La mejora del sentido de número en niños de preescolar con bajo rendimiento en matemáticas.

The present study evaluated the effectiveness of educational intervention software, Playing with Numbers-2 on early mathematics learning. This software trains learning and mathematical reasoning skills, using an evidenced-based procedure. A total of 156 second-year preschool boys and girls (Mean age = 65.39 months) were assessed by the Early Numeracy Test (ENT), a computerized test to evaluate early math competency. An experimental design with control group and pre and post-intervention assessments was used. Significant differences between pre- and post- intervention for the experimental group was obtained average increase for ENT scores achieved by the experimental group was significantly higher than the control group. The effect size was also significant (d = 1.35; and r = 0.56). This educational intervention using computer-based software, while it does not replace face-to-face instruction, may help to improve the performance of young students at risk of developing problems learning mathematics.El presente estudio evaluó la eficacia del programa de intervención educativa denominado Jugando con los números-2 en el aprendizaje matemático temprano. Este software incide en el aprendizaje y el perfeccionamiento de las habilidades de razonamiento matemático utilizando un procedimiento basado en la evidencia. Un total de 156 niños y niñas en edad preescolar (edad media = 65.39 meses) los cuales fueron evaluados mediante el instrumento Early Numeracy Test (ENT), un test computarizado para evaluar la competencia matemática temprana. Se utilizó un diseño experimental con grupo control y evaluaciones pre y post-intervención. Se obtuvieron diferencias significativas antes y después de la intervención para el grupo experimental mostrando un incremento en las puntuaciones arrojadas que fueron significativamente superiores a las alcanzadas por el grupo control.  El tamaño del efecto fue también significativo (d = 1.35; y r = .56). Esta intervención educativa utilizando como base un programa computarizado no pretende reemplazar la instrucción tradicional, pero puede ayudar a mejorar el rendimiento de los estudiantes jóvenes en riesgo de desarrollar dificultades de aprendizaje de las matemáticas

Pharmacological primary cardiovascular prevention and subclinical atherosclerosis in men: Evidence from the aragon workers'' health study

The objective of this study is to describe the profile of primary preventive treatment for cardiovascular disease in adult males and to analyze the association between treatment profile and subclinical atherosclerosis. We selected male workers who had undergone ultrasound imaging and had no previous history of cardiovascular disease (n = 2138). Data on the consumption of primary cardiovascular drugs from the previous year were obtained. We performed bivariate analyses to compare patient characteristics according to cardiovascular treatment and the presence of subclinical atherosclerosis, and logistic regression models to explore the association between these two variables. Among participants with no personal history of cardiovascular disease, subclinical atherosclerosis was present in 77.7% and 31.2% had received some form of preventive treatment. Of those who received no preventive treatment, 73.6% had subclinical atherosclerosis. Cardiovascular preventive treatment was associated only with CACS > 0 (odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.06-1.78). Statin treatment was associated with a greater risk of any type of subclinical atherosclerosis (OR, 1.73) and with CACS > 0 (OR, 1.72). Subclinical atherosclerosis existed in almost 75% of men who had no personal history of cardiovascular disease and had not received preventive treatment for cardiovascular disease

Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice

Background and Objectives To demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)- hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA re- ceptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies. Methods Four groups of mice received (days 1-14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily sub- cutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques. Results On day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups. Discussion An oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation

