Memory built in conjunction with a stressor is privileged: Reconsolidation-resistant memories in the crab Neohelice.

The dynamics of memory processes are conserved throughout evolution, a feature based on the hypothesis of a common origin of the high-order memory centers in bilateral animals. Reconsolidation is just one example. The possibility to interfere with long-term memory expression during reconsolidation has been proposed as potentially useful in clinical application to treat traumatic memories. However, several pieces of evidence in rodents show that either robust fear memories or stressful events applied before acquisition promote reconsolidation-resistant memories, i.e., memories that are resistant to the interfering effect of drugs on memory reconsolidation. Conceivably, the generation of these reconsolidation-resistant fear memories also occurs in humans. Is the induction of reconsolidation-resistant memories part of the dynamics of memory processes conserved throughout evolution? In the semiterrestrial crab Neohelice granulata, memory reconsolidation is triggered by a short reminder without reinforcement. Here, we show that an increase in the salience of the aversive stimulus augmented the memory strength; nonetheless, the protein synthesis inhibitor cycloheximide still disrupted the reconsolidation process. However, crabs stressed by a water-deprivation episode before a strong training session built up a memory that was now reconsolidation-resistant. We tested whether these reconsolidation-resistant effects can be challenged by changing parametric conditions of memory-reminder sessions; multiple memory reactivations without reinforcement were not able to trigger the labilization-reconsolidation of this resistant memory. Overall, the present findings suggest that generation of reconsolidation-resistant memories can be another part of the dynamics of memory processes conserved throughout evolution that protects privileged information from change.

Metodología para evaluar la calidad de la formación del estudiante en la Escuela Latinoamericana de Medicina / A methodology for evaluating the quality of student training in the Latin American School of Medicine

Introducción: las demandas crecientes del entorno generan cada día nuevos retos para las Instituciones de Educación Médica Superior, comprometen a las Instituciones de Educación Médicas Superior (IEMS) al cumplimiento de los parámetros mínimos de calidad en el proceso formativo de los estudiantes en aras de asegurar el ejercicio apropiado de la Medicina. De ahí la necesidad de implementar la evaluación del proceso de formación del estudiante como una vía que contribuya a elevar su calidad. Objetivos: diseñar una metodología para evaluar la calidad de la formación del estudiante en la Escuela Latinoamericana de Medicina (ELAM). Métodos: se utilizaron como métodos teóricos el análisis-síntesis, la inducción-deducción, el histórico-lógico, el enfoque sistémico y la modelación. Como métodos empíricos, el análisis documental y de contenido, la encuesta y la consulta a expertos. Resultados: se diseñó una metodología sustentada en un conjunto de relaciones esenciales y principios, estructurada en un conjunto de fases interrelacionadas entre sí, formando una unidad orgánica, cuyos objetivos, contenido, acciones y resultados responden a las exigencias de la evaluación de la calidad de la formación del estudiante. Conclusiones: el incremento de la calidad de la formación es vista como un desafío, una necesidad y un compromiso con el que se responsabilizan los estudiantes, los profesores, directivos de la ELAM. Se valoró como viable la propuesta metodológica diseñada, al ponerse de relieve la importancia de las diferentes fases que la integran, así como la relación entre el objetivo, el contenido, las acciones y los resultados contenidos en cada una de ellas(AU)

Introduction: The growing environmental demands generate new challenges for the institutions of higher medical education. They commit institutions of higher medical education to the fulfillment of the minimum parameters of quality in the training process of the students, in order to ensure the proper medical practice. Hence the need to implement the evaluation of the student training process as a way to help raise its quality. Objective: To design a methodology for evaluating the quality of student training in the Latin American School of Medicine (ELAM). Methods: Analysis-synthesis, induction-deduction, historical-logical, systemic approach and modeling were used as theoretical methods. As empirical methods, the documentary and content analysis, the survey and the consultation of experts were used. Results: A methodology was designed based on a set of essential relationships and principles, structured in a set of interrelated phases, forming an organic unit, whose objectives, content, actions and results respond to the requirements of the evaluation of quality of the students' training. Conclusions: The increased quality of training is perceived as a challenge, a necessity and a commitment with which the students, professors, and the ELAM directors are responsible. The methodological proposal designed was evaluated as viable, highlighting the importance of the different phases that comprise it, as well as the relationship between the objective, content, actions and results contained in each one of them.(AU)

