ex vivo lymphoid tissue cultures as an HIV infection model. Our results showed that human lymphoid aggregated cultures (HLACs) from tonsillar tissue displayed fully functional autophagic activity. In this system, HIV infection resulted in an increase in autophagy. Notably, we observed that both, autophagy-enhancing (rapamycin) or blocking drugs (3-methyladenine, chloroquine and bafilomycin), were able to decrease HIV-DNA levels and HIV replication. Therefore, efficient HIV-1 replication requires a fine-tuned level of autophagy, so modifications of this balance will have a negative impact on its replication. Therefore, targeting the autophagic pathway could be a new therapeutic approach to be explored to treat HIV-1 infection. Ex vivo cultures of human lymphoid tissue are a suitable model to obtain further insights into HIV and its intricate relationship with autophagy

Susceptibility of Human Lymphoid Tissue Cultured ex vivo to Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Infection

Xenotropic murine leukemia virus-related virus (XMRV) was generated after a recombination event between two endogenous murine leukemia viruses during the production of a prostate cancer cell line. Although the associations of the XMRV infection with human diseases appear unlikely, the XMRV is a retrovirus of undefined pathogenic potential, able to replicate in human cells in vitro. Since recent studies using animal models for infection have yielded conflicting results, we set out an ex vivo model for XMRV infection of human tonsillar tissue to determine whether XMRV produced by 22Rv1 cells is able to replicate in human lymphoid organs. Tonsil blocks were infected and infection kinetics and its pathogenic effects were monitored XMRV, though restricted by APOBEC, enters and integrates into the tissue cells. The infection did not result in changes of T or B-cells, immune activation, nor inflammatory chemokines. Infectious viruses could be recovered from supernatants of infected tonsils by reinfecting DERSE XMRV indicator cell line, although these supernatants could not establish a new infection in fresh tonsil culture, indicating that in our model, the viral replication is controlled by innate antiviral restriction factors. Overall, the replication-competent retrovirus XMRV, present in a high number of laboratories, is able to infect human lymphoid tissue and produce infectious viruses, even though they were unable to establish a new infection in fresh tonsillar tissue. Hereby, laboratories working with cell lines producing XMRV should have knowledge and understanding of the potential biological biohazardous risks of this virus

HIV-1 Tropism Testing in Subjects Achieving Undetectable HIV-1 RNA : Diagnostic Accuracy, Viral Evolution and Compartmentalization

Technically, HIV-1 tropism can be evaluated in plasma or peripheral blood mononuclear cells (PBMCs). However, only tropism testing of plasma HIV-1 has been validated as a tool to predict virological response to CCR5 antagonists in clinical trials. The preferable tropism testing strategy in subjects with undetectable HIV-1 viremia, in whom plasma tropism testing is not feasible, remains uncertain. We designed a proof-of-concept study including 30 chronically HIV-1-infected individuals who achieved HIV-1 RNA <50 copies/mL during at least 2 years after first-line ART initiation. First, we determined the diagnostic accuracy of 454 and population sequencing of gp120 V3-loops in plasma and PBMCs, as well as of MT-2 assays before ART initiation. The Enhanced Sensitivity Trofile Assay (ESTA) was used as the technical reference standard. 454 sequencing of plasma viruses provided the highest agreement with ESTA. The accuracy of 454 sequencing decreased in PBMCs due to reduced specificity. Population sequencing in plasma and PBMCs was slightly less accurate than plasma 454 sequencing, being less sensitive but more specific. MT-2 assays had low sensitivity but 100% specificity. Then, we used optimized 454 sequence data to investigate viral evolution in PBMCs during viremia suppression and only found evolution of R5 viruses in one subject. No de novo CXCR4-using HIV-1 production was observed over time. Finally, Slatkin-Maddison tests suggested that plasma and cell-associated V3 forms were sometimes compartmentalized. The absence of tropism shifts during viremia suppression suggests that, when available, testing of stored plasma samples is generally safe and informative, provided that HIV-1 suppression is maintained. Tropism testing in PBMCs may not necessarily produce equivalent biological results to plasma, because the structure of viral populations and the diagnostic performance of tropism assays may sometimes vary between compartments. Thereby, proviral DNA tropism testing should be specifically validated in clinical trials before it can be applied to routine clinical decision-making