Placental transfer of NMDAR antibodies causes reversible alterations in mice

Objective: To determine whether maternofetal transfer of NMDA receptor (NMDAR) antibodies has pathogenic effects on the fetus and offspring, we developed a model of placental transfer of antibodies. Methods: Pregnant C57BL/6J mice were administered via tail vein patients' or controls' immunoglobulin G (IgG) on days 14-16 of gestation, when the placenta is able to transport IgG and the immature fetal blood-brain barrier is less restrictive to IgG crossing. Immunohistochemical and DiOlistic (gene gun delivery of fluorescent dye) staining, confocal microscopy, standardized developmental and behavioral tasks, and hippocampal long-term potentiation were used to determine the antibody effects. Results: In brains of fetuses, patients' IgG, but not controls' IgG, bound to NMDAR, causing a decrease in NMDAR clusters and cortical plate thickness. No increase in neonatal mortality was observed, but offspring exposed in utero to patients' IgG had reduced levels of cell-surface and synaptic NMDAR, increased dendritic arborization, decreased density of mature (mushroom-shaped) spines, microglial activation, and thinning of brain cortical layers II-IV with cellular compaction. These animals also had a delay in innate reflexes and eye opening and during follow-up showed depressive-like behavior, deficits in nest building, poor motor coordination, and impaired social-spatial memory and hippocampal plasticity. Remarkably, all these paradigms progressively improved (becoming similar to those of controls) during follow-up until adulthood. Conclusions: In this model, placental transfer of patients' NMDAR antibodies caused severe but reversible synaptic and neurodevelopmental alterations. Reversible antibody effects may contribute to the infrequent and limited number of complications described in children of patients who develop anti-NMDAR encephalitis during pregnancy

Allosteric modulation of NMDA receptors prevents the antibody effects of patients with anti-NMDAR encephalitis

Anti-N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis is an immune-mediated disease characterized by a complex neuropsychiatric syndrome in association with an antibody-mediated decrease of NMDAR. About 85% of patients respond to immunotherapy (and removal of an associated tumor if it applies), but it often takes several months or more than 1 year for patients to recover. There are no complementary treatments, beyond immunotherapy, to accelerate this recovery. Previous studies showed that SGE-301, a synthetic analog of 24(S)-hydroxycholesterol, which is a potent, and selective positive allosteric modulator of NMDAR, reverted the memory deficit caused by phencyclidine (a non-competitive antagonist of NMDAR), and prevented the NMDAR dysfunction caused by patients' NMDAR antibodies in cultured neurons. An advantage of SGE-301 is that it is optimized for systemic delivery such that plasma and brain exposures are sufficient to modulate NMDAR activity. Here, we used SGE-301 to confirm that in cultured neurons it prevented the antibody-mediated reduction of receptors, and then we applied it to a previously reported mouse model of passive cerebroventricular transfer of patients' CSF antibodies. Four groups were established: mice receiving continuous (14-day) infusion of patients' or controls' CSF, treated with daily subcutaneous administration of SGE-301 or vehicle (no drug). The effects on memory were examined with the novel object location (NOL) test at different time points, and the effects on synaptic levels of NMDAR (assessed with confocal microscopy) and plasticity (long-term potentiation [LTP]) were examined in the hippocampus on day 18, which in this model corresponds to the last day of maximal clinical and synaptic alterations. As expected, mice infused with patients' CSF antibodies, but not those infused with controls' CSF, and treated with vehicle developed severe memory deficit without locomotor alteration, accompanied by a decrease of NMDAR clusters and impairment of LTP. All antibody-mediated pathogenic effects (memory, synaptic NMDAR, LTP) were prevented in the animals that were treated with SGE-301, despite that this compound did not antagonize antibody binding. Additional investigations on the potential mechanisms related to these SGE-301 effects showed that (1) in cultured neurons SGE-301 prolonged the decay time of NMDAR-dependent spontaneous excitatory postsynaptic currents suggesting a prolonged open time of the channel, and (2) it significantly decreased the internalization of antibody-bound receptors suggesting that additional, yet unclear mechanisms, contribute in keeping unchanged the surface NMDAR density. Overall, these findings suggest that SGE-301, or similar modulators of NMDAR, could potentially serve as complementary treatment for anti-NMDAR encephalitis and deserve future investigations

Implementación de los hallazgos de la línea de base sobre buenas prácticas de evaluación y conformación de la Red de Instituciones por la Evaluación - RIE