Metodología para evaluar la calidad de la formación del estudiante en la Escuela Latinoamericana de Medicina / A methodology for evaluating the quality of student training in the Latin American School of Medicine

Introducción: las demandas crecientes del entorno generan cada día nuevos retos para las Instituciones de Educación Médica Superior, comprometen a las Instituciones de Educación Médicas Superior (IEMS) al cumplimiento de los parámetros mínimos de calidad en el proceso formativo de los estudiantes en aras de asegurar el ejercicio apropiado de la Medicina. De ahí la necesidad de implementar la evaluación del proceso de formación del estudiante como una vía que contribuya a elevar su calidad. Objetivos: diseñar una metodología para evaluar la calidad de la formación del estudiante en la Escuela Latinoamericana de Medicina (ELAM). Métodos: se utilizaron como métodos teóricos el análisis-síntesis, la inducción-deducción, el histórico-lógico, el enfoque sistémico y la modelación. Como métodos empíricos, el análisis documental y de contenido, la encuesta y la consulta a expertos. Resultados: se diseñó una metodología sustentada en un conjunto de relaciones esenciales y principios, estructurada en un conjunto de fases interrelacionadas entre sí, formando una unidad orgánica, cuyos objetivos, contenido, acciones y resultados responden a las exigencias de la evaluación de la calidad de la formación del estudiante. Conclusiones: el incremento de la calidad de la formación es vista como un desafío, una necesidad y un compromiso con el que se responsabilizan los estudiantes, los profesores, directivos de la ELAM. Se valoró como viable la propuesta metodológica diseñada, al ponerse de relieve la importancia de las diferentes fases que la integran, así como la relación entre el objetivo, el contenido, las acciones y los resultados contenidos en cada una de ellas(AU)

Introduction: The growing environmental demands generate new challenges for the institutions of higher medical education. They commit institutions of higher medical education to the fulfillment of the minimum parameters of quality in the training process of the students, in order to ensure the proper medical practice. Hence the need to implement the evaluation of the student training process as a way to help raise its quality. Objective: To design a methodology for evaluating the quality of student training in the Latin American School of Medicine (ELAM). Methods: Analysis-synthesis, induction-deduction, historical-logical, systemic approach and modeling were used as theoretical methods. As empirical methods, the documentary and content analysis, the survey and the consultation of experts were used. Results: A methodology was designed based on a set of essential relationships and principles, structured in a set of interrelated phases, forming an organic unit, whose objectives, content, actions and results respond to the requirements of the evaluation of quality of the students' training. Conclusions: The increased quality of training is perceived as a challenge, a necessity and a commitment with which the students, professors, and the ELAM directors are responsible. The methodological proposal designed was evaluated as viable, highlighting the importance of the different phases that comprise it, as well as the relationship between the objective, content, actions and results contained in each one of them.(AU)

Association between methylation of SHP-1 isoform I and SSTR2A promoter regions with breast and prostate carcinoma development.

Methylation pattern is presented here for first time as a potential molecular marker of changes on SSTR2A and SHP-1(I) gene promoter related to breast and prostate carcinoma. Our results have shown low concordances with SSTR2A and methylated state in prostate cancer and moderate relationship with unmethylated CpG-27 in breast cancer. We found significant concordances for both cancers and SHP-1(I) unmethylation, and increased HER2 expression and SSTR2A methylation in breast cancer. Moreover, we found a correlation between methylation patterns of two genes in normal breast tissue. These data might assist to select subgroups of patients for the administration of alternative therapies.

Candida albicans delays HIV-1 replication in macrophages.

Macrophages are one of the most important HIV-1 target cells. Unlike CD4(+) T cells, macrophages are resistant to the cytophatic effect of HIV-1. They are able to produce and harbor the virus for long periods acting as a viral reservoir. Candida albicans (CA) is a commensal fungus that colonizes the portals of HIV-1 entry, such as the vagina and the rectum, and becomes an aggressive pathogen in AIDS patients. In this study, we analyzed the ability of CA to modulate the course of HIV-1 infection in human monocyte-derived macrophages. We found that CA abrogated HIV-1 replication in macrophages when it was evaluated 7 days after virus inoculation. A similar inhibitory effect was observed in monocyte-derived dendritic cells. The analysis of the mechanisms responsible for the inhibition of HIV-1 production in macrophages revealed that CA efficiently sequesters HIV-1 particles avoiding its infectivity. Moreover, by acting on macrophages themselves, CA diminishes their permissibility to HIV-1 infection by reducing the expression of CD4, enhancing the production of the CCR5-interacting chemokines CCL3/MIP-1α, CCL4/MIP-1ß, and CCL5/RANTES, and stimulating the production of interferon-α and the restriction factors APOBEC3G, APOBEC3F, and tetherin. Interestingly, abrogation of HIV-1 replication was overcome when the infection of macrophages was evaluated 2-3 weeks after virus inoculation. However, this reactivation of HIV-1 infection could be silenced by CA when added periodically to HIV-1-challenged macrophages. The induction of a silent HIV-1 infection in macrophages at the periphery, where cells are continuously confronted with CA, might help HIV-1 to evade the immune response and to promote resistance to antiretroviral therapy.