El estudio sobre prácticas de evaluación, en el 2018, implicó la conformación de una Red de Instituciones por la Evaluación RIE, basada en cuatro nodos temáticos de acuerdo con tendencias, intereses y expectativas derivadas de la fase 2017, y en prácticas evaluativas acordes con la política distrital de evaluación en grados y áreas. También se realizó la puesta en marcha de estrategias y acciones de divulgación de prácticas significativas de evaluación, la sistematización del proceso de conformación y desarrollo de acciones de la red RIE, y la puesta en marcha de escenarios virtuales de apoyo a la conformación de la Red

Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43A90V mutation display a mild reactive state and release polyP toxic to motoneurons

Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A growing number of studies have shown that soluble toxic factor(s) in the ACM cause non-cell autonomous MN death, including our recent identification of inorganic polyphosphate (polyP) that is excessively released from mouse primary astrocytes (SOD1, TARDBP, and C9ORF72) and human induced pluripotent stem cells (iPSC)-derived astrocytes (TARDBP) to kill MNs. However, others have reported that astrocytes carrying mutant TDP43 do not produce detectable MN toxicity. This controversy is likely to arise from the findings that human iPSC-derived astrocytes exhibit a rather immature and/or reactive phenotype in a number of studies. Here, we have succeeded in generating a highly homogenous population of functional quiescent mature astrocytes from control subject iPSCs. Using identical conditions, we also generated mature astrocytes from an ALS/FTD patient carrying the TDP43A90V mutation. These mutant TDP43 patient-derived astrocytes exhibit key pathological hallmarks, including enhanced cytoplasmic TDP-43 and polyP levels. Additionally, mutant TDP43 astrocytes displayed a mild reactive signature and an aberrant function as they were unable to promote synaptogenesis of hippocampal neurons. The polyP-dependent neurotoxic nature of the TDP43A90V mutation was further confirmed as neutralization of polyP in ACM derived from mutant TDP43 astrocytes prevented MN death. Our results establish that human astrocytes carrying the TDP43A90V mutation exhibit a cell-autonomous pathological signature, hence providing an experimental model to decipher the molecular mechanisms underlying the generation of the neurotoxic phenotype

Representaciones sociales en ambiente y educación ambiental de diferentes grupos poblacionales en la localidad de Chapinero

El presente artículo da cuenta de los resultados de la investigación Representaciones sociales sobre ambiente y educación ambiental de grupos poblacionales con incidencia en la localidad de Chapinero, Bogotá, sector de la capital donde el crecimiento desordenado y exponencial ha redundado en graves impactos tanto naturales como sociales. La investigación se abordó desde el paradigma el hermenéutico, con el método de teoría fundada, buscando comprender la relación de sujeto-objeto, a partir de un enfoque cualitativo. Para el estudio de las representaciones sociales se asumió, a partir de las escuelas o líneas metodológicas propuestas para esto por Pereira de Sá, la Escuela Clásica, con un enfoque procesual, empleando como técnicas de recolección de información las entrevistas semi-estructuradas y las tablas inductoras. Los resultados permitieron identificar dos perspectivas de la relación del hombre con la naturaleza, desde diversos tipos representaciones sociales de ambiente

Análisis Empírico del Efecto de la Duración del Contrato de Auditoría en la Recepción de Informes Cualificados: The Impact of Long-term Audit Engagement on the Reception of a Qualified Audit Report: Empirical Analysis

Critics of the auditing profession have often suggested a policy of mandatory rotation of audit firms as a way of countering their perception that long-term relationships between auditors and their clients impede the independence and professional scepticism of the auditors. The auditing profession has maintained that the mandatory rotation would be expensive and would, in fact, increase the number of audit failures. What is needed in this important policy debate is independent evidence to support or refute the merits of the opposing arguments. Both the proponents of rotation and the opponents have vested interests that render arguments suspect in the absence of such evidence. This paper aims to analyse the impact of long-term audit mandates in auditor reporting behaviour decisions. The results of this study suggest that long-term auditor-client relationships increase the likelihood of a qualified opinion. It means that mandatory audit firm rotation is an unnecessary auditor independence safeguard, which supports the audit profession’s arguments. Critics of the auditing profession have often suggested a policy of mandatory rotation of audit firms as a way of countering their perception that long-term relationships between auditors and their clients impede the independence and professional scepticism of the auditors. The auditing profession has maintained that the mandatory rotation would be expensive and would, in fact, increase the number of audit failures. What is needed in this important policy debate is independent evidence to support or refute the merits of the opposing arguments. Both the proponents of rotation and the opponents have vested interests that render arguments suspect in the absence of such evidence. This paper aims to analyse the impact of long-term audit mandates in auditor reporting behaviour decisions. The results of this study suggest that long-term auditor-client relationships increase the likelihood of a qualified opinion. It means that mandatory audit firm rotation is an unnecessary auditor independence safeguard, which supports the audit profession’s arguments. Críticos de la profesión auditora han sugerido a menudo que la política de rotación obligatoria de firmas de auditoría puede ser una forma de contrapesar la percepción de que los contratos a largo plazo entre auditores y sus clientes impiden la independencia y escepticismo profesional de los auditores. La profesión auditora ha mantenido que la rotación obligatoria podría ser costosa e incrementar, de hecho, el número de fallos de auditoría. Lo necesario en este debate es la obtención de evidencia objetiva para soportar o rechazar los méritos de los argumentos opuestos que se utilizan. Ambas corrientes, es decir, los proponentes y los oponentes de la rotación de firmas auditoras, tienen intereses creados, por lo que se generan argumentos que resultan sospechosos sin tal evidencia. El objetivo de este trabajo es analizar el efecto que tiene la duración del contrato de auditoría en las decisiones sobre informes de los auditores. Los resultados de este estudio sugieren que la duración del contrato aumenta la probabilidad de recibir un informe cualificado. Esto implica que la rotación obligatoria de firmas no sería una medida necesaria para garantizar la independencia de los auditores, lo cual apoya los argumentos de la profesión auditora

The Impact of Long-term Audit Engagement on the Reception of a Qualified Audit Report: Empirical Analysis

Críticos de la profesión auditora han sugerido a menudo que la política de rotación obligatoria de firmas de auditoría puede ser una forma de contrapesar la percepción de que los contratos a largo plazo entre auditores y sus clientes impiden la independencia y escepticismo profesional de los auditores. La profesión auditora ha mantenido que la rotación obligatoria podría ser costosa e incrementar, de hecho, el número de fallos de auditoría. Lo necesario en este debate es la obtención de evidencia objetiva para soportar o rechazar los méritos de los argumentos opuestos que se utilizan. Ambas corrientes, es decir, los proponentes y los oponentes de la rotación de firmas auditoras, tienen intereses creados, por lo que se generan argumentos que resultan sospechosos sin tal evidencia. El objetivo de este trabajo es analizar el efecto que tiene la duración del contrato de auditoría en las decisiones sobre informes de los auditores. Los resultados de este estudio sugieren que la duración del contrato aumenta la probabilidad de recibir un informe cualificado. Esto implica que la rotación obligatoria de firmas no sería una medida necesaria para garantizar la independencia de los auditores, lo cual apoya los argumentos de la profesión auditora.Critics of the auditing profession have often suggested a policy of mandatory rotation of audit firms as a way of countering their perception that a long-term relationships between auditors and their clients impede the independence and professional scepticism of the auditors. The auditing profession has maintained that the mandatory rotation would be expensive and would, in fact, increase the number of audit failures. What is needed in this important policy debate is independent evidence to support of refute the merits of the opposing argumetns. Both the proponents of rotation and the opponents have vested interests that render arguments suspect in the absence of such evidence. This paper aims to analyse the impact of long-term audit mandates in auditor reporting behaviour decisions. The results of this sutdy suggest that long-term audit mandates in auditor reporting behaviour decisions. The results of this study suggest that a long-term auditor-client relationships increase the likelihood of a qualified opinion. it means that mandatory audit firm rotation is an unnecessary auditor independence safeguard, which supports the audit profession's arguments