Semen promotes the differentiation of tolerogenic dendritic cells.

Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations of cytokines, chemokines, and other biological compounds that are able to exert potent effects on the immune system of the receptive partner. Previous studies have shown that semen induces an acute inflammatory response at the female genital mucosa after coitus. Moreover, it induces regulatory mechanisms that allow the fetus (a semiallograft) to grow and develop in the uterus. The mechanisms underlying these regulatory mechanisms, however, are poorly understood. In this study, we show that seminal plasma redirects the differentiation of human dendritic cells (DCs) toward a regulatory profile. DCs differentiated from human monocytes in the presence of high dilutions of seminal plasma did not express CD1a but showed high levels of CD14. They were unable to develop a fully mature phenotype in response to LPS, TNF-α, CD40L, Pam2CSK4 (TLR2/6 agonist), or Pam3CSK4 (TLR1/2 agonist). Upon activation, they produced low amounts of the inflammatory cytokines IL-12p70, IL-1ß, TNF-α, and IL-6, but expressed a high ability to produce IL-10 and TGF-ß. Inhibition of the PG receptors E-prostanoid receptors 2 and 4 prevented the tolerogenic effect induced by seminal plasma on the phenotype and function of DCs, suggesting that E-series PGs play a major role. By promoting a tolerogenic profile in DCs, seminal plasma might favor fertility, but might also compromise the capacity of the receptive partner to mount an effective immune response against sexually transmitted pathogens.

Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats.

BACKGROUND: Anesthesia given to immature rodents causes cognitive decline, raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury. METHODS: Seven-day old rats underwent sevoflurane anesthesia (1 minimum alveolar concentration, 4 h) with or without tail clamping. At 4 weeks, rats were randomized to environmental enrichment or normal housing. At 8 weeks rats underwent neurocognitive testing, which consisted of fear conditioning, spatial reference memory, and water maze-based memory consolidation tests, and interrogated working memory, short-term memory, and early long-term memory. RESULTS: Sevoflurane-treated rats had a greater escape latency when the delay between memory acquisition and memory retrieval was increased from 1 min to 1 h, indicating that short-term memory was impaired. Delayed environmental enrichment reversed the effects of sevoflurane on short-term memory and generally improved many tested aspects of cognitive function, both in sevoflurane-treated and control animals. The performance of tail-clamped rats did not differ from those rats receiving anesthesia alone. CONCLUSION: Sevoflurane-induced cognitive decline in rats is treatable. Delayed environmental enrichment rescued the sevoflurane-induced impairment in short-term memory. Tissue injury did not worsen the anesthesia-induced memory impairment. These findings may have relevance to neonatal and pediatric anesthesia.

Increasing the duration of isoflurane anesthesia decreases the minimum alveolar anesthetic concentration in 7-day-old but not in 60-day-old rats.

BACKGROUND: While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.3% at 4 h. We investigated whether kinetic or dynamic factors mediated this decrease. METHODS: In 7-day-old rats, we measured inspired and cerebral partial pressures of isoflurane at MAC as a function of duration of anesthesia. In 60-day-old rats, we measured inspired partial pressures of isoflurane at MAC as a function of duration of anesthesia. Finally, we determined the effect of administering 1 mg/kg naloxone and of delaying the initiation of the MAC determination (pinching the tail) on MAC in 7-day-old rats. RESULTS: In 7-day-old rats, both inspired and cerebral measures of MAC decreased from 1 to 4 h. The inspired MAC decreased 56%, whereas the cerebral MAC decreased 33%. At 4 h, the inspired MAC approximated the cerebral MAC (i.e., the partial pressures did not differ appreciably). Neither administration of 1 mg/kg naloxone nor delaying tail clamping until 3 h reversed the decrease in MAC. In 60-day-old rats, inspired MAC of isoflurane was stable from 1 to 4 h of anesthesia. CONCLUSIONS: MAC of isoflurane decreases over 1-4 h of anesthesia in 7-day-old but not in 60-day-old rats. Both pharmacodynamic and a pharmacokinetic components contribute to the decrease in MAC in 7-day-old rats. Neither endorphins nor sensory desensitization mediate the pharmacodynamic component.

Susceptibilidad de candida spp a fluconazol, voriconazol y caspofungina por el método de difusión con disco / Susceptibility of candida spp to fluconazol, voriconazol and caspofungina by the method of diffusion with disc

En las dos últimas décadas, el aumento de la prevalencia de las candidosis ha sido constante. En nuestro país existe un incremento notable y progresivo de especies distintas a Candida albicans asociado a candidemias, lo que señala la necesidad de identificar las levaduras del genero Candida a nivel de especie, así como la realización de las pruebas de susceptibilidad a los antifúngicos. El objetivo de este trabajo fue determinar la susceptibilidad de Candida spp., a Fluconazol (FZ), Voriconazol (VZ) y Caspofungina (CS) por el método de difusión con discos. Se recolectaron 80 aislados de Candida spp., provenientes de pacientes con candidemia hospitalizados en las UCI de 9 centros hospitalarios del área metropolitana de Caracas (junio 2006 a abril 2008). Los aislados se identificaron por métodos automatizados Vitek-2 YBC® y Walkway MicroScan®, verificando la identificación por métodos convencionales, Chromagar-Candida y morfología en agar harina de maíz. La prueba de difusión con disco se realizó según el documento CLSI M44-A, utilizando discos comerciales de FZ (25µg), VZ (1µg) y discos de CS (5µg) de preparación artesanal. La lectura se realizó a las 24 h de incubación a 35°C, se midió en milímetros el diámetro de la zona de inhibición que producía una reducción significativa ≥ 50% y el criterio de interpretación fue: FZ (S:≥19mm, S-DD:15-18mm, R:≤14mm), VZ (S:≥17mm, S-DD:14-16 mm, R:≤13mm), CS (S:≥11mm, R:≤10mm). Todas las especies de Candida resultaron susceptibles a los 3 antifúngicos ensayados a excepción de un aislado de C.krusei resistente a FZ. Los valores mínimo, máximo y media geométrica de la susceptibilidad en mm fueron: FZ (25/38/30), VZ (26/39/31) y CS (16/21/18). El método de disco difusión es una alternativa útil, rápida y de fácil ejecución para ser implementado en laboratorios de micología y así ofrecer una orientación en el tratamiento antifúngico adecuado y oportuno en candidosis invasora.

During the last two decades, the increase of prevalence of candidosis has been constant. In our country there has been a notable and progressive increment of different species of Candida albicans associated with candidemis, which indicate the need to identify the yeasts of the Candida gender at the specie level, as well as the execution of the susceptibility testing on the antifungal. The purpose of this work was to determine the susceptibility of Candida spp., to Fluconazole (FZ), Voriconazole (VZ) and Caspofungin (CS) by the method of diffusion with disc. There were collected 80 isolates of Candida spp., sampled from patients with candidemia hospitalized at the ICU of 9 hospital centers of the metropolitan area of Caracas (June 2006 to April 2008). The isolates were identified by automated methods, Vitek-2 YBC® and Walkway MicroScan®, and then the identification was verified by a conventional method, Chromagar-Candida and the morphology in corn meal agar. The test of diffusion with disc was performed as per document CLSI M44-A, using commercially available disc of FZ (25µg), VZ (1µg) and discs of CS (5µg) of in-house preparation. The readings were made at 24 h of incubation, at 35°C, thereby measuring in millimeters the diameter of the inhibition zone that generated a significant reduction ≥ 50%, being the criteria of interpretation: FZ (S:≥19mm, S-DD:15-18mm, R:≤14mm), VZ (S:≥17mm, S-DD:14-16 mm, R:≤13mm), CS (S:≥11mm, R:≤10mm). All species of Candida were susceptible against the 3 antifungal assayed with the exception of an isolate of C.krusei which was resistant to FZ. The minimum, maximum and geometric media values for the susceptibility in mm were: FZ (25/38/30), VZ (26/39/31) and CS (16/21/18). The method of diffusion with disc is a useful, quick, and easy to execute and implement alternative by mycology laboratories, in order to offer an orientation regarding the proper and opportune antifungal treatment of invasive candidosis.